{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:45:42Z","timestamp":1793727942989,"version":"4.6.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Stenotrophomonas maltophilia<\/jats:italic> exhibits wide spectrum of fluoroquinolone resistance using different mechanisms as multidrug efflux pumps and Sm<jats:italic>qnr<\/jats:italic> alleles. Here, the role of <jats:italic>smeDEF<\/jats:italic>, <jats:italic>smeVWX<\/jats:italic> efflux genes and contribution of Sm<jats:italic>qnr<\/jats:italic> alleles in the development of fluoroquinolone resistance was assessed. Ciprofloxacin, levofloxacin and moxifloxacin resistance were found in 10.9%, 3.5%, and 1.6% of isolates, respectively. More than four-fold differences in ciprofloxacin MICs were detected in the presence of reserpine and <jats:italic>smeD, F, V<\/jats:italic> expression was significantly associated with ciprofloxacin resistance (p\u2009=\u20090.017 for <jats:italic>smeD<\/jats:italic>, 0.003 for <jats:italic>smeF<\/jats:italic>, and 0.001 for <jats:italic>smeV<\/jats:italic>). Sm<jats:italic>qnr<\/jats:italic> gene was found in 52% of the ciprofloxacin-resistant isolates and Sm<jats:italic>qnr8<\/jats:italic> was the most common allele detected. Fluoroquinolone resistance in <jats:italic>S. maltophilia<\/jats:italic> clinical isolates was significantly associated with active efflux pumps. There was no correlation between the Sm<jats:italic>qnr<\/jats:italic> alleles and ciprofloxacin resistance; however, contribution of the Sm<jats:italic>qnr<\/jats:italic> genes in low-level levofloxacin resistance was revealed.<\/jats:p>","DOI":"10.1038\/s41598-021-88977-z","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T10:07:04Z","timestamp":1620209224000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Emergence of fluoroquinolone resistance and possible mechanisms in clinical isolates of Stenotrophomonas maltophilia from Iran"],"prefix":"10.1038","volume":"11","author":[{"given":"Akram","family":"Azimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Rezaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Yaseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirus","family":"Jafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rahbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Douraghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"issue":"1","key":"88977_CR1","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1186\/s12879-019-4394-4","volume":"19","author":"EJ Kim","year":"2019","unstructured":"Kim, E. J. et al. Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia and clinical impact of quinolone\u2013resistant strains. BMC Infect. Dis. 19(1), 754 (2019).","journal-title":"BMC Infect. Dis."},{"key":"88977_CR2","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.3389\/fmicb.2017.02276","volume":"8","author":"AA Adegoke","year":"2017","unstructured":"Adegoke, A. A., Stenstr\u00f6m, T. A. & Okoh, A. I. Stenotrophomonas maltophilia as an emerging ubiquitous pathogen: Looking beyond contemporary antibiotic therapy. Front. Microbiol. 8, 2276 (2017).","journal-title":"Front. Microbiol."},{"issue":"5","key":"88977_CR3","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/S1473-3099(09)70083-0","volume":"9","author":"WJ Looney","year":"2009","unstructured":"Looney, W. J., Narita, M. & M\u00fchlemann, K. Stenotrophomonas maltophilia: An emerging opportunist human pathogen. Lancet Infect. Dis. 9(5), 312\u2013323 (2009).","journal-title":"Lancet Infect. Dis."},{"issue":"1","key":"88977_CR4","doi-asserted-by":"publisher","first-page":"149","DOI":"10.4314\/ahs.v16i1.20","volume":"16","author":"A \u00c7\u0131kman","year":"2016","unstructured":"\u00c7\u0131kman, A., Parlak, M., Bayram, Y., G\u00fcd\u00fcc\u00fco\u011flu, H. & Berkta\u015f, M. Antibiotics resistance of Stenotrophomonas maltophilia strains isolated from various clinical specimens. Afr. Health Sci. 16(1), 149\u2013152 (2016).","journal-title":"Afr. Health Sci."