{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:14:28Z","timestamp":1790043268017,"version":"4.0.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0004607","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T14:56:51Z","timestamp":1460041011000},"page":"e0004607","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":87,"title":["Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever"],"prefix":"10.1371","volume":"10","author":[{"given":"Liang","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yie Hou","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tun Linn","family":"Thein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiong","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng Eong","family":"Ooi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Sin","family":"Leo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon Nam","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Tannenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"S Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref2","first-page":"334","article-title":"A reappraisal of the criteria to diagnose plasma leakage in dengue hemorrhagic fever","volume":"43","author":"S Balasubramanian","year":"2006","journal-title":"Indian Pediatr"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e3306","DOI":"10.1371\/journal.pntd.0003306","article-title":"Approaches to Refining Estimates of Global Burden and Economics of Dengue","volume":"8","author":"DS Shepard","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.imbio.2013.11.002","article-title":"Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue","volume":"219","author":"A Torrentes-Carvalho","year":"2014","journal-title":"Immunobiology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e00481","DOI":"10.7554\/eLife.00481","article-title":"Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage","volume":"2","author":"AL St John","year":"2013","journal-title":"Elife"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1111\/jth.12178","article-title":"Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases","volume":"11","author":"ED Hottz","year":"2013","journal-title":"J Thromb Haemost"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1097\/01.qco.0000244047.31135.fa","article-title":"Immunopathological mechanisms in dengue and dengue hemorrhagic fever","volume":"19","author":"S Green","year":"2006","journal-title":"Curr Opin Infect Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1182\/blood-2012-06-437392","article-title":"Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice","volume":"121","author":"D Duerschmied","year":"2013","journal-title":"Blood"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1046\/j.1538-7836.2003.00267.x","article-title":"Signaling events underlying thrombus formation","volume":"1","author":"SP Jackson","year":"2003","journal-title":"J Thromb Haemost"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0091-3057(01)00746-8","article-title":"Molecular, pharmacological and functional diversity of 5-HT receptors","volume":"71","author":"D Hoyer","year":"2002","journal-title":"Pharmacol Biochem Behav"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0092-8674(03)01014-6","article-title":"Serotonylation of Small GTPases Is a Signal Transduction Pathway that Triggers Platelet \u03b1-Granule Release","volume":"115","author":"DJ Walther","year":"2003","journal-title":"Cell"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1186\/1471-2334-13-498","article-title":"Utility of warning signs in guiding admission and predicting severe disease in adult dengue","volume":"13","author":"YS Leo","year":"2013","journal-title":"BMC Infect Dis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/ncponc0252","article-title":"REporting recommendations for tumor MARKer prognostic studies (REMARK)","volume":"2","author":"LM McShane","year":"2005","journal-title":"Nat Clin Pract Oncol"},{"key":"ref14","year":"1997"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1128\/JCM.01258-06","article-title":"Cost-effective real-time reverse transcriptase PCR (RT-PCR) to screen for Dengue virus followed by rapid single-tube multiplex RT-PCR for serotyping of the virus","volume":"45","author":"YL Lai","year":"2007","journal-title":"J Clin Microbiol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1007\/s00216-011-5436-y","article-title":"Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography-tandem mass spectrometry","volume":"401","author":"W Zhu","year":"2011","journal-title":"Anal Bioanal Chem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e2373","DOI":"10.1371\/journal.pntd.0002373","article-title":"Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection","volume":"7","author":"L Cui","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nbt0807-846b","article-title":"The Metabolomics Standards Initiative","volume":"25","author":"SA Sansone","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis","volume":"3","author":"LW Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1099\/vir.0.004416-0","article-title":"Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function","volume":"90","author":"A Becerra","year":"2009","journal-title":"J Gen Virol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.drudis.2014.11.007","article-title":"Targeting key dioxygenases in tryptophan\u2013kynurenine metabolism for immunomodulation and cancer chemotherapy","volume":"20","author":"CJD Austin","year":"2015","journal-title":"Drug Discov Today"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1471-2334-8-86","article-title":"Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity","volume":"8","author":"FA Bozza","year":"2008","journal-title":"BMC Infect Dis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1128\/JVI.75.8.3501-3508.2001","article-title":"Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis","volume":"75","author":"DH Libraty","year":"2001","journal-title":"J Virol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/jmv.20080","article-title":"IL-10 levels in Dengue patients: some findings from the exceptional epidemiological conditions in Cuba","volume":"73","author":"AB P\u00e9rez","year":"2004","journal-title":"J Med Virol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/1471-2334-13-341","article-title":"Serum