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[ { "id": "10982", "type": "title", "text": [ "[3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors." ], "offsets": [ [ 0, 151 ] ] }, { "id": "10983", "type": "abstract", "text": [ "ATP-sensitive P2X7 receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X7 receptors leads to rapid changes in intracellular calcium concentrations, release of the pro-inflammatory cytokine IL-1beta, and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Data from gene knockout studies and recently described selective antagonists indicate a role for P2X7 receptor activation in inflammation and pain. While several species selective P2X7 antagonists exist, A-804598 represents a structurally novel, competitive, and selective antagonist that has equivalent high affinity at rat (IC50 = 10 nM), mouse (IC50 = 9 nM) and human (IC50 = 11 nM) P2X7 receptors. A-804598 also potently blocked agonist stimulated release of IL-1beta and Yo-Pro uptake from differentiated THP-1 cells that natively express human P2X7 receptors. A-804598 was tritiated ([3H]A-804598; 8.1Ci/mmol) and utilized to study recombinant rat P2X7 receptors expressed in 1321N1 cells. [3H]A-804598 labeled a single class of high affinity binding sites (Kd=2.4 nM and apparent Bmax=0.56 pmol/mg). No specific binding was observed in untransfected 1321N1 cells. The pharmacological profile for P2X antagonists to inhibit [3H]A-804598 binding correlated with their ability to block functional activation of P2X7 receptors (r=0.95, P<0.05). These data demonstrate that A-804598 is one of the most potent and selective antagonists for mammalian P2X7 receptors described to date and [3H]A-804598 is a high affinity antagonist radioligand that specifically labels rat P2X7 receptors." ], "offsets": [ [ 152, 1816 ] ] } ]

[ { "id": "10984", "type": "Chemicals & Drugs", "text": [ "[3H]A-804598" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "10985", "type": "Chemicals & Drugs", "text": [ "[3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine" ], "offsets": [ [ 14, 73 ] ], "normalized": [] }, { "id": "10986", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 136, 150 ] ], "normalized": [] }, { "id": "10987", "type": "Genes & Molecular Sequences", "text": [ "ATP-sensitive P2X7 receptors" ], "offsets": [ [ 152, 180 ] ], "normalized": [] }, { "id": "10988", "type": "Chemicals & Drugs", "text": [ "ATP-sensitive P2X7 receptors" ], "offsets": [ [ 152, 180 ] ], "normalized": [] }, { "id": "10989", "type": "Genes & Molecular Sequences", "text": [ "P2X7" ], "offsets": [ [ 166, 170 ] ], "normalized": [] }, { "id": "10990", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 303, 317 ] ], "normalized": [] }, { "id": "10991", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 358, 365 ] ], "normalized": [] }, { "id": "10992", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 423, 431 ] ], "normalized": [] }, { "id": "10993", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptor" ], "offsets": [ [ 626, 639 ] ], "normalized": [] }, { "id": "10994", "type": "Chemicals & Drugs", "text": [ "selective P2X7 antagonists" ], "offsets": [ [ 699, 725 ] ], "normalized": [] }, { "id": "10995", "type": "Genes & Molecular Sequences", "text": [ "P2X7" ], "offsets": [ [ 709, 713 ] ], "normalized": [] }, { "id": "10996", "type": "Chemicals & Drugs", "text": [ "A-804598" ], "offsets": [ [ 733, 741 ] ], "normalized": [] }, { "id": "10997", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 915, 929 ] ], "normalized": [] }, { "id": "10998", "type": "Chemicals & Drugs", "text": [ "A-804598" ], "offsets": [ [ 931, 939 ] ], "normalized": [] }, { "id": "10999", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 992, 1000 ] ], "normalized": [] }, { "id": "11000", "type": "Genes & Molecular Sequences", "text": [ "Yo-Pro" ], "offsets": [ [ 1005, 1011 ] ], "normalized": [] }, { "id": "11001", "type": "Genes & Molecular Sequences", "text": [ "THP-1 cells" ], "offsets": [ [ 1039, 1050 ] ], "normalized": [] }, { "id": "11002", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 1079, 1093 ] ], "normalized": [] }, { "id": "11003", "type": "Chemicals & Drugs", "text": [ "A-804598" ], "offsets": [ [ 1095, 1103 ] ], "normalized": [] }, { "id": "11004", "type": "Chemicals & Drugs", "text": [ "[3H]A-804598" ], "offsets": [ [ 1119, 1131 ] ], "normalized": [] }, { "id": "11005", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 1183, 1197 ] ], "normalized": [] }, { "id": "11006", "type": "Chemicals & Drugs", "text": [ "[3H]A-804598" ], "offsets": [ [ 1225, 1237 ] ], "normalized": [] }, { "id": "11007", "type": "Chemicals & Drugs", "text": [ "No" ], "offsets": [ [ 1336, 1338 ] ], "normalized": [] }, { "id": "11008", "type": "Chemicals & Drugs", "text": [ "P2X antagonists" ], "offsets": [ [ 1432, 1447 ] ], "normalized": [] }, { "id": "11009", "type": "Genes & Molecular Sequences", "text": [ "P2X antagonists" ], "offsets": [ [ 1432, 1447 ] ], "normalized": [] }, { "id": "11010", "type": "Chemicals & Drugs", "text": [ "[3H]A-804598" ], "offsets": [ [ 1459, 1471 ] ], "normalized": [] }, { "id": "11011", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 1544, 1558 ] ], "normalized": [] }, { "id": "11012", "type": "Chemicals & Drugs", "text": [ "A-804598" ], "offsets": [ [ 1605, 1613 ] ], "normalized": [] }, { "id": "11013", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 1680, 1694 ] ], "normalized": [] }, { "id": "11014", "type": "Chemicals & Drugs", "text": [ "[3H]A-804598" ], "offsets": [ [ 1717, 1729 ] ], "normalized": [] }, { "id": "11015", "type": "Genes & Molecular Sequences", "text": [ "P2X7 receptors" ], "offsets": [ [ 1801, 1815 ] ], "normalized": [] }, { "id": "11016", "type": "", "text": [ "[3H]A-804598" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "11017", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 136, 150 ] ], "normalized": [] }, { "id": "11019", "type": "", "text": [ "[3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine" ], "offsets": [ [ 14, 73 ] ], "normalized": [] }, { "id": "11020", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 136, 150 ] ], "normalized": [] }, { "id": "11022", "type": "", "text": [ "calcium" ], "offsets": [ [ 358, 365 ] ], "normalized": [] }, { "id": "11023", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 303, 317 ] ], "normalized": [] }, { "id": "11025", "type": "", "text": [ "A-804598" ], "offsets": [ [ 733, 741 ] ], "normalized": [] }, { "id": "11026", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 915, 929 ] ], "normalized": [] }, { "id": "11028", "type": "", "text": [ "A-804598" ], "offsets": [ [ 931, 939 ] ], "normalized": [] }, { "id": "11029", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 992, 1000 ] ], "normalized": [] }, { "id": "11031", "type": "", "text": [ "A-804598" ], "offsets": [ [ 931, 939 ] ], "normalized": [] }, { "id": "11032", "type": "", "text": [ "Yo-Pro" ], "offsets": [ [ 1005, 1011 ] ], "normalized": [] }, { "id": "11034", "type": "", "text": [ "P2X antagonists" ], "offsets": [ [ 1432, 1447 ] ], "normalized": [] }, { "id": "11035", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1544, 1558 ] ], "normalized": [] }, { "id": "11037", "type": "", "text": [ "A-804598" ], "offsets": [ [ 1605, 1613 ] ], "normalized": [] }, { "id": "11038", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1801, 1815 ] ], "normalized": [] }, { "id": "11040", "type": "", "text": [ "[3H]A-804598" ], "offsets": [ [ 1717, 1729 ] ], "normalized": [] }, { "id": "11041", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1801, 1815 ] ], "normalized": [] }, { "id": "11043", "type": "", "text": [ "ATP-sensitive P2X7 receptors" ], "offsets": [ [ 152, 180 ] ], "normalized": [] }, { "id": "11044", "type": "", "text": [ "ATP-sensitive P2X7 receptors" ], "offsets": [ [ 152, 180 ] ], "normalized": [] }, { "id": "11046", "type": "", "text": [ "calcium" ], "offsets": [ [ 358, 365 ] ], "normalized": [] }, { "id": "11047", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 423, 431 ] ], "normalized": [] }, { "id": "11049", "type": "", "text": [ "P2X7 receptor" ], "offsets": [ [ 626, 639 ] ], "normalized": [] }, { "id": "11050", "type": "", "text": [ "inflammation" ], "offsets": [ [ 654, 666 ] ], "normalized": [] }, { "id": "11052", "type": "", "text": [ "P2X7 receptor" ], "offsets": [ [ 626, 639 ] ], "normalized": [] }, { "id": "11053", "type": "", "text": [ "pain" ], "offsets": [ [ 671, 675 ] ], "normalized": [] }, { "id": "11055", "type": "", "text": [ "A-804598" ], "offsets": [ [ 931, 939 ] ], "normalized": [] }, { "id": "11056", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1079, 1093 ] ], "normalized": [] }, { "id": "11058", "type": "", "text": [ "[3H]A-804598" ], "offsets": [ [ 1225, 1237 ] ], "normalized": [] }, { "id": "11059", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1183, 1197 ] ], "normalized": [] }, { "id": "11061", "type": "", "text": [ "[3H]A-804598" ], "offsets": [ [ 1459, 1471 ] ], "normalized": [] }, { "id": "11062", "type": "", "text": [ "P2X7 receptors" ], "offsets": [ [ 1544, 1558 ] ], "normalized": [] }, { "id": "11064", "type": "", "text": [ "[3H]A-804598" ], "offsets": [ [ 1459, 1471 ] ], "normalized": [] }, { "id": "11065", "type": "", "text": [ "P2X antagonists" ], "offsets": [ [ 1432, 1447 ] ], "normalized": [] }, { "id": "11067", "type": "", "text": [ "A-804598" ], "offsets": [ [ 733, 741 ] ], "normalized": [] }, { "id": "11068", "type": "", "text": [ "P2X7" ], "offsets": [ [ 709, 713 ] ], "normalized": [] }, { "id": "11070", "type": "", "text": [ "A-804598" ], "offsets": [ [ 931, 939 ] ], "normalized": [] }, { "id": "11071", "type": "", "text": [ "THP-1 cells" ], "offsets": [ [ 1039, 1050 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11018", "type": "PA", "arg1_id": "11016", "arg2_id": "11017", "normalized": [] }, { "id": "11021", "type": "PA", "arg1_id": "11019", "arg2_id": "11020", "normalized": [] }, { "id": "11024", "type": "PA", "arg1_id": "11022", "arg2_id": "11023", "normalized": [] }, { "id": "11027", "type": "PA", "arg1_id": "11025", "arg2_id": "11026", "normalized": [] }, { "id": "11030", "type": "PA", "arg1_id": "11028", "arg2_id": "11029", "normalized": [] }, { "id": "11033", "type": "PA", "arg1_id": "11031", "arg2_id": "11032", "normalized": [] }, { "id": "11036", "type": "PA", "arg1_id": "11034", "arg2_id": "11035", "normalized": [] }, { "id": "11039", "type": "PA", "arg1_id": "11037", "arg2_id": "11038", "normalized": [] }, { "id": "11042", "type": "PA", "arg1_id": "11040", "arg2_id": "11041", "normalized": [] }, { "id": "11045", "type": "PA", "arg1_id": "11043", "arg2_id": "11044", "normalized": [] }, { "id": "11048", "type": "PA", "arg1_id": "11046", "arg2_id": "11047", "normalized": [] }, { "id": "11051", "type": "PA", "arg1_id": "11049", "arg2_id": "11050", "normalized": [] }, { "id": "11054", "type": "PA", "arg1_id": "11052", "arg2_id": "11053", "normalized": [] }, { "id": "11057", "type": "PA", "arg1_id": "11055", "arg2_id": "11056", "normalized": [] }, { "id": "11060", "type": "PA", "arg1_id": "11058", "arg2_id": "11059", "normalized": [] }, { "id": "11063", "type": "PA", "arg1_id": "11061", "arg2_id": "11062", "normalized": [] }, { "id": "11066", "type": "PA", "arg1_id": "11064", "arg2_id": "11065", "normalized": [] }, { "id": "11069", "type": "PA", "arg1_id": "11067", "arg2_id": "11068", "normalized": [] }, { "id": "11072", "type": "PA", "arg1_id": "11070", "arg2_id": "11071", "normalized": [] } ]

[ { "id": "11075", "type": "title", "text": [ "Hypogonadism in Wegener's granulomatosis." ], "offsets": [ [ 0, 41 ] ] }, { "id": "11076", "type": "abstract", "text": [ "OBJECTIVE: Current developments in the management of Wegener's granulomatosis (WG) focus on adoption of therapeutic strategies to avoid complications of both the disease and its therapy. Systematic analyses with respect to the reproductive system in WG are missing. METHODS: Data of a cross-sectional study of sexual hormones in 19 male WG patients were analysed. Disease extension was classified according to the ears, nose, and throat (E), lungs (L), and kidneys (K) classification (ELK classification) and to the disease extent index (DEI). Laboratory investigation included measurement of gonadotrophins, oestradiol, and total serum testosterone. Hypogonadism was defined by an increase in follicle-stimulating hormone (FSH) beyond twice the upper reference range in the presence of low serum testosterone. Thirty-eight age-matched men served as controls. RESULTS: Hypogonadism was found in 52.6% of the patients but was not detectable in any of the controls (p<0.0001). No significant correlation to any clinical factor of systemic vasculitis, current or past medication was detected. In particular, testosterone or FSH levels were not correlated with current or cumulative use of cyclophosphamide or corticosteroids (p = 0.417, p = 0.293; p = 0.893, p = 0.317). CONCLUSION: Data of our study revealed an unexpected high rate of hypogonadism irrespective of cyclophosphamide use, and subclinical involvement of the testes by the vasculitis itself might be an alternative explanation. Screening during the course of the disease is reasonable as hypogonadism might severely affect patients' quality of life. Further prospective studies with respect to gender-specific changes in the reproductive system are warranted." ], "offsets": [ [ 42, 1762 ] ] } ]

[ { "id": "11077", "type": "Diseases & Disorders", "text": [ "Hypogonadism" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "11078", "type": "Diseases & Disorders", "text": [ "Wegener's granulomatosis" ], "offsets": [ [ 16, 40 ] ], "normalized": [] }, { "id": "11079", "type": "Diseases & Disorders", "text": [ "Wegener's granulomatosis" ], "offsets": [ [ 95, 119 ] ], "normalized": [] }, { "id": "11080", "type": "Diseases & Disorders", "text": [ "WG" ], "offsets": [ [ 121, 123 ] ], "normalized": [] }, { "id": "11081", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 178, 191 ] ], "normalized": [] }, { "id": "11082", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 204, 211 ] ], "normalized": [] }, { "id": "11083", "type": "Diseases & Disorders", "text": [ "WG" ], "offsets": [ [ 292, 294 ] ], "normalized": [] }, { "id": "11084", "type": "Chemicals & Drugs", "text": [ "sexual hormones" ], "offsets": [ [ 352, 367 ] ], "normalized": [] }, { "id": "11085", "type": "Diseases & Disorders", "text": [ "WG" ], "offsets": [ [ 379, 381 ] ], "normalized": [] }, { "id": "11086", "type": "Diseases & Disorders", "text": [ "Disease" ], "offsets": [ [ 406, 413 ] ], "normalized": [] }, { "id": "11087", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 558, 565 ] ], "normalized": [] }, { "id": "11088", "type": "Chemicals & Drugs", "text": [ "gonadotrophins" ], "offsets": [ [ 635, 649 ] ], "normalized": [] }, { "id": "11089", "type": "Chemicals & Drugs", "text": [ "oestradiol" ], "offsets": [ [ 651, 661 ] ], "normalized": [] }, { "id": "11090", "type": "Chemicals & Drugs", "text": [ "testosterone" ], "offsets": [ [ 679, 691 ] ], "normalized": [] }, { "id": "11091", "type": "Diseases & Disorders", "text": [ "Hypogonadism" ], "offsets": [ [ 693, 705 ] ], "normalized": [] }, { "id": "11092", "type": "Chemicals & Drugs", "text": [ "FSH" ], "offsets": [ [ 766, 769 ] ], "normalized": [] }, { "id": "11093", "type": "Chemicals & Drugs", "text": [ "testosterone" ], "offsets": [ [ 839, 851 ] ], "normalized": [] }, { "id": "11094", "type": "Diseases & Disorders", "text": [ "Hypogonadism" ], "offsets": [ [ 911, 923 ] ], "normalized": [] }, { "id": "11095", "type": "Diseases & Disorders", "text": [ "systemic vasculitis" ], "offsets": [ [ 1070, 1089 ] ], "normalized": [] }, { "id": "11096", "type": "Chemicals & Drugs", "text": [ "testosterone" ], "offsets": [ [ 1147, 1159 ] ], "normalized": [] }, { "id": "11097", "type": "Chemicals & Drugs", "text": [ "FSH" ], "offsets": [ [ 1163, 1166 ] ], "normalized": [] }, { "id": "11098", "type": "Chemicals & Drugs", "text": [ "cyclophosphamide" ], "offsets": [ [ 1228, 1244 ] ], "normalized": [] }, { "id": "11099", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 1248, 1263 ] ], "normalized": [] }, { "id": "11100", "type": "Diseases & Disorders", "text": [ "hypogonadism" ], "offsets": [ [ 1376, 1388 ] ], "normalized": [] }, { "id": "11101", "type": "Chemicals & Drugs", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11102", "type": "Diseases & Disorders", "text": [ "testes" ], "offsets": [ [ 1462, 1468 ] ], "normalized": [] }, { "id": "11103", "type": "Diseases & Disorders", "text": [ "vasculitis" ], "offsets": [ [ 1476, 1486 ] ], "normalized": [] }, { "id": "11104", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1566, 1573 ] ], "normalized": [] }, { "id": "11105", "type": "Diseases & Disorders", "text": [ "hypogonadism" ], "offsets": [ [ 1591, 1603 ] ], "normalized": [] }, { "id": "11106", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11107", "type": "", "text": [ "hypogonadism" ], "offsets": [ [ 1376, 1388 ] ], "normalized": [] }, { "id": "11109", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11110", "type": "", "text": [ "testes" ], "offsets": [ [ 1462, 1468 ] ], "normalized": [] }, { "id": "11112", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11113", "type": "", "text": [ "vasculitis" ], "offsets": [ [ 1476, 1486 ] ], "normalized": [] }, { "id": "11115", "type": "", "text": [ "testosterone" ], "offsets": [ [ 839, 851 ] ], "normalized": [] }, { "id": "11116", "type": "", "text": [ "Hypogonadism" ], "offsets": [ [ 693, 705 ] ], "normalized": [] }, { "id": "11118", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11119", "type": "", "text": [ "hypogonadism" ], "offsets": [ [ 1376, 1388 ] ], "normalized": [] }, { "id": "11121", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 1405, 1421 ] ], "normalized": [] }, { "id": "11122", "type": "", "text": [ "testes" ], "offsets": [ [ 1462, 1468 ] ], "normalized": [] }, { "id": "11124", "type": "", "text": [ "FSH" ], "offsets": [ [ 766, 769 ] ], "normalized": [] }, { "id": "11125", "type": "", "text": [ "Hypogonadism" ], "offsets": [ [ 693, 705 ] ], "normalized": [] } ]

[]

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[ { "id": "11108", "type": "NA", "arg1_id": "11106", "arg2_id": "11107", "normalized": [] }, { "id": "11111", "type": "NA", "arg1_id": "11109", "arg2_id": "11110", "normalized": [] }, { "id": "11114", "type": "PA", "arg1_id": "11112", "arg2_id": "11113", "normalized": [] }, { "id": "11117", "type": "PA", "arg1_id": "11115", "arg2_id": "11116", "normalized": [] }, { "id": "11120", "type": "PA", "arg1_id": "11118", "arg2_id": "11119", "normalized": [] }, { "id": "11123", "type": "PA", "arg1_id": "11121", "arg2_id": "11122", "normalized": [] }, { "id": "11126", "type": "PA", "arg1_id": "11124", "arg2_id": "11125", "normalized": [] } ]

[ { "id": "11129", "type": "title", "text": [ "Role of transporter genes in cisplatin resistance." ], "offsets": [ [ 0, 50 ] ] }, { "id": "11130", "type": "abstract", "text": [ "The 50% inhibitory concentration (IC50) values for cisplatin from 60 cell lines of the National Cancer Institute (NCI), USA, were correlated with the microarray-based mRNA expression levels of 55 transporter genes. The transporters are known to be involved in multiple drug resistance and belong to different classes, e.g. lysosomal H+ transporting ATPases, Cu2+ transporting ATPases, glutamate transporters of the solute carrier family 31, copper transporters of the solute carrier family 31, and ATP-binding cassette (ABC) transporter genes. The expression levels of 17 genes represented by 21 clones correlated significantly with the IC50 values for cisplatin. Hierarchical cluster analysis further enabled the prediction of the sensitivity or resistance of these cell lines to cisplatin with respect to the mRNA expression of these set of transporter genes under study. One among the 17 genes studied is ATP7B which is involved in the transport of copper ions across the cell membrane into the cell. We conclude that our microarray-based approach is a feasible and effective tool in identifying prognostic markers for drug resistance in antitumor therapy." ], "offsets": [ [ 51, 1210 ] ] } ]

[ { "id": "11131", "type": "Chemicals & Drugs", "text": [ "cisplatin" ], "offsets": [ [ 29, 38 ] ], "normalized": [] }, { "id": "11132", "type": "Chemicals & Drugs", "text": [ "cisplatin" ], "offsets": [ [ 102, 111 ] ], "normalized": [] }, { "id": "11133", "type": "Genes & Molecular Sequences", "text": [ "lysosomal H+" ], "offsets": [ [ 374, 386 ] ], "normalized": [] }, { "id": "11134", "type": "Genes & Molecular Sequences", "text": [ "transporting ATPases" ], "offsets": [ [ 387, 407 ] ], "normalized": [] }, { "id": "11135", "type": "Genes & Molecular Sequences", "text": [ "Cu2+" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "11136", "type": "Genes & Molecular Sequences", "text": [ "transporting ATPases" ], "offsets": [ [ 414, 434 ] ], "normalized": [] }, { "id": "11137", "type": "Genes & Molecular Sequences", "text": [ "glutamate transporters of the solute carrier family 31" ], "offsets": [ [ 436, 490 ] ], "normalized": [] }, { "id": "11138", "type": "Genes & Molecular Sequences", "text": [ "solute carrier" ], "offsets": [ [ 466, 480 ] ], "normalized": [] }, { "id": "11139", "type": "Genes & Molecular Sequences", "text": [ "copper transporters of the solute carrier family 31" ], "offsets": [ [ 492, 543 ] ], "normalized": [] }, { "id": "11140", "type": "Genes & Molecular Sequences", "text": [ "solute carrier" ], "offsets": [ [ 519, 533 ] ], "normalized": [] }, { "id": "11141", "type": "Genes & Molecular Sequences", "text": [ "ATP-binding cassette" ], "offsets": [ [ 549, 569 ] ], "normalized": [] }, { "id": "11142", "type": "Genes & Molecular Sequences", "text": [ "ABC) transporter" ], "offsets": [ [ 571, 587 ] ], "normalized": [] }, { "id": "11143", "type": "Chemicals & Drugs", "text": [ "ABC) transporter" ], "offsets": [ [ 571, 587 ] ], "normalized": [] }, { "id": "11144", "type": "Chemicals & Drugs", "text": [ "cisplatin" ], "offsets": [ [ 704, 713 ] ], "normalized": [] }, { "id": "11145", "type": "Chemicals & Drugs", "text": [ "cisplatin" ], "offsets": [ [ 832, 841 ] ], "normalized": [] }, { "id": "11146", "type": "Genes & Molecular Sequences", "text": [ "ATP7B" ], "offsets": [ [ 959, 964 ] ], "normalized": [] }, { "id": "11147", "type": "Chemicals & Drugs", "text": [ "copper ions" ], "offsets": [ [ 1003, 1014 ] ], "normalized": [] }, { "id": "11148", "type": "Chemicals & Drugs", "text": [ "antitumor therapy" ], "offsets": [ [ 1192, 1209 ] ], "normalized": [] }, { "id": "11149", "type": "", "text": [ "copper ions" ], "offsets": [ [ 1003, 1014 ] ], "normalized": [] }, { "id": "11150", "type": "", "text": [ "ATP7B" ], "offsets": [ [ 959, 964 ] ], "normalized": [] }, { "id": "11152", "type": "", "text": [ "ABC) transporter" ], "offsets": [ [ 571, 587 ] ], "normalized": [] }, { "id": "11153", "type": "", "text": [ "solute carrier" ], "offsets": [ [ 519, 533 ] ], "normalized": [] }, { "id": "11155", "type": "", "text": [ "glutamate transporters of the solute carrier family 31" ], "offsets": [ [ 436, 490 ] ], "normalized": [] }, { "id": "11156", "type": "", "text": [ "drug" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "11158", "type": "", "text": [ "copper transporters of the solute carrier family 31" ], "offsets": [ [ 492, 543 ] ], "normalized": [] }, { "id": "11159", "type": "", "text": [ "drug" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "11161", "type": "", "text": [ "ATP-binding cassette" ], "offsets": [ [ 549, 569 ] ], "normalized": [] }, { "id": "11162", "type": "", "text": [ "drug" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "11164", "type": "", "text": [ "ABC) transporter" ], "offsets": [ [ 571, 587 ] ], "normalized": [] }, { "id": "11165", "type": "", "text": [ "drug" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "11167", "type": "", "text": [ "transporting ATPases" ], "offsets": [ [ 414, 434 ] ], "normalized": [] }, { "id": "11168", "type": "", "text": [ "drug" ], "offsets": [ [ 320, 324 ] ], "normalized": [] } ]

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[ { "id": "11151", "type": "PA", "arg1_id": "11149", "arg2_id": "11150", "normalized": [] }, { "id": "11154", "type": "PA", "arg1_id": "11152", "arg2_id": "11153", "normalized": [] }, { "id": "11157", "type": "PA", "arg1_id": "11155", "arg2_id": "11156", "normalized": [] }, { "id": "11160", "type": "PA", "arg1_id": "11158", "arg2_id": "11159", "normalized": [] }, { "id": "11163", "type": "PA", "arg1_id": "11161", "arg2_id": "11162", "normalized": [] }, { "id": "11166", "type": "PA", "arg1_id": "11164", "arg2_id": "11165", "normalized": [] }, { "id": "11169", "type": "PA", "arg1_id": "11167", "arg2_id": "11168", "normalized": [] } ]

[ { "id": "11172", "type": "title", "text": [ "Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk." ], "offsets": [ [ 0, 101 ] ] }, { "id": "11173", "type": "abstract", "text": [ "One purpose for seeking common alleles that are associated with disease is to use them to improve models for projecting individualized disease risk. Two genome-wide association studies and a study of candidate genes recently identified seven common single-nucleotide polymorphisms (SNPs) that were associated with breast cancer risk in independent samples. These seven SNPs were located in FGFR2, TNRC9 (now known as TOX3), MAP3K1, LSP1, CASP8, chromosomal region 8q, and chromosomal region 2q35. I used estimates of relative risks and allele frequencies from these studies to estimate how much these SNPs could improve discriminatory accuracy measured as the area under the receiver operating characteristic curve (AUC). A model with these seven SNPs (AUC = 0.574) and a hypothetical model with 14 such SNPs (AUC = 0.604) have less discriminatory accuracy than a model, the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT), that is based on ages at menarche and at first live birth, family history of breast cancer, and history of breast biopsy examinations (AUC = 0.607). Adding the seven SNPs to BCRAT improved discriminatory accuracy to an AUC of 0.632, which was, however, less than the improvement from adding mammographic density. Thus, these seven common alleles provide less discriminatory accuracy than BCRAT but have the potential to improve the discriminatory accuracy of BCRAT modestly. Experience to date and quantitative arguments indicate that a huge increase in the numbers of case patients with breast cancer and control subjects would be required in genome-wide association studies to find enough SNPs to achieve high discriminatory accuracy." ], "offsets": [ [ 102, 1785 ] ] } ]

[ { "id": "11174", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 82, 95 ] ], "normalized": [] }, { "id": "11175", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 166, 173 ] ], "normalized": [] }, { "id": "11176", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 237, 244 ] ], "normalized": [] }, { "id": "11177", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 416, 429 ] ], "normalized": [] }, { "id": "11178", "type": "Genes & Molecular Sequences", "text": [ "FGFR2" ], "offsets": [ [ 492, 497 ] ], "normalized": [] }, { "id": "11179", "type": "Genes & Molecular Sequences", "text": [ "TNRC9" ], "offsets": [ [ 499, 504 ] ], "normalized": [] }, { "id": "11180", "type": "Genes & Molecular Sequences", "text": [ "TOX3" ], "offsets": [ [ 519, 523 ] ], "normalized": [] }, { "id": "11181", "type": "Genes & Molecular Sequences", "text": [ "MAP3K1" ], "offsets": [ [ 526, 532 ] ], "normalized": [] }, { "id": "11182", "type": "Genes & Molecular Sequences", "text": [ "LSP1" ], "offsets": [ [ 534, 538 ] ], "normalized": [] }, { "id": "11183", "type": "Genes & Molecular Sequences", "text": [ "CASP8" ], "offsets": [ [ 540, 545 ] ], "normalized": [] }, { "id": "11184", "type": "Genes & Molecular Sequences", "text": [ "8q" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "11185", "type": "Genes & Molecular Sequences", "text": [ "2q35" ], "offsets": [ [ 593, 597 ] ], "normalized": [] }, { "id": "11186", "type": "Diseases & Disorders", "text": [ "Cancer" ], "offsets": [ [ 986, 992 ] ], "normalized": [] }, { "id": "11187", "type": "Diseases & Disorders", "text": [ "Breast Cancer" ], "offsets": [ [ 1005, 1018 ] ], "normalized": [] }, { "id": "11188", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 1126, 1139 ] ], "normalized": [] }, { "id": "11189", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 1637, 1650 ] ], "normalized": [] } ]

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[ { "id": "11192", "type": "title", "text": [ "Molecular determinants for the interaction of human neutrophil alpha defensin 1 with its propeptide." ], "offsets": [ [ 0, 100 ] ] }, { "id": "11193", "type": "abstract", "text": [ "Human neutrophil alpha-defensins (HNPs) are cationic antimicrobial peptides that are synthesized in vivo as inactive precursors (proHNPs). Activation requires proteolytic excision of their anionic N-terminal inhibitory pro peptide. The pro peptide of proHNP1 also interacts specifically with and inhibits the antimicrobial activity of HNP1 inter-molecularly. In the light of the opposite net charges segregated in proHNP1, functional inhibition of the C-terminal defensin domain by its propeptide is generally thought to be of electrostatic nature. Using a battery of analogs of the propeptide and of proHNP1, we identified residues in the propeptide region important for HNP1 binding and inhibition. Only three anionic residues in the propeptide, Glu(15), Asp(20) and Glu(23), were modestly important for interactions with HNP1. By contrast, the hydrophobic residues in the central part of the propeptide, and the conserved hydrophobic motif Val(24)Val(25)Val(26)Leu(28) in particular, were critical for HNP1 binding and inhibition. Neutralization of all negative charges in the propeptide only partially activated the bactericidal activity of proHNP1. Our data indicate that hydrophobic forces have a dominant role in mediating the interactions between HNP1 and its propeptide--a finding largely contrasting the commonly held view that the interactions are of an electrostatic nature." ], "offsets": [ [ 101, 1487 ] ] } ]

[ { "id": "11194", "type": "Genes & Molecular Sequences", "text": [ "human neutrophil alpha defensin 1" ], "offsets": [ [ 46, 79 ] ], "normalized": [] }, { "id": "11195", "type": "Genes & Molecular Sequences", "text": [ "defensin" ], "offsets": [ [ 69, 77 ] ], "normalized": [] }, { "id": "11196", "type": "Genes & Molecular Sequences", "text": [ "Human neutrophil alpha-defensins" ], "offsets": [ [ 101, 133 ] ], "normalized": [] }, { "id": "11197", "type": "Genes & Molecular Sequences", "text": [ "HNPs" ], "offsets": [ [ 135, 139 ] ], "normalized": [] }, { "id": "11198", "type": "Genes & Molecular Sequences", "text": [ "cationic antimicrobial peptides" ], "offsets": [ [ 145, 176 ] ], "normalized": [] }, { "id": "11199", "type": "Genes & Molecular Sequences", "text": [ "proHNPs" ], "offsets": [ [ 230, 237 ] ], "normalized": [] }, { "id": "11200", "type": "Genes & Molecular Sequences", "text": [ "anionic N-terminal inhibitory pro peptide" ], "offsets": [ [ 290, 331 ] ], "normalized": [] }, { "id": "11201", "type": "Genes & Molecular Sequences", "text": [ "proHNP1" ], "offsets": [ [ 352, 359 ] ], "normalized": [] }, { "id": "11202", "type": "Genes & Molecular Sequences", "text": [ "HNP1" ], "offsets": [ [ 436, 440 ] ], "normalized": [] }, { "id": "11203", "type": "Chemicals & Drugs", "text": [ "net" ], "offsets": [ [ 489, 492 ] ], "normalized": [] }, { "id": "11204", "type": "Genes & Molecular Sequences", "text": [ "proHNP1" ], "offsets": [ [ 515, 522 ] ], "normalized": [] }, { "id": "11205", "type": "Genes & Molecular Sequences", "text": [ "C-terminal defensin domain" ], "offsets": [ [ 553, 579 ] ], "normalized": [] }, { "id": "11206", "type": "Genes & Molecular Sequences", "text": [ "proHNP1" ], "offsets": [ [ 702, 709 ] ], "normalized": [] }, { "id": "11207", "type": "Genes & Molecular Sequences", "text": [ "HNP1" ], "offsets": [ [ 773, 777 ] ], "normalized": [] }, { "id": "11208", "type": "Genes & Molecular Sequences", "text": [ "Glu(15)" ], "offsets": [ [ 849, 856 ] ], "normalized": [] }, { "id": "11209", "type": "Genes & Molecular Sequences", "text": [ "Asp(20)" ], "offsets": [ [ 858, 865 ] ], "normalized": [] }, { "id": "11210", "type": "Chemicals & Drugs", "text": [ "Asp(20)" ], "offsets": [ [ 858, 865 ] ], "normalized": [] }, { "id": "11211", "type": "Genes & Molecular Sequences", "text": [ "Glu(23)" ], "offsets": [ [ 870, 877 ] ], "normalized": [] }, { "id": "11212", "type": "Genes & Molecular Sequences", "text": [ "HNP1" ], "offsets": [ [ 925, 929 ] ], "normalized": [] }, { "id": "11213", "type": "Genes & Molecular Sequences", "text": [ "Val(24)Val(25)Val(26)Leu(28)" ], "offsets": [ [ 1044, 1072 ] ], "normalized": [] }, { "id": "11214", "type": "Genes & Molecular Sequences", "text": [ "Val" ], "offsets": [ [ 1051, 1054 ] ], "normalized": [] }, { "id": "11215", "type": "Genes & Molecular Sequences", "text": [ "Val" ], "offsets": [ [ 1058, 1061 ] ], "normalized": [] }, { "id": "11216", "type": "Genes & Molecular Sequences", "text": [ "Leu" ], "offsets": [ [ 1065, 1068 ] ], "normalized": [] }, { "id": "11217", "type": "Genes & Molecular Sequences", "text": [ "HNP1" ], "offsets": [ [ 1106, 1110 ] ], "normalized": [] }, { "id": "11218", "type": "Genes & Molecular Sequences", "text": [ "proHNP1" ], "offsets": [ [ 1246, 1253 ] ], "normalized": [] }, { "id": "11219", "type": "Genes & Molecular Sequences", "text": [ "HNP1" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] } ]

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[ { "id": "11222", "type": "title", "text": [ "Non-organ-specific autoantibodies in renal transplant recipients: relation to BK virus infection." ], "offsets": [ [ 0, 97 ] ] }, { "id": "11223", "type": "abstract", "text": [ "Polyomavirus BK reactivation is common in renal transplant recipients and may cause nephropathy with significant graft dysfunction. The induction of anti-double stranded DNA (anti-dsDNA) antibodies by BKV has been described in experimental animals and during primary infection, and has been implicated in the pathogenesis of systemic lupus erythematosus. This study evaluated the occurrence of anti-dsDNA antibodies and non-organ-specific autoantibodies (NOSA) by indirect immunofluorescence before transplantation and at 3 and 6 months post-transplantation in 90 renal transplant recipients and the association with BKV reactivation, demographic and clinical features. Moreover, the relation to HCMV infection, as detected by pp65-antigenemia, was also evaluated. Post-transplantation NOSAs were present in 23/90 (25.6%) and anti-dsDNA antibodies in 17/90 (18.9%). BK viremia was detected in at least one serum sample in 22 patients: 9 anti-dsDNA antibody-positive vs 13 negative (p<0.01). No significant correlation between the occurrence of NOSAs and anti-dsDNA antibodies and demographic and clinical features was found. No significant association with pp65-antigenemia-positivity was found, although antigenemia was positive in 6/23 NOSA-positive patients (26.1%). Although a relation seems to exist between BKV and the occurrence of anti-dsDNA antibodies in renal transplant patients, the lack of correlation with other epidemiological and clinical features does not allow any conclusion. The role of autoimmune response in this context and the relation with other patient-related factors and infectious agents should be further investigated." ], "offsets": [ [ 98, 1746 ] ] } ]

[ { "id": "11224", "type": "Diseases & Disorders", "text": [ "BK virus infection" ], "offsets": [ [ 78, 96 ] ], "normalized": [] }, { "id": "11225", "type": "Diseases & Disorders", "text": [ "Polyomavirus BK reactivation" ], "offsets": [ [ 98, 126 ] ], "normalized": [] }, { "id": "11226", "type": "Diseases & Disorders", "text": [ "nephropathy" ], "offsets": [ [ 182, 193 ] ], "normalized": [] }, { "id": "11227", "type": "Diseases & Disorders", "text": [ "graft dysfunction" ], "offsets": [ [ 211, 228 ] ], "normalized": [] }, { "id": "11228", "type": "Diseases & Disorders", "text": [ "BKV" ], "offsets": [ [ 299, 302 ] ], "normalized": [] }, { "id": "11229", "type": "Diseases & Disorders", "text": [ "primary infection" ], "offsets": [ [ 357, 374 ] ], "normalized": [] }, { "id": "11230", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 407, 419 ] ], "normalized": [] }, { "id": "11231", "type": "Diseases & Disorders", "text": [ "systemic lupus erythematosus" ], "offsets": [ [ 423, 451 ] ], "normalized": [] }, { "id": "11232", "type": "Diseases & Disorders", "text": [ "BKV" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "11233", "type": "Diseases & Disorders", "text": [ "HCMV infection" ], "offsets": [ [ 794, 808 ] ], "normalized": [] }, { "id": "11234", "type": "Diseases & Disorders", "text": [ "BK viremia" ], "offsets": [ [ 964, 974 ] ], "normalized": [] }, { "id": "11235", "type": "Diseases & Disorders", "text": [ "BKV" ], "offsets": [ [ 1411, 1414 ] ], "normalized": [] }, { "id": "11236", "type": "Diseases & Disorders", "text": [ "autoimmune response" ], "offsets": [ [ 1605, 1624 ] ], "normalized": [] }, { "id": "11237", "type": "Chemicals & Drugs", "text": [ "infectious" ], "offsets": [ [ 1697, 1707 ] ], "normalized": [] }, { "id": "11238", "type": "Diseases & Disorders", "text": [ "infectious" ], "offsets": [ [ 1697, 1707 ] ], "normalized": [] }, { "id": "11239", "type": "Chemicals & Drugs", "text": [ "agents" ], "offsets": [ [ 1708, 1714 ] ], "normalized": [] } ]

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[ { "id": "11242", "type": "title", "text": [ "Expression of VEGFR-1 (Flt-1) in breast cancer is associated with VEGF expression and with node-negative tumour stage." ], "offsets": [ [ 0, 118 ] ] }, { "id": "11243", "type": "abstract", "text": [ "BACKGROUND: Vascular endothelial growth factor (VEGF) promotes breast cancer progression by inducing angiogenesis via VEGF receptors on endothelial cells but also signals directly through receptors such as VEGFR-1 (Flt-1) expressed on tumour cells. The impact of autocrine signalling loops on treatment with VEGF inhibitors is still unclear. MATERIALS AND METHODS: Six breast cancer cell lines were tested for expression of VEGFR-1 by RT-PCR and Western blot. To assess clinical significance, 93 breast cancer lesions were evaluated for expression of VEGF and VEGFR-1 by immunohistochemistry. RESULTS: VEGFR-1 mRNA was found in all 6 cell lines, while protein expression was found in 5 cell lines. VEGF was expressed in 60% and VEGFR-1 in 39% of breast cancer specimens. VEGFR-1 expression was associated with VEGF expression and with node-negative tumour stage. CONCLUSION: Our data suggest that analysis of VEGF/VEGFR-1 expression might be relevant in identifying patients with different response rates upon treatment with antiangiogenic agents." ], "offsets": [ [ 119, 1166 ] ] } ]

[ { "id": "11244", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 14, 21 ] ], "normalized": [] }, { "id": "11245", "type": "Genes & Molecular Sequences", "text": [ "Flt-1" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "11246", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 33, 46 ] ], "normalized": [] }, { "id": "11247", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 66, 70 ] ], "normalized": [] }, { "id": "11248", "type": "Diseases & Disorders", "text": [ "node-negative tumour stage" ], "offsets": [ [ 91, 117 ] ], "normalized": [] }, { "id": "11249", "type": "Diseases & Disorders", "text": [ "tumour" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "11250", "type": "Genes & Molecular Sequences", "text": [ "Vascular endothelial growth factor" ], "offsets": [ [ 131, 165 ] ], "normalized": [] }, { "id": "11251", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 167, 171 ] ], "normalized": [] }, { "id": "11252", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 182, 195 ] ], "normalized": [] }, { "id": "11253", "type": "Genes & Molecular Sequences", "text": [ "VEGF receptors" ], "offsets": [ [ 237, 251 ] ], "normalized": [] }, { "id": "11254", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 325, 332 ] ], "normalized": [] }, { "id": "11255", "type": "Genes & Molecular Sequences", "text": [ "Flt-1" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "11256", "type": "Diseases & Disorders", "text": [ "tumour" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "11257", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "11258", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 446, 451 ] ], "normalized": [] }, { "id": "11259", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 488, 501 ] ], "normalized": [] }, { "id": "11260", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 543, 550 ] ], "normalized": [] }, { "id": "11261", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 615, 628 ] ], "normalized": [] }, { "id": "11262", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "11263", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 679, 686 ] ], "normalized": [] }, { "id": "11264", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 721, 728 ] ], "normalized": [] }, { "id": "11265", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 817, 821 ] ], "normalized": [] }, { "id": "11266", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 847, 854 ] ], "normalized": [] }, { "id": "11267", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 865, 878 ] ], "normalized": [] }, { "id": "11268", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 890, 897 ] ], "normalized": [] }, { "id": "11269", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "11270", "type": "Diseases & Disorders", "text": [ "node-negative tumour stage" ], "offsets": [ [ 954, 980 ] ], "normalized": [] }, { "id": "11271", "type": "Diseases & Disorders", "text": [ "tumour" ], "offsets": [ [ 968, 974 ] ], "normalized": [] }, { "id": "11272", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 1028, 1032 ] ], "normalized": [] }, { "id": "11273", "type": "Genes & Molecular Sequences", "text": [ "VEGFR-1" ], "offsets": [ [ 1033, 1040 ] ], "normalized": [] }, { "id": "11274", "type": "", "text": [ "Flt-1" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "11275", "type": "", "text": [ "node-negative tumour stage" ], "offsets": [ [ 91, 117 ] ], "normalized": [] }, { "id": "11277", "type": "", "text": [ "VEGF" ], "offsets": [ [ 167, 171 ] ], "normalized": [] }, { "id": "11278", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 182, 195 ] ], "normalized": [] }, { "id": "11280", "type": "", "text": [ "VEGF" ], "offsets": [ [ 817, 821 ] ], "normalized": [] }, { "id": "11281", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 865, 878 ] ], "normalized": [] }, { "id": "11283", "type": "", "text": [ "VEGFR-1" ], "offsets": [ [ 847, 854 ] ], "normalized": [] }, { "id": "11284", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 865, 878 ] ], "normalized": [] }, { "id": "11286", "type": "", "text": [ "VEGFR-1" ], "offsets": [ [ 890, 897 ] ], "normalized": [] }, { "id": "11287", "type": "", "text": [ "node-negative tumour stage" ], "offsets": [ [ 954, 980 ] ], "normalized": [] }, { "id": "11289", "type": "", "text": [ "VEGF" ], "offsets": [ [ 66, 70 ] ], "normalized": [] }, { "id": "11290", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 33, 46 ] ], "normalized": [] }, { "id": "11292", "type": "", "text": [ "VEGF" ], "offsets": [ [ 66, 70 ] ], "normalized": [] }, { "id": "11293", "type": "", "text": [ "tumour" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "11295", "type": "", "text": [ "Flt-1" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "11296", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 33, 46 ] ], "normalized": [] }, { "id": "11298", "type": "", "text": [ "Flt-1" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "11299", "type": "", "text": [ "tumour" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "11301", "type": "", "text": [ "VEGF receptors" ], "offsets": [ [ 237, 251 ] ], "normalized": [] }, { "id": "11302", "type": "", "text": [ "tumour" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "11304", "type": "", "text": [ "Flt-1" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "11305", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 182, 195 ] ], "normalized": [] }, { "id": "11307", "type": "", "text": [ "Flt-1" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "11308", "type": "", "text": [ "tumour" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "11310", "type": "", "text": [ "VEGF" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "11311", "type": "", "text": [ "still" ], "offsets": [ [ 446, 451 ] ], "normalized": [] }, { "id": "11313", "type": "", "text": [ "VEGFR-1" ], "offsets": [ [ 543, 550 ] ], "normalized": [] }, { "id": "11314", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 488, 501 ] ], "normalized": [] }, { "id": "11316", "type": "", "text": [ "VEGF" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "11317", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 615, 628 ] ], "normalized": [] }, { "id": "11319", "type": "", "text": [ "VEGFR-1" ], "offsets": [ [ 679, 686 ] ], "normalized": [] }, { "id": "11320", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 615, 628 ] ], "normalized": [] }, { "id": "11322", "type": "", "text": [ "VEGF" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "11323", "type": "", "text": [ "tumour" ], "offsets": [ [ 968, 974 ] ], "normalized": [] }, { "id": "11325", "type": "", "text": [ "VEGFR-1" ], "offsets": [ [ 890, 897 ] ], "normalized": [] }, { "id": "11326", "type": "", "text": [ "tumour" ], "offsets": [ [ 968, 974 ] ], "normalized": [] }, { "id": "11328", "type": "", "text": [ "Vascular endothelial growth factor" ], "offsets": [ [ 131, 165 ] ], "normalized": [] }, { "id": "11329", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 182, 195 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11276", "type": "PA", "arg1_id": "11274", "arg2_id": "11275", "normalized": [] }, { "id": "11279", "type": "PA", "arg1_id": "11277", "arg2_id": "11278", "normalized": [] }, { "id": "11282", "type": "PA", "arg1_id": "11280", "arg2_id": "11281", "normalized": [] }, { "id": "11285", "type": "PA", "arg1_id": "11283", "arg2_id": "11284", "normalized": [] }, { "id": "11288", "type": "PA", "arg1_id": "11286", "arg2_id": "11287", "normalized": [] }, { "id": "11291", "type": "PA", "arg1_id": "11289", "arg2_id": "11290", "normalized": [] }, { "id": "11294", "type": "PA", "arg1_id": "11292", "arg2_id": "11293", "normalized": [] }, { "id": "11297", "type": "PA", "arg1_id": "11295", "arg2_id": "11296", "normalized": [] }, { "id": "11300", "type": "PA", "arg1_id": "11298", "arg2_id": "11299", "normalized": [] }, { "id": "11303", "type": "PA", "arg1_id": "11301", "arg2_id": "11302", "normalized": [] }, { "id": "11306", "type": "PA", "arg1_id": "11304", "arg2_id": "11305", "normalized": [] }, { "id": "11309", "type": "PA", "arg1_id": "11307", "arg2_id": "11308", "normalized": [] }, { "id": "11312", "type": "PA", "arg1_id": "11310", "arg2_id": "11311", "normalized": [] }, { "id": "11315", "type": "PA", "arg1_id": "11313", "arg2_id": "11314", "normalized": [] }, { "id": "11318", "type": "PA", "arg1_id": "11316", "arg2_id": "11317", "normalized": [] }, { "id": "11321", "type": "PA", "arg1_id": "11319", "arg2_id": "11320", "normalized": [] }, { "id": "11324", "type": "PA", "arg1_id": "11322", "arg2_id": "11323", "normalized": [] }, { "id": "11327", "type": "PA", "arg1_id": "11325", "arg2_id": "11326", "normalized": [] }, { "id": "11330", "type": "PA", "arg1_id": "11328", "arg2_id": "11329", "normalized": [] } ]

[ { "id": "11333", "type": "title", "text": [ "Epigenetic mapping and functional analysis in a breast cancer metastasis model using whole-genome promoter tiling microarrays." ], "offsets": [ [ 0, 126 ] ] }, { "id": "11334", "type": "abstract", "text": [ "INTRODUCTION: Breast cancer metastasis is a complex, multi-step biological process. Genetic mutations along with epigenetic alterations in the form of DNA methylation patterns and histone modifications contribute to metastasis-related gene expression changes and genomic instability. So far, these epigenetic contributions to breast cancer metastasis have not been well characterized, and there is only a limited understanding of the functional mechanisms affected by such epigenetic alterations. Furthermore, no genome-wide assessments have been undertaken to identify altered DNA methylation patterns in the context of metastasis and their effects on specific functional pathways or gene networks. METHODS: We have used a human gene promoter tiling microarray platform to analyze a cell line model of metastasis to lymph nodes composed of a poorly metastatic MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic variant (468LN). Gene networks and pathways associated with metastasis were identified, and target genes associated with epithelial-mesenchymal transition were validated with respect to DNA methylation effects on gene expression. RESULTS: We integrated data from the tiling microarrays with targets identified by Ingenuity Pathways Analysis software and observed epigenetic variations in genes implicated in epithelial-mesenchymal transition and with tumor cell migration. We identified widespread genomic hypermethylation and hypomethylation events in these cells and we confirmed functional associations between methylation status and expression of the CDH1, CST6, EGFR, SNAI2 and ZEB2 genes by quantitative real-time PCR. Our data also suggest that the complex genomic reorganization present in cancer cells may be superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes. CONCLUSION: This is the first whole-genome approach to identify genome-wide and gene-specific epigenetic alterations, and the functional consequences of these changes, in the context of breast cancer metastasis to lymph nodes. This approach allows the development of epigenetic signatures of metastasis to be used concurrently with genomic signatures to improve mapping of the evolving molecular landscape of metastasis and to permit translational approaches to target epigenetically regulated molecular pathways related to metastatic progression." ], "offsets": [ [ 127, 2545 ] ] } ]

[ { "id": "11335", "type": "Diseases & Disorders", "text": [ "breast cancer metastasis" ], "offsets": [ [ 48, 72 ] ], "normalized": [] }, { "id": "11336", "type": "Diseases & Disorders", "text": [ "Breast cancer metastasis" ], "offsets": [ [ 141, 165 ] ], "normalized": [] }, { "id": "11337", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 219, 228 ] ], "normalized": [] }, { "id": "11338", "type": "Genes & Molecular Sequences", "text": [ "histone" ], "offsets": [ [ 307, 314 ] ], "normalized": [] }, { "id": "11339", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 343, 353 ] ], "normalized": [] }, { "id": "11340", "type": "Diseases & Disorders", "text": [ "genomic instability" ], "offsets": [ [ 390, 409 ] ], "normalized": [] }, { "id": "11341", "type": "Diseases & Disorders", "text": [ "breast cancer metastasis" ], "offsets": [ [ 453, 477 ] ], "normalized": [] }, { "id": "11342", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 748, 758 ] ], "normalized": [] }, { "id": "11343", "type": "Diseases & Disorders", "text": [ "metastasis to lymph nodes" ], "offsets": [ [ 930, 955 ] ], "normalized": [] }, { "id": "11344", "type": "Diseases & Disorders", "text": [ "breast adenocarcinoma" ], "offsets": [ [ 1008, 1029 ] ], "normalized": [] }, { "id": "11345", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 1126, 1136 ] ], "normalized": [] }, { "id": "11346", "type": "Diseases & Disorders", "text": [ "transition" ], "offsets": [ [ 1210, 1220 ] ], "normalized": [] }, { "id": "11347", "type": "Diseases & Disorders", "text": [ "transition" ], "offsets": [ [ 1497, 1507 ] ], "normalized": [] }, { "id": "11348", "type": "Diseases & Disorders", "text": [ "tumor cell migration" ], "offsets": [ [ 1517, 1537 ] ], "normalized": [] }, { "id": "11349", "type": "Genes & Molecular Sequences", "text": [ "CDH1" ], "offsets": [ [ 1721, 1725 ] ], "normalized": [] }, { "id": "11350", "type": "Genes & Molecular Sequences", "text": [ "CST6" ], "offsets": [ [ 1727, 1731 ] ], "normalized": [] }, { "id": "11351", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 1733, 1737 ] ], "normalized": [] }, { "id": "11352", "type": "Genes & Molecular Sequences", "text": [ "SNAI2" ], "offsets": [ [ 1739, 1744 ] ], "normalized": [] }, { "id": "11353", "type": "Genes & Molecular Sequences", "text": [ "ZEB2" ], "offsets": [ [ 1749, 1753 ] ], "normalized": [] }, { "id": "11354", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 1864, 1870 ] ], "normalized": [] }, { "id": "11355", "type": "Diseases & Disorders", "text": [ "breast cancer metastasis" ], "offsets": [ [ 2184, 2208 ] ], "normalized": [] }, { "id": "11356", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 2290, 2300 ] ], "normalized": [] }, { "id": "11357", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 2407, 2417 ] ], "normalized": [] } ]

[]

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[ { "id": "11360", "type": "title", "text": [ "Review of recent results of montelukast use as a monotherapy in children with mild asthma." ], "offsets": [ [ 0, 90 ] ] }, { "id": "11361", "type": "abstract", "text": [ "BACKGROUND: Asthma is a chronic disease with a heterogeneous phenotype that is often associated with allergic sensitization in childhood. The earliest definable form of asthma is mild (intermittent or persistent), a severity level that may be characteristic of a majority of children with asthma. Several asthma controllers are indicated for use in children. International guidelines recommend the use of inhaled corticosteroids as the preferred controller therapy in mild persistent asthma. OBJECTIVE: This article reviewed recent results from randomized, double-blind studies of children with mild asthma treated with montelukast, a leukotriene receptor antagonist that is approved for the treatment of asthma and allergic rhinitis in children and adults. METHODS: A literature search of MEDLINE was conducted to gather relevant, English-language articles using search terms such as randomized controlled studies, double-blind studies, montelukast, leukotriene receptor antagonist, pediatric asthma, mild asthma, exercise-induced asthma, and bronchoconstriction. Recent articles (since 1998) that described the use of montelukast as a monotherapy were chosen for this review. RESULTS: Relevant studies included a 48-week, placebo-controlled study of 2- to 5-year-old mild intermittent asthmatics (N = 549); a 12-week, placebo-controlled study of 2- to 5-year-old mild persistent asthmatics (N = 689); an analysis of a mild persistent asthmatic cohort (N = 138) from an 8-week, placebo-controlled study of 6- to 14-year-old asthmatics; a 12-month study comparing montelukast with fluticasone in 6- to 14-year-old mild persistent asthmatics (N = 949); and 3 placebo-controlled studies in children with exercise-induced asthma (N = 123). The results from these studies, encompassing end points measuring lung function and symptoms, found that montelukast provided effective and beneficial asthma control to children aged 2 to 14 years with mild asthma. CONCLUSION: The evidence suggests that montelukast is an effective monotherapy controller in children with mild asthma." ], "offsets": [ [ 91, 2162 ] ] } ]

[ { "id": "11362", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 28, 39 ] ], "normalized": [] }, { "id": "11363", "type": "Diseases & Disorders", "text": [ "mild asthma" ], "offsets": [ [ 78, 89 ] ], "normalized": [] }, { "id": "11364", "type": "Diseases & Disorders", "text": [ "Asthma" ], "offsets": [ [ 103, 109 ] ], "normalized": [] }, { "id": "11365", "type": "Diseases & Disorders", "text": [ "chronic disease" ], "offsets": [ [ 115, 130 ] ], "normalized": [] }, { "id": "11366", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "11367", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 380, 386 ] ], "normalized": [] }, { "id": "11368", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 396, 402 ] ], "normalized": [] }, { "id": "11369", "type": "Chemicals & Drugs", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 496, 519 ] ], "normalized": [] }, { "id": "11370", "type": "Diseases & Disorders", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 496, 519 ] ], "normalized": [] }, { "id": "11371", "type": "Diseases & Disorders", "text": [ "mild persistent asthma" ], "offsets": [ [ 559, 581 ] ], "normalized": [] }, { "id": "11372", "type": "Diseases & Disorders", "text": [ "mild asthma" ], "offsets": [ [ 686, 697 ] ], "normalized": [] }, { "id": "11373", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "11374", "type": "Chemicals & Drugs", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 726, 757 ] ], "normalized": [] }, { "id": "11375", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 796, 802 ] ], "normalized": [] }, { "id": "11376", "type": "Diseases & Disorders", "text": [ "allergic rhinitis" ], "offsets": [ [ 807, 824 ] ], "normalized": [] }, { "id": "11377", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [] }, { "id": "11378", "type": "Chemicals & Drugs", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 1042, 1073 ] ], "normalized": [] }, { "id": "11379", "type": "Diseases & Disorders", "text": [ "pediatric asthma" ], "offsets": [ [ 1075, 1091 ] ], "normalized": [] }, { "id": "11380", "type": "Diseases & Disorders", "text": [ "mild asthma" ], "offsets": [ [ 1093, 1104 ] ], "normalized": [] }, { "id": "11381", "type": "Diseases & Disorders", "text": [ "exercise-induced asthma" ], "offsets": [ [ 1106, 1129 ] ], "normalized": [] }, { "id": "11382", "type": "Diseases & Disorders", "text": [ "bronchoconstriction" ], "offsets": [ [ 1135, 1154 ] ], "normalized": [] }, { "id": "11383", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 1211, 1222 ] ], "normalized": [] }, { "id": "11384", "type": "Diseases & Disorders", "text": [ "mild intermittent asthmatics" ], "offsets": [ [ 1360, 1388 ] ], "normalized": [] }, { "id": "11385", "type": "Diseases & Disorders", "text": [ "asthmatics" ], "offsets": [ [ 1472, 1482 ] ], "normalized": [] }, { "id": "11386", "type": "Diseases & Disorders", "text": [ "mild persistent asthmatic" ], "offsets": [ [ 1511, 1536 ] ], "normalized": [] }, { "id": "11387", "type": "Diseases & Disorders", "text": [ "asthmatics" ], "offsets": [ [ 1616, 1626 ] ], "normalized": [] }, { "id": "11388", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "11389", "type": "Chemicals & Drugs", "text": [ "fluticasone" ], "offsets": [ [ 1672, 1683 ] ], "normalized": [] }, { "id": "11390", "type": "Diseases & Disorders", "text": [ "asthmatics" ], "offsets": [ [ 1721, 1731 ] ], "normalized": [] }, { "id": "11391", "type": "Diseases & Disorders", "text": [ "exercise-induced asthma" ], "offsets": [ [ 1793, 1816 ] ], "normalized": [] }, { "id": "11392", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 1912, 1920 ] ], "normalized": [] }, { "id": "11393", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 1933, 1944 ] ], "normalized": [] }, { "id": "11394", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 1979, 1985 ] ], "normalized": [] }, { "id": "11395", "type": "Diseases & Disorders", "text": [ "mild asthma" ], "offsets": [ [ 2030, 2041 ] ], "normalized": [] }, { "id": "11396", "type": "Chemicals & Drugs", "text": [ "montelukast" ], "offsets": [ [ 2082, 2093 ] ], "normalized": [] }, { "id": "11397", "type": "Diseases & Disorders", "text": [ "mild asthma" ], "offsets": [ [ 2150, 2161 ] ], "normalized": [] }, { "id": "11398", "type": "", "text": [ "montelukast" ], "offsets": [ [ 28, 39 ] ], "normalized": [] }, { "id": "11399", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 78, 89 ] ], "normalized": [] }, { "id": "11401", "type": "", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 496, 519 ] ], "normalized": [] }, { "id": "11402", "type": "", "text": [ "mild persistent asthma" ], "offsets": [ [ 559, 581 ] ], "normalized": [] }, { "id": "11404", "type": "", "text": [ "montelukast" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "11405", "type": "", "text": [ "asthma" ], "offsets": [ [ 796, 802 ] ], "normalized": [] }, { "id": "11407", "type": "", "text": [ "montelukast" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "11408", "type": "", "text": [ "allergic rhinitis" ], "offsets": [ [ 807, 824 ] ], "normalized": [] }, { "id": "11410", "type": "", "text": [ "montelukast" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "11411", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 686, 697 ] ], "normalized": [] }, { "id": "11413", "type": "", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 726, 757 ] ], "normalized": [] }, { "id": "11414", "type": "", "text": [ "asthma" ], "offsets": [ [ 796, 802 ] ], "normalized": [] }, { "id": "11416", "type": "", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 726, 757 ] ], "normalized": [] }, { "id": "11417", "type": "", "text": [ "allergic rhinitis" ], "offsets": [ [ 807, 824 ] ], "normalized": [] }, { "id": "11419", "type": "", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 726, 757 ] ], "normalized": [] }, { "id": "11420", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 686, 697 ] ], "normalized": [] }, { "id": "11422", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [] }, { "id": "11423", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 1093, 1104 ] ], "normalized": [] }, { "id": "11425", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1933, 1944 ] ], "normalized": [] }, { "id": "11426", "type": "", "text": [ "asthma" ], "offsets": [ [ 1979, 1985 ] ], "normalized": [] }, { "id": "11428", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1933, 1944 ] ], "normalized": [] }, { "id": "11429", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 2030, 2041 ] ], "normalized": [] }, { "id": "11431", "type": "", "text": [ "montelukast" ], "offsets": [ [ 2082, 2093 ] ], "normalized": [] }, { "id": "11432", "type": "", "text": [ "mild asthma" ], "offsets": [ [ 2150, 2161 ] ], "normalized": [] }, { "id": "11434", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [] }, { "id": "11435", "type": "", "text": [ "exercise-induced asthma" ], "offsets": [ [ 1106, 1129 ] ], "normalized": [] }, { "id": "11437", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "11438", "type": "", "text": [ "asthmatics" ], "offsets": [ [ 1721, 1731 ] ], "normalized": [] }, { "id": "11440", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "11441", "type": "", "text": [ "exercise-induced asthma" ], "offsets": [ [ 1793, 1816 ] ], "normalized": [] }, { "id": "11443", "type": "", "text": [ "fluticasone" ], "offsets": [ [ 1672, 1683 ] ], "normalized": [] }, { "id": "11444", "type": "", "text": [ "asthmatics" ], "offsets": [ [ 1721, 1731 ] ], "normalized": [] }, { "id": "11446", "type": "", "text": [ "fluticasone" ], "offsets": [ [ 1672, 1683 ] ], "normalized": [] }, { "id": "11447", "type": "", "text": [ "exercise-induced asthma" ], "offsets": [ [ 1793, 1816 ] ], "normalized": [] }, { "id": "11449", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1933, 1944 ] ], "normalized": [] }, { "id": "11450", "type": "", "text": [ "symptoms" ], "offsets": [ [ 1912, 1920 ] ], "normalized": [] }, { "id": "11452", "type": "", "text": [ "montelukast" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [] }, { "id": "11453", "type": "", "text": [ "bronchoconstriction" ], "offsets": [ [ 1135, 1154 ] ], "normalized": [] }, { "id": "11455", "type": "", "text": [ "leukotriene receptor antagonist" ], "offsets": [ [ 1042, 1073 ] ], "normalized": [] }, { "id": "11456", "type": "", "text": [ "bronchoconstriction" ], "offsets": [ [ 1135, 1154 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11400", "type": "PA", "arg1_id": "11398", "arg2_id": "11399", "normalized": [] }, { "id": "11403", "type": "PA", "arg1_id": "11401", "arg2_id": "11402", "normalized": [] }, { "id": "11406", "type": "PA", "arg1_id": "11404", "arg2_id": "11405", "normalized": [] }, { "id": "11409", "type": "PA", "arg1_id": "11407", "arg2_id": "11408", "normalized": [] }, { "id": "11412", "type": "PA", "arg1_id": "11410", "arg2_id": "11411", "normalized": [] }, { "id": "11415", "type": "PA", "arg1_id": "11413", "arg2_id": "11414", "normalized": [] }, { "id": "11418", "type": "PA", "arg1_id": "11416", "arg2_id": "11417", "normalized": [] }, { "id": "11421", "type": "PA", "arg1_id": "11419", "arg2_id": "11420", "normalized": [] }, { "id": "11424", "type": "PA", "arg1_id": "11422", "arg2_id": "11423", "normalized": [] }, { "id": "11427", "type": "PA", "arg1_id": "11425", "arg2_id": "11426", "normalized": [] }, { "id": "11430", "type": "PA", "arg1_id": "11428", "arg2_id": "11429", "normalized": [] }, { "id": "11433", "type": "PA", "arg1_id": "11431", "arg2_id": "11432", "normalized": [] }, { "id": "11436", "type": "PA", "arg1_id": "11434", "arg2_id": "11435", "normalized": [] }, { "id": "11439", "type": "PA", "arg1_id": "11437", "arg2_id": "11438", "normalized": [] }, { "id": "11442", "type": "PA", "arg1_id": "11440", "arg2_id": "11441", "normalized": [] }, { "id": "11445", "type": "PA", "arg1_id": "11443", "arg2_id": "11444", "normalized": [] }, { "id": "11448", "type": "PA", "arg1_id": "11446", "arg2_id": "11447", "normalized": [] }, { "id": "11451", "type": "PA", "arg1_id": "11449", "arg2_id": "11450", "normalized": [] }, { "id": "11454", "type": "PA", "arg1_id": "11452", "arg2_id": "11453", "normalized": [] }, { "id": "11457", "type": "PA", "arg1_id": "11455", "arg2_id": "11456", "normalized": [] } ]

[ { "id": "11460", "type": "title", "text": [ "An audit of intravenous fluid prescribing and plasma electrolyte monitoring; a comparison with guidelines from the National Patient Safety Agency." ], "offsets": [ [ 0, 146 ] ] }, { "id": "11461", "type": "abstract", "text": [ "OBJECTIVES: To audit past practice of intravenous (i.v.) fluid prescribing and electrolyte monitoring, prior to the publication of guidelines by the National Patient Safety Agency (NPSA, Ref. NPSA/2007/22) in March 2007, highlighting areas of discrepancy, in a specialist children's hospital. METHODS: We performed a retrospective case note review of 100 appendectomy patients between February 2004 and March 2007, recording; fluid type and volumes given as maintenance therapy, resuscitation boluses and nasogastric replacement; the frequency and timing of plasma electrolyte measurement; the relationship between plasma sodium [Na] concentration and i.v. fluid prescribed; and patient weight recordings. RESULTS: Ninety-eight acute appendectomies and two interval elective appendectomies. Median age 10 years (interquartile range: 8-11.25). Before surgery, hypotonic maintenance fluid was prescribed for 94% patients. During surgery, maintenance fluid was predominantly isotonic. After surgery, hypotonic maintenance fluid was prescribed for 92% patients. All maintenance fluid volumes were appropriately calculated according to weight using the Holliday and Segar formula (Paediatrics, 19, 1957, 823). Fluid boluses were isotonic on 128/129 occasions and all accurately calculated according to weight. Nasogastric losses were replaced with 0.9% sodium chloride. No patient had daily plasma electrolyte measurements whilst administered i.v. fluid. Twenty-seven patients had recorded hyponatremia ([Na] <135 mmol x l(-1); 21 at presentation, six subsequently after admission). Hypotonic maintenance fluid was continued in 26/27 patients with hyponatremia. No patient had daily weight recorded. CONCLUSIONS: Our practice of i.v. fluid prescribing and electrolyte monitoring in children, prior to the publication of guidelines by the NPSA in March 2007, did not fully meet the recommended standards." ], "offsets": [ [ 147, 2045 ] ] } ]

[ { "id": "11462", "type": "Chemicals & Drugs", "text": [ "intravenous fluid" ], "offsets": [ [ 12, 29 ] ], "normalized": [] }, { "id": "11463", "type": "Chemicals & Drugs", "text": [ "intravenous (i.v.) fluid" ], "offsets": [ [ 185, 209 ] ], "normalized": [] }, { "id": "11464", "type": "Chemicals & Drugs", "text": [ "sodium" ], "offsets": [ [ 769, 775 ] ], "normalized": [] }, { "id": "11465", "type": "Chemicals & Drugs", "text": [ "Na" ], "offsets": [ [ 777, 779 ] ], "normalized": [] }, { "id": "11466", "type": "Chemicals & Drugs", "text": [ "i.v. fluid" ], "offsets": [ [ 799, 809 ] ], "normalized": [] }, { "id": "11467", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 834, 840 ] ], "normalized": [] }, { "id": "11468", "type": "Chemicals & Drugs", "text": [ "hypotonic maintenance fluid" ], "offsets": [ [ 1006, 1033 ] ], "normalized": [] }, { "id": "11469", "type": "Diseases & Disorders", "text": [ "hypotonic maintenance fluid" ], "offsets": [ [ 1006, 1033 ] ], "normalized": [] }, { "id": "11470", "type": "Chemicals & Drugs", "text": [ "maintenance fluid" ], "offsets": [ [ 1083, 1100 ] ], "normalized": [] }, { "id": "11471", "type": "Chemicals & Drugs", "text": [ "hypotonic maintenance fluid" ], "offsets": [ [ 1144, 1171 ] ], "normalized": [] }, { "id": "11472", "type": "Diseases & Disorders", "text": [ "hypotonic maintenance fluid" ], "offsets": [ [ 1144, 1171 ] ], "normalized": [] }, { "id": "11473", "type": "Chemicals & Drugs", "text": [ "maintenance fluid" ], "offsets": [ [ 1209, 1226 ] ], "normalized": [] }, { "id": "11474", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 1278, 1284 ] ], "normalized": [] }, { "id": "11475", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 1444, 1450 ] ], "normalized": [] }, { "id": "11476", "type": "Chemicals & Drugs", "text": [ "sodium chloride" ], "offsets": [ [ 1495, 1510 ] ], "normalized": [] }, { "id": "11477", "type": "Chemicals & Drugs", "text": [ "i.v. fluid" ], "offsets": [ [ 1585, 1595 ] ], "normalized": [] }, { "id": "11478", "type": "Diseases & Disorders", "text": [ "hyponatremia" ], "offsets": [ [ 1632, 1644 ] ], "normalized": [] }, { "id": "11479", "type": "Chemicals & Drugs", "text": [ "Na" ], "offsets": [ [ 1647, 1649 ] ], "normalized": [] }, { "id": "11480", "type": "Chemicals & Drugs", "text": [ "Hypotonic maintenance fluid" ], "offsets": [ [ 1725, 1752 ] ], "normalized": [] }, { "id": "11481", "type": "Diseases & Disorders", "text": [ "Hypotonic maintenance fluid" ], "offsets": [ [ 1725, 1752 ] ], "normalized": [] }, { "id": "11482", "type": "Diseases & Disorders", "text": [ "hyponatremia" ], "offsets": [ [ 1790, 1802 ] ], "normalized": [] }, { "id": "11483", "type": "Chemicals & Drugs", "text": [ "i.v. fluid" ], "offsets": [ [ 1871, 1881 ] ], "normalized": [] }, { "id": "11484", "type": "", "text": [ "Na" ], "offsets": [ [ 1647, 1649 ] ], "normalized": [] }, { "id": "11485", "type": "", "text": [ "hyponatremia" ], "offsets": [ [ 1632, 1644 ] ], "normalized": [] }, { "id": "11487", "type": "", "text": [ "Hypotonic maintenance fluid" ], "offsets": [ [ 1725, 1752 ] ], "normalized": [] }, { "id": "11488", "type": "", "text": [ "hyponatremia" ], "offsets": [ [ 1790, 1802 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11486", "type": "PA", "arg1_id": "11484", "arg2_id": "11485", "normalized": [] }, { "id": "11489", "type": "PA", "arg1_id": "11487", "arg2_id": "11488", "normalized": [] } ]

[ { "id": "11492", "type": "title", "text": [ "Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy." ], "offsets": [ [ 0, 190 ] ] }, { "id": "11493", "type": "abstract", "text": [ "Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for example, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of >or=8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to 'Were erections good enough for satisfactory sexual activity?') occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections." ], "offsets": [ [ 191, 1232 ] ] } ]

[ { "id": "11494", "type": "Chemicals & Drugs", "text": [ "sildenafil citrate" ], "offsets": [ [ 76, 94 ] ], "normalized": [] }, { "id": "11495", "type": "Diseases & Disorders", "text": [ "erectile dysfunction" ], "offsets": [ [ 117, 137 ] ], "normalized": [] }, { "id": "11496", "type": "Chemicals & Drugs", "text": [ "sildenafil" ], "offsets": [ [ 347, 357 ] ], "normalized": [] }, { "id": "11497", "type": "Diseases & Disorders", "text": [ "blinded" ], "offsets": [ [ 680, 687 ] ], "normalized": [] }, { "id": "11498", "type": "Chemicals & Drugs", "text": [ "sildenafil" ], "offsets": [ [ 1091, 1101 ] ], "normalized": [] }, { "id": "11499", "type": "Chemicals & Drugs", "text": [ "sildenafil" ], "offsets": [ [ 1117, 1127 ] ], "normalized": [] }, { "id": "11500", "type": "", "text": [ "sildenafil citrate" ], "offsets": [ [ 76, 94 ] ], "normalized": [] }, { "id": "11501", "type": "", "text": [ "erectile dysfunction" ], "offsets": [ [ 117, 137 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11502", "type": "PA", "arg1_id": "11500", "arg2_id": "11501", "normalized": [] } ]

[ { "id": "11505", "type": "title", "text": [ "Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway." ], "offsets": [ [ 0, 130 ] ] }, { "id": "11506", "type": "abstract", "text": [ "Apoptosis of human neutrophils is a crucial mechanism for the resolution of inflammation. We previously showed that insulin-like growth factor-1 (IGF1) delays spontaneous neutrophil apoptosis without influencing the secretion of cytokines by these cells. In the present study, we further addressed the role of IGF1 in regulating neutrophil survival in the presence of other factors present during inflammation, and the mechanism involved in delaying apoptosis. We show that IGF1 delays neutrophil apoptosis triggered by the agonistic anti-Fas antibody CH11 and that the effect of IGF1 is comparable in magnitude to that of the acknowledged anti-apoptotic cytokines interferon-gamma (IFNG) and granulocyte-macrophage colony-stimulating factor (GM-CSF; now known as CSF2). Furthermore, IGF1 exerted additional effects on cell survival in the presence of these cytokines. IGF1 did not affect Fas expression or activation by anti-Fas of caspase-8, but inhibited the depolarization of the mitochondrial membrane. Inhibitor studies indicate that the phosphatidylinositol-3 kinase (PI3K) pathway, but not the MEK-ERK pathway, mediates the effects of IGF1. However, in contrast to CSF2, IGF1 did not induce phosphorylation and translocation to the membrane of AKT, the canonical downstream target of PI3K. We therefore speculate that other downstream targets of PI3K are involved in the delay of neutrophil apoptosis by IGF1, possibly through stabilization of the mitochondrial membrane." ], "offsets": [ [ 131, 1610 ] ] } ]

[ { "id": "11507", "type": "Genes & Molecular Sequences", "text": [ "Insulin-like growth factor-1" ], "offsets": [ [ 0, 28 ] ], "normalized": [] }, { "id": "11508", "type": "Genes & Molecular Sequences", "text": [ "Fas" ], "offsets": [ [ 36, 39 ] ], "normalized": [] }, { "id": "11509", "type": "Genes & Molecular Sequences", "text": [ "phosphatidylinositol-3 kinase" ], "offsets": [ [ 92, 121 ] ], "normalized": [] }, { "id": "11510", "type": "Genes & Molecular Sequences", "text": [ "insulin-like growth factor-1" ], "offsets": [ [ 247, 275 ] ], "normalized": [] }, { "id": "11511", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 277, 281 ] ], "normalized": [] }, { "id": "11512", "type": "Genes & Molecular Sequences", "text": [ "cytokines" ], "offsets": [ [ 360, 369 ] ], "normalized": [] }, { "id": "11513", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 441, 445 ] ], "normalized": [] }, { "id": "11514", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "11515", "type": "Genes & Molecular Sequences", "text": [ "anti-Fas" ], "offsets": [ [ 665, 673 ] ], "normalized": [] }, { "id": "11516", "type": "Chemicals & Drugs", "text": [ "anti-Fas" ], "offsets": [ [ 665, 673 ] ], "normalized": [] }, { "id": "11517", "type": "Genes & Molecular Sequences", "text": [ "CH11" ], "offsets": [ [ 683, 687 ] ], "normalized": [] }, { "id": "11518", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 711, 715 ] ], "normalized": [] }, { "id": "11519", "type": "Genes & Molecular Sequences", "text": [ "cytokines" ], "offsets": [ [ 786, 795 ] ], "normalized": [] }, { "id": "11520", "type": "Genes & Molecular Sequences", "text": [ "interferon-gamma" ], "offsets": [ [ 796, 812 ] ], "normalized": [] }, { "id": "11521", "type": "Chemicals & Drugs", "text": [ "interferon-gamma" ], "offsets": [ [ 796, 812 ] ], "normalized": [] }, { "id": "11522", "type": "Genes & Molecular Sequences", "text": [ "IFNG" ], "offsets": [ [ 814, 818 ] ], "normalized": [] }, { "id": "11523", "type": "Genes & Molecular Sequences", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 824, 872 ] ], "normalized": [] }, { "id": "11524", "type": "Chemicals & Drugs", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 824, 872 ] ], "normalized": [] }, { "id": "11525", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 874, 880 ] ], "normalized": [] }, { "id": "11526", "type": "Chemicals & Drugs", "text": [ "GM-CSF" ], "offsets": [ [ 874, 880 ] ], "normalized": [] }, { "id": "11527", "type": "Genes & Molecular Sequences", "text": [ "CSF2" ], "offsets": [ [ 895, 899 ] ], "normalized": [] }, { "id": "11528", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 915, 919 ] ], "normalized": [] }, { "id": "11529", "type": "Genes & Molecular Sequences", "text": [ "cytokines" ], "offsets": [ [ 989, 998 ] ], "normalized": [] }, { "id": "11530", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 1000, 1004 ] ], "normalized": [] }, { "id": "11531", "type": "Genes & Molecular Sequences", "text": [ "Fas" ], "offsets": [ [ 1020, 1023 ] ], "normalized": [] }, { "id": "11532", "type": "Genes & Molecular Sequences", "text": [ "anti-Fas" ], "offsets": [ [ 1052, 1060 ] ], "normalized": [] }, { "id": "11533", "type": "Chemicals & Drugs", "text": [ "anti-Fas" ], "offsets": [ [ 1052, 1060 ] ], "normalized": [] }, { "id": "11534", "type": "Genes & Molecular Sequences", "text": [ "caspase-8" ], "offsets": [ [ 1064, 1073 ] ], "normalized": [] }, { "id": "11535", "type": "Genes & Molecular Sequences", "text": [ "phosphatidylinositol-3 kinase" ], "offsets": [ [ 1175, 1204 ] ], "normalized": [] }, { "id": "11536", "type": "Genes & Molecular Sequences", "text": [ "PI3K" ], "offsets": [ [ 1206, 1210 ] ], "normalized": [] }, { "id": "11537", "type": "Genes & Molecular Sequences", "text": [ "MEK-ERK" ], "offsets": [ [ 1233, 1240 ] ], "normalized": [] }, { "id": "11538", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "11539", "type": "Genes & Molecular Sequences", "text": [ "CSF2" ], "offsets": [ [ 1304, 1308 ] ], "normalized": [] }, { "id": "11540", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 1310, 1314 ] ], "normalized": [] }, { "id": "11541", "type": "Genes & Molecular Sequences", "text": [ "AKT" ], "offsets": [ [ 1383, 1386 ] ], "normalized": [] }, { "id": "11542", "type": "Genes & Molecular Sequences", "text": [ "PI3K" ], "offsets": [ [ 1423, 1427 ] ], "normalized": [] }, { "id": "11543", "type": "Genes & Molecular Sequences", "text": [ "PI3K" ], "offsets": [ [ 1485, 1489 ] ], "normalized": [] }, { "id": "11544", "type": "Genes & Molecular Sequences", "text": [ "IGF1" ], "offsets": [ [ 1543, 1547 ] ], "normalized": [] }, { "id": "11545", "type": "", "text": [ "IGF1" ], "offsets": [ [ 441, 445 ] ], "normalized": [] }, { "id": "11546", "type": "", "text": [ "inflammation" ], "offsets": [ [ 528, 540 ] ], "normalized": [] }, { "id": "11548", "type": "", "text": [ "anti-Fas" ], "offsets": [ [ 665, 673 ] ], "normalized": [] }, { "id": "11549", "type": "", "text": [ "IGF1" ], "offsets": [ [ 711, 715 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11547", "type": "PA", "arg1_id": "11545", "arg2_id": "11546", "normalized": [] }, { "id": "11550", "type": "PA", "arg1_id": "11548", "arg2_id": "11549", "normalized": [] } ]

[ { "id": "11553", "type": "title", "text": [ "Management and risk factors for dyslipidemia with the ketogenic diet." ], "offsets": [ [ 0, 69 ] ] }, { "id": "11554", "type": "abstract", "text": [ "A prospective study was performed of all children started on the ketogenic diet at our institution for intractable epilepsy from January 2003 to March 2007 (n = 137), examining for baseline and follow-up total cholesterol and triglyceride levels. Interventions for dyslipidemia were analyzed for their effectiveness. At baseline, 25% of children had hypercholesterolemia (>200 mg/dL), which increased to 60% for those receiving the ketogenic diet. Children receiving a solely formula-based ketogenic diet were less likely to have hypercholesterolemia than those eating solid food after adjusting for age and initial ketogenic ratio (P < .001). Only a slightly higher likelihood of a 20% decrease in cholesterol occurred for those children in whom a dietary intervention was made compared with observation alone (60% vs 41%; P = .11). Hypercholesterolemia occurs in most children receiving a solid food based ketogenic diet but improved in approximately half, even without interventions." ], "offsets": [ [ 70, 1056 ] ] } ]

[ { "id": "11555", "type": "Diseases & Disorders", "text": [ "dyslipidemia" ], "offsets": [ [ 32, 44 ] ], "normalized": [] }, { "id": "11556", "type": "Diseases & Disorders", "text": [ "ketogenic diet" ], "offsets": [ [ 54, 68 ] ], "normalized": [] }, { "id": "11557", "type": "Diseases & Disorders", "text": [ "ketogenic diet" ], "offsets": [ [ 135, 149 ] ], "normalized": [] }, { "id": "11558", "type": "Diseases & Disorders", "text": [ "intractable epilepsy" ], "offsets": [ [ 173, 193 ] ], "normalized": [] }, { "id": "11559", "type": "Diseases & Disorders", "text": [ "dyslipidemia" ], "offsets": [ [ 335, 347 ] ], "normalized": [] }, { "id": "11560", "type": "Diseases & Disorders", "text": [ "hypercholesterolemia" ], "offsets": [ [ 420, 440 ] ], "normalized": [] }, { "id": "11561", "type": "Diseases & Disorders", "text": [ "ketogenic diet" ], "offsets": [ [ 502, 516 ] ], "normalized": [] }, { "id": "11562", "type": "Diseases & Disorders", "text": [ "ketogenic diet" ], "offsets": [ [ 560, 574 ] ], "normalized": [] }, { "id": "11563", "type": "Diseases & Disorders", "text": [ "hypercholesterolemia" ], "offsets": [ [ 600, 620 ] ], "normalized": [] }, { "id": "11564", "type": "Diseases & Disorders", "text": [ "Hypercholesterolemia" ], "offsets": [ [ 904, 924 ] ], "normalized": [] }, { "id": "11565", "type": "Diseases & Disorders", "text": [ "ketogenic diet" ], "offsets": [ [ 978, 992 ] ], "normalized": [] } ]

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[]

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[ { "id": "11568", "type": "title", "text": [ "Telomere maintenance in laser capture microdissection-purified Barrett's adenocarcinoma cells and effect of telomerase inhibition in vivo." ], "offsets": [ [ 0, 138 ] ] }, { "id": "11569", "type": "abstract", "text": [ "PURPOSE: The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of telomerase inhibition in cancer cells in vitro and in vivo. EXPERIMENTAL DESIGN: Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by beta-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L. RESULTS: Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model. CONCLUSIONS: We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo." ], "offsets": [ [ 139, 1917 ] ] } ]

[ { "id": "11570", "type": "Genes & Molecular Sequences", "text": [ "Telomere" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "11571", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 108, 118 ] ], "normalized": [] }, { "id": "11572", "type": "Genes & Molecular Sequences", "text": [ "telomere" ], "offsets": [ [ 191, 199 ] ], "normalized": [] }, { "id": "11573", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 344, 354 ] ], "normalized": [] }, { "id": "11574", "type": "Genes & Molecular Sequences", "text": [ "Telomerase" ], "offsets": [ [ 491, 501 ] ], "normalized": [] }, { "id": "11575", "type": "Genes & Molecular Sequences", "text": [ "telomere" ], "offsets": [ [ 580, 588 ] ], "normalized": [] }, { "id": "11576", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 661, 671 ] ], "normalized": [] }, { "id": "11577", "type": "Chemicals & Drugs", "text": [ "telomerase inhibitor" ], "offsets": [ [ 752, 772 ] ], "normalized": [] }, { "id": "11578", "type": "Genes & Molecular Sequences", "text": [ "telomerase inhibitor" ], "offsets": [ [ 752, 772 ] ], "normalized": [] }, { "id": "11579", "type": "Chemicals & Drugs", "text": [ "GRN163L" ], "offsets": [ [ 774, 781 ] ], "normalized": [] }, { "id": "11580", "type": "Genes & Molecular Sequences", "text": [ "Annexin" ], "offsets": [ [ 854, 861 ] ], "normalized": [] }, { "id": "11581", "type": "Genes & Molecular Sequences", "text": [ "beta-galactosidase" ], "offsets": [ [ 889, 907 ] ], "normalized": [] }, { "id": "11582", "type": "Chemicals & Drugs", "text": [ "GRN163L" ], "offsets": [ [ 1097, 1104 ] ], "normalized": [] }, { "id": "11583", "type": "Genes & Molecular Sequences", "text": [ "Telomerase" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "11584", "type": "Chemicals & Drugs", "text": [ "telomerase inhibitor" ], "offsets": [ [ 1298, 1318 ] ], "normalized": [] }, { "id": "11585", "type": "Genes & Molecular Sequences", "text": [ "telomerase inhibitor" ], "offsets": [ [ 1298, 1318 ] ], "normalized": [] }, { "id": "11586", "type": "Chemicals & Drugs", "text": [ "GRN163L" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [] }, { "id": "11587", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "11588", "type": "Genes & Molecular Sequences", "text": [ "telomere" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "11589", "type": "Chemicals & Drugs", "text": [ "GRN163L" ], "offsets": [ [ 1469, 1476 ] ], "normalized": [] }, { "id": "11590", "type": "Chemicals & Drugs", "text": [ "doxorubicin" ], "offsets": [ [ 1563, 1574 ] ], "normalized": [] }, { "id": "11591", "type": "Chemicals & Drugs", "text": [ "ritonavir" ], "offsets": [ [ 1579, 1588 ] ], "normalized": [] }, { "id": "11592", "type": "Chemicals & Drugs", "text": [ "GRN163L" ], "offsets": [ [ 1618, 1625 ] ], "normalized": [] }, { "id": "11593", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 1730, 1740 ] ], "normalized": [] }, { "id": "11594", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 1833, 1843 ] ], "normalized": [] }, { "id": "11595", "type": "", "text": [ "telomerase inhibitor" ], "offsets": [ [ 1298, 1318 ] ], "normalized": [] }, { "id": "11596", "type": "", "text": [ "telomerase" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "11598", "type": "", "text": [ "telomerase inhibitor" ], "offsets": [ [ 1298, 1318 ] ], "normalized": [] }, { "id": "11599", "type": "", "text": [ "telomere" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "11601", "type": "", "text": [ "GRN163L" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [] }, { "id": "11602", "type": "", "text": [ "telomerase" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "11604", "type": "", "text": [ "GRN163L" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [] }, { "id": "11605", "type": "", "text": [ "telomere" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "11607", "type": "", "text": [ "GRN163L" ], "offsets": [ [ 774, 781 ] ], "normalized": [] }, { "id": "11608", "type": "", "text": [ "telomerase inhibitor" ], "offsets": [ [ 752, 772 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11597", "type": "PA", "arg1_id": "11595", "arg2_id": "11596", "normalized": [] }, { "id": "11600", "type": "PA", "arg1_id": "11598", "arg2_id": "11599", "normalized": [] }, { "id": "11603", "type": "PA", "arg1_id": "11601", "arg2_id": "11602", "normalized": [] }, { "id": "11606", "type": "PA", "arg1_id": "11604", "arg2_id": "11605", "normalized": [] }, { "id": "11609", "type": "PA", "arg1_id": "11607", "arg2_id": "11608", "normalized": [] } ]

[ { "id": "11612", "type": "title", "text": [ "Clinicopathological evaluation of immunohistochemical Ki-67 and endothelial nitric oxide synthase expression in intracranial ependymoma." ], "offsets": [ [ 0, 136 ] ] }, { "id": "11613", "type": "abstract", "text": [ "PURPOSE: To analyze the association between Ki-67 and eNOS expression with the pathological grades of patients with intracranial ependymomas, and to determine its value in distinguishing the progression of the disease. METHODS: A clinicopathological study was undertaken in 82 patients with intracranial ependymomas. Tissue samples, obtained by tumour resection, were divided into three groups: low-grade, mid-grade and high-grade ependymomas. Tissue samples obtained from 15 patients with brain contusion were used as control. Immuno-histochemical staining was performed to analyze the association between Ki-67 and eNOS expression with various tumour grades. The cell proliferating marker Ki-67 was assessed by positive cell count. The levels of eNOS positive expression were evaluated as slight, moderate and intense. RESULTS: 48 of 82 cases (58.54%) expressed Ki-67 protein. Expression of Ki-67 and eNOS was negative in all control samples. Positive cell rates were 2.65+/-0.83 % in the low-grade, 9.63+/-0.08 % in the mid-grade, and 28.41+/-0.71 % in the high-grade ependymoma groups. In low-grade ependymomas there were 8 and 12 cases that expressed eNOS slightly or moderately. In the mid-grade ependymoma group eNOS was expressed moderately in 10 cases and intensely in 15. In the high-grade group 20 cases showed intense positive expression of eNOS. The Ki-67 positive cell counts for slight, moderate and intense eNOS expression were 2.20, 6.07 and 22.25, respectively. CONCLUSION: Ki-67 and eNOS expression in intracranial ependymoma tissue was associated with the histopathological grade and malignant degree." ], "offsets": [ [ 137, 1758 ] ] } ]

[ { "id": "11614", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 54, 59 ] ], "normalized": [] }, { "id": "11615", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 54, 59 ] ], "normalized": [] }, { "id": "11616", "type": "Genes & Molecular Sequences", "text": [ "endothelial nitric oxide synthase" ], "offsets": [ [ 64, 97 ] ], "normalized": [] }, { "id": "11617", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "11618", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "11619", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 191, 195 ] ], "normalized": [] }, { "id": "11620", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "11621", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "11622", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "11623", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 828, 833 ] ], "normalized": [] }, { "id": "11624", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 828, 833 ] ], "normalized": [] }, { "id": "11625", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 885, 889 ] ], "normalized": [] }, { "id": "11626", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 1001, 1006 ] ], "normalized": [] }, { "id": "11627", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 1001, 1006 ] ], "normalized": [] }, { "id": "11628", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "11629", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "11630", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "11631", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "11632", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "11633", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1490, 1494 ] ], "normalized": [] }, { "id": "11634", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] }, { "id": "11635", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] }, { "id": "11636", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1560, 1564 ] ], "normalized": [] }, { "id": "11637", "type": "Genes & Molecular Sequences", "text": [ "Ki-67" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "11638", "type": "Chemicals & Drugs", "text": [ "Ki-67" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "11639", "type": "Genes & Molecular Sequences", "text": [ "eNOS" ], "offsets": [ [ 1639, 1643 ] ], "normalized": [] }, { "id": "11640", "type": "", "text": [ "endothelial nitric oxide synthase" ], "offsets": [ [ 64, 97 ] ], "normalized": [] }, { "id": "11641", "type": "", "text": [ "ependymoma" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "11643", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 54, 59 ] ], "normalized": [] }, { "id": "11644", "type": "", "text": [ "ependymoma" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "11646", "type": "", "text": [ "eNOS" ], "offsets": [ [ 191, 195 ] ], "normalized": [] }, { "id": "11647", "type": "", "text": [ "ependymomas" ], "offsets": [ [ 266, 277 ] ], "normalized": [] }, { "id": "11649", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "11650", "type": "", "text": [ "ependymomas" ], "offsets": [ [ 266, 277 ] ], "normalized": [] }, { "id": "11652", "type": "", "text": [ "eNOS" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "11653", "type": "", "text": [ "tumour" ], "offsets": [ [ 783, 789 ] ], "normalized": [] }, { "id": "11655", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "11656", "type": "", "text": [ "tumour" ], "offsets": [ [ 783, 789 ] ], "normalized": [] }, { "id": "11658", "type": "", "text": [ "eNOS" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "11659", "type": "", "text": [ "ependymomas" ], "offsets": [ [ 1240, 1251 ] ], "normalized": [] }, { "id": "11661", "type": "", "text": [ "eNOS" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "11662", "type": "", "text": [ "ependymoma" ], "offsets": [ [ 1339, 1349 ] ], "normalized": [] }, { "id": "11664", "type": "", "text": [ "eNOS" ], "offsets": [ [ 1639, 1643 ] ], "normalized": [] }, { "id": "11665", "type": "", "text": [ "ependymoma" ], "offsets": [ [ 1671, 1681 ] ], "normalized": [] }, { "id": "11667", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "11668", "type": "", "text": [ "ependymoma" ], "offsets": [ [ 1671, 1681 ] ], "normalized": [] }, { "id": "11670", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "11671", "type": "", "text": [ "eNOS" ], "offsets": [ [ 191, 195 ] ], "normalized": [] }, { "id": "11673", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "11674", "type": "", "text": [ "eNOS" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "11676", "type": "", "text": [ "Ki-67" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] }, { "id": "11677", "type": "", "text": [ "eNOS" ], "offsets": [ [ 1560, 1564 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11642", "type": "PA", "arg1_id": "11640", "arg2_id": "11641", "normalized": [] }, { "id": "11645", "type": "PA", "arg1_id": "11643", "arg2_id": "11644", "normalized": [] }, { "id": "11648", "type": "PA", "arg1_id": "11646", "arg2_id": "11647", "normalized": [] }, { "id": "11651", "type": "PA", "arg1_id": "11649", "arg2_id": "11650", "normalized": [] }, { "id": "11654", "type": "PA", "arg1_id": "11652", "arg2_id": "11653", "normalized": [] }, { "id": "11657", "type": "PA", "arg1_id": "11655", "arg2_id": "11656", "normalized": [] }, { "id": "11660", "type": "PA", "arg1_id": "11658", "arg2_id": "11659", "normalized": [] }, { "id": "11663", "type": "PA", "arg1_id": "11661", "arg2_id": "11662", "normalized": [] }, { "id": "11666", "type": "PA", "arg1_id": "11664", "arg2_id": "11665", "normalized": [] }, { "id": "11669", "type": "PA", "arg1_id": "11667", "arg2_id": "11668", "normalized": [] }, { "id": "11672", "type": "SA", "arg1_id": "11670", "arg2_id": "11671", "normalized": [] }, { "id": "11675", "type": "SA", "arg1_id": "11673", "arg2_id": "11674", "normalized": [] }, { "id": "11678", "type": "SA", "arg1_id": "11676", "arg2_id": "11677", "normalized": [] } ]

[ { "id": "11681", "type": "title", "text": [ "Evidence-based recommendations for cancer nausea and vomiting." ], "offsets": [ [ 0, 62 ] ] }, { "id": "11682", "type": "abstract", "text": [ "The experience of patients living with cancer and being treated with chemotherapy often includes the symptoms of nausea and vomiting. To provide a framework for high-quality management of these symptoms, we developed a set of key targeted evidence-based standards through an iterative process of targeted systematic review, development, and refinement of topic areas and standards and consensus ratings by a multidisciplinary expert panel as part of the RAND Cancer Quality-Assessing Symptoms Side Effects and Indicators of Supportive Treatment Project. For nausea and vomiting, key clinical standards included screening at the initial outpatient and inpatient visit, prophylaxis for acute and delayed emesis in patients receiving moderate to highly emetic chemotherapy, and follow-up after treatment for nausea and vomiting symptoms. In addition, patients with cancer and small bowel obstruction were examined as a special subset of patients who present with nausea and vomiting. The standards presented here for preventing and managing nausea and vomiting in cancer care should be incorporated into care pathways and should become the expectation rather than the exception." ], "offsets": [ [ 63, 1238 ] ] } ]

