{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:51:42Z","timestamp":1790481102564,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1007\/s00204-021-03016-0","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T08:03:23Z","timestamp":1615449803000},"page":"1763-1778","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcriptome analysis reveals lung-specific miRNAs associated with impaired mucociliary clearance induced by cigarette smoke in an in vitro human airway tissue model"],"prefix":"10.1007","volume":"95","author":[{"given":"Rui","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leihong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levan","family":"Muskhelishvili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Rosenfeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Healy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-5102","authenticated-orcid":false,"given":"Xuefei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"issue":"5","key":"3016_CR1","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1080\/00039896.1969.10665482","volume":"18","author":"RE Albert","year":"1969","unstructured":"Albert RE, Lippmann M, Briscoe W (1969) The characteristics of bronchial clearance in humans and the effects of cigarette smoking. Arch Environ Health Int J 18(5):738\u2013755. https:\/\/doi.org\/10.1080\/00039896.1969.10665482","journal-title":"Arch Environ Health Int J"},{"issue":"2","key":"3016_CR2","doi-asserted-by":"publisher","first-page":"S30","DOI":"10.1016\/j.diff.2011.11.015","volume":"83","author":"P Avasthi","year":"2012","unstructured":"Avasthi P, Marshall WF (2012) Stages of ciliogenesis and regulation of ciliary length. Differentiation 83(2):S30-42. https:\/\/doi.org\/10.1016\/j.diff.2011.11.015","journal-title":"Differentiation"},{"issue":"17","key":"3016_CR3","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1056\/NEJM196010272631704","volume":"263","author":"JJ Ballenger","year":"1960","unstructured":"Ballenger JJ (1960) Experimental effect of cigarette smoke on human respiratory cilia. N Engl J Med 263(17):832\u2013835. https:\/\/doi.org\/10.1056\/NEJM196010272631704","journal-title":"N Engl J Med"},{"issue":"2","key":"3016_CR4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215\u2013233. https:\/\/doi.org\/10.1016\/j.cell.2009.01.002","journal-title":"Cell"},{"issue":"4","key":"3016_CR5","doi-asserted-by":"publisher","first-page":"a028241","DOI":"10.1101\/cshperspect.a028241","volume":"9","author":"XM Bustamante-Marin","year":"2017","unstructured":"Bustamante-Marin XM, Ostrowski LE (2017) Cilia and mucociliary clearance. Cold Spring Harb Perspect Biol 9(4):a028241-a28318. https:\/\/doi.org\/10.1101\/cshperspect.a028241","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"1","key":"3016_CR501","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/toxsci\/kfw239","volume":"156","author":"X Cao","year":"2017","unstructured":"Cao X, Muskhelishvili L, Latendresse J, Richter P, Heflich RH (2017) Evaluating the toxicity of cigarette whole smoke solutions in an air-liquid-interface human in vitro irway tissue model. Toxicol Sci 156(1):14\u201324. https:\/\/doi.org\/10.1093\/toxsci\/kfw239","journal-title":"Toxicol Sci"},{"key":"3016_CR502","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.tox.2018.07.015","volume":"409","author":"X Cao","year":"2018","unstructured":"Cao X, Wang Y, Xiong R, Muskhelishvili L, Davis K, Richter PA, Heflich RH (2018) Cigarette whole smoke solutions disturb mucin homeostasis in a human in vitro airway tissue model. Toxicology 409:119\u2013128. https:\/\/doi.org\/10.1016\/j.tox.2018.07.015","journal-title":"Toxicology"},{"issue":"3","key":"3016_CR6","doi-asserted-by":"publisher","first-page":"e1000422","DOI":"10.1371\/journal.pgen.1000422","volume":"5","author":"B Chhin","year":"2009","unstructured":"Chhin B, Negre D, Merrot O, Pham J, Tourneur Y, Ressnikoff D et al (2009) Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy. PloS Genet 5(3):e1000422","journal-title":"PloS Genet"},{"issue":"1","key":"3016_CR7","doi-asserted-by":"publisher","first-page":"12871","DOI":"10.1038\/s41598-017-13265-8","volume":"7","author":"G Conickx","year":"2017","unstructured":"Conickx G, Avila Cobos F, van