{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:09:40Z","timestamp":1780625380062,"version":"3.54.1"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journalofsurgicalresearch.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Surgical Research"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.jss.2021.03.025","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:47:28Z","timestamp":1620780448000},"page":"125-141","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose"],"prefix":"10.1016","volume":"266","author":[{"given":"Umar F.","family":"Bhatti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7837-7110","authenticated-orcid":false,"given":"Henriette","family":"Remmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-7904","authenticated-orcid":false,"given":"Ben E.","family":"Biesterveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Wakam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kemp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-7683","authenticated-orcid":false,"given":"Rebecca","family":"Tagett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan B.","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jss.2021.03.025_bib0001","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.injury.2008.10.007","article-title":"Exsanguination in trauma: a review of diagnostics and treatment options","volume":"40","author":"Geeraedts","year":"2009","journal-title":"Injury"},{"key":"10.1016\/j.jss.2021.03.025_bib0002","doi-asserted-by":"crossref","DOI":"10.1186\/cc10096","article-title":"The acute management of trauma hemorrhage: a systematic review of randomized controlled trials","volume":"15","author":"Curry","year":"2011","journal-title":"Crit Care"},{"key":"10.1016\/j.jss.2021.03.025_bib0003","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S1072-7515(98)00082-9","article-title":"Lethal injuries and time to death in a level I trauma center","volume":"186","author":"Acosta","year":"1998","journal-title":"J Am Coll Surg"},{"key":"10.1016\/j.jss.2021.03.025_bib0004","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.surg.2008.03.037","article-title":"Cell protective mechanism of valproic acid in lethal hemorrhagic shock","volume":"144","author":"Li","year":"2008","journal-title":"Surgery"},{"key":"10.1016\/j.jss.2021.03.025_bib0005","doi-asserted-by":"crossref","DOI":"10.1136\/tsaco-2019-000321","article-title":"Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock","volume":"4","author":"Bhatti","year":"2019","journal-title":"Trauma surgery & acute care open"},{"key":"10.1016\/j.jss.2021.03.025_bib0006","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1038\/sj.onc.1210599","article-title":"HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention","volume":"26","author":"Yang","year":"2007","journal-title":"Oncogene"},{"key":"10.1016\/j.jss.2021.03.025_bib0007","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0300-9572(02)00095-3","article-title":"cDNA array analysis of gene expression following hemorrhagic shock and resuscitation in rats","volume":"54","author":"Alam","year":"2002","journal-title":"Resuscitation"},{"key":"10.1016\/j.jss.2021.03.025_bib0008","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1097\/01.ta.0000203699.91475.f6","article-title":"Identification of expression patterns associated with hemorrhage and resuscitation: integrated approach to data analysis","volume":"60","author":"Chen","year":"2006","journal-title":"J Trauma"},{"key":"10.1016\/j.jss.2021.03.025_bib0009","doi-asserted-by":"crossref","DOI":"10.1002\/prca.201900068","article-title":"The 'Omics' of Epigenetic modulation by valproic acid treatment in traumatic brain injury-what we know and what the future holds","volume":"13","author":"Bhatti","year":"2019","journal-title":"Proteomics Clin Appl"},{"key":"10.1016\/j.jss.2021.03.025_bib0010","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cbi.2017.12.003","article-title":"Valproic acid, a histone deacetylase inhibitor, induces apoptosis in breast cancer stem cells","volume":"280","author":"Aztopal","year":"2018","journal-title":"Chem Biol Interact"},{"key":"10.1016\/j.jss.2021.03.025_bib0011","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/SHK.0000000000000319","article-title":"Creating a \u201cpro-survival phenotype\u201d through histone deacetylase inhibition: past, present, and future","volume":"44","author":"Halaweish","year":"2015","journal-title":"Shock"},{"key":"10.1016\/j.jss.2021.03.025_bib0012","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.gene.2005.09.010","article-title":"Acetylation and deacetylation of non-histone proteins","volume":"363","author":"Glozak","year":"2005","journal-title":"Gene"},{"key":"10.1016\/j.jss.2021.03.025_bib0013","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1097\/CCM.0000000000001360","article-title":"Defying