[ { "id": "11683", "type": "Diseases & Disorders", "text": [ "cancer nausea and vomiting" ], "offsets": [ [ 35, 61 ] ], "normalized": [] }, { "id": "11684", "type": "Diseases & Disorders", "text": [ "nausea" ], "offsets": [ [ 42, 48 ] ], "normalized": [] }, { "id": "11685", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 102, 108 ] ], "normalized": [] }, { "id": "11686", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 132, 144 ] ], "normalized": [] }, { "id": "11687", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 164, 172 ] ], "normalized": [] }, { "id": "11688", "type": "Diseases & Disorders", "text": [ "nausea and vomiting" ], "offsets": [ [ 176, 195 ] ], "normalized": [] }, { "id": "11689", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 257, 265 ] ], "normalized": [] }, { "id": "11690", "type": "Diseases & Disorders", "text": [ "Cancer" ], "offsets": [ [ 522, 528 ] ], "normalized": [] }, { "id": "11691", "type": "Diseases & Disorders", "text": [ "Symptoms" ], "offsets": [ [ 547, 555 ] ], "normalized": [] }, { "id": "11692", "type": "Diseases & Disorders", "text": [ "Side Effects" ], "offsets": [ [ 556, 568 ] ], "normalized": [] }, { "id": "11693", "type": "Diseases & Disorders", "text": [ "nausea and vomiting" ], "offsets": [ [ 621, 640 ] ], "normalized": [] }, { "id": "11694", "type": "Diseases & Disorders", "text": [ "emesis" ], "offsets": [ [ 765, 771 ] ], "normalized": [] }, { "id": "11695", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 820, 832 ] ], "normalized": [] }, { "id": "11696", "type": "Diseases & Disorders", "text": [ "nausea and vomiting" ], "offsets": [ [ 868, 887 ] ], "normalized": [] }, { "id": "11697", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 925, 931 ] ], "normalized": [] }, { "id": "11698", "type": "Diseases & Disorders", "text": [ "small bowel obstruction" ], "offsets": [ [ 936, 959 ] ], "normalized": [] }, { "id": "11699", "type": "Diseases & Disorders", "text": [ "nausea and vomiting" ], "offsets": [ [ 1023, 1042 ] ], "normalized": [] }, { "id": "11700", "type": "Diseases & Disorders", "text": [ "nausea and vomiting" ], "offsets": [ [ 1101, 1120 ] ], "normalized": [] }, { "id": "11701", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 1124, 1130 ] ], "normalized": [] }, { "id": "11702", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 132, 144 ] ], "normalized": [] }, { "id": "11703", "type": "", "text": [ "cancer" ], "offsets": [ [ 102, 108 ] ], "normalized": [] }, { "id": "11705", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 132, 144 ] ], "normalized": [] }, { "id": "11706", "type": "", "text": [ "nausea and vomiting" ], "offsets": [ [ 176, 195 ] ], "normalized": [] }, { "id": "11708", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 820, 832 ] ], "normalized": [] }, { "id": "11709", "type": "", "text": [ "emesis" ], "offsets": [ [ 765, 771 ] ], "normalized": [] }, { "id": "11711", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 820, 832 ] ], "normalized": [] }, { "id": "11712", "type": "", "text": [ "nausea and vomiting" ], "offsets": [ [ 868, 887 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11704", "type": "PA", "arg1_id": "11702", "arg2_id": "11703", "normalized": [] }, { "id": "11707", "type": "PA", "arg1_id": "11705", "arg2_id": "11706", "normalized": [] }, { "id": "11710", "type": "PA", "arg1_id": "11708", "arg2_id": "11709", "normalized": [] }, { "id": "11713", "type": "PA", "arg1_id": "11711", "arg2_id": "11712", "normalized": [] } ]

[ { "id": "11716", "type": "title", "text": [ "The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of beta-thalassaemia." ], "offsets": [ [ 0, 150 ] ] }, { "id": "11717", "type": "abstract", "text": [ "BACKGROUND: Fetal haemoglobin (HbF) level modifies the clinical severity of HBB disorders. Intergenic variants of HBS1L-MYB on chromosome 6q23 have recently been shown to be a major quantitative trait locus (QTL) influencing HbF levels in normal Caucasian adults. METHODS: A unique and well-characterised cohort of 238 Chinese subjects with beta-thalassaemia trait was used to conduct a single-nucleotide polymorphism (SNP) association study for HbF level. RESULTS: Within this locus, 29 trait-associated SNPs in a non-coding 56 kb segment were identified. They were divided into five linkage disequilibrium (LD) blocks in the Chinese participants. CONCLUSIONS: The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of beta-thalassaemia. Functional studies to unravel the biological significance of this region in regulating HbF production is clearly indicated, which may lead to new strategies to modify the disease course of severe HBB disorders." ], "offsets": [ [ 151, 1231 ] ] } ]

[ { "id": "11718", "type": "Genes & Molecular Sequences", "text": [ "HBS1L-MYB" ], "offsets": [ [ 4, 13 ] ], "normalized": [] }, { "id": "11719", "type": "Genes & Molecular Sequences", "text": [ "6q23" ], "offsets": [ [ 46, 50 ] ], "normalized": [] }, { "id": "11720", "type": "Genes & Molecular Sequences", "text": [ "fetal haemoglobin" ], "offsets": [ [ 93, 110 ] ], "normalized": [] }, { "id": "11721", "type": "Diseases & Disorders", "text": [ "fetal haemoglobin" ], "offsets": [ [ 93, 110 ] ], "normalized": [] }, { "id": "11722", "type": "Diseases & Disorders", "text": [ "beta-thalassaemia" ], "offsets": [ [ 132, 149 ] ], "normalized": [] }, { "id": "11723", "type": "Genes & Molecular Sequences", "text": [ "Fetal haemoglobin" ], "offsets": [ [ 163, 180 ] ], "normalized": [] }, { "id": "11724", "type": "Diseases & Disorders", "text": [ "Fetal haemoglobin" ], "offsets": [ [ 163, 180 ] ], "normalized": [] }, { "id": "11725", "type": "Genes & Molecular Sequences", "text": [ "HbF" ], "offsets": [ [ 182, 185 ] ], "normalized": [] }, { "id": "11726", "type": "Diseases & Disorders", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11727", "type": "Genes & Molecular Sequences", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11728", "type": "Genes & Molecular Sequences", "text": [ "HBS1L-MYB" ], "offsets": [ [ 265, 274 ] ], "normalized": [] }, { "id": "11729", "type": "Genes & Molecular Sequences", "text": [ "6q23" ], "offsets": [ [ 289, 293 ] ], "normalized": [] }, { "id": "11730", "type": "Genes & Molecular Sequences", "text": [ "HbF" ], "offsets": [ [ 376, 379 ] ], "normalized": [] }, { "id": "11731", "type": "Diseases & Disorders", "text": [ "beta-thalassaemia" ], "offsets": [ [ 492, 509 ] ], "normalized": [] }, { "id": "11732", "type": "Genes & Molecular Sequences", "text": [ "HbF" ], "offsets": [ [ 597, 600 ] ], "normalized": [] }, { "id": "11733", "type": "Diseases & Disorders", "text": [ "blocks" ], "offsets": [ [ 764, 770 ] ], "normalized": [] }, { "id": "11734", "type": "Genes & Molecular Sequences", "text": [ "HBS1L-MYB" ], "offsets": [ [ 888, 897 ] ], "normalized": [] }, { "id": "11735", "type": "Genes & Molecular Sequences", "text": [ "HbF" ], "offsets": [ [ 930, 933 ] ], "normalized": [] }, { "id": "11736", "type": "Diseases & Disorders", "text": [ "HbF" ], "offsets": [ [ 930, 933 ] ], "normalized": [] }, { "id": "11737", "type": "Diseases & Disorders", "text": [ "beta-thalassaemia" ], "offsets": [ [ 1002, 1019 ] ], "normalized": [] }, { "id": "11738", "type": "Genes & Molecular Sequences", "text": [ "HbF" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "11739", "type": "Diseases & Disorders", "text": [ "disease course" ], "offsets": [ [ 1192, 1206 ] ], "normalized": [] }, { "id": "11740", "type": "Diseases & Disorders", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11741", "type": "Genes & Molecular Sequences", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11742", "type": "", "text": [ "Fetal haemoglobin" ], "offsets": [ [ 163, 180 ] ], "normalized": [] }, { "id": "11743", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11745", "type": "", "text": [ "HbF" ], "offsets": [ [ 182, 185 ] ], "normalized": [] }, { "id": "11746", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11748", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11749", "type": "", "text": [ "Fetal haemoglobin" ], "offsets": [ [ 163, 180 ] ], "normalized": [] }, { "id": "11751", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11752", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "11754", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11755", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11757", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11758", "type": "", "text": [ "disease course" ], "offsets": [ [ 1192, 1206 ] ], "normalized": [] }, { "id": "11760", "type": "", "text": [ "HBS1L-MYB" ], "offsets": [ [ 4, 13 ] ], "normalized": [] }, { "id": "11761", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 132, 149 ] ], "normalized": [] }, { "id": "11763", "type": "", "text": [ "6q23" ], "offsets": [ [ 46, 50 ] ], "normalized": [] }, { "id": "11764", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 132, 149 ] ], "normalized": [] }, { "id": "11766", "type": "", "text": [ "fetal haemoglobin" ], "offsets": [ [ 93, 110 ] ], "normalized": [] }, { "id": "11767", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 132, 149 ] ], "normalized": [] }, { "id": "11769", "type": "", "text": [ "HbF" ], "offsets": [ [ 597, 600 ] ], "normalized": [] }, { "id": "11770", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 492, 509 ] ], "normalized": [] }, { "id": "11772", "type": "", "text": [ "HBS1L-MYB" ], "offsets": [ [ 888, 897 ] ], "normalized": [] }, { "id": "11773", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 1002, 1019 ] ], "normalized": [] }, { "id": "11775", "type": "", "text": [ "HbF" ], "offsets": [ [ 930, 933 ] ], "normalized": [] }, { "id": "11776", "type": "", "text": [ "beta-thalassaemia" ], "offsets": [ [ 1002, 1019 ] ], "normalized": [] }, { "id": "11778", "type": "", "text": [ "HbF" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "11779", "type": "", "text": [ "HBB disorders" ], "offsets": [ [ 1217, 1230 ] ], "normalized": [] }, { "id": "11781", "type": "", "text": [ "HBS1L-MYB" ], "offsets": [ [ 888, 897 ] ], "normalized": [] }, { "id": "11782", "type": "", "text": [ "HbF" ], "offsets": [ [ 930, 933 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11744", "type": "PA", "arg1_id": "11742", "arg2_id": "11743", "normalized": [] }, { "id": "11747", "type": "PA", "arg1_id": "11745", "arg2_id": "11746", "normalized": [] }, { "id": "11750", "type": "PA", "arg1_id": "11748", "arg2_id": "11749", "normalized": [] }, { "id": "11753", "type": "PA", "arg1_id": "11751", "arg2_id": "11752", "normalized": [] }, { "id": "11756", "type": "PA", "arg1_id": "11754", "arg2_id": "11755", "normalized": [] }, { "id": "11759", "type": "PA", "arg1_id": "11757", "arg2_id": "11758", "normalized": [] }, { "id": "11762", "type": "PA", "arg1_id": "11760", "arg2_id": "11761", "normalized": [] }, { "id": "11765", "type": "PA", "arg1_id": "11763", "arg2_id": "11764", "normalized": [] }, { "id": "11768", "type": "PA", "arg1_id": "11766", "arg2_id": "11767", "normalized": [] }, { "id": "11771", "type": "PA", "arg1_id": "11769", "arg2_id": "11770", "normalized": [] }, { "id": "11774", "type": "PA", "arg1_id": "11772", "arg2_id": "11773", "normalized": [] }, { "id": "11777", "type": "PA", "arg1_id": "11775", "arg2_id": "11776", "normalized": [] }, { "id": "11780", "type": "PA", "arg1_id": "11778", "arg2_id": "11779", "normalized": [] }, { "id": "11783", "type": "PA", "arg1_id": "11781", "arg2_id": "11782", "normalized": [] } ]

[ { "id": "11786", "type": "title", "text": [ "Could iron deposits in hepatocytes serve as a prognostic marker of HFE gene mutations?" ], "offsets": [ [ 0, 86 ] ] }, { "id": "11787", "type": "abstract", "text": [ "BACKGROUND/AIMS: The diagnosis of hereditary hemochromatosis (HH) is based on qualitative measurement of tissue iron concentration and genetic tests. The aim of this study was to evaluate the correlation between the presence of iron deposits in the liver and the HFE gene mutations in patients with chronic liver diseases (CLD). METHODOLOGY: The 182 patients, age range 18-71 years, were hospitalized in Gdansk because of CLD. The C282Y, H63D and S65C HFE mutations were screened by PCR-RFLP analysis. Liver function tests, serological examinations for viral hepatitis, serum iron and ferritin concentration and semiquantitative assessment of liver iron were done in all subjects. Patients were divided into Group A without iron deposits in the liver, and Group B with deposits. The most frequent etiology of CLD was chronic hepatitis C. RESULTS: Biochemical parameters indicating iron storage and ALT activity were significantly higher in Group B. Either typical for diagnosis HH homozygotes C282Y/C282Y and combined heterozygotes C282Y/H63D or carriers of other HFE gene mutations were found significantly more frequently in Group B. CONCLUSIONS: The finding of iron deposits in routinely obtained liver specimen correlates with occurrence of the different HFE gene mutations." ], "offsets": [ [ 87, 1365 ] ] } ]

[ { "id": "11788", "type": "SNP & Sequence variations", "text": [ "HFE gene mutations" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "11789", "type": "Genes & Molecular Sequences", "text": [ "HFE gene mutations" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "11790", "type": "Diseases & Disorders", "text": [ "HFE gene mutations" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "11791", "type": "Diseases & Disorders", "text": [ "hereditary hemochromatosis" ], "offsets": [ [ 121, 147 ] ], "normalized": [] }, { "id": "11792", "type": "Diseases & Disorders", "text": [ "HH" ], "offsets": [ [ 149, 151 ] ], "normalized": [] }, { "id": "11793", "type": "SNP & Sequence variations", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11794", "type": "Genes & Molecular Sequences", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11795", "type": "Diseases & Disorders", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11796", "type": "Diseases & Disorders", "text": [ "chronic liver diseases" ], "offsets": [ [ 386, 408 ] ], "normalized": [] }, { "id": "11797", "type": "Diseases & Disorders", "text": [ "CLD" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "11798", "type": "Genes & Molecular Sequences", "text": [ "CLD" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "11799", "type": "Diseases & Disorders", "text": [ "CLD" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "11800", "type": "Genes & Molecular Sequences", "text": [ "CLD" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "11801", "type": "SNP & Sequence variations", "text": [ "C282Y" ], "offsets": [ [ 518, 523 ] ], "normalized": [] }, { "id": "11802", "type": "SNP & Sequence variations", "text": [ "H63D" ], "offsets": [ [ 525, 529 ] ], "normalized": [] }, { "id": "11803", "type": "SNP & Sequence variations", "text": [ "S65C" ], "offsets": [ [ 534, 538 ] ], "normalized": [] }, { "id": "11804", "type": "SNP & Sequence variations", "text": [ "HFE mutations" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "11805", "type": "Genes & Molecular Sequences", "text": [ "HFE mutations" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "11806", "type": "Diseases & Disorders", "text": [ "HFE mutations" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "11807", "type": "Diseases & Disorders", "text": [ "viral hepatitis" ], "offsets": [ [ 640, 655 ] ], "normalized": [] }, { "id": "11808", "type": "Diseases & Disorders", "text": [ "Group B" ], "offsets": [ [ 843, 850 ] ], "normalized": [] }, { "id": "11809", "type": "Diseases & Disorders", "text": [ "CLD" ], "offsets": [ [ 896, 899 ] ], "normalized": [] }, { "id": "11810", "type": "Genes & Molecular Sequences", "text": [ "CLD" ], "offsets": [ [ 896, 899 ] ], "normalized": [] }, { "id": "11811", "type": "Diseases & Disorders", "text": [ "chronic hepatitis C" ], "offsets": [ [ 904, 923 ] ], "normalized": [] }, { "id": "11812", "type": "Genes & Molecular Sequences", "text": [ "ALT" ], "offsets": [ [ 985, 988 ] ], "normalized": [] }, { "id": "11813", "type": "Diseases & Disorders", "text": [ "Group B" ], "offsets": [ [ 1027, 1034 ] ], "normalized": [] }, { "id": "11814", "type": "Diseases & Disorders", "text": [ "HH" ], "offsets": [ [ 1065, 1067 ] ], "normalized": [] }, { "id": "11815", "type": "SNP & Sequence variations", "text": [ "C282Y/C282Y" ], "offsets": [ [ 1080, 1091 ] ], "normalized": [] }, { "id": "11816", "type": "SNP & Sequence variations", "text": [ "C282Y/H63D" ], "offsets": [ [ 1119, 1129 ] ], "normalized": [] }, { "id": "11817", "type": "SNP & Sequence variations", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11818", "type": "Genes & Molecular Sequences", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11819", "type": "Diseases & Disorders", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11820", "type": "Diseases & Disorders", "text": [ "Group B" ], "offsets": [ [ 1214, 1221 ] ], "normalized": [] }, { "id": "11821", "type": "SNP & Sequence variations", "text": [ "HFE gene mutations" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "11822", "type": "Genes & Molecular Sequences", "text": [ "HFE gene mutations" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "11823", "type": "Diseases & Disorders", "text": [ "HFE gene mutations" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "11824", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "11825", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "11827", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11828", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11830", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11831", "type": "", "text": [ "chronic liver diseases" ], "offsets": [ [ 386, 408 ] ], "normalized": [] }, { "id": "11833", "type": "", "text": [ "CLD" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "11834", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11836", "type": "", "text": [ "CLD" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "11837", "type": "", "text": [ "chronic liver diseases" ], "offsets": [ [ 386, 408 ] ], "normalized": [] }, { "id": "11839", "type": "", "text": [ "HFE mutations" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "11840", "type": "", "text": [ "HFE mutations" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "11842", "type": "", "text": [ "CLD" ], "offsets": [ [ 896, 899 ] ], "normalized": [] }, { "id": "11843", "type": "", "text": [ "chronic hepatitis C" ], "offsets": [ [ 904, 923 ] ], "normalized": [] }, { "id": "11845", "type": "", "text": [ "ALT" ], "offsets": [ [ 985, 988 ] ], "normalized": [] }, { "id": "11846", "type": "", "text": [ "Group B" ], "offsets": [ [ 1027, 1034 ] ], "normalized": [] }, { "id": "11848", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11849", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11851", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11852", "type": "", "text": [ "Group B" ], "offsets": [ [ 1214, 1221 ] ], "normalized": [] }, { "id": "11854", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "11855", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "11857", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 350, 368 ] ], "normalized": [] }, { "id": "11858", "type": "", "text": [ "CLD" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "11860", "type": "", "text": [ "HFE gene mutations" ], "offsets": [ [ 1151, 1169 ] ], "normalized": [] }, { "id": "11861", "type": "", "text": [ "HH" ], "offsets": [ [ 1065, 1067 ] ], "normalized": [] }, { "id": "11863", "type": "", "text": [ "C282Y/H63D" ], "offsets": [ [ 1119, 1129 ] ], "normalized": [] }, { "id": "11864", "type": "", "text": [ "HH" ], "offsets": [ [ 1065, 1067 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11826", "type": "PA", "arg1_id": "11824", "arg2_id": "11825", "normalized": [] }, { "id": "11829", "type": "PA", "arg1_id": "11827", "arg2_id": "11828", "normalized": [] }, { "id": "11832", "type": "PA", "arg1_id": "11830", "arg2_id": "11831", "normalized": [] }, { "id": "11835", "type": "PA", "arg1_id": "11833", "arg2_id": "11834", "normalized": [] }, { "id": "11838", "type": "PA", "arg1_id": "11836", "arg2_id": "11837", "normalized": [] }, { "id": "11841", "type": "PA", "arg1_id": "11839", "arg2_id": "11840", "normalized": [] }, { "id": "11844", "type": "PA", "arg1_id": "11842", "arg2_id": "11843", "normalized": [] }, { "id": "11847", "type": "PA", "arg1_id": "11845", "arg2_id": "11846", "normalized": [] }, { "id": "11850", "type": "PA", "arg1_id": "11848", "arg2_id": "11849", "normalized": [] }, { "id": "11853", "type": "PA", "arg1_id": "11851", "arg2_id": "11852", "normalized": [] }, { "id": "11856", "type": "PA", "arg1_id": "11854", "arg2_id": "11855", "normalized": [] }, { "id": "11859", "type": "SA", "arg1_id": "11857", "arg2_id": "11858", "normalized": [] }, { "id": "11862", "type": "PA", "arg1_id": "11860", "arg2_id": "11861", "normalized": [] }, { "id": "11865", "type": "PA", "arg1_id": "11863", "arg2_id": "11864", "normalized": [] } ]

[ { "id": "11868", "type": "title", "text": [ "Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese population." ], "offsets": [ [ 0, 92 ] ] }, { "id": "11869", "type": "abstract", "text": [ "BACKGROUND: The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population. METHODS: Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis. RESULTS: In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype-transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed. CONCLUSIONS: The result supports that the NRG3 gene is a susceptibility gene for schizophrenia." ], "offsets": [ [ 93, 1709 ] ] } ]

[ { "id": "11870", "type": "Genes & Molecular Sequences", "text": [ "Neuregulin 3" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "11871", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 54, 67 ] ], "normalized": [] }, { "id": "11872", "type": "Genes & Molecular Sequences", "text": [ "NRG3" ], "offsets": [ [ 156, 160 ] ], "normalized": [] }, { "id": "11873", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 170, 183 ] ], "normalized": [] }, { "id": "11874", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 256, 269 ] ], "normalized": [] }, { "id": "11875", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 349, 362 ] ], "normalized": [] }, { "id": "11876", "type": "Genes & Molecular Sequences", "text": [ "NRG3" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "11877", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 576, 589 ] ], "normalized": [] }, { "id": "11878", "type": "Genes & Molecular Sequences", "text": [ "trio" ], "offsets": [ [ 663, 667 ] ], "normalized": [] }, { "id": "11879", "type": "SNP & Sequence variations", "text": [ "rs1937970" ], "offsets": [ [ 760, 769 ] ], "normalized": [] }, { "id": "11880", "type": "SNP & Sequence variations", "text": [ "rs677221" ], "offsets": [ [ 774, 782 ] ], "normalized": [] }, { "id": "11881", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 842, 855 ] ], "normalized": [] }, { "id": "11882", "type": "SNP & Sequence variations", "text": [ "rs677221-C" ], "offsets": [ [ 875, 885 ] ], "normalized": [] }, { "id": "11883", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 912, 925 ] ], "normalized": [] }, { "id": "11884", "type": "SNP & Sequence variations", "text": [ "Haplotypes GC" ], "offsets": [ [ 1009, 1022 ] ], "normalized": [] }, { "id": "11885", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 1090, 1103 ] ], "normalized": [] }, { "id": "11886", "type": "Genes & Molecular Sequences", "text": [ "trio" ], "offsets": [ [ 1154, 1158 ] ], "normalized": [] }, { "id": "11887", "type": "SNP & Sequence variations", "text": [ "rs1937970-A" ], "offsets": [ [ 1168, 1179 ] ], "normalized": [] }, { "id": "11888", "type": "SNP & Sequence variations", "text": [ "rs677221-G" ], "offsets": [ [ 1184, 1194 ] ], "normalized": [] }, { "id": "11889", "type": "Diseases & Disorders", "text": [ "schizophrenic" ], "offsets": [ [ 1249, 1262 ] ], "normalized": [] }, { "id": "11890", "type": "Genes & Molecular Sequences", "text": [ "TDT" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [] }, { "id": "11891", "type": "SNP & Sequence variations", "text": [ "rs1937970-rs677221" ], "offsets": [ [ 1406, 1424 ] ], "normalized": [] }, { "id": "11892", "type": "SNP & Sequence variations", "text": [ "haplotype AG" ], "offsets": [ [ 1461, 1473 ] ], "normalized": [] }, { "id": "11893", "type": "SNP & Sequence variations", "text": [ "haplotype GC" ], "offsets": [ [ 1523, 1535 ] ], "normalized": [] }, { "id": "11894", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 1575, 1588 ] ], "normalized": [] }, { "id": "11895", "type": "Genes & Molecular Sequences", "text": [ "NRG3" ], "offsets": [ [ 1656, 1660 ] ], "normalized": [] }, { "id": "11896", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 1695, 1708 ] ], "normalized": [] }, { "id": "11897", "type": "", "text": [ "NRG3" ], "offsets": [ [ 156, 160 ] ], "normalized": [] }, { "id": "11898", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 170, 183 ] ], "normalized": [] }, { "id": "11900", "type": "", "text": [ "rs1937970" ], "offsets": [ [ 760, 769 ] ], "normalized": [] }, { "id": "11901", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 912, 925 ] ], "normalized": [] }, { "id": "11903", "type": "", "text": [ "rs677221" ], "offsets": [ [ 774, 782 ] ], "normalized": [] }, { "id": "11904", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 912, 925 ] ], "normalized": [] }, { "id": "11906", "type": "", "text": [ "rs677221-C" ], "offsets": [ [ 875, 885 ] ], "normalized": [] }, { "id": "11907", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 912, 925 ] ], "normalized": [] }, { "id": "11909", "type": "", "text": [ "Haplotypes GC" ], "offsets": [ [ 1009, 1022 ] ], "normalized": [] }, { "id": "11910", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1090, 1103 ] ], "normalized": [] }, { "id": "11912", "type": "", "text": [ "rs1937970-A" ], "offsets": [ [ 1168, 1179 ] ], "normalized": [] }, { "id": "11913", "type": "", "text": [ "schizophrenic" ], "offsets": [ [ 1249, 1262 ] ], "normalized": [] }, { "id": "11915", "type": "", "text": [ "rs677221-G" ], "offsets": [ [ 1184, 1194 ] ], "normalized": [] }, { "id": "11916", "type": "", "text": [ "schizophrenic" ], "offsets": [ [ 1249, 1262 ] ], "normalized": [] }, { "id": "11918", "type": "", "text": [ "rs1937970-rs677221" ], "offsets": [ [ 1406, 1424 ] ], "normalized": [] }, { "id": "11919", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1575, 1588 ] ], "normalized": [] }, { "id": "11921", "type": "", "text": [ "haplotype AG" ], "offsets": [ [ 1461, 1473 ] ], "normalized": [] }, { "id": "11922", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1575, 1588 ] ], "normalized": [] }, { "id": "11924", "type": "", "text": [ "haplotype GC" ], "offsets": [ [ 1523, 1535 ] ], "normalized": [] }, { "id": "11925", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1575, 1588 ] ], "normalized": [] }, { "id": "11927", "type": "", "text": [ "NRG3" ], "offsets": [ [ 1656, 1660 ] ], "normalized": [] }, { "id": "11928", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1695, 1708 ] ], "normalized": [] }, { "id": "11930", "type": "", "text": [ "Neuregulin 3" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "11931", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 54, 67 ] ], "normalized": [] }, { "id": "11933", "type": "", "text": [ "trio" ], "offsets": [ [ 663, 667 ] ], "normalized": [] }, { "id": "11934", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 576, 589 ] ], "normalized": [] }, { "id": "11936", "type": "", "text": [ "TDT" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [] }, { "id": "11937", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 1575, 1588 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11899", "type": "SA", "arg1_id": "11897", "arg2_id": "11898", "normalized": [] }, { "id": "11902", "type": "PA", "arg1_id": "11900", "arg2_id": "11901", "normalized": [] }, { "id": "11905", "type": "PA", "arg1_id": "11903", "arg2_id": "11904", "normalized": [] }, { "id": "11908", "type": "PA", "arg1_id": "11906", "arg2_id": "11907", "normalized": [] }, { "id": "11911", "type": "PA", "arg1_id": "11909", "arg2_id": "11910", "normalized": [] }, { "id": "11914", "type": "PA", "arg1_id": "11912", "arg2_id": "11913", "normalized": [] }, { "id": "11917", "type": "PA", "arg1_id": "11915", "arg2_id": "11916", "normalized": [] }, { "id": "11920", "type": "PA", "arg1_id": "11918", "arg2_id": "11919", "normalized": [] }, { "id": "11923", "type": "PA", "arg1_id": "11921", "arg2_id": "11922", "normalized": [] }, { "id": "11926", "type": "PA", "arg1_id": "11924", "arg2_id": "11925", "normalized": [] }, { "id": "11929", "type": "PA", "arg1_id": "11927", "arg2_id": "11928", "normalized": [] }, { "id": "11932", "type": "PA", "arg1_id": "11930", "arg2_id": "11931", "normalized": [] }, { "id": "11935", "type": "PA", "arg1_id": "11933", "arg2_id": "11934", "normalized": [] }, { "id": "11938", "type": "PA", "arg1_id": "11936", "arg2_id": "11937", "normalized": [] } ]

[ { "id": "11941", "type": "title", "text": [ "A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis." ], "offsets": [ [ 0, 95 ] ] }, { "id": "11942", "type": "abstract", "text": [ "OBJECTIVE: To assess the efficacy and safety of low-dose topiramate in migraine prophylaxis vs propranolol. PATIENTS AND METHODS: A randomized, double-blind, clinical trial including 62 patients with frequent migraine headaches (> or = 3 attacks per month) was performed for a period of 8 weeks. The patients were randomly divided into two treatment groups - treated by topiramate 50 mg/day and propranolol 80 mg/day, respectively. The patients were assessed at 0, 4, and 8 weeks of the study. Results - The topiramate group showed a reduction in the mean (+/-SD) of monthly migraine frequency from 6.07 (+/-1.89) to 1.83 (+/-1.39) episodes per month, headache intensity from 7.1 (+/-1.45) to 3.67 (+/-2.1) based on the Visual Analog Scale, and headache duration from 16.37 (+/-7.26) to 6.23 (+/-5.22) hours (P < 0.001). In the patients treated with propranolol, the mean (+/-SD) of monthly headache frequency declined from 5.83 (+/-1.98) to 2.2 (+/-1.67) per month, headache intensity lessened from 6.43 (+/-1.6) to 4.13 (+/-1.94) and headache duration decreased from 15.10 (+/-6.84) to 7.27 (+/-6.46) h (P < 0.001). CONCLUSION: This study demonstrated that both low-dose topiramate and propranolol could significantly reduce migraine headache frequency, intensity, and duration. However, compared with propranolol, low-dose topiramate showed better results." ], "offsets": [ [ 96, 1455 ] ] } ]

[ { "id": "11943", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 45, 55 ] ], "normalized": [] }, { "id": "11944", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 59, 70 ] ], "normalized": [] }, { "id": "11945", "type": "Diseases & Disorders", "text": [ "migraine" ], "offsets": [ [ 74, 82 ] ], "normalized": [] }, { "id": "11946", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "11947", "type": "Diseases & Disorders", "text": [ "migraine" ], "offsets": [ [ 167, 175 ] ], "normalized": [] }, { "id": "11948", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 191, 202 ] ], "normalized": [] }, { "id": "11949", "type": "Diseases & Disorders", "text": [ "migraine headaches" ], "offsets": [ [ 305, 323 ] ], "normalized": [] }, { "id": "11950", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 466, 476 ] ], "normalized": [] }, { "id": "11951", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 491, 502 ] ], "normalized": [] }, { "id": "11952", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 604, 614 ] ], "normalized": [] }, { "id": "11953", "type": "Diseases & Disorders", "text": [ "migraine" ], "offsets": [ [ 671, 679 ] ], "normalized": [] }, { "id": "11954", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "11955", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 841, 849 ] ], "normalized": [] }, { "id": "11956", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "11957", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 987, 995 ] ], "normalized": [] }, { "id": "11958", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 1063, 1071 ] ], "normalized": [] }, { "id": "11959", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 1132, 1140 ] ], "normalized": [] }, { "id": "11960", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 1269, 1279 ] ], "normalized": [] }, { "id": "11961", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 1284, 1295 ] ], "normalized": [] }, { "id": "11962", "type": "Diseases & Disorders", "text": [ "migraine headache" ], "offsets": [ [ 1323, 1340 ] ], "normalized": [] }, { "id": "11963", "type": "Chemicals & Drugs", "text": [ "propranolol" ], "offsets": [ [ 1400, 1411 ] ], "normalized": [] }, { "id": "11964", "type": "Chemicals & Drugs", "text": [ "topiramate" ], "offsets": [ [ 1422, 1432 ] ], "normalized": [] }, { "id": "11965", "type": "", "text": [ "topiramate" ], "offsets": [ [ 604, 614 ] ], "normalized": [] }, { "id": "11966", "type": "", "text": [ "migraine" ], "offsets": [ [ 671, 679 ] ], "normalized": [] }, { "id": "11968", "type": "", "text": [ "topiramate" ], "offsets": [ [ 604, 614 ] ], "normalized": [] }, { "id": "11969", "type": "", "text": [ "headache" ], "offsets": [ [ 841, 849 ] ], "normalized": [] }, { "id": "11971", "type": "", "text": [ "propranolol" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "11972", "type": "", "text": [ "headache" ], "offsets": [ [ 1132, 1140 ] ], "normalized": [] }, { "id": "11974", "type": "", "text": [ "topiramate" ], "offsets": [ [ 1269, 1279 ] ], "normalized": [] }, { "id": "11975", "type": "", "text": [ "migraine headache" ], "offsets": [ [ 1323, 1340 ] ], "normalized": [] }, { "id": "11977", "type": "", "text": [ "propranolol" ], "offsets": [ [ 1284, 1295 ] ], "normalized": [] }, { "id": "11978", "type": "", "text": [ "migraine headache" ], "offsets": [ [ 1323, 1340 ] ], "normalized": [] }, { "id": "11980", "type": "", "text": [ "topiramate" ], "offsets": [ [ 604, 614 ] ], "normalized": [] }, { "id": "11981", "type": "", "text": [ "headache" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "11983", "type": "", "text": [ "propranolol" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "11984", "type": "", "text": [ "headache" ], "offsets": [ [ 1063, 1071 ] ], "normalized": [] }, { "id": "11986", "type": "", "text": [ "topiramate" ], "offsets": [ [ 45, 55 ] ], "normalized": [] }, { "id": "11987", "type": "", "text": [ "migraine" ], "offsets": [ [ 74, 82 ] ], "normalized": [] }, { "id": "11989", "type": "", "text": [ "propranolol" ], "offsets": [ [ 59, 70 ] ], "normalized": [] }, { "id": "11990", "type": "", "text": [ "migraine" ], "offsets": [ [ 74, 82 ] ], "normalized": [] }, { "id": "11992", "type": "", "text": [ "topiramate" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "11993", "type": "", "text": [ "migraine" ], "offsets": [ [ 167, 175 ] ], "normalized": [] }, { "id": "11995", "type": "", "text": [ "propranolol" ], "offsets": [ [ 191, 202 ] ], "normalized": [] }, { "id": "11996", "type": "", "text": [ "migraine" ], "offsets": [ [ 167, 175 ] ], "normalized": [] }, { "id": "11998", "type": "", "text": [ "propranolol" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "11999", "type": "", "text": [ "headache" ], "offsets": [ [ 987, 995 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11967", "type": "PA", "arg1_id": "11965", "arg2_id": "11966", "normalized": [] }, { "id": "11970", "type": "PA", "arg1_id": "11968", "arg2_id": "11969", "normalized": [] }, { "id": "11973", "type": "PA", "arg1_id": "11971", "arg2_id": "11972", "normalized": [] }, { "id": "11976", "type": "PA", "arg1_id": "11974", "arg2_id": "11975", "normalized": [] }, { "id": "11979", "type": "PA", "arg1_id": "11977", "arg2_id": "11978", "normalized": [] }, { "id": "11982", "type": "PA", "arg1_id": "11980", "arg2_id": "11981", "normalized": [] }, { "id": "11985", "type": "PA", "arg1_id": "11983", "arg2_id": "11984", "normalized": [] }, { "id": "11988", "type": "PA", "arg1_id": "11986", "arg2_id": "11987", "normalized": [] }, { "id": "11991", "type": "PA", "arg1_id": "11989", "arg2_id": "11990", "normalized": [] }, { "id": "11994", "type": "PA", "arg1_id": "11992", "arg2_id": "11993", "normalized": [] }, { "id": "11997", "type": "PA", "arg1_id": "11995", "arg2_id": "11996", "normalized": [] }, { "id": "12000", "type": "PA", "arg1_id": "11998", "arg2_id": "11999", "normalized": [] } ]

[ { "id": "12003", "type": "title", "text": [ "Posaconazole: an oral triazole with an extended spectrum of activity." ], "offsets": [ [ 0, 69 ] ] }, { "id": "12004", "type": "abstract", "text": [ "OBJECTIVE: To summarize the published clinical data on posaconazole, critically review the New Drug Application data submitted to the Food and Drug Administration, and provide information critical for evaluation and formulary positioning. DATA SOURCES: Reported investigations were identified from MEDLINE (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov, and www.fda.gov. STUDY SELECTION AND DATA EXTRACTION: English-language articles were selected. All available in vitro, animal, clinical, and human studies describing the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and adverse events of posaconazole were reviewed. DATA SYNTHESIS: Posaconazole is an oral broad-spectrum triazole with activity against many yeasts and molds. Resistance to posaconazole has been reported, but has been rare to date. Posaconazole, in doses of 200 mg 3 times daily, reduced breakthrough invasive fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR 0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell transplants compared with those receiving fluconazole. Similarly, the same regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5) and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and itraconazole in neutropenic patients. Posaconazole is noninferior to fluconazole for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity for this indication remains unclear, as many other treatment options exist. Smaller investigations have analyzed use of posaconazole for patients requiring salvage or alternative treatment for zygomycosis, fusariosis, cryptococcal meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify efficacy for such expanded use, and therapeutic drug monitoring may improve outcomes. The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea. CONCLUSIONS: Posaconazole appears to be a valuable and promising addition to the antifungal armamentarium for prophylaxis and treatment of various fungal processes. At this time, posaconazole should probably be reserved for prophylaxis in patients at high risk for invasive fungal infection, as salvage therapy in refractory or resistant infections, or for patients with intolerance to other therapies." ], "offsets": [ [ 70, 2483 ] ] } ]

[ { "id": "12005", "type": "Chemicals & Drugs", "text": [ "Posaconazole" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "12006", "type": "Chemicals & Drugs", "text": [ "oral triazole" ], "offsets": [ [ 17, 30 ] ], "normalized": [] }, { "id": "12007", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 125, 137 ] ], "normalized": [] }, { "id": "12008", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 713, 725 ] ], "normalized": [] }, { "id": "12009", "type": "Chemicals & Drugs", "text": [ "Posaconazole" ], "offsets": [ [ 757, 769 ] ], "normalized": [] }, { "id": "12010", "type": "Chemicals & Drugs", "text": [ "oral broad-spectrum triazole" ], "offsets": [ [ 776, 804 ] ], "normalized": [] }, { "id": "12011", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 864, 876 ] ], "normalized": [] }, { "id": "12012", "type": "Chemicals & Drugs", "text": [ "Posaconazole" ], "offsets": [ [ 923, 935 ] ], "normalized": [] }, { "id": "12013", "type": "Diseases & Disorders", "text": [ "invasive fungal infections" ], "offsets": [ [ 992, 1018 ] ], "normalized": [] }, { "id": "12014", "type": "Diseases & Disorders", "text": [ "aspergillosis" ], "offsets": [ [ 1054, 1067 ] ], "normalized": [] }, { "id": "12015", "type": "Chemicals & Drugs", "text": [ "fluconazole" ], "offsets": [ [ 1197, 1208 ] ], "normalized": [] }, { "id": "12016", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 1241, 1253 ] ], "normalized": [] }, { "id": "12017", "type": "Diseases & Disorders", "text": [ "invasive fungal infections" ], "offsets": [ [ 1262, 1288 ] ], "normalized": [] }, { "id": "12018", "type": "Diseases & Disorders", "text": [ "aspergillosis" ], "offsets": [ [ 1315, 1328 ] ], "normalized": [] }, { "id": "12019", "type": "Chemicals & Drugs", "text": [ "fluconazole" ], "offsets": [ [ 1377, 1388 ] ], "normalized": [] }, { "id": "12020", "type": "Chemicals & Drugs", "text": [ "itraconazole" ], "offsets": [ [ 1393, 1405 ] ], "normalized": [] }, { "id": "12021", "type": "Chemicals & Drugs", "text": [ "Posaconazole" ], "offsets": [ [ 1431, 1443 ] ], "normalized": [] }, { "id": "12022", "type": "Chemicals & Drugs", "text": [ "fluconazole" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] }, { "id": "12023", "type": "Diseases & Disorders", "text": [ "oropharyngeal candidiasis" ], "offsets": [ [ 1491, 1516 ] ], "normalized": [] }, { "id": "12024", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12025", "type": "Diseases & Disorders", "text": [ "zygomycosis" ], "offsets": [ [ 1746, 1757 ] ], "normalized": [] }, { "id": "12026", "type": "Diseases & Disorders", "text": [ "fusariosis" ], "offsets": [ [ 1759, 1769 ] ], "normalized": [] }, { "id": "12027", "type": "Diseases & Disorders", "text": [ "cryptococcal meningitis" ], "offsets": [ [ 1771, 1794 ] ], "normalized": [] }, { "id": "12028", "type": "Diseases & Disorders", "text": [ "coccidioidomycosis" ], "offsets": [ [ 1796, 1814 ] ], "normalized": [] }, { "id": "12029", "type": "Diseases & Disorders", "text": [ "histoplasmosis" ], "offsets": [ [ 1820, 1834 ] ], "normalized": [] }, { "id": "12030", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 1968, 1983 ] ], "normalized": [] }, { "id": "12031", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 2011, 2023 ] ], "normalized": [] }, { "id": "12032", "type": "Diseases & Disorders", "text": [ "headache" ], "offsets": [ [ 2032, 2040 ] ], "normalized": [] }, { "id": "12033", "type": "Diseases & Disorders", "text": [ "nausea" ], "offsets": [ [ 2049, 2055 ] ], "normalized": [] }, { "id": "12034", "type": "Diseases & Disorders", "text": [ "vomiting" ], "offsets": [ [ 2057, 2065 ] ], "normalized": [] }, { "id": "12035", "type": "Diseases & Disorders", "text": [ "diarrhea" ], "offsets": [ [ 2071, 2079 ] ], "normalized": [] }, { "id": "12036", "type": "Chemicals & Drugs", "text": [ "Posaconazole" ], "offsets": [ [ 2094, 2106 ] ], "normalized": [] }, { "id": "12037", "type": "Chemicals & Drugs", "text": [ "antifungal" ], "offsets": [ [ 2162, 2172 ] ], "normalized": [] }, { "id": "12038", "type": "Chemicals & Drugs", "text": [ "posaconazole" ], "offsets": [ [ 2260, 2272 ] ], "normalized": [] }, { "id": "12039", "type": "Diseases & Disorders", "text": [ "invasive fungal infection" ], "offsets": [ [ 2346, 2371 ] ], "normalized": [] }, { "id": "12040", "type": "Diseases & Disorders", "text": [ "resistant infections" ], "offsets": [ [ 2409, 2429 ] ], "normalized": [] }, { "id": "12041", "type": "", "text": [ "Posaconazole" ], "offsets": [ [ 923, 935 ] ], "normalized": [] }, { "id": "12042", "type": "", "text": [ "aspergillosis" ], "offsets": [ [ 1054, 1067 ] ], "normalized": [] }, { "id": "12044", "type": "", "text": [ "Posaconazole" ], "offsets": [ [ 923, 935 ] ], "normalized": [] }, { "id": "12045", "type": "", "text": [ "invasive fungal infections" ], "offsets": [ [ 992, 1018 ] ], "normalized": [] }, { "id": "12047", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1241, 1253 ] ], "normalized": [] }, { "id": "12048", "type": "", "text": [ "aspergillosis" ], "offsets": [ [ 1315, 1328 ] ], "normalized": [] }, { "id": "12050", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1241, 1253 ] ], "normalized": [] }, { "id": "12051", "type": "", "text": [ "invasive fungal infections" ], "offsets": [ [ 1262, 1288 ] ], "normalized": [] }, { "id": "12053", "type": "", "text": [ "Posaconazole" ], "offsets": [ [ 1431, 1443 ] ], "normalized": [] }, { "id": "12054", "type": "", "text": [ "oropharyngeal candidiasis" ], "offsets": [ [ 1491, 1516 ] ], "normalized": [] }, { "id": "12056", "type": "", "text": [ "fluconazole" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] }, { "id": "12057", "type": "", "text": [ "oropharyngeal candidiasis" ], "offsets": [ [ 1491, 1516 ] ], "normalized": [] }, { "id": "12059", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2011, 2023 ] ], "normalized": [] }, { "id": "12060", "type": "", "text": [ "headache" ], "offsets": [ [ 2032, 2040 ] ], "normalized": [] }, { "id": "12062", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2011, 2023 ] ], "normalized": [] }, { "id": "12063", "type": "", "text": [ "nausea" ], "offsets": [ [ 2049, 2055 ] ], "normalized": [] }, { "id": "12065", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2011, 2023 ] ], "normalized": [] }, { "id": "12066", "type": "", "text": [ "vomiting" ], "offsets": [ [ 2057, 2065 ] ], "normalized": [] }, { "id": "12068", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2011, 2023 ] ], "normalized": [] }, { "id": "12069", "type": "", "text": [ "diarrhea" ], "offsets": [ [ 2071, 2079 ] ], "normalized": [] }, { "id": "12071", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2260, 2272 ] ], "normalized": [] }, { "id": "12072", "type": "", "text": [ "resistant infections" ], "offsets": [ [ 2409, 2429 ] ], "normalized": [] }, { "id": "12074", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 2260, 2272 ] ], "normalized": [] }, { "id": "12075", "type": "", "text": [ "invasive fungal infection" ], "offsets": [ [ 2346, 2371 ] ], "normalized": [] }, { "id": "12077", "type": "", "text": [ "fluconazole" ], "offsets": [ [ 1197, 1208 ] ], "normalized": [] }, { "id": "12078", "type": "", "text": [ "invasive fungal infections" ], "offsets": [ [ 992, 1018 ] ], "normalized": [] }, { "id": "12080", "type": "", "text": [ "fluconazole" ], "offsets": [ [ 1197, 1208 ] ], "normalized": [] }, { "id": "12081", "type": "", "text": [ "aspergillosis" ], "offsets": [ [ 1054, 1067 ] ], "normalized": [] }, { "id": "12083", "type": "", "text": [ "fluconazole" ], "offsets": [ [ 1377, 1388 ] ], "normalized": [] }, { "id": "12084", "type": "", "text": [ "invasive fungal infections" ], "offsets": [ [ 1262, 1288 ] ], "normalized": [] }, { "id": "12086", "type": "", "text": [ "fluconazole" ], "offsets": [ [ 1377, 1388 ] ], "normalized": [] }, { "id": "12087", "type": "", "text": [ "aspergillosis" ], "offsets": [ [ 1315, 1328 ] ], "normalized": [] }, { "id": "12089", "type": "", "text": [ "itraconazole" ], "offsets": [ [ 1393, 1405 ] ], "normalized": [] }, { "id": "12090", "type": "", "text": [ "invasive fungal infections" ], "offsets": [ [ 1262, 1288 ] ], "normalized": [] }, { "id": "12092", "type": "", "text": [ "itraconazole" ], "offsets": [ [ 1393, 1405 ] ], "normalized": [] }, { "id": "12093", "type": "", "text": [ "aspergillosis" ], "offsets": [ [ 1315, 1328 ] ], "normalized": [] }, { "id": "12095", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12096", "type": "", "text": [ "zygomycosis" ], "offsets": [ [ 1746, 1757 ] ], "normalized": [] }, { "id": "12098", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12099", "type": "", "text": [ "cryptococcal meningitis" ], "offsets": [ [ 1771, 1794 ] ], "normalized": [] }, { "id": "12101", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12102", "type": "", "text": [ "coccidioidomycosis" ], "offsets": [ [ 1796, 1814 ] ], "normalized": [] }, { "id": "12104", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12105", "type": "", "text": [ "histoplasmosis" ], "offsets": [ [ 1820, 1834 ] ], "normalized": [] }, { "id": "12107", "type": "", "text": [ "posaconazole" ], "offsets": [ [ 1673, 1685 ] ], "normalized": [] }, { "id": "12108", "type": "", "text": [ "fusariosis" ], "offsets": [ [ 1759, 1769 ] ], "normalized": [] } ]

[]

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[ { "id": "12043", "type": "PA", "arg1_id": "12041", "arg2_id": "12042", "normalized": [] }, { "id": "12046", "type": "PA", "arg1_id": "12044", "arg2_id": "12045", "normalized": [] }, { "id": "12049", "type": "PA", "arg1_id": "12047", "arg2_id": "12048", "normalized": [] }, { "id": "12052", "type": "PA", "arg1_id": "12050", "arg2_id": "12051", "normalized": [] }, { "id": "12055", "type": "PA", "arg1_id": "12053", "arg2_id": "12054", "normalized": [] }, { "id": "12058", "type": "PA", "arg1_id": "12056", "arg2_id": "12057", "normalized": [] }, { "id": "12061", "type": "PA", "arg1_id": "12059", "arg2_id": "12060", "normalized": [] }, { "id": "12064", "type": "PA", "arg1_id": "12062", "arg2_id": "12063", "normalized": [] }, { "id": "12067", "type": "PA", "arg1_id": "12065", "arg2_id": "12066", "normalized": [] }, { "id": "12070", "type": "PA", "arg1_id": "12068", "arg2_id": "12069", "normalized": [] }, { "id": "12073", "type": "SA", "arg1_id": "12071", "arg2_id": "12072", "normalized": [] }, { "id": "12076", "type": "SA", "arg1_id": "12074", "arg2_id": "12075", "normalized": [] }, { "id": "12079", "type": "PA", "arg1_id": "12077", "arg2_id": "12078", "normalized": [] }, { "id": "12082", "type": "PA", "arg1_id": "12080", "arg2_id": "12081", "normalized": [] }, { "id": "12085", "type": "PA", "arg1_id": "12083", "arg2_id": "12084", "normalized": [] }, { "id": "12088", "type": "PA", "arg1_id": "12086", "arg2_id": "12087", "normalized": [] }, { "id": "12091", "type": "PA", "arg1_id": "12089", "arg2_id": "12090", "normalized": [] }, { "id": "12094", "type": "PA", "arg1_id": "12092", "arg2_id": "12093", "normalized": [] }, { "id": "12097", "type": "SA", "arg1_id": "12095", "arg2_id": "12096", "normalized": [] }, { "id": "12100", "type": "SA", "arg1_id": "12098", "arg2_id": "12099", "normalized": [] }, { "id": "12103", "type": "SA", "arg1_id": "12101", "arg2_id": "12102", "normalized": [] }, { "id": "12106", "type": "SA", "arg1_id": "12104", "arg2_id": "12105", "normalized": [] }, { "id": "12109", "type": "SA", "arg1_id": "12107", "arg2_id": "12108", "normalized": [] } ]

[ { "id": "12112", "type": "title", "text": [ "The importance of preoperative hemoglobin evaluation in large volume liposuction: lessons learned from our 15-year experience." ], "offsets": [ [ 0, 126 ] ] }, { "id": "12113", "type": "abstract", "text": [ "Liposuction of >5 L of total aspirate at one setting is defined as large volume liposuction (LVL). A retrospective chart review was performed on all patients who underwent LVL from January 1990 to June 2005. Sixty-two patients underwent LVL. The mean volume of total aspirate was 8 L (5.0-11.7 L). There were a total of 6 patients who had complications. These included symptomatic postoperative anemia requiring blood transfusions on postoperative day 1 (n = 5), and an expanding hematoma requiring operative evacuation without transfusion (n = 1). Two of the patients who had blood transfusions had a history of gastric bypass and all of the patients were preoperatively anemic (<11.5 mg/dL). The mean follow up was 38 months. LVL is safe when performed in healthy patients under strict guidelines. Hemoglobin levels of all potential LVL patients should be checked preoperatively, and surgery should be withheld for levels <12 g/dL." ], "offsets": [ [ 127, 1060 ] ] } ]

[ { "id": "12114", "type": "Diseases & Disorders", "text": [ "aspirate" ], "offsets": [ [ 156, 164 ] ], "normalized": [] }, { "id": "12115", "type": "Diseases & Disorders", "text": [ "aspirate" ], "offsets": [ [ 394, 402 ] ], "normalized": [] }, { "id": "12116", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 466, 479 ] ], "normalized": [] }, { "id": "12117", "type": "Diseases & Disorders", "text": [ "symptomatic postoperative anemia" ], "offsets": [ [ 496, 528 ] ], "normalized": [] }, { "id": "12118", "type": "Diseases & Disorders", "text": [ "expanding hematoma" ], "offsets": [ [ 597, 615 ] ], "normalized": [] } ]

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[ { "id": "12121", "type": "title", "text": [ "Transplantation of ABO-incompatible and living unrelated donor-recipient combinations." ], "offsets": [ [ 0, 86 ] ] }, { "id": "12122", "type": "abstract", "text": [ "INTRODUCTION: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 199 (23.9%) kidneys were donated from spouses (husband/wife) and 174 (20.9%) from ABO-incompatible donors. This study summarized our experience of ABO-incompatible and living unrelated, especially spousal kidney transplantation. PATIENTS AND METHODS: We performed 44 cases of living donor kidney transplantation (LKT) between April 2003 and July 2007, including 14 (31.8%) from spouses (unrelated donor) who were divided into two groups: six patients (group 1; G1) from ABO-incompatible donors and eight patients (group 2; G2) from ABO-compatible donors. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In all G1 patients plasmapheresis was performed to remove anti-AB antibodies prior to LKT, and splenectomy performed at the time of or before LKT. RESULTS: Among G1, no patient died. Among G2, one patient died with a functioning graft due to a traumatic subdural hematoma. Graft survival rate was 100% in both groups. The incidence of acute rejection was 33.3% and 25.0% in G1 and G2, respectively. No patient experienced a lethal infectious complication. CONCLUSIONS: Our results demonstrated that transplantation from an ABO-incompatible spousal donor was equivalent to transplantation from an ABO-compatible spousal donor. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan." ], "offsets": [ [ 87, 1733 ] ] } ]

[ { "id": "12123", "type": "Chemicals & Drugs", "text": [ "tacrolimus" ], "offsets": [ [ 810, 820 ] ], "normalized": [] }, { "id": "12124", "type": "Chemicals & Drugs", "text": [ "cyclosporine" ], "offsets": [ [ 824, 836 ] ], "normalized": [] }, { "id": "12125", "type": "Chemicals & Drugs", "text": [ "mycophenolate mofetil" ], "offsets": [ [ 838, 859 ] ], "normalized": [] }, { "id": "12126", "type": "Chemicals & Drugs", "text": [ "methylprednisolone" ], "offsets": [ [ 865, 883 ] ], "normalized": [] }, { "id": "12127", "type": "Diseases & Disorders", "text": [ "immunosuppression" ], "offsets": [ [ 898, 915 ] ], "normalized": [] }, { "id": "12128", "type": "Chemicals & Drugs", "text": [ "Basiliximab" ], "offsets": [ [ 917, 928 ] ], "normalized": [] }, { "id": "12129", "type": "Diseases & Disorders", "text": [ "traumatic subdural hematoma" ], "offsets": [ [ 1221, 1248 ] ], "normalized": [] }, { "id": "12130", "type": "Diseases & Disorders", "text": [ "acute rejection" ], "offsets": [ [ 1312, 1327 ] ], "normalized": [] }, { "id": "12131", "type": "Diseases & Disorders", "text": [ "lethal infectious complication" ], "offsets": [ [ 1401, 1431 ] ], "normalized": [] }, { "id": "12132", "type": "Diseases & Disorders", "text": [ "infectious" ], "offsets": [ [ 1408, 1418 ] ], "normalized": [] }, { "id": "12133", "type": "", "text": [ "tacrolimus" ], "offsets": [ [ 810, 820 ] ], "normalized": [] }, { "id": "12134", "type": "", "text": [ "immunosuppression" ], "offsets": [ [ 898, 915 ] ], "normalized": [] }, { "id": "12136", "type": "", "text": [ "cyclosporine" ], "offsets": [ [ 824, 836 ] ], "normalized": [] }, { "id": "12137", "type": "", "text": [ "immunosuppression" ], "offsets": [ [ 898, 915 ] ], "normalized": [] }, { "id": "12139", "type": "", "text": [ "mycophenolate mofetil" ], "offsets": [ [ 838, 859 ] ], "normalized": [] }, { "id": "12140", "type": "", "text": [ "immunosuppression" ], "offsets": [ [ 898, 915 ] ], "normalized": [] }, { "id": "12142", "type": "", "text": [ "methylprednisolone" ], "offsets": [ [ 865, 883 ] ], "normalized": [] }, { "id": "12143", "type": "", "text": [ "immunosuppression" ], "offsets": [ [ 898, 915 ] ], "normalized": [] } ]

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[ { "id": "12135", "type": "PA", "arg1_id": "12133", "arg2_id": "12134", "normalized": [] }, { "id": "12138", "type": "PA", "arg1_id": "12136", "arg2_id": "12137", "normalized": [] }, { "id": "12141", "type": "PA", "arg1_id": "12139", "arg2_id": "12140", "normalized": [] }, { "id": "12144", "type": "PA", "arg1_id": "12142", "arg2_id": "12143", "normalized": [] } ]

[ { "id": "12147", "type": "title", "text": [ "Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer." ], "offsets": [ [ 0, 120 ] ] }, { "id": "12148", "type": "abstract", "text": [ "Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549LUC cells by detecting reduced bioluminescence after an i.v. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer." ], "offsets": [ [ 121, 1389 ] ] } ]

[ { "id": "12149", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 18, 45 ] ], "normalized": [] }, { "id": "12150", "type": "Chemicals & Drugs", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 18, 45 ] ], "normalized": [] }, { "id": "12151", "type": "Chemicals & Drugs", "text": [ "atelocollagen" ], "offsets": [ [ 51, 64 ] ], "normalized": [] }, { "id": "12152", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 416, 443 ] ], "normalized": [] }, { "id": "12153", "type": "Chemicals & Drugs", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 416, 443 ] ], "normalized": [] }, { "id": "12154", "type": "Genes & Molecular Sequences", "text": [ "siRNA" ], "offsets": [ [ 445, 450 ] ], "normalized": [] }, { "id": "12155", "type": "Chemicals & Drugs", "text": [ "PLK-1 siRNA with atelocollagen" ], "offsets": [ [ 509, 539 ] ], "normalized": [] }, { "id": "12156", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 siRNA with atelocollagen" ], "offsets": [ [ 509, 539 ] ], "normalized": [] }, { "id": "12157", "type": "Genes & Molecular Sequences", "text": [ "siRNA" ], "offsets": [ [ 515, 520 ] ], "normalized": [] }, { "id": "12158", "type": "Genes & Molecular Sequences", "text": [ "PLK-1" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "12159", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 siRNA" ], "offsets": [ [ 707, 718 ] ], "normalized": [] }, { "id": "12160", "type": "Chemicals & Drugs", "text": [ "PLK-1 siRNA" ], "offsets": [ [ 707, 718 ] ], "normalized": [] }, { "id": "12161", "type": "Chemicals & Drugs", "text": [ "atelocollagen" ], "offsets": [ [ 851, 864 ] ], "normalized": [] }, { "id": "12162", "type": "Genes & Molecular Sequences", "text": [ "luciferase-labeled A549LUC cells" ], "offsets": [ [ 925, 957 ] ], "normalized": [] }, { "id": "12163", "type": "Chemicals & Drugs", "text": [ "GL3 siRNA/atelocollagen" ], "offsets": [ [ 1033, 1056 ] ], "normalized": [] }, { "id": "12164", "type": "Genes & Molecular Sequences", "text": [ "GL3 siRNA/atelocollagen" ], "offsets": [ [ 1033, 1056 ] ], "normalized": [] }, { "id": "12165", "type": "Chemicals & Drugs", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1058, 1083 ] ], "normalized": [] }, { "id": "12166", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1058, 1083 ] ], "normalized": [] }, { "id": "12167", "type": "Genes & Molecular Sequences", "text": [ "siRNA" ], "offsets": [ [ 1064, 1069 ] ], "normalized": [] }, { "id": "12168", "type": "Chemicals & Drugs", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1230, 1255 ] ], "normalized": [] }, { "id": "12169", "type": "Genes & Molecular Sequences", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1230, 1255 ] ], "normalized": [] }, { "id": "12170", "type": "Genes & Molecular Sequences", "text": [ "siRNA" ], "offsets": [ [ 1236, 1241 ] ], "normalized": [] }, { "id": "12171", "type": "Genes & Molecular Sequences", "text": [ "siRNA" ], "offsets": [ [ 1304, 1309 ] ], "normalized": [] }, { "id": "12172", "type": "Chemicals & Drugs", "text": [ "siRNA" ], "offsets": [ [ 1304, 1309 ] ], "normalized": [] }, { "id": "12173", "type": "", "text": [ "atelocollagen" ], "offsets": [ [ 51, 64 ] ], "normalized": [] }, { "id": "12174", "type": "", "text": [ "liver metastases" ], "offsets": [ [ 88, 104 ] ], "normalized": [] }, { "id": "12176", "type": "", "text": [ "atelocollagen" ], "offsets": [ [ 51, 64 ] ], "normalized": [] }, { "id": "12177", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 108, 119 ] ], "normalized": [] }, { "id": "12179", "type": "", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 18, 45 ] ], "normalized": [] }, { "id": "12180", "type": "", "text": [ "liver metastases" ], "offsets": [ [ 88, 104 ] ], "normalized": [] }, { "id": "12182", "type": "", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 18, 45 ] ], "normalized": [] }, { "id": "12183", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 108, 119 ] ], "normalized": [] }, { "id": "12185", "type": "", "text": [ "PLK-1 siRNA with atelocollagen" ], "offsets": [ [ 509, 539 ] ], "normalized": [] }, { "id": "12186", "type": "", "text": [ "liver metastasis" ], "offsets": [ [ 578, 594 ] ], "normalized": [] }, { "id": "12188", "type": "", "text": [ "PLK-1 siRNA with atelocollagen" ], "offsets": [ [ 509, 539 ] ], "normalized": [] }, { "id": "12189", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 604, 615 ] ], "normalized": [] }, { "id": "12191", "type": "", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 416, 443 ] ], "normalized": [] }, { "id": "12192", "type": "", "text": [ "liver metastasis" ], "offsets": [ [ 578, 594 ] ], "normalized": [] }, { "id": "12194", "type": "", "text": [ "PLK-1 small interfering RNA" ], "offsets": [ [ 416, 443 ] ], "normalized": [] }, { "id": "12195", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 604, 615 ] ], "normalized": [] }, { "id": "12197", "type": "", "text": [ "PLK-1" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "12198", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 685, 696 ] ], "normalized": [] }, { "id": "12200", "type": "", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1058, 1083 ] ], "normalized": [] }, { "id": "12201", "type": "", "text": [ "metastases" ], "offsets": [ [ 1162, 1172 ] ], "normalized": [] }, { "id": "12203", "type": "", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1230, 1255 ] ], "normalized": [] }, { "id": "12204", "type": "", "text": [ "liver metastases" ], "offsets": [ [ 1260, 1276 ] ], "normalized": [] }, { "id": "12206", "type": "", "text": [ "PLK-1 siRNA/atelocollagen" ], "offsets": [ [ 1230, 1255 ] ], "normalized": [] }, { "id": "12207", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 1280, 1291 ] ], "normalized": [] }, { "id": "12209", "type": "", "text": [ "GL3 siRNA/atelocollagen" ], "offsets": [ [ 1033, 1056 ] ], "normalized": [] }, { "id": "12210", "type": "", "text": [ "luciferase-labeled A549LUC cells" ], "offsets": [ [ 925, 957 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12175", "type": "PA", "arg1_id": "12173", "arg2_id": "12174", "normalized": [] }, { "id": "12178", "type": "PA", "arg1_id": "12176", "arg2_id": "12177", "normalized": [] }, { "id": "12181", "type": "PA", "arg1_id": "12179", "arg2_id": "12180", "normalized": [] }, { "id": "12184", "type": "PA", "arg1_id": "12182", "arg2_id": "12183", "normalized": [] }, { "id": "12187", "type": "PA", "arg1_id": "12185", "arg2_id": "12186", "normalized": [] }, { "id": "12190", "type": "PA", "arg1_id": "12188", "arg2_id": "12189", "normalized": [] }, { "id": "12193", "type": "PA", "arg1_id": "12191", "arg2_id": "12192", "normalized": [] }, { "id": "12196", "type": "PA", "arg1_id": "12194", "arg2_id": "12195", "normalized": [] }, { "id": "12199", "type": "PA", "arg1_id": "12197", "arg2_id": "12198", "normalized": [] }, { "id": "12202", "type": "PA", "arg1_id": "12200", "arg2_id": "12201", "normalized": [] }, { "id": "12205", "type": "PA", "arg1_id": "12203", "arg2_id": "12204", "normalized": [] }, { "id": "12208", "type": "PA", "arg1_id": "12206", "arg2_id": "12207", "normalized": [] }, { "id": "12211", "type": "PA", "arg1_id": "12209", "arg2_id": "12210", "normalized": [] } ]

[ { "id": "12214", "type": "title", "text": [ "Deep vein thrombosis." ], "offsets": [ [ 0, 21 ] ] }, { "id": "12215", "type": "abstract", "text": [ "This article reviews the incidence, causes, risk factors, diagnosis, treatment, complications, and prevention of deep vein thrombosis (DVT). Various employees, including long-distance drivers or travelers, sedentary office workers, females taking estrogen, those who are obese, those who have cancer, and those who are hospitalized, may be at risk for developing this condition. Genetic testing can determine some inherited factors predisposing workers to clotting. Low-molecular weight heparins can be used to manage DVT on an outpatient basis." ], "offsets": [ [ 22, 567 ] ] } ]

[ { "id": "12216", "type": "Diseases & Disorders", "text": [ "Deep vein thrombosis" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "12217", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 102, 115 ] ], "normalized": [] }, { "id": "12218", "type": "Diseases & Disorders", "text": [ "deep vein thrombosis" ], "offsets": [ [ 135, 155 ] ], "normalized": [] }, { "id": "12219", "type": "Diseases & Disorders", "text": [ "DVT" ], "offsets": [ [ 157, 160 ] ], "normalized": [] }, { "id": "12220", "type": "Chemicals & Drugs", "text": [ "estrogen" ], "offsets": [ [ 269, 277 ] ], "normalized": [] }, { "id": "12221", "type": "Diseases & Disorders", "text": [ "obese" ], "offsets": [ [ 293, 298 ] ], "normalized": [] }, { "id": "12222", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 315, 321 ] ], "normalized": [] }, { "id": "12223", "type": "Diseases & Disorders", "text": [ "clotting" ], "offsets": [ [ 478, 486 ] ], "normalized": [] }, { "id": "12224", "type": "Chemicals & Drugs", "text": [ "Low-molecular weight heparins" ], "offsets": [ [ 488, 517 ] ], "normalized": [] }, { "id": "12225", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 502, 508 ] ], "normalized": [] }, { "id": "12226", "type": "Diseases & Disorders", "text": [ "DVT" ], "offsets": [ [ 540, 543 ] ], "normalized": [] }, { "id": "12227", "type": "", "text": [ "Low-molecular weight heparins" ], "offsets": [ [ 488, 517 ] ], "normalized": [] }, { "id": "12228", "type": "", "text": [ "DVT" ], "offsets": [ [ 540, 543 ] ], "normalized": [] }, { "id": "12230", "type": "", "text": [ "Low-molecular weight heparins" ], "offsets": [ [ 488, 517 ] ], "normalized": [] }, { "id": "12231", "type": "", "text": [ "DVT" ], "offsets": [ [ 540, 543 ] ], "normalized": [] }, { "id": "12233", "type": "", "text": [ "estrogen" ], "offsets": [ [ 269, 277 ] ], "normalized": [] }, { "id": "12234", "type": "", "text": [ "obese" ], "offsets": [ [ 293, 298 ] ], "normalized": [] }, { "id": "12236", "type": "", "text": [ "estrogen" ], "offsets": [ [ 269, 277 ] ], "normalized": [] }, { "id": "12237", "type": "", "text": [ "cancer" ], "offsets": [ [ 315, 321 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12229", "type": "PA", "arg1_id": "12227", "arg2_id": "12228", "normalized": [] }, { "id": "12232", "type": "PA", "arg1_id": "12230", "arg2_id": "12231", "normalized": [] }, { "id": "12235", "type": "PA", "arg1_id": "12233", "arg2_id": "12234", "normalized": [] }, { "id": "12238", "type": "PA", "arg1_id": "12236", "arg2_id": "12237", "normalized": [] } ]

[ { "id": "12241", "type": "title", "text": [ "The signaling hubs at the crossroad of longevity and age-related disease networks." ], "offsets": [ [ 0, 82 ] ] }, { "id": "12242", "type": "abstract", "text": [ "The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common signaling network which comprises over 40% of all hubs (proteins with multiple interactions) in the human interactome. Along with the insulin pathway, the common signaling network is remarkably enriched with the focal adhesion and adherens junction proteins whose relation to the control of lifespan is yet to be fully addressed. The examples of such candidate proteins include several hubs, focal adhesion kinase PTK2 and the extracellular proteins fibronectin FN1, paxillin PXN, and vinculin VCL. The results of the network-based analysis highlight the potential importance of these pathways, especially hubs, in linking the human longevity and age-related diseases." ], "offsets": [ [ 83, 1098 ] ] } ]

[ { "id": "12243", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 65, 72 ] ], "normalized": [] }, { "id": "12244", "type": "Genes & Molecular Sequences", "text": [ "age-related disease proteins" ], "offsets": [ [ 105, 133 ] ], "normalized": [] }, { "id": "12245", "type": "Diseases & Disorders", "text": [ "age-related disease proteins" ], "offsets": [ [ 105, 133 ] ], "normalized": [] }, { "id": "12246", "type": "Genes & Molecular Sequences", "text": [ "ARDPs" ], "offsets": [ [ 135, 140 ] ], "normalized": [] }, { "id": "12247", "type": "Genes & Molecular Sequences", "text": [ "longevity-associated proteins" ], "offsets": [ [ 146, 175 ] ], "normalized": [] }, { "id": "12248", "type": "Genes & Molecular Sequences", "text": [ "LAPs" ], "offsets": [ [ 177, 181 ] ], "normalized": [] }, { "id": "12249", "type": "Diseases & Disorders", "text": [ "LAPs" ], "offsets": [ [ 177, 181 ] ], "normalized": [] }, { "id": "12250", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 564, 571 ] ], "normalized": [] }, { "id": "12251", "type": "Diseases & Disorders", "text": [ "adhesion" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "12252", "type": "Diseases & Disorders", "text": [ "lifespan" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "12253", "type": "Diseases & Disorders", "text": [ "adhesion" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "12254", "type": "Genes & Molecular Sequences", "text": [ "PTK2" ], "offsets": [ [ 844, 848 ] ], "normalized": [] }, { "id": "12255", "type": "Genes & Molecular Sequences", "text": [ "fibronectin" ], "offsets": [ [ 880, 891 ] ], "normalized": [] }, { "id": "12256", "type": "Genes & Molecular Sequences", "text": [ "FN1" ], "offsets": [ [ 892, 895 ] ], "normalized": [] }, { "id": "12257", "type": "Genes & Molecular Sequences", "text": [ "paxillin" ], "offsets": [ [ 897, 905 ] ], "normalized": [] }, { "id": "12258", "type": "Genes & Molecular Sequences", "text": [ "PXN" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "12259", "type": "Genes & Molecular Sequences", "text": [ "vinculin" ], "offsets": [ [ 915, 923 ] ], "normalized": [] }, { "id": "12260", "type": "Genes & Molecular Sequences", "text": [ "VCL" ], "offsets": [ [ 924, 927 ] ], "normalized": [] }, { "id": "12261", "type": "Diseases & Disorders", "text": [ "diseases" ], "offsets": [ [ 1089, 1097 ] ], "normalized": [] }, { "id": "12262", "type": "", "text": [ "PXN" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "12263", "type": "", "text": [ "adhesion" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "12265", "type": "", "text": [ "VCL" ], "offsets": [ [ 924, 927 ] ], "normalized": [] }, { "id": "12266", "type": "", "text": [ "adhesion" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "12268", "type": "", "text": [ "PTK2" ], "offsets": [ [ 844, 848 ] ], "normalized": [] }, { "id": "12269", "type": "", "text": [ "adhesion" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "12271", "type": "", "text": [ "FN1" ], "offsets": [ [ 892, 895 ] ], "normalized": [] }, { "id": "12272", "type": "", "text": [ "adhesion" ], "offsets": [ [ 828, 836 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12264", "type": "PA", "arg1_id": "12262", "arg2_id": "12263", "normalized": [] }, { "id": "12267", "type": "PA", "arg1_id": "12265", "arg2_id": "12266", "normalized": [] }, { "id": "12270", "type": "PA", "arg1_id": "12268", "arg2_id": "12269", "normalized": [] }, { "id": "12273", "type": "PA", "arg1_id": "12271", "arg2_id": "12272", "normalized": [] } ]

[ { "id": "12276", "type": "title", "text": [ "Sarcomatoid carcinoma of the upper urinary tract: clinical outcome and molecular characterization." ], "offsets": [ [ 0, 98 ] ] }, { "id": "12277", "type": "abstract", "text": [ "Sarcomatoid carcinoma (carcinosarcoma) of the upper urinary collecting system is a rare aggressive malignancy composed of malignant epithelial and stromal components. Because of the paucity of reported cases, the clinical behavior, molecular alterations, and potential therapies for this malignancy are not well understood. Eight cases of sarcomatoid carcinoma involving the upper urinary tract were studied. Clinicopathologic characteristics were reviewed. Immunohistochemical expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/neu, c-kit, and p53 was analyzed in each case. Evaluation for amplification of EGFR and HER2 genes was performed by interphase fluorescence in situ hybridization (FISH). Each tumor was also examined for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 by UroVysion FISH (Vysis, Downers Grove, IL). The patients we studied were 5 females and 3 males, ranging in age from 56 to 78 years (mean age, 69 years). Presenting symptoms included gross hematuria, flank mass, urinary obstruction, fever, or sepsis. Radical nephroureterectomy was performed on all patients. Tumor size ranged from 2 to 13 cm. Coexisting urothelial carcinoma was present in all 8 cases. Heterologous osteosarcoma was identified in 2 cases. Pathologic stage was pT4 in 5 cases and pT3 in 3 cases. Lymph node metastases were present in 5 patients at the time of surgery. Of 8 patients, 7 died within 2 years after surgery. EGFR immunostaining had moderately to strongly positive results in 6 of 8 cases. Both HER2/neu and c-kit immunostaining had negative results in all cases. p53 immunostaining had positive results in 5 of 8 cases. The EGFR polysomy was demonstrated in 7 of 8 cases. No amplification of HER2/neu was present in any case. UroVysion FISH showed abnormalities typical of urothelial carcinoma in all 8 cases. In conclusion, the prognosis of sarcomatoid carcinoma of the upper urinary tract is extremely poor, most patients died within 2 years (7/8 patients). Gains of chromosome 3, 7, and 17 and loss of chromosome 9p21 were commonly observed in these tumors. Our findings suggest that targeted therapy may be a rational strategy in the management of these patients." ], "offsets": [ [ 99, 2347 ] ] } ]

[ { "id": "12278", "type": "Diseases & Disorders", "text": [ "Sarcomatoid carcinoma" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "12279", "type": "Diseases & Disorders", "text": [ "Sarcomatoid carcinoma" ], "offsets": [ [ 99, 120 ] ], "normalized": [] }, { "id": "12280", "type": "Diseases & Disorders", "text": [ "carcinosarcoma" ], "offsets": [ [ 122, 136 ] ], "normalized": [] }, { "id": "12281", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 187, 197 ] ], "normalized": [] }, { "id": "12282", "type": "Diseases & Disorders", "text": [ "malignancy" ], "offsets": [ [ 198, 208 ] ], "normalized": [] }, { "id": "12283", "type": "Diseases & Disorders", "text": [ "malignancy" ], "offsets": [ [ 387, 397 ] ], "normalized": [] }, { "id": "12284", "type": "Diseases & Disorders", "text": [ "sarcomatoid carcinoma" ], "offsets": [ [ 438, 459 ] ], "normalized": [] }, { "id": "12285", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 591, 623 ] ], "normalized": [] }, { "id": "12286", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "12287", "type": "Genes & Molecular Sequences", "text": [ "human epidermal growth factor receptor 2" ], "offsets": [ [ 632, 672 ] ], "normalized": [] }, { "id": "12288", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 638, 670 ] ], "normalized": [] }, { "id": "12289", "type": "Genes & Molecular Sequences", "text": [ "HER2" ], "offsets": [ [ 674, 678 ] ], "normalized": [] }, { "id": "12290", "type": "Genes & Molecular Sequences", "text": [ "neu" ], "offsets": [ [ 680, 683 ] ], "normalized": [] }, { "id": "12291", "type": "Genes & Molecular Sequences", "text": [ "c-kit" ], "offsets": [ [ 685, 690 ] ], "normalized": [] }, { "id": "12292", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 696, 699 ] ], "normalized": [] }, { "id": "12293", "type": "Diseases & Disorders", "text": [ "amplification" ], "offsets": [ [ 742, 755 ] ], "normalized": [] }, { "id": "12294", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 759, 763 ] ], "normalized": [] }, { "id": "12295", "type": "Genes & Molecular Sequences", "text": [ "HER2" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "12296", "type": "Genes & Molecular Sequences", "text": [ "FISH" ], "offsets": [ [ 843, 847 ] ], "normalized": [] }, { "id": "12297", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 855, 860 ] ], "normalized": [] }, { "id": "12298", "type": "SNP & Sequence variations", "text": [ "gains of chromosomes 3, 7, and 17" ], "offsets": [ [ 883, 916 ] ], "normalized": [] }, { "id": "12299", "type": "Diseases & Disorders", "text": [ "gains of chromosomes 3, 7, and 17" ], "offsets": [ [ 883, 916 ] ], "normalized": [] }, { "id": "12300", "type": "Genes & Molecular Sequences", "text": [ "gains of chromosomes 3, 7, and 17" ], "offsets": [ [ 883, 916 ] ], "normalized": [] }, { "id": "12301", "type": "Genes & Molecular Sequences", "text": [ "7" ], "offsets": [ [ 907, 908 ] ], "normalized": [] }, { "id": "12302", "type": "SNP & Sequence variations", "text": [ "loss of chromosome 9p21" ], "offsets": [ [ 925, 948 ] ], "normalized": [] }, { "id": "12303", "type": "Genes & Molecular Sequences", "text": [ "loss of chromosome 9p21" ], "offsets": [ [ 925, 948 ] ], "normalized": [] }, { "id": "12304", "type": "Genes & Molecular Sequences", "text": [ "FISH" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "12305", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "12306", "type": "Diseases & Disorders", "text": [ "gross hematuria" ], "offsets": [ [ 1133, 1148 ] ], "normalized": [] }, { "id": "12307", "type": "Diseases & Disorders", "text": [ "flank mass" ], "offsets": [ [ 1150, 1160 ] ], "normalized": [] }, { "id": "12308", "type": "Diseases & Disorders", "text": [ "urinary obstruction" ], "offsets": [ [ 1162, 1181 ] ], "normalized": [] }, { "id": "12309", "type": "Diseases & Disorders", "text": [ "fever" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "12310", "type": "Diseases & Disorders", "text": [ "sepsis" ], "offsets": [ [ 1193, 1199 ] ], "normalized": [] }, { "id": "12311", "type": "Diseases & Disorders", "text": [ "Tumor" ], "offsets": [ [ 1259, 1264 ] ], "normalized": [] }, { "id": "12312", "type": "Diseases & Disorders", "text": [ "urothelial carcinoma" ], "offsets": [ [ 1305, 1325 ] ], "normalized": [] }, { "id": "12313", "type": "Diseases & Disorders", "text": [ "Heterologous osteosarcoma" ], "offsets": [ [ 1354, 1379 ] ], "normalized": [] }, { "id": "12314", "type": "Genes & Molecular Sequences", "text": [ "pT3" ], "offsets": [ [ 1447, 1450 ] ], "normalized": [] }, { "id": "12315", "type": "Diseases & Disorders", "text": [ "Lymph node metastases" ], "offsets": [ [ 1463, 1484 ] ], "normalized": [] }, { "id": "12316", "type": "SNP & Sequence variations", "text": [ "7" ], "offsets": [ [ 1551, 1552 ] ], "normalized": [] }, { "id": "12317", "type": "Genes & Molecular Sequences", "text": [ "7" ], "offsets": [ [ 1551, 1552 ] ], "normalized": [] }, { "id": "12318", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 1588, 1592 ] ], "normalized": [] }, { "id": "12319", "type": "Genes & Molecular Sequences", "text": [ "HER2" ], "offsets": [ [ 1674, 1678 ] ], "normalized": [] }, { "id": "12320", "type": "Genes & Molecular Sequences", "text": [ "neu" ], "offsets": [ [ 1679, 1682 ] ], "normalized": [] }, { "id": "12321", "type": "Genes & Molecular Sequences", "text": [ "c-kit" ], "offsets": [ [ 1687, 1692 ] ], "normalized": [] }, { "id": "12322", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1743, 1746 ] ], "normalized": [] }, { "id": "12323", "type": "SNP & Sequence variations", "text": [ "EGFR polysomy" ], "offsets": [ [ 1804, 1817 ] ], "normalized": [] }, { "id": "12324", "type": "Genes & Molecular Sequences", "text": [ "EGFR polysomy" ], "offsets": [ [ 1804, 1817 ] ], "normalized": [] }, { "id": "12325", "type": "Diseases & Disorders", "text": [ "EGFR polysomy" ], "offsets": [ [ 1804, 1817 ] ], "normalized": [] }, { "id": "12326", "type": "SNP & Sequence variations", "text": [ "7" ], "offsets": [ [ 1838, 1839 ] ], "normalized": [] }, { "id": "12327", "type": "Genes & Molecular Sequences", "text": [ "7" ], "offsets": [ [ 1838, 1839 ] ], "normalized": [] }, { "id": "12328", "type": "Diseases & Disorders", "text": [ "amplification" ], "offsets": [ [ 1855, 1868 ] ], "normalized": [] }, { "id": "12329", "type": "Genes & Molecular Sequences", "text": [ "HER2" ], "offsets": [ [ 1872, 1876 ] ], "normalized": [] }, { "id": "12330", "type": "Genes & Molecular Sequences", "text": [ "neu" ], "offsets": [ [ 1877, 1880 ] ], "normalized": [] }, { "id": "12331", "type": "Genes & Molecular Sequences", "text": [ "FISH" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "12332", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 1928, 1941 ] ], "normalized": [] }, { "id": "12333", "type": "Diseases & Disorders", "text": [ "urothelial carcinoma" ], "offsets": [ [ 1953, 1973 ] ], "normalized": [] }, { "id": "12334", "type": "Diseases & Disorders", "text": [ "sarcomatoid carcinoma" ], "offsets": [ [ 2022, 2043 ] ], "normalized": [] }, { "id": "12335", "type": "SNP & Sequence variations", "text": [ "7" ], "offsets": [ [ 2125, 2126 ] ], "normalized": [] }, { "id": "12336", "type": "Genes & Molecular Sequences", "text": [ "7" ], "offsets": [ [ 2125, 2126 ] ], "normalized": [] }, { "id": "12337", "type": "SNP & Sequence variations", "text": [ "Gains of chromosome 3, 7, and 17" ], "offsets": [ [ 2140, 2172 ] ], "normalized": [] }, { "id": "12338", "type": "Diseases & Disorders", "text": [ "Gains of chromosome 3, 7, and 17" ], "offsets": [ [ 2140, 2172 ] ], "normalized": [] }, { "id": "12339", "type": "Genes & Molecular Sequences", "text": [ "Gains of chromosome 3, 7, and 17" ], "offsets": [ [ 2140, 2172 ] ], "normalized": [] }, { "id": "12340", "type": "Genes & Molecular Sequences", "text": [ "7" ], "offsets": [ [ 2163, 2164 ] ], "normalized": [] }, { "id": "12341", "type": "SNP & Sequence variations", "text": [ "loss of chromosome 9p21" ], "offsets": [ [ 2177, 2200 ] ], "normalized": [] }, { "id": "12342", "type": "Genes & Molecular Sequences", "text": [ "loss of chromosome 9p21" ], "offsets": [ [ 2177, 2200 ] ], "normalized": [] }, { "id": "12343", "type": "Diseases & Disorders", "text": [ "tumors" ], "offsets": [ [ 2233, 2239 ] ], "normalized": [] }, { "id": "12344", "type": "", "text": [ "loss of chromosome 9p21" ], "offsets": [ [ 2177, 2200 ] ], "normalized": [] }, { "id": "12345", "type": "", "text": [ "tumors" ], "offsets": [ [ 2233, 2239 ] ], "normalized": [] }, { "id": "12347", "type": "", "text": [ "Gains of chromosome 3, 7, and 17" ], "offsets": [ [ 2140, 2172 ] ], "normalized": [] }, { "id": "12348", "type": "", "text": [ "tumors" ], "offsets": [ [ 2233, 2239 ] ], "normalized": [] }, { "id": "12350", "type": "", "text": [ "EGFR" ], "offsets": [ [ 759, 763 ] ], "normalized": [] }, { "id": "12351", "type": "", "text": [ "amplification" ], "offsets": [ [ 742, 755 ] ], "normalized": [] }, { "id": "12353", "type": "", "text": [ "HER2" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "12354", "type": "", "text": [ "amplification" ], "offsets": [ [ 742, 755 ] ], "normalized": [] }, { "id": "12356", "type": "", "text": [ "FISH" ], "offsets": [ [ 843, 847 ] ], "normalized": [] }, { "id": "12357", "type": "", "text": [ "amplification" ], "offsets": [ [ 742, 755 ] ], "normalized": [] }, { "id": "12359", "type": "", "text": [ "FISH" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "12360", "type": "", "text": [ "tumor" ], "offsets": [ [ 855, 860 ] ], "normalized": [] }, { "id": "12362", "type": "", "text": [ "FISH" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "12363", "type": "", "text": [ "gains of chromosomes 3, 7, and 17" ], "offsets": [ [ 883, 916 ] ], "normalized": [] }, { "id": "12365", "type": "", "text": [ "EGFR polysomy" ], "offsets": [ [ 1804, 1817 ] ], "normalized": [] }, { "id": "12366", "type": "", "text": [ "EGFR polysomy" ], "offsets": [ [ 1804, 1817 ] ], "normalized": [] }, { "id": "12368", "type": "", "text": [ "neu" ], "offsets": [ [ 1877, 1880 ] ], "normalized": [] }, { "id": "12369", "type": "", "text": [ "amplification" ], "offsets": [ [ 1855, 1868 ] ], "normalized": [] }, { "id": "12371", "type": "", "text": [ "FISH" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "12372", "type": "", "text": [ "urothelial carcinoma" ], "offsets": [ [ 1953, 1973 ] ], "normalized": [] }, { "id": "12374", "type": "", "text": [ "FISH" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "12375", "type": "", "text": [ "abnormalities" ], "offsets": [ [ 1928, 1941 ] ], "normalized": [] } ]

[]

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[ { "id": "12346", "type": "PA", "arg1_id": "12344", "arg2_id": "12345", "normalized": [] }, { "id": "12349", "type": "PA", "arg1_id": "12347", "arg2_id": "12348", "normalized": [] }, { "id": "12352", "type": "PA", "arg1_id": "12350", "arg2_id": "12351", "normalized": [] }, { "id": "12355", "type": "PA", "arg1_id": "12353", "arg2_id": "12354", "normalized": [] }, { "id": "12358", "type": "PA", "arg1_id": "12356", "arg2_id": "12357", "normalized": [] }, { "id": "12361", "type": "PA", "arg1_id": "12359", "arg2_id": "12360", "normalized": [] }, { "id": "12364", "type": "PA", "arg1_id": "12362", "arg2_id": "12363", "normalized": [] }, { "id": "12367", "type": "PA", "arg1_id": "12365", "arg2_id": "12366", "normalized": [] }, { "id": "12370", "type": "PA", "arg1_id": "12368", "arg2_id": "12369", "normalized": [] }, { "id": "12373", "type": "PA", "arg1_id": "12371", "arg2_id": "12372", "normalized": [] }, { "id": "12376", "type": "PA", "arg1_id": "12374", "arg2_id": "12375", "normalized": [] } ]

[ { "id": "12379", "type": "title", "text": [ "Association of genetic profiles to Crohn's disease by linear combinations of single nucleotide polymorphisms." ], "offsets": [ [ 0, 109 ] ] }, { "id": "12380", "type": "abstract", "text": [ "MOTIVATIONS: A large number of single nucleotide polymorphisms (SNPs) are supposed to be involved in onset, differentiation and development of complex diseases. Univariate analysis is limited in studying complex traits since does not take into account gene-gene interaction, and the correlation of multiple SNPs with a specific phenotype. Moreover it might underestimate gene variants with weaker genetic contribution. Therefore more sophisticated techniques should be adopted when investigating the role of a panel of genetic markers in disease predisposition. METHODS: In this paper we describe a general method to simultaneously investigate the association between SNPs profile and Crohn's disease (CD), by evaluating the susceptibility or protective role of single or groups of markers. As an association measure we adopted a weighted linear combination of SNPs in which suitable weighting vectors belonged to predefined and over-complete vocabularies of vectors (frames), or were determined by the data. RESULTS: The proposed method found a weighted linear combination of SNPs statistically associated to CD (p=3.81 x 10(-10)) describing the role of the markers in the pathology. In particular, MCP1-A2518G gave the major contribution as protective locus, similarly to TNF-alpha-C857T, DLG5 rs124869, PTPN22 C1858T variants. The NF kappaB -94ATTG variants was found to be irrelevant for CD. For the remaining markers, a susceptibility role was attributed also confirming that markers on CARD15 gene, in particular G908R and L1007fsinsC, are involved with CD to the same extent as FcGIIIA G559T and TNF-alpha-G308A. Moreover, an odds ratio of 3.99(p<1.0 x 10(-4)) was assigned to this combination which is greater than the best odds ratio found in the single SNP analysis. CONCLUSIONS: Our methodology allowed to statistically measure the association of a panel of SNPs with a specific phenotype. Therefore this approach could be suitable for a population screening program with simultaneous evaluation of a large set of gene polymorphism." ], "offsets": [ [ 110, 2153 ] ] } ]

[ { "id": "12381", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 35, 50 ] ], "normalized": [] }, { "id": "12382", "type": "Diseases & Disorders", "text": [ "diseases" ], "offsets": [ [ 261, 269 ] ], "normalized": [] }, { "id": "12383", "type": "Genes & Molecular Sequences", "text": [ "traits" ], "offsets": [ [ 322, 328 ] ], "normalized": [] }, { "id": "12384", "type": "Diseases & Disorders", "text": [ "weaker" ], "offsets": [ [ 500, 506 ] ], "normalized": [] }, { "id": "12385", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 648, 655 ] ], "normalized": [] }, { "id": "12386", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 795, 810 ] ], "normalized": [] }, { "id": "12387", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 812, 814 ] ], "normalized": [] }, { "id": "12388", "type": "Diseases & Disorders", "text": [ "weighted" ], "offsets": [ [ 940, 948 ] ], "normalized": [] }, { "id": "12389", "type": "Diseases & Disorders", "text": [ "weighting" ], "offsets": [ [ 994, 1003 ] ], "normalized": [] }, { "id": "12390", "type": "Diseases & Disorders", "text": [ "weighted" ], "offsets": [ [ 1156, 1164 ] ], "normalized": [] }, { "id": "12391", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1220, 1222 ] ], "normalized": [] }, { "id": "12392", "type": "SNP & Sequence variations", "text": [ "MCP1-A2518G" ], "offsets": [ [ 1310, 1321 ] ], "normalized": [] }, { "id": "12393", "type": "Genes & Molecular Sequences", "text": [ "MCP1-A2518G" ], "offsets": [ [ 1310, 1321 ] ], "normalized": [] }, { "id": "12394", "type": "SNP & Sequence variations", "text": [ "TNF-alpha-C857T" ], "offsets": [ [ 1384, 1399 ] ], "normalized": [] }, { "id": "12395", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha-C857T" ], "offsets": [ [ 1384, 1399 ] ], "normalized": [] }, { "id": "12396", "type": "SNP & Sequence variations", "text": [ "DLG5 rs124869" ], "offsets": [ [ 1401, 1414 ] ], "normalized": [] }, { "id": "12397", "type": "Genes & Molecular Sequences", "text": [ "DLG5 rs124869" ], "offsets": [ [ 1401, 1414 ] ], "normalized": [] }, { "id": "12398", "type": "SNP & Sequence variations", "text": [ "PTPN22 C1858T" ], "offsets": [ [ 1416, 1429 ] ], "normalized": [] }, { "id": "12399", "type": "Genes & Molecular Sequences", "text": [ "PTPN22 C1858T" ], "offsets": [ [ 1416, 1429 ] ], "normalized": [] }, { "id": "12400", "type": "SNP & Sequence variations", "text": [ "NF kappaB -94ATTG" ], "offsets": [ [ 1444, 1461 ] ], "normalized": [] }, { "id": "12401", "type": "Genes & Molecular Sequences", "text": [ "NF kappaB -94ATTG" ], "offsets": [ [ 1444, 1461 ] ], "normalized": [] }, { "id": "12402", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1502, 1504 ] ], "normalized": [] }, { "id": "12403", "type": "Genes & Molecular Sequences", "text": [ "CARD15" ], "offsets": [ [ 1602, 1608 ] ], "normalized": [] }, { "id": "12404", "type": "SNP & Sequence variations", "text": [ "G908R" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "12405", "type": "SNP & Sequence variations", "text": [ "L1007fsinsC" ], "offsets": [ [ 1639, 1650 ] ], "normalized": [] }, { "id": "12406", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] }, { "id": "12407", "type": "SNP & Sequence variations", "text": [ "FcGIIIA G559T" ], "offsets": [ [ 1695, 1708 ] ], "normalized": [] }, { "id": "12408", "type": "Genes & Molecular Sequences", "text": [ "FcGIIIA G559T" ], "offsets": [ [ 1695, 1708 ] ], "normalized": [] }, { "id": "12409", "type": "SNP & Sequence variations", "text": [ "TNF-alpha-G308A" ], "offsets": [ [ 1713, 1728 ] ], "normalized": [] }, { "id": "12410", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha-G308A" ], "offsets": [ [ 1713, 1728 ] ], "normalized": [] }, { "id": "12411", "type": "Diseases & Disorders", "text": [ "best" ], "offsets": [ [ 1837, 1841 ] ], "normalized": [] }, { "id": "12412", "type": "Genes & Molecular Sequences", "text": [ "set of gene" ], "offsets": [ [ 2128, 2139 ] ], "normalized": [] }, { "id": "12413", "type": "", "text": [ "NF kappaB -94ATTG" ], "offsets": [ [ 1444, 1461 ] ], "normalized": [] }, { "id": "12414", "type": "", "text": [ "CD" ], "offsets": [ [ 1502, 1504 ] ], "normalized": [] }, { "id": "12416", "type": "", "text": [ "G908R" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "12417", "type": "", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] }, { "id": "12419", "type": "", "text": [ "L1007fsinsC" ], "offsets": [ [ 1639, 1650 ] ], "normalized": [] }, { "id": "12420", "type": "", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] }, { "id": "12422", "type": "", "text": [ "FcGIIIA G559T" ], "offsets": [ [ 1695, 1708 ] ], "normalized": [] }, { "id": "12423", "type": "", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] }, { "id": "12425", "type": "", "text": [ "TNF-alpha-G308A" ], "offsets": [ [ 1713, 1728 ] ], "normalized": [] }, { "id": "12426", "type": "", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] }, { "id": "12428", "type": "", "text": [ "CARD15" ], "offsets": [ [ 1602, 1608 ] ], "normalized": [] }, { "id": "12429", "type": "", "text": [ "CD" ], "offsets": [ [ 1670, 1672 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12415", "type": "NA", "arg1_id": "12413", "arg2_id": "12414", "normalized": [] }, { "id": "12418", "type": "PA", "arg1_id": "12416", "arg2_id": "12417", "normalized": [] }, { "id": "12421", "type": "PA", "arg1_id": "12419", "arg2_id": "12420", "normalized": [] }, { "id": "12424", "type": "PA", "arg1_id": "12422", "arg2_id": "12423", "normalized": [] }, { "id": "12427", "type": "PA", "arg1_id": "12425", "arg2_id": "12426", "normalized": [] }, { "id": "12430", "type": "PA", "arg1_id": "12428", "arg2_id": "12429", "normalized": [] } ]

[ { "id": "12433", "type": "title", "text": [ "Use of self-closing U-clips for dural repair in mini-invasive surgery for herniated disc." ], "offsets": [ [ 0, 89 ] ] }, { "id": "12434", "type": "abstract", "text": [ "OBJECT: The feasibility of a new technique of dural repair (self-closing U-clips) in mini-invasive surgery for herniated disk is demonstrated in this case report. MATERIALS AND METHODS: A 44-year-old male patient underwent lumbar microdiscectomy at out Institute, with subsequent dural leak as surgical complication; the dural leak re-appeared even after a second intervention in which we used muscle and dural graft and fibrin glue to repair the leak. We then decided to employ self-closing nitinol- U-clip to achieve primary dural closure. RESULTS: After the intervention the patient no more presented signs or symptoms due to the unintended durotomy, and the postoperative course was uneventful. CONCLUSION: Self-closing nitinol U-clips (Medtronic, Inc., Minneapolis) can be used for closing a dural tear through a mini-invasive approach that could make a conventional microsuturing technique very difficult." ], "offsets": [ [ 90, 1001 ] ] } ]

[ { "id": "12435", "type": "Diseases & Disorders", "text": [ "herniated disc" ], "offsets": [ [ 74, 88 ] ], "normalized": [] }, { "id": "12436", "type": "Diseases & Disorders", "text": [ "herniated disk" ], "offsets": [ [ 201, 215 ] ], "normalized": [] }, { "id": "12437", "type": "Diseases & Disorders", "text": [ "signs" ], "offsets": [ [ 694, 699 ] ], "normalized": [] }, { "id": "12438", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 703, 711 ] ], "normalized": [] }, { "id": "12439", "type": "Diseases & Disorders", "text": [ "dural tear" ], "offsets": [ [ 887, 897 ] ], "normalized": [] } ]

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[ { "id": "12442", "type": "title", "text": [ "Identification and replication of three novel myopia common susceptibility gene loci on chromosome 3q26 using linkage and linkage disequilibrium mapping." ], "offsets": [ [ 0, 153 ] ] }, { "id": "12443", "type": "abstract", "text": [ "Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505-180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533-182,688 kb) and PSARL (184,386 kb; 95% CI 184,356-184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10(-7), p<10(-10), and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia." ], "offsets": [ [ 154, 1886 ] ] } ]

