{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:23:07Z","timestamp":1775114587642,"version":"3.50.1"},"reference-count":47,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research Project of Yan-Zhao Medical Studies","award":["YZZZ2024016"],"award-info":[{"award-number":["YZZZ2024016"]}]},{"name":"Scientific Research Projects of Higher Education Institutions in Hebei Province","award":["QN2025158"],"award-info":[{"award-number":["QN2025158"]}]},{"name":"University-level Research Project of Shaanxi University of Chinese Medicine","award":["2023GP24"],"award-info":[{"award-number":["2023GP24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Objective<\/jats:title>\n               <jats:p>Recent investigations have looked at the systemic concentrations of branched-chain amino acids (BCAA), which they consider prospective indicators for health conditions and the likelihood of chronic diseases. To elucidate the equivocal link between systemic BCAA concentrations and prediabetes, our study undertook a meta-analytical investigation.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Materials and Methods<\/jats:title>\n               <jats:p>Electronic databases were comprehensively searched in April 2024, and the study quality evaluation relied on the Newcastle-Ottawa Scale (NOS). The <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> statistic was used for heterogeneity assessment, and data analysis relied on Review Manager 5.4 and Stata 12.0. Standard mean difference (SMD) was used as the effect size to account for varying units of measurement across the included studies. Sensitivity assessment was instituted to evaluate result tenacity, and subgroup examinations were concomitantly carried out, with funnel plots, Egger\u2019s regression analysis, and Begg\u2019s rank-correlation methodology deployed to discern publication bias. PROSPERO registration (CRD42024572760) validates this review\u2019s protocol compliance.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>Meta-analysis was conducted on 15 studies that involved 3,849 participants. Most individuals were over 40 years old. The prediabetes (PreDM) group exhibited significantly elevated levels of valine (Val) (SMD = 0.29; 95% confidence interval (CI) [0.14\u20130.45]; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0002), leucine (Leu) (SMD = 0.34; 95% CI [0.18\u20130.49]; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), and isoleucine (Ile) (SMD = 0.24; 95% CI [0.15\u20130.32]; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.00001) compared to controls. Affirming the soundness of the results, sensitivity analysis indicated the lack of significant publication bias.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>This meta-analysis supports the hypothesis that circulating BCAA levels increase in PreDM, suggesting that measuring BCAA levels could be investigated as a potential biomarker for the diagnosis of PreDM and a target for its treatment.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.20054","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:30:32Z","timestamp":1758789032000},"page":"e20054","source":"Crossref","is-referenced-by-count":1,"title":["Association of circulating branched-chain amino acids with risk of pre-diabetes: a systematic review and meta-analysis"],"prefix":"10.7717","volume":"13","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang-Hong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi-Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ping","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Jun","family":"Yue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi\u2019an, Shaanxi Province, China"},{"name":"International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"10.7717\/peerj.20054\/ref-1","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1136\/bmj.331.7521.903","article-title":"Standard deviations and standard errors","volume":"331","author":"Altman","year":"2005","journal-title":"Bmj"},{"key":"10.7717\/peerj.20054\/ref-2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/4207067","article-title":"Higher concentrations of BCAAs and 3-HIB are associated with insulin resistance in the transition from gestational diabetes to type 2 diabetes","volume":"2018","author":"Andersson-Hall","year":"2018","journal-title":"Journal of Diabetes Research"},{"key":"10.7717\/peerj.20054\/ref-3","doi-asserted-by":"publisher","first-page":"665292","DOI":"10.3389\/fendo.2021.665292","article-title":"Nuclear magnetic resonance derived biomarkers for evaluating cardiometabolic risk in youth and young adults across the spectrum of glucose tolerance","volume":"12","author":"Chung","year":"2021","journal-title":"Frontiers in Endocrinology"},{"key":"10.7717\/peerj.20054\/ref-4","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1177\/1932296814553622","article-title":"A novel test for IGT utilizing metabolite markers of glucose tolerance","volume":"9","author":"Cobb","year":"2014","journal-title":"Journal of Diabetes Science and Technology"},{"key":"10.7717\/peerj.20054\/ref-5","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1113\/JP275075","article-title":"Restoration of metabolic health by decreased consumption of branched-chain amino acids","volume":"596","author":"Cummings","year":"2018","journal-title":"The Journal of Physiology"},{"key":"10.7717\/peerj.20054\/ref-6","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.bbrc.2003.11.039","article-title":"Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes","volume":"312","author":"Doi","year":"2003","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.7717\/peerj.20054\/ref-7","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1093\/jn\/135.9.2103","article-title":"Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity","volume":"135","author":"Doi","year":"2005","journal-title":"The Journal of Nutrition"},{"key":"10.7717\/peerj.20054\/ref-8","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1001\/jama.2023.4063","article-title":"Diagnosis and management of