{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:19:02Z","timestamp":1784027942058,"version":"3.55.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"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":[[2021,4]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>To identify the regulatory role of protein phosphatase 2A (PP2A) in the development of liver disease, we generated a mouse model with hepatocyte\u2010specific deletion of <jats:italic toggle=\"yes\">Ppp2r1a<\/jats:italic> gene (encoding PP2A A\u03b1 subunit).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Homozygote (HO) mice and matched wild\u2010type littermates were investigated at 3, 6, 9, 12, 15, and 18\u00a0months of age. Pathological examination showed that PP2A A\u03b1 deficiency in hepatocytes resulted in progressive liver fibrosis phenotype from 9\u00a0months of age. No hepatocyte death was observed in HO mice. However, perturbation of pathways including epidermal growth factor receptor 1 (EGFR1), amino acid metabolism, and translation factors as well as leptin and adiponectin led to pronounced hepatic fibrosis.<jats:italic toggle=\"yes\">\u00a0In vitro<\/jats:italic> studies demonstrated the involvement of specific B subunit complexes in the regulation of EGFR1 signaling pathway and cross talk between defected hepatocytes and stimulation of interstitial hyperplasia. It is noteworthy that HO mice failed to develop hepatocellular carcinoma for as long as 22 months of age. We further demonstrate that PP2A A\u03b2\u2013containing holoenzymes played a critical role in preventing hepatocyte apoptosis and antagonizing tumorigenesis through specific pathways on A\u03b1 loss. Furthermore, PP2A A\u03b1 and A\u03b2 were functionally distinct, and the A\u03b2 isoform failed to substitute for A\u03b1 in the development of inflammation and liver fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These observations identify pathways that contribute to the pathogenesis of liver fibrosis and provide putative therapeutic targets for its treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31457","type":"journal-article","created":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T09:35:17Z","timestamp":1594546517000},"page":"1551-1569","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Perturbation of Specific Signaling Pathways Is Involved in Initiation of Mouse Liver Fibrosis"],"prefix":"10.1097","volume":"73","author":[{"given":"Liping","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Toxicology,Guangzhou Center for Disease Control and Prevention,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Separation Science for Analytical Chemistry,Dalian Institute of Chemical Physics,Chinese Academy of Science,National Chromatographic Research and Analysis Center,Dalian,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Toxicology,Guangzhou Center for Disease Control and Prevention,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Fan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangping","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Gao","sequence":"additional","affiliation":[{"name":"The Center for Bioinformatics and Computational Biology,Shanghai Key Laboratory of Regulatory Biology,The Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Separation Science for Analytical Chemistry,Dalian Institute of Chemical Physics,Chinese Academy of Science,National Chromatographic Research and Analysis Center,Dalian,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Xing","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daochuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieliu","family":"Shi","sequence":"additional","affiliation":[{"name":"The Center for Bioinformatics and Computational Biology,Shanghai Key Laboratory of Regulatory Biology,The Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2031-3683","authenticated-orcid":false,"given":"Dianke","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health,Qingdao University,Qingdao,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology,Albert Einstein College of Medicine,Bronx,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Separation Science for Analytical Chemistry,Dalian Institute of Chemical Physics,Chinese Academy of Science,National Chromatographic Research and Analysis Center,Dalian,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food,Nutrition and Health,Department of Toxicology,School of Public Health,Sun Yat\u2010sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"hep31457-bib-0001-20250825","doi-asserted-by":"crossref","first-page":"166","DOI":"10.15171\/mejdd.2016.29","article-title":"New concepts on pathogenesis and diagnosis of liver fibrosis; a review article","volume":"8","year":"2016","journal-title":"Middle East J Dig Dis"},{"key":"hep31457-bib-0002-20250825","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.3748\/wjg.v20.i23.7312","article-title":"Pathogenesis of liver cirrhosis","volume":"20","year":"2014","journal-title":"World J Gastroenterol"},{"key":"hep31457-bib-0003-20250825","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s00204-015-1525-6","article-title":"Strategies to prevent and reverse liver fibrosis in humans and laboratory animals","volume":"89","year":"2015","journal-title":"Arch Toxicol"},{"key":"hep31457-bib-0004-20250825","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bpg.2017.04.005","article-title":"Reversal of liver fibrosis: from fiction to reality","volume":"31","year":"2017","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"hep31457-bib-0005-20250825","article-title":"Cell signals influencing hepatic fibrosis","volume":"2012","year":"2012","journal-title":"Int J