{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:00:08Z","timestamp":1791061208099,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte\u2010derived exosomal long noncoding RNA\u2010H19 (lncRNA\u2010H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte\u2010derived lncRNA\u2010H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2<jats:sup>\u2010\/\u2010<\/jats:sup>) mouse models were used. Wild\u2010type and H19<jats:sup>maternal\u0394Exon1\/+ <\/jats:sup>(H19KO) mice were subjected to BDL. Mdr2<jats:sup>\u2010\/\u2010<\/jats:sup>H19<jats:sup>maternal\u0394Exon1\/+<\/jats:sup> (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for <jats:italic toggle=\"yes\">in vivo<\/jats:italic> transplantation and <jats:italic toggle=\"yes\">in vitro<\/jats:italic> studies. Fluorescence\u2010labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal\u2010H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)\/primary biliary cholangitis (PBC) liver samples were analyzed by real\u2010time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC.\u00a0H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2<jats:sup>\u2010\/\u2010<\/jats:sup> mice.\u00a0Transplanted cholangiocyte\u2010derived H19\u2010enriched exosomes were rapidly and preferentially taken up by HSCs and HSC\u2010derived fibroblasts, and promoted liver fibrosis in BDL\u2010H19KO mice and DKO mice. H19\u2010enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC\u2010derived fibroblasts. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Cholangiocyte\u2010derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies.<\/jats:p>","DOI":"10.1002\/hep.30662","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T11:18:40Z","timestamp":1555327120000},"page":"1317-1335","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":206,"title":["Cholangiocyte\u2010Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis"],"prefix":"10.1097","volume":"70","author":[{"given":"Runping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,Zhejiang,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"School of Pharmaceutical Science,Anhui University of Chinese Medicine,Hefei,Anhui,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Gurley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,Zhejiang,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science,Anhui University of Chinese Medicine,Hefei,Anhui,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pathology,Medical College of Virginia Campus, Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Pandak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Robert Lippman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,McGuire Veterans Affairs Medical Center,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-3681","authenticated-orcid":false,"given":"Jasmohan S.","family":"Bajaj","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip B.","family":"Hylemon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-372X","authenticated-orcid":false,"given":"Huiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"hep30662-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.mayocp.2015.03.017","article-title":"The cholangiopathies","volume":"90","year":"2015","journal-title":"Mayo Clin Proc"},{"key":"hep30662-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jhep.2012.10.011","article-title":"The dynamic biliary epithelia: molecules, pathways, and disease","volume":"58","year":"2013","journal-title":"J Hepatol"},{"key":"hep30662-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1053\/j.gastro.2004.08.006","article-title":"The cholangiopathies: disorders of biliary epithelia","volume":"127","year":"2004","journal-title":"Gastroenterology"},{"key":"hep30662-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1053\/j.gastro.2006.07.023","article-title":"Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver","volume":"132","year":"2007","journal-title":"Gastroenterology"},{"key":"hep30662-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.29076","article-title":"The role of sphingosine 1\u2010phosphate receptor 2 in bile\u2010acid\u2010induced cholangiocyte proliferation and cholestasis\u2010induced liver injury in mice","volume":"65","year":"2017","journal-title":"Hepatology"},{"key":"hep30662-bib-0006-20241017","first-page":"308","article-title":"Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1\u2010phosphate receptor 2","volume":"60","year":"2014","journal-title":"Hepatology"},{"key":"hep30662-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/hep.29145","article-title":"The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice","volume":"66","year":"2017","journal-title":"Hepatology"},{"key":"hep30662-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7150\/thno.21945","article-title":"Exosome theranostics: biology and translational