[ { "id": "12444", "type": "Diseases & Disorders", "text": [ "myopia" ], "offsets": [ [ 46, 52 ] ], "normalized": [] }, { "id": "12445", "type": "Genes & Molecular Sequences", "text": [ "3q26" ], "offsets": [ [ 99, 103 ] ], "normalized": [] }, { "id": "12446", "type": "Diseases & Disorders", "text": [ "Refractive error" ], "offsets": [ [ 154, 170 ] ], "normalized": [] }, { "id": "12447", "type": "Genes & Molecular Sequences", "text": [ "3q26" ], "offsets": [ [ 377, 381 ] ], "normalized": [] }, { "id": "12448", "type": "Genes & Molecular Sequences", "text": [ "Map 1" ], "offsets": [ [ 605, 610 ] ], "normalized": [] }, { "id": "12449", "type": "Genes & Molecular Sequences", "text": [ "Map 1" ], "offsets": [ [ 613, 618 ] ], "normalized": [] }, { "id": "12450", "type": "Genes & Molecular Sequences", "text": [ "Map 2" ], "offsets": [ [ 703, 708 ] ], "normalized": [] }, { "id": "12451", "type": "Genes & Molecular Sequences", "text": [ "MFN1" ], "offsets": [ [ 1020, 1024 ] ], "normalized": [] }, { "id": "12452", "type": "Genes & Molecular Sequences", "text": [ "SOX2OT" ], "offsets": [ [ 1138, 1144 ] ], "normalized": [] }, { "id": "12453", "type": "Genes & Molecular Sequences", "text": [ "PSARL" ], "offsets": [ [ 1189, 1194 ] ], "normalized": [] }, { "id": "12454", "type": "Genes & Molecular Sequences", "text": [ "Map 2" ], "offsets": [ [ 1307, 1312 ] ], "normalized": [] }, { "id": "12455", "type": "Genes & Molecular Sequences", "text": [ "MFN1" ], "offsets": [ [ 1470, 1474 ] ], "normalized": [] }, { "id": "12456", "type": "Genes & Molecular Sequences", "text": [ "SOX2OT" ], "offsets": [ [ 1488, 1494 ] ], "normalized": [] }, { "id": "12457", "type": "Genes & Molecular Sequences", "text": [ "PSARL" ], "offsets": [ [ 1513, 1518 ] ], "normalized": [] }, { "id": "12458", "type": "Genes & Molecular Sequences", "text": [ "MFN1" ], "offsets": [ [ 1546, 1550 ] ], "normalized": [] }, { "id": "12459", "type": "Genes & Molecular Sequences", "text": [ "PSARL" ], "offsets": [ [ 1555, 1560 ] ], "normalized": [] }, { "id": "12460", "type": "Genes & Molecular Sequences", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12461", "type": "Diseases & Disorders", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12462", "type": "Diseases & Disorders", "text": [ "mitochondrial fusion" ], "offsets": [ [ 1597, 1617 ] ], "normalized": [] }, { "id": "12463", "type": "Diseases & Disorders", "text": [ "inhibition of mitochondrial-led apoptosis" ], "offsets": [ [ 1626, 1667 ] ], "normalized": [] }, { "id": "12464", "type": "Diseases & Disorders", "text": [ "myopia" ], "offsets": [ [ 1776, 1782 ] ], "normalized": [] }, { "id": "12465", "type": "Diseases & Disorders", "text": [ "myopia" ], "offsets": [ [ 1879, 1885 ] ], "normalized": [] }, { "id": "12466", "type": "", "text": [ "3q26" ], "offsets": [ [ 99, 103 ] ], "normalized": [] }, { "id": "12467", "type": "", "text": [ "myopia" ], "offsets": [ [ 46, 52 ] ], "normalized": [] }, { "id": "12469", "type": "", "text": [ "PSARL" ], "offsets": [ [ 1555, 1560 ] ], "normalized": [] }, { "id": "12470", "type": "", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12472", "type": "", "text": [ "MFN1" ], "offsets": [ [ 1546, 1550 ] ], "normalized": [] }, { "id": "12473", "type": "", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12475", "type": "", "text": [ "PSARL" ], "offsets": [ [ 1555, 1560 ] ], "normalized": [] }, { "id": "12476", "type": "", "text": [ "inhibition of mitochondrial-led apoptosis" ], "offsets": [ [ 1626, 1667 ] ], "normalized": [] }, { "id": "12478", "type": "", "text": [ "MFN1" ], "offsets": [ [ 1546, 1550 ] ], "normalized": [] }, { "id": "12479", "type": "", "text": [ "mitochondrial fusion" ], "offsets": [ [ 1597, 1617 ] ], "normalized": [] }, { "id": "12481", "type": "", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12482", "type": "", "text": [ "inhibition of mitochondrial-led apoptosis" ], "offsets": [ [ 1626, 1667 ] ], "normalized": [] }, { "id": "12484", "type": "", "text": [ "OPA1" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "12485", "type": "", "text": [ "mitochondrial fusion" ], "offsets": [ [ 1597, 1617 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12468", "type": "PA", "arg1_id": "12466", "arg2_id": "12467", "normalized": [] }, { "id": "12471", "type": "PA", "arg1_id": "12469", "arg2_id": "12470", "normalized": [] }, { "id": "12474", "type": "PA", "arg1_id": "12472", "arg2_id": "12473", "normalized": [] }, { "id": "12477", "type": "PA", "arg1_id": "12475", "arg2_id": "12476", "normalized": [] }, { "id": "12480", "type": "PA", "arg1_id": "12478", "arg2_id": "12479", "normalized": [] }, { "id": "12483", "type": "PA", "arg1_id": "12481", "arg2_id": "12482", "normalized": [] }, { "id": "12486", "type": "PA", "arg1_id": "12484", "arg2_id": "12485", "normalized": [] } ]

[ { "id": "12489", "type": "title", "text": [ "Activated G(alpha)13 impairs cell invasiveness through p190RhoGAP-mediated inhibition of RhoA activity." ], "offsets": [ [ 0, 103 ] ] }, { "id": "12490", "type": "abstract", "text": [ "The GTPase RhoA is a downstream target of heterotrimeric G(13) proteins and plays key roles in cell migration and invasion. Here, we show that expression in human melanoma cells of a constitutively active, GTPase-deficient Galpha(13) form (G(alpha)(13)QL) or lysophosphatidylcholine (LPC)-promoted signaling through G(alpha)(13)-coupled receptors led to a blockade of chemokine-stimulated RhoA activation and cell invasion that was rescued by active RhoA. Melanoma cells expressing G(alpha)(13)QL or cells stimulated with LPC displayed an increase in p190RhoGAP activation, and defects in RhoA activation and invasion were recovered by knocking down p190RhoGAP expression, thus identifying this GTPase-activating protein (GAP) protein as a downstream G(alpha)(13) target that is responsible for these inhibitory responses. In addition, defective stress fiber assembly and reduced migration speed underlay inefficient invasion of G(alpha)(13)QL melanoma cells. Importantly, G(alpha)(13)QL expression in melanoma cells led to impairment in lung metastasis associated with prolonged survival in SCID mice. The data indicate that G(alpha)(13)-dependent downstream effects on RhoA activation and invasion tightly depend on cell type-specific GAP activities and that G(alpha)(13)-p190RhoGAP signaling might represent a potential target for intervention in melanoma metastasis." ], "offsets": [ [ 104, 1474 ] ] } ]

[ { "id": "12491", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)13" ], "offsets": [ [ 10, 20 ] ], "normalized": [] }, { "id": "12492", "type": "Genes & Molecular Sequences", "text": [ "p190RhoGAP" ], "offsets": [ [ 55, 65 ] ], "normalized": [] }, { "id": "12493", "type": "Genes & Molecular Sequences", "text": [ "RhoA" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "12494", "type": "Genes & Molecular Sequences", "text": [ "GTPase RhoA" ], "offsets": [ [ 108, 119 ] ], "normalized": [] }, { "id": "12495", "type": "Genes & Molecular Sequences", "text": [ "G(13)" ], "offsets": [ [ 161, 166 ] ], "normalized": [] }, { "id": "12496", "type": "Genes & Molecular Sequences", "text": [ "GTPase-deficient Galpha(13) form" ], "offsets": [ [ 310, 342 ] ], "normalized": [] }, { "id": "12497", "type": "Genes & Molecular Sequences", "text": [ "Galpha(13)" ], "offsets": [ [ 327, 337 ] ], "normalized": [] }, { "id": "12498", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)QL" ], "offsets": [ [ 344, 358 ] ], "normalized": [] }, { "id": "12499", "type": "Genes & Molecular Sequences", "text": [ "lysophosphatidylcholine" ], "offsets": [ [ 363, 386 ] ], "normalized": [] }, { "id": "12500", "type": "Chemicals & Drugs", "text": [ "lysophosphatidylcholine" ], "offsets": [ [ 363, 386 ] ], "normalized": [] }, { "id": "12501", "type": "Genes & Molecular Sequences", "text": [ "LPC" ], "offsets": [ [ 388, 391 ] ], "normalized": [] }, { "id": "12502", "type": "Chemicals & Drugs", "text": [ "LPC" ], "offsets": [ [ 388, 391 ] ], "normalized": [] }, { "id": "12503", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)" ], "offsets": [ [ 420, 432 ] ], "normalized": [] }, { "id": "12504", "type": "Genes & Molecular Sequences", "text": [ "chemokine" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "12505", "type": "Genes & Molecular Sequences", "text": [ "RhoA" ], "offsets": [ [ 493, 497 ] ], "normalized": [] }, { "id": "12506", "type": "Genes & Molecular Sequences", "text": [ "RhoA" ], "offsets": [ [ 554, 558 ] ], "normalized": [] }, { "id": "12507", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)QL" ], "offsets": [ [ 586, 600 ] ], "normalized": [] }, { "id": "12508", "type": "Genes & Molecular Sequences", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12509", "type": "Chemicals & Drugs", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12510", "type": "Genes & Molecular Sequences", "text": [ "p190RhoGAP" ], "offsets": [ [ 655, 665 ] ], "normalized": [] }, { "id": "12511", "type": "Genes & Molecular Sequences", "text": [ "RhoA" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "12512", "type": "Genes & Molecular Sequences", "text": [ "p190RhoGAP" ], "offsets": [ [ 754, 764 ] ], "normalized": [] }, { "id": "12513", "type": "Genes & Molecular Sequences", "text": [ "GTPase-activating protein" ], "offsets": [ [ 799, 824 ] ], "normalized": [] }, { "id": "12514", "type": "Genes & Molecular Sequences", "text": [ "GAP) protein" ], "offsets": [ [ 826, 838 ] ], "normalized": [] }, { "id": "12515", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)" ], "offsets": [ [ 855, 867 ] ], "normalized": [] }, { "id": "12516", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)QL" ], "offsets": [ [ 1033, 1047 ] ], "normalized": [] }, { "id": "12517", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)QL" ], "offsets": [ [ 1077, 1091 ] ], "normalized": [] }, { "id": "12518", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)" ], "offsets": [ [ 1230, 1242 ] ], "normalized": [] }, { "id": "12519", "type": "Genes & Molecular Sequences", "text": [ "RhoA" ], "offsets": [ [ 1275, 1279 ] ], "normalized": [] }, { "id": "12520", "type": "Genes & Molecular Sequences", "text": [ "GAP" ], "offsets": [ [ 1341, 1344 ] ], "normalized": [] }, { "id": "12521", "type": "Genes & Molecular Sequences", "text": [ "G(alpha)(13)-p190RhoGAP" ], "offsets": [ [ 1365, 1388 ] ], "normalized": [] }, { "id": "12522", "type": "", "text": [ "lysophosphatidylcholine" ], "offsets": [ [ 363, 386 ] ], "normalized": [] }, { "id": "12523", "type": "", "text": [ "RhoA" ], "offsets": [ [ 554, 558 ] ], "normalized": [] }, { "id": "12525", "type": "", "text": [ "lysophosphatidylcholine" ], "offsets": [ [ 363, 386 ] ], "normalized": [] }, { "id": "12526", "type": "", "text": [ "Galpha(13)" ], "offsets": [ [ 327, 337 ] ], "normalized": [] }, { "id": "12528", "type": "", "text": [ "lysophosphatidylcholine" ], "offsets": [ [ 363, 386 ] ], "normalized": [] }, { "id": "12529", "type": "", "text": [ "G(alpha)(13)" ], "offsets": [ [ 420, 432 ] ], "normalized": [] }, { "id": "12531", "type": "", "text": [ "LPC" ], "offsets": [ [ 388, 391 ] ], "normalized": [] }, { "id": "12532", "type": "", "text": [ "RhoA" ], "offsets": [ [ 554, 558 ] ], "normalized": [] }, { "id": "12534", "type": "", "text": [ "LPC" ], "offsets": [ [ 388, 391 ] ], "normalized": [] }, { "id": "12535", "type": "", "text": [ "Galpha(13)" ], "offsets": [ [ 327, 337 ] ], "normalized": [] }, { "id": "12537", "type": "", "text": [ "LPC" ], "offsets": [ [ 388, 391 ] ], "normalized": [] }, { "id": "12538", "type": "", "text": [ "G(alpha)(13)" ], "offsets": [ [ 420, 432 ] ], "normalized": [] }, { "id": "12540", "type": "", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12541", "type": "", "text": [ "RhoA" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "12543", "type": "", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12544", "type": "", "text": [ "GAP) protein" ], "offsets": [ [ 826, 838 ] ], "normalized": [] }, { "id": "12546", "type": "", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12547", "type": "", "text": [ "G(alpha)(13)" ], "offsets": [ [ 855, 867 ] ], "normalized": [] }, { "id": "12549", "type": "", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12550", "type": "", "text": [ "GTPase-activating protein" ], "offsets": [ [ 799, 824 ] ], "normalized": [] }, { "id": "12552", "type": "", "text": [ "LPC" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "12553", "type": "", "text": [ "p190RhoGAP" ], "offsets": [ [ 754, 764 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12524", "type": "SA", "arg1_id": "12522", "arg2_id": "12523", "normalized": [] }, { "id": "12527", "type": "PA", "arg1_id": "12525", "arg2_id": "12526", "normalized": [] }, { "id": "12530", "type": "PA", "arg1_id": "12528", "arg2_id": "12529", "normalized": [] }, { "id": "12533", "type": "PA", "arg1_id": "12531", "arg2_id": "12532", "normalized": [] }, { "id": "12536", "type": "PA", "arg1_id": "12534", "arg2_id": "12535", "normalized": [] }, { "id": "12539", "type": "PA", "arg1_id": "12537", "arg2_id": "12538", "normalized": [] }, { "id": "12542", "type": "PA", "arg1_id": "12540", "arg2_id": "12541", "normalized": [] }, { "id": "12545", "type": "PA", "arg1_id": "12543", "arg2_id": "12544", "normalized": [] }, { "id": "12548", "type": "PA", "arg1_id": "12546", "arg2_id": "12547", "normalized": [] }, { "id": "12551", "type": "PA", "arg1_id": "12549", "arg2_id": "12550", "normalized": [] }, { "id": "12554", "type": "PA", "arg1_id": "12552", "arg2_id": "12553", "normalized": [] } ]

[ { "id": "12557", "type": "title", "text": [ "Pupillary changes among Nigerian adults following the instillation of Garcinia kola nut extracts: multicentric studies." ], "offsets": [ [ 0, 119 ] ] }, { "id": "12558", "type": "abstract", "text": [ "BACKGROUND: A multi-centre, open, within-patient controlled study was performed on 106 adult volunteers to investigate the effects of Garcinia kolanut extracts on the pupillary sizes. STUDY DESIGN: 106 participants in three Nigerian Ophthalmic Centres with no pupillary defects and associated ocular or systemic co-morbidities had their pupillary diameters measured at 0, 15, 30 and 45 minutes respectively with a pupillometer (Neuroptics model # 586009). Using the left eyes as control, Garcinia kolanut extract was instilled into the right eyes at 15 minutes intervals. RESULTS: There were 63 females and 43 males ranging in age from 18 to 58 years with the mean age of 34.9 years. Average pupillary diameter measured among participants was 4.1 - 8.4 mm with the mean value of 6.0 mm prior to garcinia kola nut extract instillation. There was a gradual reduction in the baseline pupillary size with age in years at 0.2mm per decade without garcinia extract instillation. There was a significant higher baseline pupillary diameter in males than females with males and females mean values of 6.29mm (6.00 - 6.56mm) and 5.85mm (5.60 - 6.11mm) in the right eye (p=0.026) and mean pupillary diameters 6.16mm (5.90 - 6.42mm) and 5.80mm (5.56 - 6.04mm) in the left eyes (p=0.05) respectively. There were consistent significant miosis in the right eyes with instilled Garcinia kola nut extract compared to the left eyes at 15, 30 and 45 minutes (p=0.0000). CONCLUSION: 4% Garcinia kola nut extract drop has a transient miotic effect on human pupils not sustainable for more than 45 minutes." ], "offsets": [ [ 120, 1704 ] ] } ]

[ { "id": "12559", "type": "Chemicals & Drugs", "text": [ "Garcinia kola nut extracts" ], "offsets": [ [ 70, 96 ] ], "normalized": [] }, { "id": "12560", "type": "Chemicals & Drugs", "text": [ "Garcinia kolanut extracts" ], "offsets": [ [ 254, 279 ] ], "normalized": [] }, { "id": "12561", "type": "Diseases & Disorders", "text": [ "pupillary defects" ], "offsets": [ [ 380, 397 ] ], "normalized": [] }, { "id": "12562", "type": "Chemicals & Drugs", "text": [ "Garcinia kolanut extract" ], "offsets": [ [ 608, 632 ] ], "normalized": [] }, { "id": "12563", "type": "Chemicals & Drugs", "text": [ "garcinia kola nut extract" ], "offsets": [ [ 915, 940 ] ], "normalized": [] }, { "id": "12564", "type": "Chemicals & Drugs", "text": [ "gradual" ], "offsets": [ [ 967, 974 ] ], "normalized": [] }, { "id": "12565", "type": "Chemicals & Drugs", "text": [ "garcinia extract" ], "offsets": [ [ 1062, 1078 ] ], "normalized": [] }, { "id": "12566", "type": "Diseases & Disorders", "text": [ "miosis" ], "offsets": [ [ 1442, 1448 ] ], "normalized": [] }, { "id": "12567", "type": "Chemicals & Drugs", "text": [ "Garcinia kola nut extract" ], "offsets": [ [ 1482, 1507 ] ], "normalized": [] }, { "id": "12568", "type": "Chemicals & Drugs", "text": [ "Garcinia kola nut extract" ], "offsets": [ [ 1586, 1611 ] ], "normalized": [] }, { "id": "12569", "type": "Diseases & Disorders", "text": [ "miotic" ], "offsets": [ [ 1633, 1639 ] ], "normalized": [] }, { "id": "12570", "type": "", "text": [ "Garcinia kola nut extract" ], "offsets": [ [ 1482, 1507 ] ], "normalized": [] }, { "id": "12571", "type": "", "text": [ "miosis" ], "offsets": [ [ 1442, 1448 ] ], "normalized": [] }, { "id": "12573", "type": "", "text": [ "Garcinia kola nut extract" ], "offsets": [ [ 1586, 1611 ] ], "normalized": [] }, { "id": "12574", "type": "", "text": [ "miotic" ], "offsets": [ [ 1633, 1639 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12572", "type": "PA", "arg1_id": "12570", "arg2_id": "12571", "normalized": [] }, { "id": "12575", "type": "PA", "arg1_id": "12573", "arg2_id": "12574", "normalized": [] } ]

[ { "id": "12578", "type": "title", "text": [ "A novel mTOR inhibitor is efficacious in a murine model of colitis." ], "offsets": [ [ 0, 67 ] ] }, { "id": "12579", "type": "abstract", "text": [ "Ulcerative colitis is an autoimmune-inflammatory disease characterized by increased proliferation of colonic epithelial cells, dysregulation of signal transduction pathways, elevated mucosal T cell activation, increased production of proinflammatory cytokines, and enhanced leukocyte infiltration into colonic interstitium. Several compounds that possess antiproliferative properties and/or inhibit cytokine production exhibit a therapeutic effect in murine models of colitis. Mammalian target of rapamycin (mTOR), a protein kinase regulating cell proliferation, is implicated in colon carcinogenesis. In this study, we report that a novel haloacyl aminopyridine-based molecule (P2281) is a mTOR inhibitor and is efficacious in a murine model of human colitis. In vitro studies using Western blot analysis and cell-based ELISA assays showed that P2281 inhibits mTOR activity in colon cancer cells. In vitro and in vivo assays of proinflammatory cytokine production revealed that P2281 diminishes induced IFN-gamma production but not TNF-alpha production, indicating preferential inhibitory effects of P2281 on T cell function. In the dextran sulfate sodium (DSS) model of colitis, 1) macroscopic colon observations demonstrated that P2281 significantly inhibited DSS-induced weight loss, improved rectal bleeding index, decreased disease activity index, and reversed DSS-induced shortening of the colon; 2) histological analyses of colonic tissues revealed that P2281 distinctly attenuated DSS-induced edema, prominently diminished the leukocyte infiltration in the colonic mucosa, and resulted in protection against DSS-induced crypt damage; and 3) Western blot analysis showed that P2281 blocks DSS-induced activation of mTOR. Collectively, these results provide direct evidence that P2281, a novel mTOR inhibitor, suppresses DSS-induced colitis by inhibiting T cell function and is a potential therapeutic for colitis. Given that compounds with anticancer activity show promising anti-inflammatory efficacy, our findings reinforce the cross-therapeutic functionality of potential drugs." ], "offsets": [ [ 68, 2157 ] ] } ]

[ { "id": "12580", "type": "Chemicals & Drugs", "text": [ "mTOR inhibitor" ], "offsets": [ [ 8, 22 ] ], "normalized": [] }, { "id": "12581", "type": "Genes & Molecular Sequences", "text": [ "mTOR inhibitor" ], "offsets": [ [ 8, 22 ] ], "normalized": [] }, { "id": "12582", "type": "Genes & Molecular Sequences", "text": [ "T cell" ], "offsets": [ [ 259, 265 ] ], "normalized": [] }, { "id": "12583", "type": "Genes & Molecular Sequences", "text": [ "proinflammatory cytokines" ], "offsets": [ [ 302, 327 ] ], "normalized": [] }, { "id": "12584", "type": "Genes & Molecular Sequences", "text": [ "cytokine" ], "offsets": [ [ 467, 475 ] ], "normalized": [] }, { "id": "12585", "type": "Genes & Molecular Sequences", "text": [ "Mammalian target of rapamycin" ], "offsets": [ [ 545, 574 ] ], "normalized": [] }, { "id": "12586", "type": "Genes & Molecular Sequences", "text": [ "mTOR" ], "offsets": [ [ 576, 580 ] ], "normalized": [] }, { "id": "12587", "type": "Chemicals & Drugs", "text": [ "haloacyl aminopyridine-based molecule" ], "offsets": [ [ 708, 745 ] ], "normalized": [] }, { "id": "12588", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "12589", "type": "Chemicals & Drugs", "text": [ "mTOR inhibitor" ], "offsets": [ [ 759, 773 ] ], "normalized": [] }, { "id": "12590", "type": "Genes & Molecular Sequences", "text": [ "mTOR inhibitor" ], "offsets": [ [ 759, 773 ] ], "normalized": [] }, { "id": "12591", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 914, 919 ] ], "normalized": [] }, { "id": "12592", "type": "Genes & Molecular Sequences", "text": [ "mTOR" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "12593", "type": "Genes & Molecular Sequences", "text": [ "proinflammatory cytokine" ], "offsets": [ [ 997, 1021 ] ], "normalized": [] }, { "id": "12594", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1047, 1052 ] ], "normalized": [] }, { "id": "12595", "type": "Genes & Molecular Sequences", "text": [ "IFN-gamma" ], "offsets": [ [ 1072, 1081 ] ], "normalized": [] }, { "id": "12596", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 1101, 1110 ] ], "normalized": [] }, { "id": "12597", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "12598", "type": "Genes & Molecular Sequences", "text": [ "T cell" ], "offsets": [ [ 1178, 1184 ] ], "normalized": [] }, { "id": "12599", "type": "Chemicals & Drugs", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12600", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1226, 1229 ] ], "normalized": [] }, { "id": "12601", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1226, 1229 ] ], "normalized": [] }, { "id": "12602", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1301, 1306 ] ], "normalized": [] }, { "id": "12603", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1331, 1334 ] ], "normalized": [] }, { "id": "12604", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1331, 1334 ] ], "normalized": [] }, { "id": "12605", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "12606", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "12607", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1530, 1535 ] ], "normalized": [] }, { "id": "12608", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1558, 1561 ] ], "normalized": [] }, { "id": "12609", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1558, 1561 ] ], "normalized": [] }, { "id": "12610", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1685, 1688 ] ], "normalized": [] }, { "id": "12611", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1685, 1688 ] ], "normalized": [] }, { "id": "12612", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12613", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12614", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12615", "type": "Genes & Molecular Sequences", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12616", "type": "Chemicals & Drugs", "text": [ "P2281" ], "offsets": [ [ 1854, 1859 ] ], "normalized": [] }, { "id": "12617", "type": "Chemicals & Drugs", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12618", "type": "Genes & Molecular Sequences", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12619", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "12620", "type": "Genes & Molecular Sequences", "text": [ "DSS" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "12621", "type": "Genes & Molecular Sequences", "text": [ "T cell" ], "offsets": [ [ 1930, 1936 ] ], "normalized": [] }, { "id": "12622", "type": "", "text": [ "P2281" ], "offsets": [ [ 914, 919 ] ], "normalized": [] }, { "id": "12623", "type": "", "text": [ "mTOR" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "12625", "type": "", "text": [ "P2281" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "12626", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 1072, 1081 ] ], "normalized": [] }, { "id": "12628", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12629", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12631", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12632", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12634", "type": "", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12635", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12637", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12638", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12640", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 8, 22 ] ], "normalized": [] }, { "id": "12641", "type": "", "text": [ "colitis" ], "offsets": [ [ 59, 66 ] ], "normalized": [] }, { "id": "12643", "type": "", "text": [ "cytokine" ], "offsets": [ [ 467, 475 ] ], "normalized": [] }, { "id": "12644", "type": "", "text": [ "colitis" ], "offsets": [ [ 536, 543 ] ], "normalized": [] }, { "id": "12646", "type": "", "text": [ "mTOR" ], "offsets": [ [ 576, 580 ] ], "normalized": [] }, { "id": "12647", "type": "", "text": [ "carcinogenesis" ], "offsets": [ [ 654, 668 ] ], "normalized": [] }, { "id": "12649", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 759, 773 ] ], "normalized": [] }, { "id": "12650", "type": "", "text": [ "colitis" ], "offsets": [ [ 820, 827 ] ], "normalized": [] }, { "id": "12652", "type": "", "text": [ "P2281" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "12653", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 759, 773 ] ], "normalized": [] }, { "id": "12655", "type": "", "text": [ "P2281" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "12656", "type": "", "text": [ "colitis" ], "offsets": [ [ 820, 827 ] ], "normalized": [] }, { "id": "12658", "type": "", "text": [ "mTOR" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "12659", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 946, 958 ] ], "normalized": [] }, { "id": "12661", "type": "", "text": [ "P2281" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "12662", "type": "", "text": [ "TNF-alpha" ], "offsets": [ [ 1101, 1110 ] ], "normalized": [] }, { "id": "12664", "type": "", "text": [ "P2281" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "12665", "type": "", "text": [ "proinflammatory cytokine" ], "offsets": [ [ 997, 1021 ] ], "normalized": [] }, { "id": "12667", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12668", "type": "", "text": [ "colitis" ], "offsets": [ [ 1240, 1247 ] ], "normalized": [] }, { "id": "12670", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12671", "type": "", "text": [ "rectal bleeding" ], "offsets": [ [ 1365, 1380 ] ], "normalized": [] }, { "id": "12673", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12674", "type": "", "text": [ "edema" ], "offsets": [ [ 1570, 1575 ] ], "normalized": [] }, { "id": "12676", "type": "", "text": [ "mTOR" ], "offsets": [ [ 1791, 1795 ] ], "normalized": [] }, { "id": "12677", "type": "", "text": [ "crypt damage" ], "offsets": [ [ 1697, 1709 ] ], "normalized": [] }, { "id": "12679", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12680", "type": "", "text": [ "colitis" ], "offsets": [ [ 1240, 1247 ] ], "normalized": [] }, { "id": "12682", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12683", "type": "", "text": [ "rectal bleeding" ], "offsets": [ [ 1365, 1380 ] ], "normalized": [] }, { "id": "12685", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12686", "type": "", "text": [ "edema" ], "offsets": [ [ 1570, 1575 ] ], "normalized": [] }, { "id": "12688", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 1202, 1224 ] ], "normalized": [] }, { "id": "12689", "type": "", "text": [ "crypt damage" ], "offsets": [ [ 1697, 1709 ] ], "normalized": [] }, { "id": "12691", "type": "", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12692", "type": "", "text": [ "colitis" ], "offsets": [ [ 1240, 1247 ] ], "normalized": [] }, { "id": "12694", "type": "", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12695", "type": "", "text": [ "rectal bleeding" ], "offsets": [ [ 1365, 1380 ] ], "normalized": [] }, { "id": "12697", "type": "", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12698", "type": "", "text": [ "edema" ], "offsets": [ [ 1570, 1575 ] ], "normalized": [] }, { "id": "12700", "type": "", "text": [ "P2281" ], "offsets": [ [ 1752, 1757 ] ], "normalized": [] }, { "id": "12701", "type": "", "text": [ "crypt damage" ], "offsets": [ [ 1697, 1709 ] ], "normalized": [] }, { "id": "12703", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12704", "type": "", "text": [ "colitis" ], "offsets": [ [ 1240, 1247 ] ], "normalized": [] }, { "id": "12706", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12707", "type": "", "text": [ "rectal bleeding" ], "offsets": [ [ 1365, 1380 ] ], "normalized": [] }, { "id": "12709", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12710", "type": "", "text": [ "edema" ], "offsets": [ [ 1570, 1575 ] ], "normalized": [] }, { "id": "12712", "type": "", "text": [ "DSS" ], "offsets": [ [ 1765, 1768 ] ], "normalized": [] }, { "id": "12713", "type": "", "text": [ "crypt damage" ], "offsets": [ [ 1697, 1709 ] ], "normalized": [] }, { "id": "12715", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12716", "type": "", "text": [ "colitis" ], "offsets": [ [ 1981, 1988 ] ], "normalized": [] }, { "id": "12718", "type": "", "text": [ "P2281" ], "offsets": [ [ 1854, 1859 ] ], "normalized": [] }, { "id": "12719", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12721", "type": "", "text": [ "P2281" ], "offsets": [ [ 1854, 1859 ] ], "normalized": [] }, { "id": "12722", "type": "", "text": [ "colitis" ], "offsets": [ [ 1981, 1988 ] ], "normalized": [] }, { "id": "12724", "type": "", "text": [ "DSS" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "12725", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12727", "type": "", "text": [ "DSS" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "12728", "type": "", "text": [ "colitis" ], "offsets": [ [ 1981, 1988 ] ], "normalized": [] }, { "id": "12730", "type": "", "text": [ "P2281" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "12731", "type": "", "text": [ "T cell" ], "offsets": [ [ 1178, 1184 ] ], "normalized": [] }, { "id": "12733", "type": "", "text": [ "mTOR inhibitor" ], "offsets": [ [ 1869, 1883 ] ], "normalized": [] }, { "id": "12734", "type": "", "text": [ "T cell" ], "offsets": [ [ 1930, 1936 ] ], "normalized": [] }, { "id": "12736", "type": "", "text": [ "P2281" ], "offsets": [ [ 1854, 1859 ] ], "normalized": [] }, { "id": "12737", "type": "", "text": [ "T cell" ], "offsets": [ [ 1930, 1936 ] ], "normalized": [] }, { "id": "12739", "type": "", "text": [ "DSS" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "12740", "type": "", "text": [ "T cell" ], "offsets": [ [ 1930, 1936 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12624", "type": "PA", "arg1_id": "12622", "arg2_id": "12623", "normalized": [] }, { "id": "12627", "type": "PA", "arg1_id": "12625", "arg2_id": "12626", "normalized": [] }, { "id": "12630", "type": "PA", "arg1_id": "12628", "arg2_id": "12629", "normalized": [] }, { "id": "12633", "type": "PA", "arg1_id": "12631", "arg2_id": "12632", "normalized": [] }, { "id": "12636", "type": "PA", "arg1_id": "12634", "arg2_id": "12635", "normalized": [] }, { "id": "12639", "type": "PA", "arg1_id": "12637", "arg2_id": "12638", "normalized": [] }, { "id": "12642", "type": "PA", "arg1_id": "12640", "arg2_id": "12641", "normalized": [] }, { "id": "12645", "type": "PA", "arg1_id": "12643", "arg2_id": "12644", "normalized": [] }, { "id": "12648", "type": "PA", "arg1_id": "12646", "arg2_id": "12647", "normalized": [] }, { "id": "12651", "type": "PA", "arg1_id": "12649", "arg2_id": "12650", "normalized": [] }, { "id": "12654", "type": "PA", "arg1_id": "12652", "arg2_id": "12653", "normalized": [] }, { "id": "12657", "type": "PA", "arg1_id": "12655", "arg2_id": "12656", "normalized": [] }, { "id": "12660", "type": "PA", "arg1_id": "12658", "arg2_id": "12659", "normalized": [] }, { "id": "12663", "type": "NA", "arg1_id": "12661", "arg2_id": "12662", "normalized": [] }, { "id": "12666", "type": "PA", "arg1_id": "12664", "arg2_id": "12665", "normalized": [] }, { "id": "12669", "type": "PA", "arg1_id": "12667", "arg2_id": "12668", "normalized": [] }, { "id": "12672", "type": "PA", "arg1_id": "12670", "arg2_id": "12671", "normalized": [] }, { "id": "12675", "type": "PA", "arg1_id": "12673", "arg2_id": "12674", "normalized": [] }, { "id": "12678", "type": "PA", "arg1_id": "12676", "arg2_id": "12677", "normalized": [] }, { "id": "12681", "type": "PA", "arg1_id": "12679", "arg2_id": "12680", "normalized": [] }, { "id": "12684", "type": "PA", "arg1_id": "12682", "arg2_id": "12683", "normalized": [] }, { "id": "12687", "type": "PA", "arg1_id": "12685", "arg2_id": "12686", "normalized": [] }, { "id": "12690", "type": "PA", "arg1_id": "12688", "arg2_id": "12689", "normalized": [] }, { "id": "12693", "type": "PA", "arg1_id": "12691", "arg2_id": "12692", "normalized": [] }, { "id": "12696", "type": "PA", "arg1_id": "12694", "arg2_id": "12695", "normalized": [] }, { "id": "12699", "type": "PA", "arg1_id": "12697", "arg2_id": "12698", "normalized": [] }, { "id": "12702", "type": "PA", "arg1_id": "12700", "arg2_id": "12701", "normalized": [] }, { "id": "12705", "type": "PA", "arg1_id": "12703", "arg2_id": "12704", "normalized": [] }, { "id": "12708", "type": "PA", "arg1_id": "12706", "arg2_id": "12707", "normalized": [] }, { "id": "12711", "type": "PA", "arg1_id": "12709", "arg2_id": "12710", "normalized": [] }, { "id": "12714", "type": "PA", "arg1_id": "12712", "arg2_id": "12713", "normalized": [] }, { "id": "12717", "type": "PA", "arg1_id": "12715", "arg2_id": "12716", "normalized": [] }, { "id": "12720", "type": "PA", "arg1_id": "12718", "arg2_id": "12719", "normalized": [] }, { "id": "12723", "type": "PA", "arg1_id": "12721", "arg2_id": "12722", "normalized": [] }, { "id": "12726", "type": "PA", "arg1_id": "12724", "arg2_id": "12725", "normalized": [] }, { "id": "12729", "type": "PA", "arg1_id": "12727", "arg2_id": "12728", "normalized": [] }, { "id": "12732", "type": "PA", "arg1_id": "12730", "arg2_id": "12731", "normalized": [] }, { "id": "12735", "type": "PA", "arg1_id": "12733", "arg2_id": "12734", "normalized": [] }, { "id": "12738", "type": "PA", "arg1_id": "12736", "arg2_id": "12737", "normalized": [] }, { "id": "12741", "type": "PA", "arg1_id": "12739", "arg2_id": "12740", "normalized": [] } ]

[ { "id": "12744", "type": "title", "text": [ "Pediatric developmental therapies: interesting new drugs now in early-stage clinical trials." ], "offsets": [ [ 0, 92 ] ] }, { "id": "12745", "type": "abstract", "text": [ "The current high cure rates for children diagnosed with cancer can be attributed in part to emphasis on large cooperative group clinical trials. The significant improvement in pediatric cancer survival over the past few decades is the result of optimized chemotherapy drug dosing, timing, and intensity; however, further alterations in traditional chemotherapy agents are unlikely to produce substantially better outcomes. Furthermore, there remains a subset of patients who have a very poor prognosis due to tumor type or stage at presentation, or who have a dismal prognosis with relapse or recurrence. As such, innovative approaches to therapy and new drugs are clearly needed for introduction into the current pediatric oncology arsenal. A variety of biologically targeted therapies that have shown promise in preclinical studies and early-phase adult clinical trials are now being explored in pediatric clinical trials. These novel agents hold the promise for continuing to drive forward improvements in patient survival, with potentially less toxicity than exists with traditional chemotherapy drugs." ], "offsets": [ [ 93, 1199 ] ] } ]

[ { "id": "12746", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 348, 360 ] ], "normalized": [] }, { "id": "12747", "type": "Chemicals & Drugs", "text": [ "chemotherapy agents" ], "offsets": [ [ 441, 460 ] ], "normalized": [] }, { "id": "12748", "type": "Chemicals & Drugs", "text": [ "hold" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "12749", "type": "Chemicals & Drugs", "text": [ "chemotherapy drugs" ], "offsets": [ [ 1180, 1198 ] ], "normalized": [] } ]

[]

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[ { "id": "12752", "type": "title", "text": [ "Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer." ], "offsets": [ [ 0, 154 ] ] }, { "id": "12753", "type": "abstract", "text": [ "PURPOSE: There is considerable interindividual diversity in the development of adverse reactions during chemotherapy for cancers. This diversity is suggested to be attributable to differences in the disposition of chemotherapeutic agents, which is modified by genetic polymorphisms. In this study we evaluated the possible association of polymorphisms of genes involved in the metabolism, detoxification and transport of the agents with adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin therapy. MATERIALS AND METHODS: A total of 40 patients with urothelial cancer who received methotrexate, vinblastine, doxorubicin and cisplatin or high dose methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy between 1996 and 2005 at Akita University Medical Center were included in this study. Four genetic polymorphisms (ABCB1, GSTP1, CYP3A5 and MTHFR) and clinical parameters were included in the analysis to determine whether there was any association with the grade of adverse reactions at the first cycle and the worst grade of each adverse reaction throughout the chemotherapy period. RESULTS: On multivariate analysis the CYP3A5 A6986G genotype *3/*3 (OR 8.205, 95% CI 1.616-41.667, p = 0.011) and smaller number of treatment cycles (OR 0.156, 95% CI 0.037-0.659, p = 0.011) were independent factors for leukocytopenia (grade 3 or greater) throughout the period of chemotherapy. The mean white blood cell count nadir in patients with genotype *3/*3 was significantly lower than that in those with the *1 allele (1,542 +/- 903 vs 2,431 +/- 973/mm(3), p = 0.009). CONCLUSIONS: The A6986G polymorphism of CYP3A5, which is involved in the metabolism of vinblastine and doxorubicin, might be a genetic predictor of the severity of leukocytopenia induced by chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin." ], "offsets": [ [ 155, 2011 ] ] } ]

[ { "id": "12754", "type": "Diseases & Disorders", "text": [ "methotrexate" ], "offsets": [ [ 66, 78 ] ], "normalized": [] }, { "id": "12755", "type": "Diseases & Disorders", "text": [ "urothelial cancer" ], "offsets": [ [ 136, 153 ] ], "normalized": [] }, { "id": "12756", "type": "Diseases & Disorders", "text": [ "adverse reactions during chemotherapy" ], "offsets": [ [ 234, 271 ] ], "normalized": [] }, { "id": "12757", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 276, 283 ] ], "normalized": [] }, { "id": "12758", "type": "Diseases & Disorders", "text": [ "methotrexate" ], "offsets": [ [ 613, 625 ] ], "normalized": [] }, { "id": "12759", "type": "Diseases & Disorders", "text": [ "urothelial cancer" ], "offsets": [ [ 726, 743 ] ], "normalized": [] }, { "id": "12760", "type": "Genes & Molecular Sequences", "text": [ "ABCB1" ], "offsets": [ [ 1003, 1008 ] ], "normalized": [] }, { "id": "12761", "type": "Genes & Molecular Sequences", "text": [ "GSTP1" ], "offsets": [ [ 1010, 1015 ] ], "normalized": [] }, { "id": "12762", "type": "Genes & Molecular Sequences", "text": [ "CYP3A5" ], "offsets": [ [ 1017, 1023 ] ], "normalized": [] }, { "id": "12763", "type": "Genes & Molecular Sequences", "text": [ "MTHFR" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "12764", "type": "Diseases & Disorders", "text": [ "adverse reaction throughout the chemotherapy" ], "offsets": [ [ 1219, 1263 ] ], "normalized": [] }, { "id": "12765", "type": "SNP & Sequence variations", "text": [ "CYP3A5 A6986G genotype *3/*3" ], "offsets": [ [ 1310, 1338 ] ], "normalized": [] }, { "id": "12766", "type": "Genes & Molecular Sequences", "text": [ "CYP3A5 A6986G genotype *3/*3" ], "offsets": [ [ 1310, 1338 ] ], "normalized": [] }, { "id": "12767", "type": "SNP & Sequence variations", "text": [ "A6986G" ], "offsets": [ [ 1317, 1323 ] ], "normalized": [] }, { "id": "12768", "type": "Diseases & Disorders", "text": [ "leukocytopenia" ], "offsets": [ [ 1492, 1506 ] ], "normalized": [] }, { "id": "12769", "type": "SNP & Sequence variations", "text": [ "genotype *3/*3" ], "offsets": [ [ 1622, 1636 ] ], "normalized": [] }, { "id": "12770", "type": "SNP & Sequence variations", "text": [ "*1 allele" ], "offsets": [ [ 1689, 1698 ] ], "normalized": [] }, { "id": "12771", "type": "SNP & Sequence variations", "text": [ "A6986G polymorphism of CYP3A5" ], "offsets": [ [ 1767, 1796 ] ], "normalized": [] }, { "id": "12772", "type": "Genes & Molecular Sequences", "text": [ "A6986G polymorphism of CYP3A5" ], "offsets": [ [ 1767, 1796 ] ], "normalized": [] }, { "id": "12773", "type": "Diseases & Disorders", "text": [ "leukocytopenia" ], "offsets": [ [ 1914, 1928 ] ], "normalized": [] }, { "id": "12774", "type": "", "text": [ "CYP3A5 A6986G genotype *3/*3" ], "offsets": [ [ 1310, 1338 ] ], "normalized": [] }, { "id": "12775", "type": "", "text": [ "leukocytopenia" ], "offsets": [ [ 1492, 1506 ] ], "normalized": [] }, { "id": "12777", "type": "", "text": [ "A6986G polymorphism of CYP3A5" ], "offsets": [ [ 1767, 1796 ] ], "normalized": [] }, { "id": "12778", "type": "", "text": [ "leukocytopenia" ], "offsets": [ [ 1914, 1928 ] ], "normalized": [] }, { "id": "12780", "type": "", "text": [ "A6986G" ], "offsets": [ [ 1317, 1323 ] ], "normalized": [] }, { "id": "12781", "type": "", "text": [ "leukocytopenia" ], "offsets": [ [ 1492, 1506 ] ], "normalized": [] } ]

[]

[]

[ { "id": "12776", "type": "PA", "arg1_id": "12774", "arg2_id": "12775", "normalized": [] }, { "id": "12779", "type": "PA", "arg1_id": "12777", "arg2_id": "12778", "normalized": [] }, { "id": "12782", "type": "PA", "arg1_id": "12780", "arg2_id": "12781", "normalized": [] } ]

[ { "id": "12785", "type": "title", "text": [ "The role of sphingosine-1-phosphate and ceramide-1-phosphate in calcium homeostasis." ], "offsets": [ [ 0, 84 ] ] }, { "id": "12786", "type": "abstract", "text": [ "During the last several years, sphingolipids have been identified as a source of important signaling molecules. Particularly, the understanding of the distinct biological roles of ceramide, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P) and lyso-sphingomyelin in the regulation of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking has rapidly expanded. Additional studies have elucidated the biological roles of sphingolipids in maintaining a homeostatic environment in cells, as well as in regulating numerous cellular responses to environmental stimuli. This review focuses on the role of S1P and C1P in maintaining Ca2+ homeostasis. By studying changes in the metabolism of S1P and C1P in pathological conditions, it is hoped that altered sphingolipid-metabolizing enzymes and their metabolites can be used as therapeutic targets." ], "offsets": [ [ 85, 989 ] ] } ]

[ { "id": "12787", "type": "Genes & Molecular Sequences", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 12, 35 ] ], "normalized": [] }, { "id": "12788", "type": "Chemicals & Drugs", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 12, 35 ] ], "normalized": [] }, { "id": "12789", "type": "Genes & Molecular Sequences", "text": [ "ceramide-1-phosphate" ], "offsets": [ [ 40, 60 ] ], "normalized": [] }, { "id": "12790", "type": "Chemicals & Drugs", "text": [ "ceramide-1-phosphate" ], "offsets": [ [ 40, 60 ] ], "normalized": [] }, { "id": "12791", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 64, 71 ] ], "normalized": [] }, { "id": "12792", "type": "Genes & Molecular Sequences", "text": [ "sphingolipids" ], "offsets": [ [ 116, 129 ] ], "normalized": [] }, { "id": "12793", "type": "Chemicals & Drugs", "text": [ "sphingolipids" ], "offsets": [ [ 116, 129 ] ], "normalized": [] }, { "id": "12794", "type": "Genes & Molecular Sequences", "text": [ "ceramide" ], "offsets": [ [ 265, 273 ] ], "normalized": [] }, { "id": "12795", "type": "Chemicals & Drugs", "text": [ "ceramide" ], "offsets": [ [ 265, 273 ] ], "normalized": [] }, { "id": "12796", "type": "Genes & Molecular Sequences", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 275, 298 ] ], "normalized": [] }, { "id": "12797", "type": "Chemicals & Drugs", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 275, 298 ] ], "normalized": [] }, { "id": "12798", "type": "Genes & Molecular Sequences", "text": [ "S1P" ], "offsets": [ [ 300, 303 ] ], "normalized": [] }, { "id": "12799", "type": "Chemicals & Drugs", "text": [ "S1P" ], "offsets": [ [ 300, 303 ] ], "normalized": [] }, { "id": "12800", "type": "Genes & Molecular Sequences", "text": [ "ceramide-1-phosphate" ], "offsets": [ [ 306, 326 ] ], "normalized": [] }, { "id": "12801", "type": "Chemicals & Drugs", "text": [ "ceramide-1-phosphate" ], "offsets": [ [ 306, 326 ] ], "normalized": [] }, { "id": "12802", "type": "Genes & Molecular Sequences", "text": [ "C1P" ], "offsets": [ [ 328, 331 ] ], "normalized": [] }, { "id": "12803", "type": "Chemicals & Drugs", "text": [ "C1P" ], "offsets": [ [ 328, 331 ] ], "normalized": [] }, { "id": "12804", "type": "Genes & Molecular Sequences", "text": [ "lyso-sphingomyelin" ], "offsets": [ [ 337, 355 ] ], "normalized": [] }, { "id": "12805", "type": "Chemicals & Drugs", "text": [ "lyso-sphingomyelin" ], "offsets": [ [ 337, 355 ] ], "normalized": [] }, { "id": "12806", "type": "Genes & Molecular Sequences", "text": [ "sphingolipids" ], "offsets": [ [ 568, 581 ] ], "normalized": [] }, { "id": "12807", "type": "Chemicals & Drugs", "text": [ "sphingolipids" ], "offsets": [ [ 568, 581 ] ], "normalized": [] }, { "id": "12808", "type": "Genes & Molecular Sequences", "text": [ "S1P" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "12809", "type": "Chemicals & Drugs", "text": [ "S1P" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "12810", "type": "Genes & Molecular Sequences", "text": [ "C1P" ], "offsets": [ [ 755, 758 ] ], "normalized": [] }, { "id": "12811", "type": "Chemicals & Drugs", "text": [ "C1P" ], "offsets": [ [ 755, 758 ] ], "normalized": [] }, { "id": "12812", "type": "Chemicals & Drugs", "text": [ "Ca2+" ], "offsets": [ [ 774, 778 ] ], "normalized": [] }, { "id": "12813", "type": "Genes & Molecular Sequences", "text": [ "S1P" ], "offsets": [ [ 833, 836 ] ], "normalized": [] }, { "id": "12814", "type": "Chemicals & Drugs", "text": [ "S1P" ], "offsets": [ [ 833, 836 ] ], "normalized": [] }, { "id": "12815", "type": "Genes & Molecular Sequences", "text": [ "C1P" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "12816", "type": "Chemicals & Drugs", "text": [ "C1P" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "12817", "type": "Genes & Molecular Sequences", "text": [ "sphingolipid-metabolizing enzymes" ], "offsets": [ [ 898, 931 ] ], "normalized": [] }, { "id": "12818", "type": "", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 275, 298 ] ], "normalized": [] }, { "id": "12819", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12821", "type": "", "text": [ "ceramide" ], "offsets": [ [ 265, 273 ] ], "normalized": [] }, { "id": "12822", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12824", "type": "", "text": [ "S1P" ], "offsets": [ [ 300, 303 ] ], "normalized": [] }, { "id": "12825", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12827", "type": "", "text": [ "ceramide-1-phosphate" ], "offsets": [ [ 306, 326 ] ], "normalized": [] }, { "id": "12828", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12830", "type": "", "text": [ "C1P" ], "offsets": [ [ 328, 331 ] ], "normalized": [] }, { "id": "12831", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12833", "type": "", "text": [ "lyso-sphingomyelin" ], "offsets": [ [ 337, 355 ] ], "normalized": [] }, { "id": "12834", "type": "", "text": [ "inflammation" ], "offsets": [ [ 430, 442 ] ], "normalized": [] }, { "id": "12836", "type": "", "text": [ "Ca2+" ], "offsets": [ [ 774, 778 ] ], "normalized": [] }, { "id": "12837", "type": "", "text": [ "S1P" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "12839", "type": "", "text": [ "Ca2+" ], "offsets": [ [ 774, 778 ] ], "normalized": [] }, { "id": "12840", "type": "", "text": [ "C1P" ], "offsets": [ [ 755, 758 ] ], "normalized": [] } ]

[]

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[ { "id": "12820", "type": "PA", "arg1_id": "12818", "arg2_id": "12819", "normalized": [] }, { "id": "12823", "type": "PA", "arg1_id": "12821", "arg2_id": "12822", "normalized": [] }, { "id": "12826", "type": "PA", "arg1_id": "12824", "arg2_id": "12825", "normalized": [] }, { "id": "12829", "type": "PA", "arg1_id": "12827", "arg2_id": "12828", "normalized": [] }, { "id": "12832", "type": "PA", "arg1_id": "12830", "arg2_id": "12831", "normalized": [] }, { "id": "12835", "type": "PA", "arg1_id": "12833", "arg2_id": "12834", "normalized": [] }, { "id": "12838", "type": "SA", "arg1_id": "12836", "arg2_id": "12837", "normalized": [] }, { "id": "12841", "type": "SA", "arg1_id": "12839", "arg2_id": "12840", "normalized": [] } ]

[ { "id": "12844", "type": "title", "text": [ "High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study." ], "offsets": [ [ 0, 150 ] ] }, { "id": "12845", "type": "abstract", "text": [ "BACKGROUND: To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy. PATIENTS AND METHODS: High-dose MTX was applied on days 1, 15, and 30, procarbazine on days 1-10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS). RESULTS: Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57-79 years). The median initial KPS was 60% (range 30%-90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34-105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy. CONCLUSION: The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients." ], "offsets": [ [ 151, 1532 ] ] } ]

[ { "id": "12846", "type": "Chemicals & Drugs", "text": [ "High-dose methotrexate" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "12847", "type": "Chemicals & Drugs", "text": [ "procarbazine" ], "offsets": [ [ 37, 49 ] ], "normalized": [] }, { "id": "12848", "type": "Chemicals & Drugs", "text": [ "CCNU" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "12849", "type": "Diseases & Disorders", "text": [ "primary CNS lymphoma" ], "offsets": [ [ 63, 83 ] ], "normalized": [] }, { "id": "12850", "type": "Diseases & Disorders", "text": [ "primary central nervous system lymphoma" ], "offsets": [ [ 208, 247 ] ], "normalized": [] }, { "id": "12851", "type": "Diseases & Disorders", "text": [ "PCNSL" ], "offsets": [ [ 249, 254 ] ], "normalized": [] }, { "id": "12852", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 302, 314 ] ], "normalized": [] }, { "id": "12853", "type": "Chemicals & Drugs", "text": [ "MTX" ], "offsets": [ [ 316, 319 ] ], "normalized": [] }, { "id": "12854", "type": "Chemicals & Drugs", "text": [ "procarbazine" ], "offsets": [ [ 335, 347 ] ], "normalized": [] }, { "id": "12855", "type": "Chemicals & Drugs", "text": [ "CCNU" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "12856", "type": "Diseases & Disorders", "text": [ "neurotoxicity" ], "offsets": [ [ 368, 381 ] ], "normalized": [] }, { "id": "12857", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 451, 463 ] ], "normalized": [] }, { "id": "12858", "type": "Chemicals & Drugs", "text": [ "High-dose MTX" ], "offsets": [ [ 487, 500 ] ], "normalized": [] }, { "id": "12859", "type": "Chemicals & Drugs", "text": [ "procarbazine" ], "offsets": [ [ 536, 548 ] ], "normalized": [] }, { "id": "12860", "type": "Chemicals & Drugs", "text": [ "CCNU" ], "offsets": [ [ 567, 571 ] ], "normalized": [] }, { "id": "12861", "type": "Diseases & Disorders", "text": [ "PCNSL" ], "offsets": [ [ 729, 734 ] ], "normalized": [] }, { "id": "12862", "type": "Diseases & Disorders", "text": [ "primary ocular lymphoma" ], "offsets": [ [ 747, 770 ] ], "normalized": [] }, { "id": "12863", "type": "Diseases & Disorders", "text": [ "Best" ], "offsets": [ [ 883, 887 ] ], "normalized": [] }, { "id": "12864", "type": "Diseases & Disorders", "text": [ "disease progressions" ], "offsets": [ [ 1033, 1053 ] ], "normalized": [] }, { "id": "12865", "type": "Diseases & Disorders", "text": [ "signs" ], "offsets": [ [ 1271, 1276 ] ], "normalized": [] }, { "id": "12866", "type": "Diseases & Disorders", "text": [ "leukoencephalopathy" ], "offsets": [ [ 1280, 1299 ] ], "normalized": [] }, { "id": "12867", "type": "Chemicals & Drugs", "text": [ "high-dose MTX" ], "offsets": [ [ 1332, 1345 ] ], "normalized": [] }, { "id": "12868", "type": "Chemicals & Drugs", "text": [ "procarbazine" ], "offsets": [ [ 1351, 1363 ] ], "normalized": [] }, { "id": "12869", "type": "Chemicals & Drugs", "text": [ "CCNU" ], "offsets": [ [ 1368, 1372 ] ], "normalized": [] }, { "id": "12870", "type": "Diseases & Disorders", "text": [ "leukoencephalopathy" ], "offsets": [ [ 1428, 1447 ] ], "normalized": [] }, { "id": "12871", "type": "Diseases & Disorders", "text": [ "toxicity" ], "offsets": [ [ 1465, 1473 ] ], "normalized": [] }, { "id": "12872", "type": "Diseases & Disorders", "text": [ "PCNSL" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "12873", "type": "", "text": [ "procarbazine" ], "offsets": [ [ 1351, 1363 ] ], "normalized": [] }, { "id": "12874", "type": "", "text": [ "leukoencephalopathy" ], "offsets": [ [ 1428, 1447 ] ], "normalized": [] }, { "id": "12876", "type": "", "text": [ "CCNU" ], "offsets": [ [ 1368, 1372 ] ], "normalized": [] }, { "id": "12877", "type": "", "text": [ "leukoencephalopathy" ], "offsets": [ [ 1428, 1447 ] ], "normalized": [] }, { "id": "12879", "type": "", "text": [ "high-dose MTX" ], "offsets": [ [ 1332, 1345 ] ], "normalized": [] }, { "id": "12880", "type": "", "text": [ "leukoencephalopathy" ], "offsets": [ [ 1428, 1447 ] ], "normalized": [] }, { "id": "12882", "type": "", "text": [ "CCNU" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "12883", "type": "", "text": [ "primary CNS lymphoma" ], "offsets": [ [ 63, 83 ] ], "normalized": [] }, { "id": "12885", "type": "", "text": [ "High-dose methotrexate" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "12886", "type": "", "text": [ "primary CNS lymphoma" ], "offsets": [ [ 63, 83 ] ], "normalized": [] }, { "id": "12888", "type": "", "text": [ "procarbazine" ], "offsets": [ [ 37, 49 ] ], "normalized": [] }, { "id": "12889", "type": "", "text": [ "primary CNS lymphoma" ], "offsets": [ [ 63, 83 ] ], "normalized": [] }, { "id": "12891", "type": "", "text": [ "CCNU" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "12892", "type": "", "text": [ "primary central nervous system lymphoma" ], "offsets": [ [ 208, 247 ] ], "normalized": [] }, { "id": "12894", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 302, 314 ] ], "normalized": [] }, { "id": "12895", "type": "", "text": [ "primary central nervous system lymphoma" ], "offsets": [ [ 208, 247 ] ], "normalized": [] }, { "id": "12897", "type": "", "text": [ "procarbazine" ], "offsets": [ [ 335, 347 ] ], "normalized": [] }, { "id": "12898", "type": "", "text": [ "primary central nervous system lymphoma" ], "offsets": [ [ 208, 247 ] ], "normalized": [] }, { "id": "12900", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 451, 463 ] ], "normalized": [] }, { "id": "12901", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 368, 381 ] ], "normalized": [] } ]

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[ { "id": "12875", "type": "PA", "arg1_id": "12873", "arg2_id": "12874", "normalized": [] }, { "id": "12878", "type": "PA", "arg1_id": "12876", "arg2_id": "12877", "normalized": [] }, { "id": "12881", "type": "PA", "arg1_id": "12879", "arg2_id": "12880", "normalized": [] }, { "id": "12884", "type": "PA", "arg1_id": "12882", "arg2_id": "12883", "normalized": [] }, { "id": "12887", "type": "PA", "arg1_id": "12885", "arg2_id": "12886", "normalized": [] }, { "id": "12890", "type": "PA", "arg1_id": "12888", "arg2_id": "12889", "normalized": [] }, { "id": "12893", "type": "PA", "arg1_id": "12891", "arg2_id": "12892", "normalized": [] }, { "id": "12896", "type": "PA", "arg1_id": "12894", "arg2_id": "12895", "normalized": [] }, { "id": "12899", "type": "PA", "arg1_id": "12897", "arg2_id": "12898", "normalized": [] }, { "id": "12902", "type": "PA", "arg1_id": "12900", "arg2_id": "12901", "normalized": [] } ]

[ { "id": "12905", "type": "title", "text": [ "Understanding intraocular lymphomas." ], "offsets": [ [ 0, 36 ] ] }, { "id": "12906", "type": "abstract", "text": [ "The purpose of this review is to describe the clinical features, pathology and molecular biology of intraocular lymphomas, which represent a heterogenous group of malignant neoplasms; to propose an anatomical classification of these tumours according to whether they occur in the retina or uvea; and to overview laboratory investigations and highlight factors required for successful biopsy. Recent findings show that retinal lymphomas are high-grade (i.e. aggressive), B-cell malignancies and are associated with a poor prognosis, with most patients dying of central nervous system disease. Immunophenotyping and somatic mutation analyses indicate that these lymphomas are probably derived from early post-germinal centre cells. Primary choroidal lymphomas are typically low-grade (i.e. indolent), B-cell tumours with morphological, immunophenotypical and genotypic features similar to extranodal marginal zone B-cell lymphomas (EMZL) elsewhere in the body. The putative cell of origin is the post-germinal centre (memory) B cell. Primary iridal lymphomas are very rare, with an equal distribution of B- and T-cell types and with a variable clinical course, most patients succumbing to their disease as a result of systemic dissemination. Primary lymphomas limited to the ciliary body are exceptionally rare. Secondary uveal lymphomas/leukaemias occur in patients with advanced systemic lymphoma or leukaemia, respectively. In summary, the term 'primary intraocular lymphoma (PIOL)' is imprecise. It would be preferable to refer to the various forms of intraocular lymphoma according to whether they are retinal, choroidal, ciliary or iridal and whether they are primary or secondary in these locations." ], "offsets": [ [ 37, 1741 ] ] } ]

[ { "id": "12907", "type": "Diseases & Disorders", "text": [ "intraocular lymphomas" ], "offsets": [ [ 14, 35 ] ], "normalized": [] }, { "id": "12908", "type": "Diseases & Disorders", "text": [ "intraocular lymphomas" ], "offsets": [ [ 137, 158 ] ], "normalized": [] }, { "id": "12909", "type": "Diseases & Disorders", "text": [ "malignant neoplasms" ], "offsets": [ [ 200, 219 ] ], "normalized": [] }, { "id": "12910", "type": "Diseases & Disorders", "text": [ "tumours" ], "offsets": [ [ 270, 277 ] ], "normalized": [] }, { "id": "12911", "type": "Diseases & Disorders", "text": [ "retinal lymphomas" ], "offsets": [ [ 455, 472 ] ], "normalized": [] }, { "id": "12912", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 494, 504 ] ], "normalized": [] }, { "id": "12913", "type": "Diseases & Disorders", "text": [ "malignancies" ], "offsets": [ [ 514, 526 ] ], "normalized": [] }, { "id": "12914", "type": "Diseases & Disorders", "text": [ "central nervous system disease" ], "offsets": [ [ 597, 627 ] ], "normalized": [] }, { "id": "12915", "type": "Diseases & Disorders", "text": [ "somatic mutation" ], "offsets": [ [ 651, 667 ] ], "normalized": [] }, { "id": "12916", "type": "Diseases & Disorders", "text": [ "lymphomas" ], "offsets": [ [ 697, 706 ] ], "normalized": [] }, { "id": "12917", "type": "Diseases & Disorders", "text": [ "Primary choroidal lymphomas" ], "offsets": [ [ 767, 794 ] ], "normalized": [] }, { "id": "12918", "type": "Diseases & Disorders", "text": [ "choroidal" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "12919", "type": "Diseases & Disorders", "text": [ "tumours" ], "offsets": [ [ 843, 850 ] ], "normalized": [] }, { "id": "12920", "type": "Diseases & Disorders", "text": [ "extranodal marginal zone B-cell lymphomas" ], "offsets": [ [ 924, 965 ] ], "normalized": [] }, { "id": "12921", "type": "Diseases & Disorders", "text": [ "EMZL" ], "offsets": [ [ 967, 971 ] ], "normalized": [] }, { "id": "12922", "type": "Diseases & Disorders", "text": [ "Primary iridal lymphomas" ], "offsets": [ [ 1069, 1093 ] ], "normalized": [] }, { "id": "12923", "type": "Diseases & Disorders", "text": [ "iridal" ], "offsets": [ [ 1077, 1083 ] ], "normalized": [] }, { "id": "12924", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1230, 1237 ] ], "normalized": [] }, { "id": "12925", "type": "Diseases & Disorders", "text": [ "Primary lymphomas" ], "offsets": [ [ 1277, 1294 ] ], "normalized": [] }, { "id": "12926", "type": "Diseases & Disorders", "text": [ "ciliary" ], "offsets": [ [ 1310, 1317 ] ], "normalized": [] }, { "id": "12927", "type": "Diseases & Disorders", "text": [ "Secondary uveal lymphomas" ], "offsets": [ [ 1347, 1372 ] ], "normalized": [] }, { "id": "12928", "type": "Diseases & Disorders", "text": [ "leukaemias" ], "offsets": [ [ 1373, 1383 ] ], "normalized": [] }, { "id": "12929", "type": "Diseases & Disorders", "text": [ "systemic lymphoma" ], "offsets": [ [ 1416, 1433 ] ], "normalized": [] }, { "id": "12930", "type": "Diseases & Disorders", "text": [ "leukaemia" ], "offsets": [ [ 1437, 1446 ] ], "normalized": [] }, { "id": "12931", "type": "Diseases & Disorders", "text": [ "'primary intraocular lymphoma" ], "offsets": [ [ 1483, 1512 ] ], "normalized": [] }, { "id": "12932", "type": "Diseases & Disorders", "text": [ "PIOL" ], "offsets": [ [ 1514, 1518 ] ], "normalized": [] }, { "id": "12933", "type": "Diseases & Disorders", "text": [ "intraocular lymphoma" ], "offsets": [ [ 1591, 1611 ] ], "normalized": [] }, { "id": "12934", "type": "Diseases & Disorders", "text": [ "retinal" ], "offsets": [ [ 1642, 1649 ] ], "normalized": [] }, { "id": "12935", "type": "Diseases & Disorders", "text": [ "choroidal" ], "offsets": [ [ 1651, 1660 ] ], "normalized": [] }, { "id": "12936", "type": "Diseases & Disorders", "text": [ "ciliary" ], "offsets": [ [ 1662, 1669 ] ], "normalized": [] }, { "id": "12937", "type": "Diseases & Disorders", "text": [ "iridal" ], "offsets": [ [ 1673, 1679 ] ], "normalized": [] }, { "id": "12938", "type": "Diseases & Disorders", "text": [ "secondary" ], "offsets": [ [ 1712, 1721 ] ], "normalized": [] } ]

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[ { "id": "12941", "type": "title", "text": [ "A critical role for CHIP in the aggresome pathway." ], "offsets": [ [ 0, 50 ] ] }, { "id": "12942", "type": "abstract", "text": [ "Recent evidence suggests that aggresome formation is a physiologic stress response not limited to misfolded proteins. That stress response, termed \"physiologic aggresome,\" is exemplified by aggresome formation of inducible nitric oxide synthase (iNOS), an important host defense protein. CHIP (carboxy terminus of Hsp70-interacting protein) is a highly conserved protein that has been shown to mediate substrate ubiquitination and degradation by the proteasome. In this study, we show that CHIP has a previously unexpected critical role in the aggresome pathway. CHIP interacts with iNOS and promotes its ubiquitination and degradation by the proteasome as well as its sequestration to the aggresome. CHIP-mediated iNOS targeting to the proteasome sequentially precedes CHIP-mediated iNOS sequestration to the aggresome. CHIP is required for iNOS preaggresome structures to form a mature aggresome. Furthermore, CHIP is required for targeting the mutant form of cystic fibrosis transconductance regulator (CFTRDeltaF508) to the aggresome. Importantly, the ubiquitin ligase function of CHIP is required in targeting preaggresomal structures to the aggresome by promoting an iNOS interaction with histone deacetylase 6, which serves as an adaptor between ubiquitinated proteins and the dynein motor. This study reveals a critical role for CHIP in the aggresome pathway." ], "offsets": [ [ 51, 1418 ] ] } ]

[ { "id": "12943", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 20, 24 ] ], "normalized": [] }, { "id": "12944", "type": "Genes & Molecular Sequences", "text": [ "inducible nitric oxide synthase" ], "offsets": [ [ 264, 295 ] ], "normalized": [] }, { "id": "12945", "type": "Chemicals & Drugs", "text": [ "nitric oxide" ], "offsets": [ [ 274, 286 ] ], "normalized": [] }, { "id": "12946", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 297, 301 ] ], "normalized": [] }, { "id": "12947", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 339, 343 ] ], "normalized": [] }, { "id": "12948", "type": "Genes & Molecular Sequences", "text": [ "carboxy terminus of Hsp70-interacting protein" ], "offsets": [ [ 345, 390 ] ], "normalized": [] }, { "id": "12949", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 541, 545 ] ], "normalized": [] }, { "id": "12950", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 614, 618 ] ], "normalized": [] }, { "id": "12951", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "12952", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 752, 756 ] ], "normalized": [] }, { "id": "12953", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "12954", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 821, 825 ] ], "normalized": [] }, { "id": "12955", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "12956", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 872, 876 ] ], "normalized": [] }, { "id": "12957", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 893, 897 ] ], "normalized": [] }, { "id": "12958", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 963, 967 ] ], "normalized": [] }, { "id": "12959", "type": "Genes & Molecular Sequences", "text": [ "cystic fibrosis transconductance regulator" ], "offsets": [ [ 1013, 1055 ] ], "normalized": [] }, { "id": "12960", "type": "SNP & Sequence variations", "text": [ "CFTRDeltaF508" ], "offsets": [ [ 1057, 1070 ] ], "normalized": [] }, { "id": "12961", "type": "Genes & Molecular Sequences", "text": [ "ubiquitin ligase" ], "offsets": [ [ 1107, 1123 ] ], "normalized": [] }, { "id": "12962", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 1136, 1140 ] ], "normalized": [] }, { "id": "12963", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 1224, 1228 ] ], "normalized": [] }, { "id": "12964", "type": "Genes & Molecular Sequences", "text": [ "histone deacetylase 6" ], "offsets": [ [ 1246, 1267 ] ], "normalized": [] }, { "id": "12965", "type": "Genes & Molecular Sequences", "text": [ "dynein" ], "offsets": [ [ 1335, 1341 ] ], "normalized": [] }, { "id": "12966", "type": "Genes & Molecular Sequences", "text": [ "CHIP" ], "offsets": [ [ 1388, 1392 ] ], "normalized": [] } ]

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[ { "id": "12969", "type": "title", "text": [ "Identification of tumor evolution patterns by means of inductive logic programming." ], "offsets": [ [ 0, 83 ] ] }, { "id": "12970", "type": "abstract", "text": [ "In considering key events of genomic disorders in the development and progression of cancer, the correlation between genomic instability and carcinogenesis is currently under investigation. In this work, we propose an inductive logic programming approach to the problem of modeling evolution patterns for breast cancer. Using this approach, it is possible to extract fingerprints of stages of the disease that can be used in order to develop and deliver the most adequate therapies to patients. Furthermore, such a model can help physicians and biologists in the elucidation of molecular dynamics underlying the aberrations-waterfall model behind carcinogenesis. By showing results obtained on a real-world dataset, we try to give some hints about further approach to the knowledge-driven validations of such hypotheses." ], "offsets": [ [ 84, 904 ] ] } ]

[ { "id": "12971", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "12972", "type": "Diseases & Disorders", "text": [ "genomic disorders" ], "offsets": [ [ 113, 130 ] ], "normalized": [] }, { "id": "12973", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 169, 175 ] ], "normalized": [] }, { "id": "12974", "type": "Diseases & Disorders", "text": [ "genomic instability" ], "offsets": [ [ 201, 220 ] ], "normalized": [] }, { "id": "12975", "type": "Diseases & Disorders", "text": [ "carcinogenesis" ], "offsets": [ [ 225, 239 ] ], "normalized": [] }, { "id": "12976", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 389, 402 ] ], "normalized": [] }, { "id": "12977", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 481, 488 ] ], "normalized": [] }, { "id": "12978", "type": "Diseases & Disorders", "text": [ "carcinogenesis" ], "offsets": [ [ 731, 745 ] ], "normalized": [] } ]

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[ { "id": "12981", "type": "title", "text": [ "Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial." ], "offsets": [ [ 0, 187 ] ] }, { "id": "12982", "type": "abstract", "text": [ "OBJECTIVE: To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function. METHODS: Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks. RESULTS: Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol. CONCLUSION: At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function." ], "offsets": [ [ 188, 1895 ] ] } ]

[ { "id": "12983", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 11, 21 ] ], "normalized": [] }, { "id": "12984", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 29, 40 ] ], "normalized": [] }, { "id": "12985", "type": "Diseases & Disorders", "text": [ "hyperuricemia" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "12986", "type": "Diseases & Disorders", "text": [ "gout" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "12987", "type": "Diseases & Disorders", "text": [ "blind" ], "offsets": [ [ 159, 164 ] ], "normalized": [] }, { "id": "12988", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 252, 262 ] ], "normalized": [] }, { "id": "12989", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 264, 275 ] ], "normalized": [] }, { "id": "12990", "type": "Diseases & Disorders", "text": [ "hyperuricemia" ], "offsets": [ [ 323, 336 ] ], "normalized": [] }, { "id": "12991", "type": "Diseases & Disorders", "text": [ "gout" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "12992", "type": "Diseases & Disorders", "text": [ "impaired renal function" ], "offsets": [ [ 370, 393 ] ], "normalized": [] }, { "id": "12993", "type": "Diseases & Disorders", "text": [ "hyperuricemia" ], "offsets": [ [ 430, 443 ] ], "normalized": [] }, { "id": "12994", "type": "Diseases & Disorders", "text": [ "gout" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "12995", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 617, 627 ] ], "normalized": [] }, { "id": "12996", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 656, 667 ] ], "normalized": [] }, { "id": "12997", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 818, 828 ] ], "normalized": [] }, { "id": "12998", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 966, 977 ] ], "normalized": [] }, { "id": "12999", "type": "Diseases & Disorders", "text": [ "impaired renal function" ], "offsets": [ [ 1064, 1087 ] ], "normalized": [] }, { "id": "13000", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 1101, 1111 ] ], "normalized": [] }, { "id": "13001", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 1258, 1269 ] ], "normalized": [] }, { "id": "13002", "type": "Diseases & Disorders", "text": [ "diarrhea" ], "offsets": [ [ 1403, 1411 ] ], "normalized": [] }, { "id": "13003", "type": "Diseases & Disorders", "text": [ "dizziness" ], "offsets": [ [ 1416, 1425 ] ], "normalized": [] }, { "id": "13004", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 1452, 1462 ] ], "normalized": [] }, { "id": "13005", "type": "Diseases & Disorders", "text": [ "gout flares" ], "offsets": [ [ 1550, 1561 ] ], "normalized": [] }, { "id": "13006", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 1593, 1603 ] ], "normalized": [] }, { "id": "13007", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 1614, 1625 ] ], "normalized": [] }, { "id": "13008", "type": "Chemicals & Drugs", "text": [ "febuxostat" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "13009", "type": "Chemicals & Drugs", "text": [ "allopurinol" ], "offsets": [ [ 1751, 1762 ] ], "normalized": [] }, { "id": "13010", "type": "Diseases & Disorders", "text": [ "hyperuricemia" ], "offsets": [ [ 1807, 1820 ] ], "normalized": [] }, { "id": "13011", "type": "Diseases & Disorders", "text": [ "gout" ], "offsets": [ [ 1825, 1829 ] ], "normalized": [] }, { "id": "13012", "type": "Diseases & Disorders", "text": [ "impaired renal function" ], "offsets": [ [ 1871, 1894 ] ], "normalized": [] }, { "id": "13013", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1101, 1111 ] ], "normalized": [] }, { "id": "13014", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 1064, 1087 ] ], "normalized": [] }, { "id": "13016", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 1258, 1269 ] ], "normalized": [] }, { "id": "13017", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 1064, 1087 ] ], "normalized": [] }, { "id": "13019", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1452, 1462 ] ], "normalized": [] }, { "id": "13020", "type": "", "text": [ "diarrhea" ], "offsets": [ [ 1403, 1411 ] ], "normalized": [] }, { "id": "13022", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1452, 1462 ] ], "normalized": [] }, { "id": "13023", "type": "", "text": [ "dizziness" ], "offsets": [ [ 1416, 1425 ] ], "normalized": [] }, { "id": "13025", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1593, 1603 ] ], "normalized": [] }, { "id": "13026", "type": "", "text": [ "gout flares" ], "offsets": [ [ 1550, 1561 ] ], "normalized": [] }, { "id": "13028", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "13029", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 1807, 1820 ] ], "normalized": [] }, { "id": "13031", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "13032", "type": "", "text": [ "gout" ], "offsets": [ [ 1825, 1829 ] ], "normalized": [] }, { "id": "13034", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "13035", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 1871, 1894 ] ], "normalized": [] }, { "id": "13037", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 1614, 1625 ] ], "normalized": [] }, { "id": "13038", "type": "", "text": [ "gout flares" ], "offsets": [ [ 1550, 1561 ] ], "normalized": [] }, { "id": "13040", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 1751, 1762 ] ], "normalized": [] }, { "id": "13041", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 1807, 1820 ] ], "normalized": [] }, { "id": "13043", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 1751, 1762 ] ], "normalized": [] }, { "id": "13044", "type": "", "text": [ "gout" ], "offsets": [ [ 1825, 1829 ] ], "normalized": [] }, { "id": "13046", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 11, 21 ] ], "normalized": [] }, { "id": "13047", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "13049", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 11, 21 ] ], "normalized": [] }, { "id": "13050", "type": "", "text": [ "gout" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "13052", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 29, 40 ] ], "normalized": [] }, { "id": "13053", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "13055", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 29, 40 ] ], "normalized": [] }, { "id": "13056", "type": "", "text": [ "gout" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "13058", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 252, 262 ] ], "normalized": [] }, { "id": "13059", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 323, 336 ] ], "normalized": [] }, { "id": "13061", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 252, 262 ] ], "normalized": [] }, { "id": "13062", "type": "", "text": [ "gout" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "13064", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 252, 262 ] ], "normalized": [] }, { "id": "13065", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 370, 393 ] ], "normalized": [] }, { "id": "13067", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 264, 275 ] ], "normalized": [] }, { "id": "13068", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 323, 336 ] ], "normalized": [] }, { "id": "13070", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 264, 275 ] ], "normalized": [] }, { "id": "13071", "type": "", "text": [ "gout" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "13073", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 264, 275 ] ], "normalized": [] }, { "id": "13074", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 370, 393 ] ], "normalized": [] }, { "id": "13076", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 617, 627 ] ], "normalized": [] }, { "id": "13077", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 430, 443 ] ], "normalized": [] }, { "id": "13079", "type": "", "text": [ "febuxostat" ], "offsets": [ [ 617, 627 ] ], "normalized": [] }, { "id": "13080", "type": "", "text": [ "gout" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "13082", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 656, 667 ] ], "normalized": [] }, { "id": "13083", "type": "", "text": [ "hyperuricemia" ], "offsets": [ [ 430, 443 ] ], "normalized": [] }, { "id": "13085", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 656, 667 ] ], "normalized": [] }, { "id": "13086", "type": "", "text": [ "gout" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "13088", "type": "", "text": [ "allopurinol" ], "offsets": [ [ 1751, 1762 ] ], "normalized": [] }, { "id": "13089", "type": "", "text": [ "impaired renal function" ], "offsets": [ [ 1871, 1894 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13015", "type": "PA", "arg1_id": "13013", "arg2_id": "13014", "normalized": [] }, { "id": "13018", "type": "PA", "arg1_id": "13016", "arg2_id": "13017", "normalized": [] }, { "id": "13021", "type": "PA", "arg1_id": "13019", "arg2_id": "13020", "normalized": [] }, { "id": "13024", "type": "PA", "arg1_id": "13022", "arg2_id": "13023", "normalized": [] }, { "id": "13027", "type": "PA", "arg1_id": "13025", "arg2_id": "13026", "normalized": [] }, { "id": "13030", "type": "PA", "arg1_id": "13028", "arg2_id": "13029", "normalized": [] }, { "id": "13033", "type": "PA", "arg1_id": "13031", "arg2_id": "13032", "normalized": [] }, { "id": "13036", "type": "PA", "arg1_id": "13034", "arg2_id": "13035", "normalized": [] }, { "id": "13039", "type": "PA", "arg1_id": "13037", "arg2_id": "13038", "normalized": [] }, { "id": "13042", "type": "PA", "arg1_id": "13040", "arg2_id": "13041", "normalized": [] }, { "id": "13045", "type": "PA", "arg1_id": "13043", "arg2_id": "13044", "normalized": [] }, { "id": "13048", "type": "PA", "arg1_id": "13046", "arg2_id": "13047", "normalized": [] }, { "id": "13051", "type": "PA", "arg1_id": "13049", "arg2_id": "13050", "normalized": [] }, { "id": "13054", "type": "PA", "arg1_id": "13052", "arg2_id": "13053", "normalized": [] }, { "id": "13057", "type": "PA", "arg1_id": "13055", "arg2_id": "13056", "normalized": [] }, { "id": "13060", "type": "PA", "arg1_id": "13058", "arg2_id": "13059", "normalized": [] }, { "id": "13063", "type": "PA", "arg1_id": "13061", "arg2_id": "13062", "normalized": [] }, { "id": "13066", "type": "PA", "arg1_id": "13064", "arg2_id": "13065", "normalized": [] }, { "id": "13069", "type": "PA", "arg1_id": "13067", "arg2_id": "13068", "normalized": [] }, { "id": "13072", "type": "PA", "arg1_id": "13070", "arg2_id": "13071", "normalized": [] }, { "id": "13075", "type": "PA", "arg1_id": "13073", "arg2_id": "13074", "normalized": [] }, { "id": "13078", "type": "PA", "arg1_id": "13076", "arg2_id": "13077", "normalized": [] }, { "id": "13081", "type": "PA", "arg1_id": "13079", "arg2_id": "13080", "normalized": [] }, { "id": "13084", "type": "PA", "arg1_id": "13082", "arg2_id": "13083", "normalized": [] }, { "id": "13087", "type": "PA", "arg1_id": "13085", "arg2_id": "13086", "normalized": [] }, { "id": "13090", "type": "PA", "arg1_id": "13088", "arg2_id": "13089", "normalized": [] } ]

[ { "id": "13093", "type": "title", "text": [ "Chronic depression: update on classification and treatment." ], "offsets": [ [ 0, 59 ] ] }, { "id": "13094", "type": "abstract", "text": [ "A significant proportion of patients with depressive disorders suffer from chronic conditions. The DSM-IV recognizes several forms of chronic depression. Chronic depressions differ from nonchronic major depressive disorder (MDD) on many clinical, psychosocial, and familial variables. However, less support exists for current distinctions between the various forms of chronic depression. Antidepressant medications and at least some forms of psychotherapy are efficacious in treating chronic depression, and the combination of pharmacotherapy and psychotherapy appears to be superior to either monotherapy alone. Still, chronic depression is often inadequately treated, and many patients fail to respond or continue to experience residual symptoms after treatment. An important direction for future research is to elucidate the multiple pathways to chronic depression and to tailor treatments to specific etiopathogenetic subgroups." ], "offsets": [ [ 60, 992 ] ] } ]

[ { "id": "13095", "type": "Diseases & Disorders", "text": [ "Chronic depression" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "13096", "type": "Diseases & Disorders", "text": [ "depressive disorders" ], "offsets": [ [ 102, 122 ] ], "normalized": [] }, { "id": "13097", "type": "Diseases & Disorders", "text": [ "suffer" ], "offsets": [ [ 123, 129 ] ], "normalized": [] }, { "id": "13098", "type": "Diseases & Disorders", "text": [ "chronic depression" ], "offsets": [ [ 194, 212 ] ], "normalized": [] }, { "id": "13099", "type": "Diseases & Disorders", "text": [ "Chronic depressions" ], "offsets": [ [ 214, 233 ] ], "normalized": [] }, { "id": "13100", "type": "Diseases & Disorders", "text": [ "major depressive disorder" ], "offsets": [ [ 257, 282 ] ], "normalized": [] }, { "id": "13101", "type": "Diseases & Disorders", "text": [ "MDD" ], "offsets": [ [ 284, 287 ] ], "normalized": [] }, { "id": "13102", "type": "Diseases & Disorders", "text": [ "chronic depression" ], "offsets": [ [ 428, 446 ] ], "normalized": [] }, { "id": "13103", "type": "Chemicals & Drugs", "text": [ "Antidepressant" ], "offsets": [ [ 448, 462 ] ], "normalized": [] }, { "id": "13104", "type": "Diseases & Disorders", "text": [ "chronic depression" ], "offsets": [ [ 544, 562 ] ], "normalized": [] }, { "id": "13105", "type": "Diseases & Disorders", "text": [ "Still" ], "offsets": [ [ 673, 678 ] ], "normalized": [] }, { "id": "13106", "type": "Diseases & Disorders", "text": [ "chronic depression" ], "offsets": [ [ 680, 698 ] ], "normalized": [] }, { "id": "13107", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 799, 807 ] ], "normalized": [] }, { "id": "13108", "type": "Diseases & Disorders", "text": [ "chronic depression" ], "offsets": [ [ 909, 927 ] ], "normalized": [] }, { "id": "13109", "type": "", "text": [ "Antidepressant" ], "offsets": [ [ 448, 462 ] ], "normalized": [] }, { "id": "13110", "type": "", "text": [ "chronic depression" ], "offsets": [ [ 544, 562 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13111", "type": "PA", "arg1_id": "13109", "arg2_id": "13110", "normalized": [] } ]

[ { "id": "13114", "type": "title", "text": [ "Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys." ], "offsets": [ [ 0, 79 ] ] }, { "id": "13115", "type": "abstract", "text": [ "A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIV(MAC251) challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1." ], "offsets": [ [ 80, 1528 ] ] } ]

[ { "id": "13116", "type": "Genes & Molecular Sequences", "text": [ "SIV" ], "offsets": [ [ 21, 24 ] ], "normalized": [] }, { "id": "13117", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 21, 24 ] ], "normalized": [] }, { "id": "13118", "type": "Diseases & Disorders", "text": [ "adenovirus" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "13119", "type": "Genes & Molecular Sequences", "text": [ "adenovirus" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "13120", "type": "Genes & Molecular Sequences", "text": [ "rAd5" ], "offsets": [ [ 117, 121 ] ], "normalized": [] }, { "id": "13121", "type": "Diseases & Disorders", "text": [ "HIV-1" ], "offsets": [ [ 148, 153 ] ], "normalized": [] }, { "id": "13122", "type": "Genes & Molecular Sequences", "text": [ "rAd5" ], "offsets": [ [ 288, 292 ] ], "normalized": [] }, { "id": "13123", "type": "Diseases & Disorders", "text": [ "immunodeficiency" ], "offsets": [ [ 319, 335 ] ], "normalized": [] }, { "id": "13124", "type": "Diseases & Disorders", "text": [ "virus" ], "offsets": [ [ 336, 341 ] ], "normalized": [] }, { "id": "13125", "type": "Genes & Molecular Sequences", "text": [ "SIV" ], "offsets": [ [ 343, 346 ] ], "normalized": [] }, { "id": "13126", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 343, 346 ] ], "normalized": [] }, { "id": "13127", "type": "Genes & Molecular Sequences", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13128", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13129", "type": "SNP & Sequence variations", "text": [ "MHC class I allele Mamu-A*01" ], "offsets": [ [ 480, 508 ] ], "normalized": [] }, { "id": "13130", "type": "Diseases & Disorders", "text": [ "adenovirus" ], "offsets": [ [ 611, 621 ] ], "normalized": [] }, { "id": "13131", "type": "Genes & Molecular Sequences", "text": [ "rAd26" ], "offsets": [ [ 737, 742 ] ], "normalized": [] }, { "id": "13132", "type": "Genes & Molecular Sequences", "text": [ "SIV" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "13133", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "13134", "type": "Genes & Molecular Sequences", "text": [ "rAd5" ], "offsets": [ [ 918, 922 ] ], "normalized": [] }, { "id": "13135", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 938, 941 ] ], "normalized": [] }, { "id": "13136", "type": "Diseases & Disorders", "text": [ "MAC251" ], "offsets": [ [ 942, 948 ] ], "normalized": [] }, { "id": "13137", "type": "Genes & Molecular Sequences", "text": [ "rAd26" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "13138", "type": "Diseases & Disorders", "text": [ "AIDS" ], "offsets": [ [ 1112, 1116 ] ], "normalized": [] }, { "id": "13139", "type": "Genes & Molecular Sequences", "text": [ "SIV" ], "offsets": [ [ 1244, 1247 ] ], "normalized": [] }, { "id": "13140", "type": "Diseases & Disorders", "text": [ "SIV" ], "offsets": [ [ 1244, 1247 ] ], "normalized": [] }, { "id": "13141", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 1367, 1374 ] ], "normalized": [] }, { "id": "13142", "type": "Diseases & Disorders", "text": [ "HIV-1" ], "offsets": [ [ 1522, 1527 ] ], "normalized": [] }, { "id": "13143", "type": "", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13144", "type": "", "text": [ "immunodeficiency" ], "offsets": [ [ 319, 335 ] ], "normalized": [] }, { "id": "13146", "type": "", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13147", "type": "", "text": [ "virus" ], "offsets": [ [ 336, 341 ] ], "normalized": [] }, { "id": "13149", "type": "", "text": [ "rAd26" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "13150", "type": "", "text": [ "AIDS" ], "offsets": [ [ 1112, 1116 ] ], "normalized": [] }, { "id": "13152", "type": "", "text": [ "rAd5" ], "offsets": [ [ 117, 121 ] ], "normalized": [] }, { "id": "13153", "type": "", "text": [ "HIV-1" ], "offsets": [ [ 148, 153 ] ], "normalized": [] }, { "id": "13155", "type": "", "text": [ "adenovirus" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "13156", "type": "", "text": [ "HIV-1" ], "offsets": [ [ 148, 153 ] ], "normalized": [] }, { "id": "13158", "type": "", "text": [ "rAd5" ], "offsets": [ [ 288, 292 ] ], "normalized": [] }, { "id": "13159", "type": "", "text": [ "immunodeficiency" ], "offsets": [ [ 319, 335 ] ], "normalized": [] }, { "id": "13161", "type": "", "text": [ "rAd5" ], "offsets": [ [ 288, 292 ] ], "normalized": [] }, { "id": "13162", "type": "", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13164", "type": "", "text": [ "MHC class I allele Mamu-A*01" ], "offsets": [ [ 480, 508 ] ], "normalized": [] }, { "id": "13165", "type": "", "text": [ "immunodeficiency" ], "offsets": [ [ 319, 335 ] ], "normalized": [] }, { "id": "13167", "type": "", "text": [ "MHC class I allele Mamu-A*01" ], "offsets": [ [ 480, 508 ] ], "normalized": [] }, { "id": "13168", "type": "", "text": [ "SIV" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "13170", "type": "", "text": [ "rAd5" ], "offsets": [ [ 918, 922 ] ], "normalized": [] }, { "id": "13171", "type": "", "text": [ "SIV" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "13173", "type": "", "text": [ "rAd26" ], "offsets": [ [ 737, 742 ] ], "normalized": [] }, { "id": "13174", "type": "", "text": [ "SIV" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "13176", "type": "", "text": [ "rAd26" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "13177", "type": "", "text": [ "MAC251" ], "offsets": [ [ 942, 948 ] ], "normalized": [] }, { "id": "13179", "type": "", "text": [ "rAd26" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "13180", "type": "", "text": [ "SIV" ], "offsets": [ [ 938, 941 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13145", "type": "PA", "arg1_id": "13143", "arg2_id": "13144", "normalized": [] }, { "id": "13148", "type": "PA", "arg1_id": "13146", "arg2_id": "13147", "normalized": [] }, { "id": "13151", "type": "PA", "arg1_id": "13149", "arg2_id": "13150", "normalized": [] }, { "id": "13154", "type": "NA", "arg1_id": "13152", "arg2_id": "13153", "normalized": [] }, { "id": "13157", "type": "NA", "arg1_id": "13155", "arg2_id": "13156", "normalized": [] }, { "id": "13160", "type": "NA", "arg1_id": "13158", "arg2_id": "13159", "normalized": [] }, { "id": "13163", "type": "PA", "arg1_id": "13161", "arg2_id": "13162", "normalized": [] }, { "id": "13166", "type": "NA", "arg1_id": "13164", "arg2_id": "13165", "normalized": [] }, { "id": "13169", "type": "NA", "arg1_id": "13167", "arg2_id": "13168", "normalized": [] }, { "id": "13172", "type": "NA", "arg1_id": "13170", "arg2_id": "13171", "normalized": [] }, { "id": "13175", "type": "PA", "arg1_id": "13173", "arg2_id": "13174", "normalized": [] }, { "id": "13178", "type": "PA", "arg1_id": "13176", "arg2_id": "13177", "normalized": [] }, { "id": "13181", "type": "PA", "arg1_id": "13179", "arg2_id": "13180", "normalized": [] } ]

[ { "id": "13184", "type": "title", "text": [ "Disseminated tuberculosis following second unrelated cord blood transplantation for acute myelogenous leukemia." ], "offsets": [ [ 0, 111 ] ] }, { "id": "13185", "type": "abstract", "text": [ "Here we report the case of a 43-year-old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced-intensity conditioning regimen. She developed a pre-engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti-tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients." ], "offsets": [ [ 112, 1181 ] ] } ]

[ { "id": "13186", "type": "Diseases & Disorders", "text": [ "Disseminated tuberculosis" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "13187", "type": "Diseases & Disorders", "text": [ "acute myelogenous leukemia" ], "offsets": [ [ 84, 110 ] ], "normalized": [] }, { "id": "13188", "type": "Diseases & Disorders", "text": [ "acute myelogenous leukemia" ], "offsets": [ [ 173, 199 ] ], "normalized": [] }, { "id": "13189", "type": "Diseases & Disorders", "text": [ "disseminated tuberculosis" ], "offsets": [ [ 283, 308 ] ], "normalized": [] }, { "id": "13190", "type": "Diseases & Disorders", "text": [ "TB" ], "offsets": [ [ 310, 312 ] ], "normalized": [] }, { "id": "13191", "type": "Diseases & Disorders", "text": [ "chemotherapy" ], "offsets": [ [ 371, 383 ] ], "normalized": [] }, { "id": "13192", "type": "Diseases & Disorders", "text": [ "immune reaction" ], "offsets": [ [ 642, 657 ] ], "normalized": [] }, { "id": "13193", "type": "Chemicals & Drugs", "text": [ "prednisolone" ], "offsets": [ [ 683, 695 ] ], "normalized": [] }, { "id": "13194", "type": "Diseases & Disorders", "text": [ "high fever" ], "offsets": [ [ 796, 806 ] ], "normalized": [] }, { "id": "13195", "type": "Diseases & Disorders", "text": [ "pneumonia" ], "offsets": [ [ 821, 830 ] ], "normalized": [] }, { "id": "13196", "type": "Chemicals & Drugs", "text": [ "antibiotic" ], "offsets": [ [ 839, 849 ] ], "normalized": [] }, { "id": "13197", "type": "Diseases & Disorders", "text": [ "antibiotic" ], "offsets": [ [ 839, 849 ] ], "normalized": [] }, { "id": "13198", "type": "Chemicals & Drugs", "text": [ "antifungal" ], "offsets": [ [ 854, 864 ] ], "normalized": [] }, { "id": "13199", "type": "Diseases & Disorders", "text": [ "antifungal" ], "offsets": [ [ 854, 864 ] ], "normalized": [] }, { "id": "13200", "type": "Diseases & Disorders", "text": [ "Mycobacterium tuberculosis" ], "offsets": [ [ 889, 915 ] ], "normalized": [] }, { "id": "13201", "type": "Diseases & Disorders", "text": [ "disseminated TB" ], "offsets": [ [ 1004, 1019 ] ], "normalized": [] }, { "id": "13202", "type": "Chemicals & Drugs", "text": [ "anti-tuberculous" ], "offsets": [ [ 1029, 1045 ] ], "normalized": [] }, { "id": "13203", "type": "Diseases & Disorders", "text": [ "TB" ], "offsets": [ [ 1077, 1079 ] ], "normalized": [] }, { "id": "13204", "type": "Diseases & Disorders", "text": [ "febrile immunocompromised" ], "offsets": [ [ 1146, 1171 ] ], "normalized": [] }, { "id": "13205", "type": "", "text": [ "prednisolone" ], "offsets": [ [ 683, 695 ] ], "normalized": [] }, { "id": "13206", "type": "", "text": [ "immune reaction" ], "offsets": [ [ 642, 657 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13207", "type": "PA", "arg1_id": "13205", "arg2_id": "13206", "normalized": [] } ]

[ { "id": "13210", "type": "title", "text": [ "Vicarious excretion of parenteral contrast material after endovascular abdominal aortic aneurysm repair." ], "offsets": [ [ 0, 104 ] ] }, { "id": "13211", "type": "abstract", "text": [ "The aim of this study is to describe the finding of vicarious excretion of intravascular contrast media in association with endovascular management of an aortic aneurysm and to discuss the clinical significance. Vicarious excretion of intravascular contrast material through the hepatobiliary system will be encountered occasionally following endovascular procedures. Plain abdominal images obtained for the purpose of graft position and structural integrity will increase recognition of this finding. Vicarious hepatobiliary excretion of parenteral contrast media, while associated with renal obstruction or parenchymal pathology, is not pathognomonic for renal pathology." ], "offsets": [ [ 105, 778 ] ] } ]

[ { "id": "13212", "type": "Chemicals & Drugs", "text": [ "parenteral contrast material" ], "offsets": [ [ 23, 51 ] ], "normalized": [] }, { "id": "13213", "type": "Diseases & Disorders", "text": [ "abdominal aortic aneurysm" ], "offsets": [ [ 71, 96 ] ], "normalized": [] }, { "id": "13214", "type": "Chemicals & Drugs", "text": [ "intravascular contrast media" ], "offsets": [ [ 180, 208 ] ], "normalized": [] }, { "id": "13215", "type": "Diseases & Disorders", "text": [ "aortic aneurysm" ], "offsets": [ [ 259, 274 ] ], "normalized": [] }, { "id": "13216", "type": "Chemicals & Drugs", "text": [ "intravascular contrast material" ], "offsets": [ [ 340, 371 ] ], "normalized": [] }, { "id": "13217", "type": "Chemicals & Drugs", "text": [ "contrast media" ], "offsets": [ [ 655, 669 ] ], "normalized": [] }, { "id": "13218", "type": "Diseases & Disorders", "text": [ "renal obstruction" ], "offsets": [ [ 693, 710 ] ], "normalized": [] }, { "id": "13219", "type": "Diseases & Disorders", "text": [ "parenchymal pathology" ], "offsets": [ [ 714, 735 ] ], "normalized": [] }, { "id": "13220", "type": "Diseases & Disorders", "text": [ "renal pathology" ], "offsets": [ [ 762, 777 ] ], "normalized": [] }, { "id": "13221", "type": "", "text": [ "intravascular contrast media" ], "offsets": [ [ 180, 208 ] ], "normalized": [] }, { "id": "13222", "type": "", "text": [ "aortic aneurysm" ], "offsets": [ [ 259, 274 ] ], "normalized": [] }, { "id": "13224", "type": "", "text": [ "contrast media" ], "offsets": [ [ 655, 669 ] ], "normalized": [] }, { "id": "13225", "type": "", "text": [ "renal obstruction" ], "offsets": [ [ 693, 710 ] ], "normalized": [] }, { "id": "13227", "type": "", "text": [ "contrast media" ], "offsets": [ [ 655, 669 ] ], "normalized": [] }, { "id": "13228", "type": "", "text": [ "renal pathology" ], "offsets": [ [ 762, 777 ] ], "normalized": [] }, { "id": "13230", "type": "", "text": [ "contrast media" ], "offsets": [ [ 655, 669 ] ], "normalized": [] }, { "id": "13231", "type": "", "text": [ "parenchymal pathology" ], "offsets": [ [ 714, 735 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13223", "type": "PA", "arg1_id": "13221", "arg2_id": "13222", "normalized": [] }, { "id": "13226", "type": "PA", "arg1_id": "13224", "arg2_id": "13225", "normalized": [] }, { "id": "13229", "type": "NA", "arg1_id": "13227", "arg2_id": "13228", "normalized": [] }, { "id": "13232", "type": "PA", "arg1_id": "13230", "arg2_id": "13231", "normalized": [] } ]

