{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T10:08:00Z","timestamp":1786788480591,"version":"build-2736575974"},"reference-count":94,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.tox.2025.154234","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T23:44:58Z","timestamp":1753919098000},"page":"154234","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Mathematical modelling reveals compound-specific stress pathway activity"],"prefix":"10.1016","volume":"518","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-0774","authenticated-orcid":false,"given":"Elsje J.","family":"Burgers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara Y.","family":"Danilyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju P.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Verlohner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Rocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Ternes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas S.","family":"Wijaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Leist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bouwman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska M.","family":"Zickgraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schildknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"van de Water","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-3087","authenticated-orcid":false,"given":"Joost B.","family":"Beltman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.tox.2025.154234_b1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Autom. Control","ISSN":"https:\/\/id.crossref.org\/issn\/0018-9286","issn-type":"print"},{"issue":"8","key":"10.1016\/j.tox.2025.154234_b2","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1080\/10937404.2023.2261848","article-title":"Drug induced liver injury \u2013 a 2023 update","volume":"26","author":"Allison","year":"2023","journal-title":"J. Toxicol. Environ. Heal. Part B","ISSN":"https:\/\/id.crossref.org\/issn\/1093-7404","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-019-0105-0","article-title":"Drug-induced liver injury","volume":"5","author":"Andrade","year":"2019","journal-title":"Nat. Rev. Dis. Prim.","ISSN":"https:\/\/id.crossref.org\/issn\/2056-676X","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cotox.2018.03.004","article-title":"The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology","volume":"9","author":"Ankley","year":"2018","journal-title":"Curr. Opin. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/2468-2020","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1515\/BC.2009.033","article-title":"Glutathione dysregulation and the etiology and progression of human diseases","volume":"390","author":"Ballatori","year":"2009","journal-title":"Biol. Chem.","ISSN":"https:\/\/id.crossref.org\/issn\/1437-4315","issn-type":"print"},{"issue":"7","key":"10.1016\/j.tox.2025.154234_b6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.cels.2023.06.001","article-title":"Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape","volume":"14","author":"Batjargal","year":"2023","journal-title":"Cell Syst.","ISSN":"https:\/\/id.crossref.org\/issn\/2405-4712","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00204-022-03419-7","article-title":"Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries","volume":"97","author":"Bessone","year":"2023","journal-title":"Arch. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0340-5761","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b8","series-title":"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].","author":"Bethesda","year":"2012"},{"key":"10.1016\/j.tox.2025.154234_b9","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/liv.15892","article-title":"Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA\u2014Update with genetic correlations","volume":"44","author":"Bonkovsky","year":"2024","journal-title":"Liver Int.","ISSN":"https:\/\/id.crossref.org\/issn\/1478-3223","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b10","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/s41467-020-15058-6","article-title":"Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines","volume":"11","author":"Boon","year":"2020","journal-title":"Nat. Commun.","ISSN":"https:\/\/id.crossref.org\/issn\/2041-1723","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b11","series-title":"Model Selection and Multimodel Inference","isbn-type":"print","author":"Burnham","year":"2004","ISBN":"https:\/\/id.crossref.org\/isbn\/0387953647"},{"key":"10.1016\/j.tox.2025.154234_b12","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3389\/fgene.2018.00485","article-title":"A comparison of the TempO-Seq