{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:50Z","timestamp":1787028770905,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program","award":["2018YFC1002600"],"award-info":[{"award-number":["2018YFC1002600"]}]},{"name":"the Natural Science Foundation of Guangdong Province","award":["2018A030313785"],"award-info":[{"award-number":["2018A030313785"]}]},{"name":"the Natural Science Foundation of Guangdong Province","award":["2018A030313329"],"award-info":[{"award-number":["2018A030313329"]}]},{"name":"the Science and Technology Planning Project of Guangdong Province, China","award":["2014A050503048, 2017A070701013, 2017B090904034, 2017030314109, and 2019B020230003"],"award-info":[{"award-number":["2014A050503048, 2017A070701013, 2017B090904034, 2017030314109, and 2019B020230003"]}]},{"name":"the Guangdong Peak Project","award":["DFJH201802"],"award-info":[{"award-number":["DFJH201802"]}]},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease","award":["2012A061400008"],"award-info":[{"award-number":["2012A061400008"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903287"],"award-info":[{"award-number":["81903287"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)\/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004\u20132016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS\/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS\/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.<\/jats:p>","DOI":"10.3390\/life11080724","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T11:53:23Z","timestamp":1626868403000},"page":"724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-6338","authenticated-orcid":false,"given":"Yanji","family":"Qu","sequence":"first","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"},{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-7504","authenticated-orcid":false,"given":"Shao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA"},{"name":"Department of Epidemiology and Biostatistics, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-5494","authenticated-orcid":false,"given":"Michael S.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Global and Community Health, George Mason University, Fairfax, VA 22030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-1105","authenticated-orcid":false,"given":"Ximeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Nie","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Ou","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhuang","family":"Mai","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmin","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimei","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Justino","sequence":"additional","affiliation":[{"name":"Department of Health Policy, Management and Behavior, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhuan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"58","author":"Konings","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/CIRCULATIONAHA.110.958405","article-title":"Congenital heart defects in Europe: Prevalence and perinatal mortality, 2000 to 2005","volume":"123","author":"Dolk","year":"2011","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jpeds.2014.09.006","article-title":"Long-term outcomes in children with congenital heart disease: National Health Interview Survey","volume":"166","author":"Razzaghi","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S2352-4642(19)30402-X","article-title":"2017 C.H.D. Global, regional, and national burden of congenital heart disease, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"4","author":"Collaborators","year":"2020","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1161\/01.CIR.38.3.604","article-title":"Multifactorial inheritance hypothesis for the etiology of congenital heart diseases. The genetic-environmental interaction","volume":"38","author":"Nora","year":"1968","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1161\/CIRCULATIONAHA.106.183056","article-title":"Genetic basis for congenital heart defects: Current knowledge: A scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics","volume":"115","author":"Pierpont","year":"2007","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000606","article-title":"Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement from the American Heart Association","volume":"138","author":"Pierpont","year":"2018","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Russell, M.W., Chung, W.K., Kaltman, J.R., and Miller, T.A. (2018). Advances in the Understanding of the Genetic Determinants of Congenital Heart Disease and Their Impact on Clinical Outcomes. J. Am. Heart Assoc., 7.","DOI":"10.1161\/JAHA.117.006906"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: Current knowledge: A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics","volume":"115","author":"Jenkins","year":"2007","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1007\/s11356-016-8198-4","article-title":"The influence of maternal exposure history to virus and medicine during pregnancy on congenital heart defects of fetus","volume":"24","author":"Liang","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/jp.2014.76","article-title":"Congenital heart defects and maternal fever: Systematic review and meta-analysis","volume":"34","author":"Shi","year":"2014","journal-title":"J. Perinatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1007\/s00246-015-1182-9","article-title":"Maternal Hypertension during Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis","volume":"36","author":"Ramakrishnan","year":"2015","journal-title":"Pediatr. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/pr.2015.264","article-title":"Risk factors of different congenital heart defects in Guangdong, China","volume":"79","author":"Ou","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.5694\/mja12.10811","article-title":"Congenital heart disease: Current knowledge about causes and inheritance","volume":"197","author":"Blue","year":"2012","journal-title":"Med. J. Aust."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00246-014-1079-z","article-title":"Maternal reproductive history and the risk of congenital heart defects in offspring: A systematic review and meta-analysis","volume":"36","author":"Feng","year":"2015","journal-title":"Pediatr. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/2047487319874530","article-title":"Parental alcohol consumption and the risk of congenital heart diseases in offspring: An updated systematic review and meta-analysis","volume":"27","author":"Zhang","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1177\/2047487319831367","article-title":"Parental smoking and the risk of congenital heart defects in offspring: An updated meta-analysis of observational studies","volume":"27","author":"Zhao","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, Z., Li, X., Li, N., Li, S., Deng, K., Lin, Y., Chen, X., You, F., Li, J., and Mu, D. (2013). Association between maternal exposure to housing renovation and offspring with congenital heart disease: A multi-hospital case-control study. Environ. Health, 12.","DOI":"10.1186\/1476-069X-12-25"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1536\/ihj.16-054","article-title":"A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects","volume":"57","author":"Xu","year":"2016","journal-title":"Int. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yu, D., Feng, Y., Yang, L., Da, M., Fan, C., Wang, S., and Mo, X. (2014). Maternal socioeconomic status and the risk of congenital heart defects in offspring: A meta-analysis of 33 studies. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111056"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8506","DOI":"10.1038\/srep08506","article-title":"Maternal folic acid supplementation and the risk of congenital heart defects in offspring: A meta-analysis of epidemiological observational studies","volume":"5","author":"Feng","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Qu, Y., Lin, S., Zhuang, J., Bloom, M.S., Smith, M., Nie, Z., Mai, J., Ou, Y., Wu, Y., and Gao, X. (2020). First trimester maternal folic acid supplementation reduced risks of severe and most congenital heart diseases in offspring: A large case control study. J. Am. Heart Assoc.","DOI":"10.1161\/JAHA.119.015652"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1017\/S1368980014000950","article-title":"Changes in folic acid supplementation behaviour among women of reproductive age after the implementation of a massive supplementation programme in China","volume":"18","author":"Liu","year":"2015","journal-title":"Public Health Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.envpol.2017.11.023","article-title":"Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?","volume":"234","author":"Liu","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1002\/bdra.20780","article-title":"Paper 1: The EUROCAT network--organization and processes","volume":"91","author":"Boyd","year":"2011","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Slaughter, J.L., Cua, C.L., Notestine, J.L., Rivera, B.K., Marzec, L., Hade, E.M., Maitre, N.L., Klebanoff, M.A., Ilgenfritz, M., and Le, V.T. (2019). Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: A prospective cohort investigation. BMC Pediatr., 19.","DOI":"10.1186\/s12887-019-1708-z"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105859","DOI":"10.1016\/j.envint.2020.105859","article-title":"Maternal residential greenness and congenital heart defects in infants: A large case-control study in Southern China","volume":"142","author":"Nie","year":"2020","journal-title":"Environ. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e373","DOI":"10.1542\/peds.2013-3949","article-title":"Delayed diagnosis of critical congenital heart defects: Trends and associated factors","volume":"134","author":"Liberman","year":"2014","journal-title":"Pediatrics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/bdra.20403","article-title":"Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies","volume":"79","author":"Botto","year":"2007","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_30","unstructured":"Mouri, M., Hall, H., and Rupp, T.J. (2021). Threatened Abortion, StatPearls."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/EDE.0b013e31818f6651","article-title":"When one depends on the other: Reporting of interaction in case-control and cohort studies","volume":"20","author":"Knol","year":"2009","journal-title":"Epidemiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10654-011-9554-9","article-title":"Estimating measures of interaction on an additive scale for preventive exposures","volume":"26","author":"Knol","year":"2011","journal-title":"Eur. J. Epidemiol."},{"key":"ref_33","first-page":"ix","article-title":"Infectious diseases in pregnancy","volume":"41","author":"Rayburn","year":"2014","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e011264","DOI":"10.1161\/JAHA.118.011264","article-title":"Maternal Viral Infection and Risk of Fetal Congenital Heart Diseases: A Meta-Analysis of Observational Studies","volume":"8","author":"Ye","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/00001648-200109000-00004","article-title":"Congenital heart defects, maternal febrile illness, and multivitamin use: A population-based study","volume":"12","author":"Botto","year":"2001","journal-title":"Epidemiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/00001648-200207000-00019","article-title":"Maternal fever, multivitamin use, and selected birth defects: Evidence of interaction?","volume":"13","author":"Botto","year":"2002","journal-title":"Epidemiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1097\/00001648-200211000-00005","article-title":"Maternal periconceptional vitamins: Interactions with selected factors and congenital anomalies?","volume":"13","author":"Shaw","year":"2002","journal-title":"Epidemiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/oxfordjournals.aje.a117243","article-title":"Maternal flu, fever, and the risk of neural tube defects: A population-based case-control study","volume":"140","author":"Lynberg","year":"1994","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1542\/peds.92.4.559","article-title":"Association of the common cold in the first trimester of pregnancy with birth defects","volume":"92","author":"Zhang","year":"1993","journal-title":"Pediatrics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/(SICI)1096-9926(199709)56:3<210::AID-TERA4>3.0.CO;2-4","article-title":"Induction of thermotolerance in early postimplantation rat embryos is associated with increased resistance to hyperthermia-induced apoptosis","volume":"56","author":"Mirkes","year":"1997","journal-title":"Teratology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kvansakul, M. (2017). Viral Infection and Apoptosis. Viruses, 9.","DOI":"10.3390\/v9120356"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1242\/dev.125.19.3809","article-title":"Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death","volume":"125","author":"Watanabe","year":"1998","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/jn\/129.1.25","article-title":"Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells","volume":"129","author":"Huang","year":"1999","journal-title":"J. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Qu, Y., Liu, X., Zhuang, J., Chen, G., Mai, J., Guo, X., Ou, Y., Chen, J., Gong, W., and Gao, X. (2016). Incidence of Congenital Heart Disease: The 9-Year Experience of the Guangdong Registry of Congenital Heart Disease, China. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159257"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:32:54Z","timestamp":1760164374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,21]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["life11080724"],"URL":"https:\/\/doi.org\/10.3390\/life11080724","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,21]]}}}