{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:25Z","timestamp":1787027005840,"version":"build-2736575974"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    High oxygen concentrations have been identified as one factor contributing to the pathogenesis of the retinopathia of prematurity, chronic lung disease of the preterm infant and preterm brain injury. Preterm infants also show short- and long-term alterations of the endocrine system. If hyperoxia is one pathogenetic factor has not been investigated yet. With regard to the high prevalence of neurodevelopmental impairments in preterm infants, the hypothalamus-pituitary-thyroid (HPT) axis, the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-somatotropic (HPS) axis are of special interest due to their important role in neurodevelopment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    The aim of this study was to investigate the effect of hyperoxia on the endocrine system in the neonatal rat by analyzing the activities of the HPT, HPA and HPS axes, respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Three-days old Wistar rats were exposed to hyperoxia (oxygen 80%, 48 h). On postnatal day 5 (P5) and P11, transcript levels of thyroid-stimulating hormone (TSH), proopiomelanocortin and growth hormone (GH) were analyzed in pituitary sections by\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization. Serologic quantification of TSH and thyroxine (T4), adrenocorticotropic hormone and GH were performed by Multiplex analysis and Enzyme-linked Immunosorbent Assay.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    At P5, significantly lower GH levels were observed in pituitaries (mRNA) and in sera of rats exposed to hyperoxia. Serum TSH was significantly elevated without changes in T4.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This is the first study demonstrating transient endocrine alterations following hyperoxia in the neonatal rat making oxygen a possible contributor to the pathogenesis of endocrine alterations seen in preterm infants. Considering the detrimental multi-organ effects of hyperoxia on the immature organism, a rational use of therapeutic oxygen in the treatrnent of preterm infants is of utmost importance.\n                  <\/jats:p>","DOI":"10.3389\/fped.2021.723928","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T09:53:56Z","timestamp":1635242036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hyperoxia Leads to Transient Endocrine Alterations in the Neonatal Rat During Postnatal Development"],"prefix":"10.3389","volume":"9","author":[{"given":"Mirjam","family":"Kowallick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meray","family":"Serdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyka","family":"Markova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Salveridou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Felderhoff-M\u00fcser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer-Sakel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Heuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Bendix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia Vanessa","family":"Dewan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.clp.2019.05.001","article-title":"Oxygen toxicity in the neonate: thinking beyond the balance","volume":"46","author":"Tipple","year":"2019","journal-title":"Clin Perinatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1159\/000454917","article-title":"Hyperoxia and the immature brain","volume":"38","author":"Reich","year":"2016","journal-title":"Dev Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/ANC.0000000000000434","article-title":"A review of oxygen physiology and appropriate management of oxygen levels in premature neonates","volume":"18","author":"Kayton","year":"2018","journal-title":"Adv Neonatal Care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5694\/j.1326-5377.1951.tb109040.x","article-title":"Intensive oxygen therapy as a possible cause of retrolental fibroplasia; a clinical approach","volume":"2","author":"CAMPBELL","year":"1951","journal-title":"Med J Aust."},{"key":"B5","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/pr.2016.201","article-title":"Bronchopulmonary dysplasia: new becomes old again!","volume":"81","author":"Day","year":"2017","journal-title":"Pediatr Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/sj.jp.7211608","article-title":"Avoiding hyperoxia in infants < or = 1250 g is associated with improved short- and long-term outcomes","volume":"26","author":"Deulofeut","year":"2006","journal-title":"J Perinatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.nbd.2004.07.019","article-title":"Oxygen causes cell death in the developing brain","volume":"17","author":"Felderhoff-Mueser","year":"2004","journal-title":"Neurobiol Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1523\/JNEUROSCI.3213-07.2008","article-title":"Hyperoxia causes maturation-dependent cell death in the developing white matter","volume":"28","author":"Gerstner","year":"2008","journal-title":"J Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e49023","DOI":"10.1371\/journal.pone.0049023","article-title":"Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage","volume":"7","author":"Brehmer","year":"2012","journal-title":"PLoS ONE."