S1500+ platform to RNA-Seq and microarray using rat liver mode of action samples","volume":"9","author":"Bushel","year":"2018","journal-title":"Front. Genet.","ISSN":"https:\/\/id.crossref.org\/issn\/1664-8021","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0005-2728(88)90261-7","article-title":"Mechanism of nitrofurantoin toxicity and oxidative stress in mitochondria","volume":"936","author":"Carbonera","year":"1988","journal-title":"Biochim.et Biophys. Acta (BBA) - Bioenerg.","ISSN":"https:\/\/id.crossref.org\/issn\/0005-2728","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s40264-024-01486-6","article-title":"Incidence of idiosyncratic drug-induced liver injury caused by prescription drugs","volume":"48","author":"Chen","year":"2025","journal-title":"Drug Saf.","ISSN":"https:\/\/id.crossref.org\/issn\/0114-5916","issn-type":"print"},{"issue":"4","key":"10.1016\/j.tox.2025.154234_b15","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jcrc.2008.02.003","article-title":"Equation-based models of dynamic biological systems","volume":"23","author":"Daun","year":"2008","journal-title":"J. Crit. Care","ISSN":"https:\/\/id.crossref.org\/issn\/0883-9441","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0163-7258(91)90029-L","article-title":"Glutathione metabolism and its role in hepatotoxicity","volume":"52","author":"DeLeve","year":"1991","journal-title":"Pharmacol. Ther.","ISSN":"https:\/\/id.crossref.org\/issn\/0163-7258","issn-type":"print"},{"issue":"1\u20132","key":"10.1016\/j.tox.2025.154234_b17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.mam.2008.08.009","article-title":"Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase","volume":"30","author":"Franklin","year":"2009","journal-title":"Mol. Aspects Med.","ISSN":"https:\/\/id.crossref.org\/issn\/0098-2997","issn-type":"print"},{"issue":"12","key":"10.1016\/j.tox.2025.154234_b18","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1080\/14787210.2023.2279104","article-title":"Treating urinary tract infections in the era of antibiotic resistance","volume":"21","author":"Frimodt-M\u00f8ller","year":"2023","journal-title":"Expert. Rev. Anti- Infect. Ther.","ISSN":"https:\/\/id.crossref.org\/issn\/1478-7210","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b19","first-page":"1","article-title":"Cellular stress responses: Cell survival and cell death","volume":"2010","author":"Fulda","year":"2010","journal-title":"Int. J. Cell Biology","ISSN":"https:\/\/id.crossref.org\/issn\/1687-8876","issn-type":"print"},{"issue":"10","key":"10.1016\/j.tox.2025.154234_b20","article-title":"Systematic review of antifungal-induced acute liver failure","volume":"13","author":"Gadour","year":"2021","journal-title":"Cureus","ISSN":"https:\/\/id.crossref.org\/issn\/2168-8184","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b21","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ijcard.2016.08.233","article-title":"Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts","volume":"223","author":"Ghosh","year":"2016","journal-title":"Int. J. Cardiol.","ISSN":"https:\/\/id.crossref.org\/issn\/0167-5273","issn-type":"print"},{"issue":"7","key":"10.1016\/j.tox.2025.154234_b22","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1053\/j.gastro.2015.02.050","article-title":"Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system","volume":"148","author":"Goldberg","year":"2015","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b23","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1124\/dmd.110.035873","article-title":"Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes","volume":"39","author":"Guo","year":"2011","journal-title":"Drug Metab. Dispos.","ISSN":"https:\/\/id.crossref.org\/issn\/0090-9556","issn-type":"print"},{"issue":"4","key":"10.1016\/j.tox.2025.154234_b24","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/1203475415574970","article-title":"The rise and fall of oral ketoconazole","volume":"19","author":"Gupta","year":"2015","journal-title":"J. Cutan. Med. Surg.","ISSN":"https:\/\/id.crossref.org\/issn\/1203-4754","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b25","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00204-020-02937-6","article-title":"Comparing in vitro human liver models to in vivo human liver using RNA-Seq","volume":"95","author":"Gupta","year":"2021","journal-title":"Arch. