{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:18:52Z","timestamp":1792109932404,"version":"4.4.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>\u201cStress\u201d is an emerging problem in our society, health care system as well as patient care, worldwide. Especially by focusing on pre-gestational, gestational but also lactation phases \u201cstress\u201d is to be considered as an own trans-generational risk factor which is associated with adverse metabolic as well cardiovascular outcomes in mothers and their children. Hence, the maternal hypothalamic-pituitary-adrenotrophic (HPA) axis may be stimulated by various \u201cstress\u201d mechanisms as well as risk factors leading to an adverse <jats:italic>in utero<\/jats:italic> environment, e.g. by excess exposure of glucocorticoids, contributing to cardio-metabolic disorders in mothers and their offspring.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To review the evidence of <jats:italic>in utero<\/jats:italic> programming by focusing on the impact of maternal \u201cstress\u201d, on adverse cardio-metabolic outcomes on their offspring later in life, by identifying underlying (patho-) physiological mechanisms (1) as well as adverse short and long-term cardio-metabolic outcomes (2).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a systematic scoping review to identify publications systematically including reviews, interventional, observational, experimental studies as well as human and animal model studies. MEDLINE (PubMed) and EMBASE databases and reference lists were searched. Peer-reviewed articles from January 2000 until August 2020 were included.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Overall, n = 2.634 citations were identified, n = 45 eligible studies were included and synthesized according to their key findings. In brief, maternal hypothalamic-pituitary-adrenotrophic (HPA) axis might play a key role modifying <jats:italic>in utero<\/jats:italic> milieu leading to cardio-metabolic diseases in the offspring later in life. However, maternal risk factor \u201cstress\u201d, is clearly linked to adverse cardio-metabolic offspring outcomes, postnatally, such as obesity, hyperglycemia, insulin resistance, diabetes mellitus (DM), Metabolic Syndrome (MetS), cardiovascular disease (CD), hypertension, restricted fetal growth as well as reduced birth, adrenal, and pancreas weights.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Women who experienced \u201cstress\u201d as risk factor, as well as their offspring, clearly have a higher risk of adverse short- as well as long-term cardio-metabolic outcomes. Future research work is needed to understand complex transgenerational mechanisms.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0245386","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T22:25:59Z","timestamp":1611354359000},"page":"e0245386","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":80,"title":["Impact of maternal prenatal stress by glucocorticoids on metabolic and cardiovascular outcomes in their offspring: A systematic scoping review"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-2020","authenticated-orcid":true,"given":"Claudia","family":"Eberle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Fasig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Br\u00fcseke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Stichling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"pone.0245386.ref001","doi-asserted-by":"crossref","first-page":"975685","DOI":"10.5402\/2012\/975685","article-title":"Diabetic and metabolic programming: mechanisms altering the intrauterine milieu","volume":"2012","author":"C Eberle","year":"2012","journal-title":"ISRN Pediatr"},{"key":"pone.0245386.ref002","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1467-8624.2009.01385.x","article-title":"The Timing of Prenatal Exposure to Maternal Cortisol and Psychosocial Stress Is Associated With Human Infant Cognitive Development","volume":"81","author":"EP Davis","year":"2010","journal-title":"Child Development"},{"key":"pone.0245386.ref003","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000362736","article-title":"Stress, the stress system and the role of glucocorticoids","volume":"22","author":"NC Nicolaides","year":"2015","journal-title":"Neuroimmunomodulation"},{"key":"pone.0245386.ref004","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system","volume":"5","author":"GP Chrousos","year":"2009","journal-title":"Nat Rev Endocrinol"},{"key":"pone.0245386.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S2040174420000471","article-title":"A combined in vivo and in silico model shows specific predictors of individual trans-generational diabetic programming","author":"C Eberle","year":"2020","journal-title":"J Dev Orig Health Dis"},{"key":"pone.0245386.ref006","doi-asserted-by":"crossref","DOI":"10.3389\/neuro.08.019.2009","article-title":"Prenatal stress, glucocorticoids and the programming of adult disease","volume":"3","author":"EC Cottrell","year":"2009","journal-title":"Front Behav Neurosci"},{"key":"pone.0245386.ref007","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.yhbeh.2010.06.007","article-title":"Glucocorticoids, prenatal stress and the programming of disease","volume":"59","author":"A Harris","year":"2011","journal-title":"Hormones and Behavior"},{"key":"pone.0245386.ref008","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/ncpendmet0515","article-title":"Mechanisms of Disease. Glucocorticoids, their placental metabolism and fetal \u2019programming\u2019 of adult pathophysiology","volume":"3","author":"JR SECKL","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"pone.0245386.