medicine","volume":"8","year":"2018","journal-title":"Theranostics"},{"key":"hep30662-bib-0009-20241017","first-page":"1661","article-title":"Exosome\u2010mediated cell\u2010cell communication in tumor progression","volume":"8","year":"2018","journal-title":"Am J Cancer Res"},{"key":"hep30662-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jhep.2016.03.004","article-title":"Exosomes in liver pathology","volume":"65","year":"2016","journal-title":"J Hepatol"},{"key":"hep30662-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ejps.2017.06.015","article-title":"Glycyrrhetic acid, but not glycyrrhizic acid, strengthened entecavir activity by promoting its subcellular distribution in the liver via efflux inhibition","volume":"106","year":"2017","journal-title":"Eur J Pharm Sci"},{"key":"hep30662-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"e008737","DOI":"10.1161\/JAHA.118.008737","article-title":"Engineered exosomes with ischemic myocardium\u2010targeting peptide for targeted therapy in myocardial infarction","volume":"7","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"hep30662-bib-0013-20241017","first-page":"99","article-title":"Isolation and culture of hepatic stellate cells","volume":"117","year":"2005","journal-title":"Methods Mol Med"},{"key":"hep30662-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep30662-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1038\/sj.onc.1202819","article-title":"Steroid hormones modulate H19 gene expression in both mammary gland and uterus","volume":"18","year":"1999","journal-title":"Oncogene"},{"key":"hep30662-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/hep.30150","article-title":"Ductular reaction in liver diseases: pathological mechanisms and translational significances","volume":"69","year":"2019","journal-title":"Hepatology"},{"key":"hep30662-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.bbadis.2017.06.017","article-title":"Mechanisms of cholangiocyte responses to injury","volume":"1864","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"hep30662-bib-0018-20241017","article-title":"Targeting H19, an imprinted long non\u2010coding RNA, in hepatic functions and liver diseases","volume":"5","year":"2017","journal-title":"Diseases"},{"key":"hep30662-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"26589","DOI":"10.1074\/jbc.R116.757955","article-title":"Exosomes in the pathology of neurodegenerative diseases","volume":"291","year":"2016","journal-title":"J Biol Chem"},{"key":"hep30662-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"87","DOI":"10.18632\/genesandcancer.172","article-title":"Exosomes derived from cancerous and non\u2010cancerous cells regulate the anti\u2010tumor response in the tumor microenvironment","volume":"9","year":"2018","journal-title":"Genes Cancer"},{"key":"hep30662-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/ijc.30179","article-title":"Exosome\u2010encapsulated microRNAs as circulating biomarkers for breast cancer","volume":"139","year":"2016","journal-title":"Int J Cancer"},{"key":"hep30662-bib-0022-20241017","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-017-0706-8","article-title":"Role of exosomal proteins in cancer diagnosis","volume":"16","year":"2017","journal-title":"Mol Cancer"},{"key":"hep30662-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1111\/cas.13697","article-title":"Exosomes in cancer development and clinical applications","volume":"109","year":"2018","journal-title":"Cancer Sci"},{"key":"hep30662-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrurol.2016.78","article-title":"Prostate cancer: Exosome RNA expression predicts high\u2010grade disease","volume":"13","year":"2016","journal-title":"Nat Rev Urol"},{"key":"hep30662-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/hep.25873","article-title":"Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug\u2010induced, and inflammatory liver diseases","volume":"56","year":"2012","journal-title":"Hepatology"},{"key":"hep30662-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/ni.2647","article-title":"Exosomes mediate the cell\u2010to\u2010cell transmission of IFN\u2010alpha\u2010induced antiviral activity","volume":"14","year":"2013","journal-title":"Nat Immunol"},{"key":"hep30662-bib-0027-20241017","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jhep.2013.10.015","article-title":"HCV transmission by hepatic exosomes establishes a productive infection","volume":"60","year":"2014","journal-title":"J Hepatol"},{"key":"hep30662-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/hep.29409","article-title":"Hepatocyte\u2010derived exosomes promote T follicular regulatory cell expansion during hepatitis C virus infection","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep30662-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"G990","DOI":"10.1152\/ajpgi.00093.2010","article-title":"Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia","volume":"299","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"hep30662-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1053\/j.gastro.2008.09.066","article-title":"Liver