{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:48:06Z","timestamp":1784648886519,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The prognosis of people with multiple sclerosis (MS) has improved substantially in recent decades due to advances in diagnosis and treatment. Due to the unpredictable course and heterogenous treatment response in MS, there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. We conducted a systematic review with Bayesian network meta-analysis with the aim of analyzing the effects of physical exercise on neurofilaments (NfL) and glial fibrillary acidic protein (GFAP) levels in patients with MS. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, starting with a PICO (patient\/population, intervention, comparison, and outcome) question: what are the clinical effects of physical exercise (with independence of the type) on NfL and\/or GFAP levels in patients with MS compared with other interventions or no intervention whatsoever? A systematically comprehensive literature search was conducted from January to March 2024 to identify original studies that answered the PICO question, using the main data sources. The quality of the studies included was assessed using the Quality Index of Downs &amp; Black. For studies included in the systematic review that followed a randomized controlled trial (RCT) design, the methodological quality of each paper was assessed using the Physiotherapy Evidence Database (PEDro) Scale. Risk of bias was also explored by two independent reviewers. Finally, all articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. For continuous outcome measures with enough comparisons and a methodological quality greater than or equal to good according to the PEDro scale, a Bayesian network meta-analysis (NMA) was applied. The statistical analyses were performed in R (version 4.1.3, R Core Team 2023) using the \u201cBUGSnet\u201d and \u201cgemtc\u201d packages. Bayesian NMA can be used to obtain a posterior probability distribution of all the relative treatment effects, which allows us to quantify the uncertainty of parameter estimates and to rank all the treatments in the network. Results: Eight studies were included in this systematic review and six articles in the NMA, and they were appraised for quality. The characteristics of the included studies, types of training and described protocols, methodological quality, risk of bias, and clinical effects on the studied biomarkers were outlined. Qualitative synthesis, effects of different exercise modalities in NfL with the Bayesian NMA, selection of the final model and model assessment, and ranking of interventions are also shown. Conclusions: Our findings indicated that moderate-intensity exercise is more likely to reduce NfL concentration compared to high-intensity exercise, and, in turn, high-intensity exercise is more likely to reduce NfL concentration than low-intensity exercise. However, the effects of high-intensity exercise on GFAP levels were inconclusive.<\/jats:p>","DOI":"10.3390\/jcm14030839","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T08:57:48Z","timestamp":1738054668000},"page":"839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Physical Exercise on Neurofilament Light Chain and Glial Fibrillary Acidic Protein Level in Patients with Multiple Sclerosis: A Systematic Review and Bayesian Network Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Aitor","family":"Bl\u00e1zquez-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"International PhD School, Rey Juan Carlos University, 28008 Madrid, Spain"},{"name":"Asociaci\u00f3n de Legan\u00e9s de Esclerosis M\u00faltiple (ALEM), Legan\u00e9s, 28915 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-6312","authenticated-orcid":false,"given":"V\u00edctor","family":"Navarro-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Faculty of Health Sciences, Rey Juan Carlos University, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Marcos-Ant\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universidad Villanueva, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-4234","authenticated-orcid":false,"given":"Roberto","family":"Cano-de-la-Cuerda","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Faculty of Health Sciences, Rey Juan Carlos University, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","first-page":"1006","article-title":"Diagnosis of Multiple Sclerosis","volume":"28","author":"Oh","year":"2022","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.31128\/AJGP-07-21-6103","article-title":"Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis","volume":"51","author":"Travers","year":"2022","journal-title":"Aust. J. Gen. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41582-019-0170-8","article-title":"Reaching an evidence-based prognosis for personalized treatment of multiple sclerosis","volume":"15","author":"Rotstein","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Varhaug, K.N., Torkildsen, \u00d8., Myhr, K.M., and Vedeler, C.A. (2019). Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00338"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1093\/brain\/awaa098","article-title":"Neurofilaments: Neurobiological foundations for biomarker applications","volume":"143","author":"Gafson","year":"2020","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/ane.13184","article-title":"Plasma neurofilament light in progressive multiple sclerosis","volume":"141","author":"Zetterberg","year":"2020","journal-title":"Acta Neurol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","article-title":"Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker","volume":"38","author":"Yang","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jamaneurol.2022.5250","article-title":"Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis","volume":"80","author":"Meier","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jneuroim.2016.08.004","article-title":"Glial and neuronal markers in cerebrospinal fluid in different types of multiple sclerosis","volume":"299","author":"Olsson","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Filli, L., Sutter, T., Easthope, C.S., Killeen, T., Meyer, C., Reuter, K., L\u00f6rincz, L., Bolliger, M., Weller, M., and Curt, A. (2018). Profiling walking dysfunction in multiple sclerosis: Characterisation, classification and progression over time. