{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:37:45Z","timestamp":1778733465699,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK102142"],"award-info":[{"award-number":["R01 DK102142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"DOI":"10.1093\/toxsci\/kfz029","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T20:42:52Z","timestamp":1548276172000},"page":"151-166","source":"Crossref","is-referenced-by-count":15,"title":["Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange"],"prefix":"10.1093","volume":"169","author":[{"given":"Ryan C","family":"Kennedy","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew K","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen E P","family":"Ropella","sequence":"additional","affiliation":[{"name":"Tempus Dictum, Inc., Milwaukie, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell R","family":"McGill","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Anthony","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California"},{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"2019042608542194500_kfz029-B1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/hep.20256","article-title":"Connexin 32 dominant\u2010negative mutant transgenic rats are resistant to hepatic damage by chemicals","volume":"40","author":"Asamoto","year":"2004","journal-title":"Hepatology"},{"key":"2019042608542194500_kfz029-B2","doi-asserted-by":"crossref","first-page":"16070","DOI":"10.1038\/s41598-018-34309-7","article-title":"Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice","volume":"8","author":"Cho","year":"2018","journal-title":"Sci. Rep."},{"key":"2019042608542194500_kfz029-B3","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1086\/594538","article-title":"Thinking again about biological mechanisms","volume":"75","author":"Darden","year":"2008","journal-title":"Philos. Sci."},{"key":"2019042608542194500_kfz029-B4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/cdd.2008.196","article-title":"Connexin-related signaling in cell death: To live or let die?","volume":"16","author":"Decrock","year":"2009","journal-title":"Cell Death Differ"},{"issue":"Pt A","key":"2019042608542194500_kfz029-B5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.fct.2017.08.020","article-title":"Induction of mitochondrial biogenesis protects against acetaminophen hepatotoxicity","volume":"108","author":"Du","year":"2017","journal-title":"Food Chem. Toxicol"},{"key":"2019042608542194500_kfz029-B6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.toxlet.2018.11.005","article-title":"Role of extracellular vesicles in release of protein adducts after acetaminophen-induced liver injury in mice and humans","volume":"301","author":"Duan","year":"2019","journal-title":"Toxicol. Lett."},{"key":"2019042608542194500_kfz029-B8","first-page":"322","article-title":"Mode of cell death after acetaminophen overdose in mice: Apoptosis or oncotic necrosis? Toxicol","volume":"67","author":"Gujral","year":"2002","journal-title":"Sci."},{"key":"2019042608542194500_kfz029-B9","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature21065","article-title":"Single-cell spatial reconstruction reveals global division of labour in the mammalian liver","volume":"542","author":"Halpern","year":"2017","journal-title":"Nature"},{"key":"2019042608542194500_kfz029-B10","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1002\/hep.28814","article-title":"Extracellular vesicles in liver pathobiology: Small particles with big impact","volume":"64","author":"Hirsova","year":"2016","journal-title":"Hepatology"},{"key":"2019042608542194500_kfz029-B11","first-page":"365","article-title":"Subtoxic alterations in hepatocyte-derived exosomes: An early step in drug-induced liver injury? Toxicol","volume":"151","author":"Holman","year":"2016","journal-title":"Sci."},{"key":"2019042608542194500_kfz029-B12","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1093\/toxsci\/kfv319","article-title":"Low dose acetaminophen induces reversible mitochondrial dysfunction associated with transient c-Jun N-terminal kinase activation in mouse liver","volume":"150","author":"Hu","year":"2016","journal-title":"Toxicol. Sci."},{"key":"2019042608542194500_kfz029-B13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3390\/pr6050056","article-title":"The spectrum of mechanism-oriented models for explanations of biological phenomena","volume":"6","author":"Hunt","year":"2018","journal-title":"Processes"},{"key":"2019042608542194500_kfz029-B14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/wsbm.1222","article-title":"Agent-based modeling: A systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity","volume":"5","author":"Hunt","year":"2013","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med"},{"key":"2019042608542194500_kfz029-B16","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1007\/s11095-009-9958-3","article-title":"At the biological modeling and simulation frontier","volume":"26","author":"Hunt","year":"2009","journal-title":"Pharm. Res."