},{"issue":"1","key":"88977_CR5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1128\/CMR.00019-11","volume":"25","author":"JS Brooke","year":"2012","unstructured":"Brooke, J. S. Stenotrophomonas maltophilia: An emerging global opportunistic pathogen. Clin. Microbiol. Rev. 25(1), 2\u201341 (2012).","journal-title":"Clin. Microbiol. Rev."},{"issue":"4","key":"88977_CR6","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1099\/jmm.0.037309-0","volume":"61","author":"R Zhang","year":"2012","unstructured":"Zhang, R. Detection of the Smqnr quinolone protection gene and its prevalence in clinical isolates of Stenotrophomonas maltophilia in China. J. Med. Microbiol. 61(4), 535\u2013539 (2012).","journal-title":"J. Med. Microbiol."},{"key":"88977_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2020.12.012","author":"RX Wu","year":"2021","unstructured":"Wu, R. X., Yu, C. M., Hsu, S. T. & Wang, C. H. Emergence of concurrent levofloxacin- and trimethoprim\/sulfamethoxazole-resistant Stenotrophomonas maltophilia: Risk factors and antimicrobial sensitivity pattern analysisfrom a single medical center in Taiwan. J. Microbiol. Immunol. https:\/\/doi.org\/10.1016\/j.jmii.2020.12.012 (2021).","journal-title":"J. Microbiol. Immunol."},{"issue":"6","key":"88977_CR8","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1093\/jac\/42.6.683","volume":"42","author":"J Martinez","year":"1998","unstructured":"Martinez, J., Alonso, A., Gomez-Gomez, J. & Baquero, F. Quinolone resistance by mutations in chromosomal gyrase genes. Just the tip of the iceberg?. J. Antimicrob. Chemother. 42(6), 683\u2013688 (1998).","journal-title":"J. Antimicrob. Chemother."},{"issue":"3","key":"88977_CR9","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1128\/AAC.46.3.665-671.2002","volume":"46","author":"S Valdezate","year":"2002","unstructured":"Valdezate, S., Vindel, A., Echeita, A., Baquero, F. & Cant\u00f3, R. Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility. Antimicrob. Agents Chemother. 46(3), 665\u2013671 (2002).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"9105","key":"88977_CR10","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S0140-6736(97)07322-4","volume":"351","author":"L Mart\u00ednez-Mart\u00ednez","year":"1998","unstructured":"Mart\u00ednez-Mart\u00ednez, L., Pascual, A. & Jacoby, G. A. Quinolone resistance from a transferable plasmid. Lancet 351(9105), 797\u2013799 (1998).","journal-title":"Lancet"},{"key":"88977_CR11","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.PLAS-0006-2013","author":"GA Jacoby","year":"2014","unstructured":"Jacoby, G. A., Strahilevitz, J. & Hooper, D. C. Plasmid-mediated quinolone resistance. Microbiol. Spectr. https:\/\/doi.org\/10.1128\/microbiolspec.PLAS-0006-2013 (2014).","journal-title":"Microbiol. Spectr."},{"issue":"5","key":"88977_CR12","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.cmi.2015.01.007","volume":"21","author":"G Garc\u00eda-Le\u00f3n","year":"2015","unstructured":"Garc\u00eda-Le\u00f3n, G. et al. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates. Clin. Microbiol. Infect. 21(5), 464\u2013467 (2015).","journal-title":"Clin. Microbiol. Infect."},{"key":"88977_CR13","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1080\/14787210.2020.1730178","volume":"18","author":"T Gil-Gil","year":"2020","unstructured":"Gil-Gil, T., Mart\u00ednez, J. L. & Blanco, P. Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: A review of current knowledge. Expert Rev. Anti Infect. Ther. 18, 335\u2013347 (2020).","journal-title":"Expert Rev. Anti Infect. Ther."},{"issue":"4","key":"88977_CR14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1089\/10766290260469499","volume":"8","author":"A Ribera","year":"2002","unstructured":"Ribera, A. et al. Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in epidemiological unrelated Stenotrophomonas maltophilia clinical isolates. Microb. Drug Resist. 8(4), 245\u2013251 (2002).","journal-title":"Microb. Drug Resist."},{"issue":"1","key":"88977_CR15","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/1471-2180-8-148","volume":"8","author":"MB S\u00e1nchez","year":"2008","unstructured":"S\u00e1nchez, M. B., Alvaro, H., Rodr\u00edguez-Mart\u00ednez, J. M., Mart\u00ednez-Mart\u00ednez, L. & Mart\u00ednez, J. L. Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants. BMC Microbiol. 8(1), 148 (2008).","journal-title":"BMC Microbiol."},{"issue":"2","key":"88977_CR16","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1089\/mdr.2015.0228","volume":"23","author":"SY Chong","year":"2017","unstructured":"Chong, S. Y. Levofloxacin efflux and smeD in clinical isolates of Stenotrophomonas maltophilia. Microb. Drug Resist. 23(2), 163\u2013168 (2017).","journal-title":"Microb. Drug Resist."},{"key":"88977_CR17","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.3389\/fmicb.2019.01191","volume":"10","author":"N Bostanghadiri","year":"2019","unstructured":"Bostanghadiri, N. et al. Characterization of phenotypic and genotypic diversity of Stenotrophomonas maltophilia strains isolated from selected hospitals in Iran. Front. Microbiol. 10, 1191 (2019).","journal-title":"Front. Microbiol."},{"issue":"8","key":"88977_CR18","first-page":"872","volume":"22","author":"HS Ebrahim-Saraie","year":"2019","unstructured":"Ebrahim-Saraie, H. S., Heidari, H., Soltani, B., Mardaneh, J. & Motamedifar, M. Prevalence of antibiotic resistance and integrons, sul and Smqnr genes in clinical isolates of Stenotrophomonas maltophilia from a tertiary care hospital in Southwest Iran. Iran. J. Basic Med. Sci. 22(8), 872 (2019).","journal-title":"Iran. J. Basic Med. Sci."},{"issue":"1","key":"88977_CR19","first-page":"35","volume":"3","author":"AH Nemati","year":"2015","unstructured":"Nemati, A. H., Solgi, H., Vaziri, F. & Shahcheraghi, F. Antimicrobial susceptibility of Stenotrophomonas maltophilia clinical isolates from blood samples in Iran. J. Med. Microbiol. Infect. Dis. 3(1), 35\u201337 (2015).","journal-title":"J. Med. Microbiol. Infect. Dis."},{"issue":"11","key":"88977_CR20","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1111\/j.1469-0691.2005.01257.x","volume":"11","author":"D G\u00fclmez","year":"2005","unstructured":"G\u00fclmez, D. & Hascelik, G. Stenotrophomonas maltophilia: antimicrobial resistance and molecular typing of an emerging pathogen in a Turkish university hospital. Clin. Microbiol. Infect. 11(11), 880\u2013886 (2005).","journal-title":"Clin. Microbiol. Infect."},{"issue":"8","key":"88977_CR21","first-page":"e23569","volume":"8","author":"MG Gozel","year":"2015","unstructured":"Gozel, M. G., Celik, C. & Elaldi, N. Stenotrophomonas maltophilia infections in adults: Primary bacteremia and pneumonia. Jundishapur J. Microbiol. 8(8), e23569 (2015).","journal-title":"Jundishapur J. Microbiol."},{"issue":"3","key":"88977_CR22","first-page":"83","volume":"4","author":"U Ali","year":"2016","unstructured":"Ali, U., Abbasi, S. A., Kaleem, F., Butt, T. & Reza, S. Antimicrobial resistance pattern of Stenotrophomonas maltophilia isolates from a tertiary care setting in Rawalpindi, Pakistan. J. Med. Microbiol. Infect. Dis. 4(3), 83\u201387 (2016).","journal-title":"J. Med. Microbiol. Infect. Dis."},{"issue":"2","key":"88977_CR23","first-page":"30","volume":"24","author":"T Naeem","year":"2012","unstructured":"Naeem, T., Absar, M. & Somily, A. M. Antibiotic resistance among clinical isolates of Stenotrophomonas maltophilia at a teaching hospital in Riyadh, Saudi Arabia. J. Ayub. Med. Coll. Abbottab. 