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0340-5761","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b26","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","article-title":"An integrated stress response regulates amino acid metabolism and resistance to oxidative stress","volume":"11","author":"Harding","year":"2003","journal-title":"Mol. Cell","ISSN":"https:\/\/id.crossref.org\/issn\/1097-2765","issn-type":"print"},{"issue":"13","key":"10.1016\/j.tox.2025.154234_b27","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.3390\/ijms21134777","article-title":"NRF2, a transcription factor for stress response and beyond","volume":"21","author":"He","year":"2020","journal-title":"Int. J. Mol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/1422-0067","issn-type":"print"},{"issue":"7","key":"10.1016\/j.tox.2025.154234_b28","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1010264","article-title":"Model-based translation of DNA damage signaling dynamics across cell types","volume":"18","author":"Heldring","year":"2022","journal-title":"PLoS Comput. Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/1553-7358","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b29","doi-asserted-by":"crossref","first-page":"7336","DOI":"10.1038\/s41598-022-10857-x","article-title":"Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure","volume":"12","author":"Hiemstra","year":"2022","journal-title":"Sci. Rep.","ISSN":"https:\/\/id.crossref.org\/issn\/2045-2322","issn-type":"print"},{"issue":"20","key":"10.1016\/j.tox.2025.154234_b30","doi-asserted-by":"crossref","first-page":"10228","DOI":"10.1093\/nar\/gks827","article-title":"Nrf2\u2013MafG heterodimers contribute globally to antioxidant and metabolic networks","volume":"40","author":"Hirotsu","year":"2012","journal-title":"Nucleic Acids Res.","ISSN":"https:\/\/id.crossref.org\/issn\/1362-4962","issn-type":"print"},{"issue":"9","key":"10.1016\/j.tox.2025.154234_b31","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/jac\/dkv147","article-title":"Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials","volume":"70","author":"Huttner","year":"2015","journal-title":"J. Antimicrob. Chemother.","ISSN":"https:\/\/id.crossref.org\/issn\/0305-7453","issn-type":"print"},{"issue":"D1","key":"10.1016\/j.tox.2025.154234_b32","doi-asserted-by":"crossref","first-page":"D921","DOI":"10.1093\/nar\/gku955","article-title":"Open TG-GATEs: a large-scale toxicogenomics database","volume":"43","author":"Igarashi","year":"2015","journal-title":"Nucleic Acids Res.","ISSN":"https:\/\/id.crossref.org\/issn\/1362-4962","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b33","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2020.00033","article-title":"Is it time to start transitioning from 2D to 3D cell culture?","volume":"7","author":"Jensen","year":"2020","journal-title":"Front. Mol. Biosci.","ISSN":"https:\/\/id.crossref.org\/issn\/2296-889X","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b34","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3390\/ijms18030621","article-title":"Revisiting the metabolism and bioactivation of ketoconazole in human and mouse using liquid chromatography\u2013mass spectrometry-based metabolomics","volume":"18","author":"Kim","year":"2017","journal-title":"Int. J. Mol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/1422-0067","issn-type":"print"},{"issue":"20","key":"10.1016\/j.tox.2025.154234_b35","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.3390\/ijms20205179","article-title":"Mathematical modeling of p53 pathways","volume":"20","author":"Kim","year":"2019","journal-title":"Int. J. Mol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/1422-0067","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3390\/antiox13010017","article-title":"Mitochondrial H2O2 is a central mediator of diclofenac-induced hepatocellular injury","volume":"13","author":"Kim","year":"2024","journal-title":"Antioxidants","ISSN":"https:\/\/id.crossref.org\/issn\/2076-3921","issn-type":"print"},{"issue":"S3","key":"10.1016\/j.tox.2025.154234_b37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/em.22636","article-title":"AOP report: Development of an adverse outcome pathway for deposition of energy leading to abnormal vascular remodeling","volume":"65","author":"Kozbenko","year":"2024","journal-title":"Environ. Mol. Mutagen.","ISSN":"https:\/\/id.crossref.org\/issn\/0893-6692","issn-type":"print"},{"issue":"7","key":"10.1016\/j.tox.2025.154234_b38","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112724","article-title":"The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2","volume":"42","author":"Kre\u00df","year":"2023","journal-title":"Cell Rep.","ISSN":"https:\/\/id.crossref.org\/issn\/2211-1247","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/17425255.2017.1234607","article-title":"Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling","volume":"13","author":"Kuijper","year":"2017","journal-title":"Expert. Opin. Drug Metab. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/1742-5255","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b40","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1124\/jpet.102.038992","article-title":"Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: Role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide","volume":"303","author":"Kumar","year":"2002","journal-title":"J. Pharmacol. Exp. Ther.","ISSN":"https:\/\/id.crossref.org\/issn\/0022-3565","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0041-008X(86)90254-1","article-title":"Nitrofurantoin inhibition of mouse liver mitochondrial respiration involving NAD-linked substrates","volume":"84","author":"Lim","year":"1986","journal-title":"Toxicol. Appl. Pharmacol.","ISSN":"https:\/\/id.crossref.org\/issn\/0041-008X","issn-type":"print"},{"issue":"12","key":"10.1016\/j.tox.2025.154234_b42","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3390\/toxics10120788","article-title":"Applications of in silico models to predict drug-induced liver injury","volume":"10","author":"Lin","year":"2022","journal-title":"Toxics","ISSN":"https:\/\/id.crossref.org\/issn\/2305-6304","issn-type":"print"},{"issue":"12","key":"10.1016\/j.tox.2025.154234_b43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biology","ISSN":"https:\/\/id.crossref.org\/issn\/1474-760X","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b44","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim.et Biophys. Acta (BBA) - Gen. Subj.","ISSN":"https:\/\/id.crossref.org\/issn\/0304-4165","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b45","doi-asserted-by":"crossref","first-page":"342","DOI":"10.46747\/cfp.6705342","article-title":"Nitrofurantoin-induced liver failure","volume":"67","author":"Luk","year":"2021","journal-title":"Can. Fam. Physician","ISSN":"https:\/\/id.crossref.org\/issn\/0008-350X","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b46","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1021\/tx700419d","article-title":"Bioactivation of diclofenac in vitro and in vivo: Correlation to electrochemical studies","volume":"21","author":"Madsen","year":"2008","journal-title":"Chem. Res. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0893-228X","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b47","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1006\/abbi.2001.2670","article-title":"Revisiting the interaction of the radical anion metabolite of nitrofurantoin with glutathione","volume":"397","author":"Miller","year":"2002","journal-title":"Arch. Biochem. Biophys.","ISSN":"https:\/\/id.crossref.org\/issn\/0003-9861","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b48","series-title":"CRAN: Contributed Packages","article-title":"BiocManager: Access the Bioconductor Project Package Repository","author":"Morgan","year":"2018"},{"issue":"January","key":"10.1016\/j.tox.2025.154234_b49","first-page":"1","article-title":"Computational models for predicting liver toxicity in the deep learning era","volume":"5","author":"Mostafa","year":"2024","journal-title":"Front. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/2673-3080","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b50","doi-asserted-by":"crossref","first-page":"466","DOI":"10.4049\/jimmunol.182.1.466","article-title":"CHAC1\/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade","volume":"182","author":"Mungrue","year":"2009","journal-title":"J. Immunol.","ISSN":"https:\/\/id.crossref.org\/issn\/0022-1767","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b51","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2023.1112253","article-title":"A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response","volume":"16","author":"Neill","year":"2023","journal-title":"Front. Mol. Neurosci.","ISSN":"https:\/\/id.crossref.org\/issn\/1662-5099","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b52","doi-asserted-by":"crossref","DOI":"10.1289\/EHP11891","article-title":"Mapping interindividual variability of toxicodynamics using high-throughput transcriptomics and primary human hepatocytes from fifty donors","volume":"132","author":"Niemeijer","year":"2024","journal-title":"Environ. Health Perspect.","ISSN":"https:\/\/id.crossref.org\/issn\/0091-6765","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b53","doi-asserted-by":"crossref","first-page":"28016","DOI":"10.1038\/srep28016","article-title":"Translational and post-translational regulation of mouse cation transport regulator homolog 1","volume":"6","author":"Nomura","year":"2016","journal-title":"Sci. Rep.","ISSN":"https:\/\/id.crossref.org\/issn\/2045-2322","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b54","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.2517-6161.1992.tb01895.x","article-title":"A