{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:43:10Z","timestamp":1777502590315,"version":"3.51.4"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Liver malignant tumors (LMTs) represent a serious adverse drug event associated with drug-induced liver injury. Increases in endocrine-disrupting chemicals (EDCs) have attracted attention in recent years, due to their liver function-inhibiting abilities. Exposure to EDCs can induce nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which are major etiologies of LMTs, through interaction with nuclear receptors (NR) and stress response pathways (SRs). Therefore, exposure to potential EDC drugs could be associated with drug-induced LMTs. However, the drug classes associated with LMTs and the molecular initiating events (MIEs) that are specific to these drugs are not well understood. In this study, using the Food and Drug Administration Adverse Event Reporting System, we detected LMT-inducing drug signals based on adjusted odds ratios. Furthermore, based on the hypothesis that drug-induced LMTs are triggered by NR and SR modulation of potential EDCs, we used the quantitative structure\u2013activity relationship platform for toxicity prediction to identify potential MIEs that are specific to LMT-inducing drug classes. Events related to cell proliferation and apoptosis, DNA damage, and lipid accumulation were identified as potential MIEs, and their relevance to LMTs was supported by the literature. The findings of this study may contribute to drug development and research, as well as regulatory decision making.<\/jats:p>","DOI":"10.3390\/biom11070944","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Initiating Events Associated with Drug-Induced Liver Malignant Tumors: An Integrated Study of the FDA Adverse Event Reporting System and Toxicity Predictions"],"prefix":"10.3390","volume":"11","author":[{"given":"Kota","family":"Kurosaki","sequence":"first","affiliation":[{"name":"Department of Medical Molecular Informatics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-991X","authenticated-orcid":false,"given":"Yoshihiro","family":"Uesawa","sequence":"additional","affiliation":[{"name":"Department of Medical Molecular Informatics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12916-016-0553-2","article-title":"Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: A systematic review of the world literature","volume":"14","author":"Onakpoya","year":"2016","journal-title":"BMC Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Acute Liver Failure Study Group. Drug-induced acute liver failure: Results of a U.S. multicenter, prospective study","volume":"52","author":"Reuben","year":"2010","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Katarey, D., and Verma, S. (2016). Drug-induced liver injury. Clin. Med., 104\u2013109.","DOI":"10.7861\/clinmedicine.16-6-s104"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41575-018-0055-0","article-title":"The changing epidemiology of liver diseases in the Asia-Pacific region","volume":"16","author":"Wong","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.14701\/ahbps.2019.23.2.174","article-title":"Hepatocellular carcinoma in body builders; an emerging rare but serious complication of androgenic anabolic steroid use","volume":"23","author":"Woodward","year":"2019","journal-title":"Ann. Hepato-Biliary-Pancreat. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hardt, A., Stippel, D., Odenthal, M., H\u00f6lscher, A.H., Dienes, H.P., and Drebber, U. (2012). Development of hepatocellular carcinoma associated with anabolic androgenic steroid abuse in a young bodybuilder: A case report. Case Rep. Pathol.","DOI":"10.1155\/2012\/195607"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Solbach, P., Potthoff, A., Raatschen, H.J., Soudah, B., Lehmann, U., Schneider, A., Gebel, M.J., Manns, M.P., and Vogel, A. (2015). Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: A case report. BMC Gastroenterol., 60.","DOI":"10.1186\/s12876-015-0288-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1477-2574.2010.00222.x","article-title":"Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: A systematic review including more than 1600 adenoma cases","volume":"12","author":"Stoot","year":"2010","journal-title":"HPB"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-disrupting chemicals: An Endocrine Society scientific statement","volume":"30","author":"Bourguignon","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/jbt.10089","article-title":"Effects of endocrine disrupting chemicals on distinct expression patterns of estrogen receptor, cytochrome P450 aromatase and p53 genes in oryzias latipes liver","volume":"17","author":"Min","year":"2003","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrendo.2017.42","article-title":"Endocrine-disrupting chemicals and fatty liver disease","volume":"13","author":"Foulds","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8543763","DOI":"10.1155\/2018\/8543763","article-title":"Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma","volume":"2018","author":"Kutlu","year":"2018","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/etc.34","article-title":"Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment","volume":"29","author":"Ankley","year":"2010","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1021\/tx500345j","article-title":"Defining molecular initiating events in the adverse outcome pathway framework for risk assessment","volume":"27","author":"Allen","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1021\/acs.jcim.8b00297","article-title":"QSAR Modeling of ToxCast Assays Relevant to the Molecular Initiating Events of AOPs Leading to Hepatic Steatosis","volume":"58","author":"Gadaleta","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"ref_16","first-page":"73","article-title":"Replacement, reduction and refinement","volume":"19","author":"Flecknell","year":"2002","journal-title":"Altex"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2146\/ajhp170529","article-title":"Signal detection for bleeding associated with the use of direct oral anticoagulants","volume":"75","author":"Nathan","year":"2018","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/CAD.0000000000000862","article-title":"Tumor lysis syndrome associated with bortezomib: A post-hoc analysis after signal detection using the US Food and Drug Administration Adverse Event Reporting System","volume":"31","author":"Sanagawa","year":"2020","journal-title":"Anticancer Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kurosaki, K., Wu, R., and Uesawa, Y. (2020). A toxicity prediction tool for potential agonist\/antagonist activities in molecular initiating events based on chemical structures. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217853"},{"key":"ref_20","unstructured":"(2021, May 24). FDA Adverse Event Reporting System (FAERS), Available online: https:\/\/www.fda.gov\/drugs\/drug-approvals-and-databases\/fda-adverse-event-reporting-system-faers."},{"key":"ref_21","unstructured":"(2021, May 24). Multidisciplinary Guidelines. Available online: https:\/\/www.ich.org\/page\/multidisciplinary-guidelines."},{"key":"ref_22","unstructured":"(2021, May 24). WHO Drug Global. Available online: https:\/\/www.who-umc.org\/whodrug\/whodrug-portfolio\/whodrug-global\/."},{"key":"ref_23","unstructured":"(2021, May 24). FDA Adverse Event Reporting System (FAERS): Latest Quarterly Data Files, Available online: https:\/\/www.fda.gov\/drugs\/questions-and-answers-fdas-adverse-event-reporting-system-faers\/fda-adverse-event-reporting-system-faers-latest-quarterly-data-files."},{"key":"ref_24","unstructured":"(2021, May 24). Standardised MedDRA Queries. Available online: https:\/\/www.meddra.org\/standardised-meddra-queries."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s11096-020-01018-z","article-title":"Aromatase inhibitors associated osteonecrosis of jaw: Signal refining to identify pseudo safety signals","volume":"42","author":"Neha","year":"2020","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1038\/bmt.2017.158","article-title":"Association between GvHD and nivolumab in the FDA adverse event reporting system","volume":"52","author":"Oshima","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1248\/yakushi.17-00162","article-title":"Evaluation of the association between topical prostaglandin F2\u03b1 analogs and asthma using the JADER database: Comparison with \u03b2-blockers","volume":"138","author":"Ohyama","year":"2018","journal-title":"Yakugaku Zasshi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.5691\/jjb.25.37","article-title":"Early detection of important safety information","volume":"25","author":"Watanabe","year":"2004","journal-title":"Jpn. J. Biomet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/gb-2003-4-4-210","article-title":"Statistical tests for differential expression in cDNA microarray experiments","volume":"4","author":"Cui","year":"2003","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Toriumi, S., Kobayashi, A., and Uesawa, Y. (2020). Comprehensive study of the risk factors for medication-related osteonecrosis of the jaw based on the Japanese adverse drug event report database. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120467"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Okunaka, M., Kano, D., Matsui, R., Kawasaki, T., and Uesawa, Y. (2021). Evaluation of the expression profile of irinotecan-induced diarrhea in patients with colorectal cancer. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040377"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9625","DOI":"10.1038\/s41598-021-88958-2","article-title":"Evaluation of antibiotic-induced taste and smell disorders using the FDA adverse event reporting system database","volume":"11","author":"Kan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e0172057","DOI":"10.1371\/journal.pone.0172057","article-title":"Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database","volume":"12","author":"Hosoya","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1056\/NEJMoa1306218","article-title":"Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection","volume":"370","author":"Sulkowski","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","article-title":"Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals","volume":"65","author":"Conti","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.jhep.2016.06.009","article-title":"Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment","volume":"65","author":"Kozbial","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/bimj.200410135","article-title":"Estimation of the Youden Index and its Associated Cutoff Point","volume":"47","author":"Fluss","year":"2005","journal-title":"Biom. J."},{"key":"ref_38","unstructured":"(2021, May 24). Drug Induced Liver Injury Rank (DILIrank) Dataset, Available online: https:\/\/www.fda.gov\/science-research\/liver-toxicity-knowledge-base-ltkb\/drug-induced-liver-injury-rank-dilirank-dataset."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.drudis.2019.09.022","article-title":"Drug-induced liver injury severity and toxicity (DILIst): Binary classification of 1279 drugs by human hepatotoxicity","volume":"25","author":"Thakkar","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_40","unstructured":"(2021, May 24). ATC\/DDD Index 2021. Available online: https:\/\/www.whocc.no\/atc_ddd_index\/."},{"key":"ref_41","unstructured":"(2021, May 24). The Anatomical Therapeutic Chemical Classification System with Defined Daily Doses (ATC\/DDD). Available online: https:\/\/www.who.int\/standards\/classifications\/other-classifications\/the-anatomical-therapeutic-chemical-classification-system-with-defined-daily-doses."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/BF01719664","article-title":"Drug data coding and analysis in epidemiologic studies","volume":"10","author":"Pahor","year":"1994","journal-title":"Eur. J. Epidemiol."},{"key":"ref_43","first-page":"138","article-title":"Classification of drugs using the ATC system (Anatomic, Therapeutic, Chemical Classification) and the latest changes","volume":"58","author":"Skrbo","year":"2004","journal-title":"Med. Arh."