Hepatol"},{"key":"hep31457-bib-0006-20250825","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s00204-016-1814-8","article-title":"Adverse outcome pathway development from protein alkylation to liver fibrosis","volume":"91","year":"2017","journal-title":"Arch Toxicol"},{"key":"hep31457-bib-0007-20250825","article-title":"Deletion of protein kinase D3 promotes liver fibrosis in mice","year":"2020","journal-title":"Hepatology"},{"key":"hep31457-bib-0008-20250825","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/hep.29689","article-title":"New insights into the role and mechanism of c\u2010Jun\u2010N\u2010terminal kinase signaling in the pathobiology of liver diseases","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep31457-bib-0009-20250825","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1111\/febs.13573","article-title":"All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase","volume":"283","year":"2016","journal-title":"FEBS J"},{"key":"hep31457-bib-0010-20250825","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2013.02.036","article-title":"Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer","volume":"335","year":"2013","journal-title":"Cancer Lett"},{"key":"hep31457-bib-0011-20250825","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1021\/bi00465a002","article-title":"Alpha\u2010 and beta\u2010forms of the 65\u2010kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure","volume":"29","year":"1990","journal-title":"Biochemistry"},{"key":"hep31457-bib-0012-20250825","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1042\/bj20021244","article-title":"Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution","volume":"369","year":"2003","journal-title":"Biochem J"},{"key":"hep31457-bib-0013-20250825","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1158\/0008-5472.CAN-05-1103","article-title":"Cancer\u2010associated PP2A Aalpha subunits induce functional haploinsufficiency and tumorigenicity","volume":"65","year":"2005","journal-title":"Cancer Res"},{"key":"hep31457-bib-0014-20250825","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1535-6108(04)00026-1","article-title":"Identification of specific PP2A complexes involved in human cell transformation","volume":"5","year":"2004","journal-title":"Cancer Cell"},{"key":"hep31457-bib-0015-20250825","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1074\/jbc.RA119.007593","article-title":"Protein phosphatase 2A Aalpha regulates Abeta protein expression and stability","volume":"294","year":"2019","journal-title":"J Biol Chem"},{"key":"hep31457-bib-0016-20250825","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bbamcr.2018.07.010","article-title":"Physiologic functions of PP2A: lessons from genetically modified mice","volume":"1866","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"hep31457-bib-0017-20250825","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.aca.2016.09.032","article-title":"Dissolving capability difference based sequential extraction: a versatile tool for in\u2010depth membrane proteome analysis","volume":"945","year":"2016","journal-title":"Anal Chim Acta"},{"key":"hep31457-bib-0018-20250825","article-title":"Proteomics investigations into serum proteins adsorbed by high\u2010flux and low\u2010flux dialysis membranes","volume":"11","year":"2017","journal-title":"Proteomics Clin Appl"},{"key":"hep31457-bib-0019-20250825","doi-asserted-by":"crossref","first-page":"47732","DOI":"10.1074\/jbc.M408015200","article-title":"Critical role for protein phosphatase 2A heterotrimers in mammalian cell survival","volume":"279","year":"2004","journal-title":"J Biol Chem"},{"key":"hep31457-bib-0020-20250825","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2007.03.047","article-title":"The tumor suppressor PP2A Abeta regulates the RalA GTPase","volume":"129","year":"2007","journal-title":"Cell"},{"key":"hep31457-bib-0021-20250825","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/onc.2017.350","article-title":"Loss of protein phosphatase 2A regulatory subunit B56delta promotes spontaneous tumorigenesis in vivo","volume":"37","year":"2018","journal-title":"Oncogene"},{"key":"hep31457-bib-0022-20250825","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1093\/carcin\/bgt258","article-title":"Protein phosphatase 2A promotes hepatocellular carcinogenesis in the diethylnitrosamine mouse model through inhibition of p53","volume":"35","year":"2014","journal-title":"Carcinogenesis"},{"key":"hep31457-bib-0023-20250825","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1242\/dev.020842","article-title":"Two highly related regulatory subunits of PP2A exert opposite effects on TGF\u2010beta\/Activin\/Nodal signalling","volume":"135","year":"2008","journal-title":"Development"},{"key":"hep31457-bib-0024-20250825","article-title":"Up\u2010regulation of RACK1 by TGF\u2010beta1 promotes hepatic fibrosis in mice","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"hep31457-bib-0025-20250825","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.bbrc.2015.05.040","article-title":"RACK1\u2010mediated translation control promotes liver fibrogenesis","volume":"463","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"hep31457-bib-0026-20250825","doi-asserted-by":"crossref","first-page":"22952","DOI":"10.1074\/jbc.M800802200","article-title":"Tyrosine 302 in RACK1 is essential for insulin\u2010like growth factor\u2010I\u2010mediated competitive binding of PP2A and beta1 integrin and for tumor cell proliferation and migration","volume":"283","year":"2008","journal-title":"J Biol Chem"},{"key":"hep31457-bib-0027-20250825","doi-asserted-by":"crossref","first-page":"21830","DOI":"10.1073\/pnas.0912793107","article-title":"Biguanide metformin acts on tau phosphorylation via mTOR\/protein phosphatase 2A (PP2A) signaling","volume":"107","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep31457-bib-0028-20250825","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jhep.2015.02.008","article-title":"Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta\u2010dependent regulation of JNK signaling in mice","volume":"63","year":"2015","journal-title":"J Hepatol"},{"key":"hep31457-bib-0029-20250825","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.jcma.2017.05.005","article-title":"Metformin reduces intrahepatic fibrosis and intrapulmonary shunts in biliary cirrhotic rats","volume":"80","year":"2017","journal-title":"J Chin Med Assoc"},{"key":"hep31457-bib-0030-20250825","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.gene.2018.06.053","article-title":"Emerging role and therapeutic implication of Wnt signaling pathways in liver fibrosis","volume":"674","year":"2018","journal-title":"Gene"},{"issue":"Suppl. 1","key":"hep31457-bib-0031-20250825","first-page":"S79","article-title":"Molecular mechanisms of hepatic fibrogenesis","volume":"22","year":"2007","journal-title":"J Gastroenterol Hepatol"},{"key":"hep31457-bib-0032-20250825","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.jhep.2007.12.020","article-title":"Functional interaction between Wnt3 and Frizzled\u20107 leads to activation of the Wnt\/beta\u2010catenin signaling pathway in hepatocellular carcinoma cells","volume":"48","year":"2008","journal-title":"J Hepatol"},{"key":"hep31457-bib-0033-20250825","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jhep.2010.07.026","article-title":"TGF\u2010beta1 mediated activation of Rho kinase induces TGF\u2010beta2 and endothelin\u20101 expression in human hepatic stellate cells","volume":"54","year":"2011","journal-title":"J Hepatol"},{"key":"hep31457-bib-0034-20250825","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1016\/j.biochi.2013.09.003","article-title":"Wnt signaling in liver fibrosis: progress, challenges and potential directions","volume":"95","year":"2013","journal-title":"Biochimie"},{"key":"hep31457-bib-0035-20250825","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3109\/10409238.2015.1102858","article-title":"A\u2010Raf: a new star of the family of raf kinases","volume":"50","year":"2015","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"hep31457-bib-0036-20250825","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.bbapap.2018.05.009","article-title":"Revealing A\u2010Raf functions through its interactome","volume":"1866","year":"2018","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"hep31457-bib-0037-20250825","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molcel.2009.09.025","article-title":"Alpha4 is an essential regulator of PP2A phosphatase activity","volume":"36","year":"2009","journal-title":"Mol Cell"},{"key":"hep31457-bib-0038-20250825","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1128\/MCB.05744-11","article-title":"Human cancer\u2010associated mutations in the Aalpha subunit of protein phosphatase 2A increase lung cancer incidence in Aalpha knock\u2010in and knockout mice","volume":"31","year":"2011","journal-title":"Mol Cell Biol"},{"key":"hep31457-bib-0039-20250825","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.2337\/db11-1399","article-title":"Ceramide mediates vascular dysfunction in diet\u2010induced obesity by PP2A\u2010mediated dephosphorylation of the eNOS\u2010Akt complex","volume":"61","year":"2012","journal-title":"Diabetes"},{"key":"hep31457-bib-0040-20250825","article-title":"mTORc1 activity is necessary and sufficient for phosphorylation of eNOS(S1177)","volume":"6","year":"2018","journal-title":"Physiol Rep"},{"key":"hep31457-bib-0041-20250825","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s40256-017-0220-9","article-title":"The positive regulation of eNOS signaling by PPAR agonists in cardiovascular diseases","volume":"17","year":"2017","journal-title":"Am J Cardiovasc Drugs"},{"key":"hep31457-bib-0042-20250825","doi-asserted-by":"crossref","first-page":"28738","DOI":"10.1074\/jbc.M112.375915","article-title":"Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion","volume":"287","year":"2012","journal-title":"J Biol Chem"},{"key":"hep31457-bib-0043-20250825","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.phrs.2019.02.008","article-title":"PRSS23 knockdown inhibits gastric tumorigenesis through EIF2 signaling","volume":"142","year":"2019","journal-title":"Pharmacol Res"},{"key":"hep31457-bib-0044-20250825","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s10157-016-1232-5","article-title":"Context\u2010dependent mechanisms modulating aldosterone signaling in the kidney","volume":"20","year":"2016","journal-title":"Clin Exp Nephrol"},{"key":"hep31457-bib-0045-20250825","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11906-016-0626-9","article-title":"Aldosterone production and signaling dysregulation in obesity","volume":"18","year":"2016","journal-title":"Curr Hypertens Rep"}],"updated-by":[{"DOI":"10.1002\/hep.32377","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000}}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.31457","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.31457","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.31457","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T19:00:22Z","timestamp":1756148422000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.31457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,19]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.31457","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,19]]},"assertion":[{"value":"2020-05-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-11","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}