{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:01:32Z","timestamp":1790928092470,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, and SOD2 rs11968525) and skeletal fluorosis, and examined potential gene\u2013environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cross-sectional study was conducted in the Zhijin County, Guizhou Province of China. Skeletal fluorosis was identified according to the Chinese Diagnostic Criteria of Endemic Skeletal Fluorosis. Dietary information was assessed through face-to-face interviews by trained interviewers using a 75-item food frequency questionnaire. The genotype was detected by high throughput TaqMan-MGB RT-PCR technology. Odds ratios (ORs) and 95% CIs were calculated using an unconditional logistic regression model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intake of vitamin E, zinc, and selenium was found to be inversely associated with the risk of skeletal fluorosis. The multivariable-adjusted ORs were 0.438 (95% CI: 0.268 to 0.715, <jats:italic>P-<\/jats:italic>trend &amp;lt; 0.001) for vitamin E, 0.490 (95% CI: 0.298 to 0.805, <jats:italic>P-<\/jats:italic>trend = 0.001) for zinc, and 0.532 (95% CI: 0.324 to 0.873, <jats:italic>P-<\/jats:italic>trend = 0.010) for selenium when comparing the highest with the lowest quartile. The relationship for vitamin C was not observed after adjustment for risk factors. Furthermore, participants with PON1 rs662 AA genotype had a significantly decreased risk of skeletal fluorosis compared with those with the GG genotype (OR = 0.438, 95% CI: 0.231 to 0.830). GG + AG genotype carriers were 2.212 times more likely to have skeletal fluorosis than AA carriers (OR = 2.212, 95% CI: 1.197 to 4.090). Compared with AA carriers, AG carriers had a 2.182 times higher risk of skeletal fluorosis (OR = 2.182, 95% CI: 1.143 to 4.163). Although we observed the risk of skeletal fluorosis was higher with a lower intake of antioxidant nutrients, the potential interactions between nutrient intake and genetic polymorphisms were not observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Participants with a higher intake of vitamin E, zinc, and selenium have a lower likelihood of skeletal fluorosis. In addition, the PON1 rs662 polymorphism is related to skeletal fluorosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2022.849173","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T08:45:46Z","timestamp":1652431546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China"],"prefix":"10.3389","volume":"10","author":[{"given":"Na","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3967\/bes2017.020","article-title":"Treatment and Prevention of Skeletal Fluorosis","volume":"30","author":"Yang","year":"2017","journal-title":"Biomed Environ Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3967\/bes2018.057","article-title":"Association of dietary carotenoids intake with skeletal fluorosis in the coal-burning fluorosis area of guizhou province","volume":"31","author":"Liu","year":"2018","journal-title":"Biomed Environ Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"103331","DOI":"10.1016\/j.etap.2020.103331","article-title":"The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of bMP-2 and bMP-7 in rats","volume":"75","author":"Ma","year":"2020","journal-title":"Environ Toxicol Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1007\/s40572-020-00270-9","article-title":"Fluoride in drinking water and skeletal fluorosis: a review of the global impact","volume":"7","author":"Srivastava","year":"2020","journal-title":"Curr Environ Health Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cbi.2016.11.021","article-title":"Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated caspase pathways","volume":"261","author":"Li","year":"2017","journal-title":"Chem Biol Interact."},{"key":"B6","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1158\/1055-9965.EPI-14-0968","article-title":"Oxidative stress-related genetic variants, pro- and antioxidant intake and status, and advanced prostate cancer risk","volume":"24","author":"Geybels","year":"2015","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"B7","first-page":"154","article-title":"The effect of vitamin C and vitamin E on DNA damage, oxidative status, and some biochemical parameters in rats with experimental fluorosis","volume":"53","author":"Oner AC Dede","year":"2020","journal-title":"Fluoride."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.3382\/ps\/pey192","article-title":"Antagonistic effects of different selenium sources on growth inhibition, oxidative damage, and apoptosis induced by fluorine in broilers","volume":"97","author":"Wang","year":"2018","journal-title":"Poult Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1007\/s12011-020-02243-3","article-title":"Elemental status and lipid peroxidation in the blood of children with endemic fluorosis","volume":"199","author":"Tkachenko","year":"2021","journal-title":"Biol Trace Elem Res."