{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:04:51Z","timestamp":1793232291948,"version":"4.5.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010720","name":"Zewail City of Science and Technology","doi-asserted-by":"publisher","award":["ZC 004-2019"],"award-info":[{"award-number":["ZC 004-2019"]}],"id":[{"id":"10.13039\/501100010720","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BA-ASRT joint grant","award":["project number 1110"],"award-info":[{"award-number":["project number 1110"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Campylobacter<\/jats:italic>\n                    species are one of the most common causative agents of gastroenteritis worldwide. Resistance against quinolone and macrolide antimicrobials, the most commonly used therapeutic options, poses a serious risk for campylobacteriosis treatment. Owing to whole genome sequencing advancements for rapid detection of antimicrobial resistance mechanisms, phenotypic and genotypic resistance trends along the \u201cfarm-to-fork\u201d continuum can be determined. Here, we examined the resistance trends in 111\n                    <jats:italic>Campylobacter<\/jats:italic>\n                    isolates (90\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>jejuni<\/jats:italic>\n                    and 21\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    ) recovered from clinical samples, commercial broiler carcasses and dairy products in Cairo, Egypt. Multidrug resistance (MDR) was observed in 10% of the isolates, mostly from\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    . The prevalence of MDR was the highest in isolates collected from broiler carcasses (13.3%), followed by clinical isolates (10.5%), and finally isolates from dairy products (4%). The highest proportion of antimicrobial resistance in both species was against quinolones (ciprofloxacin and\/or nalidixic acid) (68.4%), followed by tetracycline (51.3%), then erythromycin (12.6%) and aminoglycosides (streptomycin and\/or gentamicin) (5.4%). Similar resistance rates were observed for quinolones, tetracycline, and erythromycin among isolates recovered from broiler carcasses and clinical samples highlighting the contribution of food of animal sources to human illness. Significant associations between phenotypic resistance and putative gene mutations was observed, with a high prevalence of the\n                    <jats:italic>gyrA<\/jats:italic>\n                    T86I substitution among quinolone resistant isolates,\n                    <jats:italic>tet(O)<\/jats:italic>\n                    ,\n                    <jats:italic>tet(W)<\/jats:italic>\n                    , and\n                    <jats:italic>tet(32)<\/jats:italic>\n                    among tetracycline resistant isolates, and 23S rRNA A2075G and A2074T mutations among erythromycin resistant isolates. Emergence of resistance was attributed to the dissemination of resistance genes among various lineages, with the dominance of distinctive clones. For example, sub-lineages of CC828 in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    and CC21 in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>jejuni<\/jats:italic>\n                    and the genetically related clonal complexes \u2018CC206 and CC48\u2019 and \u2018CC464, CC353, CC354, CC574\u2019, respectively, propagated across different niches sharing semi-homogenous resistance patterns.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0253797","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T13:36:48Z","timestamp":1624541808000},"page":"e0253797","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["High-throughput sequencing reveals genetic determinants associated with antibiotic resistance in Campylobacter spp. from farm-to-fork"],"prefix":"10.1371","volume":"16","author":[{"given":"Shaimaa F.","family":"Mouftah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 F.","family":"Cobo-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avelino","family":"\u00c1lvarez-Ord\u00f3\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-8498","authenticated-orcid":true,"given":"Menattallah","family":"Elserafy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal A.","family":"Saif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Sadat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"El-Shibiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6153-1302","authenticated-orcid":true,"given":"Mohamed","family":"Elhadidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"issue":"3","key":"pone.0253797.ref001","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1128\/CMR.00006-15","article-title":"Global Epidemiology of Campylobacter Infection","volume":"28","author":"NO Kaakoush","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"pone.0253797.ref002","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/B978-0-12-803623-5.00005-8","volume-title":"Campylobacter","author":"DG