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/632548","article-title":"Fetal Programming of Body Composition, Obesity, and Metabolic Function. The Role of Intrauterine Stress and Stress Biology","volume":"2012","author":"S Entringer","year":"2012","journal-title":"Journal of Nutrition and Metabolism"},{"key":"pone.0245386.ref010","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajog.2008.03.006","article-title":"Prenatal psychosocial stress exposure is associated with insulin resistance in young adults","volume":"199","author":"S Entringer","year":"2008","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"pone.0245386.ref011","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1017\/S0954579412000764","article-title":"Linking prenatal maternal adversity to developmental outcomes in infants. The role of epigenetic pathways","volume":"24","author":"C Monk","year":"2012","journal-title":"Dev Psychopathol"},{"key":"pone.0245386.ref012","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/bdrc.21021","article-title":"Long-term Effects of Prenatal Stress and Glucocorticoid Exposure","volume":"96","author":"RC Painter","year":"2012","journal-title":"Birth Defect Res C"},{"key":"pone.0245386.ref013","unstructured":"World Health Organization. Mental disorders. Factsheet N\u00b0396. World Health Organization 2015 [cited 23 Jan 2016]. Available from: http:\/\/www.who.int\/mediacentre\/factsheets\/fs396\/en\/."},{"key":"pone.0245386.ref014","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/XEB.0000000000000050","article-title":"Guidance for conducting systematic scoping reviews","volume":"13","author":"MDJ Peters","year":"2015","journal-title":"Int J Evid Based Healthc"},{"key":"pone.0245386.ref015","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"D Moher","year":"2009","journal-title":"PLoS Med"},{"key":"pone.0245386.ref016","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1038\/oby.2006.189","article-title":"Maternal Corticotropin-Releasing Hormone Levels during Pregnancy and Offspring Adiposity*","volume":"14","author":"MW Gillman","year":"2006","journal-title":"Obesity"},{"key":"pone.0245386.ref017","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1126\/science.1066285","article-title":"A Transgenic Model of Visceral Obesity and the Metabolic Syndrome","volume":"294","author":"H Masuzaki","year":"2001","journal-title":"Science"},{"key":"pone.0245386.ref018","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/pr.2011.18","article-title":"Prenatal exposure to a natural disaster increases risk for obesity in 5\u00bd-year-old children","volume":"71","author":"KN Dancause","year":"2012","journal-title":"Pediatr Res"},{"key":"pone.0245386.ref019","doi-asserted-by":"crossref","first-page":"e43548","DOI":"10.1371\/journal.pone.0043548","article-title":"The association between prenatal psychosocial stress and blood pressure in the child at age 5\u20137 years","volume":"7","author":"AE van Dijk","year":"2012","journal-title":"PLoS ONE"},{"key":"pone.0245386.ref020","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.0963-7214.2004.00277.x","article-title":"The Role of Prenatal Maternal Stress in Child Development","volume":"13","author":"JA DiPietro","year":"2004","journal-title":"Curr Dir Psychol Sci"},{"key":"pone.0245386.ref021","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1293\/tox.2013-0060","article-title":"A Comparison of the Histological Structure of the Placenta in Experimental Animals","volume":"27","author":"S Furukawa","year":"2014","journal-title":"J Toxicol Pathol"},{"key":"pone.0245386.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2015.02.015","article-title":"Weerth C de. Associations between maternal prenatal cortisol concentrations and child outcomes. A systematic review. Neuroscience &","volume":"53","author":"MAC Zijlmans","year":"2015","journal-title":"Biobehavioral Reviews"},{"key":"pone.0245386.ref023","first-page":"1","article-title":"Maternal Distress during Pregnancy and Offspring Childhood Overweight","volume":"2012","author":"KG Ingstrup","journal-title":"Journal of Obesity. 