{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:39:39Z","timestamp":1792507179939,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010735","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["Interagency Agreement"],"award-info":[{"award-number":["Interagency Agreement"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015764","name":"Center for Preparedness and Response","doi-asserted-by":"publisher","award":["Internal Funding"],"award-info":[{"award-number":["Internal Funding"]}],"id":[{"id":"10.13039\/100015764","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau\/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, mean\u00b1standard deviation of 58.7\u00b17.6 hours (fast progression), 11 animals had longer survival times, 113\u00b134.4 hours (slow progression), and one animal survived. Median (lower\u2013upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9\u2013326) ng\/mL], than in those with slow progression [23.8 (15.6\u201326.3) ng\/mL] (p = 0.0002), and the survivor (11.1 ng\/mL). The differences were also observed for other toxins and bacteremia. Animals with slow progression had an extended phase-2 plateau, with low variability of LF levels across all time points and animals. Characterization of phase-2 toxin levels defined upper thresholds; critical levels for exiting phase-2 and entering the critical phase-3, 342 ng\/mL (PA), 35.8 ng\/mL (LF), and 1.10 ng\/mL (EF). The thresholds were exceeded earlier in animals with fast progression (38.5\u00b17.4 hours) and later in animals with slow progression (78.7\u00b115.2 hours). Once the threshold was passed, toxin levels rose rapidly in both groups to the terminal stage. The time from threshold to terminal was rapid and similar; 20.8\u00b17.4 hours for fast and 19.9\u00b17.5 hours for slow progression. The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. This first comprehensive evaluation of anthrax toxins provides new insights into disease progression.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010735","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T18:34:41Z","timestamp":1671474881000},"page":"e1010735","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive characterization of toxins during progression of inhalation anthrax in a non-human primate model"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7495-311X","authenticated-orcid":true,"given":"Anne E.","family":"Boyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel","family":"Gallegos-Candela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato C.","family":"Lins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Solano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian R.","family":"Woolfitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Sanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A. 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evidence","volume":"66","author":"E Helgason","year":"2000","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"ppat.1010735.ref002","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12998\/wjcc.v3.i1.20","article-title":"Anthrax: A disease of biowarfare and public health importance.","volume":"3","author":"AK Goel","year":"2015","journal-title":"World J Clin Cases"},{"key":"ppat.1010735.ref003","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1749-6632.1980.tb18910.x","article-title":"Inhalation anthrax.","volume":"353","author":"PS Brachman","year":"1980","journal-title":"Ann N Y Acad Sci"},{"key":"ppat.1010735.ref004","first-page":"467","volume-title":"Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare","author":"AM Friedlander","year":"1997"},{"issue":"4","key":"ppat.1010735.ref005","doi-asserted-by":"crossref","first-page":"270","DOI":"10.7326\/0003-4819-144-4-200602210-00009","article-title":"Systematic review: a century of inhalational anthrax cases from 1900 to 2005","volume":"144","author":"JE Holty","year":"2006","journal-title":"Ann Intern Med"},{"issue":"11","key":"ppat.1010735.ref006","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJM199909093411107","article-title":"Anthrax","volume":"341","author":"TC Dixon","year":"1999","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1010735.ref007","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3201\/eid0706.010604","article-title":"Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States","volume":"7","author":"JA Jernigan","year":"2001","journal-title":"Emerg Infect Dis"},{"issue":"7","key":"ppat.1010735.ref008","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1001\/jama.287.7.863","article-title":"Fatal inhalational anthrax in a 94-year-old Connecticut woman","volume":"287","author":"LA Barakat","year":"2002","journal-title":"JAMA"},{"issue":"10","key":"ppat.1010735.ref009","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3201\/eid0810.020353","article-title":"Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings","volume":"8","author":"DB