Newell","year":"2017"},{"key":"pone.0253797.ref003","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2011.00200","article-title":"Campylobacter spp. as a Foodborne Pathogen: A Review","volume":"2","author":"J Silva","year":"2011","journal-title":"Front Microbiol"},{"issue":"8","key":"pone.0253797.ref004","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1086\/319760","article-title":"Campylobacter jejuni Infections: update on emerging issues and trends","volume":"32","author":"BM Allos","year":"2001","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"2","key":"pone.0253797.ref005","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2217\/17460913.4.2.189","article-title":"Antibiotic resistance in Campylobacter: emergence, transmission and persistence","volume":"4","author":"T Luangtongkum","year":"2009","journal-title":"Future Microbiol"},{"key":"pone.0253797.ref006","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.trsl.2020.04.009","article-title":"New and alternative strategies for the prevention, control, and treatment of antibiotic-resistant Campylobacter","volume":"223","author":"L Dai","year":"2020","journal-title":"Transl Res"},{"issue":"18","key":"pone.0253797.ref007","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1073\/pnas.1503141112","article-title":"Global trends in antimicrobial use in food animals","volume":"112","author":"TP Van Boeckel","year":"2015","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"pone.0253797.ref008","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3390\/pathogens8020087","article-title":"Campylobacter at the Human\u2013Food Interface: The African Perspective","volume":"8","author":"N Asuming-Bediako","year":"2019","journal-title":"Pathogens"},{"issue":"1\u20132","key":"pone.0253797.ref009","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ijfoodmicro.2009.02.010","article-title":"Campylobacter genotypes from food animals, environmental sources and clinical disease in Scotland 2005\/6","volume":"134","author":"SK Sheppard","year":"2009","journal-title":"Int J Food Microbiol"},{"issue":"12","key":"pone.0253797.ref010","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1111\/1462-2920.14760","article-title":"Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease","volume":"21","author":"E Mourkas","year":"2019","journal-title":"Environ Microbiol"},{"issue":"7","key":"pone.0253797.ref011","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1128\/AAC.46.7.2124-2131.2002","article-title":"CmeABC functions as a multidrug efflux system in Campylobacter jejuni","volume":"46","author":"J Lin","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pone.0253797.ref012","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/tbed.13046","article-title":"Molecular epidemiology and antimicrobial resistance mechanisms of Campylobacter coli from diarrhoeal patients and broiler carcasses in Belgium","volume":"66","author":"M Elhadidy","year":"2019","journal-title":"Transbound Emerg Dis"},{"issue":"6","key":"pone.0253797.ref013","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/03079457.2012.734915","article-title":"Molecular characterization and genotypic antimicrobial resistance analysis of Campylobacter jejuni and Campylobacter coli isolated from broiler flocks in northern Italy","volume":"41","author":"M Giacomelli","year":"2012","journal-title":"Avian Pathol"},{"issue":"10","key":"pone.0253797.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0223804","article-title":"Antimicrobial resistance genotypes and phenotypes of Campylobacter jejuni isolated in Italy from humans, birds from wild and urban habitats, and poultry","volume":"14","author":"F Marotta","year":"2019","journal-title":"PLoS ONE"},{"key":"pone.0253797.ref015","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2020.01799","article-title":"Antimicrobial Resistance and Virulence-Associated Markers in Campylobacter Strains from Diarrheic and Non-diarrheic Humans in Poland","volume":"11","author":"B Wysok","year":"2020","journal-title":"Front Microbiol"},{"issue":"2","key":"pone.0253797.ref016","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1128\/AEM.02873-15","article-title":"Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp","volume":"82","author":"S Zhao","year":"2016","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"pone.0253797.ref017","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.cmi.2016.11.012","article-title":"The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST Subcommittee","volume":"23","author":"MJ Ellington","year":"2017","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"pone.0253797.ref018","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40794-016-0028-7","article-title":"Diarrheal disease and enteric infections in LMIC communities: how big is the problem?","volume":"2","author":"BJJ McCormick","year":"2016","journal-title":"Trop Dis Travel Med