cell\u2010derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells","volume":"136","year":"2009","journal-title":"Gastroenterology"},{"key":"hep30662-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/hep.29838","article-title":"Cholangiocyte\u2010derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans","volume":"68","year":"2018","journal-title":"Hepatology"},{"key":"hep30662-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5772\/61186","article-title":"Exosomes: mechanisms of uptake","volume":"4","year":"2015","journal-title":"J Circ Biomark"},{"key":"hep30662-bib-0033-20241017","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1042\/BST0390559","article-title":"Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis","volume":"39","year":"2011","journal-title":"Biochem Soc Trans"},{"key":"hep30662-bib-0034-20241017","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1471-2407-11-108","article-title":"Interaction and uptake of exosomes by ovarian cancer cells","volume":"11","year":"2011","journal-title":"BMC Cancer"},{"key":"hep30662-bib-0035-20241017","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1038\/nprot.2012.131","article-title":"Exosome\u2010mediated delivery of siRNA in vitro and in vivo","volume":"7","year":"2012","journal-title":"Nat Protoc"},{"key":"hep30662-bib-0036-20241017","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","year":"2011","journal-title":"Nat Biotechnol"},{"key":"hep30662-bib-0037-20241017","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","year":"2015","journal-title":"Nature"},{"key":"hep30662-bib-0038-20241017","doi-asserted-by":"crossref","first-page":"9698","DOI":"10.1002\/jcp.27656","article-title":"H19\/miR\u2010148a\/USP4 axis facilitates liver fibrosis by enhancing TGF\u2010beta signaling in both hepatic stellate cells and hepatocytes","volume":"234","year":"2019","journal-title":"J Cell Physiol"},{"key":"hep30662-bib-0039-20241017","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1007\/s10753-018-0744-4","article-title":"The lncRNA H19 mediates pulmonary fibrosis by regulating the miR\u2010196a\/COL1A1 axis","volume":"41","year":"2018","journal-title":"Inflammation"},{"key":"hep30662-bib-0040-20241017","doi-asserted-by":"crossref","first-page":"51473","DOI":"10.18632\/oncotarget.10444","article-title":"Long non\u2010coding RNA\u2010H19 antagonism protects against renal fibrosis","volume":"7","year":"2016","journal-title":"Oncotarget"},{"key":"hep30662-bib-0041-20241017","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.gpb.2015.09.006","article-title":"Roles, functions, and mechanisms of long non\u2010coding RNAs in cancer","volume":"14","year":"2016","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"hep30662-bib-0042-20241017","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12943-015-0458-2","article-title":"The H19 long non\u2010coding RNA in cancer initiation, progression, and metastasis \u2010 a proposed unifying theory","volume":"14","year":"2015","journal-title":"Mol Cancer"},{"key":"hep30662-bib-0043-20241017","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s13277-015-3779-2","article-title":"H19\u2010derived miR\u2010675 contributes to bladder cancer cell proliferation by regulating p53 activation","volume":"37","year":"2016","journal-title":"Tumour Biol"},{"key":"hep30662-bib-0044-20241017","doi-asserted-by":"crossref","first-page":"29625","DOI":"10.1074\/jbc.M504033200","article-title":"H19 mRNA\u2010like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1","volume":"280","year":"2005","journal-title":"J Biol Chem"},{"key":"hep30662-bib-0045-20241017","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/carcin\/23.11.1885","article-title":"Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells","volume":"23","year":"2002","journal-title":"Carcinogenesis"},{"key":"hep30662-bib-0046-20241017","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.carpath.2016.05.005","article-title":"Long noncoding RNA H19 controls DUSP5\/ERK1\/2 axis in cardiac fibroblast proliferation and fibrosis","volume":"25","year":"2016","journal-title":"Cardiovasc Pathol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.30662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.30662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.30662","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30662","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T23:17:22Z","timestamp":1729207042000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,24]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.30662","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,24]]},"assertion":[{"value":"2019-01-30","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}