{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:37:44Z","timestamp":1779341864236,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P3-0054"],"award-info":[{"award-number":["P3-0054"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to assess the interrelation between vascular ultrasonography (US) findings, histopathological data, and the expression of selected dysregulated microRNAs (miRNAs) in giant cell arteritis (GCA). The study included data on the clinical parameters, US measurements, and temporal artery biopsies (TABs) of 46 treatment-na\u00efve patients diagnosed with GCA and 22 age-matched non-GCA patient controls. We performed a comprehensive comparative and correlation analysis along with generation of receiver operating characteristic (ROC) curves to ascertain the diagnostic performance of US examination parameters and selected miRNAs for GCA diagnosis. We showed significant differences in the US-measured intima\u2013media thickness of the temporal arteries, the presence of a halo sign, and the presence of luminal stenosis between GCA-positive\/TAB-positive, GCA-positive\/TAB-negative, and non-GCA patients. Correlation analysis revealed significant associations between several histopathological parameters, US-measured intima\u2013media thickness, and the halo sign. We found that the significant overexpression of miR-146b-5p, miR-155-5p, miR-511-5p, and miR-21-5p, and the under-expression of the miR-143\/145 cluster, miR-30a-5p, and miR-125a-5p, coincides and is associated with the presence of a halo sign in patients with GCA. Notably, we determined a high diagnostic performance of miR-146b-5p, miR-21-3p, and miR-21-5p expression profiles in discriminating GCA patients from non-GCA controls, suggesting their potential utilization as putative biomarkers of GCA. Taken together, our study provides an insight into the US-based diagnostic evaluation of GCA by revealing the complex interrelation of clearly defined image findings with underlying vascular immunopathology and altered arterial tissue-specific miRNA profiles.<\/jats:p>","DOI":"10.3390\/ijms24021572","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T02:29:57Z","timestamp":1673576997000},"page":"1572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Arterial Histopathology and microRNA Expression That Underlie Ultrasonography Findings in Temporal Arteries of Patients with Giant Cell Arteritis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4596-7931","authenticated-orcid":false,"given":"Alen","family":"Sulji\u010d","sequence":"first","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alojzija","family":"Ho\u010devar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Jur\u010di\u0107","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-8216","authenticated-orcid":false,"given":"Luka","family":"Bolha","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s11916-005-0033-4","article-title":"Horton\u2019s Disease: Past and Present","volume":"9","author":"Levin","year":"2005","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"A544","DOI":"10.1016\/j.autrev.2012.01.003","article-title":"Giant Cell Arteritis: A Review of Classification, Pathophysiology, Geoepidemiology and Treatment","volume":"11","author":"Borchers","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1001\/jamainternmed.2020.3050","article-title":"Diagnostic Accuracy of Symptoms, Physical Signs, and Laboratory Tests for Giant Cell Arteritis A Systematic Review and Meta-Analysis","volume":"180","author":"Sandovici","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1093\/rheumatology\/kez385","article-title":"Sensitivity of Temporal Artery Biopsy in the Diagnosis of Giant Cell Arteritis: A Systematic Literature Review and Meta-Analysis","volume":"59","author":"Rubenstein","year":"2020","journal-title":"Rheumatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/rheumatology\/kex173","article-title":"The Use of Ultrasound to Assess Giant Cell Arteritis: Review of the Current Evidence and Practical Guide for the Rheumatologist","volume":"57","author":"Monti","year":"2018","journal-title":"Rheumatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.5114\/ada.2019.82823","article-title":"Advantages in Diagnosis of Giant Cell Arteritis by Ultrasound","volume":"36","author":"Wojczal","year":"2019","journal-title":"Postep. Dermatol. I Alergol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1136\/annrheumdis-2017-212649","article-title":"EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice","volume":"77","author":"Dejaco","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"ii22","DOI":"10.1093\/rheumatology\/kex461","article-title":"Ultrasound in the Diagnosis and Management of Giant Cell Arteritis","volume":"57","author":"Schmidt","year":"2018","journal-title":"Rheumatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrrheum.2012.97","article-title":"Clinical Features of Polymyalgia Rheumatica and Giant Cell Arteritis","volume":"8","author":"Salvarani","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3899\/jrheum.171428","article-title":"Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT Patient-Based Reliability Exercises","volume":"45","author":"Chrysidis","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/rheumatology\/kex341","article-title":"The Proposed Role of Ultrasound in the Management of Giant Cell Arteritis in Routine Clinical Practice","volume":"57","author":"Monti","year":"2018","journal-title":"Rheumatology"},{"key":"ref_13","first-page":"393","article-title":"Novel Ultrasonographic Halo Score for Giant Cell