[ { "id": "13235", "type": "title", "text": [ "H. pylori selectively blocks EGFR endocytosis via the non-receptor kinase c-Abl and CagA." ], "offsets": [ [ 0, 89 ] ] }, { "id": "13236", "type": "abstract", "text": [ "Helicobacter pylori infection is a primary cause of peptic ulcers and is associated with gastric carcinogenesis. The H. pylori-induced pathophysiology may be linked to the deregulation of EGFR signalling. Elevated mucosal levels of EGF and the EGFR have been found in antral gastric biopsies of H. pylori-infected patients. A critical mechanism for regulating EGFR signalling is ligand-induced endocytosis. The internalized receptor recycles back to the plasma membrane for continued signalling or is targeted for degradation terminating receptor signalling. Here, we show that H. pylori blocks EGFR endocytosis and receptor degradation upon prolonged infection of gastric epithelial cells. Moreover, this inhibition occurs via a CagA-dependent, but CagA phosphorylation-independent activation of the non-receptor kinase c-Abl, which in turn phosphorylates the EGFR target site pY1173. This suggests a novel CagA-induced host cell response that is independent of CagA tyrosine phosphorylation. Our data indicate an intriguing strategy of H. pylori in host cell manipulations by altering selective receptor populations via a CagA-dependent endocytic mechanism. Furthermore, we identified a new role for c-Abl in phosphorylation of the EGFR target site pY1173 during H. pylori infection." ], "offsets": [ [ 90, 1375 ] ] } ]

[ { "id": "13237", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 29, 33 ] ], "normalized": [] }, { "id": "13238", "type": "Genes & Molecular Sequences", "text": [ "non-receptor kinase c-Abl" ], "offsets": [ [ 54, 79 ] ], "normalized": [] }, { "id": "13239", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 84, 88 ] ], "normalized": [] }, { "id": "13240", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 278, 282 ] ], "normalized": [] }, { "id": "13241", "type": "Genes & Molecular Sequences", "text": [ "EGF" ], "offsets": [ [ 322, 325 ] ], "normalized": [] }, { "id": "13242", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "13243", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 450, 454 ] ], "normalized": [] }, { "id": "13244", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 685, 689 ] ], "normalized": [] }, { "id": "13245", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 820, 824 ] ], "normalized": [] }, { "id": "13246", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 840, 844 ] ], "normalized": [] }, { "id": "13247", "type": "Genes & Molecular Sequences", "text": [ "non-receptor kinase c-Abl" ], "offsets": [ [ 891, 916 ] ], "normalized": [] }, { "id": "13248", "type": "Genes & Molecular Sequences", "text": [ "EGFR target site pY1173" ], "offsets": [ [ 951, 974 ] ], "normalized": [] }, { "id": "13249", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 998, 1002 ] ], "normalized": [] }, { "id": "13250", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 1053, 1057 ] ], "normalized": [] }, { "id": "13251", "type": "Genes & Molecular Sequences", "text": [ "CagA" ], "offsets": [ [ 1214, 1218 ] ], "normalized": [] }, { "id": "13252", "type": "Genes & Molecular Sequences", "text": [ "c-Abl" ], "offsets": [ [ 1292, 1297 ] ], "normalized": [] }, { "id": "13253", "type": "Genes & Molecular Sequences", "text": [ "EGFR target site pY1173" ], "offsets": [ [ 1324, 1347 ] ], "normalized": [] }, { "id": "13254", "type": "", "text": [ "EGFR" ], "offsets": [ [ 685, 689 ] ], "normalized": [] }, { "id": "13255", "type": "", "text": [ "infection of gastric" ], "offsets": [ [ 742, 762 ] ], "normalized": [] }, { "id": "13257", "type": "", "text": [ "EGFR target site pY1173" ], "offsets": [ [ 1324, 1347 ] ], "normalized": [] }, { "id": "13258", "type": "", "text": [ "infection" ], "offsets": [ [ 1365, 1374 ] ], "normalized": [] }, { "id": "13260", "type": "", "text": [ "c-Abl" ], "offsets": [ [ 1292, 1297 ] ], "normalized": [] }, { "id": "13261", "type": "", "text": [ "infection" ], "offsets": [ [ 1365, 1374 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13256", "type": "PA", "arg1_id": "13254", "arg2_id": "13255", "normalized": [] }, { "id": "13259", "type": "PA", "arg1_id": "13257", "arg2_id": "13258", "normalized": [] }, { "id": "13262", "type": "PA", "arg1_id": "13260", "arg2_id": "13261", "normalized": [] } ]

[ { "id": "13265", "type": "title", "text": [ "Antitumor activity of F90, an epidermal growth factor receptor tyrosine kinase inhibitor, on glioblastoma cell line SHG-44." ], "offsets": [ [ 0, 123 ] ] }, { "id": "13266", "type": "abstract", "text": [ "BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) is thought to be related to cell proliferation, invasion, metastasis, resistance to chemoradiotherapy and poor prognosis of various human cancers. Forty percent to fifty percent of glioblastoma multiforme (GBM) possess deregulated EGFR, which may contribute to the aggressive and refractory course of GBM. Therefore, blockade of EGFR signal transduction may be a promising treatment strategy for GBM. METHODS: MTT assay, cell growth curve assay and tumor xenograft model were used to evaluate the antitumor activity of F90 against SHG-44 in vitro and in vivo. Western blot assay was applied to evaluate the expression of p-EGFR, p-ERK1, p-JNK, p-P38, Bcl2 and P53 proteins. RESULTS: F90 inhibited the cell proliferation in a dose-dependent manner in vitro. The growth of SHG-44 tumor xenografts was suppressed by F90 at a high dose level (100 mg x kg(-1) x d(-1)). Phosphorylation of EGFR and activated downstream signaling proteins, such as ERK1, JNK and P38, were found to be depressed after incubation with F90 for 48 hours in vitro. Down-regulated Bcl2 protein and up-regulated P53 protein were also observed. CONCLUSIONS: The results demonstrate that F90 is effective in inhibiting the proliferation of SHG-44 cells in vitro and tumor growth in vivo, suggesting that F90 may be a new therapeutic option for treatment of GBM." ], "offsets": [ [ 124, 1524 ] ] } ]

[ { "id": "13267", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 22, 25 ] ], "normalized": [] }, { "id": "13268", "type": "Chemicals & Drugs", "text": [ "epidermal growth factor receptor tyrosine kinase inhibitor" ], "offsets": [ [ 30, 88 ] ], "normalized": [] }, { "id": "13269", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor tyrosine kinase inhibitor" ], "offsets": [ [ 30, 88 ] ], "normalized": [] }, { "id": "13270", "type": "Genes & Molecular Sequences", "text": [ "SHG-44" ], "offsets": [ [ 116, 122 ] ], "normalized": [] }, { "id": "13271", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 155, 187 ] ], "normalized": [] }, { "id": "13272", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "13273", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 426, 430 ] ], "normalized": [] }, { "id": "13274", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 524, 528 ] ], "normalized": [] }, { "id": "13275", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 714, 717 ] ], "normalized": [] }, { "id": "13276", "type": "Genes & Molecular Sequences", "text": [ "SHG-44" ], "offsets": [ [ 726, 732 ] ], "normalized": [] }, { "id": "13277", "type": "Genes & Molecular Sequences", "text": [ "p-EGFR" ], "offsets": [ [ 816, 822 ] ], "normalized": [] }, { "id": "13278", "type": "Genes & Molecular Sequences", "text": [ "p-ERK1" ], "offsets": [ [ 824, 830 ] ], "normalized": [] }, { "id": "13279", "type": "Genes & Molecular Sequences", "text": [ "p-JNK" ], "offsets": [ [ 832, 837 ] ], "normalized": [] }, { "id": "13280", "type": "Genes & Molecular Sequences", "text": [ "p-P38" ], "offsets": [ [ 839, 844 ] ], "normalized": [] }, { "id": "13281", "type": "Genes & Molecular Sequences", "text": [ "Bcl2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "13282", "type": "Genes & Molecular Sequences", "text": [ "P53" ], "offsets": [ [ 855, 858 ] ], "normalized": [] }, { "id": "13283", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 878, 881 ] ], "normalized": [] }, { "id": "13284", "type": "Genes & Molecular Sequences", "text": [ "SHG-44" ], "offsets": [ [ 966, 972 ] ], "normalized": [] }, { "id": "13285", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 1008, 1011 ] ], "normalized": [] }, { "id": "13286", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 1079, 1083 ] ], "normalized": [] }, { "id": "13287", "type": "Genes & Molecular Sequences", "text": [ "ERK1" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "13288", "type": "Genes & Molecular Sequences", "text": [ "JNK" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "13289", "type": "Genes & Molecular Sequences", "text": [ "P38" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "13290", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "13291", "type": "Genes & Molecular Sequences", "text": [ "Bcl2" ], "offsets": [ [ 1247, 1251 ] ], "normalized": [] }, { "id": "13292", "type": "Genes & Molecular Sequences", "text": [ "P53" ], "offsets": [ [ 1277, 1280 ] ], "normalized": [] }, { "id": "13293", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 1351, 1354 ] ], "normalized": [] }, { "id": "13294", "type": "Genes & Molecular Sequences", "text": [ "SHG-44" ], "offsets": [ [ 1403, 1409 ] ], "normalized": [] }, { "id": "13295", "type": "Chemicals & Drugs", "text": [ "F90" ], "offsets": [ [ 1467, 1470 ] ], "normalized": [] }, { "id": "13296", "type": "", "text": [ "F90" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "13297", "type": "", "text": [ "EGFR" ], "offsets": [ [ 1079, 1083 ] ], "normalized": [] }, { "id": "13299", "type": "", "text": [ "F90" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "13300", "type": "", "text": [ "ERK1" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "13302", "type": "", "text": [ "F90" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "13303", "type": "", "text": [ "JNK" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "13305", "type": "", "text": [ "F90" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "13306", "type": "", "text": [ "P38" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "13308", "type": "", "text": [ "epidermal growth factor receptor tyrosine kinase inhibitor" ], "offsets": [ [ 30, 88 ] ], "normalized": [] }, { "id": "13309", "type": "", "text": [ "glioblastoma" ], "offsets": [ [ 93, 105 ] ], "normalized": [] }, { "id": "13311", "type": "", "text": [ "F90" ], "offsets": [ [ 22, 25 ] ], "normalized": [] }, { "id": "13312", "type": "", "text": [ "epidermal growth factor receptor tyrosine kinase inhibitor" ], "offsets": [ [ 30, 88 ] ], "normalized": [] }, { "id": "13314", "type": "", "text": [ "F90" ], "offsets": [ [ 22, 25 ] ], "normalized": [] }, { "id": "13315", "type": "", "text": [ "glioblastoma" ], "offsets": [ [ 93, 105 ] ], "normalized": [] }, { "id": "13317", "type": "", "text": [ "EGFR" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "13318", "type": "", "text": [ "metastasis" ], "offsets": [ [ 253, 263 ] ], "normalized": [] }, { "id": "13320", "type": "", "text": [ "EGFR" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "13321", "type": "", "text": [ "cancers" ], "offsets": [ [ 333, 340 ] ], "normalized": [] }, { "id": "13323", "type": "", "text": [ "EGFR" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "13324", "type": "", "text": [ "resistance to chemoradiotherapy" ], "offsets": [ [ 265, 296 ] ], "normalized": [] }, { "id": "13326", "type": "", "text": [ "EGFR" ], "offsets": [ [ 426, 430 ] ], "normalized": [] }, { "id": "13327", "type": "", "text": [ "GBM" ], "offsets": [ [ 496, 499 ] ], "normalized": [] }, { "id": "13329", "type": "", "text": [ "EGFR" ], "offsets": [ [ 524, 528 ] ], "normalized": [] }, { "id": "13330", "type": "", "text": [ "GBM" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "13332", "type": "", "text": [ "F90" ], "offsets": [ [ 1467, 1470 ] ], "normalized": [] }, { "id": "13333", "type": "", "text": [ "GBM" ], "offsets": [ [ 1520, 1523 ] ], "normalized": [] }, { "id": "13335", "type": "", "text": [ "F90" ], "offsets": [ [ 714, 717 ] ], "normalized": [] }, { "id": "13336", "type": "", "text": [ "SHG-44" ], "offsets": [ [ 726, 732 ] ], "normalized": [] }, { "id": "13338", "type": "", "text": [ "F90" ], "offsets": [ [ 1008, 1011 ] ], "normalized": [] }, { "id": "13339", "type": "", "text": [ "SHG-44" ], "offsets": [ [ 966, 972 ] ], "normalized": [] }, { "id": "13341", "type": "", "text": [ "F90" ], "offsets": [ [ 1467, 1470 ] ], "normalized": [] }, { "id": "13342", "type": "", "text": [ "SHG-44" ], "offsets": [ [ 1403, 1409 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13298", "type": "PA", "arg1_id": "13296", "arg2_id": "13297", "normalized": [] }, { "id": "13301", "type": "PA", "arg1_id": "13299", "arg2_id": "13300", "normalized": [] }, { "id": "13304", "type": "PA", "arg1_id": "13302", "arg2_id": "13303", "normalized": [] }, { "id": "13307", "type": "PA", "arg1_id": "13305", "arg2_id": "13306", "normalized": [] }, { "id": "13310", "type": "PA", "arg1_id": "13308", "arg2_id": "13309", "normalized": [] }, { "id": "13313", "type": "PA", "arg1_id": "13311", "arg2_id": "13312", "normalized": [] }, { "id": "13316", "type": "PA", "arg1_id": "13314", "arg2_id": "13315", "normalized": [] }, { "id": "13319", "type": "PA", "arg1_id": "13317", "arg2_id": "13318", "normalized": [] }, { "id": "13322", "type": "PA", "arg1_id": "13320", "arg2_id": "13321", "normalized": [] }, { "id": "13325", "type": "PA", "arg1_id": "13323", "arg2_id": "13324", "normalized": [] }, { "id": "13328", "type": "PA", "arg1_id": "13326", "arg2_id": "13327", "normalized": [] }, { "id": "13331", "type": "PA", "arg1_id": "13329", "arg2_id": "13330", "normalized": [] }, { "id": "13334", "type": "PA", "arg1_id": "13332", "arg2_id": "13333", "normalized": [] }, { "id": "13337", "type": "SA", "arg1_id": "13335", "arg2_id": "13336", "normalized": [] }, { "id": "13340", "type": "PA", "arg1_id": "13338", "arg2_id": "13339", "normalized": [] }, { "id": "13343", "type": "PA", "arg1_id": "13341", "arg2_id": "13342", "normalized": [] } ]

[ { "id": "13346", "type": "title", "text": [ "Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review." ], "offsets": [ [ 0, 133 ] ] }, { "id": "13347", "type": "abstract", "text": [ "BACKGROUND: Safety of long-acting beta agonists (LABA) has been questioned and recent evidence suggested a detrimental effect on asthma control as well as an increased risk of death. OBJECTIVE: To evaluate the safety of regular use of LABA compared with placebo or LABA added to inhaled corticosteroids (ICS) compared with ICS in persistent asthma. METHODS: Randomized studies from MEDLINE, EMBASE, and Cochrane Controlled Trials Register were identified. Additionally, AstraZeneca, GlaxoSmithKline, Novartis and FDA clinical trials databases were searched. Primary outcomes were asthma exacerbations (AE) requiring systemic corticosteroids or hospitalization, life-threatening exacerbations and asthma-related deaths. RESULTS: We identified 92 randomized clinical trials with 74,092 subjects. LABA (as monotherapy) reduced exacerbations requiring corticosteroids (Relative Risk [RR]=0.80; 95% CI, 0.73-0.88), without detrimental effects on hospitalizations or life-threatening episodes. Contrarily, LABA showed a significant increase in asthma-related deaths (Relative Risk=3.83; 95% CI, 1.21-12.14). Subgroup analysis suggests that children, patients receiving salmeterol, and a duration of treatment>12 weeks are associated with a higher risk of serious adverse effects; also there was a protective effect of concomitant use of ICS. On the other hand, combination of LABA/ICS reduced exacerbations (RR=0.73; 95% CI, 0.67-0.79), and hospitalizations (RR=0.58, 95% CI, 0.45-0.74). Combined therapy was also equivalent to ICS in terms of life-threatening episodes and asthma-related deaths. Again, children and use of salmeterol were associated with an increased risk of some severe outcomes as compared with adults and formoterol users, respectively. CONCLUSIONS: This review reinforced the international recommendations in terms of the use of LABA remains the preferred add-on therapy to ICS for patients whose disease cannot adequately controlled with ICS, and that LABA cannot be prescribed as a monotherapy. Nevertheless, in spite of the protective effect of the ICS, children and salmeterol use still show an increased risk of non-fatal serious adverse events." ], "offsets": [ [ 134, 2300 ] ] } ]

[ { "id": "13348", "type": "Chemicals & Drugs", "text": [ "long-acting beta agonists" ], "offsets": [ [ 25, 50 ] ], "normalized": [] }, { "id": "13349", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "13350", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "13351", "type": "Chemicals & Drugs", "text": [ "long-acting beta agonists" ], "offsets": [ [ 156, 181 ] ], "normalized": [] }, { "id": "13352", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 183, 187 ] ], "normalized": [] }, { "id": "13353", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 263, 269 ] ], "normalized": [] }, { "id": "13354", "type": "Diseases & Disorders", "text": [ "death" ], "offsets": [ [ 310, 315 ] ], "normalized": [] }, { "id": "13355", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 369, 373 ] ], "normalized": [] }, { "id": "13356", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 399, 403 ] ], "normalized": [] }, { "id": "13357", "type": "Chemicals & Drugs", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 413, 436 ] ], "normalized": [] }, { "id": "13358", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 438, 441 ] ], "normalized": [] }, { "id": "13359", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 438, 441 ] ], "normalized": [] }, { "id": "13360", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "13361", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "13362", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "13363", "type": "Chemicals & Drugs", "text": [ "Novartis" ], "offsets": [ [ 634, 642 ] ], "normalized": [] }, { "id": "13364", "type": "Diseases & Disorders", "text": [ "asthma exacerbations" ], "offsets": [ [ 714, 734 ] ], "normalized": [] }, { "id": "13365", "type": "Diseases & Disorders", "text": [ "AE" ], "offsets": [ [ 736, 738 ] ], "normalized": [] }, { "id": "13366", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "13367", "type": "Diseases & Disorders", "text": [ "life-threatening exacerbations" ], "offsets": [ [ 795, 825 ] ], "normalized": [] }, { "id": "13368", "type": "Diseases & Disorders", "text": [ "asthma-related deaths" ], "offsets": [ [ 830, 851 ] ], "normalized": [] }, { "id": "13369", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 928, 932 ] ], "normalized": [] }, { "id": "13370", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 982, 997 ] ], "normalized": [] }, { "id": "13371", "type": "Diseases & Disorders", "text": [ "life-threatening episodes" ], "offsets": [ [ 1095, 1120 ] ], "normalized": [] }, { "id": "13372", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 1134, 1138 ] ], "normalized": [] }, { "id": "13373", "type": "Diseases & Disorders", "text": [ "asthma-related deaths" ], "offsets": [ [ 1172, 1193 ] ], "normalized": [] }, { "id": "13374", "type": "Chemicals & Drugs", "text": [ "salmeterol" ], "offsets": [ [ 1297, 1307 ] ], "normalized": [] }, { "id": "13375", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 1391, 1406 ] ], "normalized": [] }, { "id": "13376", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 1465, 1468 ] ], "normalized": [] }, { "id": "13377", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 1465, 1468 ] ], "normalized": [] }, { "id": "13378", "type": "Chemicals & Drugs", "text": [ "LABA/ICS" ], "offsets": [ [ 1504, 1512 ] ], "normalized": [] }, { "id": "13379", "type": "Diseases & Disorders", "text": [ "LABA/ICS" ], "offsets": [ [ 1504, 1512 ] ], "normalized": [] }, { "id": "13380", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 1656, 1659 ] ], "normalized": [] }, { "id": "13381", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 1656, 1659 ] ], "normalized": [] }, { "id": "13382", "type": "Diseases & Disorders", "text": [ "life-threatening episodes" ], "offsets": [ [ 1672, 1697 ] ], "normalized": [] }, { "id": "13383", "type": "Diseases & Disorders", "text": [ "asthma-related deaths" ], "offsets": [ [ 1702, 1723 ] ], "normalized": [] }, { "id": "13384", "type": "Chemicals & Drugs", "text": [ "salmeterol" ], "offsets": [ [ 1752, 1762 ] ], "normalized": [] }, { "id": "13385", "type": "Chemicals & Drugs", "text": [ "formoterol" ], "offsets": [ [ 1854, 1864 ] ], "normalized": [] }, { "id": "13386", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 1979, 1983 ] ], "normalized": [] }, { "id": "13387", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 2024, 2027 ] ], "normalized": [] }, { "id": "13388", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 2024, 2027 ] ], "normalized": [] }, { "id": "13389", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 2047, 2054 ] ], "normalized": [] }, { "id": "13390", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 2089, 2092 ] ], "normalized": [] }, { "id": "13391", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 2089, 2092 ] ], "normalized": [] }, { "id": "13392", "type": "Chemicals & Drugs", "text": [ "LABA" ], "offsets": [ [ 2103, 2107 ] ], "normalized": [] }, { "id": "13393", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 2202, 2205 ] ], "normalized": [] }, { "id": "13394", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 2202, 2205 ] ], "normalized": [] }, { "id": "13395", "type": "Chemicals & Drugs", "text": [ "salmeterol" ], "offsets": [ [ 2220, 2230 ] ], "normalized": [] }, { "id": "13396", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 2235, 2240 ] ], "normalized": [] }, { "id": "13397", "type": "Diseases & Disorders", "text": [ "non-fatal serious adverse events" ], "offsets": [ [ 2267, 2299 ] ], "normalized": [] }, { "id": "13398", "type": "", "text": [ "long-acting beta agonists" ], "offsets": [ [ 156, 181 ] ], "normalized": [] }, { "id": "13399", "type": "", "text": [ "death" ], "offsets": [ [ 310, 315 ] ], "normalized": [] }, { "id": "13401", "type": "", "text": [ "LABA" ], "offsets": [ [ 183, 187 ] ], "normalized": [] }, { "id": "13402", "type": "", "text": [ "death" ], "offsets": [ [ 310, 315 ] ], "normalized": [] }, { "id": "13404", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "13405", "type": "", "text": [ "asthma exacerbations" ], "offsets": [ [ 714, 734 ] ], "normalized": [] }, { "id": "13407", "type": "", "text": [ "LABA" ], "offsets": [ [ 928, 932 ] ], "normalized": [] }, { "id": "13408", "type": "", "text": [ "life-threatening episodes" ], "offsets": [ [ 1095, 1120 ] ], "normalized": [] }, { "id": "13410", "type": "", "text": [ "LABA" ], "offsets": [ [ 1134, 1138 ] ], "normalized": [] }, { "id": "13411", "type": "", "text": [ "asthma-related deaths" ], "offsets": [ [ 1172, 1193 ] ], "normalized": [] }, { "id": "13413", "type": "", "text": [ "salmeterol" ], "offsets": [ [ 2220, 2230 ] ], "normalized": [] }, { "id": "13414", "type": "", "text": [ "non-fatal serious adverse events" ], "offsets": [ [ 2267, 2299 ] ], "normalized": [] }, { "id": "13416", "type": "", "text": [ "salmeterol" ], "offsets": [ [ 2220, 2230 ] ], "normalized": [] }, { "id": "13417", "type": "", "text": [ "still" ], "offsets": [ [ 2235, 2240 ] ], "normalized": [] }, { "id": "13419", "type": "", "text": [ "long-acting beta agonists" ], "offsets": [ [ 25, 50 ] ], "normalized": [] }, { "id": "13420", "type": "", "text": [ "asthma" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "13422", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "13423", "type": "", "text": [ "asthma" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "13425", "type": "", "text": [ "LABA" ], "offsets": [ [ 183, 187 ] ], "normalized": [] }, { "id": "13426", "type": "", "text": [ "asthma" ], "offsets": [ [ 263, 269 ] ], "normalized": [] }, { "id": "13428", "type": "", "text": [ "long-acting beta agonists" ], "offsets": [ [ 156, 181 ] ], "normalized": [] }, { "id": "13429", "type": "", "text": [ "asthma" ], "offsets": [ [ 263, 269 ] ], "normalized": [] }, { "id": "13431", "type": "", "text": [ "LABA" ], "offsets": [ [ 399, 403 ] ], "normalized": [] }, { "id": "13432", "type": "", "text": [ "asthma" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "13434", "type": "", "text": [ "ICS" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "13435", "type": "", "text": [ "asthma" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "13437", "type": "", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 413, 436 ] ], "normalized": [] }, { "id": "13438", "type": "", "text": [ "asthma" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "13440", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "13441", "type": "", "text": [ "asthma-related deaths" ], "offsets": [ [ 830, 851 ] ], "normalized": [] }, { "id": "13443", "type": "", "text": [ "ICS" ], "offsets": [ [ 1656, 1659 ] ], "normalized": [] }, { "id": "13444", "type": "", "text": [ "asthma-related deaths" ], "offsets": [ [ 1702, 1723 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13400", "type": "SA", "arg1_id": "13398", "arg2_id": "13399", "normalized": [] }, { "id": "13403", "type": "SA", "arg1_id": "13401", "arg2_id": "13402", "normalized": [] }, { "id": "13406", "type": "PA", "arg1_id": "13404", "arg2_id": "13405", "normalized": [] }, { "id": "13409", "type": "NA", "arg1_id": "13407", "arg2_id": "13408", "normalized": [] }, { "id": "13412", "type": "PA", "arg1_id": "13410", "arg2_id": "13411", "normalized": [] }, { "id": "13415", "type": "PA", "arg1_id": "13413", "arg2_id": "13414", "normalized": [] }, { "id": "13418", "type": "PA", "arg1_id": "13416", "arg2_id": "13417", "normalized": [] }, { "id": "13421", "type": "PA", "arg1_id": "13419", "arg2_id": "13420", "normalized": [] }, { "id": "13424", "type": "PA", "arg1_id": "13422", "arg2_id": "13423", "normalized": [] }, { "id": "13427", "type": "PA", "arg1_id": "13425", "arg2_id": "13426", "normalized": [] }, { "id": "13430", "type": "PA", "arg1_id": "13428", "arg2_id": "13429", "normalized": [] }, { "id": "13433", "type": "PA", "arg1_id": "13431", "arg2_id": "13432", "normalized": [] }, { "id": "13436", "type": "PA", "arg1_id": "13434", "arg2_id": "13435", "normalized": [] }, { "id": "13439", "type": "PA", "arg1_id": "13437", "arg2_id": "13438", "normalized": [] }, { "id": "13442", "type": "PA", "arg1_id": "13440", "arg2_id": "13441", "normalized": [] }, { "id": "13445", "type": "PA", "arg1_id": "13443", "arg2_id": "13444", "normalized": [] } ]

[ { "id": "13448", "type": "title", "text": [ "Comparison of the Bath Ankylosing Spondylitis Disease Activity Index and a modified version of the index in assessing disease activity in patients with ankylosing spondylitis without peripheral manifestations." ], "offsets": [ [ 0, 209 ] ] }, { "id": "13449", "type": "abstract", "text": [ "OBJECTIVE: To compare the original Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) with a modified BASDAI without questions about peripheral arthritis (question 3) and enthesitis (question 4), here termed the mini-BASDAI, as an instrument to assess disease activity in patients with ankylosing spondylitis (AS) without peripheral manifestations. METHODS: The mini-BASDAI was calculated by omitting questions 3 and 4. The correlation of the original BASDAI and the mini-BASDAI with patient global and other disease parameters was assessed in a total of 692 patients from three AS cohorts including one observational AS cohort and two clinical trial populations treated with non-steroidal anti-inflammatory drugs and tumour necrosis factor alpha inhibitors. Sensitivity to change was assessed by calculating effect sizes. RESULTS: Up to 70% of AS patients did not have peripheral involvement. Patients with peripheral involvement had higher disease activity in all activity parameters. The mini-BASDAI had higher values compared with the original BASDAI, also in the subgroup with peripheral manifestations. However, the mini-BASDAI did not correlate better with other markers of disease activity compared with the original BASDAI. Furthermore, effect sizes of the original BASDAI and mini-BASDAI were comparable in the treatment trials. Interestingly, approximately 5% of active AS patients with pure axial disease manifestation were identified whose disease activity was underestimated by the original BASDAI. CONCLUSION: On a group level using the mini-BASDAI did not result in an advantage to assess disease activity or in the subgroup without peripheral involvement. In only approximately 5% of AS patients was the mini-BASDAI superior to the original BASDAI." ], "offsets": [ [ 210, 1984 ] ] } ]

[ { "id": "13450", "type": "Genes & Molecular Sequences", "text": [ "Ankylosing Spondylitis" ], "offsets": [ [ 23, 45 ] ], "normalized": [] }, { "id": "13451", "type": "Genes & Molecular Sequences", "text": [ "ankylosing spondylitis" ], "offsets": [ [ 152, 174 ] ], "normalized": [] }, { "id": "13452", "type": "Genes & Molecular Sequences", "text": [ "Ankylosing Spondylitis" ], "offsets": [ [ 250, 272 ] ], "normalized": [] }, { "id": "13453", "type": "Genes & Molecular Sequences", "text": [ "ankylosing spondylitis" ], "offsets": [ [ 505, 527 ] ], "normalized": [] }, { "id": "13454", "type": "Chemicals & Drugs", "text": [ "non-steroidal anti-inflammatory drugs" ], "offsets": [ [ 895, 932 ] ], "normalized": [] }, { "id": "13455", "type": "Chemicals & Drugs", "text": [ "tumour necrosis factor alpha inhibitors" ], "offsets": [ [ 937, 976 ] ], "normalized": [] }, { "id": "13456", "type": "", "text": [ "non-steroidal anti-inflammatory drugs" ], "offsets": [ [ 895, 932 ] ], "normalized": [] }, { "id": "13457", "type": "", "text": [ "AS" ], "offsets": [ [ 837, 839 ] ], "normalized": [] }, { "id": "13459", "type": "", "text": [ "tumour necrosis factor alpha inhibitors" ], "offsets": [ [ 937, 976 ] ], "normalized": [] }, { "id": "13460", "type": "", "text": [ "AS" ], "offsets": [ [ 837, 839 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13458", "type": "PA", "arg1_id": "13456", "arg2_id": "13457", "normalized": [] }, { "id": "13461", "type": "PA", "arg1_id": "13459", "arg2_id": "13460", "normalized": [] } ]

[ { "id": "13464", "type": "title", "text": [ "Elevation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression in growth hormone-secreting pituitary adenoma with Gsalpha protein mutation." ], "offsets": [ [ 0, 169 ] ] }, { "id": "13465", "type": "abstract", "text": [ "Growth hormone-releasing hormone (GHRH) stimulates not only the synthesis and secretion of GH but also the proliferation of normal somatotrophs. The expression of GHRH receptor (GHRHR) is regulated by GHRH, both of which are known to be expressed in human GH-secreting pituitary adenoma cells. Somatic mutations in the subunit of Gsalpha protein (gsp), lead to the constitutive activation of adenylyl cyclase in pituitary adenomas that secrete GH. It has not been examined how gsp mutations influence GHRHR expression in GH-secreting adenomas. We therefore analyzed the expression levels of GHRHR messenger ribonucleic acid (mRNA) in GH-secreting pituitary adenomas focusing on a gsp mutation. Furthermore, we investigated the effect of GHRH on the expression of GHRHR mRNA in primary cultures of GH-secreting pituitary adenoma cells. GHRHR mRNA expression levels were significantly elevated in gsp mutation-positive GH-secreting adenomas compared with those in gsp mutation-negative ones. In primary-cultured GH-secreting adenoma cells, the increase of GH secretion in response to GHRH was shown in both gsp mutation-positive and -negative adenoma cells with a significantly higher response in the latter adenoma cells. GHRH increased GHRHR mRNA expression level in gsp mutation-negative adenoma cells while it was not influenced by GHRH in gsp mutation-positive adenoma cells. These results suggest that gsp mutations up-regulate GHRHR mRNA expression in GH-secreting pituitary adenoma cells, and that gsp mutations desensitize the adenoma cells to GHRH in terms of their GHRHR mRNA expression probably because of their saturation of GHRH signaling." ], "offsets": [ [ 170, 1821 ] ] } ]

[ { "id": "13466", "type": "Genes & Molecular Sequences", "text": [ "growth hormone-releasing hormone receptor messenger ribonucleic acid" ], "offsets": [ [ 13, 81 ] ], "normalized": [] }, { "id": "13467", "type": "Diseases & Disorders", "text": [ "growth hormone-secreting pituitary adenoma" ], "offsets": [ [ 96, 138 ] ], "normalized": [] }, { "id": "13468", "type": "SNP & Sequence variations", "text": [ "Gsalpha protein mutation" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "13469", "type": "Diseases & Disorders", "text": [ "Gsalpha protein mutation" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "13470", "type": "Genes & Molecular Sequences", "text": [ "Gsalpha protein mutation" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "13471", "type": "Genes & Molecular Sequences", "text": [ "Growth hormone-releasing hormone" ], "offsets": [ [ 170, 202 ] ], "normalized": [] }, { "id": "13472", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 204, 208 ] ], "normalized": [] }, { "id": "13473", "type": "Genes & Molecular Sequences", "text": [ "GH" ], "offsets": [ [ 261, 263 ] ], "normalized": [] }, { "id": "13474", "type": "Genes & Molecular Sequences", "text": [ "GHRH receptor" ], "offsets": [ [ 333, 346 ] ], "normalized": [] }, { "id": "13475", "type": "Genes & Molecular Sequences", "text": [ "GHRHR" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "13476", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 371, 375 ] ], "normalized": [] }, { "id": "13477", "type": "Diseases & Disorders", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13478", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13479", "type": "SNP & Sequence variations", "text": [ "Somatic mutations in the subunit of Gsalpha protein" ], "offsets": [ [ 464, 515 ] ], "normalized": [] }, { "id": "13480", "type": "Diseases & Disorders", "text": [ "Somatic mutations in the subunit of Gsalpha protein" ], "offsets": [ [ 464, 515 ] ], "normalized": [] }, { "id": "13481", "type": "Genes & Molecular Sequences", "text": [ "Gsalpha" ], "offsets": [ [ 500, 507 ] ], "normalized": [] }, { "id": "13482", "type": "Genes & Molecular Sequences", "text": [ "gsp" ], "offsets": [ [ 517, 520 ] ], "normalized": [] }, { "id": "13483", "type": "Genes & Molecular Sequences", "text": [ "adenylyl cyclase" ], "offsets": [ [ 562, 578 ] ], "normalized": [] }, { "id": "13484", "type": "Diseases & Disorders", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13485", "type": "Genes & Molecular Sequences", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13486", "type": "SNP & Sequence variations", "text": [ "gsp mutations" ], "offsets": [ [ 647, 660 ] ], "normalized": [] }, { "id": "13487", "type": "Diseases & Disorders", "text": [ "gsp mutations" ], "offsets": [ [ 647, 660 ] ], "normalized": [] }, { "id": "13488", "type": "Genes & Molecular Sequences", "text": [ "gsp mutations" ], "offsets": [ [ 647, 660 ] ], "normalized": [] }, { "id": "13489", "type": "Genes & Molecular Sequences", "text": [ "GHRHR" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "13490", "type": "Diseases & Disorders", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13491", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13492", "type": "Genes & Molecular Sequences", "text": [ "GHRHR messenger ribonucleic acid" ], "offsets": [ [ 761, 793 ] ], "normalized": [] }, { "id": "13493", "type": "Diseases & Disorders", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13494", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13495", "type": "SNP & Sequence variations", "text": [ "gsp mutation" ], "offsets": [ [ 850, 862 ] ], "normalized": [] }, { "id": "13496", "type": "Diseases & Disorders", "text": [ "gsp mutation" ], "offsets": [ [ 850, 862 ] ], "normalized": [] }, { "id": "13497", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation" ], "offsets": [ [ 850, 862 ] ], "normalized": [] }, { "id": "13498", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 907, 911 ] ], "normalized": [] }, { "id": "13499", "type": "Genes & Molecular Sequences", "text": [ "GHRHR mRNA" ], "offsets": [ [ 933, 943 ] ], "normalized": [] }, { "id": "13500", "type": "Diseases & Disorders", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13501", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13502", "type": "Genes & Molecular Sequences", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] }, { "id": "13503", "type": "SNP & Sequence variations", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1065, 1086 ] ], "normalized": [] }, { "id": "13504", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1065, 1086 ] ], "normalized": [] }, { "id": "13505", "type": "Diseases & Disorders", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1065, 1086 ] ], "normalized": [] }, { "id": "13506", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 1069, 1077 ] ], "normalized": [] }, { "id": "13507", "type": "Genes & Molecular Sequences", "text": [ "GH" ], "offsets": [ [ 1087, 1089 ] ], "normalized": [] }, { "id": "13508", "type": "Diseases & Disorders", "text": [ "adenomas" ], "offsets": [ [ 1100, 1108 ] ], "normalized": [] }, { "id": "13509", "type": "SNP & Sequence variations", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1132, 1153 ] ], "normalized": [] }, { "id": "13510", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1132, 1153 ] ], "normalized": [] }, { "id": "13511", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 1136, 1144 ] ], "normalized": [] }, { "id": "13512", "type": "Diseases & Disorders", "text": [ "GH-secreting adenoma" ], "offsets": [ [ 1180, 1200 ] ], "normalized": [] }, { "id": "13513", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting adenoma" ], "offsets": [ [ 1180, 1200 ] ], "normalized": [] }, { "id": "13514", "type": "Genes & Molecular Sequences", "text": [ "GH" ], "offsets": [ [ 1224, 1226 ] ], "normalized": [] }, { "id": "13515", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "13516", "type": "SNP & Sequence variations", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1275, 1296 ] ], "normalized": [] }, { "id": "13517", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1275, 1296 ] ], "normalized": [] }, { "id": "13518", "type": "Diseases & Disorders", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1275, 1296 ] ], "normalized": [] }, { "id": "13519", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 1279, 1287 ] ], "normalized": [] }, { "id": "13520", "type": "SNP & Sequence variations", "text": [ "-negative" ], "offsets": [ [ 1301, 1310 ] ], "normalized": [] }, { "id": "13521", "type": "Diseases & Disorders", "text": [ "adenoma" ], "offsets": [ [ 1311, 1318 ] ], "normalized": [] }, { "id": "13522", "type": "Diseases & Disorders", "text": [ "adenoma" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] }, { "id": "13523", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 1391, 1395 ] ], "normalized": [] }, { "id": "13524", "type": "Genes & Molecular Sequences", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "13525", "type": "SNP & Sequence variations", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1437, 1458 ] ], "normalized": [] }, { "id": "13526", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1437, 1458 ] ], "normalized": [] }, { "id": "13527", "type": "Diseases & Disorders", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1437, 1458 ] ], "normalized": [] }, { "id": "13528", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 1441, 1449 ] ], "normalized": [] }, { "id": "13529", "type": "Diseases & Disorders", "text": [ "adenoma" ], "offsets": [ [ 1459, 1466 ] ], "normalized": [] }, { "id": "13530", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "13531", "type": "SNP & Sequence variations", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "13532", "type": "Genes & Molecular Sequences", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "13533", "type": "Diseases & Disorders", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "13534", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 1516, 1524 ] ], "normalized": [] }, { "id": "13535", "type": "Diseases & Disorders", "text": [ "adenoma" ], "offsets": [ [ 1534, 1541 ] ], "normalized": [] }, { "id": "13536", "type": "SNP & Sequence variations", "text": [ "gsp mutations" ], "offsets": [ [ 1576, 1589 ] ], "normalized": [] }, { "id": "13537", "type": "Diseases & Disorders", "text": [ "gsp mutations" ], "offsets": [ [ 1576, 1589 ] ], "normalized": [] }, { "id": "13538", "type": "Genes & Molecular Sequences", "text": [ "gsp mutations" ], "offsets": [ [ 1576, 1589 ] ], "normalized": [] }, { "id": "13539", "type": "Genes & Molecular Sequences", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1602, 1612 ] ], "normalized": [] }, { "id": "13540", "type": "Diseases & Disorders", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13541", "type": "Genes & Molecular Sequences", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13542", "type": "SNP & Sequence variations", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13543", "type": "Diseases & Disorders", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13544", "type": "Genes & Molecular Sequences", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13545", "type": "Diseases & Disorders", "text": [ "adenoma" ], "offsets": [ [ 1704, 1711 ] ], "normalized": [] }, { "id": "13546", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 1721, 1725 ] ], "normalized": [] }, { "id": "13547", "type": "Genes & Molecular Sequences", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1744, 1754 ] ], "normalized": [] }, { "id": "13548", "type": "Genes & Molecular Sequences", "text": [ "GHRH" ], "offsets": [ [ 1806, 1810 ] ], "normalized": [] }, { "id": "13549", "type": "", "text": [ "GHRH" ], "offsets": [ [ 371, 375 ] ], "normalized": [] }, { "id": "13550", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13552", "type": "", "text": [ "GHRH receptor" ], "offsets": [ [ 333, 346 ] ], "normalized": [] }, { "id": "13553", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13555", "type": "", "text": [ "GHRHR" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "13556", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13558", "type": "", "text": [ "Somatic mutations in the subunit of Gsalpha protein" ], "offsets": [ [ 464, 515 ] ], "normalized": [] }, { "id": "13559", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13561", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13562", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13564", "type": "", "text": [ "growth hormone-releasing hormone receptor messenger ribonucleic acid" ], "offsets": [ [ 13, 81 ] ], "normalized": [] }, { "id": "13565", "type": "", "text": [ "growth hormone-secreting pituitary adenoma" ], "offsets": [ [ 96, 138 ] ], "normalized": [] }, { "id": "13567", "type": "", "text": [ "growth hormone-releasing hormone receptor messenger ribonucleic acid" ], "offsets": [ [ 13, 81 ] ], "normalized": [] }, { "id": "13568", "type": "", "text": [ "Gsalpha protein mutation" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "13570", "type": "", "text": [ "adenylyl cyclase" ], "offsets": [ [ 562, 578 ] ], "normalized": [] }, { "id": "13571", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13573", "type": "", "text": [ "adenylyl cyclase" ], "offsets": [ [ 562, 578 ] ], "normalized": [] }, { "id": "13574", "type": "", "text": [ "Somatic mutations in the subunit of Gsalpha protein" ], "offsets": [ [ 464, 515 ] ], "normalized": [] }, { "id": "13576", "type": "", "text": [ "GHRHR" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "13577", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 647, 660 ] ], "normalized": [] }, { "id": "13579", "type": "", "text": [ "GHRHR" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "13580", "type": "", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13582", "type": "", "text": [ "GHRHR messenger ribonucleic acid" ], "offsets": [ [ 761, 793 ] ], "normalized": [] }, { "id": "13583", "type": "", "text": [ "gsp mutation" ], "offsets": [ [ 850, 862 ] ], "normalized": [] }, { "id": "13585", "type": "", "text": [ "GHRHR messenger ribonucleic acid" ], "offsets": [ [ 761, 793 ] ], "normalized": [] }, { "id": "13586", "type": "", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13588", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 933, 943 ] ], "normalized": [] }, { "id": "13589", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13591", "type": "", "text": [ "GHRH" ], "offsets": [ [ 907, 911 ] ], "normalized": [] }, { "id": "13592", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13594", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] }, { "id": "13595", "type": "", "text": [ "mutation" ], "offsets": [ [ 1136, 1144 ] ], "normalized": [] }, { "id": "13597", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] }, { "id": "13598", "type": "", "text": [ "adenomas" ], "offsets": [ [ 1100, 1108 ] ], "normalized": [] }, { "id": "13600", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "13601", "type": "", "text": [ "mutation" ], "offsets": [ [ 1279, 1287 ] ], "normalized": [] }, { "id": "13603", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "13604", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] }, { "id": "13606", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "13607", "type": "", "text": [ "mutation" ], "offsets": [ [ 1516, 1524 ] ], "normalized": [] }, { "id": "13609", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "13610", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1534, 1541 ] ], "normalized": [] }, { "id": "13612", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "13613", "type": "", "text": [ "mutation" ], "offsets": [ [ 1516, 1524 ] ], "normalized": [] }, { "id": "13615", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "13616", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1534, 1541 ] ], "normalized": [] }, { "id": "13618", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1744, 1754 ] ], "normalized": [] }, { "id": "13619", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13621", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1744, 1754 ] ], "normalized": [] }, { "id": "13622", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13624", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1744, 1754 ] ], "normalized": [] }, { "id": "13625", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1704, 1711 ] ], "normalized": [] }, { "id": "13627", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1806, 1810 ] ], "normalized": [] }, { "id": "13628", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13630", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1806, 1810 ] ], "normalized": [] }, { "id": "13631", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13633", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1806, 1810 ] ], "normalized": [] }, { "id": "13634", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1704, 1711 ] ], "normalized": [] }, { "id": "13636", "type": "", "text": [ "Gsalpha protein mutation" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "13637", "type": "", "text": [ "growth hormone-secreting pituitary adenoma" ], "offsets": [ [ 96, 138 ] ], "normalized": [] }, { "id": "13639", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13640", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 426, 456 ] ], "normalized": [] }, { "id": "13642", "type": "", "text": [ "Gsalpha" ], "offsets": [ [ 500, 507 ] ], "normalized": [] }, { "id": "13643", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13645", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13646", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13648", "type": "", "text": [ "gsp" ], "offsets": [ [ 517, 520 ] ], "normalized": [] }, { "id": "13649", "type": "", "text": [ "pituitary adenomas that secrete GH" ], "offsets": [ [ 582, 616 ] ], "normalized": [] }, { "id": "13651", "type": "", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13652", "type": "", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13654", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 647, 660 ] ], "normalized": [] }, { "id": "13655", "type": "", "text": [ "GH-secreting adenomas" ], "offsets": [ [ 691, 712 ] ], "normalized": [] }, { "id": "13657", "type": "", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13658", "type": "", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13660", "type": "", "text": [ "gsp mutation" ], "offsets": [ [ 850, 862 ] ], "normalized": [] }, { "id": "13661", "type": "", "text": [ "GH-secreting pituitary adenomas" ], "offsets": [ [ 804, 835 ] ], "normalized": [] }, { "id": "13663", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13664", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 967, 997 ] ], "normalized": [] }, { "id": "13666", "type": "", "text": [ "GH" ], "offsets": [ [ 1087, 1089 ] ], "normalized": [] }, { "id": "13667", "type": "", "text": [ "adenomas" ], "offsets": [ [ 1100, 1108 ] ], "normalized": [] }, { "id": "13669", "type": "", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1132, 1153 ] ], "normalized": [] }, { "id": "13670", "type": "", "text": [ "adenomas" ], "offsets": [ [ 1100, 1108 ] ], "normalized": [] }, { "id": "13672", "type": "", "text": [ "GH" ], "offsets": [ [ 1224, 1226 ] ], "normalized": [] }, { "id": "13673", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] }, { "id": "13675", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1275, 1296 ] ], "normalized": [] }, { "id": "13676", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] }, { "id": "13678", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "13679", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1534, 1541 ] ], "normalized": [] }, { "id": "13681", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13682", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13684", "type": "", "text": [ "GH-secreting pituitary adenoma" ], "offsets": [ [ 1627, 1657 ] ], "normalized": [] }, { "id": "13685", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1704, 1711 ] ], "normalized": [] }, { "id": "13687", "type": "", "text": [ "gsp mutations" ], "offsets": [ [ 1674, 1687 ] ], "normalized": [] }, { "id": "13688", "type": "", "text": [ "adenoma" ], "offsets": [ [ 1704, 1711 ] ], "normalized": [] }, { "id": "13690", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] }, { "id": "13691", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1065, 1086 ] ], "normalized": [] }, { "id": "13693", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "13694", "type": "", "text": [ "GH-secreting adenoma" ], "offsets": [ [ 1180, 1200 ] ], "normalized": [] }, { "id": "13696", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "13697", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1275, 1296 ] ], "normalized": [] }, { "id": "13699", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "13700", "type": "", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1437, 1458 ] ], "normalized": [] }, { "id": "13702", "type": "", "text": [ "GHRH" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "13703", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "13705", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "13706", "type": "", "text": [ "gsp mutation-negative" ], "offsets": [ [ 1437, 1458 ] ], "normalized": [] }, { "id": "13708", "type": "", "text": [ "GHRHR mRNA" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "13709", "type": "", "text": [ "gsp mutation-positive" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "13713", "type": "title", "text": [ "Characteristics of severe intraocular inflammation following intravitreal injection of bevacizumab (Avastin)." ], "offsets": [ [ 0, 109 ] ] }, { "id": "13714", "type": "abstract", "text": [ "BACKGROUND/AIMS: To report a series of severe intraocular inflammatory events following intravitreal injections of bevacizumab (Avastin). This procedure is performed on a rapidly increasing number worldwide, and rare complications such as intraocular inflammation, endophthalmitis or intraocular haemorrhage are gaining in importance in clinical routine. METHODS: This is a single-centre retrospective interventional case series of eight patients with severe intraocular inflammation after intravitreal injection of bevacizumab at one referral centre consecutively seen out of approximately a total of 2500 injections performed in that time period. Patients who developed severe intraocular inflammation after intravitreal injection were evaluated clinically, including slit-lamp examination, best-corrected Snellen visual acuity (VA), slit-lamp photography, optical coherence tomography and fluorescein angiography prior to the event and during follow-up. RESULTS: Patients noticed a painless drop in VA up to 2 days following the injection. All patients had a marked anterior chamber reaction with increased flare and cells, but no hypopyon. Typical posterior segment findings included vitreous cellular infiltrates of pseudogranulomatous aspect. Due to their initial clinical aspect suspicious of an endophthalmitis, three cases were treated with systemic antibiotics, but the final diagnosis was uveitis. Five cases showed a characteristic pseudogranulomatous vitreous infiltration as seen in vitritis and were treated only topically. CONCLUSIONS: Characteristic features of an inflammation induced by bevacizumab injection include an early onset with painless loss in VA mostly without conjunctival or ciliary injection. Patients respond to systemic or topical cortisone treatment with slow recovery but without permanent damage. Vitreous haemorrhage and infectious endophthalmitis might be differentiated by time course and symptoms." ], "offsets": [ [ 110, 2049 ] ] } ]

[ { "id": "13715", "type": "Diseases & Disorders", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 19, 50 ] ], "normalized": [] }, { "id": "13716", "type": "Chemicals & Drugs", "text": [ "bevacizumab" ], "offsets": [ [ 87, 98 ] ], "normalized": [] }, { "id": "13717", "type": "Chemicals & Drugs", "text": [ "Avastin" ], "offsets": [ [ 100, 107 ] ], "normalized": [] }, { "id": "13718", "type": "Diseases & Disorders", "text": [ "severe intraocular inflammatory events" ], "offsets": [ [ 149, 187 ] ], "normalized": [] }, { "id": "13719", "type": "Diseases & Disorders", "text": [ "intraocular inflammatory" ], "offsets": [ [ 156, 180 ] ], "normalized": [] }, { "id": "13720", "type": "Chemicals & Drugs", "text": [ "intravitreal injections of bevacizumab" ], "offsets": [ [ 198, 236 ] ], "normalized": [] }, { "id": "13721", "type": "Chemicals & Drugs", "text": [ "Avastin" ], "offsets": [ [ 238, 245 ] ], "normalized": [] }, { "id": "13722", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 327, 340 ] ], "normalized": [] }, { "id": "13723", "type": "Diseases & Disorders", "text": [ "intraocular inflammation" ], "offsets": [ [ 349, 373 ] ], "normalized": [] }, { "id": "13724", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 375, 390 ] ], "normalized": [] }, { "id": "13725", "type": "Diseases & Disorders", "text": [ "intraocular haemorrhage" ], "offsets": [ [ 394, 417 ] ], "normalized": [] }, { "id": "13726", "type": "Diseases & Disorders", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 562, 593 ] ], "normalized": [] }, { "id": "13727", "type": "Chemicals & Drugs", "text": [ "bevacizumab" ], "offsets": [ [ 626, 637 ] ], "normalized": [] }, { "id": "13728", "type": "Diseases & Disorders", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 782, 813 ] ], "normalized": [] }, { "id": "13729", "type": "Chemicals & Drugs", "text": [ "VA" ], "offsets": [ [ 941, 943 ] ], "normalized": [] }, { "id": "13730", "type": "Chemicals & Drugs", "text": [ "fluorescein" ], "offsets": [ [ 1002, 1013 ] ], "normalized": [] }, { "id": "13731", "type": "Chemicals & Drugs", "text": [ "VA" ], "offsets": [ [ 1112, 1114 ] ], "normalized": [] }, { "id": "13732", "type": "Diseases & Disorders", "text": [ "anterior" ], "offsets": [ [ 1179, 1187 ] ], "normalized": [] }, { "id": "13733", "type": "Diseases & Disorders", "text": [ "flare" ], "offsets": [ [ 1220, 1225 ] ], "normalized": [] }, { "id": "13734", "type": "Diseases & Disorders", "text": [ "hypopyon" ], "offsets": [ [ 1244, 1252 ] ], "normalized": [] }, { "id": "13735", "type": "Diseases & Disorders", "text": [ "posterior" ], "offsets": [ [ 1262, 1271 ] ], "normalized": [] }, { "id": "13736", "type": "Diseases & Disorders", "text": [ "cellular infiltrates" ], "offsets": [ [ 1307, 1327 ] ], "normalized": [] }, { "id": "13737", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 1413, 1428 ] ], "normalized": [] }, { "id": "13738", "type": "Chemicals & Drugs", "text": [ "systemic" ], "offsets": [ [ 1460, 1468 ] ], "normalized": [] }, { "id": "13739", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 1469, 1480 ] ], "normalized": [] }, { "id": "13740", "type": "Diseases & Disorders", "text": [ "uveitis" ], "offsets": [ [ 1510, 1517 ] ], "normalized": [] }, { "id": "13741", "type": "Diseases & Disorders", "text": [ "pseudogranulomatous vitreous infiltration" ], "offsets": [ [ 1554, 1595 ] ], "normalized": [] }, { "id": "13742", "type": "Diseases & Disorders", "text": [ "vitritis" ], "offsets": [ [ 1607, 1615 ] ], "normalized": [] }, { "id": "13743", "type": "Diseases & Disorders", "text": [ "inflammation" ], "offsets": [ [ 1692, 1704 ] ], "normalized": [] }, { "id": "13744", "type": "Chemicals & Drugs", "text": [ "bevacizumab" ], "offsets": [ [ 1716, 1727 ] ], "normalized": [] }, { "id": "13745", "type": "Chemicals & Drugs", "text": [ "VA" ], "offsets": [ [ 1783, 1785 ] ], "normalized": [] }, { "id": "13746", "type": "Diseases & Disorders", "text": [ "ciliary injection" ], "offsets": [ [ 1817, 1834 ] ], "normalized": [] }, { "id": "13747", "type": "Chemicals & Drugs", "text": [ "systemic" ], "offsets": [ [ 1856, 1864 ] ], "normalized": [] }, { "id": "13748", "type": "Chemicals & Drugs", "text": [ "topical cortisone" ], "offsets": [ [ 1868, 1885 ] ], "normalized": [] }, { "id": "13749", "type": "Diseases & Disorders", "text": [ "Vitreous haemorrhage" ], "offsets": [ [ 1945, 1965 ] ], "normalized": [] }, { "id": "13750", "type": "Diseases & Disorders", "text": [ "infectious endophthalmitis" ], "offsets": [ [ 1970, 1996 ] ], "normalized": [] }, { "id": "13751", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 2040, 2048 ] ], "normalized": [] }, { "id": "13752", "type": "", "text": [ "systemic" ], "offsets": [ [ 1460, 1468 ] ], "normalized": [] }, { "id": "13753", "type": "", "text": [ "uveitis" ], "offsets": [ [ 1510, 1517 ] ], "normalized": [] }, { "id": "13755", "type": "", "text": [ "systemic" ], "offsets": [ [ 1460, 1468 ] ], "normalized": [] }, { "id": "13756", "type": "", "text": [ "endophthalmitis" ], "offsets": [ [ 1413, 1428 ] ], "normalized": [] }, { "id": "13758", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 1716, 1727 ] ], "normalized": [] }, { "id": "13759", "type": "", "text": [ "inflammation" ], "offsets": [ [ 1692, 1704 ] ], "normalized": [] }, { "id": "13761", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 87, 98 ] ], "normalized": [] }, { "id": "13762", "type": "", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 19, 50 ] ], "normalized": [] }, { "id": "13764", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 626, 637 ] ], "normalized": [] }, { "id": "13765", "type": "", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 562, 593 ] ], "normalized": [] }, { "id": "13767", "type": "", "text": [ "VA" ], "offsets": [ [ 941, 943 ] ], "normalized": [] }, { "id": "13768", "type": "", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 782, 813 ] ], "normalized": [] }, { "id": "13770", "type": "", "text": [ "fluorescein" ], "offsets": [ [ 1002, 1013 ] ], "normalized": [] }, { "id": "13771", "type": "", "text": [ "severe intraocular inflammation" ], "offsets": [ [ 782, 813 ] ], "normalized": [] }, { "id": "13773", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 1716, 1727 ] ], "normalized": [] }, { "id": "13774", "type": "", "text": [ "ciliary injection" ], "offsets": [ [ 1817, 1834 ] ], "normalized": [] }, { "id": "13776", "type": "", "text": [ "VA" ], "offsets": [ [ 1783, 1785 ] ], "normalized": [] }, { "id": "13777", "type": "", "text": [ "inflammation" ], "offsets": [ [ 1692, 1704 ] ], "normalized": [] }, { "id": "13779", "type": "", "text": [ "VA" ], "offsets": [ [ 1783, 1785 ] ], "normalized": [] }, { "id": "13780", "type": "", "text": [ "ciliary injection" ], "offsets": [ [ 1817, 1834 ] ], "normalized": [] }, { "id": "13782", "type": "", "text": [ "Avastin" ], "offsets": [ [ 238, 245 ] ], "normalized": [] }, { "id": "13783", "type": "", "text": [ "severe intraocular inflammatory events" ], "offsets": [ [ 149, 187 ] ], "normalized": [] }, { "id": "13785", "type": "", "text": [ "antibiotics" ], "offsets": [ [ 1469, 1480 ] ], "normalized": [] }, { "id": "13786", "type": "", "text": [ "uveitis" ], "offsets": [ [ 1510, 1517 ] ], "normalized": [] }, { "id": "13788", "type": "", "text": [ "antibiotics" ], "offsets": [ [ 1469, 1480 ] ], "normalized": [] }, { "id": "13789", "type": "", "text": [ "endophthalmitis" ], "offsets": [ [ 1413, 1428 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13754", "type": "PA", "arg1_id": "13752", "arg2_id": "13753", "normalized": [] }, { "id": "13757", "type": "PA", "arg1_id": "13755", "arg2_id": "13756", "normalized": [] }, { "id": "13760", "type": "PA", "arg1_id": "13758", "arg2_id": "13759", "normalized": [] }, { "id": "13763", "type": "PA", "arg1_id": "13761", "arg2_id": "13762", "normalized": [] }, { "id": "13766", "type": "PA", "arg1_id": "13764", "arg2_id": "13765", "normalized": [] }, { "id": "13769", "type": "PA", "arg1_id": "13767", "arg2_id": "13768", "normalized": [] }, { "id": "13772", "type": "PA", "arg1_id": "13770", "arg2_id": "13771", "normalized": [] }, { "id": "13775", "type": "PA", "arg1_id": "13773", "arg2_id": "13774", "normalized": [] }, { "id": "13778", "type": "PA", "arg1_id": "13776", "arg2_id": "13777", "normalized": [] }, { "id": "13781", "type": "PA", "arg1_id": "13779", "arg2_id": "13780", "normalized": [] }, { "id": "13784", "type": "PA", "arg1_id": "13782", "arg2_id": "13783", "normalized": [] }, { "id": "13787", "type": "SA", "arg1_id": "13785", "arg2_id": "13786", "normalized": [] }, { "id": "13790", "type": "SA", "arg1_id": "13788", "arg2_id": "13789", "normalized": [] } ]

[ { "id": "13793", "type": "title", "text": [ "Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population." ], "offsets": [ [ 0, 93 ] ] }, { "id": "13794", "type": "abstract", "text": [ "OBJECT: The COL1A2 gene at 7q22.1 has been shown to be associated with familial intracranial aneurysms (IAs) in the Japanese population. In the present study, the authors investigated the correlation between the presence of the rs42524 polymorphism in COL1A2 and the occurrence of sporadic IAs in Chinese patients. METHODS: The polymorphism rs42524 of the COL1A2 gene was identified by polymerase chain reaction-based restriction analysis in genomic DNA from 226 patients with sporadic IAs (mean age 51.49 +/- 11.47 years) and 326 control participants (mean age 52.33 +/- 10.50 years). Neurological assessments were performed using the Hunt and Hess grading system, and differences in allelic and genotypic frequencies between the patient and control groups were evaluated with the chi-square test. RESULTS: There was a significant difference in either the genotype distribution (chi(2) = 11.99, p = 0.002) or allelic frequencies (chi(2) = 11.96, p = 0.001, odds ratio 2.579, 95% confidence interval 1.486-4.476) between patients with IAs and patients in the control group. CONCLUSIONS: The rs42524 polymorphism of COL1A2 could be a genetic risk factor for sporadic IAs among individuals of Chinese Han ethnicity. This study is the first to confirm the association between COL1A2 and IAs." ], "offsets": [ [ 94, 1382 ] ] } ]

[ { "id": "13795", "type": "SNP & Sequence variations", "text": [ "rs42524" ], "offsets": [ [ 13, 20 ] ], "normalized": [] }, { "id": "13796", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 24, 30 ] ], "normalized": [] }, { "id": "13797", "type": "Diseases & Disorders", "text": [ "sporadic intracranial aneurysms" ], "offsets": [ [ 35, 66 ] ], "normalized": [] }, { "id": "13798", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 106, 112 ] ], "normalized": [] }, { "id": "13799", "type": "Diseases & Disorders", "text": [ "intracranial aneurysms" ], "offsets": [ [ 174, 196 ] ], "normalized": [] }, { "id": "13800", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 198, 201 ] ], "normalized": [] }, { "id": "13801", "type": "SNP & Sequence variations", "text": [ "rs42524" ], "offsets": [ [ 322, 329 ] ], "normalized": [] }, { "id": "13802", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 346, 352 ] ], "normalized": [] }, { "id": "13803", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 384, 387 ] ], "normalized": [] }, { "id": "13804", "type": "SNP & Sequence variations", "text": [ "rs42524" ], "offsets": [ [ 435, 442 ] ], "normalized": [] }, { "id": "13805", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 450, 456 ] ], "normalized": [] }, { "id": "13806", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 580, 583 ] ], "normalized": [] }, { "id": "13807", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "13808", "type": "SNP & Sequence variations", "text": [ "rs42524" ], "offsets": [ [ 1185, 1192 ] ], "normalized": [] }, { "id": "13809", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 1209, 1215 ] ], "normalized": [] }, { "id": "13810", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "13811", "type": "Genes & Molecular Sequences", "text": [ "COL1A2" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "13812", "type": "Diseases & Disorders", "text": [ "IAs" ], "offsets": [ [ 1378, 1381 ] ], "normalized": [] }, { "id": "13813", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 106, 112 ] ], "normalized": [] }, { "id": "13814", "type": "", "text": [ "intracranial aneurysms" ], "offsets": [ [ 174, 196 ] ], "normalized": [] }, { "id": "13816", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 106, 112 ] ], "normalized": [] }, { "id": "13817", "type": "", "text": [ "IAs" ], "offsets": [ [ 198, 201 ] ], "normalized": [] }, { "id": "13819", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 346, 352 ] ], "normalized": [] }, { "id": "13820", "type": "", "text": [ "IAs" ], "offsets": [ [ 384, 387 ] ], "normalized": [] }, { "id": "13822", "type": "", "text": [ "rs42524" ], "offsets": [ [ 1185, 1192 ] ], "normalized": [] }, { "id": "13823", "type": "", "text": [ "IAs" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "13825", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "13826", "type": "", "text": [ "IAs" ], "offsets": [ [ 1378, 1381 ] ], "normalized": [] }, { "id": "13828", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 24, 30 ] ], "normalized": [] }, { "id": "13829", "type": "", "text": [ "sporadic intracranial aneurysms" ], "offsets": [ [ 35, 66 ] ], "normalized": [] }, { "id": "13831", "type": "", "text": [ "rs42524" ], "offsets": [ [ 13, 20 ] ], "normalized": [] }, { "id": "13832", "type": "", "text": [ "sporadic intracranial aneurysms" ], "offsets": [ [ 35, 66 ] ], "normalized": [] }, { "id": "13834", "type": "", "text": [ "rs42524" ], "offsets": [ [ 322, 329 ] ], "normalized": [] }, { "id": "13835", "type": "", "text": [ "IAs" ], "offsets": [ [ 384, 387 ] ], "normalized": [] }, { "id": "13837", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 450, 456 ] ], "normalized": [] }, { "id": "13838", "type": "", "text": [ "IAs" ], "offsets": [ [ 580, 583 ] ], "normalized": [] }, { "id": "13840", "type": "", "text": [ "rs42524" ], "offsets": [ [ 435, 442 ] ], "normalized": [] }, { "id": "13841", "type": "", "text": [ "IAs" ], "offsets": [ [ 580, 583 ] ], "normalized": [] }, { "id": "13843", "type": "", "text": [ "COL1A2" ], "offsets": [ [ 1209, 1215 ] ], "normalized": [] }, { "id": "13844", "type": "", "text": [ "IAs" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13815", "type": "PA", "arg1_id": "13813", "arg2_id": "13814", "normalized": [] }, { "id": "13818", "type": "PA", "arg1_id": "13816", "arg2_id": "13817", "normalized": [] }, { "id": "13821", "type": "PA", "arg1_id": "13819", "arg2_id": "13820", "normalized": [] }, { "id": "13824", "type": "SA", "arg1_id": "13822", "arg2_id": "13823", "normalized": [] }, { "id": "13827", "type": "PA", "arg1_id": "13825", "arg2_id": "13826", "normalized": [] }, { "id": "13830", "type": "PA", "arg1_id": "13828", "arg2_id": "13829", "normalized": [] }, { "id": "13833", "type": "SA", "arg1_id": "13831", "arg2_id": "13832", "normalized": [] }, { "id": "13836", "type": "SA", "arg1_id": "13834", "arg2_id": "13835", "normalized": [] }, { "id": "13839", "type": "PA", "arg1_id": "13837", "arg2_id": "13838", "normalized": [] }, { "id": "13842", "type": "PA", "arg1_id": "13840", "arg2_id": "13841", "normalized": [] }, { "id": "13845", "type": "PA", "arg1_id": "13843", "arg2_id": "13844", "normalized": [] } ]

[ { "id": "13848", "type": "title", "text": [ "A review of tigecycline." ], "offsets": [ [ 0, 24 ] ] }, { "id": "13849", "type": "abstract", "text": [ "The first article in this supplement is an overall review of the first glycylcycline, tigecycline, which includes a brief overview of the problem of tetracycline resistance as well as tigecycline's mode of action, antibacterial activity, pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability. The remaining articles in the supplement report the European clinical experience from the pivotal clinical trials in complicated intra-abdominal infections, complicated skin and skin structure infections and community acquired pneumonia." ], "offsets": [ [ 25, 580 ] ] } ]

[ { "id": "13850", "type": "Chemicals & Drugs", "text": [ "tigecycline" ], "offsets": [ [ 12, 23 ] ], "normalized": [] }, { "id": "13851", "type": "Chemicals & Drugs", "text": [ "glycylcycline" ], "offsets": [ [ 96, 109 ] ], "normalized": [] }, { "id": "13852", "type": "Chemicals & Drugs", "text": [ "tigecycline" ], "offsets": [ [ 111, 122 ] ], "normalized": [] }, { "id": "13853", "type": "Chemicals & Drugs", "text": [ "tetracycline" ], "offsets": [ [ 174, 186 ] ], "normalized": [] }, { "id": "13854", "type": "Chemicals & Drugs", "text": [ "tigecycline" ], "offsets": [ [ 209, 220 ] ], "normalized": [] }, { "id": "13855", "type": "Diseases & Disorders", "text": [ "complicated intra-abdominal infections" ], "offsets": [ [ 460, 498 ] ], "normalized": [] }, { "id": "13856", "type": "Diseases & Disorders", "text": [ "complicated skin" ], "offsets": [ [ 500, 516 ] ], "normalized": [] }, { "id": "13857", "type": "Diseases & Disorders", "text": [ "skin structure infections" ], "offsets": [ [ 521, 546 ] ], "normalized": [] }, { "id": "13858", "type": "Diseases & Disorders", "text": [ "community acquired pneumonia" ], "offsets": [ [ 551, 579 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "13861", "type": "title", "text": [ "Estrogen-dependent downregulation of hairy and enhancer of split homolog-1 gene expression in breast cancer cells is mediated via a 3' distal element." ], "offsets": [ [ 0, 150 ] ] }, { "id": "13862", "type": "abstract", "text": [ "Regulation of hairy and enhancer of split homologue-1 (HES-1) by estradiol and all-trans retinoic acid affects proliferation of human breast cancer cells. Here, we identify and characterize cis-regulatory elements involved in HES-1 regulation. In the distal 5' promoter of the HES-1 gene, we found a retinoic acid response element and in the distal 3' region, an estrogen receptor alpha(ER)alpha binding site. The ERalpha binding site, composed of an estrogen response element (ERE) and an ERE half-site, is important for both ERalpha binding and transcriptional regulation. Chromatin immunoprecipitation assays revealed that ERalpha is recruited to the ERE and associates with the HES-1 promoter. We also show recruitment of nuclear receptor co-regulators to the ERE in response to estradiol, followed by a decrease in histone acetylation and RNA polymerase II docking in the HES-1 promoter region. Our findings are consistent with a novel type of repressive estrogen response element in the distal 3' region of the HES-1 gene." ], "offsets": [ [ 151, 1179 ] ] } ]

[ { "id": "13863", "type": "Genes & Molecular Sequences", "text": [ "hairy and enhancer of split homolog-1" ], "offsets": [ [ 37, 74 ] ], "normalized": [] }, { "id": "13864", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "13865", "type": "Genes & Molecular Sequences", "text": [ "hairy and enhancer of split homologue-1" ], "offsets": [ [ 165, 204 ] ], "normalized": [] }, { "id": "13866", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 206, 211 ] ], "normalized": [] }, { "id": "13867", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 216, 225 ] ], "normalized": [] }, { "id": "13868", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 285, 298 ] ], "normalized": [] }, { "id": "13869", "type": "Genes & Molecular Sequences", "text": [ "cis-regulatory elements" ], "offsets": [ [ 341, 364 ] ], "normalized": [] }, { "id": "13870", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 377, 382 ] ], "normalized": [] }, { "id": "13871", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 428, 433 ] ], "normalized": [] }, { "id": "13872", "type": "Genes & Molecular Sequences", "text": [ "retinoic acid" ], "offsets": [ [ 451, 464 ] ], "normalized": [] }, { "id": "13873", "type": "Genes & Molecular Sequences", "text": [ "estrogen receptor alpha" ], "offsets": [ [ 514, 537 ] ], "normalized": [] }, { "id": "13874", "type": "Genes & Molecular Sequences", "text": [ "ER)alpha" ], "offsets": [ [ 538, 546 ] ], "normalized": [] }, { "id": "13875", "type": "Genes & Molecular Sequences", "text": [ "ERalpha" ], "offsets": [ [ 565, 572 ] ], "normalized": [] }, { "id": "13876", "type": "Genes & Molecular Sequences", "text": [ "estrogen response element" ], "offsets": [ [ 602, 627 ] ], "normalized": [] }, { "id": "13877", "type": "Genes & Molecular Sequences", "text": [ "ERE" ], "offsets": [ [ 629, 632 ] ], "normalized": [] }, { "id": "13878", "type": "Genes & Molecular Sequences", "text": [ "ERE" ], "offsets": [ [ 641, 644 ] ], "normalized": [] }, { "id": "13879", "type": "Genes & Molecular Sequences", "text": [ "ERalpha" ], "offsets": [ [ 678, 685 ] ], "normalized": [] }, { "id": "13880", "type": "Genes & Molecular Sequences", "text": [ "Chromatin" ], "offsets": [ [ 726, 735 ] ], "normalized": [] }, { "id": "13881", "type": "Genes & Molecular Sequences", "text": [ "ERalpha" ], "offsets": [ [ 777, 784 ] ], "normalized": [] }, { "id": "13882", "type": "Genes & Molecular Sequences", "text": [ "ERE" ], "offsets": [ [ 805, 808 ] ], "normalized": [] }, { "id": "13883", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 833, 838 ] ], "normalized": [] }, { "id": "13884", "type": "Diseases & Disorders", "text": [ "recruitment" ], "offsets": [ [ 862, 873 ] ], "normalized": [] }, { "id": "13885", "type": "Genes & Molecular Sequences", "text": [ "ERE" ], "offsets": [ [ 915, 918 ] ], "normalized": [] }, { "id": "13886", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 934, 943 ] ], "normalized": [] }, { "id": "13887", "type": "Genes & Molecular Sequences", "text": [ "histone" ], "offsets": [ [ 971, 978 ] ], "normalized": [] }, { "id": "13888", "type": "Genes & Molecular Sequences", "text": [ "RNA polymerase II" ], "offsets": [ [ 995, 1012 ] ], "normalized": [] }, { "id": "13889", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "13890", "type": "Genes & Molecular Sequences", "text": [ "estrogen response element" ], "offsets": [ [ 1111, 1136 ] ], "normalized": [] }, { "id": "13891", "type": "Diseases & Disorders", "text": [ "estrogen response element" ], "offsets": [ [ 1111, 1136 ] ], "normalized": [] }, { "id": "13892", "type": "Genes & Molecular Sequences", "text": [ "HES-1" ], "offsets": [ [ 1168, 1173 ] ], "normalized": [] }, { "id": "13893", "type": "", "text": [ "HES-1" ], "offsets": [ [ 206, 211 ] ], "normalized": [] }, { "id": "13894", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 285, 298 ] ], "normalized": [] }, { "id": "13896", "type": "", "text": [ "HES-1" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "13897", "type": "", "text": [ "recruitment" ], "offsets": [ [ 862, 873 ] ], "normalized": [] }, { "id": "13899", "type": "", "text": [ "hairy and enhancer of split homolog-1" ], "offsets": [ [ 37, 74 ] ], "normalized": [] }, { "id": "13900", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "13902", "type": "", "text": [ "hairy and enhancer of split homologue-1" ], "offsets": [ [ 165, 204 ] ], "normalized": [] }, { "id": "13903", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 285, 298 ] ], "normalized": [] }, { "id": "13905", "type": "", "text": [ "HES-1" ], "offsets": [ [ 1168, 1173 ] ], "normalized": [] }, { "id": "13906", "type": "", "text": [ "estrogen response element" ], "offsets": [ [ 1111, 1136 ] ], "normalized": [] } ]

[]

[]

[ { "id": "13895", "type": "PA", "arg1_id": "13893", "arg2_id": "13894", "normalized": [] }, { "id": "13898", "type": "PA", "arg1_id": "13896", "arg2_id": "13897", "normalized": [] }, { "id": "13901", "type": "PA", "arg1_id": "13899", "arg2_id": "13900", "normalized": [] }, { "id": "13904", "type": "PA", "arg1_id": "13902", "arg2_id": "13903", "normalized": [] }, { "id": "13907", "type": "PA", "arg1_id": "13905", "arg2_id": "13906", "normalized": [] } ]

[ { "id": "13910", "type": "title", "text": [ "Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression." ], "offsets": [ [ 0, 95 ] ] }, { "id": "13911", "type": "abstract", "text": [ "Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl-positive acute lymphoblastic leukemia. Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of Bcr-Abl tyrosine kinase such as nilotinib or dasatinib have been developed for the treatment of imatinib-resistant or imatinib-intolerant disease. In the current study, we generated nilotinib-resistant cell lines and investigated their mechanism of resistance. Overexpression of BCR-ABL and multidrug resistance gene (MDR-1) were found among the investigated mechanisms. We showed that nilotinib is a substrate of the multidrug resistance gene product, P-glycoprotein, using verapamil or PSC833 to block binding. Up-regulated expression of p53/56 Lyn kinase, both at the mRNA and protein level, was found in one of the resistant cell lines and Lyn silencing by small interfering RNA restored sensitivity to nilotinib. Moreover, failure of nilotinib treatment was accompanied by an increase of Lyn mRNA expression in patients with resistant CML. Two Src kinase inhibitors (PP1 and PP2) partially removed resistance but did not significantly inhibit Bcr-Abl tyrosine kinase activity. In contrast, dasatinib, a dual Bcr-Abl and Src kinase inhibitor, inhibited the phosphorylation of both BCR-ABL and Lyn, and induced apoptosis of the Bcr-Abl cell line overexpressing p53/56 Lyn. Such mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance." ], "offsets": [ [ 96, 1744 ] ] } ]

[ { "id": "13912", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "13913", "type": "Genes & Molecular Sequences", "text": [ "BCR-ABL" ], "offsets": [ [ 52, 59 ] ], "normalized": [] }, { "id": "13914", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 61, 64 ] ], "normalized": [] }, { "id": "13915", "type": "Genes & Molecular Sequences", "text": [ "Src kinase" ], "offsets": [ [ 69, 79 ] ], "normalized": [] }, { "id": "13916", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "13917", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 213, 216 ] ], "normalized": [] }, { "id": "13918", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 225, 232 ] ], "normalized": [] }, { "id": "13919", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 280, 288 ] ], "normalized": [] }, { "id": "13920", "type": "Chemicals & Drugs", "text": [ "selective inhibitor of Bcr-Abl" ], "offsets": [ [ 292, 322 ] ], "normalized": [] }, { "id": "13921", "type": "Genes & Molecular Sequences", "text": [ "selective inhibitor of Bcr-Abl" ], "offsets": [ [ 292, 322 ] ], "normalized": [] }, { "id": "13922", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "13923", "type": "Chemicals & Drugs", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "13924", "type": "Genes & Molecular Sequences", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "13925", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "13926", "type": "Chemicals & Drugs", "text": [ "dasatinib" ], "offsets": [ [ 459, 468 ] ], "normalized": [] }, { "id": "13927", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 510, 518 ] ], "normalized": [] }, { "id": "13928", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 532, 540 ] ], "normalized": [] }, { "id": "13929", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 596, 605 ] ], "normalized": [] }, { "id": "13930", "type": "Genes & Molecular Sequences", "text": [ "BCR-ABL" ], "offsets": [ [ 693, 700 ] ], "normalized": [] }, { "id": "13931", "type": "Genes & Molecular Sequences", "text": [ "multidrug resistance gene" ], "offsets": [ [ 705, 730 ] ], "normalized": [] }, { "id": "13932", "type": "Genes & Molecular Sequences", "text": [ "MDR-1" ], "offsets": [ [ 732, 737 ] ], "normalized": [] }, { "id": "13933", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 800, 809 ] ], "normalized": [] }, { "id": "13934", "type": "Genes & Molecular Sequences", "text": [ "multidrug resistance gene" ], "offsets": [ [ 832, 857 ] ], "normalized": [] }, { "id": "13935", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 867, 881 ] ], "normalized": [] }, { "id": "13936", "type": "Chemicals & Drugs", "text": [ "verapamil" ], "offsets": [ [ 889, 898 ] ], "normalized": [] }, { "id": "13937", "type": "Chemicals & Drugs", "text": [ "PSC833" ], "offsets": [ [ 902, 908 ] ], "normalized": [] }, { "id": "13938", "type": "Genes & Molecular Sequences", "text": [ "p53/56 Lyn" ], "offsets": [ [ 954, 964 ] ], "normalized": [] }, { "id": "13939", "type": "Genes & Molecular Sequences", "text": [ "Lyn" ], "offsets": [ [ 1058, 1061 ] ], "normalized": [] }, { "id": "13940", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "13941", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [] }, { "id": "13942", "type": "Genes & Molecular Sequences", "text": [ "Lyn mRNA" ], "offsets": [ [ 1207, 1215 ] ], "normalized": [] }, { "id": "13943", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "13944", "type": "Chemicals & Drugs", "text": [ "Src kinase inhibitors" ], "offsets": [ [ 1263, 1284 ] ], "normalized": [] }, { "id": "13945", "type": "Genes & Molecular Sequences", "text": [ "Src kinase inhibitors" ], "offsets": [ [ 1263, 1284 ] ], "normalized": [] }, { "id": "13946", "type": "Chemicals & Drugs", "text": [ "PP1" ], "offsets": [ [ 1286, 1289 ] ], "normalized": [] }, { "id": "13947", "type": "Genes & Molecular Sequences", "text": [ "PP1" ], "offsets": [ [ 1286, 1289 ] ], "normalized": [] }, { "id": "13948", "type": "Chemicals & Drugs", "text": [ "PP2" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "13949", "type": "Genes & Molecular Sequences", "text": [ "PP2" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "13950", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "13951", "type": "Chemicals & Drugs", "text": [ "dasatinib" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "13952", "type": "Chemicals & Drugs", "text": [ "dual Bcr-Abl and Src kinase inhibitor" ], "offsets": [ [ 1422, 1459 ] ], "normalized": [] }, { "id": "13953", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 1427, 1434 ] ], "normalized": [] }, { "id": "13954", "type": "Genes & Molecular Sequences", "text": [ "Src" ], "offsets": [ [ 1439, 1442 ] ], "normalized": [] }, { "id": "13955", "type": "Genes & Molecular Sequences", "text": [ "BCR-ABL" ], "offsets": [ [ 1499, 1506 ] ], "normalized": [] }, { "id": "13956", "type": "Genes & Molecular Sequences", "text": [ "Lyn" ], "offsets": [ [ 1511, 1514 ] ], "normalized": [] }, { "id": "13957", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 1545, 1552 ] ], "normalized": [] }, { "id": "13958", "type": "Genes & Molecular Sequences", "text": [ "p53/56 Lyn" ], "offsets": [ [ 1578, 1588 ] ], "normalized": [] }, { "id": "13959", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 1651, 1659 ] ], "normalized": [] }, { "id": "13960", "type": "Genes & Molecular Sequences", "text": [ "Lyn" ], "offsets": [ [ 1716, 1719 ] ], "normalized": [] }, { "id": "13961", "type": "Chemicals & Drugs", "text": [ "nilotinib" ], "offsets": [ [ 1723, 1732 ] ], "normalized": [] }, { "id": "13962", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "13963", "type": "", "text": [ "Pgp" ], "offsets": [ [ 61, 64 ] ], "normalized": [] }, { "id": "13965", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "13966", "type": "", "text": [ "BCR-ABL" ], "offsets": [ [ 52, 59 ] ], "normalized": [] }, { "id": "13968", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "13969", "type": "", "text": [ "Src kinase" ], "offsets": [ [ 69, 79 ] ], "normalized": [] }, { "id": "13971", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 800, 809 ] ], "normalized": [] }, { "id": "13972", "type": "", "text": [ "P-glycoprotein" ], "offsets": [ [ 867, 881 ] ], "normalized": [] }, { "id": "13974", "type": "", "text": [ "verapamil" ], "offsets": [ [ 889, 898 ] ], "normalized": [] }, { "id": "13975", "type": "", "text": [ "P-glycoprotein" ], "offsets": [ [ 867, 881 ] ], "normalized": [] }, { "id": "13977", "type": "", "text": [ "PSC833" ], "offsets": [ [ 902, 908 ] ], "normalized": [] }, { "id": "13978", "type": "", "text": [ "P-glycoprotein" ], "offsets": [ [ 867, 881 ] ], "normalized": [] }, { "id": "13980", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "13981", "type": "", "text": [ "Lyn" ], "offsets": [ [ 1058, 1061 ] ], "normalized": [] }, { "id": "13983", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [] }, { "id": "13984", "type": "", "text": [ "Lyn mRNA" ], "offsets": [ [ 1207, 1215 ] ], "normalized": [] }, { "id": "13986", "type": "", "text": [ "PP1" ], "offsets": [ [ 1286, 1289 ] ], "normalized": [] }, { "id": "13987", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "13989", "type": "", "text": [ "PP2" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "13990", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "13992", "type": "", "text": [ "Src kinase inhibitors" ], "offsets": [ [ 1263, 1284 ] ], "normalized": [] }, { "id": "13993", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "13995", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "13996", "type": "", "text": [ "Lyn" ], "offsets": [ [ 1511, 1514 ] ], "normalized": [] }, { "id": "13998", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "13999", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1545, 1552 ] ], "normalized": [] }, { "id": "14001", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "14002", "type": "", "text": [ "p53/56 Lyn" ], "offsets": [ [ 1578, 1588 ] ], "normalized": [] }, { "id": "14004", "type": "", "text": [ "dual Bcr-Abl and Src kinase inhibitor" ], "offsets": [ [ 1422, 1459 ] ], "normalized": [] }, { "id": "14005", "type": "", "text": [ "Lyn" ], "offsets": [ [ 1511, 1514 ] ], "normalized": [] }, { "id": "14007", "type": "", "text": [ "dual Bcr-Abl and Src kinase inhibitor" ], "offsets": [ [ 1422, 1459 ] ], "normalized": [] }, { "id": "14008", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1545, 1552 ] ], "normalized": [] }, { "id": "14010", "type": "", "text": [ "dual Bcr-Abl and Src kinase inhibitor" ], "offsets": [ [ 1422, 1459 ] ], "normalized": [] }, { "id": "14011", "type": "", "text": [ "p53/56 Lyn" ], "offsets": [ [ 1578, 1588 ] ], "normalized": [] }, { "id": "14013", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 1723, 1732 ] ], "normalized": [] }, { "id": "14014", "type": "", "text": [ "Lyn" ], "offsets": [ [ 1716, 1719 ] ], "normalized": [] }, { "id": "14016", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "14017", "type": "", "text": [ "CML" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "14019", "type": "", "text": [ "imatinib" ], "offsets": [ [ 510, 518 ] ], "normalized": [] }, { "id": "14020", "type": "", "text": [ "CML" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "14022", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 459, 468 ] ], "normalized": [] }, { "id": "14023", "type": "", "text": [ "CML" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "14025", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "14026", "type": "", "text": [ "p53/56 Lyn" ], "offsets": [ [ 954, 964 ] ], "normalized": [] }, { "id": "14028", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [] }, { "id": "14029", "type": "", "text": [ "CML" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "14031", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "14032", "type": "", "text": [ "Src" ], "offsets": [ [ 1439, 1442 ] ], "normalized": [] }, { "id": "14034", "type": "", "text": [ "imatinib" ], "offsets": [ [ 1651, 1659 ] ], "normalized": [] }, { "id": "14035", "type": "", "text": [ "Lyn" ], "offsets": [ [ 1716, 1719 ] ], "normalized": [] }, { "id": "14037", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "14038", "type": "", "text": [ "chronic myeloid leukemia" ], "offsets": [ [ 187, 211 ] ], "normalized": [] }, { "id": "14040", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "14041", "type": "", "text": [ "CML" ], "offsets": [ [ 213, 216 ] ], "normalized": [] }, { "id": "14043", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "14044", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 225, 232 ] ], "normalized": [] }, { "id": "14046", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "14047", "type": "", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "14049", "type": "", "text": [ "imatinib" ], "offsets": [ [ 532, 540 ] ], "normalized": [] }, { "id": "14050", "type": "", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "14052", "type": "", "text": [ "dasatinib" ], "offsets": [ [ 459, 468 ] ], "normalized": [] }, { "id": "14053", "type": "", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "14055", "type": "", "text": [ "second-generation inhibitors of Bcr-Abl" ], "offsets": [ [ 382, 421 ] ], "normalized": [] }, { "id": "14056", "type": "", "text": [ "CML" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "14058", "type": "", "text": [ "nilotinib" ], "offsets": [ [ 800, 809 ] ], "normalized": [] }, { "id": "14059", "type": "", "text": [ "multidrug resistance gene" ], "offsets": [ [ 832, 857 ] ], "normalized": [] }, { "id": "14061", "type": "", "text": [ "verapamil" ], "offsets": [ [ 889, 898 ] ], "normalized": [] }, { "id": "14062", "type": "", "text": [ "multidrug resistance gene" ], "offsets": [ [ 832, 857 ] ], "normalized": [] }, { "id": "14064", "type": "", "text": [ "PSC833" ], "offsets": [ [ 902, 908 ] ], "normalized": [] }, { "id": "14065", "type": "", "text": [ "multidrug resistance gene" ], "offsets": [ [ 832, 857 ] ], "normalized": [] }, { "id": "14067", "type": "", "text": [ "Lyn mRNA" ], "offsets": [ [ 1207, 1215 ] ], "normalized": [] }, { "id": "14068", "type": "", "text": [ "CML" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "14070", "type": "", "text": [ "Src kinase inhibitors" ], "offsets": [ [ 1263, 1284 ] ], "normalized": [] }, { "id": "14071", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "14073", "type": "", "text": [ "PP1" ], "offsets": [ [ 1286, 1289 ] ], "normalized": [] }, { "id": "14074", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] }, { "id": "14076", "type": "", "text": [ "PP2" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "14077", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1362, 1369 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "14081", "type": "title", "text": [ "Immunosuppression for liver transplantation." ], "offsets": [ [ 0, 44 ] ] }, { "id": "14082", "type": "abstract", "text": [ "In the last few decades liver transplantation (LTx) has become a reliable life-saving procedure for patients with chronic end-stage liver diseases. LTx has an outstanding success rate in the first few years after allografting, especially considering that many patients are on the brink of survival at the time of transplantation. The success of LTx is owed to the pioneers who developed the surgical procedures and to researchers who discovered the medications to help prevent immunological rejection of allografts. However, several problems continue to impose serious limits on LTx today, including a shortage of donor livers, recurrence of disease (eg, hepatitis, hepatocellular cancer), preservation of long-term allograft function and the side effects of anti-rejection drugs. While the dilemma of organ shortage is not a focus of this review, we will address the latter issues as they relate to the \"oldest\" and \"newest\" approaches to immunosuppression, and discuss the prospect that recipients could potentially be made immunologically tolerant to liver transplants. Due to the critical shortage of organs, new strategies to preserve transplanted liver allografts for the longest possible time are of paramount importance." ], "offsets": [ [ 45, 1273 ] ] } ]

[ { "id": "14083", "type": "Chemicals & Drugs", "text": [ "anti-rejection drugs" ], "offsets": [ [ 804, 824 ] ], "normalized": [] }, { "id": "14084", "type": "", "text": [ "anti-rejection drugs" ], "offsets": [ [ 804, 824 ] ], "normalized": [] }, { "id": "14085", "type": "", "text": [ "hepatitis" ], "offsets": [ [ 700, 709 ] ], "normalized": [] }, { "id": "14087", "type": "", "text": [ "anti-rejection drugs" ], "offsets": [ [ 804, 824 ] ], "normalized": [] }, { "id": "14088", "type": "", "text": [ "cancer" ], "offsets": [ [ 726, 732 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14086", "type": "PA", "arg1_id": "14084", "arg2_id": "14085", "normalized": [] }, { "id": "14089", "type": "PA", "arg1_id": "14087", "arg2_id": "14088", "normalized": [] } ]

[ { "id": "14092", "type": "title", "text": [ "Short-chain fatty acids induce intestinal transient receptor potential vanilloid type 6 expression in rats and Caco-2 cells." ], "offsets": [ [ 0, 124 ] ] }, { "id": "14093", "type": "abstract", "text": [ "Fructooligosaccharides (FOS) are indigestible oligosaccharides that increase calcium absorption by the colorectum in rats, but the underlying mechanisms remain unclear. We therefore investigated the effects of FOS on expressions of genes involved with calcium absorption in rat colorectal mucosa cells. After feeding a diet containing FOS (100 g/kg diet) to rats for 2 d, we investigated gene transcripts of transient receptor potential vanilloid type 6 (TRPV6), calbindin-D9k, and plasma membrane calcium-ATPase 1b (PMCA1b). The FOS diet increased expression of TRPV6 and calbindin-D9k but did not affect PMCA1b expression. Because FOS could not directly affect gene expression, SCFA formed as fermentation products of FOS were considered as likely intermediates. SCFA (2.0 mmol/L) were thus added to Caco-2 human colonic epithelial cells, resulting in significantly increased mRNA expression of TRPV6. To ascertain the effects of SCFA on mRNA expression, a genomic clone of TRPV6 was isolated. Using luciferase reporter assay, a segment between -71 nucleotides and the translation start site was found to contain a positive responsive element to SCFA. These results suggest that FOS increase calcium absorption by increasing mRNA expression of TRPV6 in rat colorectum, and cell culture analysis indicated that SCFA, as fermentation products of FOS, are involved in the increased mRNA expression of TRPV6. We found for the first time, to our knowledge, that regulation of TRPV6 gene expression by SCFA may be a molecular mechanism involved in the promotion of calcium absorption by FOS in rats." ], "offsets": [ [ 125, 1720 ] ] } ]

[ { "id": "14094", "type": "Chemicals & Drugs", "text": [ "Short-chain fatty acids" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "14095", "type": "Genes & Molecular Sequences", "text": [ "Short-chain fatty acids" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "14096", "type": "Genes & Molecular Sequences", "text": [ "intestinal transient receptor potential vanilloid type 6" ], "offsets": [ [ 31, 87 ] ], "normalized": [] }, { "id": "14097", "type": "Chemicals & Drugs", "text": [ "Fructooligosaccharides" ], "offsets": [ [ 125, 147 ] ], "normalized": [] }, { "id": "14098", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 149, 152 ] ], "normalized": [] }, { "id": "14099", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 149, 152 ] ], "normalized": [] }, { "id": "14100", "type": "Chemicals & Drugs", "text": [ "indigestible oligosaccharides" ], "offsets": [ [ 158, 187 ] ], "normalized": [] }, { "id": "14101", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 202, 209 ] ], "normalized": [] }, { "id": "14102", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "14103", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "14104", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 377, 384 ] ], "normalized": [] }, { "id": "14105", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14106", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14107", "type": "Genes & Molecular Sequences", "text": [ "transient receptor potential vanilloid type 6" ], "offsets": [ [ 533, 578 ] ], "normalized": [] }, { "id": "14108", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 580, 585 ] ], "normalized": [] }, { "id": "14109", "type": "Genes & Molecular Sequences", "text": [ "calbindin-D9k" ], "offsets": [ [ 588, 601 ] ], "normalized": [] }, { "id": "14110", "type": "Genes & Molecular Sequences", "text": [ "plasma membrane calcium-ATPase 1b" ], "offsets": [ [ 607, 640 ] ], "normalized": [] }, { "id": "14111", "type": "Genes & Molecular Sequences", "text": [ "PMCA1b" ], "offsets": [ [ 642, 648 ] ], "normalized": [] }, { "id": "14112", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14113", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14114", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 688, 693 ] ], "normalized": [] }, { "id": "14115", "type": "Genes & Molecular Sequences", "text": [ "calbindin-D9k" ], "offsets": [ [ 698, 711 ] ], "normalized": [] }, { "id": "14116", "type": "Genes & Molecular Sequences", "text": [ "PMCA1b" ], "offsets": [ [ 731, 737 ] ], "normalized": [] }, { "id": "14117", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 758, 761 ] ], "normalized": [] }, { "id": "14118", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 758, 761 ] ], "normalized": [] }, { "id": "14119", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 805, 809 ] ], "normalized": [] }, { "id": "14120", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 805, 809 ] ], "normalized": [] }, { "id": "14121", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 845, 848 ] ], "normalized": [] }, { "id": "14122", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 845, 848 ] ], "normalized": [] }, { "id": "14123", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 890, 894 ] ], "normalized": [] }, { "id": "14124", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 890, 894 ] ], "normalized": [] }, { "id": "14125", "type": "Genes & Molecular Sequences", "text": [ "mRNA" ], "offsets": [ [ 1003, 1007 ] ], "normalized": [] }, { "id": "14126", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [] }, { "id": "14127", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [] }, { "id": "14128", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [] }, { "id": "14129", "type": "Genes & Molecular Sequences", "text": [ "mRNA" ], "offsets": [ [ 1065, 1069 ] ], "normalized": [] }, { "id": "14130", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 1101, 1106 ] ], "normalized": [] }, { "id": "14131", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 1273, 1277 ] ], "normalized": [] }, { "id": "14132", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 1273, 1277 ] ], "normalized": [] }, { "id": "14133", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 1306, 1309 ] ], "normalized": [] }, { "id": "14134", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 1306, 1309 ] ], "normalized": [] }, { "id": "14135", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 1319, 1326 ] ], "normalized": [] }, { "id": "14136", "type": "Genes & Molecular Sequences", "text": [ "mRNA" ], "offsets": [ [ 1352, 1356 ] ], "normalized": [] }, { "id": "14137", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 1371, 1376 ] ], "normalized": [] }, { "id": "14138", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "14139", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "14140", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 1471, 1474 ] ], "normalized": [] }, { "id": "14141", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 1471, 1474 ] ], "normalized": [] }, { "id": "14142", "type": "Genes & Molecular Sequences", "text": [ "mRNA" ], "offsets": [ [ 1506, 1510 ] ], "normalized": [] }, { "id": "14143", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [] }, { "id": "14144", "type": "Genes & Molecular Sequences", "text": [ "TRPV6" ], "offsets": [ [ 1598, 1603 ] ], "normalized": [] }, { "id": "14145", "type": "Chemicals & Drugs", "text": [ "SCFA" ], "offsets": [ [ 1623, 1627 ] ], "normalized": [] }, { "id": "14146", "type": "Genes & Molecular Sequences", "text": [ "SCFA" ], "offsets": [ [ 1623, 1627 ] ], "normalized": [] }, { "id": "14147", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 1686, 1693 ] ], "normalized": [] }, { "id": "14148", "type": "Chemicals & Drugs", "text": [ "FOS" ], "offsets": [ [ 1708, 1711 ] ], "normalized": [] }, { "id": "14149", "type": "Genes & Molecular Sequences", "text": [ "FOS" ], "offsets": [ [ 1708, 1711 ] ], "normalized": [] }, { "id": "14150", "type": "", "text": [ "Short-chain fatty acids" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "14151", "type": "", "text": [ "intestinal transient receptor potential vanilloid type 6" ], "offsets": [ [ 31, 87 ] ], "normalized": [] }, { "id": "14153", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14154", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 580, 585 ] ], "normalized": [] }, { "id": "14156", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14157", "type": "", "text": [ "calbindin-D9k" ], "offsets": [ [ 588, 601 ] ], "normalized": [] }, { "id": "14159", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14160", "type": "", "text": [ "PMCA1b" ], "offsets": [ [ 642, 648 ] ], "normalized": [] }, { "id": "14162", "type": "", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14163", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 688, 693 ] ], "normalized": [] }, { "id": "14165", "type": "", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14166", "type": "", "text": [ "calbindin-D9k" ], "offsets": [ [ 698, 711 ] ], "normalized": [] }, { "id": "14168", "type": "", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14169", "type": "", "text": [ "PMCA1b" ], "offsets": [ [ 731, 737 ] ], "normalized": [] }, { "id": "14171", "type": "", "text": [ "SCFA" ], "offsets": [ [ 890, 894 ] ], "normalized": [] }, { "id": "14172", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [] }, { "id": "14174", "type": "", "text": [ "FOS" ], "offsets": [ [ 1471, 1474 ] ], "normalized": [] }, { "id": "14175", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [] }, { "id": "14177", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "14178", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [] }, { "id": "14180", "type": "", "text": [ "FOS" ], "offsets": [ [ 1708, 1711 ] ], "normalized": [] }, { "id": "14181", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1598, 1603 ] ], "normalized": [] }, { "id": "14183", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1623, 1627 ] ], "normalized": [] }, { "id": "14184", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1598, 1603 ] ], "normalized": [] }, { "id": "14186", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14187", "type": "", "text": [ "plasma membrane calcium-ATPase 1b" ], "offsets": [ [ 607, 640 ] ], "normalized": [] }, { "id": "14189", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14190", "type": "", "text": [ "PMCA1b" ], "offsets": [ [ 642, 648 ] ], "normalized": [] }, { "id": "14192", "type": "", "text": [ "calcium" ], "offsets": [ [ 1686, 1693 ] ], "normalized": [] }, { "id": "14193", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1598, 1603 ] ], "normalized": [] }, { "id": "14195", "type": "", "text": [ "FOS" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "14196", "type": "", "text": [ "transient receptor potential vanilloid type 6" ], "offsets": [ [ 533, 578 ] ], "normalized": [] }, { "id": "14198", "type": "", "text": [ "FOS" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "14199", "type": "", "text": [ "PMCA1b" ], "offsets": [ [ 731, 737 ] ], "normalized": [] }, { "id": "14201", "type": "", "text": [ "FOS" ], "offsets": [ [ 845, 848 ] ], "normalized": [] }, { "id": "14202", "type": "", "text": [ "SCFA" ], "offsets": [ [ 805, 809 ] ], "normalized": [] }, { "id": "14204", "type": "", "text": [ "calcium" ], "offsets": [ [ 1319, 1326 ] ], "normalized": [] }, { "id": "14205", "type": "", "text": [ "TRPV6" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [] }, { "id": "14207", "type": "", "text": [ "calcium" ], "offsets": [ [ 1319, 1326 ] ], "normalized": [] }, { "id": "14208", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "14210", "type": "", "text": [ "calcium" ], "offsets": [ [ 1319, 1326 ] ], "normalized": [] }, { "id": "14211", "type": "", "text": [ "mRNA" ], "offsets": [ [ 1506, 1510 ] ], "normalized": [] }, { "id": "14213", "type": "", "text": [ "FOS" ], "offsets": [ [ 1471, 1474 ] ], "normalized": [] }, { "id": "14214", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "14216", "type": "", "text": [ "FOS" ], "offsets": [ [ 1471, 1474 ] ], "normalized": [] }, { "id": "14217", "type": "", "text": [ "mRNA" ], "offsets": [ [ 1506, 1510 ] ], "normalized": [] }, { "id": "14219", "type": "", "text": [ "calcium" ], "offsets": [ [ 1686, 1693 ] ], "normalized": [] }, { "id": "14220", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1623, 1627 ] ], "normalized": [] }, { "id": "14222", "type": "", "text": [ "FOS" ], "offsets": [ [ 1708, 1711 ] ], "normalized": [] }, { "id": "14223", "type": "", "text": [ "SCFA" ], "offsets": [ [ 1623, 1627 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "14227", "type": "title", "text": [ "RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population." ], "offsets": [ [ 0, 122 ] ] }, { "id": "14228", "type": "abstract", "text": [ "Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity. We hypothesized that polymorphisms of genes responsible for DNA repair may be associated with risk of thyroid cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in thyroid cancer, we conducted a hospital-based case-control study in Saudi population. Two hundred and twenty-three incident papillary thyroid cancer cases and 229 controls recruited from Saudi Arabian population were analyzed for 21 loci in 8 selected DNA repair genes by PCR-restriction fragment length polymorphism including non-homologous end joining pathway genes LIGIV (LIGlV ASP62HIS, PRO231SER, TRP46TER), XRCC4 Splice 33243301G>A and XRCC7 ILE3434THR; homologous recombination pathway genes XRCC3 ARG94HIS and THR241MET, RAD51 UTR 15452658T>C, 15455419A>G, RAD52 2259 and GLN221GLU, conserved DNA damage response gene Tp53 PRO47SER, PRO72ARG, Tp53 UTR 7178189A>C and base excision repair gene XRCC1 ARG194TRP, ARG280HIS, ARG399GLN, ARG559GLN. RAD52 GLN221GLU genotypes CG and variants carrying G allele showed statistical significance and very high risk of developing thyroid cancer compared to wild type [CG vs CC; p<0.001, odds ratio (OR)=15.57, 95% confidence interval (CI)=6.56-36.98, CG+GG vs CC; p<0.001, OR=17.58, 95% CI=7.44-41.58]. Similarly, RAD52 2259 genotypes CT and variant allele T showed a significant difference in terms of risk estimation (CT vs CC; p<0.05, OR=1.53, 95% CI=1.03-2.28, CT+TT vs CC; p<0.001, OR=1.922, 95% CI=1.31-2.82). Remaining loci demonstrated no significance with risk. Of the 21 loci screened, RAD52 2259 and RAD52 GLN221GLU may be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population." ], "offsets": [ [ 123, 1893 ] ] } ]

