{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:17:33Z","timestamp":1791559053838,"version":"4.3.4"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic\n                      <jats:italic toggle=\"yes\">Lactobacillus rhamnosus<\/jats:italic>\n                      GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (\n                      <jats:italic toggle=\"yes\">Mdr2\u2212\/\u2212<\/jats:italic>\n                      ) mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Global and intestine\u2010specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine\u2010\u03b2\u2010muricholic acid (T\u2010\u03b2MCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG\u2010treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG\u2010treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF\u201015) and subsequently reduced hepatic cholesterol 7\u03b1\u2010hydroxylase and BA synthesis in BDL and\n                      <jats:italic toggle=\"yes\">Mdr2\u2212\/\u2212<\/jats:italic>\n                      mice. At the molecular level, these changes were reversed by global and intestine\u2010specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and\n                      <jats:italic toggle=\"yes\">Mdr2\u2212\/\u2212<\/jats:italic>\n                      mice.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      studies showed that LGG suppressed the inhibitory effect of T\u2010\u03b2MCA on FXR and FGF\u201019 expression in Caco\u20102 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      LGG supplementation decreases hepatic BA by increasing intestinal FXR\u2013FGF\u201015 signaling pathway\u2013mediated suppression of BA\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      synthesis and enhances BA excretion, which prevents excessive BA\u2010induced liver injury and fibrosis in mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.30975","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T02:19:03Z","timestamp":1569896343000},"page":"2050-2066","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":346,"title":["Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis Through Inhibiting Hepatic Bile Acid Synthesis and Enhancing Bile Acid Excretion in Mice"],"prefix":"10.1097","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-5347","authenticated-orcid":false,"given":"Yunhuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Liver Surgery and Liver Transplantation Center,West China Hospital,Sichuan University,Chengdu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Chemistry,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"The First Affiliated Hospital,Xi'an Jiaotong University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirish","family":"Barve","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"},{"name":"Department of Chemistry,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"McClain","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Robley Rex VA Medical Center,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology and Toxicology,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"hep30975-bib-0001-20260126","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/hep.28965","article-title":"The ascending pathophysiology of cholestatic liver disease","volume":"65","year":"2017","journal-title":"Hepatology"},{"key":"hep30975-bib-0002-20260126","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrgastro.2013.151","article-title":"Bile acid receptors as targets for drug development","volume":"11","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep30975-bib-0003-20260126","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1038\/ncomms10713","article-title":"Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis","volume":"7","year":"2016","journal-title":"Nat Commun"},{"key":"hep30975-bib-0004-20260126","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis","volume":"2","year":"2005","journal-title":"Cell Metab"},{"key":"hep30975-bib-0005-20260126","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2011.10.028","article-title":"Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"hep30975-bib-0006-20260126","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/hep.25740","article-title":"Mechanism of tissue\u2010specific farnesoid X receptor in suppressing the expression of genes in bile\u2010acid synthesis in mice","volume":"56","year":"2012","journal-title":"Hepatology"},{"key":"hep30975-bib-0007-20260126","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism","volume":"24","year":"2016","journal-title":"Cell Metab"},{"key":"hep30975-bib-0008-20260126","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut microbiota regulates bile acid metabolism by reducing the levels of tauro\u2010beta\u2010muricholic acid, a naturally occurring FXR antagonist","volume":"17","year":"2013","journal-title":"Cell Metab"},{"key":"hep30975-bib-0009-20260126","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.phrs.2017.08.001","article-title":"Probiotics and antibiotic\u2010associated diarrhea in children: a review and new evidence on Lactobacillus rhamnosus GG during and after antibiotic treatment","volume":"128","year":"2018","journal-title":"Pharmacol Res"},{"key":"hep30975-bib-0010-20260126","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.jnutbio.2013.02.001","article-title":"Lactobacillus rhamnosus GG reduces hepatic TNF\u03b1 production and inflammation in chronic alcohol\u2010induced liver injury","volume":"24","year":"2013","journal-title":"J Nutr Biochem"},{"key":"hep30975-bib-0011-20260126","doi-asserted-by":"crossref","first-page":"702","DOI":"10.20960\/nh.626","article-title":"Lactobacillus rhamnosus GG reduces hepatic fibrosis in a model of chronic liver disease in rats","volume":"34","year":"2017","journal-title":"Nutr Hosp"},{"key":"hep30975-bib-0012-20260126","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0016-5085(99)70461-0","article-title":"Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas","volume":"117","year":"1999","journal-title":"Gastroenterology"},{"key":"hep30975-bib-0013-20260126","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1194\/jlr.M071183","article-title":"Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans","volume":"57","year":"2016","journal-title":"J Lipid Res"},{"key":"hep30975-bib-0014-20260126","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrd2619","article-title":"Targeting bile\u2010acid signalling for metabolic diseases","volume":"7","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"hep30975-bib-0015-20260126","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1126\/science.1072891","article-title":"A natural product that lowers cholesterol as an antagonist ligand for FXR","volume":"296","year":"2002","journal-title":"Science"},{"key":"hep30975-bib-0016-20260126","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1038\/ncomms10166","article-title":"Intestine\u2010selective farnesoid X receptor inhibition improves obesity\u2010related metabolic dysfunction","volume":"6","year":"2015","journal-title":"Nat Commun"},{"key":"hep30975-bib-0017-20260126","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1017\/S1466252316000153","article-title":"Bacterial bile salt hydrolase: an intestinal microbiome target for enhanced animal