Jernigan","year":"2002","journal-title":"Emerg Infect Dis"},{"key":"ppat.1010735.ref010","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-micro-091014-104523","article-title":"Anthrax Pathogenesis.","volume":"69","author":"M Moayeri","year":"2015","journal-title":"Annu Rev Microbiol"},{"issue":"4410","key":"ppat.1010735.ref011","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/173869a0","article-title":"Observations on experimental anthrax; demonstration of a specific lethal factor produced in vivo by Bacillus anthracis","volume":"173","author":"H Smith","year":"1954","journal-title":"Nature"},{"key":"ppat.1010735.ref012","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.cellbio.19.111301.140655","article-title":"Anthrax toxin.","volume":"19","author":"RJ Collier","year":"2003","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"7","key":"ppat.1010735.ref013","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1074\/jbc.M210321200","article-title":"Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization","volume":"278","author":"S Liu","year":"2003","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1010735.ref014","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1073\/pnas.0431098100","article-title":"Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor","volume":"100","author":"HM Scobie","year":"2003","journal-title":"Proc Natl Acad Sci U S 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Biol"},{"issue":"3","key":"ppat.1010735.ref018","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1021\/bi015860m","article-title":"Stoichiometry of anthrax toxin complexes","volume":"41","author":"J Mogridge","year":"2002","journal-title":"Biochemistry"},{"issue":"3","key":"ppat.1010735.ref019","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1099\/00221287-138-3-543","article-title":"Serum protease cleavage of Bacillus anthracis protective antigen","volume":"138","author":"JW Ezzell","year":"1992","journal-title":"J Gen Microbiol"},{"issue":"11","key":"ppat.1010735.ref020","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1128\/IAI.00719-07","article-title":"Anthrax protective antigen cleavage and clearance from the blood of mice and rats","volume":"75","author":"M Moayeri","year":"2007","journal-title":"Infect 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Lins","year":"2019","journal-title":"Analytical and bioanalytical chemistry"},{"issue":"5364","key":"ppat.1010735.ref024","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1126\/science.280.5364.734","article-title":"Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor","volume":"280","author":"NS Duesbery","year":"1998","journal-title":"Science"},{"issue":"10","key":"ppat.1010735.ref025","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1073\/pnas.79.10.3162","article-title":"Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells","volume":"79","author":"SH Leppla","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"ppat.1010735.ref026","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.it.2006.07.002","article-title":"Anthrax toxins: A paradigm of bacterial immune suppression","volume":"27","author":"CT Baldari","year":"2006","journal-title":"Trends Immunol"},{"issue":"6","key":"ppat.1010735.ref027","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1128\/CVI.00023-06","article-title":"Detection of anthrax toxin in the serum of animals infected with Bacillus anthracis by using engineered immunoassays","volume":"13","author":"R Mabry","year":"2006","journal-title":"Clin Vaccine Immunol"},{"issue":"10","key":"ppat.1010735.ref028","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1128\/IAI.00792-06","article-title":"Protective antigen as a correlative marker for anthrax in animal models","volume":"74","author":"D Kobiler","year":"2006","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1010735.ref029","article-title":"The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B.","volume":"9","author":"DA Suffredini","year":"2017","journal-title":"anthracis Lethal and Edema Toxins. Toxins (Basel)."},{"issue":"6","key":"ppat.1010735.ref030","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/toxins3060591","article-title":"The effects of anthrax lethal toxin on host barrier function.","volume":"3","author":"T Xie","year":"2011","journal-title":"Toxins (Basel)"},{"issue":"6","key":"ppat.1010735.ref031","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/S0002-9440(10)62496-0","article-title":"Anthrax lethal toxin induces endothelial barrier dysfunction","volume":"166","author":"JM Warfel","year":"2005","journal-title":"Am J Pathol"},{"key":"ppat.1010735.ref032","first-page":"139","article-title":"Molecular determinants for a cardiovascular collapse in anthrax","volume":"6","author":"J Brojatsch","year":"2014","journal-title":"Front Biosci (Elite Ed)"},{"key":"ppat.1010735.ref033","first-page":"2485","volume-title":"Bennet\u2019s