den Berge M, Faiz A, Timens W, Hiemstra PS et al (2017) microRNA profiling in lung tissue and bronchoalveolar lavage of cigarette smoke-exposed mice and in copd patients: a translational approach. Sci Rep 7(1):12871. https:\/\/doi.org\/10.1038\/s41598-017-13265-8","journal-title":"Sci Rep"},{"issue":"2","key":"3016_CR8","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1136\/thoraxjnl-2011-200089","volume":"67","author":"ME Ezzie","year":"2012","unstructured":"Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R et al (2012) Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 67(2):122\u2013131. https:\/\/doi.org\/10.1136\/thoraxjnl-2011-200089","journal-title":"Thorax"},{"issue":"4","key":"3016_CR9","doi-asserted-by":"publisher","first-page":"e24997","DOI":"10.4161\/tisb.24997","volume":"1","author":"S Ganesan","year":"2013","unstructured":"Ganesan S, Comstock AT, Sajjan US (2013) Barrier function of airway tract epithelium. Tissue Barriers 1(4):e24997\u2013e25010. https:\/\/doi.org\/10.4161\/tisb.24997","journal-title":"Tissue Barriers"},{"key":"3016_CR10","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1086\/319511","volume":"68","author":"C Guichard","year":"2001","unstructured":"Guichard C, Harricane MC, Lafitte JJ, Godard P, Zaegel M, Tack V et al (2001) Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia. Am J Hum Genet 68:1030\u20131035","journal-title":"Am J Hum Genet"},{"issue":"4","key":"3016_CR11","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1080\/14622200600858166","volume":"8","author":"DK Hatsukami","year":"2006","unstructured":"Hatsukami DK, Benowitz NL, Rennard SI, Oncken C, Hecht SS (2006) Biomarkers to assess the utility of potential reduced exposure tobacco products. Nicotine Tob Res 8(4):600\u2013622. https:\/\/doi.org\/10.1080\/14622200600858166","journal-title":"Nicotine Tob Res"},{"issue":"1","key":"3016_CR12","doi-asserted-by":"publisher","first-page":"e85453","DOI":"10.1371\/journal.pone.0085453","volume":"9","author":"J Hessel","year":"2014","unstructured":"Hessel J, Heldrich J, Fuller J, Staudt MR, Radisch S, Hollmann C, Harvey BG, Kaner RJ, Salit J, Yee-Levin J, Sridhar S, Pillai S, Hilton H, Wolff G, Bitter H, Visvanathan S, Fine J, Stevenson CS, Crystal RG, Tilley AE (2014) Intraflagellar and COPD. PLoS ONE 9(1):e85453\u2013e85510. https:\/\/doi.org\/10.1371\/journal.pone.0085453","journal-title":"PLoS ONE"},{"key":"3016_CR13","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1158\/1055-9965.EPI-09-0965","volume":"18","author":"MD Johnson","year":"2009","unstructured":"Johnson MD, Schilz J, Djordjevic MV, Rice JR, Shields PG (2009) Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco. Cancer Epidemiol Biomarkers Prev 18:3263\u20133304","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"12","key":"3016_CR14","doi-asserted-by":"publisher","first-page":"e8157","DOI":"10.1371\/journal.pone.0008157","volume":"4","author":"PL Leopold","year":"2009","unstructured":"Leopold PL, O\u2019Mahony MJ, Lian XJ, Tilley AE, Harvey BG, Crystal RG (2009) Smoking is associated with shortened airway cilia. PLoS ONE 4(12):e8157\u2013e8211. https:\/\/doi.org\/10.1371\/journal.pone.0008157","journal-title":"PLoS ONE"},{"issue":"22","key":"3016_CR15","doi-asserted-by":"publisher","first-page":"4579","DOI":"10.4161\/cc.9.22.13870","volume":"9","author":"M Liz\u00e9","year":"2010","unstructured":"Liz\u00e9 M, Herr C, Klimke A, Bals R, Dobbelstein M (2010) MicroRNA-449a levels increase by several orders of magnitude during mucociliary differentiation of airway epithelia. Cell Cycle 9(22):4579\u20134583. https:\/\/doi.org\/10.4161\/cc.9.22.13870","journal-title":"Cell Cycle"},{"issue":"17","key":"3016_CR16","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.4161\/cc.10.17.17181","volume":"10","author":"M Liz\u00e9","year":"2014","unstructured":"Liz\u00e9 M, Klimke A, Dobbelstein M (2014) MicroRNA-449 in cell fate determination. Cell Cycle 10(17):2874\u20132882. https:\/\/doi.org\/10.4161\/cc.10.17.17181","journal-title":"Cell Cycle"},{"issue":"6","key":"3016_CR17","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/ncb2241","volume":"13","author":"B Marcet","year":"2011","unstructured":"Marcet B, Chevalier B, Luxardi G, Coraux