Death","volume":"43","author":"Alam","year":"2015","journal-title":"Crit Care Med"},{"key":"10.1016\/j.jss.2021.03.025_bib0014","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jss.2018.02.046","article-title":"Rapid valproic acid-induced modulation of the traumatic proteome in a porcine model of traumatic brain injury and hemorrhagic shock","volume":"228","author":"Weykamp","year":"2018","journal-title":"J Surg Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0015","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1097\/TA.0000000000000789","article-title":"Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock","volume":"79","author":"Halaweish","year":"2015","journal-title":"J Trauma Acute Care Surg"},{"key":"10.1016\/j.jss.2021.03.025_bib0016","first-page":"392","article-title":"Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment","volume":"35","author":"Goldenberg","year":"2010","journal-title":"P T"},{"key":"10.1016\/j.jss.2021.03.025_bib0017","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J Basic Clinical Pharm"},{"issue":"2","key":"10.1016\/j.jss.2021.03.025_bib0018","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40262-017-0553-1","article-title":"Safety and tolerability of intravenous valproic acid in healthy subjects: a phase I dose-escalation trial","volume":"57","author":"Georgoff","year":"2018","journal-title":"Clin Pharmacokinet"},{"key":"10.1016\/j.jss.2021.03.025_bib0019","first-page":"71","article-title":"Separation of lymphocytes, lymphocyte subgroups and monocytes: a review","volume":"10","author":"Boyum","year":"1977","journal-title":"Lymphology"},{"key":"10.1016\/j.jss.2021.03.025_bib0020","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201910427","article-title":"Plasma proteome profiling to detect and avoid sample-related biases in biomarker studies","volume":"11","author":"Geyer","year":"2019","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.jss.2021.03.025_bib0021","doi-asserted-by":"crossref","DOI":"10.1186\/1751-0473-7-4","article-title":"Scaffolder - software for manual genome scaffolding","volume":"7","author":"Barton","year":"2012","journal-title":"Source Code Biol Med"},{"key":"10.1016\/j.jss.2021.03.025_bib0022","article-title":"The universal protein resource (UniProt)","volume":"36","author":"UniProt","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0023","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1021\/pr060161n","article-title":"Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae","volume":"5","author":"Zybailov","year":"2006","journal-title":"J Proteome Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0024","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1089\/neu.2015.4163","article-title":"Resuscitation with valproic acid alters inflammatory genes in a porcine model of combined traumatic brain injury and hemorrhagic shock","volume":"33","author":"Bambakidis","year":"2016","journal-title":"J Neurotrauma"},{"key":"10.1016\/j.jss.2021.03.025_bib0025","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1097\/TA.0000000000000345","article-title":"Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage","volume":"77","author":"Dekker","year":"2014","journal-title":"J Trauma Acute Care Surg"},{"key":"10.1016\/j.jss.2021.03.025_bib0026","unstructured":"STAR. 2019."},{"key":"10.1016\/j.jss.2021.03.025_bib0027","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jss.2021.03.025_bib0028","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/1471-2105-5-194","article-title":"Optimized LOWESS normalization parameter selection for DNA microarray data","volume":"5","author":"Berger","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.jss.2021.03.025_bib0029","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"key":"10.1016\/j.jss.2021.03.025_bib0030","article-title":"An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation","author":"Sergushichev","year":"2016","journal-title":"bioRxiv"},{"key":"10.1016\/j.jss.2021.03.025_bib0031","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1097\/TA.0000000000002281","article-title":"Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation","volume":"87","author":"Williams","year":"2019","journal-title":"J Trauma Acute Care Surg"},{"issue":"4","key":"10.1016\/j.jss.2021.03.025_bib0032","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jnr.24125","article-title":"Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury","volume":"96","author":"Dekker","year":"2018","journal-title":"J Neurosci Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0033","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1097\/TA.0000000000001249","article-title":"Alterations in the human proteome following administration of valproic acid","volume":"81","author":"Georgoff","year":"2016","journal-title":"J Trauma Acute Care