central limit theorem for latin hypercube sampling","volume":"54","author":"Owen","year":"1992","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol.","ISSN":"https:\/\/id.crossref.org\/issn\/1369-7412","issn-type":"print"},{"issue":"10","key":"10.1016\/j.tox.2025.154234_b55","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Pakos Zebrucka","year":"2016","journal-title":"EMBO Rep.","ISSN":"https:\/\/id.crossref.org\/issn\/1469-221X","issn-type":"print"},{"issue":"13","key":"10.1016\/j.tox.2025.154234_b56","doi-asserted-by":"crossref","first-page":"10939","DOI":"10.1074\/jbc.M110.216093","article-title":"Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation","volume":"286","author":"Palam","year":"2011","journal-title":"J. Biol. Chem.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"1\u20132","key":"10.1016\/j.tox.2025.154234_b57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mam.2009.01.001","article-title":"Role of nuclear glutathione as a key regulator of cell proliferation","volume":"30","author":"Pallard\u00f3","year":"2009","journal-title":"Mol. Aspects Med.","ISSN":"https:\/\/id.crossref.org\/issn\/0098-2997","issn-type":"print"},{"issue":"12","key":"10.1016\/j.tox.2025.154234_b58","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1021\/acs.molpharmaceut.7b00406","article-title":"Model-based analysis of biopharmaceutic experiments to improve mechanistic oral absorption modeling: An integrated in vitro in vivo extrapolation perspective using ketoconazole as a model drug","volume":"14","author":"Pathak","year":"2017","journal-title":"Mol. Pharm.","ISSN":"https:\/\/id.crossref.org\/issn\/1543-8384","issn-type":"print"},{"issue":"9","key":"10.1016\/j.tox.2025.154234_b59","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1002\/etc.4505","article-title":"Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment","volume":"38","author":"Perkins","year":"2019","journal-title":"Environ. Toxicol. Chem.","ISSN":"https:\/\/id.crossref.org\/issn\/0730-7268","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b60","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2021.105133","article-title":"Effective exposure of chemicals in in vitro cell systems: A review of chemical distribution models","volume":"73","author":"Proen\u00e7a","year":"2021","journal-title":"Toxicol. Vitr.","ISSN":"https:\/\/id.crossref.org\/issn\/0887-2333","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b61","series-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2024"},{"issue":"9","key":"10.1016\/j.tox.2025.154234_b62","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0074335","article-title":"Lessons learned from quantitative dynamical modeling in systems biology","volume":"8","author":"Raue","year":"2013","journal-title":"PLoS ONE","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b63","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fcell.2016.00041","article-title":"Customized steady-state constraints for parameter estimation in non-linear ordinary differential equation models","volume":"4","author":"Rosenblatt","year":"2016","journal-title":"Front. Cell Dev. Biology","ISSN":"https:\/\/id.crossref.org\/issn\/2296-634X","issn-type":"print"},{"issue":"S3","key":"10.1016\/j.tox.2025.154234_b64","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/em.22631","article-title":"AOP Report: Development of an adverse outcome pathway for deposition of energy leading to bone loss","volume":"65","author":"Sandhu","year":"2024","journal-title":"Environ. Mol. Mutagen.","ISSN":"https:\/\/id.crossref.org\/issn\/0893-6692","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b65","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cbi.2012.05.006","article-title":"Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action","volume":"199","author":"Sandoval-Acu\u00f1a","year":"2012","journal-title":"Chem. Biol. Interact.","ISSN":"https:\/\/id.crossref.org\/issn\/0009-2797","issn-type":"print"},{"issue":"4","key":"10.1016\/j.tox.2025.154234_b66","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.jhep.2022.06.022","article-title":"2D and 3D liver models","volume":"78","author":"Saxton","year":"2023","journal-title":"J. Hepatol.","ISSN":"https:\/\/id.crossref.org\/issn\/0168-8278","issn-type":"print"},{"issue":"11","key":"10.1016\/j.tox.2025.154234_b67","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res.","ISSN":"https:\/\/id.crossref.org\/issn\/1088-9051","issn-type":"print"},{"issue":"9","key":"10.1016\/j.tox.2025.154234_b68","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.3390\/pharmaceutics15092199","article-title":"Development of a physiologically based pharmacokinetic model for nitrofurantoin in rabbits, rats, and humans","volume":"15","author":"Sharma","year":"2023","journal-title":"Pharmaceutics","ISSN":"https:\/\/id.crossref.org\/issn\/1999-4923","issn-type":"print"},{"issue":"10","key":"10.1016\/j.tox.2025.154234_b69","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1007\/s00204-021-03127-8","article-title":"Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages","volume":"95","author":"Snijders","year":"2021","journal-title":"Arch. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0340-5761","issn-type":"print"},{"issue":"9","key":"10.1016\/j.tox.2025.154234_b70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i09","article-title":"Solving differential equations in R: Package desolve","volume":"33","author":"Soetaert","year":"2010","journal-title":"J. Stat. Softw.","ISSN":"https:\/\/id.crossref.org\/issn\/1548-7660","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b71","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2024.1458716","article-title":"CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers","volume":"12","author":"Sun","year":"2024","journal-title":"Front. Cell Dev. Biology","ISSN":"https:\/\/id.crossref.org\/issn\/2296-634X","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b72","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.tiv.2015.11.020","article-title":"Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI)","volume":"31","author":"Syed","year":"2016","journal-title":"Toxicol. Vitr.","ISSN":"https:\/\/id.crossref.org\/issn\/0887-2333","issn-type":"print"},{"issue":"4","key":"10.1016\/j.tox.2025.154234_b73","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2174\/1389200033489398","article-title":"The metabolism of diclofenac - enzymology and toxicology perspectives","volume":"4","author":"Tang","year":"2003","journal-title":"Curr. Drug Metab.","ISSN":"https:\/\/id.crossref.org\/issn\/1389-2002","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b74","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41540-018-0062-3","article-title":"Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations","volume":"4","author":"Thiel","year":"2018","journal-title":"Npj Syst. Biology Appl.","ISSN":"https:\/\/id.crossref.org\/issn\/2056-7189","issn-type":"print"},{"issue":"January","key":"10.1016\/j.tox.2025.154234_b75","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.lfs.2018.05.002","article-title":"Eukaryotic cell survival mechanisms: Disease relevance and therapeutic intervention","volume":"205","author":"Twayana","year":"2018","journal-title":"Life Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/0024-3205","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b76","first-page":"133","article-title":"Mechanisms of idiosyncratic drug-induced liver injury","volume":"vol. 85","author":"Uetrecht","year":"2019"},{"key":"10.1016\/j.tox.2025.154234_b77","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2022.105143","article-title":"R-ODAF: Omics data analysis framework for regulatory application","volume":"131","author":"Verheijen","year":"2022","journal-title":"RTP","ISSN":"https:\/\/id.crossref.org\/issn\/0273-2300","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b78","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nature Methods","ISSN":"https:\/\/id.crossref.org\/issn\/1548-7091","issn-type":"print"},{"issue":"6","key":"10.1016\/j.tox.2025.154234_b79","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/clpt.2011.63","article-title":"Drug safety sciences and the bottleneck in drug development","volume":"89","author":"Watkins","year":"2011","journal-title":"Clin. Pharmacol. Ther.","ISSN":"https:\/\/id.crossref.org\/issn\/0009-9236","issn-type":"print"},{"issue":"11","key":"10.1016\/j.tox.2025.154234_b80","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.3390\/ijms23116049","article-title":"Challenges and future of drug-induced liver injury research\u2014Laboratory tests","volume":"23","author":"Weber","year":"2022","journal-title":"Int. J. Mol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/1422-0067","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b81","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00204-016-1686-y","article-title":"Characterization of chemical-induced sterile inflammation in vitro: application of the model compound ketoconazole in a human hepatic co-culture system","volume":"91","author":"Wewering","year":"2017","journal-title":"Arch. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0340-5761","issn-type":"print"},{"issue":"43","key":"10.1016\/j.tox.2025.154234_b82","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw.","ISSN":"https:\/\/id.crossref.org\/issn\/2475-9066","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/toxsci\/kfad121","article-title":"A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury","volume":"198","author":"Wijaya","year":"2024","journal-title":"Toxicol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/1096-6080","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b84","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s10565-021-09610-3","article-title":"Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes","volume":"38","author":"Wijaya","year":"2022","journal-title":"Cell Biol. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0742-2091","issn-type":"print"},{"issue":"May","key":"10.1016\/j.tox.2025.154234_b85","article-title":"Integration of temporal single cell cellular stress response activity with logic-ODE modeling reveals activation of ATF4-CHOP axis as a critical predictor of drug-induced liver injury","volume":"190","author":"Wijaya","year":"2021","journal-title":"Biochem. Pharmacol.","ISSN":"https:\/\/id.crossref.org\/issn\/0006-2952","issn-type":"print"},{"issue":"47","key":"10.1016\/j.tox.2025.154234_b86","doi-asserted-by":"crossref","first-page":"33627","DOI":"10.1074\/jbc.274.47.33627","article-title":"Regulation of \u03b3-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2","volume":"274","author":"Wild","year":"1999","journal-title":"J. Biol. Chem.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b87","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1007\/s00204-018-2178-z","article-title":"Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury","volume":"92","author":"Wink","year":"2018","journal-title":"Arch. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0340-5761","issn-type":"print"},{"issue":"11","key":"10.1016\/j.tox.2025.154234_b88","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.tem.2017.07.003","article-title":"Surviving stress: Modulation of ATF4-mediated stress responses in normal and malignant cells","volume":"28","author":"Wortel","year":"2017","journal-title":"Trends Endocrinol. Metab.","ISSN":"https:\/\/id.crossref.org\/issn\/1043-2760","issn-type":"print"},{"issue":"3","key":"10.1016\/j.tox.2025.154234_b89","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev.","ISSN":"https:\/\/id.crossref.org\/issn\/0031-9333","issn-type":"print"},{"issue":"2","key":"10.1016\/j.tox.2025.154234_b90","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.100860","article-title":"ATF6 is a critical determinant of CHOP dynamics during the unfolded protein response","volume":"23","author":"Yang","year":"2020","journal-title":"IScience","ISSN":"https:\/\/id.crossref.org\/issn\/2589-0042","issn-type":"print"},{"key":"10.1016\/j.tox.2025.154234_b91","article-title":"Dynamic modeling of mitochondrial membrane potential upon exposure to mitochondrial inhibitors","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol.","ISSN":"https:\/\/id.crossref.org\/issn\/1663-9812","issn-type":"print"},{"issue":"5","key":"10.1016\/j.tox.2025.154234_b92","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178302","article-title":"A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling","volume":"12","author":"Yeakley","year":"2017","journal-title":"PLOS ONE","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"issue":"1","key":"10.1016\/j.tox.2025.154234_b93","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-pharmtox-030220-015007","article-title":"Models of idiosyncratic drug-induced liver injury","volume":"61","author":"Yokoi","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0362-1642","issn-type":"print"},{"issue":"4","key":"10.1016\/j.tox.2025.154234_b94","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cld.2013.07.002","article-title":"Mechanisms of drug-induced liver injury","volume":"17","author":"Yuan","year":"2013","journal-title":"Clin. Liver Dis.","ISSN":"https:\/\/id.crossref.org\/issn\/1089-3261","issn-type":"print"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25001933?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25001933?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T05:08:51Z","timestamp":1760591331000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X25001933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":94,"alternative-id":["S0300483X25001933"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2025.154234","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mathematical modelling reveals compound-specific stress pathway activity","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2025.154234","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"154234"}}