},{"key":"2019042608542194500_kfz029-B17","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s10928-006-9031-3","article-title":"Physiologically based synthetic models of hepatic disposition","volume":"33","author":"Hunt","year":"2006","journal-title":"J. Pharmacokin. Pharmacodyn."},{"key":"2019042608542194500_kfz029-B18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s13194-011-0038-2","article-title":"What is a mechanism? Thinking about mechanisms across the sciences","volume":"2","author":"Illari","year":"2012","journal-title":"Eur. J. Philos. Sci."},{"key":"2019042608542194500_kfz029-B19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/wsbm.1270","article-title":"Tuneable resolution as a systems biology approach for multi-scale, multicompartment computational models","volume":"6","author":"Kirschner","year":"2014","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med"},{"key":"2019042608542194500_kfz029-B20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.semcdb.2015.03.001","article-title":"Mesenchymal stem cell exosomes","volume":"40","author":"Lai","year":"2015","journal-title":"Semin. Cell Dev. Biol"},{"key":"2019042608542194500_kfz029-B21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nrgastro.2014.7","article-title":"The emerging roles of microvesicles in liver diseases","volume":"11","author":"Lemoinne","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2019042608542194500_kfz029-B22","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1177\/0037549705058073","article-title":"MASON: A multiagent simulation environment","volume":"81","author":"Luke","year":"2005","journal-title":"Simulation"},{"key":"2019042608542194500_kfz029-B23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1057\/jos.2010.3","article-title":"Tutorial on agent-based modelling and simulation","volume":"4","author":"Macal","year":"2010","journal-title":"J. Simul."},{"key":"2019042608542194500_kfz029-B24","first-page":"88","article-title":"Connexin32: A mediator of acetaminophen-induced liver injury? Toxicol","volume":"26","author":"Maes","year":"2016","journal-title":"Mech. Meth."},{"key":"2019042608542194500_kfz029-B25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.toxlet.2017.07.007","article-title":"Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice","volume":"278","author":"Maes","year":"2017","journal-title":"Toxicol. Lett."},{"key":"2019042608542194500_kfz029-B26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1124\/jpet.115.223537","article-title":"A Cytochrome P450\u2013independent mechanism of acetaminophen-induced injury in cultured mouse hepatocytes","volume":"354","author":"Miyakawa","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2019042608542194500_kfz029-B27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/toxsci\/kfx206","article-title":"miR-122 release in exosomes precedes overt tolvaptan-induced necrosis in a primary human hepatocyte micropatterned coculture model","volume":"161","author":"Mosedale","year":"2018","journal-title":"Toxicol. Sci."},{"key":"2019042608542194500_kfz029-B28","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fninf.2018.00018","article-title":"Credibility, replicability, and reproducibility in simulation for biomedicine and clinical applications in neuroscience","volume":"12","author":"Mulugeta","year":"2018","journal-title":"Front. Neuroinform."},{"key":"2019042608542194500_kfz029-B29","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jhep.2016.04.025","article-title":"Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice","volume":"65","author":"Ni","year":"2016","journal-title":"J. Hepatol."},{"key":"2019042608542194500_kfz029-B30","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.redox.2013.08.005","article-title":"Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver","volume":"1","author":"Ni","year":"2013","journal-title":"Redox. Biol."},{"key":"2019042608542194500_kfz029-B31","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1124\/jpet.110.168526","article-title":"Tracing multiscale mechanisms of drug disposition in normal and diseased livers","volume":"334","author":"Park","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2019042608542194500_kfz029-B32","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1124\/jpet.108.142497","article-title":"Computational strategies unravel and trace how liver disease changes hepatic drug disposition","volume":"328","author":"Park","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2019042608542194500_kfz029-B33","first-page":"697","article-title":"Developing a vision for executing scientifically useful virtual biomedical experiments","volume-title":"Proceedings of the 2016 Spring Simulation Multiconference. Society for Computer Simulation International","author":"Petersen","year":"2016"},{"key":"2019042608542194500_kfz029-B34","doi-asserted-by":"crossref","first-page":"e0155855","DOI":"10.1371\/journal.pone.0155855","article-title":"Virtual experiments enable exploring and challenging explanatory mechanisms of immune-mediated P450 down-regulation","volume":"11","author":"Petersen","year":"2016","journal-title":"PLoS