Vaccines"},{"issue":"10","key":"pone.0253797.ref019","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1128\/jcm.35.10.2568-2572.1997","article-title":"PCR detection, identification to species level, and fingerprinting of Campylobacter jejuni and Campylobacter coli direct from diarrheic samples","volume":"35","author":"D Linton","year":"1997","journal-title":"J Clin Microbiol"},{"issue":"2","key":"pone.0253797.ref020","article-title":"The European union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2017","volume":"17","year":"2019","journal-title":"EFSA J"},{"key":"pone.0253797.ref021","unstructured":"Andrews, S. FASTQC. A quality control tool for high throughput sequence data. 2010. http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"issue":"5","key":"pone.0253797.ref022","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing","volume":"19","author":"A Bankevich","year":"2012","journal-title":"J Comput Biol"},{"issue":"1","key":"pone.0253797.ref023","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1186\/1471-2105-11-595","article-title":"BIGSdb: Scalable analysis of bacterial genome variation at the population level","volume":"11","author":"KA Jolley","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"9","key":"pone.0253797.ref024","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3201\/eid0809.02-0122","article-title":"Molecular Characterization of Campylobacter jejuni Clones: A Basis for Epidemiologic Investigation","volume":"8","author":"KE Dingle","year":"2002","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"pone.0253797.ref025","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1128\/JCM.39.1.14-23.2001","article-title":"Multilocus Sequence Typing System for Campylobacter jejuni","volume":"39","author":"KE Dingle","year":"2001","journal-title":"J Clin Microbiol"},{"issue":"D1","key":"pone.0253797.ref026","doi-asserted-by":"crossref","first-page":"D566","DOI":"10.1093\/nar\/gkw1004","article-title":"CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database","volume":"45","author":"B Jia","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0253797.ref027","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"E Zankari","year":"2012","journal-title":"J Antimicrob Chemother"},{"issue":"10","key":"pone.0253797.ref028","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1093\/jac\/dkx217","article-title":"PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens","volume":"72","author":"E Zankari","year":"2017","journal-title":"J Antimicrob Chemother"},{"issue":"4","key":"pone.0253797.ref029","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"3","key":"pone.0253797.ref030","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/bioinformatics\/bty648","article-title":"Scaling read aligners to hundreds of threads on general-purpose processors","volume":"35","author":"B Langmead","year":"2019","journal-title":"Bioinformatics"},{"issue":"3","key":"pone.0253797.ref031","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"issue":"6","key":"pone.0253797.ref032","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1093\/nar\/gkx1321","article-title":"PlasFlow: predicting plasmid sequences in metagenomic data using genome signatures","volume":"46","author":"PS Krawczyk","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0253797.ref033","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1128\/JCM.00051-15","article-title":"Refinement of Whole-Genome Multilocus Sequence Typing Analysis by Addressing Gene Paralogy","volume":"53","author":"J Zhang","year":"2015","journal-title":"J Clin Microbiol"},{"issue":"4","key":"pone.0253797.ref034","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1093\/bib\/bbx108","article-title":"MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization","volume":"20","author":"K Katoh","year":"2019","journal-title":"Brief Bioinform"},{"issue":"11","key":"pone.0253797.ref035","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1128\/AAC.00616-06","article-title":"Synergy between Efflux Pump CmeABC and Modifications in Ribosomal Proteins L4 and L22 in Conferring Macrolide Resistance in Campylobacter jejuni and Campylobacter coli","volume":"50","author":"C Cagliero","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"pone.0253797.ref036","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1128\/AAC.49.3.1067-1075.2005","article-title":"CmeR Functions as a Transcriptional Repressor for the Multidrug Efflux Pump CmeABC in Campylobacter jejuni","volume":"49","author":"J Lin","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0253797.