[ { "id": "14229", "type": "SNP & Sequence variations", "text": [ "RAD52 polymorphisms" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "14230", "type": "Genes & Molecular Sequences", "text": [ "RAD52 polymorphisms" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "14231", "type": "Diseases & Disorders", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 53, 77 ] ], "normalized": [] }, { "id": "14232", "type": "Diseases & Disorders", "text": [ "thyroid cancer" ], "offsets": [ [ 310, 324 ] ], "normalized": [] }, { "id": "14233", "type": "Diseases & Disorders", "text": [ "thyroid cancer" ], "offsets": [ [ 395, 409 ] ], "normalized": [] }, { "id": "14234", "type": "Diseases & Disorders", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14235", "type": "Genes & Molecular Sequences", "text": [ "LIGIV" ], "offsets": [ [ 763, 768 ] ], "normalized": [] }, { "id": "14236", "type": "SNP & Sequence variations", "text": [ "LIGlV ASP62HIS" ], "offsets": [ [ 770, 784 ] ], "normalized": [] }, { "id": "14237", "type": "Genes & Molecular Sequences", "text": [ "LIGlV ASP62HIS" ], "offsets": [ [ 770, 784 ] ], "normalized": [] }, { "id": "14238", "type": "SNP & Sequence variations", "text": [ "PRO231SER" ], "offsets": [ [ 786, 795 ] ], "normalized": [] }, { "id": "14239", "type": "SNP & Sequence variations", "text": [ "TRP46TER" ], "offsets": [ [ 797, 805 ] ], "normalized": [] }, { "id": "14240", "type": "Genes & Molecular Sequences", "text": [ "XRCC4" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "14241", "type": "SNP & Sequence variations", "text": [ "XRCC4" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "14242", "type": "SNP & Sequence variations", "text": [ "33243301G>A" ], "offsets": [ [ 821, 832 ] ], "normalized": [] }, { "id": "14243", "type": "Genes & Molecular Sequences", "text": [ "XRCC7" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "14244", "type": "SNP & Sequence variations", "text": [ "XRCC7" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "14245", "type": "SNP & Sequence variations", "text": [ "ILE3434THR" ], "offsets": [ [ 843, 853 ] ], "normalized": [] }, { "id": "14246", "type": "Genes & Molecular Sequences", "text": [ "XRCC3" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "14247", "type": "SNP & Sequence variations", "text": [ "XRCC3" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "14248", "type": "SNP & Sequence variations", "text": [ "ARG94HIS" ], "offsets": [ [ 900, 908 ] ], "normalized": [] }, { "id": "14249", "type": "SNP & Sequence variations", "text": [ "THR241MET" ], "offsets": [ [ 913, 922 ] ], "normalized": [] }, { "id": "14250", "type": "Genes & Molecular Sequences", "text": [ "RAD51" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "14251", "type": "SNP & Sequence variations", "text": [ "RAD51" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "14252", "type": "SNP & Sequence variations", "text": [ "UTR 15452658T>C" ], "offsets": [ [ 930, 945 ] ], "normalized": [] }, { "id": "14253", "type": "Genes & Molecular Sequences", "text": [ "UTR 15452658T>C" ], "offsets": [ [ 930, 945 ] ], "normalized": [] }, { "id": "14254", "type": "SNP & Sequence variations", "text": [ "15455419A>G" ], "offsets": [ [ 947, 958 ] ], "normalized": [] }, { "id": "14255", "type": "SNP & Sequence variations", "text": [ "RAD52 2259" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "14256", "type": "Genes & Molecular Sequences", "text": [ "RAD52 2259" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "14257", "type": "SNP & Sequence variations", "text": [ "GLN221GLU" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "14258", "type": "Diseases & Disorders", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14259", "type": "Genes & Molecular Sequences", "text": [ "Tp53" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "14260", "type": "SNP & Sequence variations", "text": [ "Tp53" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "14261", "type": "SNP & Sequence variations", "text": [ "PRO47SER" ], "offsets": [ [ 1026, 1034 ] ], "normalized": [] }, { "id": "14262", "type": "SNP & Sequence variations", "text": [ "PRO72ARG" ], "offsets": [ [ 1036, 1044 ] ], "normalized": [] }, { "id": "14263", "type": "Genes & Molecular Sequences", "text": [ "Tp53" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "14264", "type": "SNP & Sequence variations", "text": [ "Tp53" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "14265", "type": "SNP & Sequence variations", "text": [ "UTR 7178189A>C" ], "offsets": [ [ 1051, 1065 ] ], "normalized": [] }, { "id": "14266", "type": "Genes & Molecular Sequences", "text": [ "UTR 7178189A>C" ], "offsets": [ [ 1051, 1065 ] ], "normalized": [] }, { "id": "14267", "type": "Genes & Molecular Sequences", "text": [ "XRCC1" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "14268", "type": "SNP & Sequence variations", "text": [ "XRCC1" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "14269", "type": "SNP & Sequence variations", "text": [ "ARG194TRP" ], "offsets": [ [ 1102, 1111 ] ], "normalized": [] }, { "id": "14270", "type": "SNP & Sequence variations", "text": [ "ARG280HIS" ], "offsets": [ [ 1113, 1122 ] ], "normalized": [] }, { "id": "14271", "type": "SNP & Sequence variations", "text": [ "ARG399GLN" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "14272", "type": "SNP & Sequence variations", "text": [ "ARG559GLN" ], "offsets": [ [ 1135, 1144 ] ], "normalized": [] }, { "id": "14273", "type": "SNP & Sequence variations", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1146, 1161 ] ], "normalized": [] }, { "id": "14274", "type": "Genes & Molecular Sequences", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1146, 1161 ] ], "normalized": [] }, { "id": "14275", "type": "SNP & Sequence variations", "text": [ "CG" ], "offsets": [ [ 1172, 1174 ] ], "normalized": [] }, { "id": "14276", "type": "SNP & Sequence variations", "text": [ "G allele" ], "offsets": [ [ 1197, 1205 ] ], "normalized": [] }, { "id": "14277", "type": "Diseases & Disorders", "text": [ "thyroid cancer" ], "offsets": [ [ 1271, 1285 ] ], "normalized": [] }, { "id": "14278", "type": "SNP & Sequence variations", "text": [ "CG" ], "offsets": [ [ 1309, 1311 ] ], "normalized": [] }, { "id": "14279", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1315, 1317 ] ], "normalized": [] }, { "id": "14280", "type": "SNP & Sequence variations", "text": [ "CG" ], "offsets": [ [ 1392, 1394 ] ], "normalized": [] }, { "id": "14281", "type": "SNP & Sequence variations", "text": [ "GG" ], "offsets": [ [ 1395, 1397 ] ], "normalized": [] }, { "id": "14282", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1401, 1403 ] ], "normalized": [] }, { "id": "14283", "type": "SNP & Sequence variations", "text": [ "RAD52 2259" ], "offsets": [ [ 1455, 1465 ] ], "normalized": [] }, { "id": "14284", "type": "Genes & Molecular Sequences", "text": [ "RAD52 2259" ], "offsets": [ [ 1455, 1465 ] ], "normalized": [] }, { "id": "14285", "type": "SNP & Sequence variations", "text": [ "CT" ], "offsets": [ [ 1476, 1478 ] ], "normalized": [] }, { "id": "14286", "type": "SNP & Sequence variations", "text": [ "allele T" ], "offsets": [ [ 1491, 1499 ] ], "normalized": [] }, { "id": "14287", "type": "SNP & Sequence variations", "text": [ "CT" ], "offsets": [ [ 1561, 1563 ] ], "normalized": [] }, { "id": "14288", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1567, 1569 ] ], "normalized": [] }, { "id": "14289", "type": "SNP & Sequence variations", "text": [ "CT" ], "offsets": [ [ 1606, 1608 ] ], "normalized": [] }, { "id": "14290", "type": "SNP & Sequence variations", "text": [ "TT" ], "offsets": [ [ 1609, 1611 ] ], "normalized": [] }, { "id": "14291", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1615, 1617 ] ], "normalized": [] }, { "id": "14292", "type": "SNP & Sequence variations", "text": [ "RAD52 2259" ], "offsets": [ [ 1737, 1747 ] ], "normalized": [] }, { "id": "14293", "type": "Genes & Molecular Sequences", "text": [ "RAD52 2259" ], "offsets": [ [ 1737, 1747 ] ], "normalized": [] }, { "id": "14294", "type": "SNP & Sequence variations", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1752, 1767 ] ], "normalized": [] }, { "id": "14295", "type": "Genes & Molecular Sequences", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1752, 1767 ] ], "normalized": [] }, { "id": "14296", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1792, 1799 ] ], "normalized": [] }, { "id": "14297", "type": "Diseases & Disorders", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 1835, 1859 ] ], "normalized": [] }, { "id": "14298", "type": "", "text": [ "RAD52 polymorphisms" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "14299", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 53, 77 ] ], "normalized": [] }, { "id": "14301", "type": "", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1146, 1161 ] ], "normalized": [] }, { "id": "14302", "type": "", "text": [ "thyroid cancer" ], "offsets": [ [ 1271, 1285 ] ], "normalized": [] }, { "id": "14304", "type": "", "text": [ "CG" ], "offsets": [ [ 1392, 1394 ] ], "normalized": [] }, { "id": "14305", "type": "", "text": [ "thyroid cancer" ], "offsets": [ [ 1271, 1285 ] ], "normalized": [] }, { "id": "14307", "type": "", "text": [ "G allele" ], "offsets": [ [ 1197, 1205 ] ], "normalized": [] }, { "id": "14308", "type": "", "text": [ "thyroid cancer" ], "offsets": [ [ 1271, 1285 ] ], "normalized": [] }, { "id": "14310", "type": "", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1752, 1767 ] ], "normalized": [] }, { "id": "14311", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 1835, 1859 ] ], "normalized": [] }, { "id": "14313", "type": "", "text": [ "RAD52 2259" ], "offsets": [ [ 1737, 1747 ] ], "normalized": [] }, { "id": "14314", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 1835, 1859 ] ], "normalized": [] }, { "id": "14316", "type": "", "text": [ "RAD52 2259" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "14317", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14319", "type": "", "text": [ "RAD52 2259" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "14320", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14322", "type": "", "text": [ "UTR 7178189A>C" ], "offsets": [ [ 1051, 1065 ] ], "normalized": [] }, { "id": "14323", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14325", "type": "", "text": [ "UTR 7178189A>C" ], "offsets": [ [ 1051, 1065 ] ], "normalized": [] }, { "id": "14326", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14328", "type": "", "text": [ "XRCC4" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "14329", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14331", "type": "", "text": [ "XRCC4" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "14332", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14334", "type": "", "text": [ "XRCC7" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "14335", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14337", "type": "", "text": [ "XRCC7" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "14338", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14340", "type": "", "text": [ "XRCC3" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "14341", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14343", "type": "", "text": [ "XRCC3" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "14344", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14346", "type": "", "text": [ "RAD51" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "14347", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14349", "type": "", "text": [ "RAD51" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "14350", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14352", "type": "", "text": [ "Tp53" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "14353", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14355", "type": "", "text": [ "Tp53" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "14356", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14358", "type": "", "text": [ "XRCC1" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "14359", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14361", "type": "", "text": [ "XRCC1" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "14362", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "14364", "type": "", "text": [ "RAD52 GLN221GLU" ], "offsets": [ [ 1752, 1767 ] ], "normalized": [] }, { "id": "14365", "type": "", "text": [ "disease" ], "offsets": [ [ 1792, 1799 ] ], "normalized": [] }, { "id": "14367", "type": "", "text": [ "LIGIV" ], "offsets": [ [ 763, 768 ] ], "normalized": [] }, { "id": "14368", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14370", "type": "", "text": [ "LIGlV ASP62HIS" ], "offsets": [ [ 770, 784 ] ], "normalized": [] }, { "id": "14371", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14373", "type": "", "text": [ "PRO231SER" ], "offsets": [ [ 786, 795 ] ], "normalized": [] }, { "id": "14374", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14376", "type": "", "text": [ "TRP46TER" ], "offsets": [ [ 797, 805 ] ], "normalized": [] }, { "id": "14377", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14379", "type": "", "text": [ "33243301G>A" ], "offsets": [ [ 821, 832 ] ], "normalized": [] }, { "id": "14380", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14382", "type": "", "text": [ "ILE3434THR" ], "offsets": [ [ 843, 853 ] ], "normalized": [] }, { "id": "14383", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14385", "type": "", "text": [ "ARG94HIS" ], "offsets": [ [ 900, 908 ] ], "normalized": [] }, { "id": "14386", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14388", "type": "", "text": [ "THR241MET" ], "offsets": [ [ 913, 922 ] ], "normalized": [] }, { "id": "14389", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14391", "type": "", "text": [ "UTR 15452658T>C" ], "offsets": [ [ 930, 945 ] ], "normalized": [] }, { "id": "14392", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14394", "type": "", "text": [ "15455419A>G" ], "offsets": [ [ 947, 958 ] ], "normalized": [] }, { "id": "14395", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14397", "type": "", "text": [ "GLN221GLU" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "14398", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14400", "type": "", "text": [ "PRO47SER" ], "offsets": [ [ 1026, 1034 ] ], "normalized": [] }, { "id": "14401", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14403", "type": "", "text": [ "PRO72ARG" ], "offsets": [ [ 1036, 1044 ] ], "normalized": [] }, { "id": "14404", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14406", "type": "", "text": [ "ARG194TRP" ], "offsets": [ [ 1102, 1111 ] ], "normalized": [] }, { "id": "14407", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14409", "type": "", "text": [ "ARG280HIS" ], "offsets": [ [ 1113, 1122 ] ], "normalized": [] }, { "id": "14410", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14412", "type": "", "text": [ "ARG399GLN" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "14413", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14415", "type": "", "text": [ "ARG559GLN" ], "offsets": [ [ 1135, 1144 ] ], "normalized": [] }, { "id": "14416", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14418", "type": "", "text": [ "Tp53" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "14419", "type": "", "text": [ "papillary thyroid cancer" ], "offsets": [ [ 519, 543 ] ], "normalized": [] }, { "id": "14421", "type": "", "text": [ "CG" ], "offsets": [ [ 1309, 1311 ] ], "normalized": [] }, { "id": "14422", "type": "", "text": [ "thyroid cancer" ], "offsets": [ [ 1271, 1285 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14300", "type": "PA", "arg1_id": "14298", "arg2_id": "14299", "normalized": [] }, { "id": "14303", "type": "PA", "arg1_id": "14301", "arg2_id": "14302", "normalized": [] }, { "id": "14306", "type": "PA", "arg1_id": "14304", "arg2_id": "14305", "normalized": [] }, { "id": "14309", "type": "PA", "arg1_id": "14307", "arg2_id": "14308", "normalized": [] }, { "id": "14312", "type": "SA", "arg1_id": "14310", "arg2_id": "14311", "normalized": [] }, { "id": "14315", "type": "SA", "arg1_id": "14313", "arg2_id": "14314", "normalized": [] }, { "id": "14318", "type": "PA", "arg1_id": "14316", "arg2_id": "14317", "normalized": [] }, { "id": "14321", "type": "PA", "arg1_id": "14319", "arg2_id": "14320", "normalized": [] }, { "id": "14324", "type": "PA", "arg1_id": "14322", "arg2_id": "14323", "normalized": [] }, { "id": "14327", "type": "PA", "arg1_id": "14325", "arg2_id": "14326", "normalized": [] }, { "id": "14330", "type": "PA", "arg1_id": "14328", "arg2_id": "14329", "normalized": [] }, { "id": "14333", "type": "PA", "arg1_id": "14331", "arg2_id": "14332", "normalized": [] }, { "id": "14336", "type": "PA", "arg1_id": "14334", "arg2_id": "14335", "normalized": [] }, { "id": "14339", "type": "PA", "arg1_id": "14337", "arg2_id": "14338", "normalized": [] }, { "id": "14342", "type": "PA", "arg1_id": "14340", "arg2_id": "14341", "normalized": [] }, { "id": "14345", "type": "PA", "arg1_id": "14343", "arg2_id": "14344", "normalized": [] }, { "id": "14348", "type": "PA", "arg1_id": "14346", "arg2_id": "14347", "normalized": [] }, { "id": "14351", "type": "PA", "arg1_id": "14349", "arg2_id": "14350", "normalized": [] }, { "id": "14354", "type": "PA", "arg1_id": "14352", "arg2_id": "14353", "normalized": [] }, { "id": "14357", "type": "PA", "arg1_id": "14355", "arg2_id": "14356", "normalized": [] }, { "id": "14360", "type": "PA", "arg1_id": "14358", "arg2_id": "14359", "normalized": [] }, { "id": "14363", "type": "PA", "arg1_id": "14361", "arg2_id": "14362", "normalized": [] }, { "id": "14366", "type": "PA", "arg1_id": "14364", "arg2_id": "14365", "normalized": [] }, { "id": "14369", "type": "PA", "arg1_id": "14367", "arg2_id": "14368", "normalized": [] }, { "id": "14372", "type": "SA", "arg1_id": "14370", "arg2_id": "14371", "normalized": [] }, { "id": "14375", "type": "SA", "arg1_id": "14373", "arg2_id": "14374", "normalized": [] }, { "id": "14378", "type": "SA", "arg1_id": "14376", "arg2_id": "14377", "normalized": [] }, { "id": "14381", "type": "SA", "arg1_id": "14379", "arg2_id": "14380", "normalized": [] }, { "id": "14384", "type": "SA", "arg1_id": "14382", "arg2_id": "14383", "normalized": [] }, { "id": "14387", "type": "SA", "arg1_id": "14385", "arg2_id": "14386", "normalized": [] }, { "id": "14390", "type": "SA", "arg1_id": "14388", "arg2_id": "14389", "normalized": [] }, { "id": "14393", "type": "SA", "arg1_id": "14391", "arg2_id": "14392", "normalized": [] }, { "id": "14396", "type": "SA", "arg1_id": "14394", "arg2_id": "14395", "normalized": [] }, { "id": "14399", "type": "SA", "arg1_id": "14397", "arg2_id": "14398", "normalized": [] }, { "id": "14402", "type": "SA", "arg1_id": "14400", "arg2_id": "14401", "normalized": [] }, { "id": "14405", "type": "SA", "arg1_id": "14403", "arg2_id": "14404", "normalized": [] }, { "id": "14408", "type": "SA", "arg1_id": "14406", "arg2_id": "14407", "normalized": [] }, { "id": "14411", "type": "SA", "arg1_id": "14409", "arg2_id": "14410", "normalized": [] }, { "id": "14414", "type": "SA", "arg1_id": "14412", "arg2_id": "14413", "normalized": [] }, { "id": "14417", "type": "SA", "arg1_id": "14415", "arg2_id": "14416", "normalized": [] }, { "id": "14420", "type": "PA", "arg1_id": "14418", "arg2_id": "14419", "normalized": [] }, { "id": "14423", "type": "PA", "arg1_id": "14421", "arg2_id": "14422", "normalized": [] } ]

[ { "id": "14426", "type": "title", "text": [ "Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus." ], "offsets": [ [ 0, 96 ] ] }, { "id": "14427", "type": "abstract", "text": [ "The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE." ], "offsets": [ [ 97, 1422 ] ] } ]

[ { "id": "14428", "type": "Genes & Molecular Sequences", "text": [ "TNFSF4" ], "offsets": [ [ 19, 25 ] ], "normalized": [] }, { "id": "14429", "type": "Genes & Molecular Sequences", "text": [ "OX40L" ], "offsets": [ [ 27, 32 ] ], "normalized": [] }, { "id": "14430", "type": "Diseases & Disorders", "text": [ "systemic lupus erythematosus" ], "offsets": [ [ 67, 95 ] ], "normalized": [] }, { "id": "14431", "type": "Genes & Molecular Sequences", "text": [ "tumor necrosis factor ligand superfamily member 4" ], "offsets": [ [ 101, 150 ] ], "normalized": [] }, { "id": "14432", "type": "Genes & Molecular Sequences", "text": [ "TNFSF4" ], "offsets": [ [ 157, 163 ] ], "normalized": [] }, { "id": "14433", "type": "Genes & Molecular Sequences", "text": [ "OX40 ligand" ], "offsets": [ [ 177, 188 ] ], "normalized": [] }, { "id": "14434", "type": "Genes & Molecular Sequences", "text": [ "OX40L" ], "offsets": [ [ 190, 195 ] ], "normalized": [] }, { "id": "14435", "type": "Genes & Molecular Sequences", "text": [ "costimulatory molecule" ], "offsets": [ [ 200, 222 ] ], "normalized": [] }, { "id": "14436", "type": "SNP & Sequence variations", "text": [ "TNFSF4 haplotypes" ], "offsets": [ [ 301, 318 ] ], "normalized": [] }, { "id": "14437", "type": "Genes & Molecular Sequences", "text": [ "TNFSF4 haplotypes" ], "offsets": [ [ 301, 318 ] ], "normalized": [] }, { "id": "14438", "type": "Diseases & Disorders", "text": [ "systemic lupus erythematosus" ], "offsets": [ [ 383, 411 ] ], "normalized": [] }, { "id": "14439", "type": "Diseases & Disorders", "text": [ "SLE" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14440", "type": "Diseases & Disorders", "text": [ "tagging" ], "offsets": [ [ 494, 501 ] ], "normalized": [] }, { "id": "14441", "type": "Genes & Molecular Sequences", "text": [ "TNFSF4" ], "offsets": [ [ 691, 697 ] ], "normalized": [] }, { "id": "14442", "type": "Diseases & Disorders", "text": [ "SLE" ], "offsets": [ [ 703, 706 ] ], "normalized": [] }, { "id": "14443", "type": "Diseases & Disorders", "text": [ "tagged" ], "offsets": [ [ 786, 792 ] ], "normalized": [] }, { "id": "14444", "type": "Diseases & Disorders", "text": [ "minor" ], "offsets": [ [ 800, 805 ] ], "normalized": [] }, { "id": "14445", "type": "SNP & Sequence variations", "text": [ "rs1234317" ], "offsets": [ [ 826, 835 ] ], "normalized": [] }, { "id": "14446", "type": "SNP & Sequence variations", "text": [ "rs12039904" ], "offsets": [ [ 880, 890 ] ], "normalized": [] }, { "id": "14447", "type": "SNP & Sequence variations", "text": [ "rs844644" ], "offsets": [ [ 981, 989 ] ], "normalized": [] }, { "id": "14448", "type": "SNP & Sequence variations", "text": [ "rs1234317" ], "offsets": [ [ 1131, 1140 ] ], "normalized": [] }, { "id": "14449", "type": "SNP & Sequence variations", "text": [ "rs12039904" ], "offsets": [ [ 1145, 1155 ] ], "normalized": [] }, { "id": "14450", "type": "Genes & Molecular Sequences", "text": [ "TNFSF4" ], "offsets": [ [ 1388, 1394 ] ], "normalized": [] }, { "id": "14451", "type": "Diseases & Disorders", "text": [ "SLE" ], "offsets": [ [ 1418, 1421 ] ], "normalized": [] }, { "id": "14452", "type": "", "text": [ "TNFSF4 haplotypes" ], "offsets": [ [ 301, 318 ] ], "normalized": [] }, { "id": "14453", "type": "", "text": [ "systemic lupus erythematosus" ], "offsets": [ [ 383, 411 ] ], "normalized": [] }, { "id": "14455", "type": "", "text": [ "TNFSF4 haplotypes" ], "offsets": [ [ 301, 318 ] ], "normalized": [] }, { "id": "14456", "type": "", "text": [ "SLE" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14458", "type": "", "text": [ "TNFSF4" ], "offsets": [ [ 691, 697 ] ], "normalized": [] }, { "id": "14459", "type": "", "text": [ "SLE" ], "offsets": [ [ 703, 706 ] ], "normalized": [] }, { "id": "14461", "type": "", "text": [ "TNFSF4" ], "offsets": [ [ 1388, 1394 ] ], "normalized": [] }, { "id": "14462", "type": "", "text": [ "SLE" ], "offsets": [ [ 1418, 1421 ] ], "normalized": [] }, { "id": "14464", "type": "", "text": [ "OX40L" ], "offsets": [ [ 27, 32 ] ], "normalized": [] }, { "id": "14465", "type": "", "text": [ "systemic lupus erythematosus" ], "offsets": [ [ 67, 95 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14454", "type": "PA", "arg1_id": "14452", "arg2_id": "14453", "normalized": [] }, { "id": "14457", "type": "PA", "arg1_id": "14455", "arg2_id": "14456", "normalized": [] }, { "id": "14460", "type": "PA", "arg1_id": "14458", "arg2_id": "14459", "normalized": [] }, { "id": "14463", "type": "PA", "arg1_id": "14461", "arg2_id": "14462", "normalized": [] }, { "id": "14466", "type": "PA", "arg1_id": "14464", "arg2_id": "14465", "normalized": [] } ]

[ { "id": "14469", "type": "title", "text": [ "Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection." ], "offsets": [ [ 0, 114 ] ] }, { "id": "14470", "type": "abstract", "text": [ "BACKGROUND: Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU). METHODOLOGY/PRINCIPAL FINDINGS: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis. CONCLUSION/SIGNIFICANCE: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU." ], "offsets": [ [ 115, 1435 ] ] } ]

[ { "id": "14471", "type": "Genes & Molecular Sequences", "text": [ "Cyclophilin A" ], "offsets": [ [ 46, 59 ] ], "normalized": [] }, { "id": "14472", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 104, 113 ] ], "normalized": [] }, { "id": "14473", "type": "Genes & Molecular Sequences", "text": [ "Cyclophilin A" ], "offsets": [ [ 228, 241 ] ], "normalized": [] }, { "id": "14474", "type": "Genes & Molecular Sequences", "text": [ "CypA" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "14475", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 282, 291 ] ], "normalized": [] }, { "id": "14476", "type": "Diseases & Disorders", "text": [ "disease progression" ], "offsets": [ [ 296, 315 ] ], "normalized": [] }, { "id": "14477", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 405, 414 ] ], "normalized": [] }, { "id": "14478", "type": "Diseases & Disorders", "text": [ "disease progression" ], "offsets": [ [ 419, 438 ] ], "normalized": [] }, { "id": "14479", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "14480", "type": "Diseases & Disorders", "text": [ "AIDS" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "14481", "type": "Genes & Molecular Sequences", "text": [ "ACS" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "14482", "type": "Genes & Molecular Sequences", "text": [ "ACS" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "14483", "type": "SNP & Sequence variations", "text": [ "C1604G" ], "offsets": [ [ 638, 644 ] ], "normalized": [] }, { "id": "14484", "type": "SNP & Sequence variations", "text": [ "A1650G" ], "offsets": [ [ 649, 655 ] ], "normalized": [] }, { "id": "14485", "type": "Genes & Molecular Sequences", "text": [ "CypA" ], "offsets": [ [ 699, 703 ] ], "normalized": [] }, { "id": "14486", "type": "SNP & Sequence variations", "text": [ "1650G allele" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "14487", "type": "Diseases & Disorders", "text": [ "seronegative MSM" ], "offsets": [ [ 778, 794 ] ], "normalized": [] }, { "id": "14488", "type": "Diseases & Disorders", "text": [ "HIV-1 infected" ], "offsets": [ [ 803, 817 ] ], "normalized": [] }, { "id": "14489", "type": "SNP & Sequence variations", "text": [ "C1604G" ], "offsets": [ [ 832, 838 ] ], "normalized": [] }, { "id": "14490", "type": "SNP & Sequence variations", "text": [ "A1650G" ], "offsets": [ [ 842, 848 ] ], "normalized": [] }, { "id": "14491", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "14492", "type": "Genes & Molecular Sequences", "text": [ "ACS" ], "offsets": [ [ 921, 924 ] ], "normalized": [] }, { "id": "14493", "type": "SNP & Sequence variations", "text": [ "1604G allele" ], "offsets": [ [ 984, 996 ] ], "normalized": [] }, { "id": "14494", "type": "SNP & Sequence variations", "text": [ "A1650G" ], "offsets": [ [ 1222, 1228 ] ], "normalized": [] }, { "id": "14495", "type": "Genes & Molecular Sequences", "text": [ "CypA" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "14496", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 1329, 1338 ] ], "normalized": [] }, { "id": "14497", "type": "SNP & Sequence variations", "text": [ "1604G allele" ], "offsets": [ [ 1350, 1362 ] ], "normalized": [] }, { "id": "14498", "type": "Diseases & Disorders", "text": [ "weak" ], "offsets": [ [ 1374, 1378 ] ], "normalized": [] }, { "id": "14499", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 1419, 1428 ] ], "normalized": [] }, { "id": "14500", "type": "", "text": [ "Cyclophilin A" ], "offsets": [ [ 46, 59 ] ], "normalized": [] }, { "id": "14501", "type": "", "text": [ "infection" ], "offsets": [ [ 104, 113 ] ], "normalized": [] }, { "id": "14503", "type": "", "text": [ "Cyclophilin A" ], "offsets": [ [ 228, 241 ] ], "normalized": [] }, { "id": "14504", "type": "", "text": [ "infection" ], "offsets": [ [ 282, 291 ] ], "normalized": [] }, { "id": "14506", "type": "", "text": [ "Cyclophilin A" ], "offsets": [ [ 228, 241 ] ], "normalized": [] }, { "id": "14507", "type": "", "text": [ "disease progression" ], "offsets": [ [ 296, 315 ] ], "normalized": [] }, { "id": "14509", "type": "", "text": [ "CypA" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "14510", "type": "", "text": [ "infection" ], "offsets": [ [ 282, 291 ] ], "normalized": [] }, { "id": "14512", "type": "", "text": [ "CypA" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "14513", "type": "", "text": [ "disease progression" ], "offsets": [ [ 296, 315 ] ], "normalized": [] }, { "id": "14515", "type": "", "text": [ "ACS" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "14516", "type": "", "text": [ "infection" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "14518", "type": "", "text": [ "ACS" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "14519", "type": "", "text": [ "disease progression" ], "offsets": [ [ 419, 438 ] ], "normalized": [] }, { "id": "14521", "type": "", "text": [ "ACS" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "14522", "type": "", "text": [ "AIDS" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "14524", "type": "", "text": [ "ACS" ], "offsets": [ [ 921, 924 ] ], "normalized": [] }, { "id": "14525", "type": "", "text": [ "infection" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "14527", "type": "", "text": [ "CypA" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "14528", "type": "", "text": [ "infection" ], "offsets": [ [ 1419, 1428 ] ], "normalized": [] }, { "id": "14530", "type": "", "text": [ "CypA" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "14531", "type": "", "text": [ "weak" ], "offsets": [ [ 1374, 1378 ] ], "normalized": [] }, { "id": "14533", "type": "", "text": [ "1650G allele" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "14534", "type": "", "text": [ "HIV-1 infected" ], "offsets": [ [ 803, 817 ] ], "normalized": [] }, { "id": "14536", "type": "", "text": [ "CypA" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "14537", "type": "", "text": [ "infection" ], "offsets": [ [ 1329, 1338 ] ], "normalized": [] }, { "id": "14539", "type": "", "text": [ "A1650G" ], "offsets": [ [ 1222, 1228 ] ], "normalized": [] }, { "id": "14540", "type": "", "text": [ "infection" ], "offsets": [ [ 1329, 1338 ] ], "normalized": [] }, { "id": "14542", "type": "", "text": [ "1604G allele" ], "offsets": [ [ 1350, 1362 ] ], "normalized": [] }, { "id": "14543", "type": "", "text": [ "infection" ], "offsets": [ [ 1329, 1338 ] ], "normalized": [] }, { "id": "14545", "type": "", "text": [ "1650G allele" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "14546", "type": "", "text": [ "seronegative MSM" ], "offsets": [ [ 778, 794 ] ], "normalized": [] }, { "id": "14548", "type": "", "text": [ "C1604G" ], "offsets": [ [ 832, 838 ] ], "normalized": [] }, { "id": "14549", "type": "", "text": [ "infection" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "14551", "type": "", "text": [ "A1650G" ], "offsets": [ [ 842, 848 ] ], "normalized": [] }, { "id": "14552", "type": "", "text": [ "infection" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "14554", "type": "", "text": [ "1604G allele" ], "offsets": [ [ 1350, 1362 ] ], "normalized": [] }, { "id": "14555", "type": "", "text": [ "infection" ], "offsets": [ [ 1419, 1428 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14502", "type": "PA", "arg1_id": "14500", "arg2_id": "14501", "normalized": [] }, { "id": "14505", "type": "PA", "arg1_id": "14503", "arg2_id": "14504", "normalized": [] }, { "id": "14508", "type": "PA", "arg1_id": "14506", "arg2_id": "14507", "normalized": [] }, { "id": "14511", "type": "PA", "arg1_id": "14509", "arg2_id": "14510", "normalized": [] }, { "id": "14514", "type": "PA", "arg1_id": "14512", "arg2_id": "14513", "normalized": [] }, { "id": "14517", "type": "PA", "arg1_id": "14515", "arg2_id": "14516", "normalized": [] }, { "id": "14520", "type": "PA", "arg1_id": "14518", "arg2_id": "14519", "normalized": [] }, { "id": "14523", "type": "PA", "arg1_id": "14521", "arg2_id": "14522", "normalized": [] }, { "id": "14526", "type": "PA", "arg1_id": "14524", "arg2_id": "14525", "normalized": [] }, { "id": "14529", "type": "PA", "arg1_id": "14527", "arg2_id": "14528", "normalized": [] }, { "id": "14532", "type": "PA", "arg1_id": "14530", "arg2_id": "14531", "normalized": [] }, { "id": "14535", "type": "PA", "arg1_id": "14533", "arg2_id": "14534", "normalized": [] }, { "id": "14538", "type": "PA", "arg1_id": "14536", "arg2_id": "14537", "normalized": [] }, { "id": "14541", "type": "PA", "arg1_id": "14539", "arg2_id": "14540", "normalized": [] }, { "id": "14544", "type": "PA", "arg1_id": "14542", "arg2_id": "14543", "normalized": [] }, { "id": "14547", "type": "PA", "arg1_id": "14545", "arg2_id": "14546", "normalized": [] }, { "id": "14550", "type": "NA", "arg1_id": "14548", "arg2_id": "14549", "normalized": [] }, { "id": "14553", "type": "NA", "arg1_id": "14551", "arg2_id": "14552", "normalized": [] }, { "id": "14556", "type": "SA", "arg1_id": "14554", "arg2_id": "14555", "normalized": [] } ]

[ { "id": "14559", "type": "title", "text": [ "Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians." ], "offsets": [ [ 0, 151 ] ] }, { "id": "14560", "type": "abstract", "text": [ "OBJECTIVE: Methotrexate (MTX) is the drug of choice for rheumatoid arthritis (RA) but is effective only in around 60% of treated patients. Bioavailability of MTX may be a major determinant of response status and this may be governed by variations in MTX receptor and transporter genes and genes responsible for polyglutamation and deconjugation. We investigated the contribution of single nucleotide polymorphisms (SNPs) in RFC, FOLR1, FPGS, GGH and MDR1 genes to MTX response in RA patients from North India. METHODS: RA patients recruited using American College of Rheumatology criteria, were categorized into good and poor responders to MTX, based on disease activity score. A total of 17 SNPs from the above mentioned genes were genotyped and tested for association with MTX response using [chi]2 test; logistic regression along with clinical variables; and gene-gene interaction using multifactor dimensionality reduction (MDR). RESULTS: One novel synonymous SNP Ala324Ala (972 G > A) was identified in RFC gene. The CT genotype of C3435T in MDR1 gene conferred almost twice the risk of poor response [[chi]2 = 5.85, P = 0.01, odds ratio (95% confidence interval) = 1.97 (1.13-3.42)] and was retained in binary logistic regression [B = 0.66, P = 0.025, adjusted odds ratio (95% confidence interval) = 1.93(1.09-3.42)]. Significant interaction between SNPs in GGH and MDR1 genes seems promising. CONCLUSION: Interactions between genes coding for deconjugation and transporter seem to be important determinants of MTX response in RA but replication and functional studies would be confirmatory." ], "offsets": [ [ 152, 1749 ] ] } ]

[ { "id": "14561", "type": "Diseases & Disorders", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 107, 127 ] ], "normalized": [] }, { "id": "14562", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 177, 180 ] ], "normalized": [] }, { "id": "14563", "type": "Diseases & Disorders", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 208, 228 ] ], "normalized": [] }, { "id": "14564", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 230, 232 ] ], "normalized": [] }, { "id": "14565", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 310, 313 ] ], "normalized": [] }, { "id": "14566", "type": "Genes & Molecular Sequences", "text": [ "MTX receptor" ], "offsets": [ [ 402, 414 ] ], "normalized": [] }, { "id": "14567", "type": "Genes & Molecular Sequences", "text": [ "genes responsible for polyglutamation and deconjugation" ], "offsets": [ [ 441, 496 ] ], "normalized": [] }, { "id": "14568", "type": "Genes & Molecular Sequences", "text": [ "RFC" ], "offsets": [ [ 576, 579 ] ], "normalized": [] }, { "id": "14569", "type": "Genes & Molecular Sequences", "text": [ "FOLR1" ], "offsets": [ [ 581, 586 ] ], "normalized": [] }, { "id": "14570", "type": "Genes & Molecular Sequences", "text": [ "FPGS" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "14571", "type": "Genes & Molecular Sequences", "text": [ "GGH" ], "offsets": [ [ 594, 597 ] ], "normalized": [] }, { "id": "14572", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "14573", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 616, 619 ] ], "normalized": [] }, { "id": "14574", "type": "Diseases & Disorders", "text": [ "MTX" ], "offsets": [ [ 616, 619 ] ], "normalized": [] }, { "id": "14575", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "14576", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 671, 673 ] ], "normalized": [] }, { "id": "14577", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 792, 795 ] ], "normalized": [] }, { "id": "14578", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 806, 813 ] ], "normalized": [] }, { "id": "14579", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 927, 930 ] ], "normalized": [] }, { "id": "14580", "type": "Diseases & Disorders", "text": [ "MTX" ], "offsets": [ [ 927, 930 ] ], "normalized": [] }, { "id": "14581", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 968, 978 ] ], "normalized": [] }, { "id": "14582", "type": "SNP & Sequence variations", "text": [ "Ala324Ala" ], "offsets": [ [ 1120, 1129 ] ], "normalized": [] }, { "id": "14583", "type": "SNP & Sequence variations", "text": [ "972 G > A" ], "offsets": [ [ 1131, 1140 ] ], "normalized": [] }, { "id": "14584", "type": "Genes & Molecular Sequences", "text": [ "RFC" ], "offsets": [ [ 1160, 1163 ] ], "normalized": [] }, { "id": "14585", "type": "SNP & Sequence variations", "text": [ "CT" ], "offsets": [ [ 1174, 1176 ] ], "normalized": [] }, { "id": "14586", "type": "SNP & Sequence variations", "text": [ "C3435T" ], "offsets": [ [ 1189, 1195 ] ], "normalized": [] }, { "id": "14587", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "14588", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 1377, 1387 ] ], "normalized": [] }, { "id": "14589", "type": "Genes & Molecular Sequences", "text": [ "GGH" ], "offsets": [ [ 1516, 1519 ] ], "normalized": [] }, { "id": "14590", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1524, 1528 ] ], "normalized": [] }, { "id": "14591", "type": "Genes & Molecular Sequences", "text": [ "MTX" ], "offsets": [ [ 1669, 1672 ] ], "normalized": [] }, { "id": "14592", "type": "Diseases & Disorders", "text": [ "MTX" ], "offsets": [ [ 1669, 1672 ] ], "normalized": [] }, { "id": "14593", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1685, 1687 ] ], "normalized": [] }, { "id": "14594", "type": "", "text": [ "MDR1" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "14595", "type": "", "text": [ "regression" ], "offsets": [ [ 1377, 1387 ] ], "normalized": [] }, { "id": "14597", "type": "", "text": [ "RFC" ], "offsets": [ [ 576, 579 ] ], "normalized": [] }, { "id": "14598", "type": "", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "14600", "type": "", "text": [ "FOLR1" ], "offsets": [ [ 581, 586 ] ], "normalized": [] }, { "id": "14601", "type": "", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "14603", "type": "", "text": [ "FPGS" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "14604", "type": "", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "14606", "type": "", "text": [ "GGH" ], "offsets": [ [ 594, 597 ] ], "normalized": [] }, { "id": "14607", "type": "", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "14609", "type": "", "text": [ "MDR1" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "14610", "type": "", "text": [ "RA" ], "offsets": [ [ 632, 634 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14596", "type": "PA", "arg1_id": "14594", "arg2_id": "14595", "normalized": [] }, { "id": "14599", "type": "SA", "arg1_id": "14597", "arg2_id": "14598", "normalized": [] }, { "id": "14602", "type": "SA", "arg1_id": "14600", "arg2_id": "14601", "normalized": [] }, { "id": "14605", "type": "SA", "arg1_id": "14603", "arg2_id": "14604", "normalized": [] }, { "id": "14608", "type": "SA", "arg1_id": "14606", "arg2_id": "14607", "normalized": [] }, { "id": "14611", "type": "SA", "arg1_id": "14609", "arg2_id": "14610", "normalized": [] } ]

[ { "id": "14614", "type": "title", "text": [ "Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor secretion is impaired in Crohn's disease by nucleotide oligomerization domain 2-dependent and -independent pathways." ], "offsets": [ [ 0, 192 ] ] }, { "id": "14615", "type": "abstract", "text": [ "Pattern recognition receptors (PRRs) are an integral part of the innate immune system and govern the early control of foreign microorganisms. Single nucleotide polymorphisms (SNPs) in the intracellular pattern recognition receptor nucleotide-binding oligomerization domain-containing protein (NOD2, nucleotide oligomerization domain 2) are associated with Crohn's disease (CD). We investigated the impact of NOD2 polymorphisms on cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) in response to Toll-like receptor (TLR) and NOD2 ligands. Based on NOD2 SNP analyses, 41 CD patients and 12 healthy controls were studied. PBMCs were stimulated with NOD2 and TLR ligands. After 18 h culture supernatants were measured using multiplex assays for the presence of human cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha. In CD patients, TLR-induced GM-CSF secretion was impaired by both NOD2-dependent and -independent mechanisms. Moreover, TNF-alpha production was induced by a TLR-2 ligand, but a down-regulatory function by the NOD2 ligand, muramyl dipeptide, was impaired significantly in CD patients. Intracellular TLR ligands had minimal effect on GM-CSF, TNF-alpha and IL-1beta secretion. CD patients with NOD2 mutations were able to secrete TNF-alpha, but not GM-CSF, upon stimulation with NOD2 and TLR-7 ligands. CD patients have impaired GM-CSF secretion via NOD2-dependent and -independent pathways and display an impaired NOD2-dependent down-regulation of TNF-alpha secretion. The defect in GM-CSF secretion suggests a hitherto unknown role of NOD2 in the pathogenesis of CD and is consistent with the hypothesis that impaired GM-CSF secretion in part constitutes a NOD2-dependent disease risk factor." ], "offsets": [ [ 193, 2014 ] ] } ]

[ { "id": "14616", "type": "Genes & Molecular Sequences", "text": [ "Toll-like receptor" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "14617", "type": "Genes & Molecular Sequences", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 27, 75 ] ], "normalized": [] }, { "id": "14618", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 101, 116 ] ], "normalized": [] }, { "id": "14619", "type": "Genes & Molecular Sequences", "text": [ "nucleotide oligomerization domain 2" ], "offsets": [ [ 120, 155 ] ], "normalized": [] }, { "id": "14620", "type": "Genes & Molecular Sequences", "text": [ "Pattern recognition receptors" ], "offsets": [ [ 193, 222 ] ], "normalized": [] }, { "id": "14621", "type": "Genes & Molecular Sequences", "text": [ "PRRs" ], "offsets": [ [ 224, 228 ] ], "normalized": [] }, { "id": "14622", "type": "Genes & Molecular Sequences", "text": [ "nucleotide-binding oligomerization domain-containing protein" ], "offsets": [ [ 424, 484 ] ], "normalized": [] }, { "id": "14623", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "14624", "type": "Genes & Molecular Sequences", "text": [ "nucleotide oligomerization domain 2" ], "offsets": [ [ 492, 527 ] ], "normalized": [] }, { "id": "14625", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 549, 564 ] ], "normalized": [] }, { "id": "14626", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "14627", "type": "SNP & Sequence variations", "text": [ "NOD2 polymorphisms" ], "offsets": [ [ 601, 619 ] ], "normalized": [] }, { "id": "14628", "type": "Genes & Molecular Sequences", "text": [ "NOD2 polymorphisms" ], "offsets": [ [ 601, 619 ] ], "normalized": [] }, { "id": "14629", "type": "Genes & Molecular Sequences", "text": [ "cytokine" ], "offsets": [ [ 623, 631 ] ], "normalized": [] }, { "id": "14630", "type": "Genes & Molecular Sequences", "text": [ "Toll-like receptor" ], "offsets": [ [ 721, 739 ] ], "normalized": [] }, { "id": "14631", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 741, 744 ] ], "normalized": [] }, { "id": "14632", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 750, 754 ] ], "normalized": [] }, { "id": "14633", "type": "SNP & Sequence variations", "text": [ "NOD2 SNP" ], "offsets": [ [ 773, 781 ] ], "normalized": [] }, { "id": "14634", "type": "Genes & Molecular Sequences", "text": [ "NOD2 SNP" ], "offsets": [ [ 773, 781 ] ], "normalized": [] }, { "id": "14635", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 795, 797 ] ], "normalized": [] }, { "id": "14636", "type": "Genes & Molecular Sequences", "text": [ "PBMCs" ], "offsets": [ [ 845, 850 ] ], "normalized": [] }, { "id": "14637", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 872, 876 ] ], "normalized": [] }, { "id": "14638", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 881, 884 ] ], "normalized": [] }, { "id": "14639", "type": "Genes & Molecular Sequences", "text": [ "cytokines" ], "offsets": [ [ 989, 998 ] ], "normalized": [] }, { "id": "14640", "type": "Genes & Molecular Sequences", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 999, 1047 ] ], "normalized": [] }, { "id": "14641", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1049, 1055 ] ], "normalized": [] }, { "id": "14642", "type": "Genes & Molecular Sequences", "text": [ "interleukin" ], "offsets": [ [ 1058, 1069 ] ], "normalized": [] }, { "id": "14643", "type": "Genes & Molecular Sequences", "text": [ "IL)-1 beta" ], "offsets": [ [ 1071, 1081 ] ], "normalized": [] }, { "id": "14644", "type": "Genes & Molecular Sequences", "text": [ "tumour necrosis factor" ], "offsets": [ [ 1086, 1108 ] ], "normalized": [] }, { "id": "14645", "type": "Diseases & Disorders", "text": [ "tumour necrosis factor" ], "offsets": [ [ 1086, 1108 ] ], "normalized": [] }, { "id": "14646", "type": "Genes & Molecular Sequences", "text": [ "TNF)-alpha" ], "offsets": [ [ 1110, 1120 ] ], "normalized": [] }, { "id": "14647", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1125, 1127 ] ], "normalized": [] }, { "id": "14648", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 1138, 1141 ] ], "normalized": [] }, { "id": "14649", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1150, 1156 ] ], "normalized": [] }, { "id": "14650", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "14651", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 1242, 1251 ] ], "normalized": [] }, { "id": "14652", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 1280, 1283 ] ], "normalized": [] }, { "id": "14653", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1332, 1336 ] ], "normalized": [] }, { "id": "14654", "type": "Genes & Molecular Sequences", "text": [ "muramyl dipeptide" ], "offsets": [ [ 1345, 1362 ] ], "normalized": [] }, { "id": "14655", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1394, 1396 ] ], "normalized": [] }, { "id": "14656", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 1421, 1424 ] ], "normalized": [] }, { "id": "14657", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1455, 1461 ] ], "normalized": [] }, { "id": "14658", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 1463, 1472 ] ], "normalized": [] }, { "id": "14659", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 1477, 1485 ] ], "normalized": [] }, { "id": "14660", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14661", "type": "SNP & Sequence variations", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14662", "type": "Genes & Molecular Sequences", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14663", "type": "Diseases & Disorders", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14664", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 1550, 1559 ] ], "normalized": [] }, { "id": "14665", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1569, 1575 ] ], "normalized": [] }, { "id": "14666", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1599, 1603 ] ], "normalized": [] }, { "id": "14667", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 1608, 1611 ] ], "normalized": [] }, { "id": "14668", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1623, 1625 ] ], "normalized": [] }, { "id": "14669", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1649, 1655 ] ], "normalized": [] }, { "id": "14670", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1670, 1674 ] ], "normalized": [] }, { "id": "14671", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1735, 1739 ] ], "normalized": [] }, { "id": "14672", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 1769, 1778 ] ], "normalized": [] }, { "id": "14673", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1804, 1810 ] ], "normalized": [] }, { "id": "14674", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1857, 1861 ] ], "normalized": [] }, { "id": "14675", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 1869, 1881 ] ], "normalized": [] }, { "id": "14676", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1885, 1887 ] ], "normalized": [] }, { "id": "14677", "type": "Genes & Molecular Sequences", "text": [ "GM-CSF" ], "offsets": [ [ 1940, 1946 ] ], "normalized": [] }, { "id": "14678", "type": "Genes & Molecular Sequences", "text": [ "NOD2" ], "offsets": [ [ 1979, 1983 ] ], "normalized": [] }, { "id": "14679", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1994, 2001 ] ], "normalized": [] }, { "id": "14680", "type": "", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 27, 75 ] ], "normalized": [] }, { "id": "14681", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 101, 116 ] ], "normalized": [] }, { "id": "14683", "type": "", "text": [ "Toll-like receptor" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "14684", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 101, 116 ] ], "normalized": [] }, { "id": "14686", "type": "", "text": [ "NOD2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "14687", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 549, 564 ] ], "normalized": [] }, { "id": "14689", "type": "", "text": [ "NOD2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "14690", "type": "", "text": [ "CD" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "14692", "type": "", "text": [ "nucleotide oligomerization domain 2" ], "offsets": [ [ 492, 527 ] ], "normalized": [] }, { "id": "14693", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 549, 564 ] ], "normalized": [] }, { "id": "14695", "type": "", "text": [ "nucleotide oligomerization domain 2" ], "offsets": [ [ 492, 527 ] ], "normalized": [] }, { "id": "14696", "type": "", "text": [ "CD" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "14698", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1150, 1156 ] ], "normalized": [] }, { "id": "14699", "type": "", "text": [ "CD" ], "offsets": [ [ 1125, 1127 ] ], "normalized": [] }, { "id": "14701", "type": "", "text": [ "TLR" ], "offsets": [ [ 1138, 1141 ] ], "normalized": [] }, { "id": "14702", "type": "", "text": [ "CD" ], "offsets": [ [ 1125, 1127 ] ], "normalized": [] }, { "id": "14704", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1332, 1336 ] ], "normalized": [] }, { "id": "14705", "type": "", "text": [ "CD" ], "offsets": [ [ 1394, 1396 ] ], "normalized": [] }, { "id": "14707", "type": "", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14708", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14710", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1649, 1655 ] ], "normalized": [] }, { "id": "14711", "type": "", "text": [ "CD" ], "offsets": [ [ 1623, 1625 ] ], "normalized": [] }, { "id": "14713", "type": "", "text": [ "TNF-alpha" ], "offsets": [ [ 1769, 1778 ] ], "normalized": [] }, { "id": "14714", "type": "", "text": [ "CD" ], "offsets": [ [ 1623, 1625 ] ], "normalized": [] }, { "id": "14716", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1735, 1739 ] ], "normalized": [] }, { "id": "14717", "type": "", "text": [ "CD" ], "offsets": [ [ 1623, 1625 ] ], "normalized": [] }, { "id": "14719", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1940, 1946 ] ], "normalized": [] }, { "id": "14720", "type": "", "text": [ "CD" ], "offsets": [ [ 1885, 1887 ] ], "normalized": [] }, { "id": "14722", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1979, 1983 ] ], "normalized": [] }, { "id": "14723", "type": "", "text": [ "CD" ], "offsets": [ [ 1885, 1887 ] ], "normalized": [] }, { "id": "14725", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1049, 1055 ] ], "normalized": [] }, { "id": "14726", "type": "", "text": [ "tumour necrosis factor" ], "offsets": [ [ 1086, 1108 ] ], "normalized": [] }, { "id": "14728", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1569, 1575 ] ], "normalized": [] }, { "id": "14729", "type": "", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14731", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1599, 1603 ] ], "normalized": [] }, { "id": "14732", "type": "", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14734", "type": "", "text": [ "TNF-alpha" ], "offsets": [ [ 1550, 1559 ] ], "normalized": [] }, { "id": "14735", "type": "", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14737", "type": "", "text": [ "TLR" ], "offsets": [ [ 1608, 1611 ] ], "normalized": [] }, { "id": "14738", "type": "", "text": [ "NOD2 mutations" ], "offsets": [ [ 1514, 1528 ] ], "normalized": [] }, { "id": "14740", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1940, 1946 ] ], "normalized": [] }, { "id": "14741", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 1869, 1881 ] ], "normalized": [] }, { "id": "14743", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1940, 1946 ] ], "normalized": [] }, { "id": "14744", "type": "", "text": [ "disease" ], "offsets": [ [ 1994, 2001 ] ], "normalized": [] }, { "id": "14746", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1979, 1983 ] ], "normalized": [] }, { "id": "14747", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 1869, 1881 ] ], "normalized": [] }, { "id": "14749", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1979, 1983 ] ], "normalized": [] }, { "id": "14750", "type": "", "text": [ "disease" ], "offsets": [ [ 1994, 2001 ] ], "normalized": [] }, { "id": "14752", "type": "", "text": [ "nucleotide oligomerization domain 2" ], "offsets": [ [ 120, 155 ] ], "normalized": [] }, { "id": "14753", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 101, 116 ] ], "normalized": [] }, { "id": "14755", "type": "", "text": [ "NOD2 SNP" ], "offsets": [ [ 773, 781 ] ], "normalized": [] }, { "id": "14756", "type": "", "text": [ "CD" ], "offsets": [ [ 795, 797 ] ], "normalized": [] }, { "id": "14758", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "14759", "type": "", "text": [ "CD" ], "offsets": [ [ 1125, 1127 ] ], "normalized": [] }, { "id": "14761", "type": "", "text": [ "TLR" ], "offsets": [ [ 1280, 1283 ] ], "normalized": [] }, { "id": "14762", "type": "", "text": [ "CD" ], "offsets": [ [ 1394, 1396 ] ], "normalized": [] }, { "id": "14764", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1569, 1575 ] ], "normalized": [] }, { "id": "14765", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14767", "type": "", "text": [ "TLR" ], "offsets": [ [ 1608, 1611 ] ], "normalized": [] }, { "id": "14768", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14770", "type": "", "text": [ "nucleotide-binding oligomerization domain-containing protein" ], "offsets": [ [ 424, 484 ] ], "normalized": [] }, { "id": "14771", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 549, 564 ] ], "normalized": [] }, { "id": "14773", "type": "", "text": [ "nucleotide-binding oligomerization domain-containing protein" ], "offsets": [ [ 424, 484 ] ], "normalized": [] }, { "id": "14774", "type": "", "text": [ "CD" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "14776", "type": "", "text": [ "TNF-alpha" ], "offsets": [ [ 1242, 1251 ] ], "normalized": [] }, { "id": "14777", "type": "", "text": [ "CD" ], "offsets": [ [ 1394, 1396 ] ], "normalized": [] }, { "id": "14779", "type": "", "text": [ "muramyl dipeptide" ], "offsets": [ [ 1345, 1362 ] ], "normalized": [] }, { "id": "14780", "type": "", "text": [ "CD" ], "offsets": [ [ 1394, 1396 ] ], "normalized": [] }, { "id": "14782", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1569, 1575 ] ], "normalized": [] }, { "id": "14783", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14785", "type": "", "text": [ "NOD2" ], "offsets": [ [ 1599, 1603 ] ], "normalized": [] }, { "id": "14786", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] }, { "id": "14788", "type": "", "text": [ "TNF-alpha" ], "offsets": [ [ 1550, 1559 ] ], "normalized": [] }, { "id": "14789", "type": "", "text": [ "CD" ], "offsets": [ [ 1497, 1499 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14682", "type": "PA", "arg1_id": "14680", "arg2_id": "14681", "normalized": [] }, { "id": "14685", "type": "PA", "arg1_id": "14683", "arg2_id": "14684", "normalized": [] }, { "id": "14688", "type": "PA", "arg1_id": "14686", "arg2_id": "14687", "normalized": [] }, { "id": "14691", "type": "PA", "arg1_id": "14689", "arg2_id": "14690", "normalized": [] }, { "id": "14694", "type": "PA", "arg1_id": "14692", "arg2_id": "14693", "normalized": [] }, { "id": "14697", "type": "PA", "arg1_id": "14695", "arg2_id": "14696", "normalized": [] }, { "id": "14700", "type": "PA", "arg1_id": "14698", "arg2_id": "14699", "normalized": [] }, { "id": "14703", "type": "PA", "arg1_id": "14701", "arg2_id": "14702", "normalized": [] }, { "id": "14706", "type": "PA", "arg1_id": "14704", "arg2_id": "14705", "normalized": [] }, { "id": "14709", "type": "PA", "arg1_id": "14707", "arg2_id": "14708", "normalized": [] }, { "id": "14712", "type": "PA", "arg1_id": "14710", "arg2_id": "14711", "normalized": [] }, { "id": "14715", "type": "PA", "arg1_id": "14713", "arg2_id": "14714", "normalized": [] }, { "id": "14718", "type": "PA", "arg1_id": "14716", "arg2_id": "14717", "normalized": [] }, { "id": "14721", "type": "PA", "arg1_id": "14719", "arg2_id": "14720", "normalized": [] }, { "id": "14724", "type": "PA", "arg1_id": "14722", "arg2_id": "14723", "normalized": [] }, { "id": "14727", "type": "PA", "arg1_id": "14725", "arg2_id": "14726", "normalized": [] }, { "id": "14730", "type": "PA", "arg1_id": "14728", "arg2_id": "14729", "normalized": [] }, { "id": "14733", "type": "PA", "arg1_id": "14731", "arg2_id": "14732", "normalized": [] }, { "id": "14736", "type": "PA", "arg1_id": "14734", "arg2_id": "14735", "normalized": [] }, { "id": "14739", "type": "PA", "arg1_id": "14737", "arg2_id": "14738", "normalized": [] }, { "id": "14742", "type": "PA", "arg1_id": "14740", "arg2_id": "14741", "normalized": [] }, { "id": "14745", "type": "PA", "arg1_id": "14743", "arg2_id": "14744", "normalized": [] }, { "id": "14748", "type": "PA", "arg1_id": "14746", "arg2_id": "14747", "normalized": [] }, { "id": "14751", "type": "PA", "arg1_id": "14749", "arg2_id": "14750", "normalized": [] }, { "id": "14754", "type": "PA", "arg1_id": "14752", "arg2_id": "14753", "normalized": [] }, { "id": "14757", "type": "SA", "arg1_id": "14755", "arg2_id": "14756", "normalized": [] }, { "id": "14760", "type": "PA", "arg1_id": "14758", "arg2_id": "14759", "normalized": [] }, { "id": "14763", "type": "PA", "arg1_id": "14761", "arg2_id": "14762", "normalized": [] }, { "id": "14766", "type": "PA", "arg1_id": "14764", "arg2_id": "14765", "normalized": [] }, { "id": "14769", "type": "PA", "arg1_id": "14767", "arg2_id": "14768", "normalized": [] }, { "id": "14772", "type": "PA", "arg1_id": "14770", "arg2_id": "14771", "normalized": [] }, { "id": "14775", "type": "PA", "arg1_id": "14773", "arg2_id": "14774", "normalized": [] }, { "id": "14778", "type": "PA", "arg1_id": "14776", "arg2_id": "14777", "normalized": [] }, { "id": "14781", "type": "PA", "arg1_id": "14779", "arg2_id": "14780", "normalized": [] }, { "id": "14784", "type": "NA", "arg1_id": "14782", "arg2_id": "14783", "normalized": [] }, { "id": "14787", "type": "PA", "arg1_id": "14785", "arg2_id": "14786", "normalized": [] }, { "id": "14790", "type": "PA", "arg1_id": "14788", "arg2_id": "14789", "normalized": [] } ]

[ { "id": "14793", "type": "title", "text": [ "Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples." ], "offsets": [ [ 0, 119 ] ] }, { "id": "14794", "type": "abstract", "text": [ "BACKGROUND: Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers. RESULTS: We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent vs control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance. CONCLUSION: The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers." ], "offsets": [ [ 120, 1945 ] ] } ]

[ { "id": "14795", "type": "Diseases & Disorders", "text": [ "substance dependence" ], "offsets": [ [ 28, 48 ] ], "normalized": [] }, { "id": "14796", "type": "Diseases & Disorders", "text": [ "Dependences on" ], "offsets": [ [ 132, 146 ] ], "normalized": [] }, { "id": "14797", "type": "Diseases & Disorders", "text": [ "disorders" ], "offsets": [ [ 204, 213 ] ], "normalized": [] }, { "id": "14798", "type": "Diseases & Disorders", "text": [ "substance dependent" ], "offsets": [ [ 621, 640 ] ], "normalized": [] }, { "id": "14799", "type": "Diseases & Disorders", "text": [ "substance dependence" ], "offsets": [ [ 782, 802 ] ], "normalized": [] }, { "id": "14800", "type": "Diseases & Disorders", "text": [ "substance dependent" ], "offsets": [ [ 1215, 1234 ] ], "normalized": [] }, { "id": "14801", "type": "Diseases & Disorders", "text": [ "tags" ], "offsets": [ [ 1473, 1477 ] ], "normalized": [] }, { "id": "14802", "type": "Diseases & Disorders", "text": [ "substance dependence" ], "offsets": [ [ 1864, 1884 ] ], "normalized": [] } ]

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[ { "id": "14805", "type": "title", "text": [ "Relation of genetic variation in the gene coding for C-reactive protein with its plasma protein concentrations: findings from the Women's Health Initiative Observational Cohort." ], "offsets": [ [ 0, 177 ] ] }, { "id": "14806", "type": "abstract", "text": [ "BACKGROUND: Although common genetic variants of the CRP gene (C-reactive protein, pentraxin related) have been associated with plasma concentrations of high-sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few studies have comprehensively assessed this association in well-characterized multiethnic populations. METHODS: In a case-control study of diabetes nested in the Women's Health Initiative Observational Cohort, we comprehensively evaluated the association of genetic variation in CRP with plasma hsCRP concentrations. Thirteen haplotype-tagging single-nucleotide polymorphisms (tSNPs) were identified and subsequently genotyped in 3782 postmenopausal women. RESULTS: The allele frequencies for these tSNPs and the haplotype blocks defined by these tSNPs varied significantly by ethnic group (P < 0.0001). Consistent with prior studies of whites, rs3093068, rs1130864, and rs1417938 were significantly associated with higher hsCRP concentrations (geometric-mean increase per minor-allele change, 1.20-1.25 mg/L), and rs1205 and rs1800947 were significantly associated with lower hsCRP values (decrease of 1.28-1.48 mg/L). The associations with rs3093068 and rs1205 appeared to be stronger in Asians/Pacific Islanders than in whites (geometric-mean increase, 1.65 mg/L vs 1.25 mg/L, respectively). Minor alleles at rs3093075 and rs3093059 were associated with substantially increased hsCRP concentrations, whereas rs1800947 was associated with lower hsCRP values. All haplotype-based association results tended to be consistent with the associations seen with single CRP SNPs. CONCLUSIONS: Our large multiethnic case-control study of postmenopausal women provides evidence that common genetic variants in the CRP gene are substantially associated with plasma hsCRP concentrations in this case-control subcohort. The data also suggest ethnic variations in these associations." ], "offsets": [ [ 178, 2086 ] ] } ]

[ { "id": "14807", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 53, 71 ] ], "normalized": [] }, { "id": "14808", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 230, 233 ] ], "normalized": [] }, { "id": "14809", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 240, 258 ] ], "normalized": [] }, { "id": "14810", "type": "Genes & Molecular Sequences", "text": [ "high-sensitivity CRP" ], "offsets": [ [ 330, 350 ] ], "normalized": [] }, { "id": "14811", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 352, 357 ] ], "normalized": [] }, { "id": "14812", "type": "Diseases & Disorders", "text": [ "diabetes" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "14813", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 694, 697 ] ], "normalized": [] }, { "id": "14814", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "14815", "type": "Diseases & Disorders", "text": [ "blocks" ], "offsets": [ [ 938, 944 ] ], "normalized": [] }, { "id": "14816", "type": "SNP & Sequence variations", "text": [ "rs3093068" ], "offsets": [ [ 1060, 1069 ] ], "normalized": [] }, { "id": "14817", "type": "SNP & Sequence variations", "text": [ "rs1130864" ], "offsets": [ [ 1071, 1080 ] ], "normalized": [] }, { "id": "14818", "type": "SNP & Sequence variations", "text": [ "rs1417938" ], "offsets": [ [ 1086, 1095 ] ], "normalized": [] }, { "id": "14819", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 1138, 1143 ] ], "normalized": [] }, { "id": "14820", "type": "SNP & Sequence variations", "text": [ "rs1205" ], "offsets": [ [ 1230, 1236 ] ], "normalized": [] }, { "id": "14821", "type": "SNP & Sequence variations", "text": [ "rs1800947" ], "offsets": [ [ 1241, 1250 ] ], "normalized": [] }, { "id": "14822", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 1292, 1297 ] ], "normalized": [] }, { "id": "14823", "type": "SNP & Sequence variations", "text": [ "rs3093068" ], "offsets": [ [ 1357, 1366 ] ], "normalized": [] }, { "id": "14824", "type": "SNP & Sequence variations", "text": [ "rs1205" ], "offsets": [ [ 1371, 1377 ] ], "normalized": [] }, { "id": "14825", "type": "Diseases & Disorders", "text": [ "Minor" ], "offsets": [ [ 1510, 1515 ] ], "normalized": [] }, { "id": "14826", "type": "SNP & Sequence variations", "text": [ "rs3093075" ], "offsets": [ [ 1527, 1536 ] ], "normalized": [] }, { "id": "14827", "type": "SNP & Sequence variations", "text": [ "rs3093059" ], "offsets": [ [ 1541, 1550 ] ], "normalized": [] }, { "id": "14828", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 1596, 1601 ] ], "normalized": [] }, { "id": "14829", "type": "SNP & Sequence variations", "text": [ "rs1800947" ], "offsets": [ [ 1626, 1635 ] ], "normalized": [] }, { "id": "14830", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 1662, 1667 ] ], "normalized": [] }, { "id": "14831", "type": "SNP & Sequence variations", "text": [ "CRP SNPs" ], "offsets": [ [ 1779, 1787 ] ], "normalized": [] }, { "id": "14832", "type": "Genes & Molecular Sequences", "text": [ "CRP SNPs" ], "offsets": [ [ 1779, 1787 ] ], "normalized": [] }, { "id": "14833", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 1921, 1924 ] ], "normalized": [] }, { "id": "14834", "type": "Genes & Molecular Sequences", "text": [ "hsCRP" ], "offsets": [ [ 1971, 1976 ] ], "normalized": [] }, { "id": "14835", "type": "", "text": [ "CRP" ], "offsets": [ [ 694, 697 ] ], "normalized": [] }, { "id": "14836", "type": "", "text": [ "diabetes" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "14838", "type": "", "text": [ "hsCRP" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "14839", "type": "", "text": [ "diabetes" ], "offsets": [ [ 554, 562 ] ], "normalized": [] } ]

[]

[]

[ { "id": "14837", "type": "PA", "arg1_id": "14835", "arg2_id": "14836", "normalized": [] }, { "id": "14840", "type": "PA", "arg1_id": "14838", "arg2_id": "14839", "normalized": [] } ]

[ { "id": "14843", "type": "title", "text": [ "Susceptibility of XRCC3, XPD, and X" ], "offsets": [ [ 0, 35 ] ] }, { "id": "14844", "type": "abstract", "text": [ "OBJECTIVE: DNA repair genes play a key role in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of XRCC3 and xeroderma pigmentosum, complementation group D and G (XPD, XPG), contribute to carcinogenesis. In this study, we investigated the correlation between cervical carcinoma risk and XRCC3, XPD, XPG genetic variants. METHODS: A case-control study of 400 cases including 200 carcinoma, 200 cervical intraepithelial neoplasia (CIN) and 200 normal women was performed. Four single nucleotide polymorphisms (SNPs) (XRCC3 Thr241Met, XPG His1104Asp, XPD Asp312Asn, and XPD Lys751Gln) were genotyped by mismatch amplification polymerase chain reaction. RESULTS: Women carrying homozygous Asp1104Asp genotypes had a significantly decreased risk of cervical or cervical squamous cell carcinoma compared to His1104Asp or His1104His genotypes. Similarly, XPD Asn312Asn (AA) reduced the risk of cervical or cervical squamous cell carcinoma. No association of XRCC3 Thr241Met or XPD Lys751Gln and cervical carcinoma was found. None of the 4 SNPs influenced the risk of CIN in our study. CONCLUSION: Our results support the hypothesis that genetic variations in DNA repair genes may contribute to an inherited genetic susceptibility to cervical carcinoma.CI - Copyright 2008 S. Karger AG, Basel." ], "offsets": [ [ 36, 1362 ] ] } ]

[ { "id": "14845", "type": "Genes & Molecular Sequences", "text": [ "XRCC3" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "14846", "type": "Genes & Molecular Sequences", "text": [ "XPD" ], "offsets": [ [ 25, 28 ] ], "normalized": [] }, { "id": "14847", "type": "SNP & Sequence variations", "text": [ "XPD" ], "offsets": [ [ 25, 28 ] ], "normalized": [] }, { "id": "14848", "type": "Diseases & Disorders", "text": [ "XPD" ], "offsets": [ [ 25, 28 ] ], "normalized": [] }, { "id": "14849", "type": "Genes & Molecular Sequences", "text": [ "X O" ], "offsets": [ [ 34, 37 ] ], "normalized": [] }, { "id": "14850", "type": "Diseases & Disorders", "text": [ "X O" ], "offsets": [ [ 34, 37 ] ], "normalized": [] }, { "id": "14851", "type": "Diseases & Disorders", "text": [ "genes play a key r" ], "offsets": [ [ 58, 76 ] ], "normalized": [] }, { "id": "14852", "type": "Genes & Molecular Sequences", "text": [ "tatio" ], "offsets": [ [ 218, 223 ] ], "normalized": [] }, { "id": "14853", "type": "Diseases & Disorders", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14854", "type": "Genes & Molecular Sequences", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14855", "type": "Genes & Molecular Sequences", "text": [ "n t" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "14856", "type": "SNP & Sequence variations", "text": [ "n t" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "14857", "type": "Diseases & Disorders", "text": [ "n t" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "14858", "type": "Genes & Molecular Sequences", "text": [ "s s" ], "offsets": [ [ 287, 290 ] ], "normalized": [] }, { "id": "14859", "type": "Diseases & Disorders", "text": [ "s s" ], "offsets": [ [ 287, 290 ] ], "normalized": [] }, { "id": "14860", "type": "Diseases & Disorders", "text": [ "ated the corre" ], "offsets": [ [ 307, 321 ] ], "normalized": [] }, { "id": "14861", "type": "Diseases & Disorders", "text": [ "G genetic variants" ], "offsets": [ [ 378, 396 ] ], "normalized": [] }, { "id": "14862", "type": "Genes & Molecular Sequences", "text": [ " A ca" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "14863", "type": "Genes & Molecular Sequences", "text": [ "-co" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14864", "type": "SNP & Sequence variations", "text": [ "-co" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14865", "type": "Diseases & Disorders", "text": [ "-co" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14866", "type": "Genes & Molecular Sequences", "text": [ "rol" ], "offsets": [ [ 418, 421 ] ], "normalized": [] }, { "id": "14867", "type": "Diseases & Disorders", "text": [ "rol" ], "offsets": [ [ 418, 421 ] ], "normalized": [] }, { "id": "14868", "type": "Diseases & Disorders", "text": [ "oplasia (" ], "offsets": [ [ 497, 506 ] ], "normalized": [] }, { "id": "14869", "type": "Diseases & Disorders", "text": [ "nd 200 normal women was performed." ], "offsets": [ [ 512, 546 ] ], "normalized": [] }, { "id": "14870", "type": "Genes & Molecular Sequences", "text": [ "our" ], "offsets": [ [ 548, 551 ] ], "normalized": [] }, { "id": "14871", "type": "Diseases & Disorders", "text": [ "our" ], "offsets": [ [ 548, 551 ] ], "normalized": [] }, { "id": "14872", "type": "SNP & Sequence variations", "text": [ "2Asn, and XPD L" ], "offsets": [ [ 634, 649 ] ], "normalized": [] }, { "id": "14873", "type": "Genes & Molecular Sequences", "text": [ "2Asn, and XPD L" ], "offsets": [ [ 634, 649 ] ], "normalized": [] }, { "id": "14874", "type": "SNP & Sequence variations", "text": [ "751Gln) were g" ], "offsets": [ [ 651, 665 ] ], "normalized": [] }, { "id": "14875", "type": "Genes & Molecular Sequences", "text": [ "751Gln) were g" ], "offsets": [ [ 651, 665 ] ], "normalized": [] }, { "id": "14876", "type": "Diseases & Disorders", "text": [ "751Gln) were g" ], "offsets": [ [ 651, 665 ] ], "normalized": [] }, { "id": "14877", "type": "SNP & Sequence variations", "text": [ "otyped by mis" ], "offsets": [ [ 667, 680 ] ], "normalized": [] }, { "id": "14878", "type": "Genes & Molecular Sequences", "text": [ "otyped by mis" ], "offsets": [ [ 667, 680 ] ], "normalized": [] }, { "id": "14879", "type": "Diseases & Disorders", "text": [ "otyped by mis" ], "offsets": [ [ 667, 680 ] ], "normalized": [] }, { "id": "14880", "type": "SNP & Sequence variations", "text": [ "amplification" ], "offsets": [ [ 686, 699 ] ], "normalized": [] }, { "id": "14881", "type": "Genes & Molecular Sequences", "text": [ "amplification" ], "offsets": [ [ 686, 699 ] ], "normalized": [] }, { "id": "14882", "type": "Diseases & Disorders", "text": [ "amplification" ], "offsets": [ [ 686, 699 ] ], "normalized": [] }, { "id": "14883", "type": "Diseases & Disorders", "text": [ "ESULTS: Women" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "14884", "type": "SNP & Sequence variations", "text": [ "ecreased r" ], "offsets": [ [ 804, 814 ] ], "normalized": [] }, { "id": "14885", "type": "Diseases & Disorders", "text": [ "ma compa" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "14886", "type": "Diseases & Disorders", "text": [ "to His1104Asp or His1104His geno" ], "offsets": [ [ 875, 907 ] ], "normalized": [] }, { "id": "14887", "type": "SNP & Sequence variations", "text": [ "rly, XPD A" ], "offsets": [ [ 920, 930 ] ], "normalized": [] }, { "id": "14888", "type": "SNP & Sequence variations", "text": [ "2Asn (AA) " ], "offsets": [ [ 934, 944 ] ], "normalized": [] }, { "id": "14889", "type": "SNP & Sequence variations", "text": [ "vical or cerv" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "14890", "type": "Genes & Molecular Sequences", "text": [ "vical or cerv" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "14891", "type": "Diseases & Disorders", "text": [ "vical or cerv" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "14892", "type": "SNP & Sequence variations", "text": [ "al" ], "offsets": [ [ 982, 984 ] ], "normalized": [] }, { "id": "14893", "type": "Diseases & Disorders", "text": [ "ma. No a" ], "offsets": [ [ 1006, 1014 ] ], "normalized": [] }, { "id": "14894", "type": "Diseases & Disorders", "text": [ "iation of XRCC3 Thr241Met or XPD" ], "offsets": [ [ 1018, 1050 ] ], "normalized": [] }, { "id": "14895", "type": "SNP & Sequence variations", "text": [ "cal carcinoma w" ], "offsets": [ [ 1070, 1085 ] ], "normalized": [] }, { "id": "14896", "type": "Genes & Molecular Sequences", "text": [ "cal carcinoma w" ], "offsets": [ [ 1070, 1085 ] ], "normalized": [] }, { "id": "14897", "type": "SNP & Sequence variations", "text": [ "ound. None of" ], "offsets": [ [ 1089, 1102 ] ], "normalized": [] }, { "id": "14898", "type": "Genes & Molecular Sequences", "text": [ "ound. None of" ], "offsets": [ [ 1089, 1102 ] ], "normalized": [] }, { "id": "14899", "type": "Diseases & Disorders", "text": [ "ound. None of" ], "offsets": [ [ 1089, 1102 ] ], "normalized": [] }, { "id": "14900", "type": "Diseases & Disorders", "text": [ "4 SNPs influenced " ], "offsets": [ [ 1107, 1125 ] ], "normalized": [] }, { "id": "14901", "type": "Genes & Molecular Sequences", "text": [ "sup" ], "offsets": [ [ 1179, 1182 ] ], "normalized": [] }, { "id": "14902", "type": "Diseases & Disorders", "text": [ "sup" ], "offsets": [ [ 1179, 1182 ] ], "normalized": [] }, { "id": "14903", "type": "Diseases & Disorders", "text": [ "Karger AG, Basel." ], "offsets": [ [ 1345, 1363 ] ], "normalized": [] }, { "id": "14904", "type": "", "text": [ "n t" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "14905", "type": "", "text": [ "ated the corre" ], "offsets": [ [ 307, 321 ] ], "normalized": [] }, { "id": "14907", "type": "", "text": [ "s s" ], "offsets": [ [ 287, 290 ] ], "normalized": [] }, { "id": "14908", "type": "", "text": [ "ated the corre" ], "offsets": [ [ 307, 321 ] ], "normalized": [] }, { "id": "14910", "type": "", "text": [ "tatio" ], "offsets": [ [ 218, 223 ] ], "normalized": [] }, { "id": "14911", "type": "", "text": [ "ated the corre" ], "offsets": [ [ 307, 321 ] ], "normalized": [] }, { "id": "14913", "type": "", "text": [ "our" ], "offsets": [ [ 548, 551 ] ], "normalized": [] }, { "id": "14914", "type": "", "text": [ "oplasia (" ], "offsets": [ [ 497, 506 ] ], "normalized": [] }, { "id": "14916", "type": "", "text": [ "our" ], "offsets": [ [ 548, 551 ] ], "normalized": [] }, { "id": "14917", "type": "", "text": [ "nd 200 normal women was performed." ], "offsets": [ [ 512, 546 ] ], "normalized": [] }, { "id": "14919", "type": "", "text": [ "ecreased r" ], "offsets": [ [ 804, 814 ] ], "normalized": [] }, { "id": "14920", "type": "", "text": [ "ma compa" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "14922", "type": "", "text": [ "ecreased r" ], "offsets": [ [ 804, 814 ] ], "normalized": [] }, { "id": "14923", "type": "", "text": [ "to His1104Asp or His1104His geno" ], "offsets": [ [ 875, 907 ] ], "normalized": [] }, { "id": "14925", "type": "", "text": [ "vical or cerv" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "14926", "type": "", "text": [ "ma. No a" ], "offsets": [ [ 1006, 1014 ] ], "normalized": [] }, { "id": "14928", "type": "", "text": [ "vical or cerv" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "14929", "type": "", "text": [ "iation of XRCC3 Thr241Met or XPD" ], "offsets": [ [ 1018, 1050 ] ], "normalized": [] }, { "id": "14931", "type": "", "text": [ "ound. None of" ], "offsets": [ [ 1089, 1102 ] ], "normalized": [] }, { "id": "14932", "type": "", "text": [ "4 SNPs influenced " ], "offsets": [ [ 1107, 1125 ] ], "normalized": [] }, { "id": "14934", "type": "", "text": [ "cal carcinoma w" ], "offsets": [ [ 1070, 1085 ] ], "normalized": [] }, { "id": "14935", "type": "", "text": [ "4 SNPs influenced " ], "offsets": [ [ 1107, 1125 ] ], "normalized": [] }, { "id": "14937", "type": "", "text": [ "XPD" ], "offsets": [ [ 25, 28 ] ], "normalized": [] }, { "id": "14938", "type": "", "text": [ "genes play a key r" ], "offsets": [ [ 58, 76 ] ], "normalized": [] }, { "id": "14940", "type": "", "text": [ "X O" ], "offsets": [ [ 34, 37 ] ], "normalized": [] }, { "id": "14941", "type": "", "text": [ "genes play a key r" ], "offsets": [ [ 58, 76 ] ], "normalized": [] }, { "id": "14943", "type": "", "text": [ "XRCC3" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "14944", "type": "", "text": [ "genes play a key r" ], "offsets": [ [ 58, 76 ] ], "normalized": [] }, { "id": "14946", "type": "", "text": [ "n t" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "14947", "type": "", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14949", "type": "", "text": [ "s s" ], "offsets": [ [ 287, 290 ] ], "normalized": [] }, { "id": "14950", "type": "", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14952", "type": "", "text": [ "tatio" ], "offsets": [ [ 218, 223 ] ], "normalized": [] }, { "id": "14953", "type": "", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14955", "type": "", "text": [ "-co" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "14956", "type": "", "text": [ "G genetic variants" ], "offsets": [ [ 378, 396 ] ], "normalized": [] }, { "id": "14958", "type": "", "text": [ "rol" ], "offsets": [ [ 418, 421 ] ], "normalized": [] }, { "id": "14959", "type": "", "text": [ "G genetic variants" ], "offsets": [ [ 378, 396 ] ], "normalized": [] }, { "id": "14961", "type": "", "text": [ " A ca" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "14962", "type": "", "text": [ "G genetic variants" ], "offsets": [ [ 378, 396 ] ], "normalized": [] }, { "id": "14964", "type": "", "text": [ "amplification" ], "offsets": [ [ 686, 699 ] ], "normalized": [] }, { "id": "14965", "type": "", "text": [ "ESULTS: Women" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "14967", "type": "", "text": [ "751Gln) were g" ], "offsets": [ [ 651, 665 ] ], "normalized": [] }, { "id": "14968", "type": "", "text": [ "ESULTS: Women" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "14970", "type": "", "text": [ "2Asn, and XPD L" ], "offsets": [ [ 634, 649 ] ], "normalized": [] }, { "id": "14971", "type": "", "text": [ "ESULTS: Women" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "14973", "type": "", "text": [ "ound. None of" ], "offsets": [ [ 1089, 1102 ] ], "normalized": [] }, { "id": "14974", "type": "", "text": [ "4 SNPs influenced " ], "offsets": [ [ 1107, 1125 ] ], "normalized": [] }, { "id": "14976", "type": "", "text": [ "cal carcinoma w" ], "offsets": [ [ 1070, 1085 ] ], "normalized": [] }, { "id": "14977", "type": "", "text": [ "4 SNPs influenced " ], "offsets": [ [ 1107, 1125 ] ], "normalized": [] }, { "id": "14979", "type": "", "text": [ "up D and G (XPD, XPG)" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "14980", "type": "", "text": [ "ated the corre" ], "offsets": [ [ 307, 321 ] ], "normalized": [] }, { "id": "14982", "type": "", "text": [ "rly, XPD A" ], "offsets": [ [ 920, 930 ] ], "normalized": [] }, { "id": "14983", "type": "", "text": [ "to His1104Asp or His1104His geno" ], "offsets": [ [ 875, 907 ] ], "normalized": [] }, { "id": "14985", "type": "", "text": [ "2Asn (AA) " ], "offsets": [ [ 934, 944 ] ], "normalized": [] }, { "id": "14986", "type": "", "text": [ "to His1104Asp or His1104His geno" ], "offsets": [ [ 875, 907 ] ], "normalized": [] }, { "id": "14988", "type": "", "text": [ "rly, XPD A" ], "offsets": [ [ 920, 930 ] ], "normalized": [] }, { "id": "14989", "type": "", "text": [ "ma compa" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "14991", "type": "", "text": [ "2Asn (AA) " ], "offsets": [ [ 934, 944 ] ], "normalized": [] }, { "id": "14992", "type": "", "text": [ "ma compa" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "14994", "type": "", "text": [ "al" ], "offsets": [ [ 982, 984 ] ], "normalized": [] }, { "id": "14995", "type": "", "text": [ "ma. No a" ], "offsets": [ [ 1006, 1014 ] ], "normalized": [] }, { "id": "14997", "type": "", "text": [ "al" ], "offsets": [ [ 982, 984 ] ], "normalized": [] }, { "id": "14998", "type": "", "text": [ "iation of XRCC3 Thr241Met or XPD" ], "offsets": [ [ 1018, 1050 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "15002", "type": "title", "text": [ "A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men." ], "offsets": [ [ 0, 85 ] ] }, { "id": "15003", "type": "abstract", "text": [ "This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P=0.006, P=0.001 and P=0.002, respectively)." ], "offsets": [ [ 86, 604 ] ] } ]

[ { "id": "15004", "type": "Genes & Molecular Sequences", "text": [ "CYP4F2" ], "offsets": [ [ 19, 25 ] ], "normalized": [] }, { "id": "15005", "type": "Diseases & Disorders", "text": [ "myocardial infarction" ], "offsets": [ [ 47, 68 ] ], "normalized": [] }, { "id": "15006", "type": "Genes & Molecular Sequences", "text": [ "CYP4F2" ], "offsets": [ [ 131, 137 ] ], "normalized": [] }, { "id": "15007", "type": "Diseases & Disorders", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15008", "type": "Diseases & Disorders", "text": [ "MI" ], "offsets": [ [ 170, 172 ] ], "normalized": [] }, { "id": "15009", "type": "Diseases & Disorders", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15010", "type": "SNP & Sequence variations", "text": [ "rs3093105" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "15011", "type": "SNP & Sequence variations", "text": [ "rs3093135" ], "offsets": [ [ 314, 323 ] ], "normalized": [] }, { "id": "15012", "type": "SNP & Sequence variations", "text": [ "rs1558139" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "15013", "type": "SNP & Sequence variations", "text": [ "rs2108622" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "15014", "type": "SNP & Sequence variations", "text": [ "rs3093200" ], "offsets": [ [ 347, 356 ] ], "normalized": [] }, { "id": "15015", "type": "SNP & Sequence variations", "text": [ "G allele" ], "offsets": [ [ 368, 376 ] ], "normalized": [] }, { "id": "15016", "type": "SNP & Sequence variations", "text": [ "rs2108622" ], "offsets": [ [ 390, 399 ] ], "normalized": [] }, { "id": "15017", "type": "SNP & Sequence variations", "text": [ "T-C-G haplotype" ], "offsets": [ [ 421, 436 ] ], "normalized": [] }, { "id": "15018", "type": "SNP & Sequence variations", "text": [ "T-C-A haplotype" ], "offsets": [ [ 485, 500 ] ], "normalized": [] }, { "id": "15019", "type": "Diseases & Disorders", "text": [ "MI" ], "offsets": [ [ 529, 531 ] ], "normalized": [] }, { "id": "15020", "type": "", "text": [ "CYP4F2" ], "offsets": [ [ 19, 25 ] ], "normalized": [] }, { "id": "15021", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 47, 68 ] ], "normalized": [] }, { "id": "15023", "type": "", "text": [ "CYP4F2" ], "offsets": [ [ 131, 137 ] ], "normalized": [] }, { "id": "15024", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15026", "type": "", "text": [ "CYP4F2" ], "offsets": [ [ 131, 137 ] ], "normalized": [] }, { "id": "15027", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15029", "type": "", "text": [ "rs2108622" ], "offsets": [ [ 390, 399 ] ], "normalized": [] }, { "id": "15030", "type": "", "text": [ "MI" ], "offsets": [ [ 529, 531 ] ], "normalized": [] }, { "id": "15032", "type": "", "text": [ "G allele" ], "offsets": [ [ 368, 376 ] ], "normalized": [] }, { "id": "15033", "type": "", "text": [ "MI" ], "offsets": [ [ 529, 531 ] ], "normalized": [] }, { "id": "15035", "type": "", "text": [ "T-C-G haplotype" ], "offsets": [ [ 421, 436 ] ], "normalized": [] }, { "id": "15036", "type": "", "text": [ "MI" ], "offsets": [ [ 529, 531 ] ], "normalized": [] }, { "id": "15038", "type": "", "text": [ "T-C-A haplotype" ], "offsets": [ [ 485, 500 ] ], "normalized": [] }, { "id": "15039", "type": "", "text": [ "MI" ], "offsets": [ [ 529, 531 ] ], "normalized": [] }, { "id": "15041", "type": "", "text": [ "rs3093105" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "15042", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15044", "type": "", "text": [ "rs3093105" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "15045", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15047", "type": "", "text": [ "rs3093135" ], "offsets": [ [ 314, 323 ] ], "normalized": [] }, { "id": "15048", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15050", "type": "", "text": [ "rs3093135" ], "offsets": [ [ 314, 323 ] ], "normalized": [] }, { "id": "15051", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15053", "type": "", "text": [ "rs1558139" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "15054", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15056", "type": "", "text": [ "rs1558139" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "15057", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15059", "type": "", "text": [ "rs2108622" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "15060", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15062", "type": "", "text": [ "rs2108622" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "15063", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "15065", "type": "", "text": [ "rs3093200" ], "offsets": [ [ 347, 356 ] ], "normalized": [] }, { "id": "15066", "type": "", "text": [ "myocardial infarction" ], "offsets": [ [ 147, 168 ] ], "normalized": [] }, { "id": "15068", "type": "", "text": [ "rs3093200" ], "offsets": [ [ 347, 356 ] ], "normalized": [] }, { "id": "15069", "type": "", "text": [ "MI" ], "offsets": [ [ 225, 227 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15022", "type": "PA", "arg1_id": "15020", "arg2_id": "15021", "normalized": [] }, { "id": "15025", "type": "PA", "arg1_id": "15023", "arg2_id": "15024", "normalized": [] }, { "id": "15028", "type": "PA", "arg1_id": "15026", "arg2_id": "15027", "normalized": [] }, { "id": "15031", "type": "PA", "arg1_id": "15029", "arg2_id": "15030", "normalized": [] }, { "id": "15034", "type": "PA", "arg1_id": "15032", "arg2_id": "15033", "normalized": [] }, { "id": "15037", "type": "PA", "arg1_id": "15035", "arg2_id": "15036", "normalized": [] }, { "id": "15040", "type": "PA", "arg1_id": "15038", "arg2_id": "15039", "normalized": [] }, { "id": "15043", "type": "SA", "arg1_id": "15041", "arg2_id": "15042", "normalized": [] }, { "id": "15046", "type": "SA", "arg1_id": "15044", "arg2_id": "15045", "normalized": [] }, { "id": "15049", "type": "SA", "arg1_id": "15047", "arg2_id": "15048", "normalized": [] }, { "id": "15052", "type": "SA", "arg1_id": "15050", "arg2_id": "15051", "normalized": [] }, { "id": "15055", "type": "SA", "arg1_id": "15053", "arg2_id": "15054", "normalized": [] }, { "id": "15058", "type": "SA", "arg1_id": "15056", "arg2_id": "15057", "normalized": [] }, { "id": "15061", "type": "SA", "arg1_id": "15059", "arg2_id": "15060", "normalized": [] }, { "id": "15064", "type": "SA", "arg1_id": "15062", "arg2_id": "15063", "normalized": [] }, { "id": "15067", "type": "SA", "arg1_id": "15065", "arg2_id": "15066", "normalized": [] }, { "id": "15070", "type": "SA", "arg1_id": "15068", "arg2_id": "15069", "normalized": [] } ]

[ { "id": "15073", "type": "title", "text": [ "Development of predictive models of proliferative vitreoretinopathy based on genetic variables: the Retina 4 project." ], "offsets": [ [ 0, 117 ] ] }, { "id": "15074", "type": "abstract", "text": [ "PURPOSE: Machine learning techniques were used to identify which of 14 algorithms best predicts the genetic risk for development of proliferative vitreoretinopathy (PVR) in patients who are experiencing primary rhegmatogenous retinal detachment (RD). METHOD: Data from a total of 196 single nucleotide polymorphisms in 30 candidate genes were used. The genotypic profile of 138 patients with PVR following primary rhegmatogenous RD and 312 patients without PVR RD were analyzed. Machine learning techniques were used to develop statistical predictive models. Fourteen models were assessed. Their reproducibility was evaluated by an internal cross-validation method. RESULTS: The three best predictive models were the lineal kernel based on the Support Vector Machine (SMV), the radial kernel based on the SVM, and the Random Forest. Accuracy values were 78.4%, 70.3%, and 69.3%, respectively. The more accurate, although complex, algorithm uses 42 SNPs, whereas the simpler one uses only two SNPs, which makes them more suitable for routine diagnostic work. The radial kernel based on SVM uses 10 SNPs. The best individually predictor marker was rs2229094 in the tumor necrosis factor locus. CONCLUSION: Genetic variables may be useful to predict the likelihood of the development of PVR. The predictive capabilities of these models are as good as those observed with clinical approaches. These results need external validation to estimate the true predictive capability and select the most appropriate ones for clinical use." ], "offsets": [ [ 118, 1643 ] ] } ]

