{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:55:47Z","timestamp":1782755747545,"version":"3.54.5"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["ETPL\u201012\u2010R15GAP\u20100010"],"award-info":[{"award-number":["ETPL\u201012\u2010R15GAP\u20100010"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/EDG10nov041"],"award-info":[{"award-number":["NMRC\/EDG10nov041"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["ETPL-12-R15GAP-0010"],"award-info":[{"award-number":["ETPL-12-R15GAP-0010"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/EDG10nov041"],"award-info":[{"award-number":["NMRC\/EDG10nov041"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Circulating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)\u2010 or annexin V (AV)\u2010binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre\u2010eclampsia (PE) candidate biomarkers, TIMP\u20101\u00a0in CTB\u2010EVs (CTB\u2010TIMP) and PAI\u20101\u00a0in AV\u2010EVs (AV\u2010PAI) complement plasma PlGF in predicting PE in a low\u2010risk obstetric population. Eight hundred and forty\u2010three prospectively banked plasma samples collected at 28\u00a0+\u00a00 to 32\u00a0+\u00a00 gestation weeks in the Neonatal and Obstetrics Risk Assessment (NORA) cohort study were assayed by sandwich ELISAs for plasma PlGF, CTB\u2010TIMP1 and AV\u2010PAI1. Nineteen patients subsequently developed PE 7.3 (\u00b12.9) weeks later at a mean gestational age of 36.1\u00a0\u00b1\u00a03.5\u00a0weeks. The biomarkers were assessed for their predictive accuracy for PE using stepwise multivariate logistic regression analysis with Firth correction and Areas under the curve (AUC). To achieve 100% sensitivity in predicting PE, the cut\u2010off for plasma PlGF, CTB\u2010TIMP1 &amp; AV\u2010PAI1 were set at &lt;1235, \u2264300 or &gt;1300 and &lt;10,550\u00a0pg\/mL plasma, respectively. The corresponding AUCs, specificity and PPV at a 95% confidence interval were 0.92, 52.1% and 4.7%; 0.72, 44.5% and 4.0%; and 0.69, 21.5% and 2.9%, respectively. At 100% sensitivity, the three biomarkers had a combined AUC of 0.96, specificity of 78.6%, and PPV of 9.9%.<\/jats:p><jats:p>This is the first large cohort validation of the utility of EV\u2010associated analytes as disease biomarkers. Specifically, EV biomarkers enhanced the predictive robustness of an existing PE biomarker sufficiently to justify PE screening in a low\u2010risk general obstetric population.<\/jats:p>","DOI":"10.1080\/20013078.2017.1408390","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T23:48:46Z","timestamp":1518047326000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":30,"title":["Extracellular vesicles yield predictive pre\u2010eclampsia biomarkers"],"prefix":"10.1002","volume":"6","author":[{"given":"Kok Hian","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Maternal Fetal Medicine KK Women's and Children's Hospital Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Sim","family":"Tan","sequence":"additional","affiliation":[{"name":"Paracrine Therapeutics Pte Ltd Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mor Jack","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Obstetrics &amp; Gynaecology KK Women's and Children's Hospital Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Shi","family":"Tey","sequence":"additional","affiliation":[{"name":"Division of Obstetrics &amp; Gynaecology KK Women's and Children's Hospital Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Kian","family":"Sim","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology A*STAR Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Carson","family":"Allen","sequence":"additional","affiliation":[{"name":"Centre for Quantitative Medicine Duke\u2010NUS Medical School Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Kiang","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology A*STAR Singapore Republic of Singapore"},{"name":"Department of Surgery Yong Loo Lin School of Medicine Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"189","volume-title":"Pre\u2010eclampsia","author":"Villar J","year":"2003"},{"issue":"4","key":"e_1_2_6_3_1","article-title":"Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles","volume":"211","author":"Tan KH","year":"2014","journal-title":"Am J Obstet Gynecol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.27066"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.29828"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.22614"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/1471-2393-12-160","article-title":"A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy","volume":"12","author":"Lim WY","year":"2012","journal-title":"BMC Pregnancy Childbirth"},{"issue":"1","key":"e_1_2_6_8_1","first-page":"48","article-title":"Epidemiology of pre\u2010eclampsia and eclampsia at the KK Women's and Children's Hospital, Singapore","volume":"47","author":"Tan KH","year":"2006","journal-title":"Singapore Med J"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.27031"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.20360"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9653194"},{"issue":"3","key":"e_1_2_6_12_1","first-page":"e137","article-title":"Regulation of trophoblast invasion: the role of matrix metalloproteinases","volume":"5","author":"Zhu J\u2010Y","year":"2012","journal-title":"Rev Obstet Gynecol"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-2115(96)02484-0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414838"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.tandfonline.com\/doi\/pdf\/10.1080\/20013078.2017.1408390","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/20013078.2017.1408390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T14:01:50Z","timestamp":1760623310000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1080\/20013078.2017.1408390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1080\/20013078.2017.1408390"],"URL":"https:\/\/doi.org\/10.1080\/20013078.2017.1408390","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=zjev20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=zjev20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2017-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1408390"}}