{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:41:30Z","timestamp":1791848490203,"version":"4.3.4"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T00:00:00Z","timestamp":1515628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0190887","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T19:43:22Z","timestamp":1515699802000},"page":"e0190887","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["The optimal threshold of serum ceruloplasmin in the diagnosis of Wilson\u2019s disease: A large hospital-based study"],"prefix":"10.1371","volume":"13","author":[{"given":"Rong","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-fang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6660-6417","authenticated-orcid":true,"given":"Xu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,1,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3891\/acta.chem.scand.02-0550","article-title":"Investigations in serum copper. II. Isolation of the copper-containing protein and a description of some of its properties","volume":"2","author":"CG Holmberg","year":"1948","journal-title":"Acta Chem. Scand"},{"issue":"3018","key":"ref2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1126\/science.116.3018.484","article-title":"Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson\u2019s disease)","volume":"116","author":"IH Scheinberg","year":"1952","journal-title":"Science"},{"issue":"6","key":"ref3","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/hep.22261","article-title":"Diagnosis and treatment of Wilson disease: an update","volume":"47","author":"EA Roberts","year":"2008","journal-title":"Hepatology"},{"issue":"8","key":"ref4","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1373\/clinchem.2008.103432","article-title":"Diagnostic accuracy of serum ceruloplasmin in Wilson Disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects","volume":"54","author":"CM Mak","year":"2008","journal-title":"Clinical Chemistry"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.5223\/pghn.2015.18.3.187","article-title":"Diagnostic value of ceruloplamin in the diagnosis of pediatric Wilson\u2019s disease","volume":"18","author":"JA Kim","year":"2015","journal-title":"Pediatr Gastroenterol Hepatol Nutr"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/mds.20628","article-title":"Diagnostic significance of reduced serum caeruloplasmin concentration in neurological disease","volume":"20","author":"JM Walshe","year":"2005","journal-title":"Mov Disord"},{"key":"ref7","first-page":"893","article-title":"Factors influencing serum ceruloplasmin levels in normal individuals","volume":"68","author":"DW Cox","year":"1966","journal-title":"J Lab Clin Med"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1016\/S0021-9258(18)68783-6","article-title":"Transcriptional regulation of ceruloplasmin gene expression during inflammation","volume":"263","author":"JD Gitlin","year":"1988","journal-title":"J. Biol. Chem"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1002\/hep.27932","article-title":"Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample","volume":"62","author":"X Yang","year":"2015","journal-title":"Hepatology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1034\/j.1600-0676.2003.00824.x","article-title":"Diagnosis and phenotypic classification of Wilson disease","volume":"23","author":"P Ferenci","year":"2003","journal-title":"Liver Int"},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1002\/hep.28565","article-title":"Reply. Hepatology","volume":"64","author":"X Yang","year":"2016","journal-title":"Reply. Hepatology"},{"key":"ref12","first-page":"712","article-title":"A study of the liver pathology and direct sequencing of all exons of WD gene in a patient with fulminate Wilson disease","volume":"15","author":"G He","year":"2007","journal-title":"Chin J of Hepatol"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1373\/clinchem.2007.096032","article-title":"Bias in sensitivity and specificity caused by data-driven selection of optimal cutoff values: mechanisms, magnitude, and solutions","volume":"54","author":"MM Leeflang","year":"2008","journal-title":"Clinical Chemistry"},{"key":"ref14","article-title":"Medical decision making","author":"HC Sox","year":"1988"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1177\/0272989X05276855","article-title":"Methods to estimate the optimal threshold for normally or log-normally distributed biological tests","volume":"5","author":"J Jund","year":"2005","journal-title":"Med Dec Making"},{"key":"ref16","article-title":"Wilson\u2019s Disease","author":"IH Scheinberg","year":"1984"},{"key":"ref17","first-page":"253","article-title":"Wilson\u2019s disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients","volume":"70","author":"JM Walshe","year":"1989","journal-title":"Q J Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0016-5085(97)70097-0","article-title":"Wilson\u2019s disease in patients presenting with liver disease: a diagnostic challenge","volume":"113","author":"P Steindl","year":"1997","journal-title":"Gastroenterology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/gut.46.3.415","article-title":"Diagnosis of Wilson\u2019s disease: an experience over three decades","volume":"46","author":"PJ Gow","year":"2000","journal-title":"Gut"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0022-3476(79)80011-6","article-title":"Laboratory measures of copper metabolism in the differentiation of chronic active hepatitis and Wilson disease in