prediabetes","volume":"329","author":"Echouffo-Tcheugui","year":"2023","journal-title":"Jama"},{"key":"10.7717\/peerj.20054\/ref-9","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1161\/hypertensionaha.119.13735","article-title":"Concentration of branched-chain amino acids is a strong risk marker for incident hypertension","volume":"74","author":"Flores-Guerrero","year":"2019","journal-title":"Hypertension"},{"key":"10.7717\/peerj.20054\/ref-10","doi-asserted-by":"publisher","first-page":"e00578\u201300519","DOI":"10.1128\/mSystems.00578-19","article-title":"The gut microbial diversity of newly diagnosed diabetics but not of prediabetics is significantly different from that of healthy nondiabetics","volume":"5","author":"Gaike","year":"2020","journal-title":"MSystems"},{"key":"10.7717\/peerj.20054\/ref-11","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.3390\/nu10121977","article-title":"Foodproducts as sources of protein and amino acids\u2014the case of poland","volume":"10","author":"G\u00f3rska-Warsewicz","year":"2018","journal-title":"Nutrients"},{"key":"10.7717\/peerj.20054\/ref-12","doi-asserted-by":"publisher","first-page":"833","DOI":"10.2337\/dc15-2251","article-title":"Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis","volume":"39","author":"Guasch-Ferr\u00e9","year":"2016","journal-title":"Diabetes Care"},{"key":"10.7717\/peerj.20054\/ref-13","doi-asserted-by":"publisher","first-page":"11348","DOI":"10.1074\/jbc.M109.075184","article-title":"Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels","volume":"285","author":"Herman","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"10.7717\/peerj.20054\/ref-14","volume-title":"Cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023)","year":"2023"},{"key":"10.7717\/peerj.20054\/ref-15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.2147\/dmso.S336736","article-title":"High L-valine concentrations associate with increased oxidativestress and newly-diagnosed type 2 diabetes mellitus: a cross-sectional study","volume":"15","author":"Hu","year":"2022","journal-title":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy"},{"key":"10.7717\/peerj.20054\/ref-16","doi-asserted-by":"publisher","first-page":"00057","DOI":"10.3389\/fmed.2016.00057","article-title":"Branched-chain amino acid levels are related with surrogates of disturbed lipid metabolism among older men","volume":"3","author":"Kujala","year":"2016","journal-title":"Frontiers in Medicine"},{"key":"10.7717\/peerj.20054\/ref-17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.diabres.2018.03.028","article-title":"Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines","volume":"140","author":"Lee","year":"2018","journal-title":"Diabetes Research and Clinical Practice"},{"key":"10.7717\/peerj.20054\/ref-18","doi-asserted-by":"publisher","first-page":"195","DOI":"10.4093\/dmj.2019.0209","article-title":"Plasma targeted metabolomics analysis for amino acids and acylcarnitines in patients with prediabetes, type 2 diabetes mellitus, and diabetic vascular complications","volume":"45","author":"Li","year":"2021","journal-title":"Diabetes & Metabolism Journal"},{"key":"10.7717\/peerj.20054\/ref-19","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3389\/fphys.2017.00853","article-title":"Branched-chain amino acid negatively regulates KLF15 expression via PI3K-AKT pathway","volume":"8","author":"Liu","year":"2017","journal-title":"Frontiers in Physiology"},{"key":"10.7717\/peerj.20054\/ref-20","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12902-020-00653-x","article-title":"Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis","volume":"20","author":"Long","year":"2020","journal-title":"BMC Endocrine Disorders"},{"key":"10.7717\/peerj.20054\/ref-21","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrendo.2014.171","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance","volume":"10","author":"Lynch","year":"2014","journal-title":"Nature Reviews Endocrinology"},{"key":"10.7717\/peerj.20054\/ref-22","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.2337\/dc18-2217","article-title":"Plasma amino acids and incident type 2 diabetes in patients with coronary artery disease","volume":"42","author":"McCann","year":"2019","journal-title":"Diabetes Care"},{"key":"10.7717\/peerj.20054\/ref-23","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s00726-013-1611-0","article-title":"The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study","volume":"45","author":"Mels","year":"2013","journal-title":"Amino Acids"},{"key":"10.7717\/peerj.20054\/ref-24","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.regpep.2009.08.001","article-title":"Selective amino acid deficiency in patients with impaired glucose tolerance and type 2 diabetes","volume":"160","author":"Menge","year":"2010","journal-title":"Regulatory Peptides"},{"key":"10.7717\/peerj.20054\/ref-25","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1002\/oby.21488","article-title":"Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health","volume":"24","author":"Menni","year":"2016","journal-title":"Obesity"},{"key":"10.7717\/peerj.20054\/ref-26","doi-asserted-by":"publisher","first-page":"e1002179","DOI":"10.1371\/journal.pmed.1002179","article-title":"Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: a mendelian randomisation analysis","volume":"13","author":"Minelli","year":"2016","journal-title":"PLOS Medicine"},{"key":"10.7717\/peerj.20054\/ref-27","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.abb.2015.08.003","article-title":"Type 2 diabetes is associated with postprandial amino acid measures","volume":"589","author":"Mook-Kanamori","year":"2016","journal-title":"Archives of Biochemistry and Biophysics"},{"key":"10.7717\/peerj.20054\/ref-28","doi-asserted-by":"publisher","first-page":"e133","DOI":"10.1038\/nutd.2014.32","article-title":"Plasma amino acid profiles are associated with insulin, C-peptide and adiponectin levels in type 2 diabetic patients","volume":"4","author":"Nakamura","year":"2014","journal-title":"Nutrition & Diabetes"},{"key":"10.7717\/peerj.20054\/ref-29","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cmet.2018.10.013","article-title":"Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids","volume":"29","author":"Neinast","year":"2019","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.20054\/ref-30","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.20054\/ref-31","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3390\/ijms19040954","article-title":"Branched chain amino acids: beyond nutrition metabolism","volume":"19","author":"Nie","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.20054\/ref-32","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3945\/jn.109.108977","article-title":"Isoleucine prevents the accumulation of tissue triglycerides and upregulates the expression of PPARalpha and uncoupling protein in diet-induced obese mice","volume":"140","author":"Nishimura","year":"2010","journal-title":"The Journal of Nutrition"},{"key":"10.7717\/peerj.20054\/ref-33","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.metabol.2019.06.011","article-title":"Amino acid signature predictive of incident prediabetes: a case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort","volume":"98","author":"Owei","year":"2019","journal-title":"Metabolism-Clinical and Experimental"},{"key":"10.7717\/peerj.20054\/ref-34","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3390\/metabo12060513","article-title":"Novel plasma metabolomic markers associated with diabetes progression in older puerto ricans","volume":"12","author":"Rivas-Tumanyan","year":"2022","journal-title":"Metabolites"},{"key":"10.7717\/peerj.20054\/ref-35","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1373\/clinchem.2015.251710","article-title":"Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial","volume":"62","author":"Ruiz-Canela","year":"2016","journal-title":"Clinical Chemistry"},{"key":"10.7717\/peerj.20054\/ref-36","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1089\/met.2024.0071","article-title":"Quantification and correlation analysis of bacteroides species with diabetes-related amino acids in individuals with prediabetes and type 2 diabetes mellitus","volume":"22","author":"Safari-Alighiarloo","year":"2024","journal-title":"Metabolic Syndrome and Related Disorders"},{"key":"10.7717\/peerj.20054\/ref-37","doi-asserted-by":"publisher","first-page":"112780","DOI":"10.1016\/j.ecoenv.2021.112780","article-title":"Serum branched-chain amino acids modifies the associations between air pollutants and insulin resistance","volume":"225","author":"Shi","year":"2021","journal-title":"Ecotoxicology and Environmental Safety"},{"key":"10.7717\/peerj.20054\/ref-38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cca.2016.10.005","article-title":"Biomarkers of morbid obesity and prediabetes by metabolomic profiling of human discordant phenotypes","volume":"463","author":"Tulipani","year":"2016","journal-title":"Clinica Chimica Acta"},{"key":"10.7717\/peerj.20054\/ref-39","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41387-022-00213-3","article-title":"Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes","volume":"12","author":"Vanweert","year":"2022","journal-title":"Nutrition & Diabetes"},{"key":"10.7717\/peerj.20054\/ref-40","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1471-2288-14-135","article-title":"Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range","volume":"14","author":"Wan","year":"2014","journal-title":"BMC Medical Research Methodology"},{"key":"10.7717\/peerj.20054\/ref-41","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.atherosclerosis.2022.04.026","article-title":"Association of circulating branched-chain amino acids with risk of cardiovascular disease: a systematic review and meta-analysis","volume":"350","author":"Wang","year":"2022","journal-title":"Atherosclerosis"},{"key":"10.7717\/peerj.20054\/ref-42","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/nm.2307","article-title":"Metabolite profiles and the risk of developing diabetes","volume":"17","author":"Wang","year":"2011","journal-title":"Nature Medicine"},{"key":"10.7717\/peerj.20054\/ref-43","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD","volume":"41","author":"Wheeler","year":"2020","journal-title":"European Heart Journal"},{"key":"10.7717\/peerj.20054\/ref-44","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.cmet.2018.04.015","article-title":"The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase","volume":"27","author":"White","year":"2018","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.20054\/ref-45","doi-asserted-by":"publisher","first-page":"101261","DOI":"10.1016\/j.molmet.2021.101261","article-title":"Insulin action, type 2 diabetes, and branched-chain amino acids: a two-way street","volume":"52","author":"White","year":"2021","journal-title":"Molecular Metabolism"},{"key":"10.7717\/peerj.20054\/ref-46","doi-asserted-by":"publisher","first-page":"E1060","DOI":"10.1210\/jc.2012-4132","article-title":"Metabolic signature shift in type 2 diabetes mellitus revealed by mass spectrometry-based metabolomics","volume":"98","author":"Xu","year":"2013","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"10.7717\/peerj.20054\/ref-47","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1161\/hypertensionaha.118.10919","article-title":"Branched-chain amino acids as critical switches in health and disease","volume":"72","author":"Zhang","year":"2018","journal-title":"Hypertension"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/20054.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20054.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20054.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20054.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:30:37Z","timestamp":1758789037000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/20054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":47,"alternative-id":["10.7717\/peerj.20054"],"URL":"https:\/\/doi.org\/10.7717\/peerj.20054","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"article-number":"e20054"}}