24(2), 30\u201333 (2012).","journal-title":"J. Ayub. Med. Coll. Abbottab."},{"issue":"6","key":"88977_CR24","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1128\/AAC.45.6.1879-1881.2001","volume":"45","author":"A Alonso","year":"2001","unstructured":"Alonso, A. & Martinez, J. L. Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 45(6), 1879\u20131881 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"5","key":"88977_CR25","first-page":"5177","volume":"12","author":"W Jia","year":"2015","unstructured":"Jia, W., Wang, J., Xu, H. & Li, G. Resistance of Stenotrophomonas maltophilia to fluoroquinolones: Prevalence in a university hospital and possible mechanisms. Int. J. Environ Res. 12(5), 5177\u20135195 (2015).","journal-title":"Int. J. Environ Res."},{"issue":"9","key":"88977_CR26","first-page":"743","volume":"24","author":"S Er-lin","year":"2004","unstructured":"Er-lin, S., Shi-duo, S., Wei, Q. & Qing-lan, G. Stenotrophomonas maltophilia SmeDEF efflux pump and the regulation mechanism. Zhonghua Liu Xing Bing Xue Za Zhi 24(9), 743\u2013747 (2004).","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"88977_CR27","doi-asserted-by":"publisher","first-page":"822","DOI":"10.3389\/fmicb.2019.00822","volume":"10","author":"CJ Wu","year":"2019","unstructured":"Wu, C. J. et al. Substantial contribution of SmeDEF, SmeVWX, SmQnr, and heat shock response to fluoroquinolone resistance in clinical isolates of Stenotrophomonas maltophilia. Front. Microbiol. 10, 822 (2019).","journal-title":"Front. Microbiol."},{"key":"88977_CR28","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.nmni.2015.04.009","volume":"7","author":"H Kanamori","year":"2015","unstructured":"Kanamori, H. et al. Prevalence of Smqnr and plasmid-mediated quinolone resistance determinants in clinical isolates of Stenotrophomonas maltophilia from Japan: Novel variants of Smqnr. New Microbes New Infect. 7, 8\u201314 (2015).","journal-title":"New Microbes New Infect."},{"issue":"3","key":"88977_CR29","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1093\/jac\/dkp476","volume":"65","author":"N Gordon","year":"2010","unstructured":"Gordon, N. & Wareham, D. Novel variants of the Smqnr family of quinolone resistance genes in clinical isolates of Stenotrophomonas maltophilia. J. Antimicrob. Chemother. 65(3), 483\u2013489 (2010).","journal-title":"J. Antimicrob. Chemother."},{"issue":"10","key":"88977_CR30","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1128\/AAC.00026-08","volume":"52","author":"K Shimizu","year":"2008","unstructured":"Shimizu, K. et al. Smqnr, a new chromosome-carried quinolone resistance gene in Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 52(10), 3823\u20133825 (2008).","journal-title":"Antimicrob. Agents Chemother."},{"key":"88977_CR31","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/AAC.00997-08","volume":"53","author":"LM Cavaco","year":"2009","unstructured":"Cavaco, L. M., Hasman, H., Xia, S. & Aarestrup, F. M. qnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovar Kentucky and Bovismorbificans strains of human origin. Antimicrob. Agents Chemother. 53, 603\u2013608 (2009).","journal-title":"Antimicrob. Agents Chemother."},{"key":"88977_CR32","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1093\/jac\/dki182","volume":"56","author":"S Valdezate","year":"2005","unstructured":"Valdezate, S., Vindel, A., Sa\u00e9z-Nieto, J. A., Baquero, F. & Cant\u00f3n, R. Preservation of topoisomerase genetic sequences during in vivo and in vitro development of high-level resistance to ciprofloxacin in isogenic Stenotrophomonas maltophilia strains. J. Antimicrob. Chemother. 56, 220\u2013223 (2005).","journal-title":"J. Antimicrob. Chemother."