2012"},{"key":"pone.0245386.ref024","article-title":"Transfer of maternal psychosocial stress to the fetus","author":"F Rakers","year":"2017","journal-title":"Neurosci Biobehav Rev"},{"key":"pone.0245386.ref025","doi-asserted-by":"crossref","first-page":"U49","DOI":"10.1530\/eje.0.151u049","article-title":"Prenatal glucocorticoids and long-term programming","volume":"151","year":"2004","journal-title":"European Journal of Endocrinology"},{"key":"pone.0245386.ref026","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1017\/S2040174412000311","article-title":"Nick Hales Award Lecture 2011. Glucocorticoids and early life programming of cardiometabolic disease","volume":"3","author":"RM Reynolds","year":"2012","journal-title":"J Devel Orig Health Dis"},{"key":"pone.0245386.ref027","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1196\/annals.1314.006","article-title":"Glucocorticoid Programming","volume":"1032","author":"JR SECKL","year":"2004","journal-title":"Annals of the New York Academy of Sciences"},{"key":"pone.0245386.ref028","doi-asserted-by":"crossref","first-page":"e30413","DOI":"10.1371\/journal.pone.0030413","article-title":"Prenatal Stress and Balance of the Child\u2019s Cardiac Autonomic Nervous System at Age 5\u20136 Years","volume":"7","author":"AE van Dijk","year":"2012","journal-title":"PLoS ONE"},{"key":"pone.0245386.ref029","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.yhbeh.2008.11.006","article-title":"Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults","volume":"55","author":"S Entringer","year":"2009","journal-title":"Hormones and Behavior"},{"key":"pone.0245386.ref030","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1113\/jphysiol.2006.105254","article-title":"Fetal programming of hypothalamo-pituitary-adrenal function. Prenatal stress and glucocorticoids","volume":"572","author":"A Kapoor","year":"2006","journal-title":"The Journal of Physiology"},{"key":"pone.0245386.ref031","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1210\/endo.142.5.8139","article-title":"Maternal Undernutrition during Late Gestation Induces Fetal Overexposure to Glucocorticoids and Intrauterine Growth Retardation, and Disturbs the Hypothalamo-Pituitary Adrenal Axis in the Newborn Rat","volume":"142","author":"J Lesage","year":"2001","journal-title":"Endocrinology"},{"key":"pone.0245386.ref032","doi-asserted-by":"crossref","first-page":"R34","DOI":"10.1152\/ajpregu.00106.2004","article-title":"Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats","volume":"288","author":"AJ Drake","year":"2005","journal-title":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"},{"key":"pone.0245386.ref033","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neubiorev.2009.11.008","article-title":"Prenatal stress and the programming of the HPA axis","volume":"35","author":"V Glover","year":"2010","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"pone.0245386.ref034","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/CS20070107","article-title":"Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease","volume":"113","author":"AJ Drake","year":"2007","journal-title":"Clinical Science"},{"key":"pone.0245386.ref035","doi-asserted-by":"crossref","DOI":"10.3389\/neuro.08.019.2009","article-title":"Prenatal stress, glucocorticoids and the programming of adult disease","volume":"3","author":"EC Cottrell","year":"2009","journal-title":"Front Behav Neurosci"},{"key":"pone.0245386.ref036","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1042\/cs0980137","article-title":"Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children","volume":"98","author":"LW DOYLE","year":"2000","journal-title":"Clinical Science"},{"key":"pone.0245386.ref037","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1016\/S0140-6736(05)66617-2","article-title":"Cardiovascular risk factors after antenatal exposure to betamethasone. 30-year follow-up of a randomised controlled trial","volume":"365","author":"SR Dalziel","year":"2005","journal-title":"The Lancet"},{"key":"pone.0245386.ref038","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.psyneuen.2009.10.003","article-title":"Maternal cortisol and offspring birthweight. Results from a large prospective cohort study","volume":"35","author":"G Goedhart","year":"2010","journal-title":"Psychoneuroendocrinology"},{"key":"pone.0245386.ref039","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1161\/HYPERTENSIONAHA.109.129320","article-title":"Programming of Hypertension","volume":"53","author":"RM Reynolds","year":"2009","journal-title":"Hypertension"},{"key":"pone.0245386.ref040","first-page":"R500","article-title":"Prenatal glucocorticoid exposure in the sheep alters renal development in utero. Implications for adult renal function and blood pressure control","volume":"301","author":"KM Moritz","year":"2011","journal-title":"AJP: Regulatory, Integrative and Comparative Physiology"},{"key":"pone.0245386.ref041","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/j.1440-1681.2009.05180.x","article-title":"Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep","volume":"36","author":"KM Moritz","year":"2009","journal-title":"Clinical and Experimental Pharmacology and Physiology"},{"key":"pone.0245386.ref042","doi-asserted-by":"crossref","first-page":"E592","DOI":"10.1152\/ajpendo.2001.281.3.E592","article-title":"Glucocorticoids impair fetal beta-cell development in rats","volume":"281","author":"B Blondeau","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"pone.0245386.ref043","doi-asserted-by":"crossref","first-page":"154047","DOI":"10.1016\/j.metabol.2019.154047","article-title":"Perinatal