Arteritis: Assessment of Diagnostic Accuracy and Association with Ocular Ischaemia","volume":"79","author":"Borg","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1093\/rheumatology\/keaa806","article-title":"Ultrasonographic Halo Score in Giant Cell Arteritis: Association with Intimal Hyperplasia and Ischaemic Sight Loss","volume":"60","author":"Wolfe","year":"2021","journal-title":"Rheumatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1097\/PAS.0000000000000244","article-title":"Inflamed Temporal Artery: Histologic Findings in 354 Biopsies, with Clinical Correlations","volume":"38","author":"Cavazza","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1308\/003588414X13814021679438","article-title":"Facial Nerve Injury during Temporal Artery Biopsy","volume":"96","author":"Gunawardene","year":"2014","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta20900","article-title":"The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): A Diagnostic Accuracy and Cost-Effectiveness Study","volume":"20","author":"Luqmani","year":"2016","journal-title":"Health Technol. Assess."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00296-018-4157-3","article-title":"Diagnosis and Differential Diagnosis of Large-Vessel Vasculitides","volume":"39","author":"Keser","year":"2019","journal-title":"Rheumatol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41572-021-00327-5","article-title":"Large-Vessel Vasculitis","volume":"7","author":"Pugh","year":"2022","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Prieto-Pe\u00f1a, D., Casta\u00f1eda, S., Mart\u00ednez-Rodr\u00edguez, I., Atienza-Mateo, B., Blanco, R., and Gonz\u00e1lez-Gay, M.A. (2021). Imaging Tests in the Early Diagnosis of Giant Cell Arteritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10163704"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12388","DOI":"10.1038\/s41598-019-48709-w","article-title":"PET\/MRI in Large-Vessel Vasculitis: Clinical Value for Diagnosis and Assessment of Disease Activity","volume":"9","author":"Laurent","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"623716","DOI":"10.3389\/fimmu.2021.623716","article-title":"The Immunopathology of Giant Cell Arteritis Across Disease Spectra","volume":"12","author":"Robinette","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0140-6736(08)61077-6","article-title":"Polymyalgia Rheumatica and Giant-Cell Arteritis","volume":"372","author":"Salvarani","year":"2008","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/modpathol.2017.10","article-title":"Clinical and Pathological Evolution of Giant Cell Arteritis: A Prospective Study of Follow-up Temporal Artery Biopsies in 40 Treated Patients","volume":"30","author":"Maleszewski","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"791099","DOI":"10.3389\/fimmu.2021.791099","article-title":"Inflammatory Cell Composition and Immune-Related MicroRNA Signature of Temporal Artery Biopsies From Patients With Giant Cell Arteritis","volume":"12","author":"Bolha","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1093\/rheumatology\/keaa204","article-title":"Identification of MicroRNAs and Their Target Gene Networks Implicated in Arterial Wall Remodelling in Giant Cell Arteritis","volume":"59","author":"Bolha","year":"2020","journal-title":"Rheumatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.canlet.2018.04.016","article-title":"Dysregulation of MicroRNAs in Autoimmune Diseases: Pathogenesis, Biomarkers and Potential Therapeutic Targets","volume":"428","author":"Long","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.trsl.2011.01.007","article-title":"MicroRNA, a New Paradigm for Understanding Immunoregulation, Inflammation, and Autoimmune Diseases","volume":"157","author":"Dai","year":"2011","journal-title":"Transl. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1136\/annrheumdis-2015-207846","article-title":"MicroRNA Markers of Inflammation and Remodelling in Temporal Arteries from Patients with Giant Cell Arteritis","volume":"75","author":"Croci","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10067-018-4231-y","article-title":"Gene and MiRNA Expression in Giant Cell Arteritis\u2014A Concise Systematic Review of Significantly Modified Studies","volume":"38","author":"Kuret","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"rkab059","DOI":"10.1093\/rap\/rkab059","article-title":"Role of the Halo Sign in the Assessment of Giant Cell Arteritis: A Systematic Review and Meta-Analysis","volume":"5","author":"Sebastian","year":"2021","journal-title":"Rheumatol. Adv. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1093\/rheumatology\/keaa578","article-title":"The Cut-off Values for the Intima-Media Complex Thickness Assessed by Colour Doppler Sonography in Seven Cranial and Aortic Arch Arteries","volume":"60","author":"Rotar","year":"2021","journal-title":"Rheumatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1093\/rheumatology\/kez554","article-title":"The Impact of Disease Extent and Severity Detected by Quantitative Ultrasound Analysis in the Diagnosis and Outcome of Giant Cell Arteritis","volume":"59","author":"Monti","year":"2020","journal-title":"Rheumatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/jcp.53.2.137","article-title":"The Importance of Skip Lesions in Temporal Arteritis","volume":"53","author":"Poller","year":"2000","journal-title":"J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/acr2.11226","article-title":"Giant Cell Arteritis: A Systematic Review and Meta-Analysis of Test Accuracy and Benefits and Harms of Common