},{"key":"B10","doi-asserted-by":"publisher","first-page":"804","DOI":"10.3389\/fneur.2020.00804","article-title":"Repetitive erythropoietin treatment improves long-term neurocognitive outcome by attenuating hyperoxia-induced hypomyelination in the developing brain","volume":"11","author":"Dewan","year":"2020","journal-title":"Front Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3389\/fneur.2018.00175","article-title":"Protection of oligodendrocytes through neuronal overexpression of the small GTPase Ras in hyperoxia-induced neonatal brain injury","volume":"9","author":"Serdar","year":"2018","journal-title":"Front Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.bbi.2009.08.010","article-title":"Erythropoietin attenuates hyperoxia-induced oxidative stress in the developing rat brain","volume":"24","author":"Sifringer","year":"2010","journal-title":"Brain Behav Immun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"12939","DOI":"10.3390\/ijms131012939","article-title":"Erythropoietin modulates autophagy signaling in the developing rat brain in an in vivo model of oxygen-toxicity","volume":"13","author":"Bendix","year":"2012","journal-title":"Int J Mol Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa041367","article-title":"Neurologic and developmental disability at six years of age after extremely preterm birth","volume":"352","author":"Marlow","year":"2005","journal-title":"N Engl J Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJM200008103430601","article-title":"Neurologic and developmental disability after extremely preterm birth. EPICure Study Group","volume":"343","author":"Wood","year":"2000","journal-title":"N Engl J Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.mce.2009.09.008","article-title":"Thyroid hormone action during brain development: more questions than answers","volume":"315","author":"Horn","year":"2010","journal-title":"Mol Cell Endocrinol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1080\/17446651.2017.1356222","article-title":"Developmental origins of the human hypothalamic-pituitary-adrenal axis","volume":"12","author":"Howland","year":"2017","journal-title":"Expert Rev Endocrinol Metab."},{"key":"B18","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1159\/000089320","article-title":"The role of growth hormone in neural development","volume":"64","author":"Scheepens","year":"2005","journal-title":"Horm Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1159\/000492129","article-title":"Effect of thyroid hormones on neurons and neurodevelopment","volume":"90","author":"Prezioso","year":"2018","journal-title":"Horm Res Paediatr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"425","DOI":"10.3345\/kjp.2014.57.10.425","article-title":"Adrenal and thyroid function in the fetus and preterm infant","volume":"57","author":"Chung","year":"2014","journal-title":"Korean J Pediatr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1186\/s12887-019-1792-0","article-title":"Thyroid dysfunction in preterm infants born before 32 gestational weeks","volume":"19","author":"Kim","year":"2019","journal-title":"BMC Pediatr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3805370","DOI":"10.1155\/2017\/3805370","article-title":"Former very preterm infants show alterations in thyroid function at a preschool age","volume":"2017","author":"Posod","year":"2017","journal-title":"Biomed Res Int."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e0222018","DOI":"10.1371\/journal.pone.0222018","article-title":"Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants","volume":"14","author":"Tan","year":"2019","journal-title":"PLoS ONE."},{"key":"B24","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1136\/archdischild-2018-316742","article-title":"Thyroid function in preterm infants and neurodevelopment at 2 years","volume":"105","author":"Williams","year":"2020","journal-title":"Arch Dis Child Fetal Neonatal Ed."