},{"key":"B10","first-page":"43","article-title":"The distribution of minerals in some tissues of sheep with fluorosis","volume":"47","author":"Aydin","year":"2014","journal-title":"Fluoride."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e011980","DOI":"10.1136\/bmjopen-2016-011980","article-title":"Association between vitamin d receptor gene fokI polymorphism and skeletal fluorosis of the brick-tea type fluorosis: a cross sectional, case control study","volume":"6","author":"Yang","year":"2016","journal-title":"BMJ Open."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0171011","DOI":"10.1371\/journal.pone.0171011","article-title":"Prolactin rs1341239 t allele may have protective role against the brick tea type skeletal fluorosis","volume":"12","author":"Li","year":"2017","journal-title":"PLoS ONE."},{"key":"B13","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.sdentj.2019.05.004","article-title":"Association of cOL1A2 (PvuII) gene polymorphism with risk and severity of dental fluorosis \u2013 a case control study","volume":"31","author":"Rahila","year":"2019","journal-title":"Saudi Dental Journal"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1136\/jmg.2006.042259","article-title":"Associations of catalase gene polymorphisms with bone mineral density and bone turnover markers in postmenopausal women","volume":"44","author":"Oh","year":"2007","journal-title":"J Med Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.reprotox.2006.01.003","article-title":"Paraoxonase gene polymorphism and vitamin levels during pregnancy: relationship with maternal oxidative stress and neonatal birthweights","volume":"22","author":"Min","year":"2006","journal-title":"Reprod Toxicol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.clinbiochem.2020.11.010","article-title":"Single-nucleotide polymorphisms (SNPs) of antioxidant enzymes sOD2 and gSTP1 genes and sLE risk and severity in an egyptian pediatric population","volume":"88","author":"Abd El Azeem","year":"2021","journal-title":"Clin Biochem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s10653-013-9522-2","article-title":"Coal-burning endemic fluorosis is associated with reduced activity in antioxidative enzymes and cu\/Zn-SOD gene expression","volume":"36","author":"Wang","year":"2014","journal-title":"Environ Geochem Health."},{"key":"B18","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3390\/antiox8080252","article-title":"Paraoxonases (PON) 1, 2, and 3 polymorphisms and pON-1 activities in patients with sickle cell disease","volume":"8","author":"Reichert","year":"2019","journal-title":"Antioxidants (Basel)."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1002\/2211-5463.12991","article-title":"Gastrodin alleviates bone damage by modulating protein expression and tissue redox state","volume":"10","author":"Zheng","year":"2020","journal-title":"FEBS Open Bio."},{"key":"B20","first-page":"374","article-title":"Investigation of blood antioxidant enzyme levels and glutathione peroxidase, catalase, and superoxide dismutase gene polymorphism in sheep with fluorosis","volume":"50","author":"Ozbey","year":"2017","journal-title":"Fluoride."},{"key":"B21","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3760\/cma.j.issn.0529-5807.2012.09.012","article-title":"Effect of fluoride on oxidative stress and mn-SOD expression in rats with endemic fluorosis of coal burning","volume":"41","author":"Li HL Yu","year":"2012","journal-title":"Zhonghua Bing Li Xue Za Zhi."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000316636","article-title":"Paraoxonase 1 polymorphisms 172T \u2192 A and 584A \u2192 G modify the association between serum concentrations of the antioxidant lycopene and bone turnover markers and oxidative stress parameters in women 25-70 years of age","volume":"3","author":"Mackinnon","year":"2010","journal-title":"J Nutrigenet Nutrigenomics."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6519","DOI":"10.1007\/s11033-013-2770-5","article-title":"Investigation of the common paraoxonase 1 variants with paraoxonase activity on bone fragility in turkish patients","volume":"40","author":"Topta\u015f","year":"2013","journal-title":"Mol Biol Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1097\/gme.0b013e31822d5b10","article-title":"Antioxidant enzymes gSR, sOD1, sOD2, and cAT gene variants and bone mineral density values in postmenopausal women: a genetic association analysis","volume":"19","author":"Mlakar","year":"2012","journal-title":"Menopause."