programming of metabolic diseases: The role of glucocorticoids","volume":"104","author":"JC Facchi","year":"2020","journal-title":"Metab Clin Exp"},{"key":"pone.0245386.ref044","doi-asserted-by":"crossref","first-page":"E582","DOI":"10.1152\/ajpendo.00167.2015","article-title":"Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats","volume":"309","author":"P Balasubramanian","year":"2015","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"pone.0245386.ref045","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.2337\/db08-1129","article-title":"Prenatal Stress or High-Fat Diet Increases Susceptibility to Diet-Induced Obesity in Rat Offspring","volume":"58","author":"KLK Tamashiro","year":"2009","journal-title":"Diabetes"},{"key":"pone.0245386.ref046","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.physbeh.2006.05.019","article-title":"Impact of prenatal stress on long term body weight is dependent on timing and maternal sensitivity","volume":"88","author":"B MUELLER","year":"2006","journal-title":"Physiology & Behavior"},{"key":"pone.0245386.ref047","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.physbeh.2007.11.030","article-title":"Effects of stress on dietary preference and intake are dependent on access and stress sensitivity","volume":"93","author":"SL Teegarden","year":"2008","journal-title":"Physiology & Behavior"},{"key":"pone.0245386.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/570541","article-title":"Prenatal Stress due to a Natural Disaster Predicts Adiposity in Childhood. The Iowa Flood Study","volume":"2015","author":"KN Dancause","year":"2015","journal-title":"Journal of Obesity"},{"key":"pone.0245386.ref049","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.earlhumdev.2013.06.006","article-title":"Prenatal stress due to a natural disaster predicts insulin secretion in adolescence","volume":"89","author":"KN Dancause","year":"2013","journal-title":"Early Human Development"},{"key":"pone.0245386.ref050","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1677\/joe.0.1810291","article-title":"Prenatal stress induces intrauterine growth restriction and programmes glucose intolerance and feeding behaviour disturbances in the aged rat","volume":"181","author":"J Lesage","year":"2004","journal-title":"Journal of Endocrinology"},{"key":"pone.0245386.ref051","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1113\/jphysiol.2003.056911","article-title":"Prenatal stress alters cardiovascular responses in adult rats","volume":"557","author":"N Igosheva","year":"2004","journal-title":"The Journal of Physiology"},{"key":"pone.0245386.ref052","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/2047487313486039","article-title":"The association of maternal prenatal psychosocial stress with vascular function in the child at age 10\u201311 years: findings from the Avon longitudinal study of parents and children","volume":"21","author":"AE van Dijk","year":"2014","journal-title":"Eur J Prev Cardiolog"},{"key":"pone.0245386.ref053","first-page":"18","article-title":"Stress and the HPA Axis: Balancing Homeostasis and Fertility","author":"DN Joseph","year":"2017","journal-title":"Int J Mol Sci"},{"key":"pone.0245386.ref054","doi-asserted-by":"crossref","first-page":"e12951","DOI":"10.1111\/obr.12951","article-title":"Associations between maternal stress during pregnancy and offspring obesity risk later in life-A systematic literature review","volume":"21","author":"N Lamichhane","year":"2020","journal-title":"Obes Rev"},{"key":"pone.0245386.ref055","doi-asserted-by":"crossref","first-page":"104560","DOI":"10.1016\/j.psyneuen.2019.104560","article-title":"Prenatal stress and later metabolic consequences: Systematic review and meta-analysis in rodents","volume":"113","author":"AL Burgue\u00f1o","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"pone.0245386.ref056","doi-asserted-by":"crossref","first-page":"e0200594","DOI":"10.1371\/journal.pone.0200594","article-title":"Is the risk of low birth weight or preterm labor greater when maternal stress is experienced during pregnancy? A systematic review and meta-analysis of cohort studies","volume":"13","author":"SAM Lima","year":"2018","journal-title":"PLoS ONE"},{"key":"pone.0245386.ref057","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/bs.ctdb.2016.12.004","article-title":"Mechanisms of Glucocorticoid Action During Development","volume":"125","author":"JT Busada","year":"2017","journal-title":"Curr Top Dev Biol"},{"key":"pone.0245386.ref058","doi-asserted-by":"crossref","first-page":"T121","DOI":"10.1530\/JOE-18-0672","article-title":"Glucocorticoids and programming of the microenvironment in heart","volume":"242","author":"R Song","year":"2019","journal-title":"Journal of Endocrinology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T22:26:24Z","timestamp":1611354384000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245386"}},"subtitle":[],"editor":[{"given":"Linglin","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,22]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245386","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,22]]}}}