[ { "id": "15075", "type": "Diseases & Disorders", "text": [ "proliferative vitreoretinopathy" ], "offsets": [ [ 36, 67 ] ], "normalized": [] }, { "id": "15076", "type": "Diseases & Disorders", "text": [ "best" ], "offsets": [ [ 200, 204 ] ], "normalized": [] }, { "id": "15077", "type": "Diseases & Disorders", "text": [ "proliferative vitreoretinopathy" ], "offsets": [ [ 250, 281 ] ], "normalized": [] }, { "id": "15078", "type": "Diseases & Disorders", "text": [ "PVR" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "15079", "type": "Genes & Molecular Sequences", "text": [ "PVR" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "15080", "type": "Diseases & Disorders", "text": [ "primary rhegmatogenous retinal detachment" ], "offsets": [ [ 321, 362 ] ], "normalized": [] }, { "id": "15081", "type": "Diseases & Disorders", "text": [ "RD" ], "offsets": [ [ 364, 366 ] ], "normalized": [] }, { "id": "15082", "type": "Diseases & Disorders", "text": [ "PVR" ], "offsets": [ [ 510, 513 ] ], "normalized": [] }, { "id": "15083", "type": "Genes & Molecular Sequences", "text": [ "PVR" ], "offsets": [ [ 510, 513 ] ], "normalized": [] }, { "id": "15084", "type": "Diseases & Disorders", "text": [ "primary rhegmatogenous RD" ], "offsets": [ [ 524, 549 ] ], "normalized": [] }, { "id": "15085", "type": "Diseases & Disorders", "text": [ "PVR RD" ], "offsets": [ [ 575, 581 ] ], "normalized": [] }, { "id": "15086", "type": "Genes & Molecular Sequences", "text": [ "PVR RD" ], "offsets": [ [ 575, 581 ] ], "normalized": [] }, { "id": "15087", "type": "Diseases & Disorders", "text": [ "best" ], "offsets": [ [ 803, 807 ] ], "normalized": [] }, { "id": "15088", "type": "Diseases & Disorders", "text": [ "best" ], "offsets": [ [ 1225, 1229 ] ], "normalized": [] }, { "id": "15089", "type": "SNP & Sequence variations", "text": [ "rs2229094" ], "offsets": [ [ 1264, 1273 ] ], "normalized": [] }, { "id": "15090", "type": "Genes & Molecular Sequences", "text": [ "tumor necrosis factor" ], "offsets": [ [ 1281, 1302 ] ], "normalized": [] }, { "id": "15091", "type": "Diseases & Disorders", "text": [ "PVR" ], "offsets": [ [ 1402, 1405 ] ], "normalized": [] }, { "id": "15092", "type": "Genes & Molecular Sequences", "text": [ "PVR" ], "offsets": [ [ 1402, 1405 ] ], "normalized": [] }, { "id": "15093", "type": "", "text": [ "tumor necrosis factor" ], "offsets": [ [ 1281, 1302 ] ], "normalized": [] }, { "id": "15094", "type": "", "text": [ "best" ], "offsets": [ [ 1225, 1229 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15095", "type": "PA", "arg1_id": "15093", "arg2_id": "15094", "normalized": [] } ]

[ { "id": "15098", "type": "title", "text": [ "Common variants in the NLRP3 region contribute to Crohn's disease susceptibility." ], "offsets": [ [ 0, 81 ] ] }, { "id": "15099", "type": "abstract", "text": [ "We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (P(combined) = 3.49 x 10(-9), odds ratio = 1.78, confidence interval = 1.47-2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies. In addition, we observed significant associations between SNPs in the associated regions and NLRP3 expression and IL-1beta production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease." ], "offsets": [ [ 82, 1158 ] ] } ]

[ { "id": "15100", "type": "Genes & Molecular Sequences", "text": [ "NLRP3" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "15101", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 50, 65 ] ], "normalized": [] }, { "id": "15102", "type": "Genes & Molecular Sequences", "text": [ "1q44" ], "offsets": [ [ 198, 202 ] ], "normalized": [] }, { "id": "15103", "type": "Genes & Molecular Sequences", "text": [ "NLRP3" ], "offsets": [ [ 217, 222 ] ], "normalized": [] }, { "id": "15104", "type": "Genes & Molecular Sequences", "text": [ "CIAS1" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "15105", "type": "Genes & Molecular Sequences", "text": [ "NALP3" ], "offsets": [ [ 254, 259 ] ], "normalized": [] }, { "id": "15106", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "15107", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 557, 572 ] ], "normalized": [] }, { "id": "15108", "type": "Genes & Molecular Sequences", "text": [ "NLRP3" ], "offsets": [ [ 880, 885 ] ], "normalized": [] }, { "id": "15109", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 901, 909 ] ], "normalized": [] }, { "id": "15110", "type": "SNP & Sequence variations", "text": [ "Mutations in NLRP3" ], "offsets": [ [ 922, 940 ] ], "normalized": [] }, { "id": "15111", "type": "Diseases & Disorders", "text": [ "Mutations in NLRP3" ], "offsets": [ [ 922, 940 ] ], "normalized": [] }, { "id": "15112", "type": "Genes & Molecular Sequences", "text": [ "Mutations in NLRP3" ], "offsets": [ [ 922, 940 ] ], "normalized": [] }, { "id": "15113", "type": "Diseases & Disorders", "text": [ "rare autoinflammatory disorders" ], "offsets": [ [ 979, 1010 ] ], "normalized": [] }, { "id": "15114", "type": "Genes & Molecular Sequences", "text": [ "NLRP3" ], "offsets": [ [ 1043, 1048 ] ], "normalized": [] }, { "id": "15115", "type": "Diseases & Disorders", "text": [ "inflammatory diseases" ], "offsets": [ [ 1112, 1133 ] ], "normalized": [] }, { "id": "15116", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 1142, 1157 ] ], "normalized": [] }, { "id": "15117", "type": "", "text": [ "NLRP3" ], "offsets": [ [ 23, 28 ] ], "normalized": [] }, { "id": "15118", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 50, 65 ] ], "normalized": [] }, { "id": "15120", "type": "", "text": [ "NALP3" ], "offsets": [ [ 254, 259 ] ], "normalized": [] }, { "id": "15121", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "15123", "type": "", "text": [ "NLRP3" ], "offsets": [ [ 217, 222 ] ], "normalized": [] }, { "id": "15124", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "15126", "type": "", "text": [ "1q44" ], "offsets": [ [ 198, 202 ] ], "normalized": [] }, { "id": "15127", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "15129", "type": "", "text": [ "Mutations in NLRP3" ], "offsets": [ [ 922, 940 ] ], "normalized": [] }, { "id": "15130", "type": "", "text": [ "rare autoinflammatory disorders" ], "offsets": [ [ 979, 1010 ] ], "normalized": [] }, { "id": "15132", "type": "", "text": [ "NLRP3" ], "offsets": [ [ 1043, 1048 ] ], "normalized": [] }, { "id": "15133", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 1142, 1157 ] ], "normalized": [] }, { "id": "15135", "type": "", "text": [ "NLRP3" ], "offsets": [ [ 1043, 1048 ] ], "normalized": [] }, { "id": "15136", "type": "", "text": [ "inflammatory diseases" ], "offsets": [ [ 1112, 1133 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15119", "type": "PA", "arg1_id": "15117", "arg2_id": "15118", "normalized": [] }, { "id": "15122", "type": "PA", "arg1_id": "15120", "arg2_id": "15121", "normalized": [] }, { "id": "15125", "type": "PA", "arg1_id": "15123", "arg2_id": "15124", "normalized": [] }, { "id": "15128", "type": "PA", "arg1_id": "15126", "arg2_id": "15127", "normalized": [] }, { "id": "15131", "type": "PA", "arg1_id": "15129", "arg2_id": "15130", "normalized": [] }, { "id": "15134", "type": "SA", "arg1_id": "15132", "arg2_id": "15133", "normalized": [] }, { "id": "15137", "type": "SA", "arg1_id": "15135", "arg2_id": "15136", "normalized": [] } ]

[ { "id": "15140", "type": "title", "text": [ "Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese." ], "offsets": [ [ 0, 98 ] ] }, { "id": "15141", "type": "abstract", "text": [ "PURPOSE: The lysyl oxidase-like protein 1 (LOXL1) gene is strongly associated with exfoliation glaucoma, which is very rare in the Chinese population. The implicated LOXL1 polymorphisms have not been associated with primary open-angle glaucoma (POAG). In this study, we investigated three of the LOXL1 polymorphisms in POAG in a southern Chinese population of Hong Kong and northern Chinese from Beijing. METHODS: The Hong Kong group included 293 POAG patients and 250 controls, and the Beijing group included 169 POAG patients and 197 controls. LOXL1 single nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, were genotyped by direct DNA sequencing. Individual association was analyzed using the chi(2) test, and haplotype-based association analysis was performed in WHAP. RESULTS: Each of the candidate SNPs was not statistically associated with POAG in either group (p>0.017, Bonferroni correction). Haplotype-based association analysis had identified a significant omnibus association (Omnibus chi(2)=18.16, p=0.00115) between these SNPs and POAG in the Hong Kong group. A minor haplotype (T-G-T) showed significant statistical association with POAG. It presented in 2.1% of cases and 0.4% of controls, conferring a 5.24 fold of increased risk to the disease (95% CI: 1.17-23.54, P(perm)=0.00108). However, this haplotype was absent in the Beijing group. CONCLUSIONS: Individual LOXL1 SNPs, rs1048661, rs3825942, and rs2165241, were not associated with POAG in the Chinese population. However, a minor haplotype T-G-T was found to be associated with the disorder in the southern Chinese. The low frequencies of the at-risk alleles at rs1048661 and rs2165241 may be one of the factors that led to the low prevalence of exfoliation syndrome in the general populations of the Chinese." ], "offsets": [ [ 99, 1903 ] ] } ]

[ { "id": "15142", "type": "SNP & Sequence variations", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 14, 33 ] ], "normalized": [] }, { "id": "15143", "type": "Genes & Molecular Sequences", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 14, 33 ] ], "normalized": [] }, { "id": "15144", "type": "Diseases & Disorders", "text": [ "primary open-angle glaucoma" ], "offsets": [ [ 37, 64 ] ], "normalized": [] }, { "id": "15145", "type": "Genes & Molecular Sequences", "text": [ "lysyl oxidase-like protein 1" ], "offsets": [ [ 112, 140 ] ], "normalized": [] }, { "id": "15146", "type": "Genes & Molecular Sequences", "text": [ "LOXL1" ], "offsets": [ [ 142, 147 ] ], "normalized": [] }, { "id": "15147", "type": "Diseases & Disorders", "text": [ "exfoliation glaucoma" ], "offsets": [ [ 182, 202 ] ], "normalized": [] }, { "id": "15148", "type": "SNP & Sequence variations", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 265, 284 ] ], "normalized": [] }, { "id": "15149", "type": "Genes & Molecular Sequences", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 265, 284 ] ], "normalized": [] }, { "id": "15150", "type": "Diseases & Disorders", "text": [ "primary open-angle glaucoma" ], "offsets": [ [ 315, 342 ] ], "normalized": [] }, { "id": "15151", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "15152", "type": "SNP & Sequence variations", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 395, 414 ] ], "normalized": [] }, { "id": "15153", "type": "Genes & Molecular Sequences", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 395, 414 ] ], "normalized": [] }, { "id": "15154", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 418, 422 ] ], "normalized": [] }, { "id": "15155", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "15156", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 613, 617 ] ], "normalized": [] }, { "id": "15157", "type": "Genes & Molecular Sequences", "text": [ "LOXL1" ], "offsets": [ [ 645, 650 ] ], "normalized": [] }, { "id": "15158", "type": "SNP & Sequence variations", "text": [ "rs1048661" ], "offsets": [ [ 691, 700 ] ], "normalized": [] }, { "id": "15159", "type": "SNP & Sequence variations", "text": [ "rs3825942" ], "offsets": [ [ 702, 711 ] ], "normalized": [] }, { "id": "15160", "type": "SNP & Sequence variations", "text": [ "rs2165241" ], "offsets": [ [ 717, 726 ] ], "normalized": [] }, { "id": "15161", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 966, 970 ] ], "normalized": [] }, { "id": "15162", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 1164, 1168 ] ], "normalized": [] }, { "id": "15163", "type": "Diseases & Disorders", "text": [ "minor" ], "offsets": [ [ 1195, 1200 ] ], "normalized": [] }, { "id": "15164", "type": "SNP & Sequence variations", "text": [ "T-G-T" ], "offsets": [ [ 1212, 1217 ] ], "normalized": [] }, { "id": "15165", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 1267, 1271 ] ], "normalized": [] }, { "id": "15166", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1373, 1380 ] ], "normalized": [] }, { "id": "15167", "type": "Genes & Molecular Sequences", "text": [ "LOXL1" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "15168", "type": "SNP & Sequence variations", "text": [ "rs1048661" ], "offsets": [ [ 1513, 1522 ] ], "normalized": [] }, { "id": "15169", "type": "SNP & Sequence variations", "text": [ "rs3825942" ], "offsets": [ [ 1524, 1533 ] ], "normalized": [] }, { "id": "15170", "type": "SNP & Sequence variations", "text": [ "rs2165241" ], "offsets": [ [ 1539, 1548 ] ], "normalized": [] }, { "id": "15171", "type": "Diseases & Disorders", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "15172", "type": "Diseases & Disorders", "text": [ "minor" ], "offsets": [ [ 1618, 1623 ] ], "normalized": [] }, { "id": "15173", "type": "SNP & Sequence variations", "text": [ "haplotype T-G-T" ], "offsets": [ [ 1624, 1639 ] ], "normalized": [] }, { "id": "15174", "type": "Diseases & Disorders", "text": [ "disorder" ], "offsets": [ [ 1676, 1684 ] ], "normalized": [] }, { "id": "15175", "type": "SNP & Sequence variations", "text": [ "rs1048661" ], "offsets": [ [ 1756, 1765 ] ], "normalized": [] }, { "id": "15176", "type": "SNP & Sequence variations", "text": [ "rs2165241" ], "offsets": [ [ 1770, 1779 ] ], "normalized": [] }, { "id": "15177", "type": "Diseases & Disorders", "text": [ "exfoliation syndrome" ], "offsets": [ [ 1840, 1860 ] ], "normalized": [] }, { "id": "15178", "type": "", "text": [ "LOXL1" ], "offsets": [ [ 142, 147 ] ], "normalized": [] }, { "id": "15179", "type": "", "text": [ "exfoliation glaucoma" ], "offsets": [ [ 182, 202 ] ], "normalized": [] }, { "id": "15181", "type": "", "text": [ "T-G-T" ], "offsets": [ [ 1212, 1217 ] ], "normalized": [] }, { "id": "15182", "type": "", "text": [ "POAG" ], "offsets": [ [ 1267, 1271 ] ], "normalized": [] }, { "id": "15184", "type": "", "text": [ "rs1048661" ], "offsets": [ [ 1513, 1522 ] ], "normalized": [] }, { "id": "15185", "type": "", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "15187", "type": "", "text": [ "rs3825942" ], "offsets": [ [ 1524, 1533 ] ], "normalized": [] }, { "id": "15188", "type": "", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "15190", "type": "", "text": [ "rs2165241" ], "offsets": [ [ 1539, 1548 ] ], "normalized": [] }, { "id": "15191", "type": "", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "15193", "type": "", "text": [ "rs1048661" ], "offsets": [ [ 1756, 1765 ] ], "normalized": [] }, { "id": "15194", "type": "", "text": [ "exfoliation syndrome" ], "offsets": [ [ 1840, 1860 ] ], "normalized": [] }, { "id": "15196", "type": "", "text": [ "rs2165241" ], "offsets": [ [ 1770, 1779 ] ], "normalized": [] }, { "id": "15197", "type": "", "text": [ "exfoliation syndrome" ], "offsets": [ [ 1840, 1860 ] ], "normalized": [] }, { "id": "15199", "type": "", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 14, 33 ] ], "normalized": [] }, { "id": "15200", "type": "", "text": [ "primary open-angle glaucoma" ], "offsets": [ [ 37, 64 ] ], "normalized": [] }, { "id": "15202", "type": "", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 265, 284 ] ], "normalized": [] }, { "id": "15203", "type": "", "text": [ "POAG" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "15205", "type": "", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 395, 414 ] ], "normalized": [] }, { "id": "15206", "type": "", "text": [ "POAG" ], "offsets": [ [ 418, 422 ] ], "normalized": [] }, { "id": "15208", "type": "", "text": [ "LOXL1" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "15209", "type": "", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "15211", "type": "", "text": [ "lysyl oxidase-like protein 1" ], "offsets": [ [ 112, 140 ] ], "normalized": [] }, { "id": "15212", "type": "", "text": [ "exfoliation glaucoma" ], "offsets": [ [ 182, 202 ] ], "normalized": [] }, { "id": "15214", "type": "", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 265, 284 ] ], "normalized": [] }, { "id": "15215", "type": "", "text": [ "POAG" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "15217", "type": "", "text": [ "LOXL1 polymorphisms" ], "offsets": [ [ 265, 284 ] ], "normalized": [] }, { "id": "15218", "type": "", "text": [ "primary open-angle glaucoma" ], "offsets": [ [ 315, 342 ] ], "normalized": [] }, { "id": "15220", "type": "", "text": [ "LOXL1" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "15221", "type": "", "text": [ "POAG" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15180", "type": "PA", "arg1_id": "15178", "arg2_id": "15179", "normalized": [] }, { "id": "15183", "type": "PA", "arg1_id": "15181", "arg2_id": "15182", "normalized": [] }, { "id": "15186", "type": "NA", "arg1_id": "15184", "arg2_id": "15185", "normalized": [] }, { "id": "15189", "type": "NA", "arg1_id": "15187", "arg2_id": "15188", "normalized": [] }, { "id": "15192", "type": "NA", "arg1_id": "15190", "arg2_id": "15191", "normalized": [] }, { "id": "15195", "type": "SA", "arg1_id": "15193", "arg2_id": "15194", "normalized": [] }, { "id": "15198", "type": "SA", "arg1_id": "15196", "arg2_id": "15197", "normalized": [] }, { "id": "15201", "type": "PA", "arg1_id": "15199", "arg2_id": "15200", "normalized": [] }, { "id": "15204", "type": "PA", "arg1_id": "15202", "arg2_id": "15203", "normalized": [] }, { "id": "15207", "type": "PA", "arg1_id": "15205", "arg2_id": "15206", "normalized": [] }, { "id": "15210", "type": "PA", "arg1_id": "15208", "arg2_id": "15209", "normalized": [] }, { "id": "15213", "type": "PA", "arg1_id": "15211", "arg2_id": "15212", "normalized": [] }, { "id": "15216", "type": "NA", "arg1_id": "15214", "arg2_id": "15215", "normalized": [] }, { "id": "15219", "type": "NA", "arg1_id": "15217", "arg2_id": "15218", "normalized": [] }, { "id": "15222", "type": "NA", "arg1_id": "15220", "arg2_id": "15221", "normalized": [] } ]

[ { "id": "15225", "type": "title", "text": [ "Thoracic aortic aneurysm: reading the enemy's playbook." ], "offsets": [ [ 0, 55 ] ] }, { "id": "15226", "type": "abstract", "text": [ "BACKGROUND: At the Yale University Center for Thoracic Aortic Disease, we have been using our clinical experience and laboratory investigations to shed light on the pathophysiology of thoracic aortic aneurysm (TAA), the clinical behavior of thoracic aortic aneurysm, and the optimal clinical management. MATERIALS AND METHODS: The Yale database contains information on 3,000 patients with thoracic aortic aneurysm, with 9,000 patient-years of follow-up and 9,000 imaging studies. Advanced statistical techniques were applied to this information. RESULTS: Analysis yielded the following Yale-generated observations: (1) TAA is a genetic disease with a predominantly autosomal dominant mode of inheritance; (2) matrix metalloproteinase (MMP) enzymes are activated in the pathogenesis of TAA; (3) wall tension in TAA approaches the tensile limits of aortic tissue at a diameter of 6 cm; (4) by the time a TAA reaches a clinical diameter of 6 cm, 34 percent of affected patients have suffered dissection or rupture; (5) extreme physical exertion or severe emotion often precipitate acute dissection; and (6) single nucleotide polymorphisms (SNPs) and RNA expression profile changes are being identified that predispose a patient to TAA and can serve as biomarkers for screening for this virulent disease. CONCLUSIONS: The \"playbook\" of TAA is gradually being read, with the help of scientific investigations, positioning practitioners to combat this lethal disease more effectively than ever before." ], "offsets": [ [ 56, 1551 ] ] } ]

[ { "id": "15227", "type": "Diseases & Disorders", "text": [ "Thoracic aortic aneurysm" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "15228", "type": "Diseases & Disorders", "text": [ "Thoracic" ], "offsets": [ [ 102, 110 ] ], "normalized": [] }, { "id": "15229", "type": "Diseases & Disorders", "text": [ "Aortic Disease" ], "offsets": [ [ 111, 125 ] ], "normalized": [] }, { "id": "15230", "type": "Diseases & Disorders", "text": [ "pathophysiology" ], "offsets": [ [ 221, 236 ] ], "normalized": [] }, { "id": "15231", "type": "Diseases & Disorders", "text": [ "thoracic aortic aneurysm" ], "offsets": [ [ 240, 264 ] ], "normalized": [] }, { "id": "15232", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 266, 269 ] ], "normalized": [] }, { "id": "15233", "type": "Diseases & Disorders", "text": [ "thoracic aortic aneurysm" ], "offsets": [ [ 297, 321 ] ], "normalized": [] }, { "id": "15234", "type": "Diseases & Disorders", "text": [ "thoracic aortic aneurysm" ], "offsets": [ [ 445, 469 ] ], "normalized": [] }, { "id": "15235", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 675, 678 ] ], "normalized": [] }, { "id": "15236", "type": "Diseases & Disorders", "text": [ "genetic disease" ], "offsets": [ [ 684, 699 ] ], "normalized": [] }, { "id": "15237", "type": "Genes & Molecular Sequences", "text": [ "matrix metalloproteinase" ], "offsets": [ [ 765, 789 ] ], "normalized": [] }, { "id": "15238", "type": "Genes & Molecular Sequences", "text": [ "MMP" ], "offsets": [ [ 791, 794 ] ], "normalized": [] }, { "id": "15239", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 825, 837 ] ], "normalized": [] }, { "id": "15240", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "15241", "type": "Diseases & Disorders", "text": [ "tension" ], "offsets": [ [ 855, 862 ] ], "normalized": [] }, { "id": "15242", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 866, 869 ] ], "normalized": [] }, { "id": "15243", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "15244", "type": "Diseases & Disorders", "text": [ "suffered" ], "offsets": [ [ 1036, 1044 ] ], "normalized": [] }, { "id": "15245", "type": "Diseases & Disorders", "text": [ "dissection" ], "offsets": [ [ 1045, 1055 ] ], "normalized": [] }, { "id": "15246", "type": "Diseases & Disorders", "text": [ "rupture" ], "offsets": [ [ 1059, 1066 ] ], "normalized": [] }, { "id": "15247", "type": "Diseases & Disorders", "text": [ "acute dissection" ], "offsets": [ [ 1134, 1150 ] ], "normalized": [] }, { "id": "15248", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] }, { "id": "15249", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1348, 1355 ] ], "normalized": [] }, { "id": "15250", "type": "Diseases & Disorders", "text": [ "TAA" ], "offsets": [ [ 1388, 1391 ] ], "normalized": [] }, { "id": "15251", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1509, 1516 ] ], "normalized": [] }, { "id": "15252", "type": "", "text": [ "matrix metalloproteinase" ], "offsets": [ [ 765, 789 ] ], "normalized": [] }, { "id": "15253", "type": "", "text": [ "TAA" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] }, { "id": "15255", "type": "", "text": [ "MMP" ], "offsets": [ [ 791, 794 ] ], "normalized": [] }, { "id": "15256", "type": "", "text": [ "TAA" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15254", "type": "PA", "arg1_id": "15252", "arg2_id": "15253", "normalized": [] }, { "id": "15257", "type": "PA", "arg1_id": "15255", "arg2_id": "15256", "normalized": [] } ]

[ { "id": "15260", "type": "title", "text": [ "Clinical utility of genetic tests for inherited hypertrophic and dilated cardiomyopathies." ], "offsets": [ [ 0, 90 ] ] }, { "id": "15261", "type": "abstract", "text": [ "Genetic testing has become an increasingly important part of medical practice for heritable form of cardiomyopathies. Hypertrophic cardiomyopathy and about 50% of idiopathic dilatative cardiomyopathy are familial diseases, with an autosomal dominant pattern of inheritance.Some genotype-phenotype correlations can provide important information to target DNA analyses in specific genes. Genetic testing may clarify diagnosis and help the optimal treatment strategies for more malignant phenotypes. In addition, genetic screening of first-degree relatives can help early identification and diagnosis of individuals at greatest risk for developing cardiomyopathy, allowing to focus clinical resources on high-risk family members.This paper provides a concise overview of the genetic etiology as well as the clinical utilities and limitations of genetic testing for the heritable cardiomyopathies." ], "offsets": [ [ 91, 984 ] ] } ]

[ { "id": "15262", "type": "Diseases & Disorders", "text": [ "inherited hypertrophic" ], "offsets": [ [ 38, 60 ] ], "normalized": [] }, { "id": "15263", "type": "Diseases & Disorders", "text": [ "dilated cardiomyopathies" ], "offsets": [ [ 65, 89 ] ], "normalized": [] }, { "id": "15264", "type": "Diseases & Disorders", "text": [ "cardiomyopathies" ], "offsets": [ [ 191, 207 ] ], "normalized": [] }, { "id": "15265", "type": "Diseases & Disorders", "text": [ "Hypertrophic cardiomyopathy" ], "offsets": [ [ 209, 236 ] ], "normalized": [] }, { "id": "15266", "type": "Diseases & Disorders", "text": [ "idiopathic dilatative cardiomyopathy" ], "offsets": [ [ 254, 290 ] ], "normalized": [] }, { "id": "15267", "type": "Diseases & Disorders", "text": [ "familial diseases" ], "offsets": [ [ 295, 312 ] ], "normalized": [] }, { "id": "15268", "type": "Diseases & Disorders", "text": [ "cardiomyopathy" ], "offsets": [ [ 736, 750 ] ], "normalized": [] }, { "id": "15269", "type": "Diseases & Disorders", "text": [ "heritable cardiomyopathies" ], "offsets": [ [ 957, 983 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "15272", "type": "title", "text": [ "Influence of single-nucleotide polymorphisms on C-reactive protein levels in chronic kidney disease before and after kidney transplantation." ], "offsets": [ [ 0, 140 ] ] }, { "id": "15273", "type": "abstract", "text": [ "INTRODUCTION: We sought to evaluate 2 single-nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene promoter region for their effects on CRP levels in chronic kidney disease (CKD) patients before and after a successful kidney transplantation. METHODS: Fifty CKD patients were evaluated before and at the first and second years after the graft. Two SNPs were studied, a bi-allelic (G-->A) at the -409 and a tri-allelic (C-->T-->A) variation at the -390 position in the CRP gene. RESULTS: All patients presented the -409GG genotype. At the -390 position, the \"A\" allele was not found; there were 15 \"CC\" patients, 11 \"TT\" patients, and 24 \"CT\" patients. CRP levels were different among patients with various genotypes (P < .019). Also the presence of the allele \"T\" was sufficient to determine differences in CRP levels both in pretransplantation (P = .045) and at 1 year posttransplantation (P = .011), but not at the second year (P = .448). CONCLUSION: SNPs at the -390 position of the CRP gene promoter region influence CRP basal levels in such a way that the \"C\" allele correlated with the lowest and the \"T\" with the highest. We did not observe this influence in our patients at the second year posttransplantation." ], "offsets": [ [ 141, 1373 ] ] } ]

[ { "id": "15274", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 48, 66 ] ], "normalized": [] }, { "id": "15275", "type": "Diseases & Disorders", "text": [ "chronic kidney disease" ], "offsets": [ [ 77, 99 ] ], "normalized": [] }, { "id": "15276", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 225, 243 ] ], "normalized": [] }, { "id": "15277", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 245, 248 ] ], "normalized": [] }, { "id": "15278", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 292, 295 ] ], "normalized": [] }, { "id": "15279", "type": "Diseases & Disorders", "text": [ "chronic kidney disease" ], "offsets": [ [ 306, 328 ] ], "normalized": [] }, { "id": "15280", "type": "Diseases & Disorders", "text": [ "CKD" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "15281", "type": "Diseases & Disorders", "text": [ "CKD" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "15282", "type": "SNP & Sequence variations", "text": [ "-409" ], "offsets": [ [ 550, 554 ] ], "normalized": [] }, { "id": "15283", "type": "SNP & Sequence variations", "text": [ "-390" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "15284", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 623, 626 ] ], "normalized": [] }, { "id": "15285", "type": "SNP & Sequence variations", "text": [ "-409GG" ], "offsets": [ [ 669, 675 ] ], "normalized": [] }, { "id": "15286", "type": "SNP & Sequence variations", "text": [ "-390" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "15287", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 807, 810 ] ], "normalized": [] }, { "id": "15288", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 962, 965 ] ], "normalized": [] }, { "id": "15289", "type": "Diseases & Disorders", "text": [ "1 year posttransplantation" ], "offsets": [ [ 1018, 1044 ] ], "normalized": [] }, { "id": "15290", "type": "SNP & Sequence variations", "text": [ "-390" ], "offsets": [ [ 1120, 1124 ] ], "normalized": [] }, { "id": "15291", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 1141, 1144 ] ], "normalized": [] }, { "id": "15292", "type": "Genes & Molecular Sequences", "text": [ "CRP" ], "offsets": [ [ 1176, 1179 ] ], "normalized": [] }, { "id": "15293", "type": "Diseases & Disorders", "text": [ "posttransplantation" ], "offsets": [ [ 1353, 1372 ] ], "normalized": [] }, { "id": "15294", "type": "", "text": [ "C-reactive protein" ], "offsets": [ [ 48, 66 ] ], "normalized": [] }, { "id": "15295", "type": "", "text": [ "chronic kidney disease" ], "offsets": [ [ 77, 99 ] ], "normalized": [] }, { "id": "15297", "type": "", "text": [ "CRP" ], "offsets": [ [ 292, 295 ] ], "normalized": [] }, { "id": "15298", "type": "", "text": [ "chronic kidney disease" ], "offsets": [ [ 306, 328 ] ], "normalized": [] }, { "id": "15300", "type": "", "text": [ "CRP" ], "offsets": [ [ 292, 295 ] ], "normalized": [] }, { "id": "15301", "type": "", "text": [ "CKD" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "15303", "type": "", "text": [ "CRP" ], "offsets": [ [ 962, 965 ] ], "normalized": [] }, { "id": "15304", "type": "", "text": [ "1 year posttransplantation" ], "offsets": [ [ 1018, 1044 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15296", "type": "PA", "arg1_id": "15294", "arg2_id": "15295", "normalized": [] }, { "id": "15299", "type": "PA", "arg1_id": "15297", "arg2_id": "15298", "normalized": [] }, { "id": "15302", "type": "PA", "arg1_id": "15300", "arg2_id": "15301", "normalized": [] }, { "id": "15305", "type": "PA", "arg1_id": "15303", "arg2_id": "15304", "normalized": [] } ]

[ { "id": "15308", "type": "title", "text": [ "Conversion to sirolimus in kidney-pancreas and pancreas transplantation." ], "offsets": [ [ 0, 72 ] ] }, { "id": "15309", "type": "abstract", "text": [ "Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF." ], "offsets": [ [ 73, 1762 ] ] } ]

[ { "id": "15310", "type": "Chemicals & Drugs", "text": [ "sirolimus" ], "offsets": [ [ 14, 23 ] ], "normalized": [] }, { "id": "15311", "type": "Chemicals & Drugs", "text": [ "sirolimus" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "15312", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 106, 109 ] ], "normalized": [] }, { "id": "15313", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "15314", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 211, 214 ] ], "normalized": [] }, { "id": "15315", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 383, 386 ] ], "normalized": [] }, { "id": "15316", "type": "Chemicals & Drugs", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15317", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 444, 447 ] ], "normalized": [] }, { "id": "15318", "type": "Diseases & Disorders", "text": [ "nephrotoxicity" ], "offsets": [ [ 449, 463 ] ], "normalized": [] }, { "id": "15319", "type": "Diseases & Disorders", "text": [ "neurotoxicity" ], "offsets": [ [ 486, 499 ] ], "normalized": [] }, { "id": "15320", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15321", "type": "Diseases & Disorders", "text": [ "acute rejection" ], "offsets": [ [ 550, 565 ] ], "normalized": [] }, { "id": "15322", "type": "Diseases & Disorders", "text": [ "gastrointestinal" ], "offsets": [ [ 589, 605 ] ], "normalized": [] }, { "id": "15323", "type": "Diseases & Disorders", "text": [ "GI) side effects" ], "offsets": [ [ 607, 623 ] ], "normalized": [] }, { "id": "15324", "type": "Chemicals & Drugs", "text": [ "mycophenolate mofetil" ], "offsets": [ [ 627, 648 ] ], "normalized": [] }, { "id": "15325", "type": "Chemicals & Drugs", "text": [ "MMF" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "15326", "type": "Diseases & Disorders", "text": [ "hyperglycemia" ], "offsets": [ [ 672, 685 ] ], "normalized": [] }, { "id": "15327", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 753, 756 ] ], "normalized": [] }, { "id": "15328", "type": "Chemicals & Drugs", "text": [ "MMF" ], "offsets": [ [ 758, 761 ] ], "normalized": [] }, { "id": "15329", "type": "Chemicals & Drugs", "text": [ "steroids" ], "offsets": [ [ 776, 784 ] ], "normalized": [] }, { "id": "15330", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 819, 822 ] ], "normalized": [] }, { "id": "15331", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 846, 849 ] ], "normalized": [] }, { "id": "15332", "type": "Chemicals & Drugs", "text": [ "MMF" ], "offsets": [ [ 853, 856 ] ], "normalized": [] }, { "id": "15333", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 938, 941 ] ], "normalized": [] }, { "id": "15334", "type": "Diseases & Disorders", "text": [ "nephrotoxicity" ], "offsets": [ [ 942, 956 ] ], "normalized": [] }, { "id": "15335", "type": "Diseases & Disorders", "text": [ "leucoencephalopathy" ], "offsets": [ [ 1245, 1264 ] ], "normalized": [] }, { "id": "15336", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 1305, 1308 ] ], "normalized": [] }, { "id": "15337", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 1347, 1350 ] ], "normalized": [] }, { "id": "15338", "type": "Diseases & Disorders", "text": [ "GI side effects" ], "offsets": [ [ 1362, 1377 ] ], "normalized": [] }, { "id": "15339", "type": "Chemicals & Drugs", "text": [ "MMF" ], "offsets": [ [ 1381, 1384 ] ], "normalized": [] }, { "id": "15340", "type": "Diseases & Disorders", "text": [ "hyperglycemia" ], "offsets": [ [ 1445, 1458 ] ], "normalized": [] }, { "id": "15341", "type": "Diseases & Disorders", "text": [ "acute rejection" ], "offsets": [ [ 1510, 1525 ] ], "normalized": [] }, { "id": "15342", "type": "Chemicals & Drugs", "text": [ "SRL" ], "offsets": [ [ 1576, 1579 ] ], "normalized": [] }, { "id": "15343", "type": "Chemicals & Drugs", "text": [ "CNI" ], "offsets": [ [ 1681, 1684 ] ], "normalized": [] }, { "id": "15344", "type": "Diseases & Disorders", "text": [ "nephrotoxicity" ], "offsets": [ [ 1685, 1699 ] ], "normalized": [] }, { "id": "15345", "type": "Diseases & Disorders", "text": [ "neurotoxicity" ], "offsets": [ [ 1704, 1717 ] ], "normalized": [] }, { "id": "15346", "type": "Diseases & Disorders", "text": [ "severe diarrhea" ], "offsets": [ [ 1735, 1750 ] ], "normalized": [] }, { "id": "15347", "type": "Chemicals & Drugs", "text": [ "MMF" ], "offsets": [ [ 1758, 1761 ] ], "normalized": [] }, { "id": "15348", "type": "", "text": [ "MMF" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "15349", "type": "", "text": [ "gastrointestinal" ], "offsets": [ [ 589, 605 ] ], "normalized": [] }, { "id": "15351", "type": "", "text": [ "MMF" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "15352", "type": "", "text": [ "GI) side effects" ], "offsets": [ [ 607, 623 ] ], "normalized": [] }, { "id": "15354", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15355", "type": "", "text": [ "GI) side effects" ], "offsets": [ [ 607, 623 ] ], "normalized": [] }, { "id": "15357", "type": "", "text": [ "SRL" ], "offsets": [ [ 1305, 1308 ] ], "normalized": [] }, { "id": "15358", "type": "", "text": [ "leucoencephalopathy" ], "offsets": [ [ 1245, 1264 ] ], "normalized": [] }, { "id": "15360", "type": "", "text": [ "MMF" ], "offsets": [ [ 1381, 1384 ] ], "normalized": [] }, { "id": "15361", "type": "", "text": [ "GI side effects" ], "offsets": [ [ 1362, 1377 ] ], "normalized": [] }, { "id": "15363", "type": "", "text": [ "SRL" ], "offsets": [ [ 1347, 1350 ] ], "normalized": [] }, { "id": "15364", "type": "", "text": [ "GI side effects" ], "offsets": [ [ 1362, 1377 ] ], "normalized": [] }, { "id": "15366", "type": "", "text": [ "MMF" ], "offsets": [ [ 1758, 1761 ] ], "normalized": [] }, { "id": "15367", "type": "", "text": [ "severe diarrhea" ], "offsets": [ [ 1735, 1750 ] ], "normalized": [] }, { "id": "15369", "type": "", "text": [ "mycophenolate mofetil" ], "offsets": [ [ 627, 648 ] ], "normalized": [] }, { "id": "15370", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 449, 463 ] ], "normalized": [] }, { "id": "15372", "type": "", "text": [ "mycophenolate mofetil" ], "offsets": [ [ 627, 648 ] ], "normalized": [] }, { "id": "15373", "type": "", "text": [ "gastrointestinal" ], "offsets": [ [ 589, 605 ] ], "normalized": [] }, { "id": "15375", "type": "", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15376", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 449, 463 ] ], "normalized": [] }, { "id": "15378", "type": "", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15379", "type": "", "text": [ "gastrointestinal" ], "offsets": [ [ 589, 605 ] ], "normalized": [] }, { "id": "15381", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15382", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 486, 499 ] ], "normalized": [] }, { "id": "15384", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15385", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 449, 463 ] ], "normalized": [] }, { "id": "15387", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15388", "type": "", "text": [ "gastrointestinal" ], "offsets": [ [ 589, 605 ] ], "normalized": [] }, { "id": "15390", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 486, 499 ] ], "normalized": [] }, { "id": "15391", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 449, 463 ] ], "normalized": [] }, { "id": "15393", "type": "", "text": [ "CNI" ], "offsets": [ [ 938, 941 ] ], "normalized": [] }, { "id": "15394", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 942, 956 ] ], "normalized": [] }, { "id": "15396", "type": "", "text": [ "SRL" ], "offsets": [ [ 1576, 1579 ] ], "normalized": [] }, { "id": "15397", "type": "", "text": [ "severe diarrhea" ], "offsets": [ [ 1735, 1750 ] ], "normalized": [] }, { "id": "15399", "type": "", "text": [ "SRL" ], "offsets": [ [ 1576, 1579 ] ], "normalized": [] }, { "id": "15400", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 1685, 1699 ] ], "normalized": [] }, { "id": "15402", "type": "", "text": [ "CNI" ], "offsets": [ [ 1681, 1684 ] ], "normalized": [] }, { "id": "15403", "type": "", "text": [ "severe diarrhea" ], "offsets": [ [ 1735, 1750 ] ], "normalized": [] }, { "id": "15405", "type": "", "text": [ "CNI" ], "offsets": [ [ 1681, 1684 ] ], "normalized": [] }, { "id": "15406", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 1704, 1717 ] ], "normalized": [] }, { "id": "15408", "type": "", "text": [ "CNI" ], "offsets": [ [ 1681, 1684 ] ], "normalized": [] }, { "id": "15409", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 1685, 1699 ] ], "normalized": [] }, { "id": "15411", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 1704, 1717 ] ], "normalized": [] }, { "id": "15412", "type": "", "text": [ "nephrotoxicity" ], "offsets": [ [ 1685, 1699 ] ], "normalized": [] }, { "id": "15414", "type": "", "text": [ "sirolimus" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "15415", "type": "", "text": [ "still" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "15417", "type": "", "text": [ "MMF" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "15418", "type": "", "text": [ "hyperglycemia" ], "offsets": [ [ 672, 685 ] ], "normalized": [] }, { "id": "15420", "type": "", "text": [ "MMF" ], "offsets": [ [ 1381, 1384 ] ], "normalized": [] }, { "id": "15421", "type": "", "text": [ "hyperglycemia" ], "offsets": [ [ 1445, 1458 ] ], "normalized": [] }, { "id": "15423", "type": "", "text": [ "MMF" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "15424", "type": "", "text": [ "acute rejection" ], "offsets": [ [ 550, 565 ] ], "normalized": [] }, { "id": "15426", "type": "", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15427", "type": "", "text": [ "hyperglycemia" ], "offsets": [ [ 672, 685 ] ], "normalized": [] }, { "id": "15429", "type": "", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15430", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 486, 499 ] ], "normalized": [] }, { "id": "15432", "type": "", "text": [ "calcineurin inhibitors" ], "offsets": [ [ 420, 442 ] ], "normalized": [] }, { "id": "15433", "type": "", "text": [ "acute rejection" ], "offsets": [ [ 550, 565 ] ], "normalized": [] }, { "id": "15435", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15436", "type": "", "text": [ "hyperglycemia" ], "offsets": [ [ 672, 685 ] ], "normalized": [] }, { "id": "15438", "type": "", "text": [ "CNI" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "15439", "type": "", "text": [ "acute rejection" ], "offsets": [ [ 550, 565 ] ], "normalized": [] }, { "id": "15441", "type": "", "text": [ "SRL" ], "offsets": [ [ 1347, 1350 ] ], "normalized": [] }, { "id": "15442", "type": "", "text": [ "hyperglycemia" ], "offsets": [ [ 1445, 1458 ] ], "normalized": [] }, { "id": "15444", "type": "", "text": [ "SRL" ], "offsets": [ [ 1576, 1579 ] ], "normalized": [] }, { "id": "15445", "type": "", "text": [ "neurotoxicity" ], "offsets": [ [ 1704, 1717 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15350", "type": "PA", "arg1_id": "15348", "arg2_id": "15349", "normalized": [] }, { "id": "15353", "type": "PA", "arg1_id": "15351", "arg2_id": "15352", "normalized": [] }, { "id": "15356", "type": "PA", "arg1_id": "15354", "arg2_id": "15355", "normalized": [] }, { "id": "15359", "type": "PA", "arg1_id": "15357", "arg2_id": "15358", "normalized": [] }, { "id": "15362", "type": "PA", "arg1_id": "15360", "arg2_id": "15361", "normalized": [] }, { "id": "15365", "type": "PA", "arg1_id": "15363", "arg2_id": "15364", "normalized": [] }, { "id": "15368", "type": "PA", "arg1_id": "15366", "arg2_id": "15367", "normalized": [] }, { "id": "15371", "type": "PA", "arg1_id": "15369", "arg2_id": "15370", "normalized": [] }, { "id": "15374", "type": "PA", "arg1_id": "15372", "arg2_id": "15373", "normalized": [] }, { "id": "15377", "type": "PA", "arg1_id": "15375", "arg2_id": "15376", "normalized": [] }, { "id": "15380", "type": "PA", "arg1_id": "15378", "arg2_id": "15379", "normalized": [] }, { "id": "15383", "type": "PA", "arg1_id": "15381", "arg2_id": "15382", "normalized": [] }, { "id": "15386", "type": "PA", "arg1_id": "15384", "arg2_id": "15385", "normalized": [] }, { "id": "15389", "type": "PA", "arg1_id": "15387", "arg2_id": "15388", "normalized": [] }, { "id": "15392", "type": "PA", "arg1_id": "15390", "arg2_id": "15391", "normalized": [] }, { "id": "15395", "type": "PA", "arg1_id": "15393", "arg2_id": "15394", "normalized": [] }, { "id": "15398", "type": "PA", "arg1_id": "15396", "arg2_id": "15397", "normalized": [] }, { "id": "15401", "type": "PA", "arg1_id": "15399", "arg2_id": "15400", "normalized": [] }, { "id": "15404", "type": "PA", "arg1_id": "15402", "arg2_id": "15403", "normalized": [] }, { "id": "15407", "type": "PA", "arg1_id": "15405", "arg2_id": "15406", "normalized": [] }, { "id": "15410", "type": "PA", "arg1_id": "15408", "arg2_id": "15409", "normalized": [] }, { "id": "15413", "type": "PA", "arg1_id": "15411", "arg2_id": "15412", "normalized": [] }, { "id": "15416", "type": "PA", "arg1_id": "15414", "arg2_id": "15415", "normalized": [] }, { "id": "15419", "type": "PA", "arg1_id": "15417", "arg2_id": "15418", "normalized": [] }, { "id": "15422", "type": "PA", "arg1_id": "15420", "arg2_id": "15421", "normalized": [] }, { "id": "15425", "type": "PA", "arg1_id": "15423", "arg2_id": "15424", "normalized": [] }, { "id": "15428", "type": "PA", "arg1_id": "15426", "arg2_id": "15427", "normalized": [] }, { "id": "15431", "type": "PA", "arg1_id": "15429", "arg2_id": "15430", "normalized": [] }, { "id": "15434", "type": "PA", "arg1_id": "15432", "arg2_id": "15433", "normalized": [] }, { "id": "15437", "type": "PA", "arg1_id": "15435", "arg2_id": "15436", "normalized": [] }, { "id": "15440", "type": "PA", "arg1_id": "15438", "arg2_id": "15439", "normalized": [] }, { "id": "15443", "type": "PA", "arg1_id": "15441", "arg2_id": "15442", "normalized": [] }, { "id": "15446", "type": "PA", "arg1_id": "15444", "arg2_id": "15445", "normalized": [] } ]

[ { "id": "15449", "type": "title", "text": [ "Analysis of DNA variations in promoter region of HCNP gene with Alzheimer's disease." ], "offsets": [ [ 0, 84 ] ] }, { "id": "15450", "type": "abstract", "text": [ "Hippocampal cholinergic neurostimulating peptide (HCNP), which enhances acetylcholine synthesis and induces cholinergic phenotype development of the septohippocampal system, is derived from HCNP precursor protein (HCNPpp), also known as phosphatidylethanolamine binding protein (PEBP) and Raf kinase inhibitor protein (RKIP). Our previous study demonstrated that expression of HCNPpp mRNA was decreased in the hippocampi of autopsied brains of Alzheimer's disease (AD) patients, indicating the association of HCNP with the pathogenesis of AD. To clarify the involvement of gene variations in the promoter region of the gene encoding HCNPpp in this mRNA reduction, we analyzed DNA polymorphisms or mutations within this gene promoter region in AD patients by direct sequencing. The promoter was found to contain a CpG island without a TATA box, an element of housekeeping gene promoters. Moreover, no disease-specific polymorphisms or mutations were identified, suggesting that the decrease of mRNA can be ascribed to transcriptional or posttranscriptional changes in activity." ], "offsets": [ [ 85, 1161 ] ] } ]

[ { "id": "15451", "type": "Genes & Molecular Sequences", "text": [ "HCNP" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "15452", "type": "Diseases & Disorders", "text": [ "Alzheimer's disease" ], "offsets": [ [ 64, 83 ] ], "normalized": [] }, { "id": "15453", "type": "Genes & Molecular Sequences", "text": [ "Hippocampal cholinergic neurostimulating peptide" ], "offsets": [ [ 85, 133 ] ], "normalized": [] }, { "id": "15454", "type": "Genes & Molecular Sequences", "text": [ "HCNP" ], "offsets": [ [ 135, 139 ] ], "normalized": [] }, { "id": "15455", "type": "Genes & Molecular Sequences", "text": [ "HCNP precursor protein" ], "offsets": [ [ 275, 297 ] ], "normalized": [] }, { "id": "15456", "type": "Genes & Molecular Sequences", "text": [ "HCNPpp" ], "offsets": [ [ 299, 305 ] ], "normalized": [] }, { "id": "15457", "type": "Genes & Molecular Sequences", "text": [ "phosphatidylethanolamine binding protein" ], "offsets": [ [ 322, 362 ] ], "normalized": [] }, { "id": "15458", "type": "Genes & Molecular Sequences", "text": [ "PEBP" ], "offsets": [ [ 364, 368 ] ], "normalized": [] }, { "id": "15459", "type": "Genes & Molecular Sequences", "text": [ "Raf kinase inhibitor protein" ], "offsets": [ [ 374, 402 ] ], "normalized": [] }, { "id": "15460", "type": "Genes & Molecular Sequences", "text": [ "RKIP" ], "offsets": [ [ 404, 408 ] ], "normalized": [] }, { "id": "15461", "type": "Genes & Molecular Sequences", "text": [ "HCNPpp" ], "offsets": [ [ 462, 468 ] ], "normalized": [] }, { "id": "15462", "type": "Diseases & Disorders", "text": [ "Alzheimer's disease" ], "offsets": [ [ 529, 548 ] ], "normalized": [] }, { "id": "15463", "type": "Diseases & Disorders", "text": [ "AD" ], "offsets": [ [ 550, 552 ] ], "normalized": [] }, { "id": "15464", "type": "Genes & Molecular Sequences", "text": [ "HCNP" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "15465", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 608, 620 ] ], "normalized": [] }, { "id": "15466", "type": "Diseases & Disorders", "text": [ "AD" ], "offsets": [ [ 624, 626 ] ], "normalized": [] }, { "id": "15467", "type": "Genes & Molecular Sequences", "text": [ "HCNPpp" ], "offsets": [ [ 718, 724 ] ], "normalized": [] }, { "id": "15468", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 782, 791 ] ], "normalized": [] }, { "id": "15469", "type": "Diseases & Disorders", "text": [ "AD" ], "offsets": [ [ 828, 830 ] ], "normalized": [] }, { "id": "15470", "type": "Genes & Molecular Sequences", "text": [ "CpG island" ], "offsets": [ [ 898, 908 ] ], "normalized": [] }, { "id": "15471", "type": "Genes & Molecular Sequences", "text": [ "TATA box" ], "offsets": [ [ 919, 927 ] ], "normalized": [] }, { "id": "15472", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 985, 992 ] ], "normalized": [] }, { "id": "15473", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 1019, 1028 ] ], "normalized": [] }, { "id": "15474", "type": "", "text": [ "HCNP" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "15475", "type": "", "text": [ "Alzheimer's disease" ], "offsets": [ [ 529, 548 ] ], "normalized": [] }, { "id": "15477", "type": "", "text": [ "HCNP" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "15478", "type": "", "text": [ "AD" ], "offsets": [ [ 624, 626 ] ], "normalized": [] }, { "id": "15480", "type": "", "text": [ "HCNPpp" ], "offsets": [ [ 462, 468 ] ], "normalized": [] }, { "id": "15481", "type": "", "text": [ "Alzheimer's disease" ], "offsets": [ [ 529, 548 ] ], "normalized": [] }, { "id": "15483", "type": "", "text": [ "HCNPpp" ], "offsets": [ [ 462, 468 ] ], "normalized": [] }, { "id": "15484", "type": "", "text": [ "AD" ], "offsets": [ [ 624, 626 ] ], "normalized": [] }, { "id": "15486", "type": "", "text": [ "HCNP" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "15487", "type": "", "text": [ "Alzheimer's disease" ], "offsets": [ [ 64, 83 ] ], "normalized": [] }, { "id": "15489", "type": "", "text": [ "HCNP" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "15490", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 608, 620 ] ], "normalized": [] }, { "id": "15492", "type": "", "text": [ "HCNPpp" ], "offsets": [ [ 462, 468 ] ], "normalized": [] }, { "id": "15493", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 608, 620 ] ], "normalized": [] }, { "id": "15495", "type": "", "text": [ "HCNPpp" ], "offsets": [ [ 718, 724 ] ], "normalized": [] }, { "id": "15496", "type": "", "text": [ "mutations" ], "offsets": [ [ 782, 791 ] ], "normalized": [] }, { "id": "15498", "type": "", "text": [ "acetylcholine" ], "offsets": [ [ 157, 170 ] ], "normalized": [] }, { "id": "15499", "type": "", "text": [ "HCNP precursor protein" ], "offsets": [ [ 275, 297 ] ], "normalized": [] }, { "id": "15501", "type": "", "text": [ "acetylcholine" ], "offsets": [ [ 157, 170 ] ], "normalized": [] }, { "id": "15502", "type": "", "text": [ "RKIP" ], "offsets": [ [ 404, 408 ] ], "normalized": [] }, { "id": "15504", "type": "", "text": [ "acetylcholine" ], "offsets": [ [ 157, 170 ] ], "normalized": [] }, { "id": "15505", "type": "", "text": [ "Hippocampal cholinergic neurostimulating peptide" ], "offsets": [ [ 85, 133 ] ], "normalized": [] }, { "id": "15507", "type": "", "text": [ "HCNPpp" ], "offsets": [ [ 718, 724 ] ], "normalized": [] }, { "id": "15508", "type": "", "text": [ "AD" ], "offsets": [ [ 828, 830 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "15512", "type": "title", "text": [ "Association analysis between the Cdc6 G1321A polymorphism and the risk for non-Hodgkin lymphoma and hepatocellular carcinoma." ], "offsets": [ [ 0, 125 ] ] }, { "id": "15513", "type": "abstract", "text": [ "Cdc6 play crucial roles in DNA replication and carcinogenesis. The biological significance of the Cdc6 G1321A polymorphism (V441I, rs13706) is still not elucidated. Here we examined the influence of this polymorphism on the function of Cdc6 and the individual's susceptibility to non-Hodgkin lymphoma (NHL) and hepatocellular carcinoma (HCC). Unconditional logistic regression analysis revealed that the risk for NHL was significantly reduced in both AG heterozygotes [odds ratio (OR)=0.67, P=0.019] and AA homozygotes (OR=0.54, P=0.026), compared with GG homozygotes. Further stratification by subtypes of NHL showed that the AG as well as combined AA/AG genotypes were associated with decreased risk for B-cell-NHL (OR=0.62, P=0.011 and OR=0.61, P=0.006, respectively), especially for diffuse large B-cell lymphoma (DLBCL, OR=0.63, P=0.025 and OR=0.62, P=0.012, respectively). In addition, male individuals with the AA genotype displayed borderline significantly reduced risk for HCC (OR=0.48, P=0.054). Interestingly, the G1321A polymorphism did not affect caspase-mediated cleavage of Cdc6 during etoposide-induced apoptosis, but it was predicted to alter the secondary structure of Cdc6 mRNA. Our data provide the first evidence that the Cdc6 G1321A polymorphism is associated with decreased risk of cancer. Further studies are necessary to confirm the general validity of our findings." ], "offsets": [ [ 126, 1517 ] ] } ]

[ { "id": "15514", "type": "SNP & Sequence variations", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 33, 44 ] ], "normalized": [] }, { "id": "15515", "type": "Genes & Molecular Sequences", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 33, 44 ] ], "normalized": [] }, { "id": "15516", "type": "Diseases & Disorders", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 75, 95 ] ], "normalized": [] }, { "id": "15517", "type": "Diseases & Disorders", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 100, 124 ] ], "normalized": [] }, { "id": "15518", "type": "Genes & Molecular Sequences", "text": [ "Cdc6" ], "offsets": [ [ 126, 130 ] ], "normalized": [] }, { "id": "15519", "type": "Diseases & Disorders", "text": [ "carcinogenesis" ], "offsets": [ [ 173, 187 ] ], "normalized": [] }, { "id": "15520", "type": "SNP & Sequence variations", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "15521", "type": "Genes & Molecular Sequences", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "15522", "type": "SNP & Sequence variations", "text": [ "V441I" ], "offsets": [ [ 250, 255 ] ], "normalized": [] }, { "id": "15523", "type": "SNP & Sequence variations", "text": [ "rs13706" ], "offsets": [ [ 257, 264 ] ], "normalized": [] }, { "id": "15524", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 269, 274 ] ], "normalized": [] }, { "id": "15525", "type": "Genes & Molecular Sequences", "text": [ "Cdc6" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "15526", "type": "Diseases & Disorders", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 406, 426 ] ], "normalized": [] }, { "id": "15527", "type": "Diseases & Disorders", "text": [ "NHL" ], "offsets": [ [ 428, 431 ] ], "normalized": [] }, { "id": "15528", "type": "Genes & Molecular Sequences", "text": [ "NHL" ], "offsets": [ [ 428, 431 ] ], "normalized": [] }, { "id": "15529", "type": "Diseases & Disorders", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 437, 461 ] ], "normalized": [] }, { "id": "15530", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "15531", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "15532", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 492, 502 ] ], "normalized": [] }, { "id": "15533", "type": "Diseases & Disorders", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "15534", "type": "Genes & Molecular Sequences", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "15535", "type": "SNP & Sequence variations", "text": [ "AG" ], "offsets": [ [ 577, 579 ] ], "normalized": [] }, { "id": "15536", "type": "SNP & Sequence variations", "text": [ "AA" ], "offsets": [ [ 630, 632 ] ], "normalized": [] }, { "id": "15537", "type": "SNP & Sequence variations", "text": [ "GG" ], "offsets": [ [ 679, 681 ] ], "normalized": [] }, { "id": "15538", "type": "Diseases & Disorders", "text": [ "NHL" ], "offsets": [ [ 733, 736 ] ], "normalized": [] }, { "id": "15539", "type": "Genes & Molecular Sequences", "text": [ "NHL" ], "offsets": [ [ 733, 736 ] ], "normalized": [] }, { "id": "15540", "type": "SNP & Sequence variations", "text": [ "AG" ], "offsets": [ [ 753, 755 ] ], "normalized": [] }, { "id": "15541", "type": "SNP & Sequence variations", "text": [ "AA/AG" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "15542", "type": "Diseases & Disorders", "text": [ "B-cell-NHL" ], "offsets": [ [ 832, 842 ] ], "normalized": [] }, { "id": "15543", "type": "Diseases & Disorders", "text": [ "diffuse large B-cell lymphoma" ], "offsets": [ [ 913, 942 ] ], "normalized": [] }, { "id": "15544", "type": "Diseases & Disorders", "text": [ "DLBCL" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "15545", "type": "SNP & Sequence variations", "text": [ "AA" ], "offsets": [ [ 1044, 1046 ] ], "normalized": [] }, { "id": "15546", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "15547", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "15548", "type": "SNP & Sequence variations", "text": [ "G1321A" ], "offsets": [ [ 1151, 1157 ] ], "normalized": [] }, { "id": "15549", "type": "Genes & Molecular Sequences", "text": [ "Cdc6" ], "offsets": [ [ 1215, 1219 ] ], "normalized": [] }, { "id": "15550", "type": "Diseases & Disorders", "text": [ "etoposide" ], "offsets": [ [ 1227, 1236 ] ], "normalized": [] }, { "id": "15551", "type": "Diseases & Disorders", "text": [ "secondary" ], "offsets": [ [ 1290, 1299 ] ], "normalized": [] }, { "id": "15552", "type": "Genes & Molecular Sequences", "text": [ "Cdc6" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "15553", "type": "SNP & Sequence variations", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 1369, 1380 ] ], "normalized": [] }, { "id": "15554", "type": "Genes & Molecular Sequences", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 1369, 1380 ] ], "normalized": [] }, { "id": "15555", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 1431, 1437 ] ], "normalized": [] }, { "id": "15556", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 126, 130 ] ], "normalized": [] }, { "id": "15557", "type": "", "text": [ "carcinogenesis" ], "offsets": [ [ 173, 187 ] ], "normalized": [] }, { "id": "15559", "type": "", "text": [ "AG" ], "offsets": [ [ 577, 579 ] ], "normalized": [] }, { "id": "15560", "type": "", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "15562", "type": "", "text": [ "AA" ], "offsets": [ [ 630, 632 ] ], "normalized": [] }, { "id": "15563", "type": "", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "15565", "type": "", "text": [ "AG" ], "offsets": [ [ 753, 755 ] ], "normalized": [] }, { "id": "15566", "type": "", "text": [ "DLBCL" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "15568", "type": "", "text": [ "AG" ], "offsets": [ [ 753, 755 ] ], "normalized": [] }, { "id": "15569", "type": "", "text": [ "diffuse large B-cell lymphoma" ], "offsets": [ [ 913, 942 ] ], "normalized": [] }, { "id": "15571", "type": "", "text": [ "AG" ], "offsets": [ [ 753, 755 ] ], "normalized": [] }, { "id": "15572", "type": "", "text": [ "B-cell-NHL" ], "offsets": [ [ 832, 842 ] ], "normalized": [] }, { "id": "15574", "type": "", "text": [ "AA/AG" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "15575", "type": "", "text": [ "DLBCL" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "15577", "type": "", "text": [ "AA/AG" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "15578", "type": "", "text": [ "diffuse large B-cell lymphoma" ], "offsets": [ [ 913, 942 ] ], "normalized": [] }, { "id": "15580", "type": "", "text": [ "AA/AG" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "15581", "type": "", "text": [ "B-cell-NHL" ], "offsets": [ [ 832, 842 ] ], "normalized": [] }, { "id": "15583", "type": "", "text": [ "AA" ], "offsets": [ [ 1044, 1046 ] ], "normalized": [] }, { "id": "15584", "type": "", "text": [ "HCC" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "15586", "type": "", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 1369, 1380 ] ], "normalized": [] }, { "id": "15587", "type": "", "text": [ "cancer" ], "offsets": [ [ 1431, 1437 ] ], "normalized": [] }, { "id": "15589", "type": "", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 33, 44 ] ], "normalized": [] }, { "id": "15590", "type": "", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 75, 95 ] ], "normalized": [] }, { "id": "15592", "type": "", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 33, 44 ] ], "normalized": [] }, { "id": "15593", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 100, 124 ] ], "normalized": [] }, { "id": "15595", "type": "", "text": [ "Cdc6 G1321A" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "15596", "type": "", "text": [ "still" ], "offsets": [ [ 269, 274 ] ], "normalized": [] }, { "id": "15598", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "15599", "type": "", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 406, 426 ] ], "normalized": [] }, { "id": "15601", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "15602", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 437, 461 ] ], "normalized": [] }, { "id": "15604", "type": "", "text": [ "NHL" ], "offsets": [ [ 428, 431 ] ], "normalized": [] }, { "id": "15605", "type": "", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 406, 426 ] ], "normalized": [] }, { "id": "15607", "type": "", "text": [ "NHL" ], "offsets": [ [ 428, 431 ] ], "normalized": [] }, { "id": "15608", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 437, 461 ] ], "normalized": [] }, { "id": "15610", "type": "", "text": [ "HCC" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "15611", "type": "", "text": [ "non-Hodgkin lymphoma" ], "offsets": [ [ 406, 426 ] ], "normalized": [] }, { "id": "15613", "type": "", "text": [ "HCC" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "15614", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 437, 461 ] ], "normalized": [] }, { "id": "15616", "type": "", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "15617", "type": "", "text": [ "regression" ], "offsets": [ [ 492, 502 ] ], "normalized": [] }, { "id": "15619", "type": "", "text": [ "NHL" ], "offsets": [ [ 733, 736 ] ], "normalized": [] }, { "id": "15620", "type": "", "text": [ "DLBCL" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "15622", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "15623", "type": "", "text": [ "secondary" ], "offsets": [ [ 1290, 1299 ] ], "normalized": [] }, { "id": "15625", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "15626", "type": "", "text": [ "NHL" ], "offsets": [ [ 428, 431 ] ], "normalized": [] }, { "id": "15628", "type": "", "text": [ "Cdc6" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "15629", "type": "", "text": [ "HCC" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "15631", "type": "", "text": [ "GG" ], "offsets": [ [ 679, 681 ] ], "normalized": [] }, { "id": "15632", "type": "", "text": [ "NHL" ], "offsets": [ [ 539, 542 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15558", "type": "PA", "arg1_id": "15556", "arg2_id": "15557", "normalized": [] }, { "id": "15561", "type": "PA", "arg1_id": "15559", "arg2_id": "15560", "normalized": [] }, { "id": "15564", "type": "PA", "arg1_id": "15562", "arg2_id": "15563", "normalized": [] }, { "id": "15567", "type": "PA", "arg1_id": "15565", "arg2_id": "15566", "normalized": [] }, { "id": "15570", "type": "PA", "arg1_id": "15568", "arg2_id": "15569", "normalized": [] }, { "id": "15573", "type": "PA", "arg1_id": "15571", "arg2_id": "15572", "normalized": [] }, { "id": "15576", "type": "PA", "arg1_id": "15574", "arg2_id": "15575", "normalized": [] }, { "id": "15579", "type": "PA", "arg1_id": "15577", "arg2_id": "15578", "normalized": [] }, { "id": "15582", "type": "PA", "arg1_id": "15580", "arg2_id": "15581", "normalized": [] }, { "id": "15585", "type": "PA", "arg1_id": "15583", "arg2_id": "15584", "normalized": [] }, { "id": "15588", "type": "PA", "arg1_id": "15586", "arg2_id": "15587", "normalized": [] }, { "id": "15591", "type": "PA", "arg1_id": "15589", "arg2_id": "15590", "normalized": [] }, { "id": "15594", "type": "PA", "arg1_id": "15592", "arg2_id": "15593", "normalized": [] }, { "id": "15597", "type": "PA", "arg1_id": "15595", "arg2_id": "15596", "normalized": [] }, { "id": "15600", "type": "PA", "arg1_id": "15598", "arg2_id": "15599", "normalized": [] }, { "id": "15603", "type": "PA", "arg1_id": "15601", "arg2_id": "15602", "normalized": [] }, { "id": "15606", "type": "PA", "arg1_id": "15604", "arg2_id": "15605", "normalized": [] }, { "id": "15609", "type": "PA", "arg1_id": "15607", "arg2_id": "15608", "normalized": [] }, { "id": "15612", "type": "PA", "arg1_id": "15610", "arg2_id": "15611", "normalized": [] }, { "id": "15615", "type": "PA", "arg1_id": "15613", "arg2_id": "15614", "normalized": [] }, { "id": "15618", "type": "PA", "arg1_id": "15616", "arg2_id": "15617", "normalized": [] }, { "id": "15621", "type": "PA", "arg1_id": "15619", "arg2_id": "15620", "normalized": [] }, { "id": "15624", "type": "PA", "arg1_id": "15622", "arg2_id": "15623", "normalized": [] }, { "id": "15627", "type": "SA", "arg1_id": "15625", "arg2_id": "15626", "normalized": [] }, { "id": "15630", "type": "SA", "arg1_id": "15628", "arg2_id": "15629", "normalized": [] }, { "id": "15633", "type": "NA", "arg1_id": "15631", "arg2_id": "15632", "normalized": [] } ]

[ { "id": "15636", "type": "title", "text": [ "Expansion of the human mu-opioid receptor gene architecture: novel functional variants." ], "offsets": [ [ 0, 87 ] ] }, { "id": "15637", "type": "abstract", "text": [ "The mu-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and obtained evidence for the existence of an expanded human OPRM1 gene locus with new promoters, alternative exons and regulatory elements. Examination of polymorphisms within the human OPRM1 gene locus identified strong association between single nucleotide polymorphism (SNP) rs563649 and individual variations in pain perception. SNP rs563649 is located within a structurally conserved internal ribosome entry site (IRES) in the 5'-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and affects both mRNA levels and translation efficiency of these variants. Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the entire OPRM1 gene locus and thus affects the functional contribution of the corresponding haplotype that includes other functional OPRM1 SNPs. Our results provide evidence for an essential role for MOR-1K isoforms in nociceptive signaling and suggest that genetic variations in alternative OPRM1 isoforms may contribute to individual differences in opiate responses." ], "offsets": [ [ 88, 1458 ] ] } ]

[ { "id": "15638", "type": "Genes & Molecular Sequences", "text": [ "mu-opioid receptor" ], "offsets": [ [ 23, 41 ] ], "normalized": [] }, { "id": "15639", "type": "Genes & Molecular Sequences", "text": [ "mu-opioid receptor" ], "offsets": [ [ 92, 110 ] ], "normalized": [] }, { "id": "15640", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 112, 117 ] ], "normalized": [] }, { "id": "15641", "type": "Diseases & Disorders", "text": [ "responses to painful stimuli" ], "offsets": [ [ 259, 287 ] ], "normalized": [] }, { "id": "15642", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 353, 358 ] ], "normalized": [] }, { "id": "15643", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 503, 508 ] ], "normalized": [] }, { "id": "15644", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "15645", "type": "SNP & Sequence variations", "text": [ "rs563649" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "15646", "type": "Diseases & Disorders", "text": [ "pain perception" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "15647", "type": "SNP & Sequence variations", "text": [ "rs563649" ], "offsets": [ [ 780, 788 ] ], "normalized": [] }, { "id": "15648", "type": "Genes & Molecular Sequences", "text": [ "internal ribosome entry site" ], "offsets": [ [ 832, 860 ] ], "normalized": [] }, { "id": "15649", "type": "Genes & Molecular Sequences", "text": [ "IRES" ], "offsets": [ [ 862, 866 ] ], "normalized": [] }, { "id": "15650", "type": "Genes & Molecular Sequences", "text": [ "5'-UTR" ], "offsets": [ [ 875, 881 ] ], "normalized": [] }, { "id": "15651", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 912, 917 ] ], "normalized": [] }, { "id": "15652", "type": "SNP & Sequence variations", "text": [ "MOR-1K" ], "offsets": [ [ 928, 934 ] ], "normalized": [] }, { "id": "15653", "type": "Genes & Molecular Sequences", "text": [ "MOR-1K" ], "offsets": [ [ 928, 934 ] ], "normalized": [] }, { "id": "15654", "type": "SNP & Sequence variations", "text": [ "rs563649" ], "offsets": [ [ 1024, 1032 ] ], "normalized": [] }, { "id": "15655", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 1099, 1104 ] ], "normalized": [] }, { "id": "15656", "type": "SNP & Sequence variations", "text": [ "OPRM1 SNPs" ], "offsets": [ [ 1223, 1233 ] ], "normalized": [] }, { "id": "15657", "type": "Genes & Molecular Sequences", "text": [ "OPRM1 SNPs" ], "offsets": [ [ 1223, 1233 ] ], "normalized": [] }, { "id": "15658", "type": "SNP & Sequence variations", "text": [ "MOR-1K" ], "offsets": [ [ 1290, 1296 ] ], "normalized": [] }, { "id": "15659", "type": "Genes & Molecular Sequences", "text": [ "MOR-1K" ], "offsets": [ [ 1290, 1296 ] ], "normalized": [] }, { "id": "15660", "type": "Diseases & Disorders", "text": [ "nociceptive signaling" ], "offsets": [ [ 1309, 1330 ] ], "normalized": [] }, { "id": "15661", "type": "Genes & Molecular Sequences", "text": [ "OPRM1" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "15662", "type": "Diseases & Disorders", "text": [ "opiate responses" ], "offsets": [ [ 1441, 1457 ] ], "normalized": [] }, { "id": "15663", "type": "", "text": [ "OPRM1" ], "offsets": [ [ 353, 358 ] ], "normalized": [] }, { "id": "15664", "type": "", "text": [ "responses to painful stimuli" ], "offsets": [ [ 259, 287 ] ], "normalized": [] }, { "id": "15666", "type": "", "text": [ "OPRM1" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "15667", "type": "", "text": [ "pain perception" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "15669", "type": "", "text": [ "rs563649" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "15670", "type": "", "text": [ "pain perception" ], "offsets": [ [ 759, 774 ] ], "normalized": [] }, { "id": "15672", "type": "", "text": [ "OPRM1" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "15673", "type": "", "text": [ "opiate responses" ], "offsets": [ [ 1441, 1457 ] ], "normalized": [] }, { "id": "15675", "type": "", "text": [ "MOR-1K" ], "offsets": [ [ 1290, 1296 ] ], "normalized": [] }, { "id": "15676", "type": "", "text": [ "nociceptive signaling" ], "offsets": [ [ 1309, 1330 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15665", "type": "PA", "arg1_id": "15663", "arg2_id": "15664", "normalized": [] }, { "id": "15668", "type": "PA", "arg1_id": "15666", "arg2_id": "15667", "normalized": [] }, { "id": "15671", "type": "PA", "arg1_id": "15669", "arg2_id": "15670", "normalized": [] }, { "id": "15674", "type": "PA", "arg1_id": "15672", "arg2_id": "15673", "normalized": [] }, { "id": "15677", "type": "PA", "arg1_id": "15675", "arg2_id": "15676", "normalized": [] } ]

[ { "id": "15680", "type": "title", "text": [ "Association between donor MBL promoter haplotype and graft survival and the development of BOS after lung transplantation." ], "offsets": [ [ 0, 122 ] ] }, { "id": "15681", "type": "abstract", "text": [ "BACKGROUND: Lung transplantation is a well accepted therapy for end-stage lung disease, despite high mortality rates. Mortality after transplantation is mainly caused by allograft failure in the first years after transplantation. Mannose binding lectin (MBL), a recognition molecule of innate immunity, has been associated with transplant outcome in other solid organ transplantation. In this study, the effect of donor- and recipient-MBL genotype on lung transplant outcome was investigated. MATERIALS AND METHODS: All lung transplantations performed in our center, except from retransplantations and combined lung-liver or heart-lung transplantations, were included. Genotyping of the MBL2 variants (promoter: L/H, Y/X, and P/Q allele and exon 1: A/D, A/B, and A/C allele) was performed in donor and recipient DNA. Analyses on graft survival and the development of bronchiolitis obliterans syndrome were performed with Kaplan-Meier (log rank) survival analysis. RESULTS: Of the 277 included cases, DNA was available from 189 donors and 200 recipients and genotyping of the promoter single nucleotide polymorphisms was successful in 184 donors and 198 recipients and of the exon 1 single nucleotide polymorphisms in 181 donors and 193 recipients. Patients who received a graft from a donor with an X-allele had better graft survival (P=0.007) and bronchiolitis obliterans syndrome free survival (P=0.007). Recipient MBL genotype was not associated with transplant outcome. CONCLUSION: The donor X-allele, which corresponds to the LXPA haplotype is associated with superior lung transplant outcome. Our findings might prove to be important in finding ways to optimize outcome after lung transplantation." ], "offsets": [ [ 123, 1826 ] ] } ]

[ { "id": "15682", "type": "SNP & Sequence variations", "text": [ "MBL promoter haplotype" ], "offsets": [ [ 26, 48 ] ], "normalized": [] }, { "id": "15683", "type": "Genes & Molecular Sequences", "text": [ "MBL promoter haplotype" ], "offsets": [ [ 26, 48 ] ], "normalized": [] }, { "id": "15684", "type": "Diseases & Disorders", "text": [ "BOS" ], "offsets": [ [ 91, 94 ] ], "normalized": [] }, { "id": "15685", "type": "Diseases & Disorders", "text": [ "end-stage lung disease" ], "offsets": [ [ 187, 209 ] ], "normalized": [] }, { "id": "15686", "type": "Genes & Molecular Sequences", "text": [ "Mannose binding lectin" ], "offsets": [ [ 353, 375 ] ], "normalized": [] }, { "id": "15687", "type": "Genes & Molecular Sequences", "text": [ "MBL" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "15688", "type": "Genes & Molecular Sequences", "text": [ "MBL" ], "offsets": [ [ 558, 561 ] ], "normalized": [] }, { "id": "15689", "type": "Genes & Molecular Sequences", "text": [ "MBL2" ], "offsets": [ [ 810, 814 ] ], "normalized": [] }, { "id": "15690", "type": "SNP & Sequence variations", "text": [ "L/H" ], "offsets": [ [ 835, 838 ] ], "normalized": [] }, { "id": "15691", "type": "SNP & Sequence variations", "text": [ "Y/X" ], "offsets": [ [ 840, 843 ] ], "normalized": [] }, { "id": "15692", "type": "SNP & Sequence variations", "text": [ "P/Q allele" ], "offsets": [ [ 849, 859 ] ], "normalized": [] }, { "id": "15693", "type": "SNP & Sequence variations", "text": [ "A/D" ], "offsets": [ [ 872, 875 ] ], "normalized": [] }, { "id": "15694", "type": "SNP & Sequence variations", "text": [ "A/B" ], "offsets": [ [ 877, 880 ] ], "normalized": [] }, { "id": "15695", "type": "SNP & Sequence variations", "text": [ "A/C allele" ], "offsets": [ [ 886, 896 ] ], "normalized": [] }, { "id": "15696", "type": "Diseases & Disorders", "text": [ "bronchiolitis obliterans syndrome" ], "offsets": [ [ 990, 1023 ] ], "normalized": [] }, { "id": "15697", "type": "Genes & Molecular Sequences", "text": [ "rank" ], "offsets": [ [ 1062, 1066 ] ], "normalized": [] }, { "id": "15698", "type": "SNP & Sequence variations", "text": [ "X-allele" ], "offsets": [ [ 1422, 1430 ] ], "normalized": [] }, { "id": "15699", "type": "Diseases & Disorders", "text": [ "bronchiolitis obliterans syndrome" ], "offsets": [ [ 1471, 1504 ] ], "normalized": [] }, { "id": "15700", "type": "Genes & Molecular Sequences", "text": [ "MBL" ], "offsets": [ [ 1540, 1543 ] ], "normalized": [] }, { "id": "15701", "type": "SNP & Sequence variations", "text": [ "X-allele" ], "offsets": [ [ 1619, 1627 ] ], "normalized": [] }, { "id": "15702", "type": "SNP & Sequence variations", "text": [ "LXPA haplotype" ], "offsets": [ [ 1654, 1668 ] ], "normalized": [] }, { "id": "15703", "type": "Genes & Molecular Sequences", "text": [ "LXPA haplotype" ], "offsets": [ [ 1654, 1668 ] ], "normalized": [] }, { "id": "15704", "type": "", "text": [ "MBL promoter haplotype" ], "offsets": [ [ 26, 48 ] ], "normalized": [] }, { "id": "15705", "type": "", "text": [ "BOS" ], "offsets": [ [ 91, 94 ] ], "normalized": [] }, { "id": "15707", "type": "", "text": [ "X-allele" ], "offsets": [ [ 1422, 1430 ] ], "normalized": [] }, { "id": "15708", "type": "", "text": [ "bronchiolitis obliterans syndrome" ], "offsets": [ [ 1471, 1504 ] ], "normalized": [] }, { "id": "15710", "type": "", "text": [ "rank" ], "offsets": [ [ 1062, 1066 ] ], "normalized": [] }, { "id": "15711", "type": "", "text": [ "bronchiolitis obliterans syndrome" ], "offsets": [ [ 990, 1023 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15706", "type": "SA", "arg1_id": "15704", "arg2_id": "15705", "normalized": [] }, { "id": "15709", "type": "PA", "arg1_id": "15707", "arg2_id": "15708", "normalized": [] }, { "id": "15712", "type": "PA", "arg1_id": "15710", "arg2_id": "15711", "normalized": [] } ]

[ { "id": "15715", "type": "title", "text": [ "Prostate cancer genomics: towards a new understanding." ], "offsets": [ [ 0, 54 ] ] }, { "id": "15716", "type": "abstract", "text": [ "Recent genetics and genomics studies of prostate cancer have helped to clarify the genetic basis of this common but complex disease. Genome-wide studies have detected numerous variants associated with disease as well as common gene fusions and expression 'signatures' in prostate tumours. On the basis of these results, some advocate gene-based individualized screening for prostate cancer, although such testing might only be worthwhile to distinguish disease aggressiveness. Lessons learned from these studies provide strategies for further deciphering the genetic causes of prostate cancer and other diseases." ], "offsets": [ [ 55, 667 ] ] } ]

[ { "id": "15717", "type": "Diseases & Disorders", "text": [ "Prostate cancer" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "15718", "type": "Diseases & Disorders", "text": [ "prostate cancer" ], "offsets": [ [ 95, 110 ] ], "normalized": [] }, { "id": "15719", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 179, 186 ] ], "normalized": [] }, { "id": "15720", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 256, 263 ] ], "normalized": [] }, { "id": "15721", "type": "Diseases & Disorders", "text": [ "gene fusions" ], "offsets": [ [ 282, 294 ] ], "normalized": [] }, { "id": "15722", "type": "Genes & Molecular Sequences", "text": [ "gene fusions" ], "offsets": [ [ 282, 294 ] ], "normalized": [] }, { "id": "15723", "type": "Genes & Molecular Sequences", "text": [ "expression 'signatures'" ], "offsets": [ [ 299, 322 ] ], "normalized": [] }, { "id": "15724", "type": "Diseases & Disorders", "text": [ "prostate tumours" ], "offsets": [ [ 326, 342 ] ], "normalized": [] }, { "id": "15725", "type": "Diseases & Disorders", "text": [ "prostate cancer" ], "offsets": [ [ 429, 444 ] ], "normalized": [] }, { "id": "15726", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 508, 515 ] ], "normalized": [] }, { "id": "15727", "type": "Diseases & Disorders", "text": [ "aggressiveness" ], "offsets": [ [ 516, 530 ] ], "normalized": [] }, { "id": "15728", "type": "Diseases & Disorders", "text": [ "prostate cancer" ], "offsets": [ [ 632, 647 ] ], "normalized": [] }, { "id": "15729", "type": "Diseases & Disorders", "text": [ "diseases" ], "offsets": [ [ 658, 666 ] ], "normalized": [] }, { "id": "15730", "type": "", "text": [ "gene fusions" ], "offsets": [ [ 282, 294 ] ], "normalized": [] }, { "id": "15731", "type": "", "text": [ "prostate tumours" ], "offsets": [ [ 326, 342 ] ], "normalized": [] }, { "id": "15733", "type": "", "text": [ "expression 'signatures'" ], "offsets": [ [ 299, 322 ] ], "normalized": [] }, { "id": "15734", "type": "", "text": [ "prostate tumours" ], "offsets": [ [ 326, 342 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15732", "type": "PA", "arg1_id": "15730", "arg2_id": "15731", "normalized": [] }, { "id": "15735", "type": "PA", "arg1_id": "15733", "arg2_id": "15734", "normalized": [] } ]

[ { "id": "15738", "type": "title", "text": [ "Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer." ], "offsets": [ [ 0, 120 ] ] }, { "id": "15739", "type": "abstract", "text": [ "The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T genotypes. A total of 180 patients with metastatic colorectal cancer were categorized as high IL-1RA producers if they were carriers of at least one of the rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times were 35.8 months (95% confidence interval: 29.7-43.7 months) and 28.6 months (95% confidence interval: 25.6-30 months) in 56 T/T carriers and in 124 non-T/T carriers, respectively. The favorable association between T/T carriers' status and survival was significant in the multivariate analysis (P=0.018). Also, T/T carriers and non-T/T carriers were prevalent among patients with Karnofsky performance status 90-100 and 70-80, respectively (P=0.002). These findings encourage additional studies in this field and the evaluation of a recombinant-IL-1RA for anticancer activity." ], "offsets": [ [ 121, 1252 ] ] } ]

[ { "id": "15740", "type": "Genes & Molecular Sequences", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 18, 51 ] ], "normalized": [] }, { "id": "15741", "type": "Diseases & Disorders", "text": [ "survival" ], "offsets": [ [ 67, 75 ] ], "normalized": [] }, { "id": "15742", "type": "Diseases & Disorders", "text": [ "colorectal cancer" ], "offsets": [ [ 102, 119 ] ], "normalized": [] }, { "id": "15743", "type": "Genes & Molecular Sequences", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 125, 158 ] ], "normalized": [] }, { "id": "15744", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA" ], "offsets": [ [ 160, 166 ] ], "normalized": [] }, { "id": "15745", "type": "Diseases & Disorders", "text": [ "tumor angiogenesis" ], "offsets": [ [ 202, 220 ] ], "normalized": [] }, { "id": "15746", "type": "Diseases & Disorders", "text": [ "metastasis" ], "offsets": [ [ 221, 231 ] ], "normalized": [] }, { "id": "15747", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA" ], "offsets": [ [ 276, 282 ] ], "normalized": [] }, { "id": "15748", "type": "SNP & Sequence variations", "text": [ "rs4251961 T/C" ], "offsets": [ [ 289, 302 ] ], "normalized": [] }, { "id": "15749", "type": "SNP & Sequence variations", "text": [ "rs579543 C/T" ], "offsets": [ [ 307, 319 ] ], "normalized": [] }, { "id": "15750", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA" ], "offsets": [ [ 331, 337 ] ], "normalized": [] }, { "id": "15751", "type": "SNP & Sequence variations", "text": [ "rs4251961 T/T" ], "offsets": [ [ 411, 424 ] ], "normalized": [] }, { "id": "15752", "type": "SNP & Sequence variations", "text": [ "rs579543 T/T" ], "offsets": [ [ 429, 441 ] ], "normalized": [] }, { "id": "15753", "type": "Diseases & Disorders", "text": [ "metastatic colorectal cancer" ], "offsets": [ [ 482, 510 ] ], "normalized": [] }, { "id": "15754", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA" ], "offsets": [ [ 536, 542 ] ], "normalized": [] }, { "id": "15755", "type": "SNP & Sequence variations", "text": [ "rs4251961 T/T" ], "offsets": [ [ 598, 611 ] ], "normalized": [] }, { "id": "15756", "type": "SNP & Sequence variations", "text": [ "rs579543 T/T" ], "offsets": [ [ 615, 627 ] ], "normalized": [] }, { "id": "15757", "type": "SNP & Sequence variations", "text": [ "T/T" ], "offsets": [ [ 639, 642 ] ], "normalized": [] }, { "id": "15758", "type": "Diseases & Disorders", "text": [ "survival" ], "offsets": [ [ 661, 669 ] ], "normalized": [] }, { "id": "15759", "type": "SNP & Sequence variations", "text": [ "T/T" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "15760", "type": "SNP & Sequence variations", "text": [ "non-T/T" ], "offsets": [ [ 825, 832 ] ], "normalized": [] }, { "id": "15761", "type": "SNP & Sequence variations", "text": [ "T/T" ], "offsets": [ [ 891, 894 ] ], "normalized": [] }, { "id": "15762", "type": "Diseases & Disorders", "text": [ "survival" ], "offsets": [ [ 916, 924 ] ], "normalized": [] }, { "id": "15763", "type": "SNP & Sequence variations", "text": [ "T/T" ], "offsets": [ [ 987, 990 ] ], "normalized": [] }, { "id": "15764", "type": "SNP & Sequence variations", "text": [ "non-T/T" ], "offsets": [ [ 1004, 1011 ] ], "normalized": [] }, { "id": "15765", "type": "Diseases & Disorders", "text": [ "performance status" ], "offsets": [ [ 1066, 1084 ] ], "normalized": [] }, { "id": "15766", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA" ], "offsets": [ [ 1221, 1227 ] ], "normalized": [] }, { "id": "15767", "type": "Diseases & Disorders", "text": [ "anticancer activity" ], "offsets": [ [ 1232, 1251 ] ], "normalized": [] }, { "id": "15768", "type": "", "text": [ "IL-1RA" ], "offsets": [ [ 160, 166 ] ], "normalized": [] }, { "id": "15769", "type": "", "text": [ "tumor angiogenesis" ], "offsets": [ [ 202, 220 ] ], "normalized": [] }, { "id": "15771", "type": "", "text": [ "IL-1RA" ], "offsets": [ [ 160, 166 ] ], "normalized": [] }, { "id": "15772", "type": "", "text": [ "metastasis" ], "offsets": [ [ 221, 231 ] ], "normalized": [] }, { "id": "15774", "type": "", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 18, 51 ] ], "normalized": [] }, { "id": "15775", "type": "", "text": [ "colorectal cancer" ], "offsets": [ [ 102, 119 ] ], "normalized": [] }, { "id": "15777", "type": "", "text": [ "IL-1RA" ], "offsets": [ [ 536, 542 ] ], "normalized": [] }, { "id": "15778", "type": "", "text": [ "metastatic colorectal cancer" ], "offsets": [ [ 482, 510 ] ], "normalized": [] }, { "id": "15780", "type": "", "text": [ "rs4251961 T/T" ], "offsets": [ [ 598, 611 ] ], "normalized": [] }, { "id": "15781", "type": "", "text": [ "metastatic colorectal cancer" ], "offsets": [ [ 482, 510 ] ], "normalized": [] }, { "id": "15783", "type": "", "text": [ "rs579543 T/T" ], "offsets": [ [ 615, 627 ] ], "normalized": [] }, { "id": "15784", "type": "", "text": [ "metastatic colorectal cancer" ], "offsets": [ [ 482, 510 ] ], "normalized": [] }, { "id": "15786", "type": "", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 18, 51 ] ], "normalized": [] }, { "id": "15787", "type": "", "text": [ "survival" ], "offsets": [ [ 67, 75 ] ], "normalized": [] }, { "id": "15789", "type": "", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 125, 158 ] ], "normalized": [] }, { "id": "15790", "type": "", "text": [ "tumor angiogenesis" ], "offsets": [ [ 202, 220 ] ], "normalized": [] }, { "id": "15792", "type": "", "text": [ "interleukin-1 receptor antagonist" ], "offsets": [ [ 125, 158 ] ], "normalized": [] }, { "id": "15793", "type": "", "text": [ "metastasis" ], "offsets": [ [ 221, 231 ] ], "normalized": [] }, { "id": "15795", "type": "", "text": [ "T/T" ], "offsets": [ [ 639, 642 ] ], "normalized": [] }, { "id": "15796", "type": "", "text": [ "metastatic colorectal cancer" ], "offsets": [ [ 482, 510 ] ], "normalized": [] }, { "id": "15798", "type": "", "text": [ "T/T" ], "offsets": [ [ 891, 894 ] ], "normalized": [] }, { "id": "15799", "type": "", "text": [ "survival" ], "offsets": [ [ 916, 924 ] ], "normalized": [] }, { "id": "15801", "type": "", "text": [ "T/T" ], "offsets": [ [ 987, 990 ] ], "normalized": [] }, { "id": "15802", "type": "", "text": [ "performance status" ], "offsets": [ [ 1066, 1084 ] ], "normalized": [] }, { "id": "15804", "type": "", "text": [ "non-T/T" ], "offsets": [ [ 1004, 1011 ] ], "normalized": [] }, { "id": "15805", "type": "", "text": [ "performance status" ], "offsets": [ [ 1066, 1084 ] ], "normalized": [] }, { "id": "15807", "type": "", "text": [ "IL-1RA" ], "offsets": [ [ 1221, 1227 ] ], "normalized": [] }, { "id": "15808", "type": "", "text": [ "anticancer activity" ], "offsets": [ [ 1232, 1251 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15770", "type": "SA", "arg1_id": "15768", "arg2_id": "15769", "normalized": [] }, { "id": "15773", "type": "SA", "arg1_id": "15771", "arg2_id": "15772", "normalized": [] }, { "id": "15776", "type": "PA", "arg1_id": "15774", "arg2_id": "15775", "normalized": [] }, { "id": "15779", "type": "PA", "arg1_id": "15777", "arg2_id": "15778", "normalized": [] }, { "id": "15782", "type": "PA", "arg1_id": "15780", "arg2_id": "15781", "normalized": [] }, { "id": "15785", "type": "PA", "arg1_id": "15783", "arg2_id": "15784", "normalized": [] }, { "id": "15788", "type": "PA", "arg1_id": "15786", "arg2_id": "15787", "normalized": [] }, { "id": "15791", "type": "SA", "arg1_id": "15789", "arg2_id": "15790", "normalized": [] }, { "id": "15794", "type": "SA", "arg1_id": "15792", "arg2_id": "15793", "normalized": [] }, { "id": "15797", "type": "SA", "arg1_id": "15795", "arg2_id": "15796", "normalized": [] }, { "id": "15800", "type": "PA", "arg1_id": "15798", "arg2_id": "15799", "normalized": [] }, { "id": "15803", "type": "PA", "arg1_id": "15801", "arg2_id": "15802", "normalized": [] }, { "id": "15806", "type": "PA", "arg1_id": "15804", "arg2_id": "15805", "normalized": [] }, { "id": "15809", "type": "SA", "arg1_id": "15807", "arg2_id": "15808", "normalized": [] } ]

[ { "id": "15812", "type": "title", "text": [ "Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies." ], "offsets": [ [ 0, 123 ] ] }, { "id": "15813", "type": "abstract", "text": [ "BACKGROUND: Vitamin D serum levels have been found to be related to sun exposure and diet, together with cell differentiation, growth control and consequently, cancer risk. Vitamin D receptor (VDR) genotypes may influence cancer risk; however, no epidemiological studies in sporadic breast cancer (BC) or malignant melanoma (MM) have been performed in a southern European population. In this study, the VDR gene has been evaluated in two epithelial cancers BC and MM. METHODS: We have conducted an analysis in 549 consecutive and non-related sporadic BC cases and 556 controls, all from the Spanish population, and 283 MM cases and 245 controls. Genotyping analyses were carried out on four putatively functional SNPs within the VDR gene. RESULTS: An association with the minor allele A of the non-synonymous SNP rs2228570 (rs10735810, FokI, Met1Thr) was observed for BC, with an estimated odds ratio (OR) of 1.26 (95% CI = 1.02-1.57; p = 0.036). The synonymous variant rs731236 (TaqI) appeared to be associated with protection from BC (OR = 0.80, 95%CI = 0.64-0.99; p = 0.047). No statistically significant associations with MM were observed for any SNP. Nevertheless, sub-group analyses revealed an association between rs2228570 (FokI) and absence of childhood sunburns (OR = 0.65, p = 0.003), between the 3'utr SNP rs739837 (BglI) and fair skin (OR = 1.31, p = 0.048), and between the promoter SNP rs4516035 and the more aggressive tumour location in head-neck and trunk (OR = 1.54, p = 0.020). CONCLUSION: In summary, we observed associations between SNPs in the VDR gene and BC risk, and a comprehensive analysis using clinical and tumour characteristics as outcome variables has revealed potential associations with MM. These associations required confirmation in independent studies." ], "offsets": [ [ 124, 1914 ] ] } ]

