{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:10:14Z","timestamp":1788419414424,"version":"build-2803163510"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Divers"],"DOI":"10.1007\/s11030-025-11373-6","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:41:40Z","timestamp":1760096500000},"page":"4245-4257","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of GPX3 as a key biomarker of placental ferroptosis in gestational diabetes mellitus via bioinformatics and clinical analysis"],"prefix":"10.1007","volume":"30","author":[{"given":"Padmanaban M.","family":"Abirami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. L.","family":"Milan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Anuradha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunka Mohanram","family":"Ramkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"11373_CR1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.tem.2018.09.004","volume":"29","author":"EC Johns","year":"2018","unstructured":"Johns EC, Denison FC, Norman JE, Reynolds RM (2018) Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab 29:743\u2013754. https:\/\/doi.org\/10.1016\/j.tem.2018.09.004","journal-title":"Trends Endocrinol Metab"},{"key":"11373_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2020.105219","author":"NP Pace","year":"2021","unstructured":"Pace NP, Vassallo J, Calleja-Agius J (2021) Gestational diabetes, environmental temperature and climate factors\u2014from epidemiological evidence to physiological mechanisms. Early Hum Dev. https:\/\/doi.org\/10.1016\/j.earlhumdev.2020.105219","journal-title":"Early Hum Dev"},{"key":"11373_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113342","author":"JF Plows","year":"2018","unstructured":"Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH (2018) The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms19113342","journal-title":"Int J Mol Sci"},{"key":"11373_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0935-9","author":"A Lorenzo-Almor\u00f3s","year":"2019","unstructured":"Lorenzo-Almor\u00f3s A, Hang T, Peir\u00f3 C, Soriano-Guill\u00e9n L, Egido J, Tu\u00f1\u00f3n J, Lorenzo \u00d3 (2019) Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases. Cardiovasc Diabetol. https:\/\/doi.org\/10.1186\/s12933-019-0935-9","journal-title":"Cardiovasc Diabetol"},{"key":"11373_CR5","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1007\/s00125-016-3985-5","volume":"59","author":"P Damm","year":"2016","unstructured":"Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg J, Mathiesen ER, Clausen TD (2016) Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia 59:1396\u20131399. https:\/\/doi.org\/10.1007\/s00125-016-3985-5","journal-title":"Diabetologia"},{"key":"11373_CR6","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1007\/s40200-021-00911-2","volume":"20","author":"S Gautam","year":"2021","unstructured":"Gautam S, Alam F, Moin S, Noor N, Arif SH (2021) Role of ferritin and oxidative stress index in gestational diabetes mellitus. J Diabetes Metab Disord 20:1615\u20131619. https:\/\/doi.org\/10.1007\/s40200-021-00911-2","journal-title":"J Diabetes Metab Disord"},{"key":"11373_CR7","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/apha.12256","volume":"210","author":"JB Hansen","year":"2014","unstructured":"Hansen JB, Moen IW, Mandrup-Poulsen T (2014) Iron: the hard player in diabetes pathophysiology. Acta Physiol 210:717\u2013732. https:\/\/doi.org\/10.1111\/apha.12256","journal-title":"Acta Physiol"},{"key":"11373_CR8","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1007\/s00125-012-2633-y","volume":"55","author":"J Montonen","year":"2012","unstructured":"Montonen J, Boeing H, Steffen A, Lehmann R, Fritsche A, Joost HG, Schulze MB, Pischon T (2012) Body iron stores and risk of type 2 diabetes: results from the European prospective investigation into cancer and nutrition (EPIC)-Potsdam study. Diabetologia 55:2613\u20132621. https:\/\/doi.org\/10.1007\/s00125-012-2633-y","journal-title":"Diabetologia"},{"key":"11373_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041641","author":"J Ye","year":"2012","unstructured":"Ye J, Zhao