{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:18:47Z","timestamp":1789712327544,"version":"4.0.1"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Blood biomarkers hold potential for the early diagnosis of ischaemic stroke (IS). We aimed to evaluate the current weight of evidence and identify potential biomarkers and biological pathways for further investigation. We searched PubMed, EMBASE, the Cochrane Library and Web of Science, used R package meta4diag for diagnostic meta-analysis and applied Gene Ontology (GO) analysis to identify vital biological processes (BPs). Among 8544 studies, we included 182 articles with a total of 30,446 participants: 15675 IS, 2317 haemorrhagic stroke (HS), 1798 stroke mimics, 846 transient ischaemic attack and 9810 control subjects. There were 518 pooled biomarkers including 203 proteins, 114 genes, 108 metabolites and 88 transcripts. Our study generated two shortlists of biomarkers for future research: one with optimal diagnostic performance and another with low selection bias. Glial fibrillary acidic protein was eligible for diagnostic meta-analysis, with summary sensitivities and specificities for differentiating HS from IS between 3 h and 24 h after stroke onset ranging from 73% to 80% and 77% to 97%, respectively. GO analysis revealed the top five BPs associated with IS. This study provides a holistic view of early diagnostic biomarkers in IS. Two shortlists of biomarkers and five BPs warrant future investigation.<\/jats:p>","DOI":"10.3390\/ijms241813821","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:51:37Z","timestamp":1694080297000},"page":"13821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Multi-Level Biomarkers for Early Diagnosis of Ischaemic Stroke: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Qianyun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Long","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"See Wai","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-7011","authenticated-orcid":false,"given":"Joshua Wing Kei","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-4166","authenticated-orcid":false,"given":"Yaqing","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3355-3237","authenticated-orcid":false,"given":"Timothy Hudson","family":"Rainer","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1474-4422(19)30034-1","article-title":"Global, regional, and national burden of stroke, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Collaborators","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1161\/STR.0000000000000158","article-title":"2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association\/American Stroke Association","volume":"49","author":"Powers","year":"2018","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E3","DOI":"10.3171\/2013.10.FOCUS13396","article-title":"The role of imaging in acute ischemic stroke","volume":"36","author":"Tong","year":"2014","journal-title":"Neurosurg. Focus."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Asci Erkocyigit, B., Ozufuklar, O., Yardim, A., Guler Celik, E., and Timur, S. (2023). Biomarker Detection in Early Diagnosis of Cancer: Recent Achievements in Point-of-Care Devices Based on Paper Microfluidics. Biosensors, 13.","DOI":"10.3390\/bios13030387"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1158672","DOI":"10.3389\/fbioe.2023.1158672","article-title":"CRISPR-cas technology: A key approach for SARS-CoV-2 detection","volume":"11","author":"Fang","year":"2023","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_7","first-page":"5619","article-title":"Rapid and quantitative detection of C-reactive protein using quantum dots and immunochromatographic test strips","volume":"9","author":"Cheng","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"168","DOI":"10.5858\/arpa.2020-0112-RA","article-title":"Current Status of Clinical Application of Point-of-Care Testing","volume":"145","author":"Park","year":"2021","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e032132","DOI":"10.1136\/bmjopen-2019-032132","article-title":"Impact of point-of-care panel tests in ambulatory care: A systematic review and meta-analysis","volume":"10","author":"Goyder","year":"2020","journal-title":"BMJ Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e000086","DOI":"10.1136\/bmjresp-2015-000086","article-title":"Narrative review of primary care point-of-care testing (POCT) and antibacterial use in respiratory tract infection (RTI)","volume":"2","author":"Cooke","year":"2015","journal-title":"BMJ Open Respir. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jstrokecerebrovasdis.2009.10.008","article-title":"Matrix metalloproteinase-9 as a marker for acute ischemic stroke: A systematic review","volume":"20","author":"Bellolio","year":"2011","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1177\/1747493020946157","article-title":"Blood biomarkers for the diagnosis and differentiation of stroke: A systematic review and meta-analysis","volume":"15","author":"Misra","year":"2020","journal-title":"Int. J. Stroke"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1007\/s12031-022-01991-2","article-title":"Circulating Non-coding RNAs as Potential Biomarkers for Ischemic Stroke: A Systematic Review","volume":"72","author":"Zhao","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s11306-019-1615-1","article-title":"Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: A systematic review","volume":"15","author":"Ke","year":"2019","journal-title":"Metabolomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"638693","DOI":"10.3389\/fneur.2021.638693","article-title":"Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review","volume":"12","author":"Baez","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41582-020-0350-6","article-title":"Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke","volume":"16","author":"Montaner","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association\/American Stroke Association","volume":"50","author":"Powers","year":"2019","journal-title":"Stroke"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1001\/jama.2017.19163","article-title":"Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement","volume":"319","author":"McInnes","year":"2018","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2 a revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Guo, J., and Riebler, A. (2018). meta4diag: Bayesian Bivariate Meta-Analysis of Diagnostic Test Studies for Routine Practice. arXiv.","DOI":"10.18637\/jss.v083.i01"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1177\/0194599817728898","article-title":"Null Hypotheses, Interval Estimation, and Bayesian Analysis","volume":"157","author":"Shin","year":"2017","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.bja.2019.08.015","article-title":"Use of the GRADE approach in systematic reviews and guidelines","volume":"123","author":"Granholm","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1373\/49.10.1752","article-title":"Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke","volume":"49","author":"Dambinova","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1016\/j.ajem.2019.02.037","article-title":"Clinical usefulness of brain-derived neurotrophic factor and visinin-like protein-1 in early diagnostic tests for acute stroke","volume":"37","author":"Algin","year":"2019","journal-title":"Am. J. Emerg. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10072-010-0457-4","article-title":"The usefulness of albumin-adjusted ischemia-modified albumin index as early detecting marker for ischemic stroke","volume":"32","author":"Ahn","year":"2011","journal-title":"Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dambinova, S.A., Bettermann, K., Glynn, T., Tews, M., Olson, D., Weissman, J.D., and Sowell, R.L. (2012). Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042362"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/jnnp-2017-316084","article-title":"New biomarker for acute ischaemic stroke: Plasma glycogen phosphorylase isoenzyme BB","volume":"89","author":"Park","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.37506\/ijfmt.v15i3.15534","article-title":"Evaluation of glycogen phosphorylase bb (GPBB) level in serum as marker in diagnosis of acute ischemic stroke","volume":"15","author":"AlGawwam","year":"2021","journal-title":"Indian J. Forensic Med. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1021\/pr501324n","article-title":"Proteomic Signature of Endothelial Dysfunction Identified in the Serum of Acute Ischemic Stroke Patients by the iTRAQ-Based LC-MS Approach","volume":"14","author":"Sharma","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5507\/bp.2011.049","article-title":"Determination of serum visinin like protein-1 and its potential for the diagnosis of brain injury due to the stroke: A pilot study","volume":"155","author":"Stejskal","year":"2011","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc Czech Repub."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1373\/clinchem.2006.070912","article-title":"Identification of novel brain biomarkers","volume":"52","author":"Laterza","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.2169\/internalmedicine.55.5925","article-title":"The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke","volume":"55","author":"Yang","year":"2016","journal-title":"Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10760296211035446","DOI":"10.1177\/10760296211035446","article-title":"miR-124 Is Downregulated in Serum of Acute Cerebral Infarct Patients and Shows Diagnostic and Prognostic Value","volume":"27","author":"Zhou","year":"2021","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ji, Q., Ji, Y., Peng, J., Zhou, X., Chen, X., Zhao, H., Xu, T., Chen, L., and Xu, Y. (2016). Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163645"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jocn.2014.05.042","article-title":"Downregulation of serum brain specific microRNA is associated with inflammation and infarct volume in acute ischemic stroke","volume":"22","author":"Liu","year":"2015","journal-title":"J. Clin. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, X., Yu, Y., Xu, W., Dong, L., Wang, Y., Gao, B., Li, G., and Zhang, W. (2016). Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040458"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1007\/s12035-021-02440-8","article-title":"Circulating lncRNAs HIF1A-AS2 and LINLK-A: Role and Relation to Hypoxia-Inducible Factor-1alpha in Cerebral Stroke Patients","volume":"58","author":"Ewida","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.gdata.2017.08.006","article-title":"Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population","volume":"14","author":"Chantler","year":"2017","journal-title":"Genom. Data"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16038","DOI":"10.1038\/npjgenmed.2016.38","article-title":"Machine-learning approach identifies a pattern of gene expression in peripheral blood that can accurately detect ischaemic stroke","volume":"1","author":"Petrone","year":"2016","journal-title":"NPJ Genom. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1373\/49.10.1733","article-title":"Early Biomarkers of Stroke","volume":"49","author":"Reynolds","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1111\/jcmm.12614","article-title":"GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases","volume":"19","author":"Stanca","year":"2015","journal-title":"J. Cell Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1007\/s13311-019-00720-9","article-title":"High-Throughput Profiling of Circulating Antibody Signatures for Stroke Diagnosis Using Small Volumes of Whole Blood","volume":"16","author":"Stafford","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/jnc.13419","article-title":"Plasmatic retinol-binding protein 4 and glial fibrillary acidic protein as biomarkers to differentiate ischemic stroke and intracerebral hemorrhage","volume":"136","author":"Llombart","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1373\/clinchem.2016.263335","article-title":"Glial Fibrillary Acidic Protein Serum Levels Distinguish between Intracerebral Hemorrhage and Cerebral Ischemia in the Early Phase of Stroke","volume":"63","author":"Luger","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41582-021-00616-3","article-title":"Blood GFAP as an emerging biomarker in brain and spinal cord disorders","volume":"18","author":"Abdelhak","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13049-022-01065-7","article-title":"Diagnostic performance of Glial Fibrillary Acidic Protein and Prehospital Stroke Scale for identification of stroke and stroke subtypes in an unselected patient cohort with symptom onset < 4.5 h","volume":"31","author":"Jaeger","year":"2023","journal-title":"Scand. J. Trauma. Resusc. Emerg. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/ana.25859","article-title":"Circulating Metabolites Differentiate Acute Ischemic Stroke from Stroke Mimics","volume":"88","author":"Tiedt","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1074\/mcp.RA120.002283","article-title":"A Mouse Brain-based Multi-omics Integrative Approach Reveals Potential Blood Biomarkers for Ischemic Stroke","volume":"19","author":"Simats","year":"2020","journal-title":"Mol. Cell Proteom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1038\/s41467-021-23774-w","article-title":"MOGONET integrates multi-omics data using graph convolutional networks allowing patient classification and biomarker identification","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0166-2236(99)01401-0","article-title":"Pathobiology of ischaemic stroke: An integrated view","volume":"22","author":"Dirnagl","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1177\/1747493018806167","article-title":"Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy","volume":"14","author":"Perry","year":"2019","journal-title":"Int. J. Stroke"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/1354750X.2019.1691657","article-title":"Role of glial fibrillary acidic protein as a biomarker in differentiating intracerebral haemorrhage from ischaemic stroke and stroke mimics: A meta-analysis","volume":"25","author":"Kumar","year":"2020","journal-title":"Biomarkers"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e012799","DOI":"10.1136\/bmjopen-2016-012799","article-title":"STARD 2015 guidelines for reporting diagnostic accuracy studies: Explanation and elaboration","volume":"6","author":"Cohen","year":"2016","journal-title":"BMJ Open"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:46:58Z","timestamp":1760129218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,7]]},"references-count":57,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241813821"],"URL":"https:\/\/doi.org\/10.3390\/ijms241813821","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,7]]}}}