[ { "id": "15814", "type": "Genes & Molecular Sequences", "text": [ "vitamin D receptor" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "15815", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 66, 73 ] ], "normalized": [] }, { "id": "15816", "type": "Diseases & Disorders", "text": [ "melanoma" ], "offsets": [ [ 75, 83 ] ], "normalized": [] }, { "id": "15817", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 88, 101 ] ], "normalized": [] }, { "id": "15818", "type": "Genes & Molecular Sequences", "text": [ "Vitamin D" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "15819", "type": "Diseases & Disorders", "text": [ "cell differentiation" ], "offsets": [ [ 229, 249 ] ], "normalized": [] }, { "id": "15820", "type": "Diseases & Disorders", "text": [ "growth" ], "offsets": [ [ 251, 257 ] ], "normalized": [] }, { "id": "15821", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 284, 290 ] ], "normalized": [] }, { "id": "15822", "type": "Genes & Molecular Sequences", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15823", "type": "Genes & Molecular Sequences", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15824", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 346, 352 ] ], "normalized": [] }, { "id": "15825", "type": "Diseases & Disorders", "text": [ "sporadic breast cancer" ], "offsets": [ [ 398, 420 ] ], "normalized": [] }, { "id": "15826", "type": "Diseases & Disorders", "text": [ "BC" ], "offsets": [ [ 422, 424 ] ], "normalized": [] }, { "id": "15827", "type": "Diseases & Disorders", "text": [ "malignant melanoma" ], "offsets": [ [ 429, 447 ] ], "normalized": [] }, { "id": "15828", "type": "Diseases & Disorders", "text": [ "MM" ], "offsets": [ [ 449, 451 ] ], "normalized": [] }, { "id": "15829", "type": "Genes & Molecular Sequences", "text": [ "VDR" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "15830", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 573, 580 ] ], "normalized": [] }, { "id": "15831", "type": "Diseases & Disorders", "text": [ "BC" ], "offsets": [ [ 581, 583 ] ], "normalized": [] }, { "id": "15832", "type": "Diseases & Disorders", "text": [ "MM" ], "offsets": [ [ 588, 590 ] ], "normalized": [] }, { "id": "15833", "type": "Diseases & Disorders", "text": [ "sporadic BC" ], "offsets": [ [ 666, 677 ] ], "normalized": [] }, { "id": "15834", "type": "Diseases & Disorders", "text": [ "MM" ], "offsets": [ [ 743, 745 ] ], "normalized": [] }, { "id": "15835", "type": "Genes & Molecular Sequences", "text": [ "VDR" ], "offsets": [ [ 853, 856 ] ], "normalized": [] }, { "id": "15836", "type": "SNP & Sequence variations", "text": [ "minor allele A" ], "offsets": [ [ 896, 910 ] ], "normalized": [] }, { "id": "15837", "type": "Diseases & Disorders", "text": [ "minor allele A" ], "offsets": [ [ 896, 910 ] ], "normalized": [] }, { "id": "15838", "type": "SNP & Sequence variations", "text": [ "rs2228570" ], "offsets": [ [ 937, 946 ] ], "normalized": [] }, { "id": "15839", "type": "SNP & Sequence variations", "text": [ "rs10735810" ], "offsets": [ [ 948, 958 ] ], "normalized": [] }, { "id": "15840", "type": "Genes & Molecular Sequences", "text": [ "FokI" ], "offsets": [ [ 960, 964 ] ], "normalized": [] }, { "id": "15841", "type": "SNP & Sequence variations", "text": [ "Met1Thr" ], "offsets": [ [ 966, 973 ] ], "normalized": [] }, { "id": "15842", "type": "Genes & Molecular Sequences", "text": [ "Met1Thr" ], "offsets": [ [ 966, 973 ] ], "normalized": [] }, { "id": "15843", "type": "Diseases & Disorders", "text": [ "BC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "15844", "type": "SNP & Sequence variations", "text": [ "rs731236" ], "offsets": [ [ 1094, 1102 ] ], "normalized": [] }, { "id": "15845", "type": "Genes & Molecular Sequences", "text": [ "TaqI" ], "offsets": [ [ 1104, 1108 ] ], "normalized": [] }, { "id": "15846", "type": "Diseases & Disorders", "text": [ "BC" ], "offsets": [ [ 1157, 1159 ] ], "normalized": [] }, { "id": "15847", "type": "Diseases & Disorders", "text": [ "MM" ], "offsets": [ [ 1250, 1252 ] ], "normalized": [] }, { "id": "15848", "type": "SNP & Sequence variations", "text": [ "rs2228570" ], "offsets": [ [ 1345, 1354 ] ], "normalized": [] }, { "id": "15849", "type": "Genes & Molecular Sequences", "text": [ "FokI" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "15850", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 1366, 1373 ] ], "normalized": [] }, { "id": "15851", "type": "Diseases & Disorders", "text": [ "childhood sunburns" ], "offsets": [ [ 1377, 1395 ] ], "normalized": [] }, { "id": "15852", "type": "SNP & Sequence variations", "text": [ "rs739837" ], "offsets": [ [ 1442, 1450 ] ], "normalized": [] }, { "id": "15853", "type": "Genes & Molecular Sequences", "text": [ "BglI" ], "offsets": [ [ 1452, 1456 ] ], "normalized": [] }, { "id": "15854", "type": "SNP & Sequence variations", "text": [ "rs4516035" ], "offsets": [ [ 1525, 1534 ] ], "normalized": [] }, { "id": "15855", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 1548, 1558 ] ], "normalized": [] }, { "id": "15856", "type": "Diseases & Disorders", "text": [ "tumour" ], "offsets": [ [ 1559, 1565 ] ], "normalized": [] }, { "id": "15857", "type": "SNP & Sequence variations", "text": [ "SNPs in the VDR" ], "offsets": [ [ 1679, 1694 ] ], "normalized": [] }, { "id": "15858", "type": "Genes & Molecular Sequences", "text": [ "SNPs in the VDR" ], "offsets": [ [ 1679, 1694 ] ], "normalized": [] }, { "id": "15859", "type": "Diseases & Disorders", "text": [ "BC" ], "offsets": [ [ 1704, 1706 ] ], "normalized": [] }, { "id": "15860", "type": "Diseases & Disorders", "text": [ "tumour" ], "offsets": [ [ 1761, 1767 ] ], "normalized": [] }, { "id": "15861", "type": "Diseases & Disorders", "text": [ "MM" ], "offsets": [ [ 1846, 1848 ] ], "normalized": [] }, { "id": "15862", "type": "", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15863", "type": "", "text": [ "sporadic breast cancer" ], "offsets": [ [ 398, 420 ] ], "normalized": [] }, { "id": "15865", "type": "", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15866", "type": "", "text": [ "malignant melanoma" ], "offsets": [ [ 429, 447 ] ], "normalized": [] }, { "id": "15868", "type": "", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15869", "type": "", "text": [ "MM" ], "offsets": [ [ 449, 451 ] ], "normalized": [] }, { "id": "15871", "type": "", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15872", "type": "", "text": [ "BC" ], "offsets": [ [ 422, 424 ] ], "normalized": [] }, { "id": "15874", "type": "", "text": [ "rs10735810" ], "offsets": [ [ 948, 958 ] ], "normalized": [] }, { "id": "15875", "type": "", "text": [ "BC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "15877", "type": "", "text": [ "rs731236" ], "offsets": [ [ 1094, 1102 ] ], "normalized": [] }, { "id": "15878", "type": "", "text": [ "BC" ], "offsets": [ [ 1157, 1159 ] ], "normalized": [] }, { "id": "15880", "type": "", "text": [ "SNPs in the VDR" ], "offsets": [ [ 1679, 1694 ] ], "normalized": [] }, { "id": "15881", "type": "", "text": [ "MM" ], "offsets": [ [ 1846, 1848 ] ], "normalized": [] }, { "id": "15883", "type": "", "text": [ "SNPs in the VDR" ], "offsets": [ [ 1679, 1694 ] ], "normalized": [] }, { "id": "15884", "type": "", "text": [ "BC" ], "offsets": [ [ 1704, 1706 ] ], "normalized": [] }, { "id": "15886", "type": "", "text": [ "vitamin D receptor" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "15887", "type": "", "text": [ "cancers" ], "offsets": [ [ 66, 73 ] ], "normalized": [] }, { "id": "15889", "type": "", "text": [ "vitamin D receptor" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "15890", "type": "", "text": [ "melanoma" ], "offsets": [ [ 75, 83 ] ], "normalized": [] }, { "id": "15892", "type": "", "text": [ "vitamin D receptor" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "15893", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 88, 101 ] ], "normalized": [] }, { "id": "15895", "type": "", "text": [ "VDR" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "15896", "type": "", "text": [ "cancer" ], "offsets": [ [ 346, 352 ] ], "normalized": [] }, { "id": "15898", "type": "", "text": [ "VDR" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "15899", "type": "", "text": [ "cancers" ], "offsets": [ [ 573, 580 ] ], "normalized": [] }, { "id": "15901", "type": "", "text": [ "SNPs in the VDR" ], "offsets": [ [ 1679, 1694 ] ], "normalized": [] }, { "id": "15902", "type": "", "text": [ "tumour" ], "offsets": [ [ 1761, 1767 ] ], "normalized": [] }, { "id": "15904", "type": "", "text": [ "Vitamin D" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "15905", "type": "", "text": [ "cancer" ], "offsets": [ [ 284, 290 ] ], "normalized": [] }, { "id": "15907", "type": "", "text": [ "VDR" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "15908", "type": "", "text": [ "BC" ], "offsets": [ [ 581, 583 ] ], "normalized": [] }, { "id": "15910", "type": "", "text": [ "VDR" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "15911", "type": "", "text": [ "MM" ], "offsets": [ [ 588, 590 ] ], "normalized": [] }, { "id": "15913", "type": "", "text": [ "rs2228570" ], "offsets": [ [ 937, 946 ] ], "normalized": [] }, { "id": "15914", "type": "", "text": [ "BC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "15916", "type": "", "text": [ "rs2228570" ], "offsets": [ [ 1345, 1354 ] ], "normalized": [] }, { "id": "15917", "type": "", "text": [ "childhood sunburns" ], "offsets": [ [ 1377, 1395 ] ], "normalized": [] }, { "id": "15919", "type": "", "text": [ "rs4516035" ], "offsets": [ [ 1525, 1534 ] ], "normalized": [] }, { "id": "15920", "type": "", "text": [ "aggressive" ], "offsets": [ [ 1548, 1558 ] ], "normalized": [] }, { "id": "15922", "type": "", "text": [ "Vitamin D" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "15923", "type": "", "text": [ "growth" ], "offsets": [ [ 251, 257 ] ], "normalized": [] }, { "id": "15925", "type": "", "text": [ "Vitamin D" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "15926", "type": "", "text": [ "cell differentiation" ], "offsets": [ [ 229, 249 ] ], "normalized": [] }, { "id": "15928", "type": "", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15929", "type": "", "text": [ "BC" ], "offsets": [ [ 422, 424 ] ], "normalized": [] }, { "id": "15931", "type": "", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15932", "type": "", "text": [ "MM" ], "offsets": [ [ 449, 451 ] ], "normalized": [] }, { "id": "15934", "type": "", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15935", "type": "", "text": [ "malignant melanoma" ], "offsets": [ [ 429, 447 ] ], "normalized": [] }, { "id": "15937", "type": "", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15938", "type": "", "text": [ "cancer" ], "offsets": [ [ 346, 352 ] ], "normalized": [] }, { "id": "15940", "type": "", "text": [ "Vitamin D receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "15941", "type": "", "text": [ "sporadic breast cancer" ], "offsets": [ [ 398, 420 ] ], "normalized": [] }, { "id": "15943", "type": "", "text": [ "FokI" ], "offsets": [ [ 960, 964 ] ], "normalized": [] }, { "id": "15944", "type": "", "text": [ "BC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "15946", "type": "", "text": [ "Met1Thr" ], "offsets": [ [ 966, 973 ] ], "normalized": [] }, { "id": "15947", "type": "", "text": [ "BC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "15949", "type": "", "text": [ "TaqI" ], "offsets": [ [ 1104, 1108 ] ], "normalized": [] }, { "id": "15950", "type": "", "text": [ "BC" ], "offsets": [ [ 1157, 1159 ] ], "normalized": [] }, { "id": "15952", "type": "", "text": [ "rs4516035" ], "offsets": [ [ 1525, 1534 ] ], "normalized": [] }, { "id": "15953", "type": "", "text": [ "tumour" ], "offsets": [ [ 1559, 1565 ] ], "normalized": [] }, { "id": "15955", "type": "", "text": [ "FokI" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "15956", "type": "", "text": [ "childhood sunburns" ], "offsets": [ [ 1377, 1395 ] ], "normalized": [] } ]

[]

[]

[ { "id": "15864", "type": "SA", "arg1_id": "15862", "arg2_id": "15863", "normalized": [] }, { "id": "15867", "type": "SA", "arg1_id": "15865", "arg2_id": "15866", "normalized": [] }, { "id": "15870", "type": "SA", "arg1_id": "15868", "arg2_id": "15869", "normalized": [] }, { "id": "15873", "type": "SA", "arg1_id": "15871", "arg2_id": "15872", "normalized": [] }, { "id": "15876", "type": "PA", "arg1_id": "15874", "arg2_id": "15875", "normalized": [] }, { "id": "15879", "type": "SA", "arg1_id": "15877", "arg2_id": "15878", "normalized": [] }, { "id": "15882", "type": "SA", "arg1_id": "15880", "arg2_id": "15881", "normalized": [] }, { "id": "15885", "type": "PA", "arg1_id": "15883", "arg2_id": "15884", "normalized": [] }, { "id": "15888", "type": "PA", "arg1_id": "15886", "arg2_id": "15887", "normalized": [] }, { "id": "15891", "type": "PA", "arg1_id": "15889", "arg2_id": "15890", "normalized": [] }, { "id": "15894", "type": "PA", "arg1_id": "15892", "arg2_id": "15893", "normalized": [] }, { "id": "15897", "type": "PA", "arg1_id": "15895", "arg2_id": "15896", "normalized": [] }, { "id": "15900", "type": "PA", "arg1_id": "15898", "arg2_id": "15899", "normalized": [] }, { "id": "15903", "type": "PA", "arg1_id": "15901", "arg2_id": "15902", "normalized": [] }, { "id": "15906", "type": "PA", "arg1_id": "15904", "arg2_id": "15905", "normalized": [] }, { "id": "15909", "type": "SA", "arg1_id": "15907", "arg2_id": "15908", "normalized": [] }, { "id": "15912", "type": "SA", "arg1_id": "15910", "arg2_id": "15911", "normalized": [] }, { "id": "15915", "type": "PA", "arg1_id": "15913", "arg2_id": "15914", "normalized": [] }, { "id": "15918", "type": "PA", "arg1_id": "15916", "arg2_id": "15917", "normalized": [] }, { "id": "15921", "type": "PA", "arg1_id": "15919", "arg2_id": "15920", "normalized": [] }, { "id": "15924", "type": "PA", "arg1_id": "15922", "arg2_id": "15923", "normalized": [] }, { "id": "15927", "type": "PA", "arg1_id": "15925", "arg2_id": "15926", "normalized": [] }, { "id": "15930", "type": "SA", "arg1_id": "15928", "arg2_id": "15929", "normalized": [] }, { "id": "15933", "type": "SA", "arg1_id": "15931", "arg2_id": "15932", "normalized": [] }, { "id": "15936", "type": "SA", "arg1_id": "15934", "arg2_id": "15935", "normalized": [] }, { "id": "15939", "type": "SA", "arg1_id": "15937", "arg2_id": "15938", "normalized": [] }, { "id": "15942", "type": "SA", "arg1_id": "15940", "arg2_id": "15941", "normalized": [] }, { "id": "15945", "type": "PA", "arg1_id": "15943", "arg2_id": "15944", "normalized": [] }, { "id": "15948", "type": "PA", "arg1_id": "15946", "arg2_id": "15947", "normalized": [] }, { "id": "15951", "type": "PA", "arg1_id": "15949", "arg2_id": "15950", "normalized": [] }, { "id": "15954", "type": "PA", "arg1_id": "15952", "arg2_id": "15953", "normalized": [] }, { "id": "15957", "type": "PA", "arg1_id": "15955", "arg2_id": "15956", "normalized": [] } ]

[ { "id": "15960", "type": "title", "text": [ "INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men." ], "offsets": [ [ 0, 128 ] ] }, { "id": "15961", "type": "abstract", "text": [ "BACKGROUND: A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. METHODS: We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18-40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. RESULTS: Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 +/- 5713 mm3 vs. GC/CC: n = 181; 268521 +/- 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% +/- 1.74% vs. GC/CC: n = 93; 6.39% +/- 1.82%; p = 0.035). CONCLUSION: Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation." ], "offsets": [ [ 129, 2290 ] ] } ]

[ { "id": "15962", "type": "Genes & Molecular Sequences", "text": [ "INSIG2" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "15963", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 54, 70 ] ], "normalized": [] }, { "id": "15964", "type": "Diseases & Disorders", "text": [ "poor response to resistance training" ], "offsets": [ [ 84, 120 ] ], "normalized": [] }, { "id": "15965", "type": "Genes & Molecular Sequences", "text": [ "INSIG2" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "15966", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 183, 192 ] ], "normalized": [] }, { "id": "15967", "type": "SNP & Sequence variations", "text": [ "g.-10,1025G>C" ], "offsets": [ [ 194, 207 ] ], "normalized": [] }, { "id": "15968", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 277, 284 ] ], "normalized": [] }, { "id": "15969", "type": "Diseases & Disorders", "text": [ "adiposity" ], "offsets": [ [ 469, 478 ] ], "normalized": [] }, { "id": "15970", "type": "SNP & Sequence variations", "text": [ "INSIG2 SNP" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "15971", "type": "Genes & Molecular Sequences", "text": [ "INSIG2 SNP" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "15972", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 593, 609 ] ], "normalized": [] }, { "id": "15973", "type": "SNP & Sequence variations", "text": [ "INSIG2 SNP" ], "offsets": [ [ 689, 699 ] ], "normalized": [] }, { "id": "15974", "type": "Genes & Molecular Sequences", "text": [ "INSIG2 SNP" ], "offsets": [ [ 689, 699 ] ], "normalized": [] }, { "id": "15975", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 700, 709 ] ], "normalized": [] }, { "id": "15976", "type": "Genes & Molecular Sequences", "text": [ "yrs" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "15977", "type": "SNP & Sequence variations", "text": [ "INSIG2 polymorphism" ], "offsets": [ [ 972, 991 ] ], "normalized": [] }, { "id": "15978", "type": "Genes & Molecular Sequences", "text": [ "INSIG2 polymorphism" ], "offsets": [ [ 972, 991 ] ], "normalized": [] }, { "id": "15979", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 995, 1011 ] ], "normalized": [] }, { "id": "15980", "type": "Diseases & Disorders", "text": [ "resistance training" ], "offsets": [ [ 1120, 1139 ] ], "normalized": [] }, { "id": "15981", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 1232, 1238 ] ], "normalized": [] }, { "id": "15982", "type": "SNP & Sequence variations", "text": [ "C allele" ], "offsets": [ [ 1438, 1446 ] ], "normalized": [] }, { "id": "15983", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 1477, 1493 ] ], "normalized": [] }, { "id": "15984", "type": "SNP & Sequence variations", "text": [ "GG" ], "offsets": [ [ 1495, 1497 ] ], "normalized": [] }, { "id": "15985", "type": "SNP & Sequence variations", "text": [ "GC/CC" ], "offsets": [ [ 1532, 1537 ] ], "normalized": [] }, { "id": "15986", "type": "SNP & Sequence variations", "text": [ "G ancestral allele" ], "offsets": [ [ 1648, 1666 ] ], "normalized": [] }, { "id": "15987", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 1684, 1700 ] ], "normalized": [] }, { "id": "15988", "type": "SNP & Sequence variations", "text": [ "C allele" ], "offsets": [ [ 1744, 1752 ] ], "normalized": [] }, { "id": "15989", "type": "Diseases & Disorders", "text": [ "subcutaneous fat" ], "offsets": [ [ 1784, 1800 ] ], "normalized": [] }, { "id": "15990", "type": "Diseases & Disorders", "text": [ "resistance training" ], "offsets": [ [ 1806, 1825 ] ], "normalized": [] }, { "id": "15991", "type": "SNP & Sequence variations", "text": [ "GG" ], "offsets": [ [ 1827, 1829 ] ], "normalized": [] }, { "id": "15992", "type": "SNP & Sequence variations", "text": [ "GC/CC" ], "offsets": [ [ 1860, 1865 ] ], "normalized": [] }, { "id": "15993", "type": "SNP & Sequence variations", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 1942, 1958 ] ], "normalized": [] }, { "id": "15994", "type": "Genes & Molecular Sequences", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 1942, 1958 ] ], "normalized": [] }, { "id": "15995", "type": "Diseases & Disorders", "text": [ "adiposity" ], "offsets": [ [ 2008, 2017 ] ], "normalized": [] }, { "id": "15996", "type": "Diseases & Disorders", "text": [ "resistance training" ], "offsets": [ [ 2078, 2097 ] ], "normalized": [] }, { "id": "15997", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 2202, 2209 ] ], "normalized": [] }, { "id": "15998", "type": "SNP & Sequence variations", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 2214, 2230 ] ], "normalized": [] }, { "id": "15999", "type": "Genes & Molecular Sequences", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 2214, 2230 ] ], "normalized": [] }, { "id": "16000", "type": "", "text": [ "INSIG2" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "16001", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 183, 192 ] ], "normalized": [] }, { "id": "16003", "type": "", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 2214, 2230 ] ], "normalized": [] }, { "id": "16004", "type": "", "text": [ "obesity" ], "offsets": [ [ 2202, 2209 ] ], "normalized": [] }, { "id": "16006", "type": "", "text": [ "INSIG2" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "16007", "type": "", "text": [ "obesity" ], "offsets": [ [ 277, 284 ] ], "normalized": [] }, { "id": "16009", "type": "", "text": [ "INSIG2 SNP" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "16010", "type": "", "text": [ "adiposity" ], "offsets": [ [ 469, 478 ] ], "normalized": [] }, { "id": "16012", "type": "", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 1942, 1958 ] ], "normalized": [] }, { "id": "16013", "type": "", "text": [ "adiposity" ], "offsets": [ [ 2008, 2017 ] ], "normalized": [] }, { "id": "16015", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 183, 192 ] ], "normalized": [] }, { "id": "16016", "type": "", "text": [ "obesity" ], "offsets": [ [ 277, 284 ] ], "normalized": [] }, { "id": "16018", "type": "", "text": [ "g.-10,1025G>C" ], "offsets": [ [ 194, 207 ] ], "normalized": [] }, { "id": "16019", "type": "", "text": [ "obesity" ], "offsets": [ [ 277, 284 ] ], "normalized": [] }, { "id": "16021", "type": "", "text": [ "INSIG2" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "16022", "type": "", "text": [ "subcutaneous fat" ], "offsets": [ [ 54, 70 ] ], "normalized": [] }, { "id": "16024", "type": "", "text": [ "INSIG2" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "16025", "type": "", "text": [ "poor response to resistance training" ], "offsets": [ [ 84, 120 ] ], "normalized": [] }, { "id": "16027", "type": "", "text": [ "INSIG2 SNP" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "16028", "type": "", "text": [ "subcutaneous fat" ], "offsets": [ [ 593, 609 ] ], "normalized": [] }, { "id": "16030", "type": "", "text": [ "C allele" ], "offsets": [ [ 1438, 1446 ] ], "normalized": [] }, { "id": "16031", "type": "", "text": [ "subcutaneous fat" ], "offsets": [ [ 1477, 1493 ] ], "normalized": [] }, { "id": "16033", "type": "", "text": [ "C allele" ], "offsets": [ [ 1744, 1752 ] ], "normalized": [] }, { "id": "16034", "type": "", "text": [ "subcutaneous fat" ], "offsets": [ [ 1784, 1800 ] ], "normalized": [] }, { "id": "16036", "type": "", "text": [ "C allele" ], "offsets": [ [ 1744, 1752 ] ], "normalized": [] }, { "id": "16037", "type": "", "text": [ "resistance training" ], "offsets": [ [ 1806, 1825 ] ], "normalized": [] }, { "id": "16039", "type": "", "text": [ "G ancestral allele" ], "offsets": [ [ 1648, 1666 ] ], "normalized": [] }, { "id": "16040", "type": "", "text": [ "subcutaneous fat" ], "offsets": [ [ 1784, 1800 ] ], "normalized": [] }, { "id": "16042", "type": "", "text": [ "G ancestral allele" ], "offsets": [ [ 1648, 1666 ] ], "normalized": [] }, { "id": "16043", "type": "", "text": [ "resistance training" ], "offsets": [ [ 1806, 1825 ] ], "normalized": [] }, { "id": "16045", "type": "", "text": [ "INSIG2 rs7566605" ], "offsets": [ [ 1942, 1958 ] ], "normalized": [] }, { "id": "16046", "type": "", "text": [ "resistance training" ], "offsets": [ [ 2078, 2097 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16002", "type": "PA", "arg1_id": "16000", "arg2_id": "16001", "normalized": [] }, { "id": "16005", "type": "PA", "arg1_id": "16003", "arg2_id": "16004", "normalized": [] }, { "id": "16008", "type": "PA", "arg1_id": "16006", "arg2_id": "16007", "normalized": [] }, { "id": "16011", "type": "PA", "arg1_id": "16009", "arg2_id": "16010", "normalized": [] }, { "id": "16014", "type": "PA", "arg1_id": "16012", "arg2_id": "16013", "normalized": [] }, { "id": "16017", "type": "PA", "arg1_id": "16015", "arg2_id": "16016", "normalized": [] }, { "id": "16020", "type": "PA", "arg1_id": "16018", "arg2_id": "16019", "normalized": [] }, { "id": "16023", "type": "PA", "arg1_id": "16021", "arg2_id": "16022", "normalized": [] }, { "id": "16026", "type": "PA", "arg1_id": "16024", "arg2_id": "16025", "normalized": [] }, { "id": "16029", "type": "SA", "arg1_id": "16027", "arg2_id": "16028", "normalized": [] }, { "id": "16032", "type": "PA", "arg1_id": "16030", "arg2_id": "16031", "normalized": [] }, { "id": "16035", "type": "PA", "arg1_id": "16033", "arg2_id": "16034", "normalized": [] }, { "id": "16038", "type": "PA", "arg1_id": "16036", "arg2_id": "16037", "normalized": [] }, { "id": "16041", "type": "PA", "arg1_id": "16039", "arg2_id": "16040", "normalized": [] }, { "id": "16044", "type": "PA", "arg1_id": "16042", "arg2_id": "16043", "normalized": [] }, { "id": "16047", "type": "PA", "arg1_id": "16045", "arg2_id": "16046", "normalized": [] } ]

[ { "id": "16050", "type": "title", "text": [ "Genetic association between the interleukin-2 receptor-alpha gene and mode of onset of type 1 diabetes in the Japanese population." ], "offsets": [ [ 0, 130 ] ] }, { "id": "16051", "type": "abstract", "text": [ "CONTEXT/OBJECTIVE: The IL-2 receptor-alpha (IL2RA), also known as CD25, is expressed on the regulatory T cells, which play an important role in the control of immune responses and the maintenance of immune homeostasis. Our objective was to determine whether variants in the IL2RA gene are associated with type 1 diabetes in the Japanese population. DESIGN/PATIENTS: We genotyped the four single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656) of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of Japanese origin. The allele and genotype frequencies were examined in the patient groups stratified by their mode of onset in a case-control study. RESULTS: We found evidence of association with acute-onset, but not slow-onset and fulminant, type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were associated with an increased disease risk [odds ratio (OR) for rs706778 AA genotype 1.54, P = 4.2 x 10(-4) and OR for rs3118470 GG genotype 1.50, P = 0.0019, respectively]. Furthermore, the A-G haplotype was associated with increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002). CONCLUSIONS: The present data confirm the type 1 diabetes association with IL2RA and provide evidence that the different contributions of the IL2RA in the susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese population." ], "offsets": [ [ 131, 1627 ] ] } ]

[ { "id": "16052", "type": "Genes & Molecular Sequences", "text": [ "interleukin-2 receptor-alpha" ], "offsets": [ [ 32, 60 ] ], "normalized": [] }, { "id": "16053", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 87, 102 ] ], "normalized": [] }, { "id": "16054", "type": "Genes & Molecular Sequences", "text": [ "IL-2 receptor-alpha" ], "offsets": [ [ 154, 173 ] ], "normalized": [] }, { "id": "16055", "type": "Genes & Molecular Sequences", "text": [ "IL2RA" ], "offsets": [ [ 175, 180 ] ], "normalized": [] }, { "id": "16056", "type": "Genes & Molecular Sequences", "text": [ "CD25" ], "offsets": [ [ 197, 201 ] ], "normalized": [] }, { "id": "16057", "type": "Genes & Molecular Sequences", "text": [ "IL2RA" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "16058", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 436, 451 ] ], "normalized": [] }, { "id": "16059", "type": "SNP & Sequence variations", "text": [ "rs706778" ], "offsets": [ [ 552, 560 ] ], "normalized": [] }, { "id": "16060", "type": "SNP & Sequence variations", "text": [ "rs3118470" ], "offsets": [ [ 562, 571 ] ], "normalized": [] }, { "id": "16061", "type": "SNP & Sequence variations", "text": [ "ss52580101" ], "offsets": [ [ 573, 583 ] ], "normalized": [] }, { "id": "16062", "type": "SNP & Sequence variations", "text": [ "rs11594656" ], "offsets": [ [ 589, 599 ] ], "normalized": [] }, { "id": "16063", "type": "Genes & Molecular Sequences", "text": [ "IL2RA" ], "offsets": [ [ 608, 613 ] ], "normalized": [] }, { "id": "16064", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16065", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 921, 936 ] ], "normalized": [] }, { "id": "16066", "type": "SNP & Sequence variations", "text": [ "rs706778" ], "offsets": [ [ 1000, 1008 ] ], "normalized": [] }, { "id": "16067", "type": "SNP & Sequence variations", "text": [ "rs3118470" ], "offsets": [ [ 1013, 1022 ] ], "normalized": [] }, { "id": "16068", "type": "SNP & Sequence variations", "text": [ "rs706778 A" ], "offsets": [ [ 1029, 1039 ] ], "normalized": [] }, { "id": "16069", "type": "SNP & Sequence variations", "text": [ "rs3118470 G" ], "offsets": [ [ 1055, 1066 ] ], "normalized": [] }, { "id": "16070", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1108, 1115 ] ], "normalized": [] }, { "id": "16071", "type": "SNP & Sequence variations", "text": [ "rs706778 AA" ], "offsets": [ [ 1142, 1153 ] ], "normalized": [] }, { "id": "16072", "type": "SNP & Sequence variations", "text": [ "rs3118470 GG" ], "offsets": [ [ 1197, 1209 ] ], "normalized": [] }, { "id": "16073", "type": "SNP & Sequence variations", "text": [ "A-G haplotype" ], "offsets": [ [ 1269, 1282 ] ], "normalized": [] }, { "id": "16074", "type": "Genes & Molecular Sequences", "text": [ "A-G haplotype" ], "offsets": [ [ 1269, 1282 ] ], "normalized": [] }, { "id": "16075", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 1313, 1328 ] ], "normalized": [] }, { "id": "16076", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 1422, 1437 ] ], "normalized": [] }, { "id": "16077", "type": "Genes & Molecular Sequences", "text": [ "IL2RA" ], "offsets": [ [ 1455, 1460 ] ], "normalized": [] }, { "id": "16078", "type": "Genes & Molecular Sequences", "text": [ "IL2RA" ], "offsets": [ [ 1522, 1527 ] ], "normalized": [] }, { "id": "16079", "type": "Diseases & Disorders", "text": [ "type 1 diabetes" ], "offsets": [ [ 1584, 1599 ] ], "normalized": [] }, { "id": "16080", "type": "", "text": [ "rs706778" ], "offsets": [ [ 1000, 1008 ] ], "normalized": [] }, { "id": "16081", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 921, 936 ] ], "normalized": [] }, { "id": "16083", "type": "", "text": [ "rs3118470" ], "offsets": [ [ 1013, 1022 ] ], "normalized": [] }, { "id": "16084", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 921, 936 ] ], "normalized": [] }, { "id": "16086", "type": "", "text": [ "A-G haplotype" ], "offsets": [ [ 1269, 1282 ] ], "normalized": [] }, { "id": "16087", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 1313, 1328 ] ], "normalized": [] }, { "id": "16089", "type": "", "text": [ "IL2RA" ], "offsets": [ [ 1522, 1527 ] ], "normalized": [] }, { "id": "16090", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 1584, 1599 ] ], "normalized": [] }, { "id": "16092", "type": "", "text": [ "interleukin-2 receptor-alpha" ], "offsets": [ [ 32, 60 ] ], "normalized": [] }, { "id": "16093", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 87, 102 ] ], "normalized": [] }, { "id": "16095", "type": "", "text": [ "IL2RA" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "16096", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 436, 451 ] ], "normalized": [] }, { "id": "16098", "type": "", "text": [ "IL2RA" ], "offsets": [ [ 608, 613 ] ], "normalized": [] }, { "id": "16099", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16101", "type": "", "text": [ "rs706778" ], "offsets": [ [ 552, 560 ] ], "normalized": [] }, { "id": "16102", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16104", "type": "", "text": [ "rs3118470" ], "offsets": [ [ 562, 571 ] ], "normalized": [] }, { "id": "16105", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16107", "type": "", "text": [ "ss52580101" ], "offsets": [ [ 573, 583 ] ], "normalized": [] }, { "id": "16108", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16110", "type": "", "text": [ "rs11594656" ], "offsets": [ [ 589, 599 ] ], "normalized": [] }, { "id": "16111", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 635, 650 ] ], "normalized": [] }, { "id": "16113", "type": "", "text": [ "rs706778 AA" ], "offsets": [ [ 1142, 1153 ] ], "normalized": [] }, { "id": "16114", "type": "", "text": [ "disease" ], "offsets": [ [ 1108, 1115 ] ], "normalized": [] }, { "id": "16116", "type": "", "text": [ "rs3118470 GG" ], "offsets": [ [ 1197, 1209 ] ], "normalized": [] }, { "id": "16117", "type": "", "text": [ "disease" ], "offsets": [ [ 1108, 1115 ] ], "normalized": [] }, { "id": "16119", "type": "", "text": [ "IL2RA" ], "offsets": [ [ 1522, 1527 ] ], "normalized": [] }, { "id": "16120", "type": "", "text": [ "type 1 diabetes" ], "offsets": [ [ 1422, 1437 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "16124", "type": "title", "text": [ "Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy." ], "offsets": [ [ 0, 88 ] ] }, { "id": "16125", "type": "abstract", "text": [ "RATIONALE: Atopy or atopic syndrome is an allergic hypersensitivity subject to hereditary influences. Aberrant expression of chitinase 3-like 1 (CHI3L1), also known as YKL-40 or HC gp-39, is involved in the pathogenesis of inflammatory and allergic diseases. OBJECTIVES: The genetic contribution of CHI3L1 gene to atopic susceptibility was investigated using an integrated population genetic and molecular analysis. METHODS: Genetic variations in CHI3L1 were identified and genotyped in 295 unrelated patients with atopy and 180 control subjects. Serum YKL-40 and IgE levels were analyzed according to genotype. The effects of a promoter polymorphism (g.-247C/T) on promoter activity were examined in reporter and protein binding assays. MEASUREMENTS AND MAIN RESULTS: In the case-control association analysis, the g.-247C/T polymorphism at the promoter region (rs10399805; P = 0.0062) and the IVS7+82C/T polymorphism at intron 7 (rs2275353; P = 0.0056) of CHI3L1 showed a significant association with atopy. Subjects with the g.-247T risk allele had significantly higher serum YKL-40 (P < 0.0001) and IgE (P = 0.012) levels. An in vitro promoter assay using THP-1 human monocyte cells revealed that the C to T conversion at g.-247 induced a more than twofold increase of reporter gene expression. Moreover, the g.-247T allele showed an increased affinity for CCAAT enhancer-binding protein, a well known transcriptional activator, by electrophoretic mobility shift assay. Accordingly, subjects with the g.-247TT genotype showed a 2.5-fold increase in CHI3L1 mRNA expression in peripheral blood cells compared with those with the g.-247CC genotype. CONCLUSIONS: These results strongly suggest that the g.-247C/T polymorphism in the CHI3L1 promoter region is associated with the risk of atopy." ], "offsets": [ [ 89, 1881 ] ] } ]

[ { "id": "16126", "type": "Genes & Molecular Sequences", "text": [ "chitinase 3-like 1" ], "offsets": [ [ 44, 62 ] ], "normalized": [] }, { "id": "16127", "type": "Diseases & Disorders", "text": [ "atopy" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "16128", "type": "Diseases & Disorders", "text": [ "Atopy" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "16129", "type": "Diseases & Disorders", "text": [ "atopic syndrome" ], "offsets": [ [ 109, 124 ] ], "normalized": [] }, { "id": "16130", "type": "Diseases & Disorders", "text": [ "hypersensitivity" ], "offsets": [ [ 140, 156 ] ], "normalized": [] }, { "id": "16131", "type": "Genes & Molecular Sequences", "text": [ "chitinase 3-like 1" ], "offsets": [ [ 214, 232 ] ], "normalized": [] }, { "id": "16132", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 234, 240 ] ], "normalized": [] }, { "id": "16133", "type": "Genes & Molecular Sequences", "text": [ "YKL-40" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "16134", "type": "Genes & Molecular Sequences", "text": [ "HC gp-39" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "16135", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 296, 308 ] ], "normalized": [] }, { "id": "16136", "type": "Diseases & Disorders", "text": [ "inflammatory and allergic diseases" ], "offsets": [ [ 312, 346 ] ], "normalized": [] }, { "id": "16137", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 388, 394 ] ], "normalized": [] }, { "id": "16138", "type": "Diseases & Disorders", "text": [ "atopic" ], "offsets": [ [ 403, 409 ] ], "normalized": [] }, { "id": "16139", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 536, 542 ] ], "normalized": [] }, { "id": "16140", "type": "Diseases & Disorders", "text": [ "atopy" ], "offsets": [ [ 604, 609 ] ], "normalized": [] }, { "id": "16141", "type": "Genes & Molecular Sequences", "text": [ "YKL-40" ], "offsets": [ [ 642, 648 ] ], "normalized": [] }, { "id": "16142", "type": "Genes & Molecular Sequences", "text": [ "IgE" ], "offsets": [ [ 653, 656 ] ], "normalized": [] }, { "id": "16143", "type": "SNP & Sequence variations", "text": [ "g.-247C/T" ], "offsets": [ [ 741, 750 ] ], "normalized": [] }, { "id": "16144", "type": "SNP & Sequence variations", "text": [ "g.-247C/T" ], "offsets": [ [ 904, 913 ] ], "normalized": [] }, { "id": "16145", "type": "SNP & Sequence variations", "text": [ "rs10399805" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "16146", "type": "SNP & Sequence variations", "text": [ "IVS7+82C/T" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "16147", "type": "Genes & Molecular Sequences", "text": [ "IVS7+82C/T" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "16148", "type": "SNP & Sequence variations", "text": [ "rs2275353" ], "offsets": [ [ 1020, 1029 ] ], "normalized": [] }, { "id": "16149", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 1046, 1052 ] ], "normalized": [] }, { "id": "16150", "type": "Diseases & Disorders", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16151", "type": "SNP & Sequence variations", "text": [ "g.-247T" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "16152", "type": "Genes & Molecular Sequences", "text": [ "YKL-40" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "16153", "type": "Genes & Molecular Sequences", "text": [ "IgE" ], "offsets": [ [ 1191, 1194 ] ], "normalized": [] }, { "id": "16154", "type": "Genes & Molecular Sequences", "text": [ "THP-1" ], "offsets": [ [ 1248, 1253 ] ], "normalized": [] }, { "id": "16155", "type": "SNP & Sequence variations", "text": [ "C to T conversion at g.-247" ], "offsets": [ [ 1293, 1320 ] ], "normalized": [] }, { "id": "16156", "type": "SNP & Sequence variations", "text": [ "g.-247T" ], "offsets": [ [ 1401, 1408 ] ], "normalized": [] }, { "id": "16157", "type": "Genes & Molecular Sequences", "text": [ "CCAAT enhancer-binding protein" ], "offsets": [ [ 1449, 1479 ] ], "normalized": [] }, { "id": "16158", "type": "SNP & Sequence variations", "text": [ "g.-247TT" ], "offsets": [ [ 1593, 1601 ] ], "normalized": [] }, { "id": "16159", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 1641, 1647 ] ], "normalized": [] }, { "id": "16160", "type": "SNP & Sequence variations", "text": [ "g.-247CC" ], "offsets": [ [ 1719, 1727 ] ], "normalized": [] }, { "id": "16161", "type": "SNP & Sequence variations", "text": [ "g.-247C/T" ], "offsets": [ [ 1791, 1800 ] ], "normalized": [] }, { "id": "16162", "type": "Genes & Molecular Sequences", "text": [ "CHI3L1" ], "offsets": [ [ 1821, 1827 ] ], "normalized": [] }, { "id": "16163", "type": "Diseases & Disorders", "text": [ "atopy" ], "offsets": [ [ 1875, 1880 ] ], "normalized": [] }, { "id": "16164", "type": "", "text": [ "HC gp-39" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "16165", "type": "", "text": [ "inflammatory and allergic diseases" ], "offsets": [ [ 312, 346 ] ], "normalized": [] }, { "id": "16167", "type": "", "text": [ "g.-247C/T" ], "offsets": [ [ 904, 913 ] ], "normalized": [] }, { "id": "16168", "type": "", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16170", "type": "", "text": [ "rs10399805" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "16171", "type": "", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16173", "type": "", "text": [ "IVS7+82C/T" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "16174", "type": "", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16176", "type": "", "text": [ "rs2275353" ], "offsets": [ [ 1020, 1029 ] ], "normalized": [] }, { "id": "16177", "type": "", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16179", "type": "", "text": [ "g.-247C/T" ], "offsets": [ [ 1791, 1800 ] ], "normalized": [] }, { "id": "16180", "type": "", "text": [ "atopy" ], "offsets": [ [ 1875, 1880 ] ], "normalized": [] }, { "id": "16182", "type": "", "text": [ "chitinase 3-like 1" ], "offsets": [ [ 44, 62 ] ], "normalized": [] }, { "id": "16183", "type": "", "text": [ "atopy" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "16185", "type": "", "text": [ "HC gp-39" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "16186", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 296, 308 ] ], "normalized": [] }, { "id": "16188", "type": "", "text": [ "CHI3L1" ], "offsets": [ [ 388, 394 ] ], "normalized": [] }, { "id": "16189", "type": "", "text": [ "atopic" ], "offsets": [ [ 403, 409 ] ], "normalized": [] }, { "id": "16191", "type": "", "text": [ "CHI3L1" ], "offsets": [ [ 536, 542 ] ], "normalized": [] }, { "id": "16192", "type": "", "text": [ "atopy" ], "offsets": [ [ 604, 609 ] ], "normalized": [] }, { "id": "16194", "type": "", "text": [ "CHI3L1" ], "offsets": [ [ 1046, 1052 ] ], "normalized": [] }, { "id": "16195", "type": "", "text": [ "atopy" ], "offsets": [ [ 1091, 1096 ] ], "normalized": [] }, { "id": "16197", "type": "", "text": [ "CHI3L1" ], "offsets": [ [ 1821, 1827 ] ], "normalized": [] }, { "id": "16198", "type": "", "text": [ "atopy" ], "offsets": [ [ 1875, 1880 ] ], "normalized": [] }, { "id": "16200", "type": "", "text": [ "YKL-40" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "16201", "type": "", "text": [ "inflammatory and allergic diseases" ], "offsets": [ [ 312, 346 ] ], "normalized": [] }, { "id": "16203", "type": "", "text": [ "chitinase 3-like 1" ], "offsets": [ [ 214, 232 ] ], "normalized": [] }, { "id": "16204", "type": "", "text": [ "inflammatory and allergic diseases" ], "offsets": [ [ 312, 346 ] ], "normalized": [] }, { "id": "16206", "type": "", "text": [ "CHI3L1" ], "offsets": [ [ 234, 240 ] ], "normalized": [] }, { "id": "16207", "type": "", "text": [ "inflammatory and allergic diseases" ], "offsets": [ [ 312, 346 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "16211", "type": "title", "text": [ "Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study." ], "offsets": [ [ 0, 135 ] ] }, { "id": "16212", "type": "abstract", "text": [ "Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC) region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662) were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir) are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir." ], "offsets": [ [ 136, 1330 ] ] } ]

[ { "id": "16213", "type": "Genes & Molecular Sequences", "text": [ "HIV-RNA" ], "offsets": [ [ 37, 44 ] ], "normalized": [] }, { "id": "16214", "type": "Genes & Molecular Sequences", "text": [ "HIV-DNA" ], "offsets": [ [ 58, 65 ] ], "normalized": [] }, { "id": "16215", "type": "Diseases & Disorders", "text": [ "HIV-1" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "16216", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 82, 91 ] ], "normalized": [] }, { "id": "16217", "type": "Diseases & Disorders", "text": [ "HIV-1 disease" ], "offsets": [ [ 160, 173 ] ], "normalized": [] }, { "id": "16218", "type": "Genes & Molecular Sequences", "text": [ "HLA" ], "offsets": [ [ 190, 193 ] ], "normalized": [] }, { "id": "16219", "type": "Genes & Molecular Sequences", "text": [ "Chemokine receptor" ], "offsets": [ [ 198, 216 ] ], "normalized": [] }, { "id": "16220", "type": "Diseases & Disorders", "text": [ "disease progression" ], "offsets": [ [ 244, 263 ] ], "normalized": [] }, { "id": "16221", "type": "Diseases & Disorders", "text": [ "HIV-1-infected seroconverters" ], "offsets": [ [ 350, 379 ] ], "normalized": [] }, { "id": "16222", "type": "Genes & Molecular Sequences", "text": [ "HIV-RNA" ], "offsets": [ [ 441, 448 ] ], "normalized": [] }, { "id": "16223", "type": "Genes & Molecular Sequences", "text": [ "HIV-DNA" ], "offsets": [ [ 462, 469 ] ], "normalized": [] }, { "id": "16224", "type": "Genes & Molecular Sequences", "text": [ "HIV-RNA" ], "offsets": [ [ 520, 527 ] ], "normalized": [] }, { "id": "16225", "type": "Genes & Molecular Sequences", "text": [ "6p21 major histocompatibility complex" ], "offsets": [ [ 557, 594 ] ], "normalized": [] }, { "id": "16226", "type": "Genes & Molecular Sequences", "text": [ "MHC" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "16227", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 697, 704 ] ], "normalized": [] }, { "id": "16228", "type": "Genes & Molecular Sequences", "text": [ "MHC" ], "offsets": [ [ 728, 731 ] ], "normalized": [] }, { "id": "16229", "type": "SNP & Sequence variations", "text": [ "rs2395029" ], "offsets": [ [ 739, 748 ] ], "normalized": [] }, { "id": "16230", "type": "SNP & Sequence variations", "text": [ "rs13199524" ], "offsets": [ [ 750, 760 ] ], "normalized": [] }, { "id": "16231", "type": "SNP & Sequence variations", "text": [ "rs12198173" ], "offsets": [ [ 762, 772 ] ], "normalized": [] }, { "id": "16232", "type": "SNP & Sequence variations", "text": [ "rs3093662" ], "offsets": [ [ 777, 786 ] ], "normalized": [] }, { "id": "16233", "type": "Diseases & Disorders", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16234", "type": "Genes & Molecular Sequences", "text": [ "HIV-DNA" ], "offsets": [ [ 895, 902 ] ], "normalized": [] }, { "id": "16235", "type": "Diseases & Disorders", "text": [ "HIV" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "16236", "type": "Genes & Molecular Sequences", "text": [ "chromosome 17" ], "offsets": [ [ 1018, 1031 ] ], "normalized": [] }, { "id": "16237", "type": "SNP & Sequence variations", "text": [ "rs6503919" ], "offsets": [ [ 1033, 1042 ] ], "normalized": [] }, { "id": "16238", "type": "Genes & Molecular Sequences", "text": [ "DDX40" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "16239", "type": "Genes & Molecular Sequences", "text": [ "YPEL2" ], "offsets": [ [ 1087, 1092 ] ], "normalized": [] }, { "id": "16240", "type": "Genes & Molecular Sequences", "text": [ "chromosome 8" ], "offsets": [ [ 1104, 1116 ] ], "normalized": [] }, { "id": "16241", "type": "SNP & Sequence variations", "text": [ "rs2575735" ], "offsets": [ [ 1118, 1127 ] ], "normalized": [] }, { "id": "16242", "type": "Genes & Molecular Sequences", "text": [ "Syndecan 2" ], "offsets": [ [ 1140, 1150 ] ], "normalized": [] }, { "id": "16243", "type": "Genes & Molecular Sequences", "text": [ "MHC" ], "offsets": [ [ 1193, 1196 ] ], "normalized": [] }, { "id": "16244", "type": "Diseases & Disorders", "text": [ "HIV" ], "offsets": [ [ 1211, 1214 ] ], "normalized": [] }, { "id": "16245", "type": "Diseases & Disorders", "text": [ "HIV" ], "offsets": [ [ 1231, 1234 ] ], "normalized": [] }, { "id": "16246", "type": "Diseases & Disorders", "text": [ "HIV" ], "offsets": [ [ 1316, 1319 ] ], "normalized": [] }, { "id": "16247", "type": "", "text": [ "HLA" ], "offsets": [ [ 190, 193 ] ], "normalized": [] }, { "id": "16248", "type": "", "text": [ "HIV-1 disease" ], "offsets": [ [ 160, 173 ] ], "normalized": [] }, { "id": "16250", "type": "", "text": [ "Chemokine receptor" ], "offsets": [ [ 198, 216 ] ], "normalized": [] }, { "id": "16251", "type": "", "text": [ "HIV-1 disease" ], "offsets": [ [ 160, 173 ] ], "normalized": [] }, { "id": "16253", "type": "", "text": [ "DDX40" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "16254", "type": "", "text": [ "HIV" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "16256", 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{ "id": "16271", "type": "", "text": [ "HIV-DNA" ], "offsets": [ [ 462, 469 ] ], "normalized": [] }, { "id": "16272", "type": "", "text": [ "HIV-1-infected seroconverters" ], "offsets": [ [ 350, 379 ] ], "normalized": [] }, { "id": "16274", "type": "", "text": [ "MHC" ], "offsets": [ [ 728, 731 ] ], "normalized": [] }, { "id": "16275", "type": "", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16277", "type": "", "text": [ "rs2395029" ], "offsets": [ [ 739, 748 ] ], "normalized": [] }, { "id": "16278", "type": "", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16280", "type": "", "text": [ "rs13199524" ], "offsets": [ [ 750, 760 ] ], "normalized": [] }, { "id": "16281", "type": "", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16283", "type": "", "text": [ "rs12198173" ], "offsets": [ [ 762, 772 ] ], "normalized": [] }, { "id": "16284", "type": "", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16286", "type": "", "text": [ "rs3093662" ], "offsets": [ [ 777, 786 ] ], "normalized": [] }, { "id": "16287", "type": "", "text": [ "HIV" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "16289", "type": "", "text": [ "HIV-DNA" ], "offsets": [ [ 895, 902 ] ], "normalized": [] }, { "id": "16290", "type": "", "text": [ "HIV" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "16292", "type": "", "text": [ "rs6503919" ], "offsets": [ [ 1033, 1042 ] ], "normalized": [] }, { "id": "16293", "type": "", "text": [ "HIV" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "16295", "type": "", "text": [ "rs2575735" ], "offsets": [ [ 1118, 1127 ] ], "normalized": [] }, { "id": "16296", "type": "", "text": [ "HIV" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "16298", "type": "", "text": [ "MHC" ], "offsets": [ [ 1193, 1196 ] ], "normalized": [] }, { "id": "16299", "type": "", "text": [ "HIV" ], "offsets": [ [ 1231, 1234 ] ], "normalized": [] }, { "id": "16301", "type": "", "text": [ "MHC" ], "offsets": [ [ 1193, 1196 ] ], "normalized": [] }, { "id": "16302", "type": "", "text": [ "HIV" ], "offsets": [ [ 1211, 1214 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16249", "type": "PA", "arg1_id": "16247", "arg2_id": "16248", "normalized": [] }, { "id": "16252", "type": "PA", "arg1_id": "16250", "arg2_id": "16251", "normalized": [] }, { "id": "16255", "type": "PA", "arg1_id": "16253", "arg2_id": "16254", "normalized": [] }, { "id": "16258", "type": "PA", "arg1_id": "16256", "arg2_id": "16257", "normalized": [] }, { "id": "16261", "type": "PA", "arg1_id": "16259", "arg2_id": "16260", "normalized": [] }, { "id": "16264", "type": "PA", "arg1_id": "16262", "arg2_id": "16263", "normalized": [] }, { "id": "16267", "type": "PA", "arg1_id": "16265", "arg2_id": "16266", "normalized": [] }, { "id": "16270", "type": "PA", "arg1_id": "16268", "arg2_id": "16269", "normalized": [] }, { "id": "16273", "type": "PA", "arg1_id": "16271", "arg2_id": "16272", "normalized": [] }, { "id": "16276", "type": "PA", "arg1_id": "16274", "arg2_id": "16275", "normalized": [] }, { "id": "16279", "type": "PA", "arg1_id": "16277", "arg2_id": "16278", "normalized": [] }, { "id": "16282", "type": "PA", "arg1_id": "16280", "arg2_id": "16281", "normalized": [] }, { "id": "16285", "type": "PA", "arg1_id": "16283", "arg2_id": "16284", "normalized": [] }, { "id": "16288", "type": "PA", "arg1_id": "16286", "arg2_id": "16287", "normalized": [] }, { "id": "16291", "type": "PA", "arg1_id": "16289", "arg2_id": "16290", "normalized": [] }, { "id": "16294", "type": "PA", "arg1_id": "16292", "arg2_id": "16293", "normalized": [] }, { "id": "16297", "type": "PA", "arg1_id": "16295", "arg2_id": "16296", "normalized": [] }, { "id": "16300", "type": "PA", "arg1_id": "16298", "arg2_id": "16299", "normalized": [] }, { "id": "16303", "type": "PA", "arg1_id": "16301", "arg2_id": "16302", "normalized": [] } ]

[ { "id": "16306", "type": "title", "text": [ "Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan." ], "offsets": [ [ 0, 211 ] ] }, { "id": "16307", "type": "abstract", "text": [ "BACKGROUND: The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection. METHODS: The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed. RESULTS: No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level. CONCLUSIONS: The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers." ], "offsets": [ [ 212, 1838 ] ] } ]

[ { "id": "16308", "type": "Genes & Molecular Sequences", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase 1" ], "offsets": [ [ 41, 91 ] ], "normalized": [] }, { "id": "16309", "type": "Diseases & Disorders", "text": [ "hepatitis C virus infection" ], "offsets": [ [ 97, 124 ] ], "normalized": [] }, { "id": "16310", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "16311", "type": "Genes & Molecular Sequences", "text": [ "hepatitis C" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "16312", "type": "Diseases & Disorders", "text": [ "virus" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "16313", "type": "Diseases & Disorders", "text": [ "chronic hepatitis C virus" ], "offsets": [ [ 247, 272 ] ], "normalized": [] }, { "id": "16314", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 255, 266 ] ], "normalized": [] }, { "id": "16315", "type": "Diseases & Disorders", "text": [ "HCV) infection" ], "offsets": [ [ 274, 288 ] ], "normalized": [] }, { "id": "16316", "type": "Diseases & Disorders", "text": [ "insulin resistance" ], "offsets": [ [ 317, 335 ] ], "normalized": [] }, { "id": "16317", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 340, 347 ] ], "normalized": [] }, { "id": "16318", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 353, 358 ] ], "normalized": [] }, { "id": "16319", "type": "Genes & Molecular Sequences", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase" ], "offsets": [ [ 379, 427 ] ], "normalized": [] }, { "id": "16320", "type": "Genes & Molecular Sequences", "text": [ "ENPP)-1" ], "offsets": [ [ 429, 436 ] ], "normalized": [] }, { "id": "16321", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 450, 459 ] ], "normalized": [] }, { "id": "16322", "type": "Genes & Molecular Sequences", "text": [ "insulin-induced gene 2" ], "offsets": [ [ 482, 504 ] ], "normalized": [] }, { "id": "16323", "type": "Diseases & Disorders", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16324", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16325", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 607, 612 ] ], "normalized": [] }, { "id": "16326", "type": "Genes & Molecular Sequences", "text": [ "ENPP1" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "16327", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 642, 651 ] ], "normalized": [] }, { "id": "16328", "type": "Diseases & Disorders", "text": [ "HCV infection" ], "offsets": [ [ 703, 716 ] ], "normalized": [] }, { "id": "16329", "type": "Genes & Molecular Sequences", "text": [ "anti-HCV antibody" ], "offsets": [ [ 789, 806 ] ], "normalized": [] }, { "id": "16330", "type": "Genes & Molecular Sequences", "text": [ "HCV core antigen" ], "offsets": [ [ 852, 868 ] ], "normalized": [] }, { "id": "16331", "type": "Genes & Molecular Sequences", "text": [ "HCV RNA" ], "offsets": [ [ 907, 914 ] ], "normalized": [] }, { "id": "16332", "type": "Diseases & Disorders", "text": [ "body mass index" ], "offsets": [ [ 992, 1007 ] ], "normalized": [] }, { "id": "16333", "type": "Diseases & Disorders", "text": [ "glucose" ], "offsets": [ [ 1016, 1023 ] ], "normalized": [] }, { "id": "16334", "type": "Diseases & Disorders", "text": [ "insulin" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "16335", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 1158, 1163 ] ], "normalized": [] }, { "id": "16336", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 1180, 1189 ] ], "normalized": [] }, { "id": "16337", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 1245, 1250 ] ], "normalized": [] }, { "id": "16338", "type": "Diseases & Disorders", "text": [ "HCV" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "16339", "type": "Genes & Molecular Sequences", "text": [ "HCV RNA" ], "offsets": [ [ 1346, 1353 ] ], "normalized": [] }, { "id": "16340", "type": "Diseases & Disorders", "text": [ "HCV" ], "offsets": [ [ 1396, 1399 ] ], "normalized": [] }, { "id": "16341", "type": "Genes & Molecular Sequences", "text": [ "HCV core antigen" ], "offsets": [ [ 1410, 1426 ] ], "normalized": [] }, { "id": "16342", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 1487, 1492 ] ], "normalized": [] }, { "id": "16343", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 1552, 1557 ] ], "normalized": [] }, { "id": "16344", "type": "SNP & Sequence variations", "text": [ "rs7566605" ], "offsets": [ [ 1616, 1625 ] ], "normalized": [] }, { "id": "16345", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 1659, 1670 ] ], "normalized": [] }, { "id": "16346", "type": "Diseases & Disorders", "text": [ "viremia" ], "offsets": [ [ 1671, 1678 ] ], "normalized": [] }, { "id": "16347", "type": "Genes & Molecular Sequences", "text": [ "HCV core antigen" ], "offsets": [ [ 1691, 1707 ] ], "normalized": [] }, { "id": "16348", "type": "SNP & Sequence variations", "text": [ "K121Q" ], "offsets": [ [ 1732, 1737 ] ], "normalized": [] }, { "id": "16349", "type": "Genes & Molecular Sequences", "text": [ "ENPP1" ], "offsets": [ [ 1749, 1754 ] ], "normalized": [] }, { "id": "16350", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 1778, 1789 ] ], "normalized": [] }, { "id": "16351", "type": "Diseases & Disorders", "text": [ "viremia" ], "offsets": [ [ 1790, 1797 ] ], "normalized": [] }, { "id": "16352", "type": "Genes & Molecular Sequences", "text": [ "core antigen" ], "offsets": [ [ 1802, 1814 ] ], "normalized": [] }, { "id": "16353", "type": "Diseases & Disorders", "text": [ "HCV" ], "offsets": [ [ 1825, 1828 ] ], "normalized": [] }, { "id": "16354", "type": "", "text": [ "K121Q" ], "offsets": [ [ 353, 358 ] ], "normalized": [] }, { "id": "16355", "type": "", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16357", "type": "", "text": [ "K121Q" ], "offsets": [ [ 353, 358 ] ], "normalized": [] }, { "id": "16358", "type": "", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16360", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 450, 459 ] ], "normalized": [] }, { "id": "16361", "type": "", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16363", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 450, 459 ] ], "normalized": [] }, { "id": "16364", "type": "", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16366", "type": "", "text": [ "K121Q" ], "offsets": [ [ 607, 612 ] ], "normalized": [] }, { "id": "16367", "type": "", "text": [ "HCV infection" ], "offsets": [ [ 703, 716 ] ], "normalized": [] }, { "id": "16369", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 642, 651 ] ], "normalized": [] }, { "id": "16370", "type": "", "text": [ "HCV infection" ], "offsets": [ [ 703, 716 ] ], "normalized": [] }, { "id": "16372", "type": "", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase 1" ], "offsets": [ [ 41, 91 ] ], "normalized": [] }, { "id": "16373", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "16375", "type": "", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase 1" ], "offsets": [ [ 41, 91 ] ], "normalized": [] }, { "id": "16376", "type": "", "text": [ "virus" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "16378", "type": "", "text": [ "insulin-induced gene 2" ], "offsets": [ [ 482, 504 ] ], "normalized": [] }, { "id": "16379", "type": "", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16381", "type": "", "text": [ "insulin-induced gene 2" ], "offsets": [ [ 482, 504 ] ], "normalized": [] }, { "id": "16382", "type": "", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16384", "type": "", "text": [ "ENPP1" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "16385", "type": "", "text": [ "HCV infection" ], "offsets": [ [ 703, 716 ] ], "normalized": [] }, { "id": "16387", "type": "", "text": [ "ENPP1" ], "offsets": [ [ 1749, 1754 ] ], "normalized": [] }, { "id": "16388", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 1778, 1789 ] ], "normalized": [] }, { "id": "16390", "type": "", "text": [ "ENPP1" ], "offsets": [ [ 1749, 1754 ] ], "normalized": [] }, { "id": "16391", "type": "", "text": [ "viremia" ], "offsets": [ [ 1790, 1797 ] ], "normalized": [] }, { "id": "16393", "type": "", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase 1" ], "offsets": [ [ 41, 91 ] ], "normalized": [] }, { "id": "16394", "type": "", "text": [ "hepatitis C virus infection" ], "offsets": [ [ 97, 124 ] ], "normalized": [] }, { "id": "16396", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "16397", "type": "", "text": [ "hepatitis C virus infection" ], "offsets": [ [ 97, 124 ] ], "normalized": [] }, { "id": "16399", "type": "", "text": [ "ENPP)-1" ], "offsets": [ [ 429, 436 ] ], "normalized": [] }, { "id": "16400", "type": "", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16402", "type": "", "text": [ "ENPP)-1" ], "offsets": [ [ 429, 436 ] ], "normalized": [] }, { "id": "16403", "type": "", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16405", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 1616, 1625 ] ], "normalized": [] }, { "id": "16406", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 1659, 1670 ] ], "normalized": [] }, { "id": "16408", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1732, 1737 ] ], "normalized": [] }, { "id": "16409", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 1778, 1789 ] ], "normalized": [] }, { "id": "16411", "type": "", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase" ], "offsets": [ [ 379, 427 ] ], "normalized": [] }, { "id": "16412", "type": "", "text": [ "insulin resistance" ], "offsets": [ [ 543, 561 ] ], "normalized": [] }, { "id": "16414", "type": "", "text": [ "ectonucleotide pyrophosphatase/phosphodiesterase" ], "offsets": [ [ 379, 427 ] ], "normalized": [] }, { "id": "16415", "type": "", "text": [ "obesity" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "16417", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1158, 1163 ] ], "normalized": [] }, { "id": "16418", "type": "", "text": [ "body mass index" ], "offsets": [ [ 992, 1007 ] ], "normalized": [] }, { "id": "16420", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1158, 1163 ] ], "normalized": [] }, { "id": "16421", "type": "", "text": [ "glucose" ], "offsets": [ [ 1016, 1023 ] ], "normalized": [] }, { "id": "16423", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1158, 1163 ] ], "normalized": [] }, { "id": "16424", "type": "", "text": [ "insulin" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "16426", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 1180, 1189 ] ], "normalized": [] }, { "id": "16427", "type": "", "text": [ "body mass index" ], "offsets": [ [ 992, 1007 ] ], "normalized": [] }, { "id": "16429", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 1180, 1189 ] ], "normalized": [] }, { "id": "16430", "type": "", "text": [ "glucose" ], "offsets": [ [ 1016, 1023 ] ], "normalized": [] }, { "id": "16432", "type": "", "text": [ "rs7566605" ], "offsets": [ [ 1180, 1189 ] ], "normalized": [] }, { "id": "16433", "type": "", "text": [ "insulin" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "16435", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1245, 1250 ] ], "normalized": [] }, { "id": "16436", "type": "", "text": [ "HCV" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "16438", "type": "", "text": [ "HCV RNA" ], "offsets": [ [ 1346, 1353 ] ], "normalized": [] }, { "id": "16439", "type": "", "text": [ "HCV" ], "offsets": [ [ 1254, 1257 ] ], "normalized": [] }, { "id": "16441", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1552, 1557 ] ], "normalized": [] }, { "id": "16442", "type": "", "text": [ "HCV" ], "offsets": [ [ 1396, 1399 ] ], "normalized": [] }, { "id": "16444", "type": "", "text": [ "HCV core antigen" ], "offsets": [ [ 1410, 1426 ] ], "normalized": [] }, { "id": "16445", "type": "", "text": [ "HCV" ], "offsets": [ [ 1396, 1399 ] ], "normalized": [] }, { "id": "16447", "type": "", "text": [ "ENPP1" ], "offsets": [ [ 1749, 1754 ] ], "normalized": [] }, { "id": "16448", "type": "", "text": [ "HCV" ], "offsets": [ [ 1825, 1828 ] ], "normalized": [] }, { "id": "16450", "type": "", "text": [ "K121Q" ], "offsets": [ [ 1732, 1737 ] ], "normalized": [] }, { "id": "16451", "type": "", "text": [ "HCV" ], "offsets": [ [ 1825, 1828 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "16455", "type": "title", "text": [ "Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations." ], "offsets": [ [ 0, 122 ] ] }, { "id": "16456", "type": "abstract", "text": [ "Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease characterized by the chromosomal translocation t(15;17), resulting in the formation of the PML-RARA gene. Here, 47 t(15;17) APL samples were analyzed with high-density single-nucleotide polymorphism microarray (50-K and 250-K SNP-chips) using the new algorithm AsCNAR (allele-specific copy-number analysis using anonymous references). Copy-number-neutral loss of heterozygosity (CNN-LOH) was identified at chromosomes 10q (3 cases), 11p (3 cases), and 19q (1 case). Twenty-eight samples (60%) did not have an obvious alteration (normal-copy-number [NC] group). Nineteen samples (40%) showed either one or more genomic abnormalities: 8 samples (17%) had trisomy 8 either with or without an additional duplication, deletion, or CNN-LOH (+8 group); and 11 samples (23%) had genomic abnormalities without trisomy 8 (other abnormalities group). These chromosomal abnormalities were acquired somatic mutations. Interestingly, FLT3-ITD mutations (11/47 cases) occurred only in the group with no genomic alteration (NC group). Taken together, these results suggest that the pathway of development of APL differs in each group: FLT3-ITD, trisomy 8, and other genomic changes. Here, we showed for the first time hidden abnormalities and novel disease-related genomic changes in t(15;17) APL." ], "offsets": [ [ 123, 1476 ] ] } ]

[ { "id": "16457", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 7, 20 ] ], "normalized": [] }, { "id": "16458", "type": "Diseases & Disorders", "text": [ "t(15;17) acute promyelocytic leukemia" ], "offsets": [ [ 49, 86 ] ], "normalized": [] }, { "id": "16459", "type": "Genes & Molecular Sequences", "text": [ "15;17" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "16460", "type": "Diseases & Disorders", "text": [ "APL" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "16461", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "16462", "type": "Diseases & Disorders", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16463", "type": "Diseases & Disorders", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16464", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16465", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 187, 194 ] ], "normalized": [] }, { "id": "16466", "type": "SNP & Sequence variations", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16467", "type": "Diseases & Disorders", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16468", "type": "SNP & Sequence variations", "text": [ "t(15;17)" ], "offsets": [ [ 242, 250 ] ], "normalized": [] }, { "id": "16469", "type": "Genes & Molecular Sequences", "text": [ "15;17" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "16470", "type": "Genes & Molecular Sequences", "text": [ "PML-RARA" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "16471", "type": "Diseases & Disorders", "text": [ "t(15;17) APL" ], "offsets": [ [ 310, 322 ] ], "normalized": [] }, { "id": "16472", "type": "Genes & Molecular Sequences", "text": [ "t(15;17) APL" ], "offsets": [ [ 310, 322 ] ], "normalized": [] }, { "id": "16473", "type": "Genes & Molecular Sequences", "text": [ "15;17" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "16474", "type": "SNP & Sequence variations", "text": [ "Copy-number-neutral loss of heterozygosity" ], "offsets": [ [ 530, 572 ] ], "normalized": [] }, { "id": "16475", "type": "SNP & Sequence variations", "text": [ "CNN-LOH" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "16476", "type": "Genes & Molecular Sequences", "text": [ "CNN-LOH" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "16477", "type": "Genes & Molecular Sequences", "text": [ "10q" ], "offsets": [ [ 613, 616 ] ], "normalized": [] }, { "id": "16478", "type": "Genes & Molecular Sequences", "text": [ "11p" ], "offsets": [ [ 628, 631 ] ], "normalized": [] }, { "id": "16479", "type": "Genes & Molecular Sequences", "text": [ "19q" ], "offsets": [ [ 647, 650 ] ], "normalized": [] }, { "id": "16480", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 813, 826 ] ], "normalized": [] }, { "id": "16481", "type": "SNP & Sequence variations", "text": [ "trisomy 8" ], "offsets": [ [ 848, 857 ] ], "normalized": [] }, { "id": "16482", "type": "Diseases & Disorders", "text": [ "trisomy 8" ], "offsets": [ [ 848, 857 ] ], "normalized": [] }, { "id": "16483", "type": "Diseases & Disorders", "text": [ "duplication" ], "offsets": [ [ 895, 906 ] ], "normalized": [] }, { "id": "16484", "type": "Diseases & Disorders", "text": [ "deletion" ], "offsets": [ [ 908, 916 ] ], "normalized": [] }, { "id": "16485", "type": "SNP & Sequence variations", "text": [ "CNN-LOH" ], "offsets": [ [ 921, 928 ] ], "normalized": [] }, { "id": "16486", "type": "Genes & Molecular Sequences", "text": [ "CNN-LOH" ], "offsets": [ [ 921, 928 ] ], "normalized": [] }, { "id": "16487", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 974, 987 ] ], "normalized": [] }, { "id": "16488", "type": "SNP & Sequence variations", "text": [ "trisomy 8" ], "offsets": [ [ 996, 1005 ] ], "normalized": [] }, { "id": "16489", "type": "Diseases & Disorders", "text": [ "trisomy 8" ], "offsets": [ [ 996, 1005 ] ], "normalized": [] }, { "id": "16490", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 1013, 1026 ] ], "normalized": [] }, { "id": "16491", "type": "Diseases & Disorders", "text": [ "chromosomal abnormalities" ], "offsets": [ [ 1041, 1066 ] ], "normalized": [] }, { "id": "16492", "type": "Diseases & Disorders", "text": [ "somatic mutations" ], "offsets": [ [ 1081, 1098 ] ], "normalized": [] }, { "id": "16493", "type": "SNP & Sequence variations", "text": [ "FLT3-ITD" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "16494", "type": "Genes & Molecular Sequences", "text": [ "FLT3-ITD" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "16495", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "16496", "type": "Diseases & Disorders", "text": [ "APL" ], "offsets": [ [ 1287, 1290 ] ], "normalized": [] }, { "id": "16497", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 1287, 1290 ] ], "normalized": [] }, { "id": "16498", "type": "SNP & Sequence variations", "text": [ "FLT3-ITD" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] }, { "id": "16499", "type": "Genes & Molecular Sequences", "text": [ "FLT3-ITD" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] }, { "id": "16500", "type": "SNP & Sequence variations", "text": [ "trisomy 8" ], "offsets": [ [ 1324, 1333 ] ], "normalized": [] }, { "id": "16501", "type": "Diseases & Disorders", "text": [ "trisomy 8" ], "offsets": [ [ 1324, 1333 ] ], "normalized": [] }, { "id": "16502", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 1404, 1417 ] ], "normalized": [] }, { "id": "16503", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1428, 1435 ] ], "normalized": [] }, { "id": "16504", "type": "Diseases & Disorders", "text": [ "t(15;17) APL" ], "offsets": [ [ 1463, 1475 ] ], "normalized": [] }, { "id": "16505", "type": "Genes & Molecular Sequences", "text": [ "t(15;17) APL" ], "offsets": [ [ 1463, 1475 ] ], "normalized": [] }, { "id": "16506", "type": "Genes & Molecular Sequences", "text": [ "15;17" ], "offsets": [ [ 1465, 1470 ] ], "normalized": [] }, { "id": "16507", "type": "", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16508", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16510", "type": "", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16511", "type": "", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16513", "type": "", "text": [ "t(15;17)" ], "offsets": [ [ 242, 250 ] ], "normalized": [] }, { "id": "16514", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16516", "type": "", "text": [ "t(15;17)" ], "offsets": [ [ 242, 250 ] ], "normalized": [] }, { "id": "16517", "type": "", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16519", "type": "", "text": [ "APL" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "16520", "type": "", "text": [ "abnormalities" ], "offsets": [ [ 7, 20 ] ], "normalized": [] }, { "id": "16522", "type": "", "text": [ "APL" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "16523", "type": "", "text": [ "t(15;17) acute promyelocytic leukemia" ], "offsets": [ [ 49, 86 ] ], "normalized": [] }, { "id": "16525", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16526", "type": "", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16528", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16529", "type": "", "text": [ "disease" ], "offsets": [ [ 187, 194 ] ], "normalized": [] }, { "id": "16531", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16532", "type": "", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16534", "type": "", "text": [ "APL" ], "offsets": [ [ 1287, 1290 ] ], "normalized": [] }, { "id": "16535", "type": "", "text": [ "trisomy 8" ], "offsets": [ [ 1324, 1333 ] ], "normalized": [] }, { "id": "16537", "type": "", "text": [ "t(15;17) APL" ], "offsets": [ [ 1463, 1475 ] ], "normalized": [] }, { "id": "16538", "type": "", "text": [ "abnormalities" ], "offsets": [ [ 1404, 1417 ] ], "normalized": [] }, { "id": "16540", "type": "", "text": [ "t(15;17) APL" ], "offsets": [ [ 1463, 1475 ] ], "normalized": [] }, { "id": "16541", "type": "", "text": [ "disease" ], "offsets": [ [ 1428, 1435 ] ], "normalized": [] }, { "id": "16543", "type": "", "text": [ "PML-RARA" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "16544", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16546", "type": "", "text": [ "PML-RARA" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "16547", "type": "", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16549", "type": "", "text": [ "PML-RARA" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "16550", "type": "", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16552", "type": "", "text": [ "FLT3-ITD" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "16553", "type": "", "text": [ "mutations" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "16555", "type": "", "text": [ "FLT3-ITD" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] }, { "id": "16556", "type": "", "text": [ "APL" ], "offsets": [ [ 1287, 1290 ] ], "normalized": [] }, { "id": "16558", "type": "", "text": [ "15;17" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "16559", "type": "", "text": [ "Acute promyelocytic leukemia" ], "offsets": [ [ 123, 151 ] ], "normalized": [] }, { "id": "16561", "type": "", "text": [ "15;17" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "16562", "type": "", "text": [ "chromosomal translocation" ], "offsets": [ [ 216, 241 ] ], "normalized": [] }, { "id": "16564", "type": "", "text": [ "15;17" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "16565", "type": "", "text": [ "APL" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "16567", "type": "", "text": [ "15;17" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "16568", "type": "", "text": [ "t(15;17) APL" ], "offsets": [ [ 310, 322 ] ], "normalized": [] }, { "id": "16570", "type": "", "text": [ "CNN-LOH" ], "offsets": [ [ 921, 928 ] ], "normalized": [] }, { "id": "16571", "type": "", "text": [ "trisomy 8" ], "offsets": [ [ 996, 1005 ] ], "normalized": [] }, { "id": "16573", "type": "", "text": [ "FLT3-ITD" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] }, { "id": "16574", "type": "", "text": [ "trisomy 8" ], "offsets": [ [ 1324, 1333 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16509", "type": "PA", "arg1_id": "16507", "arg2_id": "16508", "normalized": [] }, { "id": "16512", "type": "PA", "arg1_id": "16510", "arg2_id": "16511", "normalized": [] }, { "id": "16515", "type": "PA", "arg1_id": "16513", "arg2_id": "16514", "normalized": [] }, { "id": "16518", "type": "PA", "arg1_id": "16516", "arg2_id": "16517", "normalized": [] }, { "id": "16521", "type": "PA", "arg1_id": "16519", "arg2_id": "16520", "normalized": [] }, { "id": "16524", "type": "PA", "arg1_id": "16522", "arg2_id": "16523", "normalized": [] }, { "id": "16527", "type": "PA", "arg1_id": "16525", "arg2_id": "16526", "normalized": [] }, { "id": "16530", "type": "PA", "arg1_id": "16528", "arg2_id": "16529", "normalized": [] }, { "id": "16533", "type": "PA", "arg1_id": "16531", "arg2_id": "16532", "normalized": [] }, { "id": "16536", "type": "PA", "arg1_id": "16534", "arg2_id": "16535", "normalized": [] }, { "id": "16539", "type": "PA", "arg1_id": "16537", "arg2_id": "16538", "normalized": [] }, { "id": "16542", "type": "PA", "arg1_id": "16540", "arg2_id": "16541", "normalized": [] }, { "id": "16545", "type": "PA", "arg1_id": "16543", "arg2_id": "16544", "normalized": [] }, { "id": "16548", "type": "PA", "arg1_id": "16546", "arg2_id": "16547", "normalized": [] }, { "id": "16551", "type": "PA", "arg1_id": "16549", "arg2_id": "16550", "normalized": [] }, { "id": "16554", "type": "PA", "arg1_id": "16552", "arg2_id": "16553", "normalized": [] }, { "id": "16557", "type": "PA", "arg1_id": "16555", "arg2_id": "16556", "normalized": [] }, { "id": "16560", "type": "PA", "arg1_id": "16558", "arg2_id": "16559", "normalized": [] }, { "id": "16563", "type": "PA", "arg1_id": "16561", "arg2_id": "16562", "normalized": [] }, { "id": "16566", "type": "PA", "arg1_id": "16564", "arg2_id": "16565", "normalized": [] }, { "id": "16569", "type": "PA", "arg1_id": "16567", "arg2_id": "16568", "normalized": [] }, { "id": "16572", "type": "SA", "arg1_id": "16570", "arg2_id": "16571", "normalized": [] }, { "id": "16575", "type": "NA", "arg1_id": "16573", "arg2_id": "16574", "normalized": [] } ]

[ { "id": "16578", "type": "title", "text": [ "Fetuin-A and arterial stiffness in patients with normal kidney function." ], "offsets": [ [ 0, 72 ] ] }, { "id": "16579", "type": "abstract", "text": [ "AIM: To evaluate the association between fetuin-A level (AHSG), its encoding gene (Thr256Ser) and arterial function in subjects with normal kidney function. INTRODUCTION: The aortic pulse wave velocity (aPWV) is a predictor for cardiovascular mortality. Fetuin-A is a calcification inhibitor and correlates negatively with increased vascular stiffness in dialysis patients. The fetuin-A polymorphism (Thr256Ser) is associated with reduced fetuin levels and accelerated vascular calcification in dialysis patients. Little is known about the role of fetuin-A as an independent predictor for the development of arterial stiffness in healthy subjects. MATERIALS AND METHODS: We studied 116 subjects with normal kidney function (age 47+/-12 years, 50 females and 66 males) of the FLEMENGHO study. Calcium measurements, plasma fetuin-A, its encoding gene (Thr256Ser) and indexes of arterial stiffness, such as aPWV and arterial distensibility, were determined. RESULTS: Fetuin-A levels were negatively correlated with aPWV (r=-0.21, p=0.029). After an adjustment for multiple covariables, fetuin-A levels were independently associated with aPWV (r=-0.30, p=0.022) in males but not in females. Male fetuin-A SerSer carrier had lower fetuin-A levels and higher aPWV (fetuin-A: 61.9+/-29.0 microg/ml; aPWV: 14.3+/-0.9 m/s) as compared to ThrThr (fetuin-A: 109.9+/-54.9 microg/ml; aPWV: 6.4+/-1.3 m/s) and ThrSer carrier (fetuin-A: 100.8+/-52.5 microg/ml; aPWV: 6.6+/-1.3 m/s). Other calcium variables were not significantly associated with arterial stiffness. CONCLUSION: With respect to common calcium variables, only fetuin-A level showed an inverse relation with aPWV in men with normal renal function. Male fetuin-A SerSer carriers demonstrate particularly high aortic stiffness, possibly implying a status of increased cardiovascular risk." ], "offsets": [ [ 73, 1908 ] ] } ]

[ { "id": "16580", "type": "Genes & Molecular Sequences", "text": [ "Fetuin-A" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "16581", "type": "Diseases & Disorders", "text": [ "arterial stiffness" ], "offsets": [ [ 13, 31 ] ], "normalized": [] }, { "id": "16582", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 114, 122 ] ], "normalized": [] }, { "id": "16583", "type": "Genes & Molecular Sequences", "text": [ "AHSG" ], "offsets": [ [ 130, 134 ] ], "normalized": [] }, { "id": "16584", "type": "SNP & Sequence variations", "text": [ "Thr256Ser" ], "offsets": [ [ 156, 165 ] ], "normalized": [] }, { "id": "16585", "type": "Genes & Molecular Sequences", "text": [ "Thr256Ser" ], "offsets": [ [ 156, 165 ] ], "normalized": [] }, { "id": "16586", "type": "Diseases & Disorders", "text": [ "arterial function" ], "offsets": [ [ 171, 188 ] ], "normalized": [] }, { "id": "16587", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 276, 280 ] ], "normalized": [] }, { "id": "16588", "type": "Diseases & Disorders", "text": [ "cardiovascular mortality" ], "offsets": [ [ 301, 325 ] ], "normalized": [] }, { "id": "16589", "type": "Genes & Molecular Sequences", "text": [ "Fetuin-A" ], "offsets": [ [ 327, 335 ] ], "normalized": [] }, { "id": "16590", "type": "Genes & Molecular Sequences", "text": [ "calcification inhibitor" ], "offsets": [ [ 341, 364 ] ], "normalized": [] }, { "id": "16591", "type": "Diseases & Disorders", "text": [ "calcification inhibitor" ], "offsets": [ [ 341, 364 ] ], "normalized": [] }, { "id": "16592", "type": "Diseases & Disorders", "text": [ "vascular stiffness" ], "offsets": [ [ 406, 424 ] ], "normalized": [] }, { "id": "16593", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 451, 459 ] ], "normalized": [] }, { "id": "16594", "type": "SNP & Sequence variations", "text": [ "Thr256Ser" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "16595", "type": "Genes & Molecular Sequences", "text": [ "Thr256Ser" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "16596", "type": "Diseases & Disorders", "text": [ "fetuin levels" ], "offsets": [ [ 512, 525 ] ], "normalized": [] }, { "id": "16597", "type": "Diseases & Disorders", "text": [ "vascular calcification" ], "offsets": [ [ 542, 564 ] ], "normalized": [] }, { "id": "16598", "type": "Diseases & Disorders", "text": [ "Little" ], "offsets": [ [ 587, 593 ] ], "normalized": [] }, { "id": "16599", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 621, 629 ] ], "normalized": [] }, { "id": "16600", "type": "Diseases & Disorders", "text": [ "arterial stiffness" ], "offsets": [ [ 681, 699 ] ], "normalized": [] }, { "id": "16601", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 894, 902 ] ], "normalized": [] }, { "id": "16602", "type": "SNP & Sequence variations", "text": [ "Thr256Ser" ], "offsets": [ [ 923, 932 ] ], "normalized": [] }, { "id": "16603", "type": "Genes & Molecular Sequences", "text": [ "Thr256Ser" ], "offsets": [ [ 923, 932 ] ], "normalized": [] }, { "id": "16604", "type": "Diseases & Disorders", "text": [ "arterial stiffness" ], "offsets": [ [ 949, 967 ] ], "normalized": [] }, { "id": "16605", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "16606", "type": "Diseases & Disorders", "text": [ "arterial distensibility" ], "offsets": [ [ 986, 1009 ] ], "normalized": [] }, { "id": "16607", "type": "Genes & Molecular Sequences", "text": [ "Fetuin-A" ], "offsets": [ [ 1037, 1045 ] ], "normalized": [] }, { "id": "16608", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "16609", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1156, 1164 ] ], "normalized": [] }, { "id": "16610", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1207, 1211 ] ], "normalized": [] }, { "id": "16611", "type": "SNP & Sequence variations", "text": [ "Male fetuin-A SerSer carrier" ], "offsets": [ [ 1260, 1288 ] ], "normalized": [] }, { "id": "16612", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1265, 1273 ] ], "normalized": [] }, { "id": "16613", "type": "SNP & Sequence variations", "text": [ "SerSer" ], "offsets": [ [ 1274, 1280 ] ], "normalized": [] }, { "id": "16614", "type": "Genes & Molecular Sequences", "text": [ "SerSer" ], "offsets": [ [ 1274, 1280 ] ], "normalized": [] }, { "id": "16615", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1299, 1307 ] ], "normalized": [] }, { "id": "16616", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1326, 1330 ] ], "normalized": [] }, { "id": "16617", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1332, 1340 ] ], "normalized": [] }, { "id": "16618", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1365, 1369 ] ], "normalized": [] }, { "id": "16619", "type": "SNP & Sequence variations", "text": [ "ThrThr" ], "offsets": [ [ 1402, 1408 ] ], "normalized": [] }, { "id": "16620", "type": "Genes & Molecular Sequences", "text": [ "ThrThr" ], "offsets": [ [ 1402, 1408 ] ], "normalized": [] }, { "id": "16621", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1410, 1418 ] ], "normalized": [] }, { "id": "16622", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1444, 1448 ] ], "normalized": [] }, { "id": "16623", "type": "SNP & Sequence variations", "text": [ "ThrSer carrier" ], "offsets": [ [ 1469, 1483 ] ], "normalized": [] }, { "id": "16624", "type": "Genes & Molecular Sequences", "text": [ "ThrSer carrier" ], "offsets": [ [ 1469, 1483 ] ], "normalized": [] }, { "id": "16625", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1485, 1493 ] ], "normalized": [] }, { "id": "16626", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "16627", "type": "Diseases & Disorders", "text": [ "stiffness" ], "offsets": [ [ 1613, 1622 ] ], "normalized": [] }, { "id": "16628", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1683, 1691 ] ], "normalized": [] }, { "id": "16629", "type": "Diseases & Disorders", "text": [ "aPWV" ], "offsets": [ [ 1730, 1734 ] ], "normalized": [] }, { "id": "16630", "type": "SNP & Sequence variations", "text": [ "Male fetuin-A SerSer carriers" ], "offsets": [ [ 1770, 1799 ] ], "normalized": [] }, { "id": "16631", "type": "Genes & Molecular Sequences", "text": [ "fetuin-A" ], "offsets": [ [ 1775, 1783 ] ], "normalized": [] }, { "id": "16632", "type": "SNP & Sequence variations", "text": [ "SerSer" ], "offsets": [ [ 1784, 1790 ] ], "normalized": [] }, { "id": "16633", "type": "Genes & Molecular Sequences", "text": [ "SerSer" ], "offsets": [ [ 1784, 1790 ] ], "normalized": [] }, { "id": "16634", "type": "Diseases & Disorders", "text": [ "aortic stiffness" ], "offsets": [ [ 1830, 1846 ] ], "normalized": [] }, { "id": "16635", "type": "Diseases & Disorders", "text": [ "cardiovascular risk" ], "offsets": [ [ 1888, 1907 ] ], "normalized": [] }, { "id": "16636", "type": "", "text": [ "Fetuin-A" ], "offsets": [ [ 327, 335 ] ], "normalized": [] }, { "id": "16637", "type": "", "text": [ "vascular stiffness" ], "offsets": [ [ 406, 424 ] ], "normalized": [] }, { "id": "16639", "type": "", "text": [ "Thr256Ser" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "16640", "type": "", "text": [ "vascular calcification" ], "offsets": [ [ 542, 564 ] ], "normalized": [] }, { "id": "16642", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 621, 629 ] ], "normalized": [] }, { "id": "16643", "type": "", "text": [ "arterial stiffness" ], "offsets": [ [ 681, 699 ] ], "normalized": [] }, { "id": "16645", "type": "", "text": [ "Male fetuin-A SerSer carriers" ], "offsets": [ [ 1770, 1799 ] ], "normalized": [] }, { "id": "16646", "type": "", "text": [ "aortic stiffness" ], "offsets": [ [ 1830, 1846 ] ], "normalized": [] }, { "id": "16648", "type": "", "text": [ "Male fetuin-A SerSer carriers" ], "offsets": [ [ 1770, 1799 ] ], "normalized": [] }, { "id": "16649", "type": "", "text": [ "cardiovascular risk" ], "offsets": [ [ 1888, 1907 ] ], "normalized": [] }, { "id": "16651", "type": "", "text": [ "Fetuin-A" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "16652", "type": "", "text": [ "arterial stiffness" ], "offsets": [ [ 13, 31 ] ], "normalized": [] }, { "id": "16654", "type": "", "text": [ "Fetuin-A" ], "offsets": [ [ 327, 335 ] ], "normalized": [] }, { "id": "16655", "type": "", "text": [ "calcification inhibitor" ], "offsets": [ [ 341, 364 ] ], "normalized": [] }, { "id": "16657", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 451, 459 ] ], "normalized": [] }, { "id": "16658", "type": "", "text": [ "vascular calcification" ], "offsets": [ [ 542, 564 ] ], "normalized": [] }, { "id": "16660", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 621, 629 ] ], "normalized": [] }, { "id": "16661", "type": "", "text": [ "Little" ], "offsets": [ [ 587, 593 ] ], "normalized": [] }, { "id": "16663", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 894, 902 ] ], "normalized": [] }, { "id": "16664", "type": "", "text": [ "arterial stiffness" ], "offsets": [ [ 949, 967 ] ], "normalized": [] }, { "id": "16666", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 1775, 1783 ] ], "normalized": [] }, { "id": "16667", "type": "", "text": [ "aortic stiffness" ], "offsets": [ [ 1830, 1846 ] ], "normalized": [] }, { "id": "16669", "type": "", "text": [ "SerSer" ], "offsets": [ [ 1784, 1790 ] ], "normalized": [] }, { "id": "16670", "type": "", "text": [ "aortic stiffness" ], "offsets": [ [ 1830, 1846 ] ], "normalized": [] }, { "id": "16672", "type": "", "text": [ "AHSG" ], "offsets": [ [ 130, 134 ] ], "normalized": [] }, { "id": "16673", "type": "", "text": [ "arterial function" ], "offsets": [ [ 171, 188 ] ], "normalized": [] }, { "id": "16675", "type": "", "text": [ "Thr256Ser" ], "offsets": [ [ 156, 165 ] ], "normalized": [] }, { "id": "16676", "type": "", "text": [ "arterial function" ], "offsets": [ [ 171, 188 ] ], "normalized": [] }, { "id": "16678", "type": "", "text": [ "calcification inhibitor" ], "offsets": [ [ 341, 364 ] ], "normalized": [] }, { "id": "16679", "type": "", "text": [ "vascular stiffness" ], "offsets": [ [ 406, 424 ] ], "normalized": [] }, { "id": "16681", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 451, 459 ] ], "normalized": [] }, { "id": "16682", "type": "", "text": [ "fetuin levels" ], "offsets": [ [ 512, 525 ] ], "normalized": [] }, { "id": "16684", "type": "", "text": [ "Thr256Ser" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "16685", "type": "", "text": [ "fetuin levels" ], "offsets": [ [ 512, 525 ] ], "normalized": [] }, { "id": "16687", "type": "", "text": [ "Fetuin-A" ], "offsets": [ [ 1037, 1045 ] ], "normalized": [] }, { "id": "16688", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "16690", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 1156, 1164 ] ], "normalized": [] }, { "id": "16691", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1207, 1211 ] ], "normalized": [] }, { "id": "16693", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 1265, 1273 ] ], "normalized": [] }, { "id": "16694", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "16696", "type": "", "text": [ "SerSer" ], "offsets": [ [ 1274, 1280 ] ], "normalized": [] }, { "id": "16697", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "16699", "type": "", "text": [ "ThrThr" ], "offsets": [ [ 1402, 1408 ] ], "normalized": [] }, { "id": "16700", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "16702", "type": "", "text": [ "ThrSer carrier" ], "offsets": [ [ 1469, 1483 ] ], "normalized": [] }, { "id": "16703", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "16705", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 1683, 1691 ] ], "normalized": [] }, { "id": "16706", "type": "", "text": [ "aPWV" ], "offsets": [ [ 1730, 1734 ] ], "normalized": [] }, { "id": "16708", "type": "", "text": [ "fetuin-A" ], "offsets": [ [ 1775, 1783 ] ], "normalized": [] }, { "id": "16709", "type": "", "text": [ "cardiovascular risk" ], "offsets": [ [ 1888, 1907 ] ], "normalized": [] }, { "id": "16711", "type": "", "text": [ "SerSer" ], "offsets": [ [ 1784, 1790 ] ], "normalized": [] }, { "id": "16712", "type": "", "text": [ "cardiovascular risk" ], "offsets": [ [ 1888, 1907 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16638", "type": "PA", "arg1_id": "16636", "arg2_id": "16637", "normalized": [] }, { "id": "16641", "type": "PA", "arg1_id": "16639", "arg2_id": "16640", "normalized": [] }, { "id": "16644", "type": "SA", "arg1_id": "16642", "arg2_id": "16643", "normalized": [] }, { "id": "16647", "type": "PA", "arg1_id": "16645", "arg2_id": "16646", "normalized": [] }, { "id": "16650", "type": "SA", "arg1_id": "16648", "arg2_id": "16649", "normalized": [] }, { "id": "16653", "type": "PA", "arg1_id": "16651", "arg2_id": "16652", "normalized": [] }, { "id": "16656", "type": "PA", "arg1_id": "16654", "arg2_id": "16655", "normalized": [] }, { "id": "16659", "type": "PA", "arg1_id": "16657", "arg2_id": "16658", "normalized": [] }, { "id": "16662", "type": "PA", "arg1_id": "16660", "arg2_id": "16661", "normalized": [] }, { "id": "16665", "type": "PA", "arg1_id": "16663", "arg2_id": "16664", "normalized": [] }, { "id": "16668", "type": "PA", "arg1_id": "16666", "arg2_id": "16667", "normalized": [] }, { "id": "16671", "type": "PA", "arg1_id": "16669", "arg2_id": "16670", "normalized": [] }, { "id": "16674", "type": "SA", "arg1_id": "16672", "arg2_id": "16673", "normalized": [] }, { "id": "16677", "type": "SA", "arg1_id": "16675", "arg2_id": "16676", "normalized": [] }, { "id": "16680", "type": "PA", "arg1_id": "16678", "arg2_id": "16679", "normalized": [] }, { "id": "16683", "type": "PA", "arg1_id": "16681", "arg2_id": "16682", "normalized": [] }, { "id": "16686", "type": "PA", "arg1_id": "16684", "arg2_id": "16685", "normalized": [] }, { "id": "16689", "type": "PA", "arg1_id": "16687", "arg2_id": "16688", "normalized": [] }, { "id": "16692", "type": "PA", "arg1_id": "16690", "arg2_id": "16691", "normalized": [] }, { "id": "16695", "type": "PA", "arg1_id": "16693", "arg2_id": "16694", "normalized": [] }, { "id": "16698", "type": "PA", "arg1_id": "16696", "arg2_id": "16697", "normalized": [] }, { "id": "16701", "type": "NA", "arg1_id": "16699", "arg2_id": "16700", "normalized": [] }, { "id": "16704", "type": "NA", "arg1_id": "16702", "arg2_id": "16703", "normalized": [] }, { "id": "16707", "type": "PA", "arg1_id": "16705", "arg2_id": "16706", "normalized": [] }, { "id": "16710", "type": "PA", "arg1_id": "16708", "arg2_id": "16709", "normalized": [] }, { "id": "16713", "type": "PA", "arg1_id": "16711", "arg2_id": "16712", "normalized": [] } ]

[ { "id": "16716", "type": "title", "text": [ "Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population." ], "offsets": [ [ 0, 119 ] ] }, { "id": "16717", "type": "abstract", "text": [ "Cytochrome P450 1A1 is a major enzyme in the bioactivation of exogenous procarcinogens of hepatocellular carcinoma (HCC). However, the contribution of common genetic variants in CYP1A1 to the HCC risk in Chinese populations has not been thoroughly investigated. In this study, we examined the association between HCC and four selected tagging single nucleotide polymorphisms (SNPs) of CYP1A1, and the risk of CYP1A1 haplotypes/diplotypes in 1006 pathologically confirmed HCC patients and 1015 cancer-free controls, from a Han Chinese population. Haplotypes/diplotypes were constructed from observed genotypes using the Haplo.Stats program. Relative risk was estimated by using multivariable logistic regression method. To summarise, we detected an increased HCC risk in rs4646421 variant carriers (OR 1.30, 95% CI 1.05-1.61) and rs2198843 variant carriers (OR 1.33, 95% CI 1.05-1.69), and a reduced risk of HCC (OR 0.70. 95% CI 0.52-0.94) associated with homozygote carriers of rs4886605 variant. These association signals were also observed in non-smokers with rs4646421 (OR 1.56, 95% CI 1.16-2.08) and rs4886605 (OR 0.61, 95% CI 0.40-0.91). Compared to the most common CYP1A1 haplotype CCAG, the haplotype TTGC conferred an increased risk of HCC (OR 1.26, 95% CI 1.04-1.52). Similarly, the TTGC/TTGC diplotype conferred an increased risk of HCC compared with diplotype CCAG/CCAG (OR 2.06, 95% CI 1.23-3.45, P=0.006). Interestingly, the diplotype TTAC/CCAG also conferred an increased risk of HCC (OR 1.76, 95% CI 1.22-2.54, P=0.003). Our results suggested that common genetic variants in CYP1A1 may modulate the risk of developing HCC in the study population, particularly in non-smokers. However, our findings need to be validated in at least one independent study of Han Chinese population." ], "offsets": [ [ 120, 1914 ] ] } ]