C, Zaragosi LE, Cibois M et al (2011) Control of vertebrate multiciliogenesis by miR-449 through direct repression of the delta\/notch pathway. Nat Cell Biol 13(6):693\u2013699. https:\/\/doi.org\/10.1038\/ncb2241","journal-title":"Nat Cell Biol"},{"issue":"3","key":"3016_CR18","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1165\/rcmb.2012-0368OC","volume":"49","author":"A Martinez-Anton","year":"2013","unstructured":"Martinez-Anton A, Sokolowska M, Kern S, Davis AS, Alsaaty S, Taubenberger JK et al (2013) Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells. Am J Respir Cell Mol Biol 49(3):384\u2013395. https:\/\/doi.org\/10.1165\/rcmb.2012-0368OC","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"3016_CR19","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.molmed.2013.10.005","volume":"20","author":"N Momi","year":"2014","unstructured":"Momi N, Kaur S, Rachagani S, Ganti AK, Batra SK (2014) Smoking and microRNA DYSREGULATION: A CANCEROUS COMBINATION. Trends Mol Med 20(1):36\u201347. https:\/\/doi.org\/10.1016\/j.molmed.2013.10.005","journal-title":"Trends Mol Med"},{"key":"3016_CR20","unstructured":"National Center for Health Statistics (US). (2015). Health, United States, 2015: With Special Feature on Racial and Ethnic Health Disparities."},{"key":"3016_CR21","doi-asserted-by":"publisher","unstructured":"Osei ET, Florez-Sampedro L, Timens W, Postma DS, Heijink IH, Brandsma, CA (2015) Unravelling the Complexity of COPD by microRNAs: it's a Small World after all, 1\u201312. https:\/\/doi.org\/10.1183\/13993003.02139-2014","DOI":"10.1183\/13993003.02139-2014"},{"issue":"40","key":"3016_CR22","doi-asserted-by":"publisher","first-page":"10660","DOI":"10.1073\/pnas.1702914114","volume":"114","author":"T Otto","year":"2017","unstructured":"Otto T, Candido SV, Pilarz MS, Sicinska E, Bronson RT, Bowden M et al (2017) Cell cycle-targeting microRNAs promote differentiation by enforcing cell-cycle exit. Proc Natl Acad Sci 114(40):10660\u201310665. https:\/\/doi.org\/10.1073\/pnas.1702914114","journal-title":"Proc Natl Acad Sci"},{"issue":"7","key":"3016_CR23","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1164\/rccm.201002-0304OC","volume":"183","author":"GRV Pottelberge","year":"2011","unstructured":"Pottelberge GRV, Mestdagh P, Bracke KR, Thas O, van Durme YMTA, Joos GF et al (2011) MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 183(7):898\u2013906. https:\/\/doi.org\/10.1164\/rccm.201002-0304OC","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"3016_CR24","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.canlet.2013.10.031","volume":"344","author":"XS Ren","year":"2014","unstructured":"Ren XS, Yin MH, Zhang X, Wang Z, Feng SP, Wang GX et al (2014) Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells. Cancer Lett 344(2):195\u2013203. https:\/\/doi.org\/10.1016\/j.canlet.2013.10.031","journal-title":"Cancer Lett"},{"issue":"8","key":"3016_CR25","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s10654-016-0132-z","volume":"31","author":"N Terzikhan","year":"2016","unstructured":"Terzikhan N, Verhamme KMC, Hofman A, Stricker BH, Brusselle GG, Lahousse L (2016) Prevalence and Incidence of COPD in smokers and non-smokers: the rotterdam study. Eur J Epidemiol 31(8):785\u2013792. https:\/\/doi.org\/10.1007\/s10654-016-0132-z","journal-title":"Eur J Epidemiol"},{"issue":"1","key":"3016_CR26","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-physiol-021014-071931","volume":"77","author":"AE Tilley","year":"2015","unstructured":"Tilley AE, Walters MS, Shaykhiev R, Crystal RG (2015) Cilia dysfunction in lung disease. Annu Rev Physiol 77(1):379\u2013406. https:\/\/doi.org\/10.1146\/annurev-physiol-021014-071931","journal-title":"Annu Rev Physiol"},{"key":"3016_CR27","first-page":"93","volume":"139","author":"E Vastag","year":"1985","unstructured":"Vastag E, Matthys H, K\u00f6hler D, Gronbeck L, Daikeler G (1985) Mucociliary clearance and airways obstruction in smokers, ex-smokers and normal subjects who never smoked. Eur J Respir Dis Suppl 139:93\u2013100","journal-title":"Eur J Respir Dis Suppl"},{"issue":"3 Pt 1","key":"3016_CR28","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1164\/ajrccm\/151.3_Pt_1.630","volume":"151","author":"F