{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:16:13Z","timestamp":1789420573064,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The objective of this study was to assess the value of serum leptin, adiponectin, apelin, and ghrelin as biomarkers for the prediction and diagnosis of intra-hepatic cholestasis (ICP). This prospective study included pregnant women in the third trimester of pregnancy: 63 with ICP, 48 and 15 of whom had mild and severe disease, respectively, and 32 as controls. ICP women had increased median levels of serum leptin, adiponectin, apelin, and ghrelin compared to the controls (p &lt; 0.05). These biomarkers meaningfully changed regarding the severity of ICP: While leptin was reduced, apelin and ghrelin were increased, and adiponectin was increased somewhat. To predict and diagnose ICP, the predictive values of serum leptin, adiponectin, and apelin need to be accepted as comparable, with moderate to high sensitivity and specificity; however, the predictive value of serum ghrelin was somewhat lower. More research is needed to clarify the potential properties of adipokines to gain acceptance as a predictive or diagnostic biomarker for ICP.<\/jats:p>","DOI":"10.3390\/ijerph19042254","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"2254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Predictive and Diagnostic Value of Serum Adipokines in Pregnant Women with Intrahepatic Cholestasis"],"prefix":"10.3390","volume":"19","author":[{"given":"Nazan","family":"Yurtcu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sivas Cumhuriyet University Faculty of Medicine, Sivas 58140, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-5249","authenticated-orcid":false,"given":"Canan Soyer","family":"Caliskan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Samsun Training and Research Hospital, Health Sciences University, Samsun 55270, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-6981","authenticated-orcid":false,"given":"Huri","family":"Guvey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Private K\u00fctahya Parkhayat Hospital, K\u00fctahya 43100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samettin","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Samsun Training and Research Hospital, Health Sciences University, Samsun 55270, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8859-0639","authenticated-orcid":false,"given":"Safak","family":"Hatirnaz","sequence":"additional","affiliation":[{"name":"In Vitro Fertilization Unit, Medicana International Hospital, Samsun 55080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-8490","authenticated-orcid":false,"given":"Andrea","family":"Tinelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Veris delli Ponti Hospital, 73020 Lecce, Italy"},{"name":"Department of Obstetrics and Gynecology, Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Vito Fazzi Hospital, 73100 Lecce, Italy"},{"name":"Phystech BioMed School, Faculty of Biological & Medical Physics, Moscow Institute of Physics and Technology, State University, 141701 Moscow, Russia"},{"name":"Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ejogrb.2018.10.041","article-title":"Intrahepatic cholestasis of pregnancy: Review of six national and regional guidelines","volume":"231","author":"Bicocca","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1136\/bmj.324.7330.123","article-title":"Obstetric cholestasis","volume":"324","author":"Milkiewicz","year":"2002","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.3109\/00016349.2010.515665","article-title":"Decreased 1,25-dihydroxy vitamin D levels in women with intrahepatic cholestasis of pregnancy","volume":"89","author":"Marschall","year":"2010","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/AOG.0000000000000346","article-title":"Intrahepatic cholestasis of pregnancy","volume":"124","author":"Williamson","year":"2014","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Casado-Espada, N.M., De Alarc\u00f3n, R., De La Iglesia-Larrad, J.I., Bote-Bonaechea, B., and Montejo \u00c1ngel, L. (2019). Hormonal Contraceptives, Female Sexual Dysfunction, and Managing Strategies: A Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8060908"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/GRF.0000000000000495","article-title":"Intrahepatic Cholestasis of Pregnancy","volume":"63","author":"Smith","year":"2020","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Geenes, V., L\u00f6vgren-Sandblom, A., Benthin, L., Lawrance, D., Chambers, J., Gurung, V., Thornton, J., Chappell, L., Khan, E., and Dixon, P. (2014). The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083828"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: Results of aggregate and individual patient data meta-analyses","volume":"393","author":"Ovadia","year":"2019","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1159\/000478958","article-title":"Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-\u03b1 in Patients with Intrahepatic Cholestasis of Pregnancy","volume":"42","author":"Shao","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12884-020-03240-z","article-title":"Whole-exome sequencing reveals ANO8 as a genetic risk factor for intrahepatic cholestasis of pregnancy","volume":"20","author":"Liu","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ajpath.2010.11.026","article-title":"Bile Acids Induce Inflammatory Genes in Hepatocytes: A Novel Mechanism of Inflammation during Obstructive Cholestasis","volume":"178","author":"Allen","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3109\/14767058.2015.1028354","article-title":"The role of interleukin-17 in intrahepatic cholestasis of