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4898","DOI":"10.1210\/jc.2010-0743","article-title":"Levels of neonatal thyroid hormone in preterm infants and neurodevelopmental outcome at 5 1\/2 years: millennium cohort study","volume":"95","author":"Delahunty","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1007\/s00247-014-2911-6","article-title":"Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study","volume":"44","author":"Ng","year":"2014","journal-title":"Pediatr Radiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"CD005948","DOI":"10.1002\/14651858.CD005948.pub2","article-title":"Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants","volume":"1","author":"Osborn","year":"2007","journal-title":"Cochrane Database Syst Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/1745-6215-14-211","article-title":"An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks' gestation: results of the TIPIT trial","volume":"14","author":"Ng","year":"2013","journal-title":"Trials."},{"key":"B29","doi-asserted-by":"publisher","first-page":"R61","DOI":"10.1530\/JME-18-0077","article-title":"Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation","volume":"61","author":"Agnew","year":"2018","journal-title":"J Mol Endocrinol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"F250","DOI":"10.1136\/fn.82.3.F250","article-title":"The fetal and neonatal hypothalamic-pituitary-adrenal axis","volume":"82","author":"Ng","year":"2000","journal-title":"Arch Dis Child Fetal Neonatal Ed."},{"key":"B31","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1159\/000443734","article-title":"Glucocorticoid programming in very preterm birth","volume":"85","author":"Finken","year":"2016","journal-title":"Horm Res Paediatr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/jnr.23416","article-title":"Adrenocorticotropin hormone 1-39 promotes proliferation and differentiation of oligodendroglial progenitor cells and protects from excitotoxic and inflammation-related damage","volume":"92","author":"Benjamins","year":"2014","journal-title":"J Neurosci Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"17734","DOI":"10.1038\/s41598-020-74712-7","article-title":"Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats","volume":"10","author":"Bagatini","year":"2020","journal-title":"Sci Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1172\/JCI107135","article-title":"The ontogenesis of human fetal hormones. I. Growth hormone and insulin","volume":"51","author":"Kaplan","year":"1972","journal-title":"J Clin Invest."},{"key":"B35","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1203\/00006450-199209000-00008","article-title":"Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate","volume":"32","author":"Wright","year":"1992","journal-title":"Pediatr Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1210\/jc.2014-4342","article-title":"High postnatal growth hormone levels are related to cognitive deficits in a group of children born very preterm","volume":"100","author":"Scratch","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"key":"B37","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1203\/00006450-198003000-00014","article-title":"Free thyroid hormone concentrations during postnatal development in the rat","volume":"14","author":"Walker","year":"1980","journal-title":"Pediatr Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species","author":"Semple","year":"2013","journal-title":"Prog Neurobiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1210\/en.2003-1227","article-title":"Expression of pituitary hormones in the Pax8-\/- mouse model of congenital hypothyroidism","volume":"145","author":"Friedrichsen","year":"2004","journal-title":"Endocrinology."},{"key":"B40","doi-asserted-by":"publisher","first-page":"16880","DOI":"10.1073\/pnas.0508202102","article-title":"Revealing the large-scale network organization of growth hormone-secreting cells","volume":"102","author":"Bonnefont","year":"2005","journal-title":"Proc Natl Acad Sci USA."},{"key":"B41","doi-asserted-by":"publisher","first-page":"12515","DOI":"10.1073\/pnas.1105929108","article-title":"Related pituitary cell lineages develop into interdigitated 3D cell networks","volume":"108","author":"Budry","year":"2011","journal-title":"Proc Natl Acad Sci USA."},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.5772\/32002","article-title":"Thyroid-stimulating hormone regulation and transcription in hypothyroidism","author":"Sugimoto","year":"2012","journal-title":"Hypothyroidism - Influences and Treatments"},{"key":"B43","doi-asserted-by":"publisher","first-page":"4347","DOI":"10.1210\/jcem.85.11.6991","article-title":"Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary","volume":"85","author":"Prummel","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"key":"B44","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s11154-016-9375-y","article-title":"Advances in TRH signaling","volume":"17","author":"Joseph-Bravo","year":"2016","journal-title":"Rev Endocr Metab Disord."},{"key":"B45","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1001\/jama.2019.9052","article-title":"Subclinical hypothyroidism: a review","volume":"322","author":"Biondi","year":"2019","journal-title":"JAMA."