Principles and Practice of Infectious Diseases","author":"D. Lucey","year":"2005"},{"key":"ppat.1010735.ref034","article-title":"An Improved Clinical Staging System for Inhalational Anthrax","author":"D. Lucey","year":"2005","journal-title":"Clinicians\u2019 Biosecurity News. Johns Hopkins Center for Health Security"},{"issue":"6","key":"ppat.1010735.ref035","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/hs.2015.0032","article-title":"Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.","volume":"13","author":"E Huang","year":"2015","journal-title":"Health Secur"},{"issue":"1","key":"ppat.1010735.ref036","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/cts.12433","article-title":"Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.","volume":"10","author":"CF Nagy","year":"2017","journal-title":"Clin Transl Sci."},{"issue":"8","key":"ppat.1010735.ref037","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/01.LAB.0000080599.43791.01","article-title":"Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis).","volume":"83","author":"D Vasconcelos","year":"2003","journal-title":"Lab Invest"},{"issue":"5","key":"ppat.1010735.ref038","first-page":"691","article-title":"Pathology of experimental inhalation anthrax in the rhesus monkey","volume":"73","author":"DL Fritz","year":"1995","journal-title":"Lab Invest"},{"issue":"34","key":"ppat.1010735.ref039","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1016\/j.vaccine.2016.06.031","article-title":"Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine","volume":"34","author":"DJ Chabot","year":"2016","journal-title":"Vaccine"},{"issue":"11","key":"ppat.1010735.ref040","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1128\/CVI.00469-14","article-title":"Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques","volume":"21","author":"L Chen","year":"2014","journal-title":"Clin Vaccine Immunol"},{"issue":"1","key":"ppat.1010735.ref041","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1017\/S0022172400044272","article-title":"Observations on the prophylaxis of experimental pulmonary anthrax in the monkey","volume":"54","author":"DW Henderson","year":"1956","journal-title":"J Hyg (Lond)"},{"issue":"11","key":"ppat.1010735.ref042","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1128\/CVI.00288-12","article-title":"Development of an inhalational Bacillus anthracis exposure therapeutic model in cynomolgus macaques","volume":"19","author":"LN Henning","year":"2012","journal-title":"Clin Vaccine Immunol"},{"issue":"20","key":"ppat.1010735.ref043","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1073\/pnas.0602748103","article-title":"Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax","volume":"103","author":"NJ Vietri","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010735.ref044","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ab.2017.12.007","article-title":"Validated MALDI-TOF-MS method for anthrax lethal factor provides early diagnosis and evaluation of therapeutics","volume":"543","author":"M Gallegos-Candela","year":"2017","journal-title":"Anal Biochem"},{"issue":"7","key":"ppat.1010735.ref045","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1039\/C8AN02479K","article-title":"Accurate and selective quantification of anthrax protective antigen in plasma by immunocapture and isotope dilution mass spectrometry.","volume":"144","author":"MI Solano","year":"2019","journal-title":"Analyst"},{"issue":"8","key":"ppat.1010735.ref046","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1128\/IAI.00346-09","article-title":"Kinetics of lethal factor and poly-D-glutamic acid antigenemia during inhalation anthrax in rhesus macaques","volume":"77","author":"AE Boyer","year":"2009","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1010735.ref047","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1128\/CVI.00292-12","article-title":"Characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in New Zealand white rabbits as a trigger for treatment","volume":"19","author":"JE Comer","year":"2012","journal-title":"Clin Vaccine Immunol"},{"key":"ppat.1010735.ref048","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/0002-9343(60)90079-6","article-title":"An epidemic of inhalation anthrax, the first in the twentieth century. I. Clinical features","volume":"29","author":"SA Plotkin","year":"1960","journal-title":"Am J Med"},{"issue":"5","key":"ppat.1010735.ref049","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1001\/jama.1997.03550050061035","article-title":"Clinical recognition and management of patients exposed to biological warfare agents","volume":"278","author":"DR Franz","year":"1997","journal-title":"JAMA"},{"issue":"5188","key":"ppat.1010735.ref050","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1126\/science.7973702","article-title":"The Sverdlovsk anthrax outbreak of 1979","volume":"266","author":"M