Z, Li S, Liu G, Yan F, Ma X, Huang Z, Tian H (2012) Body iron stores and heme-iron intake in relation to risk of type 2 diabetes: a systematic review and meta-analysis. PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0041641","journal-title":"PLoS ONE"},{"key":"11373_CR10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006203","author":"H Feng","year":"2018","unstructured":"Feng H, Stockwell BR (2018) Unsolved mysteries: how does lipid peroxidation cause ferroptosis? PLoS Biol. https:\/\/doi.org\/10.1371\/journal.pbio.2006203","journal-title":"PLoS Biol"},{"key":"11373_CR11","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s12020-021-02933-5","volume":"75","author":"Y Zheng","year":"2021","unstructured":"Zheng Y, Hu Q, Wu J (2021) Adiponectin ameliorates placental injury in gestational diabetes mice by correcting fatty acid oxidation\/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity. Endocrine 75:781\u2013793. https:\/\/doi.org\/10.1007\/s12020-021-02933-5","journal-title":"Endocrine"},{"key":"11373_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1018829","author":"G Du","year":"2022","unstructured":"Du G, Zhang Q, Huang X, Wang Y (2022) Molecular mechanism of ferroptosis and its role in the occurrence and treatment of diabetes. Front Genet. https:\/\/doi.org\/10.3389\/fgene.2022.1018829","journal-title":"Front Genet"},{"key":"11373_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-01028-x","author":"Q Zhang","year":"2024","unstructured":"Zhang Q, Yuan X, Luan X, Lei T, Li Y, Chu W, Yao Q, Baker PN, Qi H, Li H (2024) GLUT1 exacerbates trophoblast ferroptosis by modulating AMPK\/ACC mediated lipid metabolism and promotes gestational diabetes mellitus associated fetal growth restriction. Mol Med. https:\/\/doi.org\/10.1186\/s10020-024-01028-x","journal-title":"Mol Med"},{"key":"11373_CR14","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","volume":"28","author":"JT Leek","year":"2012","unstructured":"Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD (2012) The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28:882\u2013883. https:\/\/doi.org\/10.1093\/bioinformatics\/bts034","journal-title":"Bioinformatics"},{"key":"11373_CR15","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43:e47\u2013e47. https:\/\/doi.org\/10.1093\/nar\/gkv007","journal-title":"Nucleic Acids Res"},{"key":"11373_CR16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L-G, Han Y, He Q-Y (2012) Clusterprofiler: an R package for comparing biological themes among gene clusters. OMICS 16:284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS"},{"key":"11373_CR17","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i11","author":"MB Kursa","year":"2010","unstructured":"Kursa MB, Rudnicki WR (2010) Feature selection with the Boruta package. J Stat Softw. https:\/\/doi.org\/10.18637\/jss.v036.i11","journal-title":"J Stat Softw"},{"key":"11373_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0730-1","author":"S Engebretsen","year":"2019","unstructured":"Engebretsen S, Bohlin J (2019) Statistical predictions with glmnet. Clin Epigenetics. https:\/\/doi.org\/10.1186\/s13148-019-0730-1","journal-title":"Clin Epigenetics"},{"key":"11373_CR19","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","volume":"49","author":"D Szklarczyk","year":"2021","unstructured":"Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P et al (2021) The STRING database in 2021: customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets. Nucleic Acids Res 49:D605\u2013D612. https:\/\/doi.org\/10.1093\/nar\/gkaa1074","journal-title":"Nucleic Acids Res"},{"key":"11373_CR20","first-page":"291","volume-title":"Cytoscape: software for visualization and analysis of biological networks data mining in proteomics","author":"M Kohl","year":"2011","unstructured":"Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks data mining in proteomics. Springer, Cham, pp 291\u2013303"},{"key":"11373_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau4996","author":"J Runge","year":"2019","unstructured":"Runge J, Nowack P, Kretschmer M, Flaxman S, Sejdinovic D (2019) Detecting and quantifying causal