},{"key":"B46","doi-asserted-by":"publisher","first-page":"E628","DOI":"10.1152\/ajpendo.1978.235.6.E628","article-title":"Role of thyroid gland in oxygen toxicity","volume":"235","author":"Galton","year":"1978","journal-title":"Am J Physiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1756-6614-5-25","article-title":"Oxidative damage to macromolecules in the thyroid - experimental evidence","volume":"5","author":"Karbownik-Lewi\u0144ska","year":"2012","journal-title":"Thyroid Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/BF00318674","article-title":"Cellular proliferation in the anterior pituitary of the rat during the postnatal period","volume":"261","author":"Carbajo-P\u00e9rez","year":"1990","journal-title":"Cell Tissue Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1210\/endo-128-2-937","article-title":"Growth hormone regulation in primary fetal and neonatal rat pituitary cell cultures: the role of thyroid hormone","volume":"128","author":"Ezzat","year":"1991","journal-title":"Endocrinology."},{"key":"B50","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.alcohol.2005.03.005","article-title":"Exposure to ethanol induces oxidative damage in the pituitary gland","volume":"35","author":"Ren","year":"2005","journal-title":"Alcohol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1136\/adc.48.10.757","article-title":"Quantitative growth and development of human brain","volume":"48","author":"Dobbing","year":"1973","journal-title":"Arch Dis Child."},{"key":"B52","doi-asserted-by":"publisher","first-page":"207","DOI":"10.3164\/jcbn.09-33","article-title":"Elevation by oxidative stress and aging of hypothalamic-pituitary-adrenal activity in rats and its prevention by vitamin E","volume":"45","author":"Kobayashi","year":"2009","journal-title":"J Clin Biochem Nutr."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1210\/endo-118-4-1445","article-title":"Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus","volume":"118","author":"Walker","year":"1986","journal-title":"Endocrinology."},{"key":"B54","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/0165-0173(86)90010-X","article-title":"Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period","volume":"396","author":"Sapolsky","year":"1986","journal-title":"Brain Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"R1195","DOI":"10.1152\/ajpregu.90400.2008","article-title":"Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat","volume":"295","author":"Bruder","year":"2008","journal-title":"Am J Physiol Regul Integr Comp Physiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/j.1749-6632.1994.tb39245.x","article-title":"The ontogeny of the hypothalamic-pituitary-adrenal axis. The influence of maternal factors","volume":"746","author":"Levine","year":"1994","journal-title":"Ann N Y Acad Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"9247493","DOI":"10.1155\/2016\/9247493","article-title":"Erythropoietin restores long-term neurocognitive function involving mechanisms of neuronal plasticity in a model of hyperoxia-induced preterm brain injury","volume":"2016","author":"Hoeber","year":"2016","journal-title":"Oxid Med Cell Longev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.neulet.2003.09.070","article-title":"Protective effect of growth hormone on neuronal apoptosis after hypoxia-ischemia in the neonatal rat brain","volume":"354","author":"Shin","year":"2004","journal-title":"Neurosci Lett."},{"key":"B59","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.1210\/jc.2003-031187","article-title":"Intelligence and psychosocial functioning during long-term growth hormone therapy in children born small for gestational age","volume":"89","author":"van Pareren","year":"2004","journal-title":"J Clin Endocrinol Metab."},{"key":"B60","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1159\/000089324","article-title":"Effects of growth hormone treatment on cognitive function and head circumference in children born small for gestational age","volume":"64","author":"Hokken-Koelega","year":"2005","journal-title":"Horm Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/S2213-8587(15)00225-9","article-title":"Thyroid function in critically ill patients","volume":"3","author":"Fliers","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.bbi.2013.11.005","article-title":"Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain","volume":"37","author":"Schang","year":"2014","journal-title":"Brain Behav Immun."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.723928\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T08:36:09Z","timestamp":1635928569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.723928\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":62,"alternative-id":["10.3389\/fped.2021.723928"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.723928","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]},"article-number":"723928"}}