pregnancy","volume":"29","author":"Kirbas","year":"2015","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.metabol.2014.08.004","article-title":"Physiology of leptin: Energy homeostasis, neuroendocrine function and metabolism","volume":"64","author":"Park","year":"2015","journal-title":"Metabolism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nri1350","article-title":"The weight of leptin in immunity","volume":"4","author":"Matarese","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.lfs.2005.04.004","article-title":"Leptin enhances TNF-\u03b1 production via p38 and JNK MAPK in LPS-stimulated Kupffer cells","volume":"77","author":"Shen","year":"2005","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/hep.20282","article-title":"Adiponectin protects LPS-induced liver injury through modulation of TNF-? in KK-Ay obese mice","volume":"40","author":"Masaki","year":"2004","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.bbrc.2004.08.145","article-title":"Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes","volume":"323","author":"Wolf","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1210\/en.2004-1427","article-title":"Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity","volume":"146","author":"Boucher","year":"2005","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21061","DOI":"10.1074\/jbc.M908417199","article-title":"Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin","volume":"275","author":"Hosoya","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.2353\/ajpath.2007.070471","article-title":"Requirement of Apelin-Apelin Receptor System for Oxidative Stress-Linked Atherosclerosis","volume":"171","author":"Hashimoto","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.regpep.2003.11.002","article-title":"Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells","volume":"118","author":"Kleinz","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11972","DOI":"10.1128\/JVI.74.24.11972-11976.2000","article-title":"Apelin, the Natural Ligand of the Orphan Seven-Transmembrane Receptor APJ, Inhibits Human Immunodeficiency Virus Type 1 Entry","volume":"74","author":"Cayabyab","year":"2000","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fphar.2017.00221","article-title":"The Role of the Apelin\/APJ System in the Regulation of Liver Disease","volume":"8","author":"Lv","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1136\/gut.2010.234690","article-title":"Hypoxia and proinflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytes","volume":"60","author":"Pauta","year":"2011","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1210\/endo.141.11.7757","article-title":"Ghrelin, a Novel Growth Hormone-Releasing Acylated Peptide, Is Synthesized in a Distinct Endocrine Cell Type in the Gastrointestinal Tracts of Rats and Humans","volume":"141","author":"Date","year":"2000","journal-title":"Endocrinology"},{"key":"ref_26","first-page":"90","article-title":"Ghrelin\u2014Physiological Functions and Regulation","volume":"11","year":"2015","journal-title":"Eur. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"518909","DOI":"10.1155\/2013\/518909","article-title":"Structure and Physiological Actions of Ghrelin","volume":"2013","author":"Delporte","year":"2013","journal-title":"Scientifica"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.tins.2016.12.003","article-title":"Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity","volume":"40","author":"Nogueiras","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12785","DOI":"10.1111\/jne.12785","article-title":"Growth hormone secretagogue receptor signalling affects high-fat intake independently of plasma levels of ghrelin and LEAP 2, in a 4-day binge eating model","volume":"31","author":"Cornejo","year":"2019","journal-title":"J. Neuroendocr."},{"key":"ref_31","first-page":"45","article-title":"Ghrelin and liver disease","volume":"21","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1002\/hep.23421","article-title":"Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans","volume":"51","author":"Moreno","year":"2010","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/oby.20454","article-title":"Acylated ghrelin limits fat accumulation and improves redox state and inflammation markers in the liver of high-fat-fed rats","volume":"22","author":"Barazzoni","year":"2014","journal-title":"Obesity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.5603\/GP.2020.0051","article-title":"Evaluation of predictive value of biochemical markers for adverse obstetrics outcomes in pregnancies complicated by cholestasis","volume":"91","author":"Wirstlein","year":"2020","journal-title":"Ginekol. Polska"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.21873\/anticanres.14155","article-title":"The Alterations in Alcohol Dehydrogenase Activity in the Sera of Women with Intrahepatic Cholestasis of Pregnancy","volume":"40","author":"Jelski","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3329\/bmrcb.v39i1.15805","article-title":"Leptin to adiponectin ratio in preeclampsia","volume":"39","author":"Khosrowbeygi","year":"2013","journal-title":"Bangladesh Med. Res. Counc. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1007\/s11033-021-06785-0","article-title":"GDM-complicated pregnancies: Focus on adipokines","volume":"48","author":"Mallardo","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/1471-0528.12174","article-title":"Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: A 12-year population-based cohort study","volume":"120","author":"Marschall","year":"2013","journal-title":"BJOG"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1080\/10641955.2020.1758939","article-title":"Association between intrahepatic cholestasis of pregnancy and risk of gestational diabetes and preeclampsia: A systematic review and meta-analysis","volume":"39","author":"Arafa","year":"2020","journal-title":"Hypertens. Pregnancy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1600-0897.2009.00798.x","article-title":"OPINION: Immunologic Abnormality of Intrahepatic Cholestasis of Pregnancy","volume":"63","author":"Yayi","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1055\/s-0030-1253227","article-title":"The Role of Inflammation in Cholestasis: Clinical and Basic Aspects","volume":"30","author":"Kosters","year":"2010","journal-title":"Semin. Liver Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Achari, A.E., and Jain, S.K. (2017). Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061321"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1590\/S0004-27302009000200012","article-title":"Protective roles of adiponectin in obesity-related fatty liver diseases: Mechanisms and therapeutic implications","volume":"53","author":"Wang","year":"2009","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1161\/01.CIR.103.8.1057","article-title":"Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages","volume":"103","author":"Ouchi","year":"2001","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1042\/CS20100008","article-title":"Significance of serum adiponectin levels in patients with chronic liver disease","volume":"119","author":"Balmer","year":"2010","journal-title":"Clin. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jhep.2004.12.024","article-title":"High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo","volume":"42","author":"Tacke","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3803\/EnM.2018.33.1.33","article-title":"Association of Adipokines with Development and Progression of Nonalcoholic Fatty Liver Disease","volume":"33","author":"Boutari","year":"2018","journal-title":"Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s12072-010-9216-0","article-title":"Study of adiponectin in chronic liver disease and cholestasis","volume":"4","author":"Salman","year":"2010","journal-title":"Hepatol Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.5114\/ceh.2021.104419","article-title":"Influence of ursodeoxycholic acid therapy on levels of fibroblast growth factor 21, adiponectin and biochemical parameters in intrahepatic cholestasis of pregnancy","volume":"7","author":"Kukla","year":"2021","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cmet.2016.04.011","article-title":"Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk","volume":"23","author":"Stern","year":"2016","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bcpt.12109","article-title":"Adiponectin and Leptin: New Targets in Inflammation","volume":"114","author":"Scotece","year":"2013","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1210\/jc.2002-021393","article-title":"Endotoxin Stimulates Leptin in the Human and Nonhuman Primate","volume":"88","author":"Landman","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","first-page":"183","article-title":"Alterations in serum leptin in chronic liver disease","volume":"47","author":"Schafer","year":"2002","journal-title":"Am. J. Dig. Dis."},{"key":"ref_54","first-page":"47","article-title":"Plasma leptin levels in patients with primary biliary cirrhosis and their relationship with degree of fibrosis","volume":"27","author":"Crespo","year":"2004","journal-title":"Gastroenterolog\u00eda y Hepatolog\u00eda"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1196\/annals.1361.124","article-title":"Decreased Serum Leptin Levels in Primary Biliary Cirrhosis: A Link between Metabolism and Autoimmunity?","volume":"1051","author":"Rieger","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1136\/gut.2003.037689","article-title":"Bile secretory function in the obese Zucker rat: Evidence of cholestasis and altered canalicular transport function","volume":"53","author":"Pizarro","year":"2004","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/hep.22467","article-title":"The hepatic apelin system: A new therapeutic target for liver disease","volume":"48","author":"Principe","year":"2008","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/liv.12006","article-title":"Involvement of the apelin receptor APJ in Fas-induced liver injury","volume":"33","author":"Yasuzaki","year":"2013","journal-title":"Liver Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1002\/hep.31545","article-title":"The Apelin\u2013Apelin Receptor Axis Triggers Cholangiocyte Proliferation and Liver Fibrosis During Mouse Models of Cholestasis","volume":"73","author":"Chen","year":"2021","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0168-8278(02)00438-5","article-title":"Ghrelin in chronic liver disease","volume":"38","author":"Tacke","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1055\/s-2004-817819","article-title":"Ghrelin\/Leptin-Imbalance in Patients with Primary Biliary Cirrhosis","volume":"112","author":"Breidert","year":"2004","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16024","DOI":"10.1038\/s41598-020-72681-5","article-title":"Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis","volume":"10","author":"Petrescu","year":"2020","journal-title":"Sci. Rep."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/4\/2254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:21:00Z","timestamp":1760134860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/4\/2254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijerph19042254"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19042254","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]}}}