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/340605","article-title":"Antimicrobial Resistance Mechanisms among Campylobacter","volume":"2013","author":"K Wieczorek","year":"2013","journal-title":"BioMed Res Int"},{"key":"pone.0253797.ref038","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.cimid.2019.06.001","article-title":"Antimicrobial resistances, and molecular typing of Campylobacter jejuni isolates, separated from food-producing animals and diarrhea patients in Iran","volume":"65","author":"G Divsalar","year":"2019","journal-title":"Comp Immunol Microbiol Infect Dis"},{"issue":"0","key":"pone.0253797.ref039","doi-asserted-by":"crossref","first-page":"21","DOI":"10.21608\/zvjz.2019.6003.1008","article-title":"Effect of Antibiotics Growth Promoters Alternatives on Growth Performance, Hematobiochemical and Immunological Profile of Healthy Broiler Chickens","volume":"0","author":"A Abd El-Monsef","year":"2019","journal-title":"Zagazig Vet J"},{"issue":"1","key":"pone.0253797.ref040","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.4102\/ojvr.v84i1.1411","article-title":"Detection and prevalence of antimicrobial resistance genes in Campylobacter spp. isolated from chickens and humans","volume":"84","author":"S Reddy","year":"2017","journal-title":"Onderstepoort J Vet Res"},{"issue":"2","key":"pone.0253797.ref041","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1017\/S1466252317000135","article-title":"Antibiotic resistance trends and mechanisms in the foodborne pathogen, Campylobacter","volume":"18","author":"Y Tang","year":"2017","journal-title":"Anim Health Res Rev"},{"issue":"10","key":"pone.0253797.ref042","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/mec.12742","article-title":"Cryptic ecology among host generalist Campylobacter jejuni in domestic animals","volume":"23","author":"SK Sheppard","year":"2014","journal-title":"Mol Ecol"},{"issue":"5873","key":"pone.0253797.ref043","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.1155532","article-title":"Convergence of Campylobacter Species: Implications for Bacterial Evolution","volume":"320","author":"SK Sheppard","year":"2008","journal-title":"Science"},{"issue":"8","key":"pone.0253797.ref044","doi-asserted-by":"crossref","DOI":"10.1099\/mgen.0.000198","article-title":"Trends in fluoroquinolone resistance in Campylobacter","volume":"4","author":"EL Sproston","year":"2018","journal-title":"Microb Genomics"},{"issue":"1","key":"pone.0253797.ref045","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/jac\/dkg033","article-title":"Fluoroquinolone resistance in Campylobacter species from man and animals: detection of mutations in topoisomerase genes","volume":"51","author":"LJV Piddock","year":"2003","journal-title":"J Antimicrob Chemother"},{"issue":"6770","key":"pone.0253797.ref046","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/35001088","article-title":"The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences","volume":"403","author":"J Parkhill","year":"2000","journal-title":"Nature"},{"issue":"1","key":"pone.0253797.ref047","doi-asserted-by":"crossref","first-page":"e0227833","DOI":"10.1371\/journal.pone.0227833","article-title":"Antimicrobial resistance patterns and molecular resistance markers of Campylobacter jejuni isolates from human diarrheal cases","volume":"15","author":"M Elhadidy","year":"2020","journal-title":"PLOS ONE"},{"issue":"1","key":"pone.0253797.ref048","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijantimicag.2005.08.019","article-title":"An investigation of the molecular mechanisms contributing to high-level erythromycin resistance in Campylobacter","volume":"27","author":"D Corcoran","year":"2006","journal-title":"Int J Antimicrob Agents"},{"issue":"3","key":"pone.0253797.ref049","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1128\/AAC.01927-12","article-title":"Mutational and Transcriptomic Changes Involved in the Development of Macrolide Resistance in Campylobacter jejuni","volume":"57","author":"H Hao","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pone.0253797.ref050","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1128\/AAC.49.6.2515-2518.2005","article-title":"Isolation and expression of a novel molecular class D beta-lactamase, OXA-61, from Campylobacter jejuni","volume":"49","author":"DA Alfredson","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0253797.ref051","doi-asserted-by":"crossref","first-page":"108553","DOI":"10.1016\/j.vetmic.2019.108553","article-title":"Beta-lactam resistance in Campylobacter coli and Campylobacter jejuni chicken isolates and the association between blaOXA-61 gene expression and the action of \u03b2-lactamase inhibitors","volume":"241","author":"P Casagrande Proietti","year":"2020","journal-title":"Vet Microbiol"},{"issue":"7","key":"pone.0253797.ref052","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1128\/AAC.00131-06","article-title":"The Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics","volume":"50","author":"KS Long","year":"2006","journal-title":"Antimicrob Agents Chemother"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T13:37:38Z","timestamp":1624541858000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253797"}},"subtitle":[],"editor":[{"given":"Zhi","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253797","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]}}}