[ { "id": "16718", "type": "Genes & Molecular Sequences", "text": [ "cytochrome P450 1A1" ], "offsets": [ [ 33, 52 ] ], "normalized": [] }, { "id": "16719", "type": "Diseases & Disorders", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 70, 94 ] ], "normalized": [] }, { "id": "16720", "type": "Genes & Molecular Sequences", "text": [ "Cytochrome P450 1A1" ], "offsets": [ [ 120, 139 ] ], "normalized": [] }, { "id": "16721", "type": "Diseases & Disorders", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 210, 234 ] ], "normalized": [] }, { "id": "16722", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 236, 239 ] ], "normalized": [] }, { "id": "16723", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 236, 239 ] ], "normalized": [] }, { "id": "16724", "type": "Genes & Molecular Sequences", "text": [ "CYP1A1" ], "offsets": [ [ 298, 304 ] ], "normalized": [] }, { "id": "16725", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 312, 315 ] ], "normalized": [] }, { "id": "16726", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 312, 315 ] ], "normalized": [] }, { "id": "16727", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 433, 436 ] ], "normalized": [] }, { "id": "16728", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 433, 436 ] ], "normalized": [] }, { "id": "16729", "type": "Diseases & Disorders", "text": [ "tagging" ], "offsets": [ [ 455, 462 ] ], "normalized": [] }, { "id": "16730", "type": "Genes & Molecular Sequences", "text": [ "CYP1A1" ], "offsets": [ [ 505, 511 ] ], "normalized": [] }, { "id": "16731", "type": "Genes & Molecular Sequences", "text": [ "CYP1A1" ], "offsets": [ [ 529, 535 ] ], "normalized": [] }, { "id": "16732", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "16733", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "16734", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "16735", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 820, 830 ] ], "normalized": [] }, { "id": "16736", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 878, 881 ] ], "normalized": [] }, { "id": "16737", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 878, 881 ] ], "normalized": [] }, { "id": "16738", "type": "SNP & Sequence variations", "text": [ "rs4646421" ], "offsets": [ [ 890, 899 ] ], "normalized": [] }, { "id": "16739", "type": "SNP & Sequence variations", "text": [ "rs2198843" ], "offsets": [ [ 949, 958 ] ], "normalized": [] }, { "id": "16740", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "16741", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "16742", "type": "SNP & Sequence variations", "text": [ "rs4886605" ], "offsets": [ [ 1098, 1107 ] ], "normalized": [] }, { "id": "16743", "type": "SNP & Sequence variations", "text": [ "rs4646421" ], "offsets": [ [ 1182, 1191 ] ], "normalized": [] }, { "id": "16744", "type": "SNP & Sequence variations", "text": [ "rs4886605" ], "offsets": [ [ 1224, 1233 ] ], "normalized": [] }, { "id": "16745", "type": "Genes & Molecular Sequences", "text": [ "CYP1A1" ], "offsets": [ [ 1291, 1297 ] ], "normalized": [] }, { "id": "16746", "type": "SNP & Sequence variations", "text": [ "CCAG" ], "offsets": [ [ 1308, 1312 ] ], "normalized": [] }, { "id": "16747", "type": "Genes & Molecular Sequences", "text": [ "CCAG" ], "offsets": [ [ 1308, 1312 ] ], "normalized": [] }, { "id": "16748", "type": "SNP & Sequence variations", "text": [ "TTGC" ], "offsets": [ [ 1328, 1332 ] ], "normalized": [] }, { "id": "16749", "type": "Genes & Molecular Sequences", "text": [ "TTGC" ], "offsets": [ [ 1328, 1332 ] ], "normalized": [] }, { "id": "16750", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "16751", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "16752", "type": "SNP & Sequence variations", "text": [ "TTGC/TTGC" ], "offsets": [ [ 1412, 1421 ] ], "normalized": [] }, { "id": "16753", "type": "Genes & Molecular Sequences", "text": [ "TTGC/TTGC" ], "offsets": [ [ 1412, 1421 ] ], "normalized": [] }, { "id": "16754", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "16755", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "16756", "type": "SNP & Sequence variations", "text": [ "CCAG/CCAG" ], "offsets": [ [ 1491, 1500 ] ], "normalized": [] }, { "id": "16757", "type": "Genes & Molecular Sequences", "text": [ "CCAG/CCAG" ], "offsets": [ [ 1491, 1500 ] ], "normalized": [] }, { "id": "16758", "type": "SNP & Sequence variations", "text": [ "TTAC/CCAG" ], "offsets": [ [ 1568, 1577 ] ], "normalized": [] }, { "id": "16759", "type": "Genes & Molecular Sequences", "text": [ "TTAC/CCAG" ], "offsets": [ [ 1568, 1577 ] ], "normalized": [] }, { "id": "16760", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1614, 1617 ] ], "normalized": [] }, { "id": "16761", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1614, 1617 ] ], "normalized": [] }, { "id": "16762", "type": "Genes & Molecular Sequences", "text": [ "CYP1A1" ], "offsets": [ [ 1710, 1716 ] ], "normalized": [] }, { "id": "16763", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 1753, 1756 ] ], "normalized": [] }, { "id": "16764", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 1753, 1756 ] ], "normalized": [] }, { "id": "16765", "type": "", "text": [ "Cytochrome P450 1A1" ], "offsets": [ [ 120, 139 ] ], "normalized": [] }, { "id": "16766", "type": "", "text": [ "HCC" ], "offsets": [ [ 236, 239 ] ], "normalized": [] }, { "id": "16768", "type": "", "text": [ "Cytochrome P450 1A1" ], "offsets": [ [ 120, 139 ] ], "normalized": [] }, { "id": "16769", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 210, 234 ] ], "normalized": [] }, { "id": "16771", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 298, 304 ] ], "normalized": [] }, { "id": "16772", "type": "", "text": [ "HCC" ], "offsets": [ [ 312, 315 ] ], "normalized": [] }, { "id": "16774", "type": "", "text": [ "rs4646421" ], "offsets": [ [ 890, 899 ] ], "normalized": [] }, { "id": "16775", "type": "", "text": [ "HCC" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "16777", "type": "", "text": [ "rs2198843" ], "offsets": [ [ 949, 958 ] ], "normalized": [] }, { "id": "16778", "type": "", "text": [ "HCC" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "16780", "type": "", "text": [ "rs4886605" ], "offsets": [ [ 1098, 1107 ] ], "normalized": [] }, { "id": "16781", "type": "", "text": [ "HCC" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "16783", "type": "", "text": [ "TTGC" ], "offsets": [ [ 1328, 1332 ] ], "normalized": [] }, { "id": "16784", "type": "", "text": [ "HCC" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "16786", "type": "", "text": [ "TTGC/TTGC" ], "offsets": [ [ 1412, 1421 ] ], "normalized": [] }, { "id": "16787", "type": "", "text": [ "HCC" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "16789", "type": "", "text": [ "TTAC/CCAG" ], "offsets": [ [ 1568, 1577 ] ], "normalized": [] }, { "id": "16790", "type": "", "text": [ "HCC" ], "offsets": [ [ 1614, 1617 ] ], "normalized": [] }, { "id": "16792", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 1710, 1716 ] ], "normalized": [] }, { "id": "16793", "type": "", "text": [ "HCC" ], "offsets": [ [ 1753, 1756 ] ], "normalized": [] }, { "id": "16795", "type": "", "text": [ "cytochrome P450 1A1" ], "offsets": [ [ 33, 52 ] ], "normalized": [] }, { "id": "16796", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 70, 94 ] ], "normalized": [] }, { "id": "16798", "type": "", "text": [ "HCC" ], "offsets": [ [ 236, 239 ] ], "normalized": [] }, { "id": "16799", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 210, 234 ] ], "normalized": [] }, { "id": "16801", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 529, 535 ] ], "normalized": [] }, { "id": "16802", "type": "", "text": [ "tagging" ], "offsets": [ [ 455, 462 ] ], "normalized": [] }, { "id": "16804", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 529, 535 ] ], "normalized": [] }, { "id": "16805", "type": "", "text": [ "cancer" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "16807", "type": "", "text": [ "HCC" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "16808", "type": "", "text": [ "tagging" ], "offsets": [ [ 455, 462 ] ], "normalized": [] }, { "id": "16810", "type": "", "text": [ "HCC" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "16811", "type": "", "text": [ "cancer" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "16813", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 529, 535 ] ], "normalized": [] }, { "id": "16814", "type": "", "text": [ "HCC" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "16816", "type": "", "text": [ "CYP1A1" ], "offsets": [ [ 1291, 1297 ] ], "normalized": [] }, { "id": "16817", "type": "", "text": [ "HCC" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "16819", "type": "", "text": [ "CCAG" ], "offsets": [ [ 1308, 1312 ] ], "normalized": [] }, { "id": "16820", "type": "", "text": [ "HCC" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "16822", "type": "", "text": [ "CCAG/CCAG" ], "offsets": [ [ 1491, 1500 ] ], "normalized": [] }, { "id": "16823", "type": "", "text": [ "HCC" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16767", "type": "PA", "arg1_id": "16765", "arg2_id": "16766", "normalized": [] }, { "id": "16770", "type": "PA", "arg1_id": "16768", "arg2_id": "16769", "normalized": [] }, { "id": "16773", "type": "SA", "arg1_id": "16771", "arg2_id": "16772", "normalized": [] }, { "id": "16776", "type": "PA", "arg1_id": "16774", "arg2_id": "16775", "normalized": [] }, { "id": "16779", "type": "PA", "arg1_id": "16777", "arg2_id": "16778", "normalized": [] }, { "id": "16782", "type": "PA", "arg1_id": "16780", "arg2_id": "16781", "normalized": [] }, { "id": "16785", "type": "PA", "arg1_id": "16783", "arg2_id": "16784", "normalized": [] }, { "id": "16788", "type": "PA", "arg1_id": "16786", "arg2_id": "16787", "normalized": [] }, { "id": "16791", "type": "PA", "arg1_id": "16789", "arg2_id": "16790", "normalized": [] }, { "id": "16794", "type": "SA", "arg1_id": "16792", "arg2_id": "16793", "normalized": [] }, { "id": "16797", "type": "PA", "arg1_id": "16795", "arg2_id": "16796", "normalized": [] }, { "id": "16800", "type": "PA", "arg1_id": "16798", "arg2_id": "16799", "normalized": [] }, { "id": "16803", "type": "PA", "arg1_id": "16801", "arg2_id": "16802", "normalized": [] }, { "id": "16806", "type": "PA", "arg1_id": "16804", "arg2_id": "16805", "normalized": [] }, { "id": "16809", "type": "PA", "arg1_id": "16807", "arg2_id": "16808", "normalized": [] }, { "id": "16812", "type": "PA", "arg1_id": "16810", "arg2_id": "16811", "normalized": [] }, { "id": "16815", "type": "PA", "arg1_id": "16813", "arg2_id": "16814", "normalized": [] }, { "id": "16818", "type": "PA", "arg1_id": "16816", "arg2_id": "16817", "normalized": [] }, { "id": "16821", "type": "PA", "arg1_id": "16819", "arg2_id": "16820", "normalized": [] }, { "id": "16824", "type": "PA", "arg1_id": "16822", "arg2_id": "16823", "normalized": [] } ]

[ { "id": "16827", "type": "title", "text": [ "Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for -819C/T in leprosy susceptibility." ], "offsets": [ [ 0, 173 ] ] }, { "id": "16828", "type": "abstract", "text": [ "Leprosy is a complex infectious disease influenced by genetic and environmental factors. The genetic contributing factors are considered heterogeneous and several genes have been consistently associated with susceptibility like PARK2, tumor necrosis factor (TNF), lymphotoxin-alpha (LTA) and vitamin-D receptor (VDR). Here, we combined a case-control study (374 patients and 380 controls), with meta-analysis (5 studies; 2702 individuals) and biological study to test the epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic markers in leprosy. We observed that the -819T allele is associated with leprosy susceptibility either in the case-control or in the meta-analysis studies. Haplotypes combining promoter single-nucleotide polymorphisms also implicated a haplotype carrying the -819T allele in leprosy susceptibility (odds ratio (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood mononuclear cells stimulated with Mycobacterium leprae antigens and found that -819T carriers produced lower levels of IL-10 when compared with non-carriers. Taken together, these data suggest that low levels of IL-10 during the disease outcome can drive patients to a chronic and unprotective response that culminates with leprosy." ], "offsets": [ [ 174, 1446 ] ] } ]

[ { "id": "16829", "type": "SNP & Sequence variations", "text": [ "interleukin-10 promoter single-nucleotide polymorphisms" ], "offsets": [ [ 52, 107 ] ], "normalized": [] }, { "id": "16830", "type": "Genes & Molecular Sequences", "text": [ "interleukin-10 promoter single-nucleotide polymorphisms" ], "offsets": [ [ 52, 107 ] ], "normalized": [] }, { "id": "16831", "type": "SNP & Sequence variations", "text": [ "-819C/T" ], "offsets": [ [ 139, 146 ] ], "normalized": [] }, { "id": "16832", "type": "Diseases & Disorders", "text": [ "leprosy" ], "offsets": [ [ 150, 157 ] ], "normalized": [] }, { "id": "16833", "type": "Diseases & Disorders", "text": [ "Leprosy" ], "offsets": [ [ 174, 181 ] ], "normalized": [] }, { "id": "16834", "type": "Diseases & Disorders", "text": [ "infectious disease" ], "offsets": [ [ 195, 213 ] ], "normalized": [] }, { "id": "16835", "type": "Genes & Molecular Sequences", "text": [ "PARK2" ], "offsets": [ [ 402, 407 ] ], "normalized": [] }, { "id": "16836", "type": "Diseases & Disorders", "text": [ "PARK2" ], "offsets": [ [ 402, 407 ] ], "normalized": [] }, { "id": "16837", "type": "Genes & Molecular Sequences", "text": [ "tumor necrosis factor" ], "offsets": [ [ 409, 430 ] ], "normalized": [] }, { "id": "16838", "type": "Genes & Molecular Sequences", "text": [ "TNF" ], "offsets": [ [ 432, 435 ] ], "normalized": [] }, { "id": "16839", "type": "Genes & Molecular Sequences", "text": [ "lymphotoxin-alpha" ], "offsets": [ [ 438, 455 ] ], "normalized": [] }, { "id": "16840", "type": "Genes & Molecular Sequences", "text": [ "LTA" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "16841", "type": "Genes & Molecular Sequences", "text": [ "vitamin-D receptor" ], "offsets": [ [ 466, 484 ] ], "normalized": [] }, { "id": "16842", "type": "Genes & Molecular Sequences", "text": [ "VDR" ], "offsets": [ [ 486, 489 ] ], "normalized": [] }, { "id": "16843", "type": "Genes & Molecular Sequences", "text": [ "interleukin-10" ], "offsets": [ [ 697, 711 ] ], "normalized": [] }, { "id": "16844", "type": "Genes & Molecular Sequences", "text": [ "IL-10" ], "offsets": [ [ 713, 718 ] ], "normalized": [] }, { "id": "16845", "type": "Diseases & Disorders", "text": [ "leprosy" ], "offsets": [ [ 739, 746 ] ], "normalized": [] }, { "id": "16846", "type": "SNP & Sequence variations", "text": [ "-819T" ], "offsets": [ [ 769, 774 ] ], "normalized": [] }, { "id": "16847", "type": "Diseases & Disorders", "text": [ "leprosy" ], "offsets": [ [ 801, 808 ] ], "normalized": [] }, { "id": "16848", "type": "SNP & Sequence variations", "text": [ "-819T" ], "offsets": [ [ 987, 992 ] ], "normalized": [] }, { "id": "16849", "type": "Diseases & Disorders", "text": [ "leprosy" ], "offsets": [ [ 1003, 1010 ] ], "normalized": [] }, { "id": "16850", "type": "Genes & Molecular Sequences", "text": [ "IL-10" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "16851", "type": "Genes & Molecular Sequences", "text": [ "Mycobacterium leprae antigens" ], "offsets": [ [ 1148, 1177 ] ], "normalized": [] }, { "id": "16852", "type": "Diseases & Disorders", "text": [ "Mycobacterium leprae antigens" ], "offsets": [ [ 1148, 1177 ] ], "normalized": [] }, { "id": "16853", "type": "SNP & Sequence variations", "text": [ "-819T" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "16854", "type": "Genes & Molecular Sequences", "text": [ "IL-10" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "16855", "type": "Genes & Molecular Sequences", "text": [ "IL-10" ], "offsets": [ [ 1326, 1331 ] ], "normalized": [] }, { "id": "16856", "type": "Diseases & Disorders", "text": [ "leprosy" ], "offsets": [ [ 1438, 1445 ] ], "normalized": [] }, { "id": "16857", "type": "", "text": [ "-819C/T" ], "offsets": [ [ 139, 146 ] ], "normalized": [] }, { "id": "16858", "type": "", "text": [ "leprosy" ], "offsets": [ [ 150, 157 ] ], "normalized": [] }, { "id": "16860", "type": "", "text": [ "interleukin-10 promoter single-nucleotide polymorphisms" ], "offsets": [ [ 52, 107 ] ], "normalized": [] }, { "id": "16861", "type": "", "text": [ "leprosy" ], "offsets": [ [ 150, 157 ] ], "normalized": [] }, { "id": "16863", "type": "", "text": [ "-819T" ], "offsets": [ [ 769, 774 ] ], "normalized": [] }, { "id": "16864", "type": "", "text": [ "leprosy" ], "offsets": [ [ 801, 808 ] ], "normalized": [] }, { "id": "16866", "type": "", "text": [ "-819T" ], "offsets": [ [ 987, 992 ] ], "normalized": [] }, { "id": "16867", "type": "", "text": [ "leprosy" ], "offsets": [ [ 1003, 1010 ] ], "normalized": [] }, { "id": "16869", "type": "", "text": [ "IL-10" ], "offsets": [ [ 1326, 1331 ] ], "normalized": [] }, { "id": "16870", "type": "", "text": [ "leprosy" ], "offsets": [ [ 1438, 1445 ] ], "normalized": [] }, { "id": "16872", "type": "", "text": [ "TNF" ], "offsets": [ [ 432, 435 ] ], "normalized": [] }, { "id": "16873", "type": "", "text": [ "PARK2" ], "offsets": [ [ 402, 407 ] ], "normalized": [] }, { "id": "16875", "type": "", "text": [ "LTA" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "16876", "type": "", "text": [ "PARK2" ], "offsets": [ [ 402, 407 ] ], "normalized": [] }, { "id": "16878", "type": "", "text": [ "VDR" ], "offsets": [ [ 486, 489 ] ], "normalized": [] }, { "id": "16879", "type": "", "text": [ "PARK2" ], "offsets": [ [ 402, 407 ] ], "normalized": [] }, { "id": "16881", "type": "", "text": [ "IL-10" ], "offsets": [ [ 713, 718 ] ], "normalized": [] }, { "id": "16882", "type": "", "text": [ "leprosy" ], "offsets": [ [ 739, 746 ] ], "normalized": [] }, { "id": "16884", "type": "", "text": [ "IL-10" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "16885", "type": "", "text": [ "Mycobacterium leprae antigens" ], "offsets": [ [ 1148, 1177 ] ], "normalized": [] }, { "id": "16887", "type": "", "text": [ "-819T" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "16888", "type": "", "text": [ "Mycobacterium leprae antigens" ], "offsets": [ [ 1148, 1177 ] ], "normalized": [] }, { "id": "16890", "type": "", "text": [ "interleukin-10" ], "offsets": [ [ 697, 711 ] ], "normalized": [] }, { "id": "16891", "type": "", "text": [ "leprosy" ], "offsets": [ [ 739, 746 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16859", "type": "PA", "arg1_id": "16857", "arg2_id": "16858", "normalized": [] }, { "id": "16862", "type": "PA", "arg1_id": "16860", "arg2_id": "16861", "normalized": [] }, { "id": "16865", "type": "PA", "arg1_id": "16863", "arg2_id": "16864", "normalized": [] }, { "id": "16868", "type": "PA", "arg1_id": "16866", "arg2_id": "16867", "normalized": [] }, { "id": "16871", "type": "SA", "arg1_id": "16869", "arg2_id": "16870", "normalized": [] }, { "id": "16874", "type": "PA", "arg1_id": "16872", "arg2_id": "16873", "normalized": [] }, { "id": "16877", "type": "PA", "arg1_id": "16875", "arg2_id": "16876", "normalized": [] }, { "id": "16880", "type": "PA", "arg1_id": "16878", "arg2_id": "16879", "normalized": [] }, { "id": "16883", "type": "PA", "arg1_id": "16881", "arg2_id": "16882", "normalized": [] }, { "id": "16886", "type": "PA", "arg1_id": "16884", "arg2_id": "16885", "normalized": [] }, { "id": "16889", "type": "PA", "arg1_id": "16887", "arg2_id": "16888", "normalized": [] }, { "id": "16892", "type": "SA", "arg1_id": "16890", "arg2_id": "16891", "normalized": [] } ]

[ { "id": "16895", "type": "title", "text": [ "Role of epidermal growth factor gene in the development of pancreatic cancer and efficiency of inhibitors of this gene in the treatment of pancreatic carcinoma." ], "offsets": [ [ 0, 160 ] ] }, { "id": "16896", "type": "abstract", "text": [ "The expression of epidermal growth factor receptors in normal and tumor cells of the pancreas, the type and incidence of EGFR gene polymorphism were studied. EGFR gene expression in pancreatic adenocarcinoma cells significantly surpassed that in normal pancreatic cells. On the other hand, AA genome and A allele polymorphism in the EGF gene nucleotide pair G-A 61 is a significant risk factor for pancreatic cancer. The effect of AG-1478 preparation (a new-generation inhibitor of EGFR) on apoptosis and cell proliferation in pancreatic cancer was evaluated. This preparation is not inferior to 5FU by its apoptotic effect and significantly reduces cell proliferation, its antiproliferative effect being 1.5 times higher than that of 5FU." ], "offsets": [ [ 161, 900 ] ] } ]

[ { "id": "16897", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor" ], "offsets": [ [ 8, 31 ] ], "normalized": [] }, { "id": "16898", "type": "Diseases & Disorders", "text": [ "pancreatic cancer" ], "offsets": [ [ 59, 76 ] ], "normalized": [] }, { "id": "16899", "type": "Diseases & Disorders", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 139, 159 ] ], "normalized": [] }, { "id": "16900", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor" ], "offsets": [ [ 179, 202 ] ], "normalized": [] }, { "id": "16901", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "16902", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 282, 286 ] ], "normalized": [] }, { "id": "16903", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 319, 323 ] ], "normalized": [] }, { "id": "16904", "type": "Diseases & Disorders", "text": [ "pancreatic adenocarcinoma" ], "offsets": [ [ 343, 368 ] ], "normalized": [] }, { "id": "16905", "type": "SNP & Sequence variations", "text": [ "AA genome" ], "offsets": [ [ 451, 460 ] ], "normalized": [] }, { "id": "16906", "type": "SNP & Sequence variations", "text": [ "A allele polymorphism" ], "offsets": [ [ 465, 486 ] ], "normalized": [] }, { "id": "16907", "type": "Genes & Molecular Sequences", "text": [ "EGF" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "16908", "type": "SNP & Sequence variations", "text": [ "EGF" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "16909", "type": "Genes & Molecular Sequences", "text": [ "G-A 61" ], "offsets": [ [ 519, 525 ] ], "normalized": [] }, { "id": "16910", "type": "SNP & Sequence variations", "text": [ "G-A 61" ], "offsets": [ [ 519, 525 ] ], "normalized": [] }, { "id": "16911", "type": "Diseases & Disorders", "text": [ "pancreatic cancer" ], "offsets": [ [ 559, 576 ] ], "normalized": [] }, { "id": "16912", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 643, 647 ] ], "normalized": [] }, { "id": "16913", "type": "Diseases & Disorders", "text": [ "pancreatic cancer" ], "offsets": [ [ 688, 705 ] ], "normalized": [] }, { "id": "16914", "type": "", "text": [ "epidermal growth factor" ], "offsets": [ [ 8, 31 ] ], "normalized": [] }, { "id": "16915", "type": "", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 139, 159 ] ], "normalized": [] }, { "id": "16917", "type": "", "text": [ "EGFR" ], "offsets": [ [ 319, 323 ] ], "normalized": [] }, { "id": "16918", "type": "", "text": [ "pancreatic adenocarcinoma" ], "offsets": [ [ 343, 368 ] ], "normalized": [] }, { "id": "16920", "type": "", "text": [ "AA genome" ], "offsets": [ [ 451, 460 ] ], "normalized": [] }, { "id": "16921", "type": "", "text": [ "pancreatic cancer" ], "offsets": [ [ 559, 576 ] ], "normalized": [] }, { "id": "16923", "type": "", "text": [ "A allele polymorphism" ], "offsets": [ [ 465, 486 ] ], "normalized": [] }, { "id": "16924", "type": "", "text": [ "pancreatic cancer" ], "offsets": [ [ 559, 576 ] ], "normalized": [] }, { "id": "16926", "type": "", "text": [ "epidermal growth factor" ], "offsets": [ [ 179, 202 ] ], "normalized": [] }, { "id": "16927", "type": "", "text": [ "tumor" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "16929", "type": "", "text": [ "EGFR" ], "offsets": [ [ 282, 286 ] ], "normalized": [] }, { "id": "16930", "type": "", "text": [ "tumor" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "16932", "type": "", "text": [ "EGF" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "16933", "type": "", "text": [ "pancreatic cancer" ], "offsets": [ [ 559, 576 ] ], "normalized": [] }, { "id": "16935", "type": "", "text": [ "EGFR" ], "offsets": [ [ 643, 647 ] ], "normalized": [] }, { "id": "16936", "type": "", "text": [ "pancreatic cancer" ], "offsets": [ [ 688, 705 ] ], "normalized": [] }, { "id": "16938", "type": "", "text": [ "G-A 61" ], "offsets": [ [ 519, 525 ] ], "normalized": [] }, { "id": "16939", "type": "", "text": [ "pancreatic cancer" ], "offsets": [ [ 559, 576 ] ], "normalized": [] } ]

[]

[]

[ { "id": "16916", "type": "PA", "arg1_id": "16914", "arg2_id": "16915", "normalized": [] }, { "id": "16919", "type": "PA", "arg1_id": "16917", "arg2_id": "16918", "normalized": [] }, { "id": "16922", "type": "PA", "arg1_id": "16920", "arg2_id": "16921", "normalized": [] }, { "id": "16925", "type": "PA", "arg1_id": "16923", "arg2_id": "16924", "normalized": [] }, { "id": "16928", "type": "PA", "arg1_id": "16926", "arg2_id": "16927", "normalized": [] }, { "id": "16931", "type": "PA", "arg1_id": "16929", "arg2_id": "16930", "normalized": [] }, { "id": "16934", "type": "PA", "arg1_id": "16932", "arg2_id": "16933", "normalized": [] }, { "id": "16937", "type": "PA", "arg1_id": "16935", "arg2_id": "16936", "normalized": [] }, { "id": "16940", "type": "PA", "arg1_id": "16938", "arg2_id": "16939", "normalized": [] } ]

[ { "id": "16943", "type": "title", "text": [ "Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits." ], "offsets": [ [ 0, 226 ] ] }, { "id": "16944", "type": "abstract", "text": [ "BACKGROUND: Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase and NOS1AP encoding the nitric oxide synthase 1 (neuronal) adaptor protein (CAPON) are positioned within this chromosomal region and are thus positional candidates for the observed linkage peak. The C-allele of PKLR rs3020781 and the T-allele of NOS1AP rs7538490 are reported to strongly associate with type 2 diabetes in various European-descent populations comprising a total of 2,198 individuals with a combined odds ratio (OR) of 1.33 [1.16-1.54] and 1.53 [1.28-1.81], respectively. Our aim was to validate these findings by investigating the impact of the two variants on type 2 diabetes and related quantitative metabolic phenotypes in a large study sample of Danes. Further, we intended to expand the analyses by examining the effect of the variants in relation to overweight and obesity. METHODS: PKLR rs3020781 and NOS1AP rs7538490 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising a total of 16,801 and 16,913 individuals, respectively. The participants were ascertained from four different study groups; the population-based Inter99 cohort (nPKLR = 5,962, nNOS1AP = 6,008), a type 2 diabetic patient group (nPKLR = 1,873, nNOS1AP = 1,874) from Steno Diabetes Center, a population-based study sample (nPKLR = 599, nNOS1AP = 596) from Steno Diabetes Center and the ADDITION Denmark screening study cohort (nPKLR = 8,367, nNOS1AP = 8,435). RESULTS: In case-control studies we evaluated the potential association between rs3020781 and rs7538490 and type 2 diabetes and obesity. No significant associations were observed for type 2 diabetes (rs3020781: pAF = 0.49, OR = 1.02 [0.96-1.10]; rs7538490: pAF = 0.84, OR = 0.99 [0.93-1.06]). Neither did we show association with overweight or obesity. Additionally, the PKLR and the NOS1AP genotypes were demonstrated not to have a major influence on diabetes-related quantitative metabolic phenotypes. CONCLUSION: We failed to provide evidence of an association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity or related quantitative metabolic phenotypes in large-scale studies of Danes." ], "offsets": [ [ 227, 2503 ] ] } ]

[ { "id": "16945", "type": "SNP & Sequence variations", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "16946", "type": "Genes & Molecular Sequences", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "16947", "type": "SNP & Sequence variations", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "16948", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "16949", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "16950", "type": "Diseases & Disorders", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "16951", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "16952", "type": "Diseases & Disorders", "text": [ "metabolic phenotypes" ], "offsets": [ [ 117, 137 ] ], "normalized": [] }, { "id": "16953", "type": "Genes & Molecular Sequences", "text": [ "traits" ], "offsets": [ [ 219, 225 ] ], "normalized": [] }, { "id": "16954", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 304, 319 ] ], "normalized": [] }, { "id": "16955", "type": "Genes & Molecular Sequences", "text": [ "1q21-25" ], "offsets": [ [ 334, 341 ] ], "normalized": [] }, { "id": "16956", "type": "Genes & Molecular Sequences", "text": [ "PKLR" ], "offsets": [ [ 348, 352 ] ], "normalized": [] }, { "id": "16957", "type": "Genes & Molecular Sequences", "text": [ "liver pyruvate kinase" ], "offsets": [ [ 366, 387 ] ], "normalized": [] }, { "id": "16958", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP" ], "offsets": [ [ 392, 398 ] ], "normalized": [] }, { "id": "16959", "type": "Genes & Molecular Sequences", "text": [ "nitric oxide synthase 1 (neuronal) adaptor protein" ], "offsets": [ [ 412, 462 ] ], "normalized": [] }, { "id": "16960", "type": "Genes & Molecular Sequences", "text": [ "CAPON" ], "offsets": [ [ 464, 469 ] ], "normalized": [] }, { "id": "16961", "type": "SNP & Sequence variations", "text": [ "C-allele of PKLR rs3020781" ], "offsets": [ [ 587, 613 ] ], "normalized": [] }, { "id": "16962", "type": "Genes & Molecular Sequences", "text": [ "PKLR" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "16963", "type": "SNP & Sequence variations", "text": [ "T-allele of NOS1AP rs7538490" ], "offsets": [ [ 622, 650 ] ], "normalized": [] }, { "id": "16964", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP" ], "offsets": [ [ 634, 640 ] ], "normalized": [] }, { "id": "16965", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "16966", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 965, 980 ] ], "normalized": [] }, { "id": "16967", "type": "Diseases & Disorders", "text": [ "metabolic phenotypes" ], "offsets": [ [ 1006, 1026 ] ], "normalized": [] }, { "id": "16968", "type": "Diseases & Disorders", "text": [ "overweight and obesity" ], "offsets": [ [ 1160, 1182 ] ], "normalized": [] }, { "id": "16969", "type": "SNP & Sequence variations", "text": [ "PKLR rs3020781" ], "offsets": [ [ 1193, 1207 ] ], "normalized": [] }, { "id": "16970", "type": "Genes & Molecular Sequences", "text": [ "PKLR rs3020781" ], "offsets": [ [ 1193, 1207 ] ], "normalized": [] }, { "id": "16971", "type": "SNP & Sequence variations", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 1212, 1228 ] ], "normalized": [] }, { "id": "16972", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 1212, 1228 ] ], "normalized": [] }, { "id": "16973", "type": "Genes & Molecular Sequences", "text": [ "nPKLR" ], "offsets": [ [ 1481, 1486 ] ], "normalized": [] }, { "id": "16974", "type": "Genes & Molecular Sequences", "text": [ "nNOS1AP" ], "offsets": [ [ 1496, 1503 ] ], "normalized": [] }, { "id": "16975", "type": "Genes & Molecular Sequences", "text": [ "nPKLR" ], "offsets": [ [ 1547, 1552 ] ], "normalized": [] }, { "id": "16976", "type": "Genes & Molecular Sequences", "text": [ "nNOS1AP" ], "offsets": [ [ 1562, 1569 ] ], "normalized": [] }, { "id": "16977", "type": "Diseases & Disorders", "text": [ "Diabetes" ], "offsets": [ [ 1590, 1598 ] ], "normalized": [] }, { "id": "16978", "type": "Genes & Molecular Sequences", "text": [ "nPKLR" ], "offsets": [ [ 1640, 1645 ] ], "normalized": [] }, { "id": "16979", "type": "Genes & Molecular Sequences", "text": [ "nNOS1AP" ], "offsets": [ [ 1653, 1660 ] ], "normalized": [] }, { "id": "16980", "type": "Diseases & Disorders", "text": [ "Diabetes" ], "offsets": [ [ 1679, 1687 ] ], "normalized": [] }, { "id": "16981", "type": "Genes & Molecular Sequences", "text": [ "nPKLR" ], "offsets": [ [ 1744, 1749 ] ], "normalized": [] }, { "id": "16982", "type": "Genes & Molecular Sequences", "text": [ "nNOS1AP" ], "offsets": [ [ 1759, 1766 ] ], "normalized": [] }, { "id": "16983", "type": "SNP & Sequence variations", "text": [ "rs3020781" ], "offsets": [ [ 1857, 1866 ] ], "normalized": [] }, { "id": "16984", "type": "SNP & Sequence variations", "text": [ "rs7538490" ], "offsets": [ [ 1871, 1880 ] ], "normalized": [] }, { "id": "16985", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 1885, 1900 ] ], "normalized": [] }, { "id": "16986", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 1905, 1912 ] ], "normalized": [] }, { "id": "16987", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 1960, 1975 ] ], "normalized": [] }, { "id": "16988", "type": "SNP & Sequence variations", "text": [ "rs3020781" ], "offsets": [ [ 1977, 1986 ] ], "normalized": [] }, { "id": "16989", "type": "SNP & Sequence variations", "text": [ "rs7538490" ], "offsets": [ [ 2023, 2032 ] ], "normalized": [] }, { "id": "16990", "type": "Diseases & Disorders", "text": [ "overweight" ], "offsets": [ [ 2107, 2117 ] ], "normalized": [] }, { "id": "16991", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 2121, 2128 ] ], "normalized": [] }, { "id": "16992", "type": "Genes & Molecular Sequences", "text": [ "PKLR" ], "offsets": [ [ 2148, 2152 ] ], "normalized": [] }, { "id": "16993", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP" ], "offsets": [ [ 2161, 2167 ] ], "normalized": [] }, { "id": "16994", "type": "Diseases & Disorders", "text": [ "diabetes-related quantitative metabolic phenotypes" ], "offsets": [ [ 2229, 2279 ] ], "normalized": [] }, { "id": "16995", "type": "SNP & Sequence variations", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "16996", "type": "Genes & Molecular Sequences", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "16997", "type": "SNP & Sequence variations", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "16998", "type": "Genes & Molecular Sequences", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "16999", "type": "Diseases & Disorders", "text": [ "type 2 diabetes" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "17000", "type": "Diseases & Disorders", "text": [ "overweight" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "17001", "type": "Diseases & Disorders", "text": [ "obesity" ], "offsets": [ [ 2418, 2425 ] ], "normalized": [] }, { "id": "17002", "type": "Diseases & Disorders", "text": [ "metabolic phenotypes" ], "offsets": [ [ 2450, 2470 ] ], "normalized": [] }, { "id": "17003", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17004", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "17006", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17007", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "17009", "type": "", "text": [ "1q21-25" ], "offsets": [ [ 334, 341 ] ], "normalized": [] }, { "id": "17010", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 304, 319 ] ], "normalized": [] }, { "id": "17012", "type": "", "text": [ "C-allele of PKLR rs3020781" ], "offsets": [ [ 587, 613 ] ], "normalized": [] }, { "id": "17013", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "17015", "type": "", "text": [ "T-allele of NOS1AP rs7538490" ], "offsets": [ [ 622, 650 ] ], "normalized": [] }, { "id": "17016", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "17018", "type": "", "text": [ "rs3020781" ], "offsets": [ [ 1977, 1986 ] ], "normalized": [] }, { "id": "17019", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 1960, 1975 ] ], "normalized": [] }, { "id": "17021", "type": "", "text": [ "rs7538490" ], "offsets": [ [ 2023, 2032 ] ], "normalized": [] }, { "id": "17022", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 1960, 1975 ] ], "normalized": [] }, { "id": "17024", "type": "", "text": [ "PKLR" ], "offsets": [ [ 2148, 2152 ] ], "normalized": [] }, { "id": "17025", "type": "", "text": [ "diabetes-related quantitative metabolic phenotypes" ], "offsets": [ [ 2229, 2279 ] ], "normalized": [] }, { "id": "17027", "type": "", "text": [ "NOS1AP" ], "offsets": [ [ 2161, 2167 ] ], "normalized": [] }, { "id": "17028", "type": "", "text": [ "diabetes-related quantitative metabolic phenotypes" ], "offsets": [ [ 2229, 2279 ] ], "normalized": [] }, { "id": "17030", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17031", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "17033", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17034", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "17036", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17037", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "17039", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17040", "type": "", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "17042", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17043", "type": "", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "17045", "type": "", "text": [ "traits" ], "offsets": [ [ 219, 225 ] ], "normalized": [] }, { "id": "17046", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "17048", "type": "", "text": [ "traits" ], "offsets": [ [ 219, 225 ] ], "normalized": [] }, { "id": "17049", "type": "", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "17051", "type": "", "text": [ "traits" ], "offsets": [ [ 219, 225 ] ], "normalized": [] }, { "id": "17052", "type": "", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "17054", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17055", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 68, 83 ] ], "normalized": [] }, { "id": "17057", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17058", "type": "", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "17060", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17061", "type": "", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "17063", "type": "", "text": [ "PKLR" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "17064", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "17066", "type": "", "text": [ "NOS1AP" ], "offsets": [ [ 634, 640 ] ], "normalized": [] }, { "id": "17067", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "17069", "type": "", "text": [ "PKLR" ], "offsets": [ [ 2148, 2152 ] ], "normalized": [] }, { "id": "17070", "type": "", "text": [ "diabetes-related quantitative metabolic phenotypes" ], "offsets": [ [ 2229, 2279 ] ], "normalized": [] }, { "id": "17072", "type": "", "text": [ "NOS1AP" ], "offsets": [ [ 2161, 2167 ] ], "normalized": [] }, { "id": "17073", "type": "", "text": [ "diabetes-related quantitative metabolic phenotypes" ], "offsets": [ [ 2229, 2279 ] ], "normalized": [] }, { "id": "17075", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17076", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "17078", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17079", "type": "", "text": [ "overweight" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "17081", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17082", "type": "", "text": [ "obesity" ], "offsets": [ [ 2418, 2425 ] ], "normalized": [] }, { "id": "17084", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17085", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "17087", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17088", "type": "", "text": [ "overweight" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "17090", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17091", "type": "", "text": [ "obesity" ], "offsets": [ [ 2418, 2425 ] ], "normalized": [] }, { "id": "17093", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17094", "type": "", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "17096", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17097", "type": "", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "17099", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17100", "type": "", "text": [ "overweight" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "17102", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17103", "type": "", "text": [ "obesity" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "17105", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17106", "type": "", "text": [ "overweight" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "17108", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17109", "type": "", "text": [ "obesity" ], "offsets": [ [ 2418, 2425 ] ], "normalized": [] }, { "id": "17111", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17112", "type": "", "text": [ "overweight" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "17114", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17115", "type": "", "text": [ "obesity" ], "offsets": [ [ 2418, 2425 ] ], "normalized": [] }, { "id": "17117", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "17118", "type": "", "text": [ "metabolic phenotypes" ], "offsets": [ [ 117, 137 ] ], "normalized": [] }, { "id": "17120", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "17121", "type": "", "text": [ "metabolic phenotypes" ], "offsets": [ [ 117, 137 ] ], "normalized": [] }, { "id": "17123", "type": "", "text": [ "rs3020781" ], "offsets": [ [ 1857, 1866 ] ], "normalized": [] }, { "id": "17124", "type": "", "text": [ "obesity" ], "offsets": [ [ 1905, 1912 ] ], "normalized": [] }, { "id": "17126", "type": "", "text": [ "rs3020781" ], "offsets": [ [ 1857, 1866 ] ], "normalized": [] }, { "id": "17127", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 1885, 1900 ] ], "normalized": [] }, { "id": "17129", "type": "", "text": [ "rs7538490" ], "offsets": [ [ 1871, 1880 ] ], "normalized": [] }, { "id": "17130", "type": "", "text": [ "obesity" ], "offsets": [ [ 1905, 1912 ] ], "normalized": [] }, { "id": "17132", "type": "", "text": [ "rs7538490" ], "offsets": [ [ 1871, 1880 ] ], "normalized": [] }, { "id": "17133", "type": "", "text": [ "type 2 diabetes" ], "offsets": [ [ 1885, 1900 ] ], "normalized": [] }, { "id": "17135", "type": "", "text": [ "PKLR rs3020781" ], "offsets": [ [ 2349, 2363 ] ], "normalized": [] }, { "id": "17136", "type": "", "text": [ "metabolic phenotypes" ], "offsets": [ [ 2450, 2470 ] ], "normalized": [] }, { "id": "17138", "type": "", "text": [ "NOS1AP rs7538490" ], "offsets": [ [ 2368, 2384 ] ], "normalized": [] }, { "id": "17139", "type": "", "text": [ "metabolic phenotypes" ], "offsets": [ [ 2450, 2470 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "17143", "type": "title", "text": [ "Otosclerosis and TGF-beta 1 gene in black South Africans." ], "offsets": [ [ 0, 57 ] ] }, { "id": "17144", "type": "abstract", "text": [ "Limited literature is available on the epidemiology and genetics of otosclerosis in South African blacks, among whom it is extremely rare. We undertook this study because we had documented and surgically confirmed cases of clinical oval window otosclerosis in this population." ], "offsets": [ [ 58, 334 ] ] } ]

[ { "id": "17145", "type": "Diseases & Disorders", "text": [ "Otosclerosis" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "17146", "type": "Genes & Molecular Sequences", "text": [ "TGF-beta 1" ], "offsets": [ [ 17, 27 ] ], "normalized": [] }, { "id": "17147", "type": "Diseases & Disorders", "text": [ "otosclerosis" ], "offsets": [ [ 126, 138 ] ], "normalized": [] }, { "id": "17148", "type": "Diseases & Disorders", "text": [ "otosclerosis" ], "offsets": [ [ 302, 314 ] ], "normalized": [] }, { "id": "17149", "type": "", "text": [ "TGF-beta 1" ], "offsets": [ [ 17, 27 ] ], "normalized": [] }, { "id": "17150", "type": "", "text": [ "Otosclerosis" ], "offsets": [ [ 0, 12 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17151", "type": "PA", "arg1_id": "17149", "arg2_id": "17150", "normalized": [] } ]

[ { "id": "17154", "type": "title", "text": [ "From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene." ], "offsets": [ [ 0, 102 ] ] }, { "id": "17155", "type": "abstract", "text": [ "Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10(-6)). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell-based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na(+) excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway." ], "offsets": [ [ 103, 1662 ] ] } ]

[ { "id": "17156", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 58, 63 ] ], "normalized": [] }, { "id": "17157", "type": "Diseases & Disorders", "text": [ "hypertension" ], "offsets": [ [ 69, 81 ] ], "normalized": [] }, { "id": "17158", "type": "Diseases & Disorders", "text": [ "Hypertension" ], "offsets": [ [ 103, 115 ] ], "normalized": [] }, { "id": "17159", "type": "Diseases & Disorders", "text": [ "disorder" ], "offsets": [ [ 209, 217 ] ], "normalized": [] }, { "id": "17160", "type": "Genes & Molecular Sequences", "text": [ "SBP" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "17161", "type": "Diseases & Disorders", "text": [ "SBP" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "17162", "type": "Genes & Molecular Sequences", "text": [ "DBP" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "17163", "type": "Diseases & Disorders", "text": [ "DBP" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "17164", "type": "Genes & Molecular Sequences", "text": [ "serine/threonine kinase" ], "offsets": [ [ 421, 444 ] ], "normalized": [] }, { "id": "17165", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "17166", "type": "Diseases & Disorders", "text": [ "Diabetes" ], "offsets": [ [ 560, 568 ] ], "normalized": [] }, { "id": "17167", "type": "Diseases & Disorders", "text": [ "BP" ], "offsets": [ [ 710, 712 ] ], "normalized": [] }, { "id": "17168", "type": "Genes & Molecular Sequences", "text": [ "SBP" ], "offsets": [ [ 811, 814 ] ], "normalized": [] }, { "id": "17169", "type": "Diseases & Disorders", "text": [ "SBP" ], "offsets": [ [ 811, 814 ] ], "normalized": [] }, { "id": "17170", "type": "Genes & Molecular Sequences", "text": [ "DBP" ], "offsets": [ [ 815, 818 ] ], "normalized": [] }, { "id": "17171", "type": "Diseases & Disorders", "text": [ "DBP" ], "offsets": [ [ 815, 818 ] ], "normalized": [] }, { "id": "17172", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "17173", "type": "Genes & Molecular Sequences", "text": [ "WNK" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "17174", "type": "Genes & Molecular Sequences", "text": [ "cation-chloride cotransporters" ], "offsets": [ [ 1005, 1035 ] ], "normalized": [] }, { "id": "17175", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 1037, 1046 ] ], "normalized": [] }, { "id": "17176", "type": "Diseases & Disorders", "text": [ "BP dysregulation" ], "offsets": [ [ 1081, 1097 ] ], "normalized": [] }, { "id": "17177", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 1128, 1133 ] ], "normalized": [] }, { "id": "17178", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 1473, 1478 ] ], "normalized": [] }, { "id": "17179", "type": "Diseases & Disorders", "text": [ "BP" ], "offsets": [ [ 1493, 1495 ] ], "normalized": [] }, { "id": "17180", "type": "Genes & Molecular Sequences", "text": [ "STK39" ], "offsets": [ [ 1510, 1515 ] ], "normalized": [] }, { "id": "17181", "type": "Diseases & Disorders", "text": [ "renal Na" ], "offsets": [ [ 1553, 1561 ] ], "normalized": [] }, { "id": "17182", "type": "Diseases & Disorders", "text": [ "BP" ], "offsets": [ [ 1606, 1608 ] ], "normalized": [] }, { "id": "17183", "type": "", "text": [ "STK39" ], "offsets": [ [ 58, 63 ] ], "normalized": [] }, { "id": "17184", "type": "", "text": [ "hypertension" ], "offsets": [ [ 69, 81 ] ], "normalized": [] }, { "id": "17186", "type": "", "text": [ "cation-chloride cotransporters" ], "offsets": [ [ 1005, 1035 ] ], "normalized": [] }, { "id": "17187", "type": "", "text": [ "BP dysregulation" ], "offsets": [ [ 1081, 1097 ] ], "normalized": [] }, { "id": "17189", "type": "", "text": [ "STK39" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "17190", "type": "", "text": [ "mutations" ], "offsets": [ [ 1037, 1046 ] ], "normalized": [] }, { "id": "17192", "type": "", "text": [ "STK39" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "17193", "type": "", "text": [ "DBP" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "17195", "type": "", "text": [ "STK39" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "17196", "type": "", "text": [ "SBP" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "17198", "type": "", "text": [ "serine/threonine kinase" ], "offsets": [ [ 421, 444 ] ], "normalized": [] }, { "id": "17199", "type": "", "text": [ "DBP" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "17201", "type": "", "text": [ "serine/threonine kinase" ], "offsets": [ [ 421, 444 ] ], "normalized": [] }, { "id": "17202", "type": "", "text": [ "SBP" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "17204", "type": "", "text": [ "STK39" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "17205", "type": "", "text": [ "BP dysregulation" ], "offsets": [ [ 1081, 1097 ] ], "normalized": [] }, { "id": "17207", "type": "", "text": [ "WNK" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "17208", "type": "", "text": [ "BP dysregulation" ], "offsets": [ [ 1081, 1097 ] ], "normalized": [] }, { "id": "17210", "type": "", "text": [ "STK39" ], "offsets": [ [ 1473, 1478 ] ], "normalized": [] }, { "id": "17211", "type": "", "text": [ "BP" ], "offsets": [ [ 1606, 1608 ] ], "normalized": [] }, { "id": "17213", "type": "", "text": [ "STK39" ], "offsets": [ [ 1473, 1478 ] ], "normalized": [] }, { "id": "17214", "type": "", "text": [ "renal Na" ], "offsets": [ [ 1553, 1561 ] ], "normalized": [] }, { "id": "17216", "type": "", "text": [ "STK39" ], "offsets": [ [ 1510, 1515 ] ], "normalized": [] }, { "id": "17217", "type": "", "text": [ "BP" ], "offsets": [ [ 1606, 1608 ] ], "normalized": [] }, { "id": "17219", "type": "", "text": [ "STK39" ], "offsets": [ [ 1510, 1515 ] ], "normalized": [] }, { "id": "17220", "type": "", "text": [ "renal Na" ], "offsets": [ [ 1553, 1561 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17185", "type": "PA", "arg1_id": "17183", "arg2_id": "17184", "normalized": [] }, { "id": "17188", "type": "PA", "arg1_id": "17186", "arg2_id": "17187", "normalized": [] }, { "id": "17191", "type": "PA", "arg1_id": "17189", "arg2_id": "17190", "normalized": [] }, { "id": "17194", "type": "PA", "arg1_id": "17192", "arg2_id": "17193", "normalized": [] }, { "id": "17197", "type": "PA", "arg1_id": "17195", "arg2_id": "17196", "normalized": [] }, { "id": "17200", "type": "PA", "arg1_id": "17198", "arg2_id": "17199", "normalized": [] }, { "id": "17203", "type": "PA", "arg1_id": "17201", "arg2_id": "17202", "normalized": [] }, { "id": "17206", "type": "PA", "arg1_id": "17204", "arg2_id": "17205", "normalized": [] }, { "id": "17209", "type": "PA", "arg1_id": "17207", "arg2_id": "17208", "normalized": [] }, { "id": "17212", "type": "PA", "arg1_id": "17210", "arg2_id": "17211", "normalized": [] }, { "id": "17215", "type": "PA", "arg1_id": "17213", "arg2_id": "17214", "normalized": [] }, { "id": "17218", "type": "PA", "arg1_id": "17216", "arg2_id": "17217", "normalized": [] }, { "id": "17221", "type": "PA", "arg1_id": "17219", "arg2_id": "17220", "normalized": [] } ]

[ { "id": "17224", "type": "title", "text": [ "Effects of polymorphism in G2677T/A triallelic region of MDR1 gene in Turkish patients with inflammatory bowel disease." ], "offsets": [ [ 0, 119 ] ] }, { "id": "17225", "type": "abstract", "text": [ "BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. Crohn's disease and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of P-glycoprotein, encoded by the MDR1 gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the MDR1 gene are thought to be related with the pathogenesis of inflammatory bowel disease. The aim of this study was to investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with inflammatory bowel disease and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed Crohn's disease (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the MDR1 gene. RESULTS: In this study, the frequency of alleles at position 2677 of the MDR1 gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the MDR1 gene was not found to be a risk factor for Crohn's disease or ulcerative colitis." ], "offsets": [ [ 120, 1767 ] ] } ]

[ { "id": "17226", "type": "SNP & Sequence variations", "text": [ "G2677T/A" ], "offsets": [ [ 27, 35 ] ], "normalized": [] }, { "id": "17227", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 57, 61 ] ], "normalized": [] }, { "id": "17228", "type": "Diseases & Disorders", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 92, 118 ] ], "normalized": [] }, { "id": "17229", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 137, 152 ] ], "normalized": [] }, { "id": "17230", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 157, 175 ] ], "normalized": [] }, { "id": "17231", "type": "Diseases & Disorders", "text": [ "chronic inflammatory disorders" ], "offsets": [ [ 185, 215 ] ], "normalized": [] }, { "id": "17232", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 288, 303 ] ], "normalized": [] }, { "id": "17233", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 308, 326 ] ], "normalized": [] }, { "id": "17234", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 463, 477 ] ], "normalized": [] }, { "id": "17235", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 494, 498 ] ], "normalized": [] }, { "id": "17236", "type": "Genes & Molecular Sequences", "text": [ "gut" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "17237", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 602, 611 ] ], "normalized": [] }, { "id": "17238", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "17239", "type": "SNP & Sequence variations", "text": [ "MDR1" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "17240", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 664, 676 ] ], "normalized": [] }, { "id": "17241", "type": "Diseases & Disorders", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 680, 706 ] ], "normalized": [] }, { "id": "17242", "type": "SNP & Sequence variations", "text": [ "G2677T/A" ], "offsets": [ [ 753, 761 ] ], "normalized": [] }, { "id": "17243", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 782, 786 ] ], "normalized": [] }, { "id": "17244", "type": "Diseases & Disorders", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 817, 843 ] ], "normalized": [] }, { "id": "17245", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 961, 976 ] ], "normalized": [] }, { "id": "17246", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 1001, 1019 ] ], "normalized": [] }, { "id": "17247", "type": "SNP & Sequence variations", "text": [ "G2677T" ], "offsets": [ [ 1255, 1261 ] ], "normalized": [] }, { "id": "17248", "type": "SNP & Sequence variations", "text": [ "G2677A" ], "offsets": [ [ 1266, 1272 ] ], "normalized": [] }, { "id": "17249", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1281, 1285 ] ], "normalized": [] }, { "id": "17250", "type": "SNP & Sequence variations", "text": [ "alleles at position 2677" ], "offsets": [ [ 1333, 1357 ] ], "normalized": [] }, { "id": "17251", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1365, 1369 ] ], "normalized": [] }, { "id": "17252", "type": "SNP & Sequence variations", "text": [ "2677A" ], "offsets": [ [ 1523, 1528 ] ], "normalized": [] }, { "id": "17253", "type": "SNP & Sequence variations", "text": [ "G2677T/A" ], "offsets": [ [ 1643, 1651 ] ], "normalized": [] }, { "id": "17254", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1681, 1685 ] ], "normalized": [] }, { "id": "17255", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 1729, 1744 ] ], "normalized": [] }, { "id": "17256", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 1748, 1766 ] ], "normalized": [] }, { "id": "17257", "type": "", "text": [ "MDR1" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "17258", "type": "", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 680, 706 ] ], "normalized": [] }, { "id": "17260", "type": "", "text": [ "G2677T/A" ], "offsets": [ [ 1643, 1651 ] ], "normalized": [] }, { "id": "17261", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 1729, 1744 ] ], "normalized": [] }, { "id": "17263", "type": "", "text": [ "G2677T/A" ], "offsets": [ [ 1643, 1651 ] ], "normalized": [] }, { "id": "17264", "type": "", "text": [ "ulcerative colitis" ], "offsets": [ [ 1748, 1766 ] ], "normalized": [] }, { "id": "17266", "type": "", "text": [ "MDR1" ], "offsets": [ [ 57, 61 ] ], "normalized": [] }, { "id": "17267", "type": "", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 92, 118 ] ], "normalized": [] }, { "id": "17269", "type": "", "text": [ "MDR1" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "17270", "type": "", "text": [ "mutations" ], "offsets": [ [ 602, 611 ] ], "normalized": [] }, { "id": "17272", "type": "", "text": [ "MDR1" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "17273", "type": "", "text": [ "pathogenesis" ], "offsets": [ [ 664, 676 ] ], "normalized": [] }, { "id": "17275", "type": "", "text": [ "MDR1" ], "offsets": [ [ 782, 786 ] ], "normalized": [] }, { "id": "17276", "type": "", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 817, 843 ] ], "normalized": [] }, { "id": "17278", "type": "", "text": [ "MDR1" ], "offsets": [ [ 1681, 1685 ] ], "normalized": [] }, { "id": "17279", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 1729, 1744 ] ], "normalized": [] }, { "id": "17281", "type": "", "text": [ "MDR1" ], "offsets": [ [ 1681, 1685 ] ], "normalized": [] }, { "id": "17282", "type": "", "text": [ "ulcerative colitis" ], "offsets": [ [ 1748, 1766 ] ], "normalized": [] }, { "id": "17284", "type": "", "text": [ "G2677T/A" ], "offsets": [ [ 27, 35 ] ], "normalized": [] }, { "id": "17285", "type": "", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 92, 118 ] ], "normalized": [] }, { "id": "17287", "type": "", "text": [ "G2677T/A" ], "offsets": [ [ 753, 761 ] ], "normalized": [] }, { "id": "17288", "type": "", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 817, 843 ] ], "normalized": [] }, { "id": "17290", "type": "", "text": [ "MDR1" ], "offsets": [ [ 1681, 1685 ] ], "normalized": [] }, { "id": "17291", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 1729, 1744 ] ], "normalized": [] }, { "id": "17293", "type": "", "text": [ "MDR1" ], "offsets": [ [ 1681, 1685 ] ], "normalized": [] }, { "id": "17294", "type": "", "text": [ "ulcerative colitis" ], "offsets": [ [ 1748, 1766 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17259", "type": "SA", "arg1_id": "17257", "arg2_id": "17258", "normalized": [] }, { "id": "17262", "type": "NA", "arg1_id": "17260", "arg2_id": "17261", "normalized": [] }, { "id": "17265", "type": "NA", "arg1_id": "17263", "arg2_id": "17264", "normalized": [] }, { "id": "17268", "type": "PA", "arg1_id": "17266", "arg2_id": "17267", "normalized": [] }, { "id": "17271", "type": "PA", "arg1_id": "17269", "arg2_id": "17270", "normalized": [] }, { "id": "17274", "type": "PA", "arg1_id": "17272", "arg2_id": "17273", "normalized": [] }, { "id": "17277", "type": "PA", "arg1_id": "17275", "arg2_id": "17276", "normalized": [] }, { "id": "17280", "type": "PA", "arg1_id": "17278", "arg2_id": "17279", "normalized": [] }, { "id": "17283", "type": "PA", "arg1_id": "17281", "arg2_id": "17282", "normalized": [] }, { "id": "17286", "type": "SA", "arg1_id": "17284", "arg2_id": "17285", "normalized": [] }, { "id": "17289", "type": "SA", "arg1_id": "17287", "arg2_id": "17288", "normalized": [] }, { "id": "17292", "type": "NA", "arg1_id": "17290", "arg2_id": "17291", "normalized": [] }, { "id": "17295", "type": "NA", "arg1_id": "17293", "arg2_id": "17294", "normalized": [] } ]

[ { "id": "17298", "type": "title", "text": [ "Etonogestrel implant in women with diabetes mellitus." ], "offsets": [ [ 0, 53 ] ] }, { "id": "17299", "type": "abstract", "text": [ "OBJECTIVES: To evaluate the effect of etonogestrel implant on the control of the carbohydrate and lipid metabolism and on the progression of vascular complications in diabetic women treated with insulin, and to assess the acceptability of this modality of contraception in these patients. METHODS: Prospective-observational study of 23 women with insulin-treated diabetes. Clinical and metabolic evaluation was performed before and at 3, 6, 12, and 24 months after implant insertion. Changes from baseline were compared using the mixed effects models or Wilcoxon matched-pairs signed-rank tests. RESULTS: There were no significant changes in BMI, in daily insulin requirement and in mean HbA1c. There was a significant reduction of total serum cholesterol (TC) at 6 and 12 months, of triglyceride levels at 6, 12 and 24 months, and of high-density lipoprotein cholesterol (HDL-C) at 6, 12 and 24 months. Neither the low-density lipoprotein (LDL) levels nor the HDL/TC ratio changed. Albuminuria decreased significantly at 12 and 24 months. No deterioration of the retina was observed over the study period. Amenorrhoea and infrequent bleeding were the most common menstrual bleeding patterns. One woman discontinued the method due to frequent bleeding. CONCLUSION: We found no evidence of impaired control of the carbohydrate and lipid metabolism or aggravation of vascular lesions during the two years an etonogestrel implant was used by diabetic women." ], "offsets": [ [ 54, 1508 ] ] } ]

[ { "id": "17300", "type": "Chemicals & Drugs", "text": [ "Etonogestrel" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "17301", "type": "Diseases & Disorders", "text": [ "diabetes mellitus" ], "offsets": [ [ 35, 52 ] ], "normalized": [] }, { "id": "17302", "type": "Chemicals & Drugs", "text": [ "etonogestrel" ], "offsets": [ [ 92, 104 ] ], "normalized": [] }, { "id": "17303", "type": "Diseases & Disorders", "text": [ "vascular complications" ], "offsets": [ [ 195, 217 ] ], "normalized": [] }, { "id": "17304", "type": "Chemicals & Drugs", "text": [ "insulin" ], "offsets": [ [ 249, 256 ] ], "normalized": [] }, { "id": "17305", "type": "Diseases & Disorders", "text": [ "insulin-treated diabetes" ], "offsets": [ [ 401, 425 ] ], "normalized": [] }, { "id": "17306", "type": "Chemicals & Drugs", "text": [ "insulin-treated diabetes" ], "offsets": [ [ 401, 425 ] ], "normalized": [] }, { "id": "17307", "type": "Diseases & Disorders", "text": [ "insertion" ], "offsets": [ [ 527, 536 ] ], "normalized": [] }, { "id": "17308", "type": "Chemicals & Drugs", "text": [ "insulin" ], "offsets": [ [ 710, 717 ] ], "normalized": [] }, { "id": "17309", "type": "Chemicals & Drugs", "text": [ "TC" ], "offsets": [ [ 811, 813 ] ], "normalized": [] }, { "id": "17310", "type": "Chemicals & Drugs", "text": [ "TC" ], "offsets": [ [ 1019, 1021 ] ], "normalized": [] }, { "id": "17311", "type": "Diseases & Disorders", "text": [ "Albuminuria" ], "offsets": [ [ 1037, 1048 ] ], "normalized": [] }, { "id": "17312", "type": "Diseases & Disorders", "text": [ "deterioration of the retina" ], "offsets": [ [ 1097, 1124 ] ], "normalized": [] }, { "id": "17313", "type": "Diseases & Disorders", "text": [ "Amenorrhoea" ], "offsets": [ [ 1161, 1172 ] ], "normalized": [] }, { "id": "17314", "type": "Diseases & Disorders", "text": [ "bleeding" ], "offsets": [ [ 1188, 1196 ] ], "normalized": [] }, { "id": "17315", "type": "Diseases & Disorders", "text": [ "bleeding" ], "offsets": [ [ 1228, 1236 ] ], "normalized": [] }, { "id": "17316", "type": "Diseases & Disorders", "text": [ "bleeding" ], "offsets": [ [ 1297, 1305 ] ], "normalized": [] }, { "id": "17317", "type": "Diseases & Disorders", "text": [ "vascular lesions" ], "offsets": [ [ 1419, 1435 ] ], "normalized": [] }, { "id": "17318", "type": "Chemicals & Drugs", "text": [ "etonogestrel" ], "offsets": [ [ 1460, 1472 ] ], "normalized": [] }, { "id": "17319", "type": "", "text": [ "etonogestrel" ], "offsets": [ [ 1460, 1472 ] ], "normalized": [] }, { "id": "17320", "type": "", "text": [ "vascular lesions" ], "offsets": [ [ 1419, 1435 ] ], "normalized": [] }, { "id": "17322", "type": "", "text": [ "Etonogestrel" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "17323", "type": "", "text": [ "diabetes mellitus" ], "offsets": [ [ 35, 52 ] ], "normalized": [] }, { "id": "17325", "type": "", "text": [ "etonogestrel" ], "offsets": [ [ 92, 104 ] ], "normalized": [] }, { "id": "17326", "type": "", "text": [ "vascular complications" ], "offsets": [ [ 195, 217 ] ], "normalized": [] }, { "id": "17328", "type": "", "text": [ "etonogestrel" ], "offsets": [ [ 1460, 1472 ] ], "normalized": [] }, { "id": "17329", "type": "", "text": [ "vascular lesions" ], "offsets": [ [ 1419, 1435 ] ], "normalized": [] }, { "id": "17331", "type": "", "text": [ "insulin" ], "offsets": [ [ 249, 256 ] ], "normalized": [] }, { "id": "17332", "type": "", "text": [ "vascular complications" ], "offsets": [ [ 195, 217 ] ], "normalized": [] }, { "id": "17334", "type": "", "text": [ "insulin-treated diabetes" ], "offsets": [ [ 401, 425 ] ], "normalized": [] }, { "id": "17335", "type": "", "text": [ "insulin-treated diabetes" ], "offsets": [ [ 401, 425 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17321", "type": "NA", "arg1_id": "17319", "arg2_id": "17320", "normalized": [] }, { "id": "17324", "type": "PA", "arg1_id": "17322", "arg2_id": "17323", "normalized": [] }, { "id": "17327", "type": "PA", "arg1_id": "17325", "arg2_id": "17326", "normalized": [] }, { "id": "17330", "type": "PA", "arg1_id": "17328", "arg2_id": "17329", "normalized": [] }, { "id": "17333", "type": "PA", "arg1_id": "17331", "arg2_id": "17332", "normalized": [] }, { "id": "17336", "type": "PA", "arg1_id": "17334", "arg2_id": "17335", "normalized": [] } ]

[ { "id": "17339", "type": "title", "text": [ "From Hans Selye's discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: implication in stress-related functional bowel diseases." ], "offsets": [ [ 0, 181 ] ] }, { "id": "17340", "type": "abstract", "text": [ "Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF(1) and CRF(2) receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF(1) receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF(1) receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF(1) receptor antagonists in blunting these stress-related components. The importance of CRF(1) signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients." ], "offsets": [ [ 182, 1696 ] ] } ]

[ { "id": "17341", "type": "Genes & Molecular Sequences", "text": [ "corticotropin-releasing factor" ], "offsets": [ [ 74, 104 ] ], "normalized": [] }, { "id": "17342", "type": "Genes & Molecular Sequences", "text": [ "corticotropin-releasing factor" ], "offsets": [ [ 281, 311 ] ], "normalized": [] }, { "id": "17343", "type": "Genes & Molecular Sequences", "text": [ "CRF" ], "offsets": [ [ 313, 316 ] ], "normalized": [] }, { "id": "17344", "type": "Genes & Molecular Sequences", "text": [ "CRF" ], "offsets": [ [ 420, 423 ] ], "normalized": [] }, { "id": "17345", "type": "Genes & Molecular Sequences", "text": [ "CRF" ], "offsets": [ [ 467, 470 ] ], "normalized": [] }, { "id": "17346", "type": "Genes & Molecular Sequences", "text": [ "urocortin 1" ], "offsets": [ [ 479, 490 ] ], "normalized": [] }, { "id": "17347", "type": "Genes & Molecular Sequences", "text": [ "urocortin 2" ], "offsets": [ [ 492, 503 ] ], "normalized": [] }, { "id": "17348", "type": "Genes & Molecular Sequences", "text": [ "urocortin 3" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "17349", "type": "Genes & Molecular Sequences", "text": [ "CRF(1)" ], "offsets": [ [ 541, 547 ] ], "normalized": [] }, { "id": "17350", "type": "Genes & Molecular Sequences", "text": [ "1" ], "offsets": [ [ 545, 546 ] ], "normalized": [] }, { "id": "17351", "type": "Genes & Molecular Sequences", "text": [ "CRF(2) receptors" ], "offsets": [ [ 552, 568 ] ], "normalized": [] }, { "id": "17352", "type": "Chemicals & Drugs", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17353", "type": "Genes & Molecular Sequences", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17354", "type": "Chemicals & Drugs", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17355", "type": "Genes & Molecular Sequences", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17356", "type": "Genes & Molecular Sequences", "text": [ "CRF(1) receptor" ], "offsets": [ [ 726, 741 ] ], "normalized": [] }, { "id": "17357", "type": "Genes & Molecular Sequences", "text": [ "CRF(1)" ], "offsets": [ [ 958, 964 ] ], "normalized": [] }, { "id": "17358", "type": "Genes & Molecular Sequences", "text": [ "receptors" ], "offsets": [ [ 965, 974 ] ], "normalized": [] }, { "id": "17359", "type": "Genes & Molecular Sequences", "text": [ "gut" ], "offsets": [ [ 1052, 1055 ] ], "normalized": [] }, { "id": "17360", "type": "Chemicals & Drugs", "text": [ "CRF(1) receptor antagonists" ], "offsets": [ [ 1191, 1218 ] ], "normalized": [] }, { "id": "17361", "type": "Genes & Molecular Sequences", "text": [ "CRF(1) receptor antagonists" ], "offsets": [ [ 1191, 1218 ] ], "normalized": [] }, { "id": "17362", "type": "Genes & Molecular Sequences", "text": [ "1) receptor" ], "offsets": [ [ 1195, 1206 ] ], "normalized": [] }, { "id": "17363", "type": "Genes & Molecular Sequences", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17364", "type": "Genes & Molecular Sequences", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17365", "type": "", "text": [ "corticotropin-releasing factor" ], "offsets": [ [ 74, 104 ] ], "normalized": [] }, { "id": "17366", "type": "", "text": [ "functional bowel diseases" ], "offsets": [ [ 155, 180 ] ], "normalized": [] }, { "id": "17368", "type": "", "text": [ "urocortin 2" ], "offsets": [ [ 492, 503 ] ], "normalized": [] }, { "id": "17369", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17371", "type": "", "text": [ "urocortin 3" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "17372", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17374", "type": "", "text": [ "CRF(2) receptors" ], "offsets": [ [ 552, 568 ] ], "normalized": [] }, { "id": "17375", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17377", "type": "", "text": [ "1" ], "offsets": [ [ 545, 546 ] ], "normalized": [] }, { "id": "17378", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17380", "type": "", "text": [ "CRF(1) receptor" ], "offsets": [ [ 726, 741 ] ], "normalized": [] }, { "id": "17381", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17383", "type": "", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17384", "type": "", "text": [ "urocortin 2" ], "offsets": [ [ 492, 503 ] ], "normalized": [] }, { "id": "17386", "type": "", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17387", "type": "", "text": [ "urocortin 3" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "17389", "type": "", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17390", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17392", "type": "", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17393", "type": "", "text": [ "CRF(1) receptor" ], "offsets": [ [ 726, 741 ] ], "normalized": [] }, { "id": "17395", "type": "", "text": [ "CRF ligands" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "17396", "type": "", "text": [ "urocortin 1" ], "offsets": [ [ 479, 490 ] ], "normalized": [] }, { "id": "17398", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17399", "type": "", "text": [ "urocortin 2" ], "offsets": [ [ 492, 503 ] ], "normalized": [] }, { "id": "17401", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17402", "type": "", "text": [ "urocortin 3" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "17404", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17405", "type": "", "text": [ "CRF(2) receptors" ], "offsets": [ [ 552, 568 ] ], "normalized": [] }, { "id": "17407", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17408", "type": "", "text": [ "1" ], "offsets": [ [ 545, 546 ] ], "normalized": [] }, { "id": "17410", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17411", "type": "", "text": [ "CRF(1) receptor" ], "offsets": [ [ 726, 741 ] ], "normalized": [] }, { "id": "17413", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17414", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17416", "type": "", "text": [ "selective CRF receptor antagonists" ], "offsets": [ [ 652, 686 ] ], "normalized": [] }, { "id": "17417", "type": "", "text": [ "urocortin 1" ], "offsets": [ [ 479, 490 ] ], "normalized": [] }, { "id": "17419", "type": "", "text": [ "urocortin 1" ], "offsets": [ [ 479, 490 ] ], "normalized": [] }, { "id": "17420", "type": "", "text": [ "anxiety/depression" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "17422", "type": "", "text": [ "1) receptor" ], "offsets": [ [ 1195, 1206 ] ], "normalized": [] }, { "id": "17423", "type": "", "text": [ "hypersensitivity" ], "offsets": [ [ 1117, 1133 ] ], "normalized": [] }, { "id": "17425", "type": "", "text": [ "1) receptor" ], "offsets": [ [ 1195, 1206 ] ], "normalized": [] }, { "id": "17426", "type": "", "text": [ "distension" ], "offsets": [ [ 1148, 1158 ] ], "normalized": [] }, { "id": "17428", "type": "", "text": [ "CRF(1) receptor antagonists" ], "offsets": [ [ 1191, 1218 ] ], "normalized": [] }, { "id": "17429", "type": "", "text": [ "hypersensitivity" ], "offsets": [ [ 1117, 1133 ] ], "normalized": [] }, { "id": "17431", "type": "", "text": [ "CRF(1) receptor antagonists" ], "offsets": [ [ 1191, 1218 ] ], "normalized": [] }, { "id": "17432", "type": "", "text": [ "distension" ], "offsets": [ [ 1148, 1158 ] ], "normalized": [] }, { "id": "17434", "type": "", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17435", "type": "", "text": [ "irritable bowel syndrome" ], "offsets": [ [ 1453, 1477 ] ], "normalized": [] }, { "id": "17437", "type": "", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17438", "type": "", "text": [ "functional bowel disorder" ], "offsets": [ [ 1419, 1444 ] ], "normalized": [] }, { "id": "17440", "type": "", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17441", "type": "", "text": [ "altered bowel habits" ], "offsets": [ [ 1530, 1550 ] ], "normalized": [] }, { "id": "17443", "type": "", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17444", "type": "", "text": [ "visceral pain" ], "offsets": [ [ 1555, 1568 ] ], "normalized": [] }, { "id": "17446", "type": "", "text": [ "1" ], "offsets": [ [ 1286, 1287 ] ], "normalized": [] }, { "id": "17447", "type": "", "text": [ "with anxiety-depression" ], "offsets": [ [ 1648, 1671 ] ], "normalized": [] }, { "id": "17449", "type": "", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17450", "type": "", "text": [ "irritable bowel syndrome" ], "offsets": [ [ 1453, 1477 ] ], "normalized": [] }, { "id": "17452", "type": "", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17453", "type": "", "text": [ "functional bowel disorder" ], "offsets": [ [ 1419, 1444 ] ], "normalized": [] }, { "id": "17455", "type": "", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17456", "type": "", "text": [ "altered bowel habits" ], "offsets": [ [ 1530, 1550 ] ], "normalized": [] }, { "id": "17458", "type": "", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17459", "type": "", "text": [ "visceral pain" ], "offsets": [ [ 1555, 1568 ] ], "normalized": [] }, { "id": "17461", "type": "", "text": [ "CRF(1)" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "17462", "type": "", "text": [ "with anxiety-depression" ], "offsets": [ [ 1648, 1671 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17367", "type": "PA", "arg1_id": "17365", "arg2_id": "17366", "normalized": [] }, { "id": "17370", "type": "PA", "arg1_id": "17368", "arg2_id": "17369", "normalized": [] }, { "id": "17373", "type": "PA", "arg1_id": "17371", "arg2_id": "17372", "normalized": [] }, { "id": "17376", "type": "PA", "arg1_id": "17374", "arg2_id": "17375", "normalized": [] }, { "id": "17379", "type": "PA", "arg1_id": "17377", "arg2_id": "17378", "normalized": [] }, { "id": "17382", "type": "PA", "arg1_id": "17380", "arg2_id": "17381", "normalized": [] }, { "id": "17385", "type": "PA", "arg1_id": "17383", "arg2_id": "17384", "normalized": [] }, { "id": "17388", "type": "PA", "arg1_id": "17386", "arg2_id": "17387", "normalized": [] }, { "id": "17391", "type": "PA", "arg1_id": "17389", "arg2_id": "17390", "normalized": [] }, { "id": "17394", "type": "PA", "arg1_id": "17392", "arg2_id": "17393", "normalized": [] }, { "id": "17397", "type": "PA", "arg1_id": "17395", "arg2_id": "17396", "normalized": [] }, { "id": "17400", "type": "PA", "arg1_id": "17398", "arg2_id": "17399", "normalized": [] }, { "id": "17403", "type": "PA", "arg1_id": "17401", "arg2_id": "17402", "normalized": [] }, { "id": "17406", "type": "PA", "arg1_id": "17404", "arg2_id": "17405", "normalized": [] }, { "id": "17409", "type": "PA", "arg1_id": "17407", "arg2_id": "17408", "normalized": [] }, { "id": "17412", "type": "PA", "arg1_id": "17410", "arg2_id": "17411", "normalized": [] }, { "id": "17415", "type": "PA", "arg1_id": "17413", "arg2_id": "17414", "normalized": [] }, { "id": "17418", "type": "PA", "arg1_id": "17416", "arg2_id": "17417", "normalized": [] }, { "id": "17421", "type": "PA", "arg1_id": "17419", "arg2_id": "17420", "normalized": [] }, { "id": "17424", "type": "PA", "arg1_id": "17422", "arg2_id": "17423", "normalized": [] }, { "id": "17427", "type": "PA", "arg1_id": "17425", "arg2_id": "17426", "normalized": [] }, { "id": "17430", "type": "PA", "arg1_id": "17428", "arg2_id": "17429", "normalized": [] }, { "id": "17433", "type": "PA", "arg1_id": "17431", "arg2_id": "17432", "normalized": [] }, { "id": "17436", "type": "PA", "arg1_id": "17434", "arg2_id": "17435", "normalized": [] }, { "id": "17439", "type": "PA", "arg1_id": "17437", "arg2_id": "17438", "normalized": [] }, { "id": "17442", "type": "PA", "arg1_id": "17440", "arg2_id": "17441", "normalized": [] }, { "id": "17445", "type": "PA", "arg1_id": "17443", "arg2_id": "17444", "normalized": [] }, { "id": "17448", "type": "PA", "arg1_id": "17446", "arg2_id": "17447", "normalized": [] }, { "id": "17451", "type": "PA", "arg1_id": "17449", "arg2_id": "17450", "normalized": [] }, { "id": "17454", "type": "PA", "arg1_id": "17452", "arg2_id": "17453", "normalized": [] }, { "id": "17457", "type": "PA", "arg1_id": "17455", "arg2_id": "17456", "normalized": [] }, { "id": "17460", "type": "PA", "arg1_id": "17458", "arg2_id": "17459", "normalized": [] }, { "id": "17463", "type": "PA", "arg1_id": "17461", "arg2_id": "17462", "normalized": [] } ]

[ { "id": "17466", "type": "title", "text": [ "Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin." ], "offsets": [ [ 0, 118 ] ] }, { "id": "17467", "type": "abstract", "text": [ "BACKGROUND & AIMS: Sustained virologic response (SVR) rates of 50%-60% have been achieved in patients with chronic hepatitis C genotype 4 treated with peginterferon plus ribavirin. The safety and efficacy of nitazoxanide plus peginterferon alfa-2a, with or without ribavirin, were evaluated in a randomized controlled trial at 2 centers in Egypt. METHODS: Previously untreated patients with chronic hepatitis C and genotype 4 infection were assigned randomly to groups that were given standard of care (peginterferon alfa-2a and ribavirin for 48 weeks, n = 40), nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a for 36 weeks (n = 28), or nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a and ribavirin for 36 weeks (n = 28). Therapeutics included nitazoxanide (500 mg) twice daily, peginterferon alfa-2a (180 microg) once weekly, and weight-based ribavirin (1000-1200 mg/day). RESULTS: The percentages of rapid virologic response (RVR), defined as undetectable HCV RNA at week 4 of combination therapy, and SVR were significantly higher in patients given the triple therapy compared with the standard of care (64% vs 38%, P = .048; and 79% vs 50%, P = .023; respectively). Patients given nitazoxanide plus peginterferon alfa-2a had intermediate rates of RVR (54%) and SVR (61%). Adverse events were similar across treatment groups except for higher rates of anemia in the groups receiving ribavirin. CONCLUSIONS: The combination of nitazoxanide, peginterferon alfa-2a, and ribavirin increased the percentages of patients with RVR and SVR, compared with patients given peginterferon plus ribavirin, without an increase in adverse events." ], "offsets": [ [ 119, 1835 ] ] } ]

[ { "id": "17468", "type": "Diseases & Disorders", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 31, 61 ] ], "normalized": [] }, { "id": "17469", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 39, 50 ] ], "normalized": [] }, { "id": "17470", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 75, 87 ] ], "normalized": [] }, { "id": "17471", "type": "Chemicals & Drugs", "text": [ "peginterferon" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "17472", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 108, 117 ] ], "normalized": [] }, { "id": "17473", "type": "Diseases & Disorders", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 226, 256 ] ], "normalized": [] }, { "id": "17474", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 234, 245 ] ], "normalized": [] }, { "id": "17475", "type": "Chemicals & Drugs", "text": [ "peginterferon" ], "offsets": [ [ 270, 283 ] ], "normalized": [] }, { "id": "17476", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 289, 298 ] ], "normalized": [] }, { "id": "17477", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 327, 339 ] ], "normalized": [] }, { "id": "17478", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 345, 366 ] ], "normalized": [] }, { "id": "17479", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 384, 393 ] ], "normalized": [] }, { "id": "17480", "type": "Diseases & Disorders", "text": [ "chronic hepatitis" ], "offsets": [ [ 510, 527 ] ], "normalized": [] }, { "id": "17481", "type": "Diseases & Disorders", "text": [ "genotype 4 infection" ], "offsets": [ [ 534, 554 ] ], "normalized": [] }, { "id": "17482", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 622, 643 ] ], "normalized": [] }, { "id": "17483", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 648, 657 ] ], "normalized": [] }, { "id": "17484", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 681, 693 ] ], "normalized": [] }, { "id": "17485", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 731, 743 ] ], "normalized": [] }, { "id": "17486", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 749, 770 ] ], "normalized": [] }, { "id": "17487", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 797, 809 ] ], "normalized": [] }, { "id": "17488", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 847, 859 ] ], "normalized": [] }, { "id": "17489", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 865, 886 ] ], "normalized": [] }, { "id": "17490", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 891, 900 ] ], "normalized": [] }, { "id": "17491", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 946, 958 ] ], "normalized": [] }, { "id": "17492", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 981, 1002 ] ], "normalized": [] }, { "id": "17493", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 1033, 1039 ] ], "normalized": [] }, { "id": "17494", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 1046, 1055 ] ], "normalized": [] }, { "id": "17495", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 1387, 1399 ] ], "normalized": [] }, { "id": "17496", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 1405, 1426 ] ], "normalized": [] }, { "id": "17497", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 1557, 1563 ] ], "normalized": [] }, { "id": "17498", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 1588, 1597 ] ], "normalized": [] }, { "id": "17499", "type": "Chemicals & Drugs", "text": [ "nitazoxanide" ], "offsets": [ [ 1631, 1643 ] ], "normalized": [] }, { "id": "17500", "type": "Chemicals & Drugs", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 1645, 1666 ] ], "normalized": [] }, { "id": "17501", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 1672, 1681 ] ], "normalized": [] }, { "id": "17502", "type": "Chemicals & Drugs", "text": [ "peginterferon" ], "offsets": [ [ 1767, 1780 ] ], "normalized": [] }, { "id": "17503", "type": "Chemicals & Drugs", "text": [ "ribavirin" ], "offsets": [ [ 1786, 1795 ] ], "normalized": [] }, { "id": "17504", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 289, 298 ] ], "normalized": [] }, { "id": "17505", "type": "", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 226, 256 ] ], "normalized": [] }, { "id": "17507", "type": "", "text": [ "peginterferon" ], "offsets": [ [ 270, 283 ] ], "normalized": [] }, { "id": "17508", "type": "", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 226, 256 ] ], "normalized": [] }, { "id": "17510", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 1588, 1597 ] ], "normalized": [] }, { "id": "17511", "type": "", "text": [ "anemia" ], "offsets": [ [ 1557, 1563 ] ], "normalized": [] }, { "id": "17513", "type": "", "text": [ "nitazoxanide" ], "offsets": [ [ 75, 87 ] ], "normalized": [] }, { "id": "17514", "type": "", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 31, 61 ] ], "normalized": [] }, { "id": "17516", "type": "", "text": [ "nitazoxanide" ], "offsets": [ [ 75, 87 ] ], "normalized": [] }, { "id": "17517", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 39, 50 ] ], "normalized": [] }, { "id": "17519", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 108, 117 ] ], "normalized": [] }, { "id": "17520", "type": "", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 31, 61 ] ], "normalized": [] }, { "id": "17522", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 108, 117 ] ], "normalized": [] }, { "id": "17523", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 39, 50 ] ], "normalized": [] }, { "id": "17525", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 289, 298 ] ], "normalized": [] }, { "id": "17526", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 234, 245 ] ], "normalized": [] }, { "id": "17528", "type": "", "text": [ "nitazoxanide" ], "offsets": [ [ 847, 859 ] ], "normalized": [] }, { "id": "17529", "type": "", "text": [ "chronic hepatitis" ], "offsets": [ [ 510, 527 ] ], "normalized": [] }, { "id": "17531", "type": "", "text": [ "nitazoxanide" ], "offsets": [ [ 847, 859 ] ], "normalized": [] }, { "id": "17532", "type": "", "text": [ "genotype 4 infection" ], "offsets": [ [ 534, 554 ] ], "normalized": [] }, { "id": "17534", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 891, 900 ] ], "normalized": [] }, { "id": "17535", "type": "", "text": [ "chronic hepatitis" ], "offsets": [ [ 510, 527 ] ], "normalized": [] }, { "id": "17537", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 891, 900 ] ], "normalized": [] }, { "id": "17538", "type": "", "text": [ "genotype 4 infection" ], "offsets": [ [ 534, 554 ] ], "normalized": [] }, { "id": "17540", "type": "", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 865, 886 ] ], "normalized": [] }, { "id": "17541", "type": "", "text": [ "chronic hepatitis" ], "offsets": [ [ 510, 527 ] ], "normalized": [] }, { "id": "17543", "type": "", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 865, 886 ] ], "normalized": [] }, { "id": "17544", "type": "", "text": [ "genotype 4 infection" ], "offsets": [ [ 534, 554 ] ], "normalized": [] }, { "id": "17546", "type": "", "text": [ "nitazoxanide" ], "offsets": [ [ 946, 958 ] ], "normalized": [] }, { "id": "17547", "type": "", "text": [ "weight" ], "offsets": [ [ 1033, 1039 ] ], "normalized": [] }, { "id": "17549", "type": "", "text": [ "ribavirin" ], "offsets": [ [ 1046, 1055 ] ], "normalized": [] }, { "id": "17550", "type": "", "text": [ "weight" ], "offsets": [ [ 1033, 1039 ] ], "normalized": [] }, { "id": "17552", "type": "", "text": [ "peginterferon alfa-2a" ], "offsets": [ [ 981, 1002 ] ], "normalized": [] }, { "id": "17553", "type": "", "text": [ "weight" ], "offsets": [ [ 1033, 1039 ] ], "normalized": [] }, { "id": "17555", "type": "", "text": [ "peginterferon" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "17556", "type": "", "text": [ "chronic hepatitis C genotype 4" ], "offsets": [ [ 31, 61 ] ], "normalized": [] }, { "id": "17558", "type": "", "text": [ "peginterferon" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "17559", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 39, 50 ] ], "normalized": [] }, { "id": "17561", "type": "", "text": [ "peginterferon" ], "offsets": [ [ 270, 283 ] ], "normalized": [] }, { "id": "17562", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 234, 245 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17506", "type": "PA", "arg1_id": "17504", "arg2_id": "17505", "normalized": [] }, { "id": "17509", "type": "PA", "arg1_id": "17507", "arg2_id": "17508", "normalized": [] }, { "id": "17512", "type": "PA", "arg1_id": "17510", "arg2_id": "17511", "normalized": [] }, { "id": "17515", "type": "PA", "arg1_id": "17513", "arg2_id": "17514", "normalized": [] }, { "id": "17518", "type": "PA", "arg1_id": "17516", "arg2_id": "17517", "normalized": [] }, { "id": "17521", "type": "PA", "arg1_id": "17519", "arg2_id": "17520", "normalized": [] }, { "id": "17524", "type": "PA", "arg1_id": "17522", "arg2_id": "17523", "normalized": [] }, { "id": "17527", "type": "PA", "arg1_id": "17525", "arg2_id": "17526", "normalized": [] }, { "id": "17530", "type": "PA", "arg1_id": "17528", "arg2_id": "17529", "normalized": [] }, { "id": "17533", "type": "PA", "arg1_id": "17531", "arg2_id": "17532", "normalized": [] }, { "id": "17536", "type": "PA", "arg1_id": "17534", "arg2_id": "17535", "normalized": [] }, { "id": "17539", "type": "PA", "arg1_id": "17537", "arg2_id": "17538", "normalized": [] }, { "id": "17542", "type": "PA", "arg1_id": "17540", "arg2_id": "17541", "normalized": [] }, { "id": "17545", "type": "PA", "arg1_id": "17543", "arg2_id": "17544", "normalized": [] }, { "id": "17548", "type": "PA", "arg1_id": "17546", "arg2_id": "17547", "normalized": [] }, { "id": "17551", "type": "PA", "arg1_id": "17549", "arg2_id": "17550", "normalized": [] }, { "id": "17554", "type": "PA", "arg1_id": "17552", "arg2_id": "17553", "normalized": [] }, { "id": "17557", "type": "PA", "arg1_id": "17555", "arg2_id": "17556", "normalized": [] }, { "id": "17560", "type": "PA", "arg1_id": "17558", "arg2_id": "17559", "normalized": [] }, { "id": "17563", "type": "PA", "arg1_id": "17561", "arg2_id": "17562", "normalized": [] } ]

[ { "id": "17566", "type": "title", "text": [ "Analysis of additional virulence genes and virulence gene regions in Listeria monocytogenes confirms the epidemiologic relevance of multi-virulence-locus sequence typing." ], "offsets": [ [ 0, 170 ] ] }, { "id": "17567", "type": "abstract", "text": [ "Previous molecular subtyping studies have defined four epidemic clones (ECs) of Listeria monocytogenes (ECI, ECII, ECIII, and ECIV). Partial sequences of eight virulence genes were previously shown to be identical within individual ECs of L. monocytogenes. The present study was conducted to determine if the sequences of other virulence genes and virulence gene regions are also conserved within these ECs. Six additional virulence genes--bsh, hly, inlJ, IplA1, pgdA, and srtA--and three additional virulence gene regions of actA, inlA, and inlB were selected based on their role in L. monocytogenes virulence, and intragenic regions of each gene were sequenced. Sequencing was performed on a diverse set of 44 to 48 L. monocytogenes strains. Results demonstrated that the sequenced regions of the nine virulence genes were identical within each of the ECs, and 257 new single nucleotide polymorphism (SNPs) were identified. ECIII (lineage II) was easily distinguishable from the other ECs, as 238 SNPs were observed in ECIII due to its significant evolutionary divergence from lineage I. With regard to the other ECs, there were 5 SNPs that represented an informative set, since these SNPs were able to differentiate specific ECs from all other unrelated strains used in this study. This study confirms our previous finding that virulence gene sequences are highly conserved within individual ECs and contain stable SNPs that can be used to very accurately differentiate ECs of L. monocytogenes from each other and from other diverse strains." ], "offsets": [ [ 171, 1715 ] ] } ]

[ { "id": "17568", "type": "Genes & Molecular Sequences", "text": [ "virulence gene regions in Listeria monocytogenes" ], "offsets": [ [ 43, 91 ] ], "normalized": [] }, { "id": "17569", "type": "Genes & Molecular Sequences", "text": [ "ECI" ], "offsets": [ [ 275, 278 ] ], "normalized": [] }, { "id": "17570", "type": "Genes & Molecular Sequences", "text": [ "ECII" ], "offsets": [ [ 280, 284 ] ], "normalized": [] }, { "id": "17571", "type": "Genes & Molecular Sequences", "text": [ "ECIII" ], "offsets": [ [ 286, 291 ] ], "normalized": [] }, { "id": "17572", "type": "Genes & Molecular Sequences", "text": [ "ECIV" ], "offsets": [ [ 297, 301 ] ], "normalized": [] }, { "id": "17573", "type": "Genes & Molecular Sequences", "text": [ "bsh" ], "offsets": [ [ 611, 614 ] ], "normalized": [] }, { "id": "17574", "type": "Genes & Molecular Sequences", "text": [ "hly" ], "offsets": [ [ 616, 619 ] ], "normalized": [] }, { "id": "17575", "type": "Genes & Molecular Sequences", "text": [ "inlJ" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "17576", "type": "Genes & Molecular Sequences", "text": [ "IplA1" ], "offsets": [ [ 627, 632 ] ], "normalized": [] }, { "id": "17577", "type": "Genes & Molecular Sequences", "text": [ "pgdA" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "17578", "type": "Genes & Molecular Sequences", "text": [ "srtA" ], "offsets": [ [ 644, 648 ] ], "normalized": [] }, { "id": "17579", "type": "Genes & Molecular Sequences", "text": [ "actA" ], "offsets": [ [ 697, 701 ] ], "normalized": [] }, { "id": "17580", "type": "Genes & Molecular Sequences", "text": [ "inlA" ], "offsets": [ [ 703, 707 ] ], "normalized": [] }, { "id": "17581", "type": "Genes & Molecular Sequences", "text": [ "inlB" ], "offsets": [ [ 713, 717 ] ], "normalized": [] }, { "id": "17582", "type": "Diseases & Disorders", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17583", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 906, 913 ] ], "normalized": [] }, { "id": "17584", "type": "Genes & Molecular Sequences", "text": [ "nine virulence genes" ], "offsets": [ [ 970, 990 ] ], "normalized": [] }, { "id": "17585", "type": "Genes & Molecular Sequences", "text": [ "ECIII" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "17586", "type": "Genes & Molecular Sequences", "text": [ "ECIII" ], "offsets": [ [ 1192, 1197 ] ], "normalized": [] }, { "id": "17587", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 1428, 1435 ] ], "normalized": [] }, { "id": "17588", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 1707, 1714 ] ], "normalized": [] }, { "id": "17589", "type": "", "text": [ "pgdA" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "17590", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17592", "type": "", "text": [ "actA" ], "offsets": [ [ 697, 701 ] ], "normalized": [] }, { "id": "17593", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17595", "type": "", "text": [ "inlA" ], "offsets": [ [ 703, 707 ] ], "normalized": [] }, { "id": "17596", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17598", "type": "", "text": [ "hly" ], "offsets": [ [ 616, 619 ] ], "normalized": [] }, { "id": "17599", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17601", "type": "", "text": [ "inlJ" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "17602", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17604", "type": "", "text": [ "IplA1" ], "offsets": [ [ 627, 632 ] ], "normalized": [] }, { "id": "17605", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17607", "type": "", "text": [ "srtA" ], "offsets": [ [ 644, 648 ] ], "normalized": [] }, { "id": "17608", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17610", "type": "", "text": [ "inlB" ], "offsets": [ [ 713, 717 ] ], "normalized": [] }, { "id": "17611", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] }, { "id": "17613", "type": "", "text": [ "bsh" ], "offsets": [ [ 611, 614 ] ], "normalized": [] }, { "id": "17614", "type": "", "text": [ "L. monocytogenes virulence" ], "offsets": [ [ 755, 781 ] ], "normalized": [] } ]

[]

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[ { "id": "17591", "type": "PA", "arg1_id": "17589", "arg2_id": "17590", "normalized": [] }, { "id": "17594", "type": "PA", "arg1_id": "17592", "arg2_id": "17593", "normalized": [] }, { "id": "17597", "type": "PA", "arg1_id": "17595", "arg2_id": "17596", "normalized": [] }, { "id": "17600", "type": "PA", "arg1_id": "17598", "arg2_id": "17599", "normalized": [] }, { "id": "17603", "type": "PA", "arg1_id": "17601", "arg2_id": "17602", "normalized": [] }, { "id": "17606", "type": "PA", "arg1_id": "17604", "arg2_id": "17605", "normalized": [] }, { "id": "17609", "type": "PA", "arg1_id": "17607", "arg2_id": "17608", "normalized": [] }, { "id": "17612", "type": "PA", "arg1_id": "17610", "arg2_id": "17611", "normalized": [] }, { "id": "17615", "type": "PA", "arg1_id": "17613", "arg2_id": "17614", "normalized": [] } ]

[ { "id": "17618", "type": "title", "text": [ "Mass defect filtering on high resolution LC/MS data as a methodology for detecting metabolites with unpredictable structures: identification of oxazole-ring opened metabolites of muraglitazar." ], "offsets": [ [ 0, 192 ] ] }, { "id": "17619", "type": "abstract", "text": [ "This study describes the application of the mass defect filter method for the detection of two unpredicted oxazole-ring opened metabolites of muraglitazar in the feces of humans following oral administration. Unlike other muraglitazar metabolites, these metabolites formed little to no protonated ions, and the NH(4)(+) or Na(+) adduct ions that were formed were weak and not discernible from fecal interferences even after background subtraction. With mass defect filtering on high resolution LC/MS data, the resulting total ion chromatogram and the simplified mass spectra allowed for the identification and characterization of these metabolite ions, and their structures were confirmed by synthesis." ], "offsets": [ [ 193, 895 ] ] } ]

[ { "id": "17620", "type": "Chemicals & Drugs", "text": [ "oxazole-ring opened metabolites of muraglitazar" ], "offsets": [ [ 144, 191 ] ], "normalized": [] }, { "id": "17621", "type": "Chemicals & Drugs", "text": [ "oxazole-ring opened metabolites of muraglitazar" ], "offsets": [ [ 300, 347 ] ], "normalized": [] }, { "id": "17622", "type": "Chemicals & Drugs", "text": [ "muraglitazar metabolites" ], "offsets": [ [ 415, 439 ] ], "normalized": [] }, { "id": "17623", "type": "Chemicals & Drugs", "text": [ "NH(4)(+)" ], "offsets": [ [ 504, 512 ] ], "normalized": [] }, { "id": "17624", "type": "Chemicals & Drugs", "text": [ "Na(+)" ], "offsets": [ [ 516, 521 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "17627", "type": "title", "text": [ "Compound heterozygosity for the C677T and A1298C mutations of the MTHFR gene in a case of hyperhomocysteinemia with recurrent deep thrombosis at young age." ], "offsets": [ [ 0, 155 ] ] }, { "id": "17628", "type": "abstract", "text": [ "We report a case of a young woman with an extensive, recurrent deep vein thrombosis (DVT) diagnosed by CT scan and duplex ultrasound examination. All blood investigations for etiology of recurrent DVT were normal except for serum homocysteine level, which was mildly increased. No other thrombophilic factors could be found. The three main causes of hyperhomocysteinemia are genetic defects, nutritional deficiencies and insufficient elimination. In our case a genetic defect for one of the key enzymes of homocysteine metabolism was found to be the underlying cause. Oral anticoagulation and supplementation with pyridoxine, cyanocobalamine and folate was recommended. Whether therapy with B vitamins and folate can substantially reduce the recurrence of venous thromboembolic disease remains to be established." ], "offsets": [ [ 156, 968 ] ] } ]

[ { "id": "17629", "type": "SNP & Sequence variations", "text": [ "C677T" ], "offsets": [ [ 32, 37 ] ], "normalized": [] }, { "id": "17630", "type": "SNP & Sequence variations", "text": [ "A1298C mutations of the MTHFR" ], "offsets": [ [ 42, 71 ] ], "normalized": [] }, { "id": "17631", "type": "Genes & Molecular Sequences", "text": [ "A1298C mutations of the MTHFR" ], "offsets": [ [ 42, 71 ] ], "normalized": [] }, { "id": "17632", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 49, 58 ] ], "normalized": [] }, { "id": "17633", "type": "Diseases & Disorders", "text": [ "hyperhomocysteinemia" ], "offsets": [ [ 90, 110 ] ], "normalized": [] }, { "id": "17634", "type": "Diseases & Disorders", "text": [ "deep thrombosis" ], "offsets": [ [ 126, 141 ] ], "normalized": [] }, { "id": "17635", "type": "Diseases & Disorders", "text": [ "deep vein thrombosis" ], "offsets": [ [ 219, 239 ] ], "normalized": [] }, { "id": "17636", "type": "Diseases & Disorders", "text": [ "DVT" ], "offsets": [ [ 241, 244 ] ], "normalized": [] }, { "id": "17637", "type": "Diseases & Disorders", "text": [ "DVT" ], "offsets": [ [ 353, 356 ] ], "normalized": [] }, { "id": "17638", "type": "Genes & Molecular Sequences", "text": [ "homocysteine" ], "offsets": [ [ 386, 398 ] ], "normalized": [] }, { "id": "17639", "type": "Diseases & Disorders", "text": [ "hyperhomocysteinemia" ], "offsets": [ [ 506, 526 ] ], "normalized": [] }, { "id": "17640", "type": "Diseases & Disorders", "text": [ "nutritional deficiencies" ], "offsets": [ [ 548, 572 ] ], "normalized": [] }, { "id": "17641", "type": "Genes & Molecular Sequences", "text": [ "homocysteine" ], "offsets": [ [ 662, 674 ] ], "normalized": [] }, { "id": "17642", "type": "Genes & Molecular Sequences", "text": [ "folate" ], "offsets": [ [ 802, 808 ] ], "normalized": [] }, { "id": "17643", "type": "Genes & Molecular Sequences", "text": [ "B vitamins" ], "offsets": [ [ 847, 857 ] ], "normalized": [] }, { "id": "17644", "type": "Genes & Molecular Sequences", "text": [ "folate" ], "offsets": [ [ 862, 868 ] ], "normalized": [] }, { "id": "17645", "type": "Diseases & Disorders", "text": [ "venous thromboembolic disease" ], "offsets": [ [ 912, 941 ] ], "normalized": [] }, { "id": "17646", "type": "", "text": [ "B vitamins" ], "offsets": [ [ 847, 857 ] ], "normalized": [] }, { "id": "17647", "type": "", "text": [ "venous thromboembolic disease" ], "offsets": [ [ 912, 941 ] ], "normalized": [] }, { "id": "17649", "type": "", "text": [ "folate" ], "offsets": [ [ 862, 868 ] ], "normalized": [] }, { "id": "17650", "type": "", "text": [ "venous thromboembolic disease" ], "offsets": [ [ 912, 941 ] ], "normalized": [] }, { "id": "17652", "type": "", "text": [ "A1298C mutations of the MTHFR" ], "offsets": [ [ 42, 71 ] ], "normalized": [] }, { "id": "17653", "type": "", "text": [ "mutations" ], "offsets": [ [ 49, 58 ] ], "normalized": [] }, { "id": "17655", "type": "", "text": [ "A1298C mutations of the MTHFR" ], "offsets": [ [ 42, 71 ] ], "normalized": [] }, { "id": "17656", "type": "", "text": [ "hyperhomocysteinemia" ], "offsets": [ [ 90, 110 ] ], "normalized": [] }, { "id": "17658", "type": "", "text": [ "A1298C mutations of the MTHFR" ], "offsets": [ [ 42, 71 ] ], "normalized": [] }, { "id": "17659", "type": "", "text": [ "deep thrombosis" ], "offsets": [ [ 126, 141 ] ], "normalized": [] }, { "id": "17661", "type": "", "text": [ "C677T" ], "offsets": [ [ 32, 37 ] ], "normalized": [] }, { "id": "17662", "type": "", "text": [ "hyperhomocysteinemia" ], "offsets": [ [ 90, 110 ] ], "normalized": [] }, { "id": "17664", "type": "", "text": [ "C677T" ], "offsets": [ [ 32, 37 ] ], "normalized": [] }, { "id": "17665", "type": "", "text": [ "deep thrombosis" ], "offsets": [ [ 126, 141 ] ], "normalized": [] } ]

[]

[]

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