{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:19:44Z","timestamp":1791566384628,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US National Institute of Mental Health","award":["R61\/R33 MH122647"],"award-info":[{"award-number":["R61\/R33 MH122647"]}]},{"name":"Brain &amp; Behavior Research Foundation","award":["R61\/R33 MH122647"],"award-info":[{"award-number":["R61\/R33 MH122647"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels in the dorsolateral prefrontal cortex (dlPFC) and their correlations with clinical outcomes. Methods: In this randomized, sham-controlled, cross-over study, 33 adults with MDD received one session of t-PBM at low, medium, and high doses and a sham treatment. Proton magnetic resonance spectroscopy (1H-MRS) measured NAA, Cho, and Cr pre- and post-treatment. Clinical outcomes were assessed using the Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ). Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for neurometabolite changes, and linear mixed-effects regression models for t-PBM dose, neurometabolites, and time effects. Results: NAA levels increased significantly (7.52 \u00b1 0.777 to 8.12 \u00b1 1.05 mmol\/L for one session; 7.36 \u00b1 0.85 to 7.85 \u00b1 0.68 mmol\/L across all sessions); however, these changes were not associated with specific t-PBM doses or sham. No significant changes were observed for Cho and Cr levels. Positive correlations were found between Cho levels and MADRS scores (r = 0.59, p = 0.017), and negative correlations between Cr levels and SDQ scores at the medium dose (r = \u22120.91, p = 0.011). Conclusions: While NAA levels increased, and correlations between neurometabolites and clinical outcomes were observed, these findings do not suggest a specific effect of t-PBM. Larger randomized controlled trials with optimized dosing protocols, extended follow-up, and advanced spectroscopy are needed to clarify the neurometabolic therapeutic potential of t-PBM in MDD.<\/jats:p>","DOI":"10.3390\/jcm14103402","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T09:26:48Z","timestamp":1747128408000},"page":"3402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurometabolite Changes After Transcranial Photobiomodulation in Major Depressive Disorder: A Randomized Controlled Trial Investigating Dose-Dependent Effects"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4217-2399","authenticated-orcid":false,"given":"David R. A.","family":"Coelho","sequence":"first","affiliation":[{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-2180","authenticated-orcid":false,"given":"\u00dcmit","family":"Tural","sequence":"additional","affiliation":[{"name":"Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura Maria","family":"Hurtado Puerto","sequence":"additional","affiliation":[{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-879X","authenticated-orcid":false,"given":"Katherine Anne","family":"Collins","sequence":"additional","affiliation":[{"name":"Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia Beth","family":"Gersten","sequence":"additional","affiliation":[{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zamfira","family":"Parincu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8161-2089","authenticated-orcid":false,"given":"Kari","family":"Siu","sequence":"additional","affiliation":[{"name":"Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan Vlad","family":"Iosifescu","sequence":"additional","affiliation":[{"name":"Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"},{"name":"Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Ratai","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, USA"},{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-199X","authenticated-orcid":false,"given":"Paolo","family":"Cassano","sequence":"additional","affiliation":[{"name":"Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-7604","authenticated-orcid":false,"given":"Akila","family":"Weerasekera","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, USA"},{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Psychotic Disorders Division, McLean Hospital, Belmont, MA 02478, USA"},{"name":"McLean Imaging Center, McLean Hospital, Belmont, MA 02478, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major Depressive Disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alberti, A., Araujo Coelho, D.R., Vieira, W.F., Moehlecke Iser, B., Lampert, R.M.F., Traebert, E., da Silva, B.B., de Oliveira, B.H., Le\u00e3o, G.M., and de Souza, G. (2024). Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review. Biomedicines, 12.","DOI":"10.3390\/biomedicines12091994"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/978-981-32-9271-0_10","article-title":"Standardized Treatment Strategy for Depressive Disorder","volume":"1180","author":"Wang","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bbacli.2016.09.002","article-title":"Shining Light on the Head: Photobiomodulation for Brain Disorders","volume":"6","author":"Hamblin","year":"2016","journal-title":"BBA Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3934\/biophy.2017.3.337","article-title":"Mechanisms and Applications of the Anti-Inflammatory Effects of Photobiomodulation","volume":"4","author":"Hamblin","year":"2017","journal-title":"AIMS Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.psc.2023.02.013","article-title":"Photobiomodulation: An Emerging Treatment Modality for Depression","volume":"46","author":"Vieira","year":"2023","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/HRP.0000000000000363","article-title":"Photobiomodulation for Major Depressive Disorder: Linking Transcranial Infrared Light, Biophotons and Oxidative Stress","volume":"31","author":"Vieira","year":"2023","journal-title":"Harv. Rev. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alberti, A., Vieira, W.F., Coelho, D.R.A., and Fernandes Martins, D. (2024). A Grant Report: Examining the Efficacy of Remote Photobiomodulation Therapy in Adolescents with Major Depressive Disorder. Photonics, 11.","DOI":"10.3390\/photonics11090839"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Coelho, D.R.A., Puerto, A.M.H., Vieira, W.F., Lohmann, C.A., Shahab, M.H., Gersten, M.B., Vahedifard, F., McEachern, K.M., Clancy, J.A., and Cassano, P. (2024). Transcranial Photobiomodulation for Executive Function in Bipolar Disorder (TPEB): Study Protocol. Photonics, 11.","DOI":"10.3390\/photonics11080761"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.brs.2024.02.012","article-title":"Transcranial Photobiomodulation Increases Intrinsic Brain Activity within Irradiated Areas in Early Alzheimer\u2019s Disease: Potential Link with Cerebral Metabolism","volume":"17","author":"Gaggi","year":"2024","journal-title":"Brain Stimul."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/papr.13370","article-title":"Treating Neuropathic Pain and Comorbid Affective Disorders: Preclinical and Clinical Evidence","volume":"24","author":"Coelho","year":"2024","journal-title":"Pain. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liebert, A., Bicknell, B., Laakso, E.-L., Heller, G., Jalilitabaei, P., Tilley, S., Mitrofanis, J., and Kiat, H. (2021). Improvements in Clinical Signs of Parkinson\u2019s Disease Using Photobiomodulation: A Prospective Proof-of-Concept Study. BMC Neurol., 21.","DOI":"10.1186\/s12883-021-02248-y"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s43630-024-00613-7","article-title":"Transcranial Photobiomodulation for Neurodevelopmental Disorders: A Narrative Review","volume":"23","author":"Coelho","year":"2024","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vieira, W.F., Coelho, D.R.A., Gersten, M., Puerto, A.M.H., Kalli, S., Gonzalez-Garibay, G., McEachern, K., Clancy, J.A., Skotko, B.G., and Abbeduto, L. (2024). TransPhoM-DS Study Grant Report: Rationale and Protocol for Investigating the Efficacy of Low-Power Transcranial Photobiomodulation on Language, Executive Function, Attention, and Memory in Down Syndrome. Photonics, 11.","DOI":"10.3390\/photonics11070670"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e25317","DOI":"10.1002\/jnr.25317","article-title":"Inflammation in Obsessive-Compulsive Disorder: A Literature Review and Hypothesis-Based Potential of Transcranial Photobiomodulation","volume":"102","author":"Coelho","year":"2024","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gaggi, N.L., Roy, N.L., Song, X., Peterson, A.L., Iosifescu, D.V., Diaz-Arrastia, R., Cassano, P., and Kim, J.J. (2024). Transcranial Photobiomodulation and Chronic Traumatic Brain Injury. Photonics, 11.","DOI":"10.3390\/photonics11030260"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"352979","DOI":"10.1155\/2015\/352979","article-title":"Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study","volume":"2015","author":"Cassano","year":"2015","journal-title":"Psychiatry J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1089\/pho.2018.4490","article-title":"Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial","volume":"36","author":"Cassano","year":"2018","journal-title":"Photomed. Laser Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10103-024-04198-6","article-title":"Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Temperature in Patients with Major Depressive Disorder: A Spectroscopy Study","volume":"39","author":"Weerasekera","year":"2024","journal-title":"Lasers Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.31887\/DCNS.2013.15.3\/jbustillo","article-title":"Use of Proton Magnetic Resonance Spectroscopy in the Treatment of Psychiatric Disorders: A Critical Update","volume":"15","author":"Bustillo","year":"2013","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/0-387-30172-0_17","article-title":"N-Acetylaspartate as a Marker of Neuronal Injury in Neurodegenerative Disease","volume":"576","author":"Schuff","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ymgme.2012.11.283","article-title":"Role of Creatine as Biomarker of Mitochondrial Diseases","volume":"108","author":"Pajares","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1177\/153537020623100503","article-title":"Choline Transport for Phospholipid Synthesis","volume":"231","author":"Michel","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1016\/j.neuroimage.2010.10.017","article-title":"In Vivo Mapping of Brain Myo-Inositol","volume":"54","author":"Haris","year":"2011","journal-title":"Neuroimage"},{"key":"ref_25","first-page":"75","article-title":"Study on Dorsolateral Prefrontal Cortex Neurochemical Metabolite Levels of Patients with Major Depression Using H-MRS Technique","volume":"31","year":"2020","journal-title":"Turk. Psikiyatr. Derg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jad.2022.12.020","article-title":"Altered Neurometabolite Levels in the Brains of Patients with Depression: A Systematic Analysis of Magnetic Resonance Spectroscopy Studies","volume":"328","author":"Xie","year":"2023","journal-title":"J. Affect. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Iosifescu, D.V., Collins, K.A., Hurtado-Puerto, A., Irvin, M.K., Clancy, J.A., Sparpana, A.M., Sullivan, E.F., Parincu, Z., Ratai, E.-M., and Funes, C.J. (2023). Grant Report on the Transcranial near Infrared Radiation and Cerebral Blood Flow in Depression (TRIADE) Study. Photonics, 10.","DOI":"10.3390\/photonics10010090"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1749-6632.1987.tb32915.x","article-title":"Spatial localization in NMR spectroscopy in vivo","volume":"508","author":"Bottomley","year":"1987","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/jmri.24903","article-title":"Tissue Correction for GABA-Edited MRS: Considerations of Voxel Composition, Tissue Segmentation, and Tissue Relaxations","volume":"42","author":"Harris","year":"2015","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_30","unstructured":"Penny, W., Friston, K., Ashburner, J., Kiebel, S., and Nichols, T. (2007). Statistical Parametric Mapping: The Analysis of Functional Brain Images, Academic Press."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/mrm.20901","article-title":"Use of Tissue Water as a Concentration Reference for Proton Spectroscopic Imaging","volume":"55","author":"Gasparovic","year":"2006","journal-title":"Magn. Reson. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jmri.20053","article-title":"1H Metabolite Relaxation Times at 3.0 Tesla: Measurements of T1 and T2 Values in Normal Brain and Determination of Regional Differences in Transverse Relaxation","volume":"19","author":"Block","year":"2004","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/(SICI)1522-2586(199904)9:4<531::AID-JMRI4>3.0.CO;2-L","article-title":"NMR Relaxation Times in the Human Brain at 3.0 Tesla","volume":"9","author":"Wansapura","year":"1999","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1600-0447.1986.tb02723.x","article-title":"The Montgomery-Asberg Depression Scale: Reliability and Validity","volume":"73","author":"Davidson","year":"1986","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1017\/S1092852914000406","article-title":"Reliability and Validity of the Symptoms of Depression Questionnaire (SDQ)","volume":"19","author":"Pedrelli","year":"2014","journal-title":"CNS Spectr."},{"key":"ref_36","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pneurobio.2006.12.003","article-title":"N-Acetylaspartate in the CNS: From Neurodiagnostics to Neurobiology","volume":"81","author":"Moffett","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jad.2024.03.150","article-title":"Proton Magnetic Resonance Spectroscopy of N-Acetyl Aspartate in First Depressive Episode and Chronic Major Depressive Disorder: A Systematic Review and Meta-Analysis","volume":"355","author":"Saccaro","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103049","DOI":"10.1016\/j.nicl.2022.103049","article-title":"Repetitive Transcranial Magnetic Stimulation-Associated Changes in Neocortical Metabolites in Major Depression: A Systematic Review","volume":"35","author":"Gonsalves","year":"2022","journal-title":"Neuroimage Clin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3233\/ADR-220022","article-title":"Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy","volume":"7","author":"Naeser","year":"2023","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"988759","DOI":"10.3389\/fncel.2022.988759","article-title":"Effects of Choline Containing Phospholipids on the Neurovascular Unit: A Review","volume":"16","author":"Roy","year":"2022","journal-title":"Front. Cell Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.pscychresns.2017.11.009","article-title":"Brain Choline in Major Depression: A Review of the Literature","volume":"271","author":"Riley","year":"2018","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/pcn.12392","article-title":"Proton Spectroscopy Study of the Dorsolateral Prefrontal Cortex in Youth with Familial Depression","volume":"70","author":"Yang","year":"2016","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kreider, R.B., and Stout, J.R. (2021). Creatine in Health and Disease. Nutrients, 13.","DOI":"10.3390\/nu13020447"},{"key":"ref_46","first-page":"1169","article-title":"Creatine Activity as a Neuromodulator in the Central Nervous System","volume":"78","author":"Meftahi","year":"2023","journal-title":"Arch. Razi Inst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1177\/02698811211050550","article-title":"Relationship between Depression, Prefrontal Creatine and Grey Matter Volume","volume":"35","author":"Faulkner","year":"2021","journal-title":"J. Psychopharmacol."},{"key":"ref_48","first-page":"659","article-title":"Quantitative and Integrative Photobiomodulation","volume":"40","author":"Guo","year":"2022","journal-title":"Photobiomodul. Photomed. Laser Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:31:54Z","timestamp":1760031114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14103402"],"URL":"https:\/\/doi.org\/10.3390\/jcm14103402","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]}}}