Meselson","year":"1994","journal-title":"Science"},{"issue":"4","key":"ppat.1010735.ref051","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1128\/IAI.01289-12","article-title":"Pathology and pathophysiology of inhalational anthrax in a guinea pig model","volume":"81","author":"V Savransky","year":"2013","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1010735.ref052","first-page":"257","article-title":"The physiologic responses of Dutch belted rabbits infected with inhalational anthrax.","volume":"59","author":"WS Lawrence","year":"2009","journal-title":"Comp Med"},{"issue":"3","key":"ppat.1010735.ref053","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.2337\/dc09-1707","article-title":"Higher red blood cell distribution width is associated with the metabolic syndrome: results of the Ibermutuamur CArdiovascular RIsk assessment study","volume":"33","author":"MA Sanchez-Chaparro","year":"2010","journal-title":"Diabetes Care"},{"issue":"3","key":"ppat.1010735.ref054","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/gerona\/glp163","article-title":"Red cell distribution width and mortality in older adults: a meta-analysis","volume":"65","author":"KV Patel","year":"2010","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"6","key":"ppat.1010735.ref055","doi-asserted-by":"crossref","first-page":"R282","DOI":"10.1186\/cc13145","article-title":"An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock","volume":"17","author":"CH Kim","year":"2013","journal-title":"Crit Care"},{"issue":"4","key":"ppat.1010735.ref056","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4103\/2229-5151.147518","article-title":"Broadening of the red blood cell distribution width is associated with increased severity of illness in patients with sepsis","volume":"4","author":"NA Mahmood","year":"2014","journal-title":"Int J Crit Illn Inj Sci"},{"issue":"8","key":"ppat.1010735.ref057","doi-asserted-by":"crossref","first-page":"e71718","DOI":"10.1371\/journal.pone.0071718","article-title":"Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.","volume":"8","author":"HH Chang","year":"2013","journal-title":"PLoS One."},{"key":"ppat.1010735.ref058","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13104-016-1955-0","article-title":"A case report of inhalation anthrax acquired naturally.","volume":"9","author":"Z Azarkar","year":"2016","journal-title":"BMC Res Notes"},{"issue":"7","key":"ppat.1010735.ref059","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1128\/IAI.00006-11","article-title":"Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis","volume":"79","author":"CM Ebrahimi","year":"2011","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1010735.ref060","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/infdis\/jir543","article-title":"Lethal factor toxemia and anti-protective antigen antibody activity in naturally acquired cutaneous anthrax","volume":"204","author":"AE Boyer","year":"2011","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1010735.ref061","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1365-2958.1999.01137.x","article-title":"Germination of Bacillus anthracis spores within alveolar macrophages","volume":"31","author":"C Guidi-Rontani","year":"1999","journal-title":"Mol Microbiol"},{"key":"ppat.1010735.ref062","first-page":"111","volume-title":"Proteolytic activation of anthrax toxin bound to cellular receptors","author":"S Leppla","year":"1988"},{"issue":"3","key":"ppat.1010735.ref063","first-page":"315","article-title":"The chemical basis of the virulence of Bacillus anthracis. III. The role of the terminal bacteraemia in death of guinea-pigs from anthrax","volume":"36","author":"J Keppie","year":"1955","journal-title":"Br J Exp Pathol"},{"issue":"22","key":"ppat.1010735.ref064","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1021\/ac701741s","article-title":"Detection and quantification of anthrax lethal factor in serum by mass spectrometry","volume":"79","author":"AE Boyer","year":"2007","journal-title":"Anal Chem"},{"issue":"10","key":"ppat.1010735.ref065","doi-asserted-by":"crossref","first-page":"5796","DOI":"10.1128\/AAC.01102-16","article-title":"Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax","volume":"60","author":"BJ Yamamoto","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"ppat.1010735.ref066","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1213\/ANE.0000000000005101","article-title":"Nonparametric Statistical Methods in Medical Research","volume":"131","author":"P Schober","year":"2020","journal-title":"Anesth Analg."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010735","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010735","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T20:05:00Z","timestamp":1672776300000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010735"}},"subtitle":[],"editor":[{"given":"Karla J. 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