children","volume":"94","author":"JA Perman","year":"1979","journal-title":"J Pediatr"},{"key":"ref21","first-page":"831","article-title":"Distinct clinical courses according to presenting phenotype sand their correlations to ATP7B mutations in a large Wilson\u2019s disease cohort","volume":"6","author":"BH Lee","year":"2011","journal-title":"Liver International"},{"issue":"1","key":"ref22","first-page":"128","article-title":"Clinical characteristics of Wilson's disease: a retrospective analysis of admission data among 126 Patients","volume":"47","author":"L Feng","year":"2016","journal-title":"Sichuan Da Xue Xue Bao Yi Xue Band"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.arcmed.2015.02.001","article-title":"Genetic and clinical analysis in a cohort of patients with Wilson\u2019s disease in Southwestern China","volume":"46","author":"Y Liu","year":"2015","journal-title":"Archives of Medical Research"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00005792-199205000-00004","article-title":"Wilson disease","volume":"71","author":"FJ Brewer","year":"1992","journal-title":"Medicine (Baltimore)"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/hep.1840150410","article-title":"Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson\u2019s disease","volume":"15","author":"C Martins da Costa","year":"1992","journal-title":"Hepatology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/gut.2005.087262","article-title":"Clinical presentation, diagnosis and long-term outcome of Wilson\u2019s disease: a cohort study","volume":"56","author":"U Merle","year":"2007","journal-title":"Gut"},{"issue":"3","key":"ref27","first-page":"179","article-title":"Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre","volume":"13","author":"L Gheorghe","year":"2004","journal-title":"Rom J Gastroenterol"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jhep.2007.03.011","article-title":"Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson\u2019s disease in children","volume":"47","author":"T M\u00fcller","year":"2007","journal-title":"J Hepatol"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/MPG.0b013e31817d80b8","article-title":"Wilson Disease in Children: Analysis of 57 Cases","volume":"48","author":"N Manolaki","year":"2009","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1002\/hep.23910","article-title":"Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease","volume":"52","author":"E Nicastro","year":"2010","journal-title":"Hepatology"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ajg.2011.07.007","article-title":"A clinical study of Wilson\u2019s disease: The experience of a single Egyptian Paediatric Hepatology Unit","author":"H EI-Karaksy","year":"2011","journal-title":"Arab Journal of Gastroenterology"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/MD.0b013e318045a00e","article-title":"Wilson disease: description of 282 patients evaluated over 3 decades","volume":"86","author":"AB Taly","year":"2007","journal-title":"Medicine (Baltimore)"},{"issue":"2","key":"ref33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.5223\/pghn.2015.18.2.121","article-title":"Wilson\u2019s Disease in Bangladeshi Children: Analysis of 100 Cases of Wilson\u2019s Disease in Bangladeshi Children","volume":"18","author":"MD Rukunuzzaman","year":"2015","journal-title":"Pediatr Gastroenterol Hepatol Nutr"},{"issue":"4","key":"ref34","first-page":"295","article-title":"Serum and urinary ceruloplasmin in experimental nephrotic syndrome","volume":"15","author":"A Mainero","year":"1992","journal-title":"Clin Invest Med"},{"issue":"1","key":"ref35","first-page":"13","article-title":"Ceruloplasmin level of patients with liver disease in China","volume":"44","author":"X Yang","year":"2005","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00018-002-8519-2","article-title":"Structure and function relationships in ceruloplasmin: a \u2018moonlighting\u2019 protein","volume":"59","author":"P Bielli","year":"2002","journal-title":"Cell. Mol. Life Sci."},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1042\/BJ20081983","article-title":"Copper proteins and ferroxidase in human plasma and that of wild-type and ceruloplasmin knochout mice","volume":"419","author":"LW Gray","year":"2009","journal-title":"Biochem J"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1006\/abbi.1993.1224","article-title":"Synthesis and turnover of ceruloplasmin in rats treated with 17 beta-estradiol","volume":"302","author":"RB Middleton","year":"1993","journal-title":"Arch. Biochem. Biophys"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1042\/bj2530851","article-title":"Regulation of rabbit acute phase protein biosynthesis","volume":"253","author":"A Mackiewicz","year":"1988","journal-title":"Biochem. J"},{"issue":"9","key":"ref40","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1039\/C6MT00103C","article-title":"C. Ceruloplamin and other copper binding components of blood plasma and their functions: an update","volume":"8","author":"M Linder","year":"2016","journal-title":"Metallomics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0190887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T07:55:02Z","timestamp":1660290902000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0190887"}},"subtitle":[],"editor":[{"given":"Rosanna","family":"Squitti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,1,11]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0190887","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,11]]}}}