associations in large nonlinear time series datasets. Sci Adv. https:\/\/doi.org\/10.1126\/sciadv.aau4996","journal-title":"Sci Adv"},{"key":"11373_CR22","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ (2019) DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst 8:329-337.e324. https:\/\/doi.org\/10.1016\/j.cels.2019.03.003","journal-title":"Cell Syst"},{"key":"11373_CR23","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh P-r, Raychaudhuri S (2019) Fast, sensitive and accurate integration of single-cell data with harmony. Nat Methods 16:1289\u20131296. https:\/\/doi.org\/10.1038\/s41592-019-0619-0","journal-title":"Nat Methods"},{"key":"11373_CR24","first-page":"243","volume-title":"Profiling tumor infiltrating immune cells with CIBERSORT cancer systems biology","author":"B Chen","year":"2018","unstructured":"Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA (2018) Profiling tumor infiltrating immune cells with CIBERSORT cancer systems biology. Springer, Cham, pp 243\u2013259"},{"key":"11373_CR25","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1080\/02648725.2023.2215966","volume":"40","author":"Y Jin","year":"2023","unstructured":"Jin Y, Wang H (2023) Identification of hub genes affecting gestational diabetes mellitus based on GEO database. Biotechnol Genet Eng Rev 40:4653\u20134663. https:\/\/doi.org\/10.1080\/02648725.2023.2215966","journal-title":"Biotechnol Genet Eng Rev"},{"key":"11373_CR26","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.2174\/0118715303275367240103102801","volume":"24","author":"X Lv","year":"2024","unstructured":"Lv X, An Y (2024) Bioinformatics-based identification of ferroptosis-related genes and their diagnostic value in gestational diabetes mellitus. Endocr Metab Immune Disord Drug Targets 24:1611\u20131621. https:\/\/doi.org\/10.2174\/0118715303275367240103102801","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"11373_CR27","doi-asserted-by":"publisher","first-page":"F1244","DOI":"10.1152\/ajprenal.00662.2009","volume":"298","author":"GE Olson","year":"2010","unstructured":"Olson GE, Whitin JC, Hill KE, Winfrey VP, Motley AK, Austin LM, Deal J, Cohen HJ, Burk RF (2010) Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells. Am J Physiol-Renal Physiol 298:F1244\u2013F1253. https:\/\/doi.org\/10.1152\/ajprenal.00662.2009","journal-title":"Am J Physiol-Renal Physiol"},{"key":"11373_CR28","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1593\/neo.05328","volume":"7","author":"O-J Lee","year":"2005","unstructured":"Lee O-J, Schneider-Stock R, McChesney PA, Kuester D, Roessner A, Vieth M, Moskaluk CA, El-Rifai We (2005) Hypermethylation, loss of expression of glutathione peroxidase-3 in Barrett\u2019s tumorigenesis. Neoplasia 7:854\u2013861. https:\/\/doi.org\/10.1593\/neo.05328","journal-title":"Neoplasia"},{"key":"11373_CR29","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.3892\/or.2016.5071","volume":"36","author":"H Chen","year":"2016","unstructured":"Chen H, Zheng Z, Kim K-Y, Jin X, Roh MR, Jin Z (2016) Hypermethylation and downregulation of glutathione peroxidase 3 are related to pathogenesis of melanoma. Oncol Rep 36:2737\u20132744. https:\/\/doi.org\/10.3892\/or.2016.5071","journal-title":"Oncol Rep"},{"key":"11373_CR30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.136283","author":"R Hauffe","year":"2020","unstructured":"Hauffe R, Stein V, Chudoba C, Flore T, Rath M, Ritter K, Schell M, Wardelmann K, Deubel S, Kopp JF et al (2020) GPx3 dysregulation impacts adipose tissue insulin receptor expression and sensitivity. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.136283","journal-title":"JCI Insight"},{"key":"11373_CR31","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1016\/j.ajcnut.2023.09.025","volume":"118","author":"K Demircan","year":"2023","unstructured":"Demircan K, Jensen RC, Chillon TS, Jensen TK, Sun Q, Bonnema SJ, Hackler J, Korevaar TIM, Glintborg D, Schomburg L et al (2023) Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: prospective Odense child cohort. Am J Clin Nutr 118:1224\u20131234. https:\/\/doi.org\/10.1016\/j.ajcnut.2023.09.025","journal-title":"Am J Clin Nutr"},{"key":"11373_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04432-9","author":"Y Li","year":"2023","unstructured":"Li Y, Zhou Y, Liu D, Wang Z, Qiu J, Zhang J, Chen P, Zeng G, Guo Y, Wang X et al (2023) Glutathione peroxidase 3 induced mitochondria-mediated apoptosis via AMPK \/ERK1\/2 pathway and resisted autophagy-related ferroptosis via AMPK\/mTOR pathway in hyperplastic prostate. J Transl Med. https:\/\/doi.org\/10.1186\/s12967-023-04432-9","journal-title":"J Transl Med"},{"key":"11373_CR33","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1016\/j.bbadis.2013.07.009","volume":"1832","author":"G Sisino","year":"2013","unstructured":"Sisino G, Bouckenooghe T, Aurientis S, Fontaine P, Storme L, Vambergue A (2013) Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype. Biochim Biophys Acta 1832:1959\u20131968. https:\/\/doi.org\/10.1016\/j.bbadis.2013.07.009","journal-title":"Biochim Biophys Acta"},{"key":"11373_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.990551","author":"Q Hu","year":"2023","unstructured":"Hu Q, Chen J, Yang W, Xu M, Zhou J, Tan J, Huang T (2023) GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers. Front Oncol. https:\/\/doi.org\/10.3389\/fonc.2023.990551","journal-title":"Front Oncol"},{"key":"11373_CR35","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1111\/j.1365-313X.2008.03698.x","volume":"57","author":"K Ravet","year":"2009","unstructured":"Ravet K, Touraine B, Boucherez J, Briat JF, Gaymard F, Cellier F (2009) Ferritins control interaction between iron homeostasis and oxidative stress in Arabidopsis. Plant J 57:400\u2013412. https:\/\/doi.org\/10.1111\/j.1365-313X.2008.03698.x","journal-title":"Plant J"},{"key":"11373_CR36","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41430-019-0542-6","volume":"74","author":"Y Cheng","year":"2020","unstructured":"Cheng Y, Li T, He M, Liu J, Wu K, Liu S, Ma Z, Lu J, Zhang Q, Cheng H (2020) The association of elevated serum ferritin concentration in early pregnancy with gestational diabetes mellitus: a prospective observational study. Eur J Clin Nutr 74:741\u2013748. https:\/\/doi.org\/10.1038\/s41430-019-0542-6","journal-title":"Eur J Clin Nutr"},{"key":"11373_CR37","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s00125-016-4149-3","volume":"60","author":"S Rawal","year":"2016","unstructured":"Rawal S, Hinkle SN, Bao W, Zhu Y, Grewal J, Albert PS, Weir NL, Tsai MY, Zhang C (2016) A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort. Diabetologia 60:249\u2013257. https:\/\/doi.org\/10.1007\/s00125-016-4149-3","journal-title":"Diabetologia"},{"key":"11373_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1177547","author":"Y Zhao","year":"2023","unstructured":"Zhao Y, Gao Q, Li B, Wang Y, Wang Y (2023) Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy. Front Endocrinol. https:\/\/doi.org\/10.3389\/fendo.2023.1177547","journal-title":"Front Endocrinol"},{"key":"11373_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05708-0","author":"R Miao","year":"2023","unstructured":"Miao R, Fang X, Zhang Y, Wei J, Zhang Y, Tian J (2023) Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities. Cell Death Dis. https:\/\/doi.org\/10.1038\/s41419-023-05708-0","journal-title":"Cell Death Dis"}],"container-title":["Molecular Diversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-025-11373-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11030-025-11373-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-025-11373-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T11:33:11Z","timestamp":1779535991000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11030-025-11373-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["11373"],"URL":"https:\/\/doi.org\/10.1007\/s11030-025-11373-6","relation":{},"ISSN":["1573-501X"],"issn-type":[{"value":"1573-501X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]},"assertion":[{"value":"9 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The Institutional Ethical Committee of SRM Medical College and Hospital approved the experiments performed in this study (SRMIEC-01-25-8989).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}