health","volume":"17","year":"2016","journal-title":"Anim Health Res Rev"},{"key":"hep30975-bib-0018-20260126","doi-asserted-by":"crossref","first-page":"13580","DOI":"10.1073\/pnas.0804437105","article-title":"Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome","volume":"105","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"hep30975-bib-0019-20260126","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/hep.28991","article-title":"New therapeutic concepts in bile acid transport and signaling for management of cholestasis","volume":"65","year":"2017","journal-title":"Hepatology"},{"key":"hep30975-bib-0020-20260126","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jhep.2017.04.026","article-title":"Biliary bile acids in hepatobiliary injury\u2014what is the link?","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"hep30975-bib-0021-20260126","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(15)00154-3","article-title":"Primary biliary cirrhosis","volume":"386","year":"2015","journal-title":"Lancet"},{"issue":"1 Suppl.","key":"hep30975-bib-0022-20260126","first-page":"S25","article-title":"New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond","volume":"62","year":"2015","journal-title":"J Hepatol"},{"key":"hep30975-bib-0023-20260126","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1136\/gutjnl-2017-314553","article-title":"Colesevelam attenuates cholestatic liver and bile duct injury in Mdr2\u2212\/\u2212 mice by modulating composition, signalling and excretion of faecal bile acids","volume":"67","year":"2018","journal-title":"Gut"},{"key":"hep30975-bib-0024-20260126","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.dld.2015.11.003","article-title":"Pediatric parenteral nutrition\u2013associated liver disease and cholestasis: novel advances in pathomechanisms\u2010based prevention and treatment","volume":"48","year":"2016","journal-title":"Dig Liver Dis"},{"key":"hep30975-bib-0025-20260126","doi-asserted-by":"crossref","first-page":"11055","DOI":"10.1074\/jbc.M117.784322","article-title":"Farnesoid X receptor induces Takeda G\u2010protein receptor 5 cross\u2010talk to regulate bile acid synthesis and hepatic metabolism","volume":"292","year":"2017","journal-title":"J Biol Chem"},{"key":"hep30975-bib-0026-20260126","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1194\/jlr.R900010-JLR200","article-title":"Bile acids: regulation of synthesis","volume":"50","year":"2009","journal-title":"J Lipid Res"},{"key":"hep30975-bib-0027-20260126","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jhep.2012.08.002","article-title":"Bile acid transporters and regulatory nuclear receptors in the liver and beyond","volume":"58","year":"2013","journal-title":"J Hepatol"},{"key":"hep30975-bib-0028-20260126","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3389\/fphar.2017.00256","article-title":"SRT1720 alleviates ANIT\u2010induced cholestasis in a mouse model","volume":"8","year":"2017","journal-title":"Front Pharmacol"},{"key":"hep30975-bib-0029-20260126","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11596-018-1861-x","article-title":"Pharmacokinetic characteristics of baicalin in rats with 17alpha\u2010ethynyl\u2010estradiol\u2010induced intrahepatic cholestasis","volume":"38","year":"2018","journal-title":"Curr Med Sci"},{"key":"hep30975-bib-0030-20260126","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1172\/JCI18945","article-title":"Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra\u2010 and extrahepatic cholestasis","volume":"112","year":"2003","journal-title":"J Clin Invest"},{"key":"hep30975-bib-0031-20260126","doi-asserted-by":"crossref","first-page":"G184","DOI":"10.1152\/ajpgi.00215.2001","article-title":"Induction of short heterodimer partner 1 precedes downregulation of Ntcp in bile duct\u2010ligated mice","volume":"282","year":"2002","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"hep30975-bib-0032-20260126","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism","volume":"24","year":"2016","journal-title":"Cell Metab"},{"key":"hep30975-bib-0033-20260126","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nature25010","article-title":"Structures of beta\u2010klotho reveal a \u201czip code\u201d\u2010like mechanism for endocrine FGF signalling","volume":"553","year":"2018","journal-title":"Nature"},{"key":"hep30975-bib-0034-20260126","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/hep.22627","article-title":"Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7\u03b1\u2010hydroxylase gene expression","volume":"49","year":"2009","journal-title":"Hepatology"},{"key":"hep30975-bib-0035-20260126","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/hep.22771","article-title":"High expression of the bile salt\u2010homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis","volume":"49","year":"2009","journal-title":"Hepatology"},{"key":"hep30975-bib-0036-20260126","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/hep.29676","article-title":"Modulation of the intestinal bile acid\/farnesoid X receptor\/fibroblast growth factor 15 axis improves alcoholic liver disease in mice","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep30975-bib-0037-20260126","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000450982","article-title":"Crosstalk between bile acids and gut microbiota and its impact on farnesoid X receptor signalling","volume":"35","year":"2017","journal-title":"Dig Dis"},{"key":"hep30975-bib-0038-20260126","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1128\/AEM.72.3.1729-1738.2006","article-title":"Bile salt hydrolase activity in probiotics","volume":"72","year":"2006","journal-title":"Appl Environ Microbiol"},{"key":"hep30975-bib-0039-20260126","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.celrep.2014.02.032","article-title":"Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr\u2013Fgf15 axis in mice","volume":"7","year":"2014","journal-title":"Cell Rep"},{"key":"hep30975-bib-0040-20260126","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s40168-018-0510-8","article-title":"The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism","volume":"6","year":"2018","journal-title":"Microbiome"},{"key":"hep30975-bib-0041-20260126","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/apt.12695","article-title":"Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis","volume":"39","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"key":"hep30975-bib-0042-20260126","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/hep.22431","article-title":"The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor","volume":"48","year":"2008","journal-title":"Hepatology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.30975","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.30975","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.30975","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:01:24Z","timestamp":1769436084000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.30975","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736694313.793575457","asserted-by":"object"}]},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]},"assertion":[{"value":"2019-04-01","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-22","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}