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22676-0"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103802","DOI":"10.1016\/j.msard.2022.103802","article-title":"Prognosis of walking function in multiple sclerosis supported by gait pattern analysis","volume":"63","author":"Hostettler","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103969","DOI":"10.1016\/j.msard.2022.103969","article-title":"Long-term prognosis communication preferences in early-stage relapsing-remitting multiple sclerosis","volume":"64","author":"Borges","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104138","DOI":"10.1016\/j.msard.2022.104138","article-title":"Delayed cognitive processing and treatment status quo bias in early-stage multiple sclerosis","volume":"68","author":"Saposnik","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1007\/s00415-021-10935-6","article-title":"Fitness, physical activity, and exercise in multiple sclerosis: A systematic review on current evidence for interactions with disease activity and progression","volume":"269","author":"Proschinger","year":"2022","journal-title":"J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zong, B., Yu, F., Zhang, X., Zhao, W., Li, S., and Li, L. (2023). Mechanisms underlying the beneficial effects of physical exercise on multiple sclerosis: Focus on immune cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1260663"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2165\/00007256-200838020-00001","article-title":"Exercise and brain health--implications for multiple sclerosis: Part 1\u2014Neuronal growth factors","volume":"38","author":"White","year":"2008","journal-title":"Sports Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2165\/00007256-200838030-00001","article-title":"Exercise and brain health--implications for multiple sclerosis: Part II\u2014Immune factors and stress hormones","volume":"38","author":"White","year":"2008","journal-title":"Sports Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00234-011-0879-6","article-title":"Fractional anisotropy and mean diffusivity in the corpus callosum of patients with multiple sclerosis: The effect of physiotherapy","volume":"53","author":"Ibrahim","year":"2011","journal-title":"Neuroradiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.brainres.2009.06.063","article-title":"Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis","volume":"1341","author":"Prakash","year":"2010","journal-title":"Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/S1474-4422(17)30281-8","article-title":"Exercise in patients with multiple sclerosis","volume":"16","author":"Motl","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrneurol.2012.136","article-title":"The benefits of exercise training in multiple sclerosis","volume":"8","author":"Motl","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., and Altman, D.G. (2009). PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jshs.2023.10.010","article-title":"Adult Compendium of Physical Activities: A third update of the energy costs of human activities","volume":"13","author":"Herrmann","year":"2024","journal-title":"J. Sport Health Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e182421","DOI":"10.1001\/jamanetworkopen.2018.2421","article-title":"Association of Levels of Physical Activity with Risk of Parkinson Disease: A Systematic Review and Meta-analysis","volume":"1","author":"Fang","year":"2018","journal-title":"JAMA Netw. Open."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111675","DOI":"10.1016\/j.jpsychores.2024.111675","article-title":"The association of fear of falling and falls with sedentary behavior in people with multiple sclerosis","volume":"181","author":"Farber","year":"2024","journal-title":"J. Psychosom. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1136\/jech.52.6.377","article-title":"The feasibility of creating a checklist for the assessment of the methodological quality both randomised and no-randomised studies of health care interventions","volume":"52","author":"Downs","year":"1998","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jphys.2019.08.005","article-title":"Clinimetrics: Physiotherapy Evidence Database (PEDro) Scale","volume":"66","author":"Cashin","year":"2020","journal-title":"J. Physiother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Higgins, J.P.T., Savovi\u2019c, J., Page, M.J., Elbers, R.G., and Sterne, J.A.C. (2019). Assessing risk of bias in a randomized trial. Cochrane Handbook for Systematic Reviews of Interventions, JohnWiley & Sons, Ltd.. [2nd ed.].","DOI":"10.1002\/9781119536604.ch8"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments","volume":"12","author":"McGuinness","year":"2021","journal-title":"Res. Synth. Methods"},{"key":"ref_30","unstructured":"Oxford CEBM (2024, March 26). Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). Available online: https:\/\/www.cebm.ox.ac.uk\/resources\/levels-of-evidence\/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kupjetz, M., Joisten, N., Rademacher, A., Gonzenbach, R., Bansi, J., and Zimmer, P. (2023). Cycling in primary progressive multiple sclerosis (CYPRO): Study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis. BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03187-6"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gravesteijn, A.S., Beckerman, H., de Jong, B.A., Hulst, H.E., and de Groot, V. (2020). Neuroprotective effects of exercise in people with progressive multiple sclerosis (Exercise PRO-MS): Study protocol of a phase II trial. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01765-6"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/jnr.23528","article-title":"Chronic exercise confers neuroprotection in experimental autoimmune encephalomyelitis","volume":"93","author":"Pryor","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"999","DOI":"10.17219\/acem\/148112","article-title":"Efficacy of different intensity of aquatic exercise in enhancing remyelination and neuronal plasticity using cuprizone model in male Wistar rats","volume":"31","author":"Begum","year":"2022","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbr.2016.11.007","article-title":"Antidepressant-like effect of pramipexole in an inflammatory model of depression","volume":"320","author":"Lieberknecht","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Frederiksen, K.S., Jensen, C.S., H\u00f8gh, P., Gergelyffy, R., Waldemar, G., Andersen, B.B., Gottrup, H., Vestergaard, K., Wermuth, L., and S\u00f8ndergaard, H.B. (2023). Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer\u2019s disease. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1108191"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104489","DOI":"10.1016\/j.msard.2022.104489","article-title":"Brain-derived neurotrophic factor, neurofilament light and glial fibrillary acidic protein do not change in response to aerobic training in people with MS-related fatigue\u2014A secondary analysis of a randomized controlled trial","volume":"70","author":"Gravesteijn","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103219","DOI":"10.1016\/j.msard.2021.103219","article-title":"The effect of aerobic exercise on Neurofilament light chain and glial Fibrillary acidic protein level in patients with relapsing remitting type multiple sclerosis","volume":"55","author":"Ercan","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e982","DOI":"10.1212\/NXI.0000000000000982","article-title":"Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis","volume":"8","author":"Joisten","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1007\/s10072-023-06896-5","article-title":"Effect of resistance exercise training on plasma neurofilaments in multiple sclerosis: A proof of concept for future designs","volume":"44","author":"Mulero","year":"2023","journal-title":"Neurol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.61186\/mlj.17.3.55","article-title":"Decreased serum neurofilament light chain and fatigue severity in patients with multiple sclerosis after home-based and outdoor Pilates training","volume":"17","author":"Askari","year":"2023","journal-title":"Med. Lab. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.52547\/mlj.15.4.33","article-title":"Effect of eight weeks of resistance training on serum levels of neurofilament light chain and Tau protein in women with multiple sclerosis","volume":"15","author":"Amiri","year":"2021","journal-title":"Med. Lab. J."},{"key":"ref_43","first-page":"e203","article-title":"Efficacy of High-Intensity Aerobic Exercise on Brain MRI Measures in Multiple Sclerosis","volume":"96","author":"Nygaard","year":"2021","journal-title":"Neurology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Maroto-Izquierdo, S., Mulero, P., Men\u00e9ndez, H., Pinto-Fraga, J., Lista, S., Santos-Lozano, A., and T\u00e9llez, N. (2024). Pumping up the Fight against Multiple Sclerosis: The Effects of High-Intensity Resistance Training on Functional Capacity, Muscle Mass, and Axonal Damage. Healthcare, 12.","DOI":"10.3390\/healthcare12080837"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.33588\/rn.7303.2020691","article-title":"Plasma determination of neurofilaments as biomarkers in multiple sclerosis: Conclusions of the EMotion Forum","volume":"73","author":"Llaneza","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yang, J., Hamade, M., Wu, Q., Wang, Q., Axtell, R., Giri, S., and Mao-Draayer, Y. (2022). Current and Future Biomarkers in Multiple Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115877"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/ene.13929","article-title":"Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: A systematic review of intervention studies","volume":"26","author":"Negaresh","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jneuroim.2017.12.001","article-title":"Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training","volume":"314","author":"Bansi","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.apmr.2023.12.012","article-title":"Is High-Intensity Interval Training More Effective Than Moderate Continuous Training in Rehabilitation of Multiple Sclerosis: A Comprehensive Systematic Review and Meta-analysis","volume":"105","author":"Youssef","year":"2024","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1177\/1352458520951382","article-title":"High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple clorosis during inpatient rehabilitation","volume":"27","author":"Joisten","year":"2021","journal-title":"Mult. Scler."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mahalakshmi, B., Maurya, N., Lee, S.D., and Bharath Kumar, V. (2020). Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165895"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/FBP.0000000000000514","article-title":"A systematic review of aerobic and resistance exercise and inflammatory markers in people with multiple sclerosis","volume":"30","author":"Wong","year":"2019","journal-title":"Behav. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","article-title":"Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa","volume":"54","author":"Kuhle","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104177","DOI":"10.1016\/j.msard.2022.104177","article-title":"Serum neurofilament levels in patients with multiple sclerosis: A comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels","volume":"67","author":"Revendova","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_55","first-page":"e733","article-title":"Prognostic value of serum neurofilaments in patients with clinically isolated syndromes","volume":"92","author":"Martinelli","year":"2019","journal-title":"Neurology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/3\/839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:06Z","timestamp":1759919826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/3\/839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["jcm14030839"],"URL":"https:\/\/doi.org\/10.3390\/jcm14030839","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}