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1002\/jbmr.471","article-title":"An integrative study ascertained sOD2 as a susceptibility gene for osteoporosis in chinese","volume":"26","author":"Deng","year":"2011","journal-title":"J Bone Miner Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12263-017-0590-2","article-title":"Ruiz-de-Santiago D, Galicia-Castillo O, Buenrostro-Jauregui M, Diaz-Gutierrez C. Genetic polymorphisms of antioxidant enzymes cAT and sOD affect the outcome of clinical, biochemical, and anthropometric variables in people with obesity under a dietary intervention","volume":"13","author":"Hernandez-Guerrero","year":"2018","journal-title":"Genes Nutr."},{"key":"B27","first-page":"231","article-title":"Effects of polymorphisms in vitamin E-, vitamin C-, and glutathione peroxidase-related genes on serum biomarkers and associations with glaucoma","volume":"19","author":"Zanon-Moreno","year":"2013","journal-title":"Mol Vis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00394-015-0896-z","article-title":"Habitual dietary intake of beta-carotene, vitamin c, folate, or vitamin e may interact with single nucleotide polymorphisms on brachial-ankle pulse wave velocity in healthy adults","volume":"55","author":"Park","year":"2016","journal-title":"Eur J Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"826","DOI":"10.3390\/nu14040826","article-title":"Genetic variation interacts with selenium exposure regarding breast cancer risk: assessing dietary intake, serum levels and genetically elevated selenium levels","volume":"14","author":"Sandsveden","year":"2022","journal-title":"Nutrients"},{"key":"B30","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1093\/carcin\/bgp310","article-title":"Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer","volume":"31","author":"Tang","year":"2010","journal-title":"Carcinogenesis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"700726","DOI":"10.3389\/fnut.2021.700726","article-title":"Association between dietary intake of one-Carbon metabolism-Related nutrients and fluorosis in guizhou, china","volume":"8","author":"Chen","year":"2021","journal-title":"Front Nutr."},{"key":"B32","article-title":"Industry Standard of the People's Republic of China Diagnosis for Endemic Skeletal Fluorosis (WS\/T 192-2008)","year":"2008"},{"key":"B33","volume-title":"China Food Composition","author":"Yang","year":"2004"},{"key":"B34","doi-asserted-by":"publisher","first-page":"240","DOI":"10.6133\/apjcn.2009.18.2.13","article-title":"Validity and reproducibility of a food frequency Questionnaire among Chinese women in Guangdong province","volume":"18","author":"Zhang","year":"2009","journal-title":"Asia Pac J Clin Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3389\/fnut.2019.00189","article-title":"Association between dietary patterns and fluorosis in guizhou, china","volume":"6","author":"Liu","year":"2019","journal-title":"Front Nutr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"182","DOI":"10.4103\/0971-6580.97220","article-title":"To study the effect of vitamin d and e on sodium-Fluoride-induced toxicity in reproductive functions of male rabbits","volume":"19","author":"Kumar","year":"2012","journal-title":"Toxicol Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.etap.2015.06.022","article-title":"Study of the relationship between the lifestyle of residents residing in fluorosis endemic areas and adult skeletal fluorosis","volume":"40","author":"Liu","year":"2015","journal-title":"Environ Toxicol Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"72","DOI":"10.4103\/2277-9531.171785","article-title":"Fluoride exposure and its health risk assessment in drinking water and staple food in the population of dayyer, iran, in 2013","volume":"4","author":"Keshavarz","year":"2015","journal-title":"J Educ Health Promot"},{"key":"B39","doi-asserted-by":"publisher","first-page":"BSR20171003","DOI":"10.1042\/BSR20171003","article-title":"Vitamin e and lycopene reduce coal burning fluorosis-induced spermatogenic cell apoptosis via oxidative stress-mediated jNK and eRK signaling pathways","volume":"38","author":"Tian","year":"2018","journal-title":"Biosci Rep"},{"key":"B40","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s12011-011-9251-2","article-title":"Influence of methionine and vitamin e on fluoride concentration in bones and teeth of rats exposed to sodium fluoride in drinking water","volume":"146","author":"Blaszczyk","year":"2012","journal-title":"Biol Trace Elem Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s12011-018-1271-8","article-title":"Fluoride alters serum elemental (Calcium, magnesium, copper, and zinc) homeostasis along with erythrocyte carbonic anhydrase activity in fluorosis endemic villages and restores on supply of safe drinking water in school-going children of nalgonda district, india","volume":"185","author":"Khandare","year":"2018","journal-title":"Biol Trace Elem Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s12011-010-8892-x","article-title":"Serum copper, zinc, and magnesium levels in patients with chronic