One"},{"key":"2019042608542194500_kfz029-B35","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12918-014-0095-1","article-title":"Toward modular biological models: Defining analog modules based on referent physiological mechanisms","volume":"8","author":"Petersen","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"2019042608542194500_kfz029-B36","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biosystems.2006.02.004","article-title":"Formal agent-based modelling of intracellular chemical interactions","volume":"85","author":"Pogson","year":"2006","journal-title":"Biosystems"},{"key":"2019042608542194500_kfz029-B37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cplx.20253","article-title":"Evaluating an hepatic enzyme induction mechanism through coarse\u2010and fine\u2010grained measurements of an in silico liver","volume":"14","author":"Ropella","year":"2009","journal-title":"Complexity"},{"key":"2019042608542194500_kfz029-B38","doi-asserted-by":"crossref","first-page":"5169","DOI":"10.1038\/srep05169","article-title":"Synchronized necrotic death of attached hepatocytes mediated via gap junctions","volume":"4","author":"Saito","year":"2014","journal-title":"Sci. Rep."},{"key":"2019042608542194500_kfz029-B39","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1007\/s00204-018-2271-3","article-title":"Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI","volume":"92","author":"Sezgin","year":"2018","journal-title":"Arch. Toxicol."},{"key":"2019042608542194500_kfz029-B40","doi-asserted-by":"crossref","first-page":"e1005253","DOI":"10.1371\/journal.pcbi.1005253","article-title":"Competing mechanistic hypotheses of acetaminophen-induced hepatotoxicity challenged by virtual experiments","volume":"12","author":"Smith","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"2019042608542194500_kfz029-B41","article-title":"Mechanistic agent-based damage and repair models as hypotheses for patterns of necrosis caused by drug induced liver injury","volume-title":"Proceedings of the 2014 Summer Simulation Multiconference, Jul. 6 (no. 16)","author":"Smith","year":"2014"},{"key":"2019042608542194500_kfz029-B42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1124\/jpet.117.245019","article-title":"A model mechanism-based explanation of an in\u00a0vitro-in\u00a0vivo disconnect for improving extrapolation and translation","volume":"365","author":"Smith","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2019042608542194500_kfz029-B43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrgastro.2017.71","article-title":"Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets","volume":"14","author":"Szabo","year":"2017","journal-title":"Nat. Rev. Gastroent. Hepatol."},{"key":"2019042608542194500_kfz029-B44","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1124\/dmd.117.079244","article-title":"Liver zonation index of drug transporter and metabolizing enzyme protein expressions in mouse liver acinus","volume":"46","author":"Tachikawa","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"2019042608542194500_kfz029-B45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12020-012-9839-0","article-title":"Extracellular vesicles as an emerging mechanism of cell-to-cell communication","volume":"44","author":"Tetta","year":"2013","journal-title":"Endocrine"},{"key":"2019042608542194500_kfz029-B46","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/toxsci\/kfy015","article-title":"Optimized methods to explore the mechanistic and biomarker potential of hepatocyte-derived exosomes in drug-induced liver injury","volume":"163","author":"Thacker","year":"2018","journal-title":"Toxicol. Sci."},{"key":"2019042608542194500_kfz029-B47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcancer.2014.04.009","article-title":"Sorting it out: Regulation of exosome loading","volume":"28","author":"Villarroya-Beltri","year":"2014","journal-title":"Semin. Cancer Biol"},{"key":"2019042608542194500_kfz029-B48","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s11095-007-9494-y","article-title":"Modeling and simulation of hepatic drug disposition using a physiologically based, multi-agent in silico liver","volume":"25","author":"Yan","year":"2008","journal-title":"Pharm. Res."},{"key":"2019042608542194500_kfz029-B49","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1124\/dmd.107.019067","article-title":"Predictions of hepatic disposition properties using a mechanistically realistic, physiologically based model","volume":"36","author":"Yan","year":"2008","journal-title":"Drug. Metab. Disp."}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/169\/1\/151\/28527411\/kfz029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T22:00:09Z","timestamp":1573768809000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/169\/1\/151\/5303845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,29]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1,29]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfz029","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5]]},"published":{"date-parts":[[2019,1,29]]}}}