Surg"},{"key":"10.1016\/j.jss.2021.03.025_bib0034","doi-asserted-by":"crossref","first-page":"81","DOI":"10.21873\/cgp.20114","article-title":"A comprehensive proteome analysis of Peripheral Blood Mononuclear Cells (PBMCs) to identify candidate biomarkers of pancreatic cancer","volume":"16","author":"Li","year":"2019","journal-title":"Cancer Genomics Proteomics"},{"key":"10.1016\/j.jss.2021.03.025_bib0035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1182\/bloodadvances.2019000467","article-title":"GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets","volume":"4","author":"Chen","year":"2020","journal-title":"Blood Adv"},{"key":"10.1016\/j.jss.2021.03.025_bib0036","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.cellimm.2007.03.009","article-title":"Ischemia-reperfusion and immediate T cell responses","volume":"248","author":"Huang","year":"2007","journal-title":"Cell Immunol"},{"key":"10.1016\/j.jss.2021.03.025_bib0037","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1189\/jlb.0107062","article-title":"Lymphocyte function during hepatic ischemia\/reperfusion injury","volume":"82","author":"Caldwell","year":"2007","journal-title":"J Leukoc Biol"},{"key":"10.1016\/j.jss.2021.03.025_bib0038","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.2741\/2759","article-title":"Integration of cytokine biology and lipid metabolism in stroke","volume":"13","author":"Adibhatla","year":"2008","journal-title":"Front Biosci"},{"key":"10.1016\/j.jss.2021.03.025_bib0039","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.surg.2014.03.038","article-title":"Development of a novel neuroprotective strategy: combined treatment with hypothermia and valproic acid improves survival in hypoxic hippocampal cells","volume":"156","author":"Jin","year":"2014","journal-title":"Surgery"},{"key":"10.1016\/j.jss.2021.03.025_bib0040","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jss.2013.09.016","article-title":"Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study","volume":"186","author":"Hwabejire","year":"2014","journal-title":"J Surg Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0041","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jss.2005.04.015","article-title":"Preconditioning: gender effects","volume":"129","author":"Pitcher","year":"2005","journal-title":"J Surg Res"},{"key":"10.1016\/j.jss.2021.03.025_bib0042","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1089\/109629601317202713","article-title":"The female gender protects against pulmonary injury after trauma hemorrhagic shock","volume":"2","author":"Caruso","year":"2001","journal-title":"Surg Infect (Larchmt)"},{"key":"10.1016\/j.jss.2021.03.025_bib0043","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2119\/2008-00001.Raju","article-title":"Estrogen: a novel therapeutic adjunct for the treatment of trauma-hemorrhage-induced immunological alterations","volume":"14","author":"Raju","year":"2008","journal-title":"Mol Med"},{"key":"10.1016\/j.jss.2021.03.025_bib0044","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/TA.0000000000001763","article-title":"Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock","volume":"84","author":"Georgoff","year":"2018","journal-title":"J Trauma Acute Care Surgery"},{"key":"10.1016\/j.jss.2021.03.025_bib0045","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fendo.2017.00016","article-title":"New insights in glucocorticoid receptor signaling-more than just a ligand-binding receptor","volume":"8","author":"Scheschowitsch","year":"2017","journal-title":"Front Endocrinol (Lausanne)"},{"key":"10.1016\/j.jss.2021.03.025_bib0046","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nm1160","article-title":"Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway","volume":"11","author":"Insinga","year":"2005","journal-title":"Nat Med"},{"key":"10.1016\/j.jss.2021.03.025_bib0047","first-page":"4460","article-title":"Novel mechanisms of apoptosis induced by histone deacetylase inhibitors","volume":"63","author":"Peart","year":"2003","journal-title":"Cancer Res"}],"container-title":["Journal of Surgical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002248042100175X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002248042100175X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T14:55:05Z","timestamp":1758380105000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002248042100175X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":47,"alternative-id":["S002248042100175X"],"URL":"https:\/\/doi.org\/10.1016\/j.jss.2021.03.025","relation":{},"ISSN":["0022-4804"],"issn-type":[{"value":"0022-4804","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose","name":"articletitle","label":"Article Title"},{"value":"Journal of Surgical Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jss.2021.03.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}