Treatments","volume":"3","author":"Dua","year":"2021","journal-title":"ACR Open Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kuret, T., Lakota, K., \u010cu\u010dnik, S., Jur\u010di\u010d, V., Distler, O., Rotar, \u017d., Ho\u010devar, A., Sodin-\u0161emrl, S., and Frank-Bertoncelj, M. (2021). Dysregulated Expression of Arterial Micrornas and Their Target Gene Networks in Temporal Arteries of Treatment-Na\u00efve Patients with Giant Cell Arteritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126520"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28097","DOI":"10.1074\/jbc.M111.236950","article-title":"Down-Regulation of Kr\u00fcppel-like Factor-4 (KLF4) by MicroRNA-143\/145 Is Critical for Modulation of Vascular Smooth Muscle Cell Phenotype by Transforming Growth Factor-\u03b2 and Bone Morphogenetic Protein 4","volume":"286","author":"Chan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nature08195","article-title":"MiR-145 and MiR-143 Regulate Smooth Muscle Cell Fate and Plasticity","volume":"460","author":"Cordes","year":"2009","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1083\/jcb.200912096","article-title":"MicroRNA Control of Podosome Formation in Vascular Smooth Muscle Cells in Vivo and in Vitro","volume":"189","author":"Quintavalle","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1161\/CIRCRESAHA.109.197517","article-title":"MicroRNA-145, a Novel Smooth Muscle Cell Phenotypic Marker and Modulator, Controls Vascular Neointimal Lesion Formation","volume":"105","author":"Cheng","year":"2009","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.jmb.2017.05.008","article-title":"MiR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle Cells by Targeting ETS-1","volume":"429","author":"Gareri","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_42","first-page":"1","article-title":"MicroRNA-30 Inhibits Neointimal Hyperplasia by Targeting Ca 2+ \/Calmodulin-Dependent Protein Kinase II\u03b4 (CaMKII\u03b4)","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1161\/CIRCRESAHA.106.141986","article-title":"MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation","volume":"100","author":"Ji","year":"2007","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1152\/ajplung.00201.2010","article-title":"MicroRNA-21 Plays a Role in Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration","volume":"299","author":"Sarkar","year":"2010","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_45","first-page":"12901","article-title":"MiR-146b-5p Promotes VSMC Proliferation and Migration","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.autrev.2017.05.014","article-title":"Recent Advances in Our Understanding of Giant Cell Arteritis Pathogenesis","volume":"16","author":"Samson","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"ii51","DOI":"10.1093\/rheumatology\/kex423","article-title":"Pathogenesis of Giant-Cell Arteritis: How Targeted Therapies Are Influencing Our Understanding of the Mechanisms Involved","volume":"57","author":"Cid","year":"2018","journal-title":"Rheumatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nrrheum.2013.161","article-title":"Immune Mechanisms in Medium and Large-Vessel Vasculitis","volume":"9","author":"Weyand","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/cvr\/cvw039","article-title":"The Multifactorial Nature of MicroRNAs in Vascular Remodelling","volume":"110","author":"Welten","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1161\/CIRCRESAHA.115.308237","article-title":"MicroRNAs for Restenosis and Thrombosis after Vascular Injury","volume":"118","author":"Gareri","year":"2016","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1093\/rheumatology\/kex143","article-title":"Ultrasound Cut-off Values for Intima-Media Thickness of Temporal, Facial and Axillary Arteries in Giant Cell Arteritis","volume":"56","author":"Juche","year":"2017","journal-title":"Rheumatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1186\/s12859-018-2264-5","article-title":"Random Forest versus Logistic Regression: A Large-Scale Benchmark Experiment","volume":"19","author":"Probst","year":"2018","journal-title":"BMC Bioinform."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fimmu.2015.00019","article-title":"Turning 21: Induction of MiR-21 as a Key Switch in the Inflammatory Response","volume":"6","author":"Sheedy","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1016\/j.celrep.2018.10.074","article-title":"Activation of MiR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells","volume":"25","author":"Kim","year":"2018","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1002\/art.1780330810","article-title":"The American College of Rheumatology 1990 Criteria for the Classification of Giant Cell Arteritis","volume":"33","author":"Hunder","year":"1990","journal-title":"Arthritis Rheum."},{"key":"ref_56","unstructured":"R Core Team (2022). R: A Language and Environment for Statistical Computing, R Core Team."},{"key":"ref_57","unstructured":"Warnes, G.R., Bolker, B., Bonebakker, L., Gentleman, R., Huber, W., Liaw, A., Lumley, T., Maechler, M., Magnusson, A., and Moeller, S. (2022, September 26). Gplots: Various R Programming Tools for Plotting Data. Version 3.1.3. Available online: https:\/\/github.com\/talgalili\/gplots."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:05:01Z","timestamp":1760119501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,13]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021572"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021572","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,13]]}}}