},{"key":"88977_CR33","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.micpath.2016.08.034","volume":"99","author":"A Aliramezani","year":"2016","unstructured":"Aliramezani, A., Douraghi, M., Hajihasani, A., Mohammadzadeh, M. & Rahbar, M. Clonal relatedness and biofilm formation of OXA-23-producing carbapenem resistant Acinetobacter baumannii isolates from hospital environment. Microb. Pathog. 99, 204\u2013208 (2016).","journal-title":"Microb. Pathog."},{"issue":"12","key":"88977_CR34","doi-asserted-by":"publisher","first-page":"4305","DOI":"10.1128\/JCM.38.12.4305-4309.2000","volume":"38","author":"PW Whitby","year":"2000","unstructured":"Whitby, P. W. et al. Identification and detection of Stenotrophomonas maltophilia by rRNA-directed PCR. J. Clin. Microbiol. 38(12), 4305\u20134309 (2000).","journal-title":"J. Clin. Microbiol."},{"key":"88977_CR35","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing. CLSI Supplement M100","author":"CLSI","year":"2020","unstructured":"CLSI. Performance Standards for Antimicrobial Susceptibility Testing. CLSI Supplement M100 30th edn. (Clinical and laboratory Standards Institute, 2020).","edition":"30"},{"key":"88977_CR36","unstructured":"BSAC Methods for antimicrobial susceptibility testing\u00a0(accessed May 2013); http:\/\/www.bsac.org.uk\/Susceptibility+Testing\/GUIDELINES+Standardized+Disc+Susceptibility+Testing+Method."},{"issue":"3","key":"88977_CR37","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1093\/jac\/49.3.471","volume":"49","author":"J Vila","year":"2002","unstructured":"Vila, J. et al. Activity of clinafloxacin, compared with six other quinolones, against Acinetobacter baumannii clinical isolates. J. Antimicrob. Chemother. 49(3), 471\u2013477 (2002).","journal-title":"J. Antimicrob. Chemother."},{"issue":"12","key":"88977_CR38","first-page":"757","volume":"28","author":"S Er-lin","year":"2003","unstructured":"Er-lin, S., Shi-duo, S. & Dian-jun, W. Effect of efflux inhibitor on the activity of fluoroquinlone to Stenotrophomonas maltophilia. Zhongguo Kang Sheng Su Za Zhi. 28(12), 757\u2013760 (2003).","journal-title":"Zhongguo Kang Sheng Su Za Zhi."},{"issue":"11","key":"88977_CR39","doi-asserted-by":"publisher","first-page":"e01263","DOI":"10.1128\/AAC.01263-18","volume":"62","author":"P Blanco","year":"2018","unstructured":"Blanco, P., Corona, F. & Martinez, J. L. Biolog phenotype microarray is a tool for the identification of multidrug resistance efflux pump inducers. Antimicrob. Agents Chemother. 62(11), e01263\u2013e01318 (2018).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"12","key":"88977_CR40","doi-asserted-by":"publisher","first-page":"5826","DOI":"10.1128\/AAC.00317-11","volume":"55","author":"CH Chen","year":"2011","unstructured":"Chen, C. H. et al. Contribution of resistance-nodulation-division efflux pump operon smeU1-VW-U2-X to multidrug resistance of Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 55(12), 5826\u20135833 (2011).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"15","key":"88977_CR41","doi-asserted-by":"publisher","first-page":"4559","DOI":"10.1128\/AEM.01058-14","volume":"80","author":"G Garc\u00eda-Le\u00f3n","year":"2014","unstructured":"Garc\u00eda-Le\u00f3n, G. et al. A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots. Appl. Environ. Microbiol. 80(15), 4559\u20134565 (2014).","journal-title":"Appl. Environ. Microbiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-88977-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-88977-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-88977-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T07:38:27Z","timestamp":1670053107000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-88977-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["88977"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-88977-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"11 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9582"}}