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6638306","DOI":"10.1155\/2020\/6638306","article-title":"Nonalcoholic fatty liver disease and type 2 diabetes mellitus: A bidirectional relationship","volume":"2020","author":"Muzica","year":"2020","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s40264-020-00975-8","article-title":"Liver Injury with Ulipristal Acetate: Exploring the Underlying Pharmacological Basis","volume":"43","author":"Gatti","year":"2020","journal-title":"Drug Saf."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1345\/aph.18172","article-title":"Quinine-induced hepatotoxicity","volume":"33","author":"Farver","year":"1999","journal-title":"Ann. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Friedrich, M.E., Akimova, E., Huf, W., Konstantinidis, A., Papageorgiou, K., Winkler, D., Toto, S., Greil, W., Grohmann, R., and Kasper, S. (2016). Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program. Int. J. Neuropsychopharmacol., 19.","DOI":"10.1093\/ijnp\/pyv126"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1176\/appi.ajp.2013.13050709","article-title":"Antidepressant-induced liver injury: A review for clinicians","volume":"171","author":"Voican","year":"2014","journal-title":"Am. J. Psychiatry"},{"key":"ref_49","first-page":"465","article-title":"Drug-Induced Liver Injury Caused by Telotristat Etiprate","volume":"10","author":"Geboes","year":"2020","journal-title":"J. Clin. Toxicol."},{"key":"ref_50","unstructured":"(2012). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet], National Institute of Diabetes and Digestive and Kidney Diseases. Telotristat. 2019."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.jhep.2016.07.027","article-title":"High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis","volume":"65","author":"Cardoso","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Villani, R., Vendemiale, G., and Serviddio, G. (2018). Molecular mechanisms involved in HCC recurrence after direct-acting antiviral therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010049"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/jvh.12726","article-title":"The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C-infected patients treated with direct-acting antivirals with and without pegylated interferon: A Belgian experience","volume":"24","author":"Bielen","year":"2017","journal-title":"J. Viral Hepat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-981-10-5765-6_2","article-title":"Hepatitis B virus-associated hepatocellular carcinoma","volume":"1018","author":"Xie","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: Current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1093\/aje\/kws377","article-title":"On a closed-form doubly robust estimator of the adjusted odds ratio for a binary exposure","volume":"177","author":"Tchetgen","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jogn.2019.12.004","article-title":"Effects of delayed newborn bathing on breastfeeding, hypothermia, and hypoglycemia","volume":"49","author":"Warren","year":"2020","journal-title":"J. Obstet. Gynecol. Neonatal Nurs."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s12253-016-0136-8","article-title":"E2\/ER\u03b2 inhibits PPAR\u03b1 to regulate cell-proliferation and enhance apoptosis in Hep3B-hepatocellular carcinoma","volume":"23","author":"Hsu","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1177\/0300060519871373","article-title":"Molecular mechanisms of estrogen receptor \u03b2-induced apoptosis and autophagy in tumors: Implication for treating osteosarcoma","volume":"47","author":"Yang","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"bqaa134","DOI":"10.1210\/endocr\/bqaa134","article-title":"NAFLD and NASH in postmenopausal women: Implications for diagnosis and treatment","volume":"161","author":"DiStefano","year":"2020","journal-title":"Endocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1177\/1535370216688569","article-title":"An estrogen receptor \u03b2-selective agonist inhibits non-alcoholic steatohepatitis in preclinical models by regulating bile acid and xenobiotic receptors","volume":"242","author":"Ponnusamy","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_62","unstructured":"(2021, May 24). qHTS Assay to Identify Small Molecule Agonists of the Estrogen Related Receptor (ERR) Signaling Pathway from Tox21 Library: Summary, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/bioassay\/1259404."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2147\/CMAR.S35024","article-title":"Novel drugs that target the estrogen-related receptor alpha: Their therapeutic potential in breast cancer","volume":"6","author":"May","year":"2014","journal-title":"Cancer Manag. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1073\/pnas.1114278109","article-title":"High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death","volume":"109","author":"Fox","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"30","DOI":"10.7150\/ijbs.12310","article-title":"Hepatitis B virus X protein upregulates hELG1\/ ATAD5 expression through E2F1 in hepatocellular carcinoma","volume":"12","author":"Ghosh","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.3748\/wjg.v26.i38.5812","article-title":"Is vitamin D receptor a druggable target for non-alcoholic steatohepatitis?","volume":"26","author":"Cao","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3389\/fendo.2019.00532","article-title":"The role of thyroid hormones in hepatocyte proliferation and liver cancer","volume":"10","author":"Gionfra","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1001\/archinternmed.2011.89","article-title":"The FDA drug safety surveillance program: Adverse event reporting trends","volume":"171","author":"Deshpande","year":"2011","journal-title":"Arch. Intern. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:04Z","timestamp":1760163844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11070944"],"URL":"https:\/\/doi.org\/10.3390\/biom11070944","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]}}}