Verra","year":"1995","unstructured":"Verra F, Escudier E, Lebargy F, Bernaudin JF, De Cr\u00e9moux H, Bignon J (1995) Ciliary abnormalities in bronchial epithelium of smokers, ex-smokers, and nonsmokers. Am J Respir Crit Care Med 151(3 Pt 1):630\u2013634. https:\/\/doi.org\/10.1164\/ajrccm\/151.3_Pt_1.630","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"3016_CR29","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1159\/000348398","volume":"86","author":"RF Xavier","year":"2013","unstructured":"Xavier RF, Ramos D, Ito JT, Rodrigues FMM, Bertolini GN, Macchione M et al (2013) Effects of cigarette smoking intensity on the mucociliary clearance of active smokers. Respiration 86(6):479\u2013485. https:\/\/doi.org\/10.1159\/000348398","journal-title":"Respiration"},{"issue":"5","key":"3016_CR30","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1039\/C3MB70564A","volume":"10","author":"L Xie","year":"2014","unstructured":"Xie L, Wu M, Lin H, Liu C, Yang H, Zhan J, Sun S (2014) An Increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers. Mol BioSyst 10(5):1072\u20131081. https:\/\/doi.org\/10.1039\/C3MB70564A","journal-title":"Mol BioSyst"},{"issue":"2","key":"3016_CR31","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1093\/toxsci\/kfy226","volume":"166","author":"R Xiong","year":"2018","unstructured":"Xiong R, Wu Q, Muskhelishvili L, Davis K, Shemansky JM, Bryant M et al (2018) Evaluating mode of action of acrolein toxicity in an in vitro human airway tissue model. Toxicol Sci 166(2):451\u2013464. https:\/\/doi.org\/10.1093\/toxsci\/kfy226","journal-title":"Toxicol Sci"},{"key":"3016_CR32","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.toxlet.2018.12.009","volume":"303","author":"R Xiong","year":"2019","unstructured":"Xiong R, Wu Q, Trbojevich R, Muskhelishvili L, Davis K, Bryant M et al (2019) Disease-related responses induced by cadmium in an in vitro human airway tissue model. Toxicol Lett 303:16\u201327. https:\/\/doi.org\/10.1016\/j.toxlet.2018.12.009","journal-title":"Toxicol Lett"},{"key":"3016_CR500","doi-asserted-by":"publisher","unstructured":"Xiong R, Wu Y, Wu Q, Muskhelishvili L, Davis K, Tripathi P, Chen Y, Chen T, Bryant M, Rosenfeldt H, Healy SH, Cao X (2021) Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. https:\/\/doi.org\/10.1007\/s00204-021-03008-0","DOI":"10.1007\/s00204-021-03008-0"},{"issue":"4","key":"3016_CR33","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/cells5040040","volume":"5","author":"A Yaghi","year":"2016","unstructured":"Yaghi A, Dolovich M (2016) Airway epithelial cell cilia and obstructive lung disease. Cells 5(4):40\u201319. https:\/\/doi.org\/10.3390\/cells5040040","journal-title":"Cells"},{"issue":"8","key":"3016_CR34","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.rmed.2012.04.001","volume":"106","author":"A Yaghi","year":"2012","unstructured":"Yaghi A, Zaman A, Cox G, Dolovich MB (2012) Ciliary beating is depressed in nasal cilia from chronic obstructive pulmonary disease subjects. Respir Med 106(8):1139\u20131147. https:\/\/doi.org\/10.1016\/j.rmed.2012.04.001","journal-title":"Respir Med"},{"issue":"20","key":"3016_CR35","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1101\/gad.1819009","volume":"23","author":"X Yang","year":"2009","unstructured":"Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, Yu Q (2009) miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 Activity through a Feedback Loop by Targeting CDK6 and CDC25A. Genes Dev 23(20):2388\u20132393. https:\/\/doi.org\/10.1101\/gad.1819009","journal-title":"Genes Dev"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-021-03016-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-021-03016-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-021-03016-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T18:04:42Z","timestamp":1620756282000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-021-03016-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,11]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["3016"],"URL":"https:\/\/doi.org\/10.1007\/s00204-021-03016-0","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,11]]},"assertion":[{"value":"17 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}