IL-10 as a marker of severe dengue infection","volume":"13","author":"G Malavige","year":"2013","journal-title":"BMC Infect Dis"},{"key":"ref26","first-page":"142","article-title":"Pathogenic Parameters Derived from Activated Platelets in Dengue Patients","volume":"1","author":"JJ Tsai","year":"2013","journal-title":"Trop Med Surg"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1161\/01.RES.58.1.58","article-title":"Correlation of plasma serotonin changes with platelet aggregation in an in vivo dog model of spontaneous occlusive coronary thrombus formation","volume":"58","author":"CR Benedict","year":"1986","journal-title":"Circ Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.med.60.042307.110802","article-title":"The expanded biology of serotonin","volume":"60","author":"M Berger","year":"2009","journal-title":"Annu Rev Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s007050050127","article-title":"The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin\/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis","volume":"142","author":"AK Falconar","year":"1997","journal-title":"Arch Virol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3844\/ajidsp.2008.69.75","article-title":"Patient and Mouse Antibodies against Dengue Virus Nonstructural Protein 1 Cross-React with Platelets and Cause Their Dysfunction or Depletion","volume":"4","author":"CF Lin","year":"2008","journal-title":"Am J Infect Dis"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molimm.2009.08.033","article-title":"Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation","volume":"47","author":"HJ Cheng","year":"2009","journal-title":"Mol Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1086\/343813","article-title":"High Circulating Levels of the Dengue Virus Nonstructural Protein NS1 Early in Dengue Illness Correlate with the Development of Dengue Hemorrhagic Fever","volume":"186","author":"DH Libraty","year":"2002","journal-title":"J Infect Dis"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1086\/500949","article-title":"Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement","volume":"193","author":"P Avirutnan","year":"2006","journal-title":"J Infect Dis"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1111\/j.1538-7836.2007.02754.x","article-title":"Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice","volume":"5","author":"DS Sun","year":"2007","journal-title":"J Thromb Haemost"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1172\/JCI33374","article-title":"Interactions between integrin \u03b1IIb\u03b23 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans","volume":"118","author":"AMD Carneiro","year":"2008","journal-title":"J Clin Invest"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"841","DOI":"10.4269\/ajtmh.2009.80.841","article-title":"Increased phagocytosis of platelets from patients with secondary dengue virus infection by human macrophages","volume":"80","author":"S Honda","year":"2009","journal-title":"Am J Trop Med Hyg"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1365-2249.2004.02626.x","article-title":"Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections","volume":"138","author":"M Saito","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/1096-9071(20000201)63:2<143::AID-JMV1009>3.0.CO;2-L","article-title":"Generation of IgM anti-platelet autoantibody in dengue patients","volume":"63","author":"CF Lin","year":"2001","journal-title":"J Med Virol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s12185-012-1175-x","article-title":"Role of CD61+ cells in thrombocytopenia of dengue patients","volume":"96","author":"S Noisakran","year":"2012","journal-title":"Int J Hematol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e25595","DOI":"10.1371\/journal.pone.0025595","article-title":"Monocyte-Platelet Interaction Induces a Pro-Inflammatory Phenotype in Circulating Monocytes","volume":"6","author":"G Passacquale","year":"2011","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"435","DOI":"10.4269\/ajtmh.2002.66.435","article-title":"Platelet adhesion to dengue-2 virus-infected endothelial cells","volume":"66","author":"C Krishnamurti","year":"2002","journal-title":"Am J Trop Med Hyg"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1182\/blood-2009-09-242990","article-title":"Dengue virus-induced hemorrhage in a nonhuman primate model","volume":"115","author":"N Onlamoon","year":"2010","journal-title":"Blood"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1126\/science.1256478","article-title":"Neutrophils scan for activated platelets to initiate inflammation","volume":"346","author":"V Sreeramkumar","year":"2014","journal-title":"Science"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1159\/000322904","article-title":"Frequency Alterations in Key Innate Immune Cell Components in the Peripheral Blood of Dengue Patients Detected by FACS Analysis","volume":"3","author":"JJ Tsai","year":"2011","journal-title":"J Innate Immun"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.blre.2006.06.001","article-title":"Platelet-neutrophil-interactions: linking hemostasis and inflammation","volume":"21","author":"A Zarbock","year":"2007","journal-title":"Blood Rev"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1111\/j.1538-7836.2005.01274.x","article-title":"Coated-platelets: An emerging component of the procoagulant response","volume":"3","author":"GL Dale","year":"2005","journal-title":"J Thromb Haemost"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"e1887","DOI":"10.1371\/journal.pntd.0001887","article-title":"Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF","volume":"6","author":"Y Kumar","year":"2012","journal-title":"PLoS Negl Trop Dis"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0004607","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T10:51:55Z","timestamp":1589021515000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0004607"}},"subtitle":[],"editor":[{"given":"Alan L","family":"Rothman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,4,7]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0004607","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726270877.793519658","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,7]]}}}