fluorosis","volume":"143","author":"Ersoy","year":"2011","journal-title":"Biol Trace Elem Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.etp.2010.11.014","article-title":"Influence of selenium and fluoride on blood antioxidant capacity of rats","volume":"64","author":"Feng","year":"2012","journal-title":"Exp Toxicol Pathol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1007\/s12011-011-9087-9","article-title":"Intervention of selenium on chronic fluorosis-induced injury of blood antioxidant capacity in rats","volume":"144","author":"Feng","year":"2011","journal-title":"Biol Trace Elem Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1007\/s12011-020-02185-w","article-title":"Selenium exerts protective effects against fluoride-Induced apoptosis and oxidative stress and altered the expression of bcl-2\/caspase family","volume":"199","author":"Gao","year":"2021","journal-title":"Biol Trace Elem Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"173098","DOI":"10.1016\/j.ejphar.2020.173098","article-title":"Selenium may suppress peripheral blood mononuclear cell apoptosis by modulating hSP70 and regulate levels of sIRT1 through reproductive hormone secretion and oxidant stress in women suffering fluorosis","volume":"878","author":"Li","year":"2020","journal-title":"Eur J Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.etap.2013.08.003","article-title":"Intervention of selenium on apoptosis and fas\/FasL expressions in the liver of fluoride-exposed rats","volume":"36","author":"Miao","year":"2013","journal-title":"Environ Toxicol Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e8198","DOI":"10.1097\/MD.0000000000008198","article-title":"The genetic association between pON1 polymorphisms and osteonecrosis of femoral head: a case-control study","volume":"96","author":"Li JM Li","year":"2017","journal-title":"Medicine (Baltimore)."},{"key":"B49","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s11657-020-00854-w","article-title":"Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis","volume":"16","author":"Zhao","year":"2021","journal-title":"Arch Osteoporos."},{"key":"B50","doi-asserted-by":"publisher","first-page":"210","DOI":"10.3390\/life10090210","article-title":"Association of genes related to oxidative stress with the extent of coronary atherosclerosis","volume":"10","author":"Racis","year":"2020","journal-title":"Life (Basel)."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1540949","DOI":"10.1155\/2017\/1540949","article-title":"Relationship between rs854560 pON1 gene polymorphism and tobacco smoking with coronary artery disease","volume":"2017","author":"Iwanicka","year":"2017","journal-title":"Dis Markers."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1111\/jcmm.13453","article-title":"European versus asian differences for the associations between paraoxonase-1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus","volume":"22","author":"Luo","year":"2018","journal-title":"J Cell Mol Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e7416","DOI":"10.1097\/MD.0000000000007416","article-title":"Correlation of pON1 polymorphisms with ankylosing spondylitis susceptibility: a case-control study in chinese han population","volume":"96","author":"Xu","year":"2017","journal-title":"Medicine (Baltimore)."},{"key":"B54","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3858\/emm.2011.43.2.009","article-title":"Association of paraoxonase 1 (PON1) polymorphisms with osteoporotic fracture risk in postmenopausal korean women","volume":"43","author":"Kim","year":"2011","journal-title":"Exp Mol Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"27438","DOI":"10.1074\/jbc.M109.023572","article-title":"Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic wnt signaling in the skeleton","volume":"284","author":"Almeida","year":"2009","journal-title":"J Biol Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.freeradbiomed.2014.07.005","article-title":"Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study","volume":"74","author":"Galan-Chilet","year":"2014","journal-title":"Free Radic Biol Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1080\/09637486.2019.1680958","article-title":"Impact of oxidative stress sNPs and dietary antioxidant quality score on prostate cancer","volume":"71","author":"Pascual-Geler","year":"2020","journal-title":"Int J Food Sci Nutr."}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.849173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T08:46:02Z","timestamp":1652431562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.849173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,13]]},"references-count":57,"alternative-id":["10.3389\/fpubh.2022.849173"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2022.849173","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,13]]},"article-number":"849173"}}