{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:14:28Z","timestamp":1782782068302,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cardiovascular Medical Research and Education","award":["CLP0032"],"award-info":[{"award-number":["CLP0032"]}]},{"name":"Cardiovascular Medical Research and Education","award":["21\/06\/2015(i)EU-V"],"award-info":[{"award-number":["21\/06\/2015(i)EU-V"]}]},{"name":"Cardiovascular Medical Research and Education","award":["74\/6\/2015- Pers. EMS"],"award-info":[{"award-number":["74\/6\/2015- Pers. EMS"]}]},{"name":"CSIR-UGC","award":["CLP0032"],"award-info":[{"award-number":["CLP0032"]}]},{"name":"CSIR-UGC","award":["21\/06\/2015(i)EU-V"],"award-info":[{"award-number":["21\/06\/2015(i)EU-V"]}]},{"name":"CSIR-UGC","award":["74\/6\/2015- Pers. EMS"],"award-info":[{"award-number":["74\/6\/2015- Pers. EMS"]}]},{"name":"Indian Council of Medical Research","award":["CLP0032"],"award-info":[{"award-number":["CLP0032"]}]},{"name":"Indian Council of Medical Research","award":["21\/06\/2015(i)EU-V"],"award-info":[{"award-number":["21\/06\/2015(i)EU-V"]}]},{"name":"Indian Council of Medical Research","award":["74\/6\/2015- Pers. EMS"],"award-info":[{"award-number":["74\/6\/2015- Pers. EMS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Endothelin 1 (EDN1) encodes a potent endogenous vasoconstrictor, ET1, to maintain vascular homeostasis and redistribution of tissue blood flow during exercise. One of the EDN1 missense polymorphisms, rs5370 G\/T, has strongly been associated with cardiopulmonary diseases. This study investigated the impact of rs5370 polymorphism in high-altitude pulmonary oedema (HAPE) disorder or maladaptation and adaptation physiology in a well-characterized case\u2013control study of high-altitude and low-altitude populations comprising 310 samples each of HAPE-patients, HAPE-free controls and native highlanders. The rs5370 polymorphism was genotyped, and the gene expression and plasma level of EDN1 were evaluated. The functional relevance of each allele was investigated in the human embryonic kidney 293 cell line after exposure to hypoxia and computationally. The T allele was significantly more prevalent in HAPE-p compared to HAPE-f and HLs. The EDN1 gene expression and ET1 bio-level were significantly elevated in HAPE-p compared to controls. Compared to the G allele, the T allele was significantly associated with elevated levels of ET-1 in all three study groups and cells exposed to hypoxia. The in silico studies further confirmed the stabilizing effect of the T allele on the structural integrity and function of ET1 protein. The ET1 rs5370 T allele is associated with an increased concentration of ET-1 in vivo and in vitro, establishing it as a potent marker in the adaptation\/maladaptation physiology under the high-altitude environment. This could also be pertinent in endurance exercises at high altitudes.<\/jats:p>","DOI":"10.3390\/ijerph191811174","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T20:52:51Z","timestamp":1662497571000},"page":"11174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The EDN1 Missense Variant rs5370G &gt; T Regulates Adaptation and Maladaptation under Hypobaric Hypoxia"],"prefix":"10.3390","volume":"19","author":[{"given":"Tsering","family":"Palmo","sequence":"first","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"},{"name":"Department of Biotechnology, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal Ahmed","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Chanana","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-3901","authenticated-orcid":false,"given":"Kavita","family":"Sharma","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-8396","authenticated-orcid":false,"given":"Mohammed","family":"Faruq","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tashi","family":"Thinlas","sequence":"additional","affiliation":[{"name":"Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik Z.","family":"Abdin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qadar","family":"Pasha","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India"},{"name":"Institute of Hypoxia Research, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/gb-2012-13-1-r1","article-title":"Genetic Adaptation to High Altitude in the Ethiopian Highlands","volume":"13","author":"Scheinfeldt","year":"2012","journal-title":"Genome Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1152\/japplphysiol.00321.2017","article-title":"Measuring High-Altitude Adaptation","volume":"123","author":"Moore","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17215","DOI":"10.1073\/pnas.252649199","article-title":"An Ethiopian Pattern of Human Adaptation to High-Altitude Hypoxia","volume":"99","author":"Beall","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1073\/pnas.0701985104","article-title":"Two Routes to Functional Adaptation: Tibetan and Andean High-Altitude Natives","volume":"104","author":"Beall","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1378\/chest.130.5.1511","article-title":"Heterozygotes of NOS3 Polymorphisms Contribute to Reduced Nitrogen Oxides in High-Altitude Pulmonary Edema","volume":"130","author":"Ahsan","year":"2006","journal-title":"Chest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1146\/annurev.med.47.1.267","article-title":"High-Altitude Pulmonary Edema: Current Concepts","volume":"47","author":"Hultgren","year":"1996","journal-title":"Annu. Rev. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1164\/rccm.201207-1323CI","article-title":"High-Altitude Medicine","volume":"186","author":"West","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1152\/japplphysiol.01167.2004","article-title":"Physiological Aspects of High-Altitude Pulmonary Edema","volume":"98","author":"Maggiorini","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.1378\/chest.09-2445","article-title":"High-Altitude Disorders: Pulmonary Hypertension: Pulmonary Vascular Disease: The Global Perspective","volume":"137","author":"Newman","year":"2010","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/jcp.1041320210","article-title":"Endothelial Cells in Culture Produce a Vasoconstrictor Substance","volume":"132","author":"Robbins","year":"1987","journal-title":"J. Cell. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1146\/annurev.pharmtox.47.120505.105134","article-title":"Contrasting Actions of Endothelin ETA and ETB Receptors in Cardiovascular Disease","volume":"47","author":"Schneider","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nature00767","article-title":"Structural Basis for the Recognition of Hydroxyproline in HIF-1 Alpha by PVHL","volume":"417","author":"Hon","year":"2002","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1172\/JCI137558","article-title":"Hypoxia-Inducible Factor Signaling in Pulmonary Hypertension","volume":"130","author":"Pullamsetti","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1161\/01.CIR.0000038362.16740.A2","article-title":"Involvement of Endogenous Endothelin-1 in Exercise-Induced Redistribution of Tissue Blood Flow: An Endothelin Receptor Antagonist Reduces the Redistribution","volume":"106","author":"Maeda","year":"2002","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1136\/bjsm.37.1.92-a","article-title":"Increased Endothelin-1 Levels in Athletes","volume":"37","author":"Legakis","year":"2003","journal-title":"Br. J. Sports Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H162","DOI":"10.1152\/ajpheart.00603.2012","article-title":"Taming the \u201cSleeping Giant\u201d: The Role of Endothelin-1 in the Regulation of Skeletal Muscle Blood Flow and Arterial Blood Pressure during Exercise","volume":"304","author":"Ives","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-physiol-021113-170322","article-title":"Hypoxia-Inducible Factor 1 and Cardiovascular Disease","volume":"76","author":"Semenza","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1023\/A:1007042729486","article-title":"Regulation of Endothelin-1 Gene Expression in Human Microvascular Endothelial Cells by Hypoxia and Cobalt: Role of Hypoxia Responsive Element","volume":"208","author":"Minchenko","year":"2000","journal-title":"Mol. Cell. Biochem."},{"key":"ref_19","first-page":"344","article-title":"Endothelin-1 Genetic Polymorphism as Predictive Marker for Bevacizumab in Metastatic Breast Cancer","volume":"17","author":"Gampenrieder","year":"2017","journal-title":"Pharm. J."},{"key":"ref_20","first-page":"1602","article-title":"Potential Correlation between EDN1 Gene Polymorphisms with Preeclampsia","volume":"24","author":"Li","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/10623320802228708","article-title":"Polymorphisms of the Endothelin-1 Gene Associate with Hypertension in Patients with Rheumatoid Arthritis","volume":"15","author":"Panoulas","year":"2008","journal-title":"Endothelium"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s12013-014-9887-6","article-title":"Effect of SNP Polymorphisms of EDN1, EDNRA, and EDNRB Gene on Ischemic Stroke","volume":"70","author":"Zhang","year":"2014","journal-title":"Cell Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1136\/thx.2006.066019","article-title":"Susceptibility to High Altitude Pulmonary Oedema: Role of ACE and ET-1 Polymorphisms","volume":"61","author":"Charu","year":"2006","journal-title":"Thorax"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT Web Server: Predicting Effects of Amino Acid Substitutions on Proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN Web Server: A Tool to Predict the Functional Effect of Amino Acid Substitutions and Indels","volume":"31","author":"Choi","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_27","first-page":"7.20.1","article-title":"Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W236","DOI":"10.1093\/nar\/gkx412","article-title":"SODA: Prediction of Protein Solubility from Disorder and Aggregation Propensity","volume":"45","author":"Paladin","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: An Improved Methodology to Estimate and Visualize Evolutionary Conservation in Macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1093\/bioinformatics\/btab176","article-title":"FrustratometeR: An R-Package to Compute Local Frustration in Protein Structures, Point Mutants and MD Simulations","volume":"37","author":"Rausch","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"174501","DOI":"10.1063\/1.4872239","article-title":"Structure and Dynamics of TIP3P, TIP4P, and TIP5P Water near Smooth and Atomistic Walls of Different Hydroaffinity","volume":"140","author":"Harrach","year":"2014","journal-title":"J. Chem. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh Ewald: An N\u22c5log(N) Method for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.bbrc.2006.01.086","article-title":"Endothelin-1 Gene Variants and Levels Associate with Adaptation to Hypobaric Hypoxia in High-Altitude Natives","volume":"341","author":"Rajput","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1161\/01.CIR.99.20.2665","article-title":"Exaggerated Endothelin Release in High-Altitude Pulmonary Edema","volume":"99","author":"Sartori","year":"1999","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"taw005","DOI":"10.1093\/jtm\/taw005","article-title":"Biomarkers of Hypoxia, Endothelial and Circulatory Dysfunction among Climbers in Nepal with AMS and HAPE: A Prospective Case-Control Study","volume":"23","author":"Barker","year":"2016","journal-title":"J. Travel. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ali, Z., Mishra, A., Kumar, R., Alam, P., Pandey, P., Ram, R., Thinlas, T., Mohammad, G., and Qadar Pasha, M.A. (2012). Interactions among Vascular-Tone Modulators Contribute to High Altitude Pulmonary Edema and Augmented Vasoreactivity in Highlanders. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044049"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/japplphysiol.00513.2014","article-title":"Lungs at High-Altitude: Genomic Insights into Hypoxic Responses","volume":"119","author":"Mishra","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1161\/01.CIR.0000051459.74466.46","article-title":"Endothelin-1 Increases Vascular Superoxide via Endothelin(A)-NADPH Oxidase Pathway in Low-Renin Hypertension","volume":"107","author":"Li","year":"2003","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1089\/dna.2009.0865","article-title":"Endothelin-1 Impairs Nitric Oxide Signaling in Endothelial Cells Through a Protein Kinase C\u03b4-Dependent Activation of STAT3 and Decreased Endothelial Nitric Oxide Synthase Expression","volume":"28","author":"Sud","year":"2009","journal-title":"DNA Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1038\/s41440-021-00728-9","article-title":"Sex-Dependent Blood Pressure Regulation in Acute Hypoxia","volume":"44","author":"Burtscher","year":"2021","journal-title":"Hypertens. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1183\/09031936.96.09091947","article-title":"Endothelin-1 and Interleukin-8 in High Altitude Pulmonary Oedema","volume":"9","author":"Droma","year":"1996","journal-title":"Eur. Respir. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1089\/ham.2008.1053","article-title":"Transpulmonary Plasma ET-1 and Nitrite Differences in High Altitude Pulmonary Hypertension","volume":"10","author":"Berger","year":"2009","journal-title":"High Alt. Med. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/sj.gene.6364441","article-title":"Polymorphisms in the Endothelin-1 (EDN1) Are Associated with Asthma in Two Populations","volume":"9","author":"Zhu","year":"2008","journal-title":"Genes Immun."},{"key":"ref_47","first-page":"2982","article-title":"Relationship of the Polymorphism Lys198Asn Endothelin-1 Gene with COPD and Coronary Heart Disease","volume":"56","author":"Lilevska","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Tomar, A., Malhotra, S., and Sarkar, S. (2015). Polymorphism Profiling of Nine High Altitude Relevant Candidate Gene Loci in Acclimatized Sojourners and Adapted Natives. BMC Genet., 16.","DOI":"10.1186\/s12863-015-0268-y"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2478\/enr-2019-0025","article-title":"Hypoxic Regulation of EDN1, EDNRA, EDNRB, and ECE1 Gene Expressions in ERN1 Knockdown U87 Glioma Cells","volume":"53","author":"Minchenko","year":"2019","journal-title":"Endocr. Regul."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1042\/CS20120371","article-title":"EGLN1 variants influence expression and S ao2 levels to associate with high-altitude pulmonary oedema and adaptation","volume":"124","author":"Mishra","year":"2013","journal-title":"Clin. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6134","DOI":"10.1073\/pnas.1422759112","article-title":"Genetic differences and aberrant methylation in the apelin system predict the risk of high-altitude pulmonary edema","volume":"112","author":"Mishra","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","first-page":"502","article-title":"Arterial Oxygen Saturation under Hypoxic Environment of High-Altitude Associates with Routine Physical Activities of Natives","volume":"85","author":"Kocherlakota","year":"2003","journal-title":"Curr. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.3389\/fphys.2018.01504","article-title":"Preparation for Endurance Competitions at Altitude: Physiological, Psychological, Dietary and Coaching Aspects. A Narrative Review","volume":"9","author":"Burtscher","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Burtscher, M., Millet, G.P., and Burtscher, J. (2022). Hypoxia Conditioning for High-Altitude Pre-Acclimatization. J. Sci. Sport Exerc., 1\u201315.","DOI":"10.1007\/s42978-021-00150-0"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1046\/j.1365-2362.1997.1870736.x","article-title":"Both Plasma and Renal Endothelin-1 Participate in the Acute Cardiovascular Response to Exercise","volume":"27","author":"Cecioni","year":"1997","journal-title":"Eur. J. Clin. Investig."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/18\/11174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:24:16Z","timestamp":1760142256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/18\/11174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":55,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijerph191811174"],"URL":"https:\/\/doi.org\/10.3390\/ijerph191811174","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]}}}