{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T18:58:42Z","timestamp":1782327522214,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed\/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M\/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC.<\/jats:p>","DOI":"10.3390\/medsci14020233","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:15:27Z","timestamp":1777630527000},"page":"233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Variant Allele Frequency (VAF) Levels on Clinical Efficacy of Osimertinib in Patients with Metastatic NSCLC"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-2959","authenticated-orcid":false,"given":"Abed","family":"Agbarya","sequence":"first","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Department of Oncology, Bnai-Zion Medical Center, Haifa 3339419, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Mhameed","sequence":"additional","affiliation":[{"name":"The Joseph Fishman Oncology Center, Rambam Medical Center, Haifa 3525409, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina","family":"Soklakova","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitam","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"The Joseph Fishman Oncology Center, Rambam Medical Center, Haifa 3525409, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0571-9287","authenticated-orcid":false,"given":"Mahmoud","family":"Abu Amna","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabri","family":"El-Saied","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben Gurion University of the Negev, Ben Gurion Avenue, Beer Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Sheikh-Ahmad","sequence":"additional","affiliation":[{"name":"Department of Oncology, Bnai-Zion Medical Center, Haifa 3339419, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-4550","authenticated-orcid":false,"given":"Walid","family":"Shalata","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben Gurion University of the Negev, Ben Gurion Avenue, Beer Sheva 8410501, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1097\/JTO.0000000000000663","article-title":"Introduction to the 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_3","first-page":"2892","article-title":"EGFR Mutation Incidence in Non-Small-Cell Lung Cancer of Adenocarcinoma Histology: A Systematic Review and Global Map by Ethnicity (mutMapII)","volume":"5","author":"Midha","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrc2088","article-title":"Epidermal Growth Factor Receptor Mutations in Lung Cancer","volume":"7","author":"Sharma","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1158\/2159-8290.CD-14-0337","article-title":"AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer","volume":"4","author":"Cross","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jmoldx.2017.01.011","article-title":"Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists","volume":"19","author":"Jennings","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.jtho.2018.05.030","article-title":"Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC","volume":"13","author":"Rolfo","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1002\/ijc.33053","article-title":"An EGFR Signature Predicts Cell Line and Patient Sensitivity to Multiple Tyrosine Kinase Inhibitors","volume":"147","author":"Cheng","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1158\/1078-0432.CCR-13-2482","article-title":"Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA","volume":"20","author":"Oxnard","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_11","first-page":"18","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"10","author":"Baethge","year":"2019","journal-title":"Res. Synth. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Costa, J., Membrino, A., Zanchetta, C., Rizzato, S., Cortiula, F., Rossetto, C., Pelizzari, G., Aprile, G., and Macerelli, M. (2024). The Role of ctDNA in the Management of Non-Small-Cell Lung Cancer in the AI and NGS Era. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413669"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41416-018-0238-z","article-title":"The amount of activating EGFR mutations in circulating cell-free DNA is a marker to monitor osimertinib response","volume":"119","author":"Bordi","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Morikawa, K., Takashima, Y., Oki, M., Tsuzuku, A., Murakami, S., Minami, D., Fujii, S., Shinagawa, N., Asano, F., and Nakamura, S. (2025). Prospective multicenter validation of a next-generation sequencing panel using cytology specimens for lung cancer: cPANEL. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14770-0"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1056\/NEJMoa2306434","article-title":"Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC","volume":"389","author":"Planchard","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1080\/14796694.2025.2463880","article-title":"A plain language summary of results from the FLAURA2 study: Initial (first-line) osimertinib treatment with or without chemotherapy in patients with untreated EGFR-mutated advanced NSCLC","volume":"21","author":"Planchard","year":"2025","journal-title":"Future Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1097\/CM9.0000000000004016","article-title":"Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997\u20132026)","volume":"139","author":"Xie","year":"2026","journal-title":"Chin. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Stepien, N., Senfter, D., Furtner, J., Haberler, C., Dorfer, C., Czech, T., L\u00f6tsch-Gojo, D., Mayr, L., Hedrich, C., and Baumgartner, A. (2023). Proof-of-Concept for Liquid Biopsy Disease Monitoring of MYC-Amplified Group 3 Medulloblastoma by Droplet Digital PCR. Cancers, 15.","DOI":"10.3390\/cancers15092525"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.2217\/fon-2021-0549","article-title":"Neoadjuvant osimertinib with\/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA","volume":"17","author":"Tsuboi","year":"2021","journal-title":"Future Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.annonc.2023.02.012","article-title":"Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial","volume":"34","author":"Remon","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.21037\/atm.2017.07.10","article-title":"Circulating DNA in EGFR-Mutated Lung Cancer","volume":"5","author":"Singh","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature22364","article-title":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","volume":"545","author":"Abbosh","year":"2017","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1158\/1078-0432.CCR-18-0386","article-title":"Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder Cancer Treated with Durvalumab","volume":"24","author":"Raja","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1080\/14656566.2021.1888928","article-title":"An overview of osimertinib as a treatment of non-small cell lung cancer (NSCLC): An update","volume":"22","author":"Cerbone","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"662","DOI":"10.21037\/tlcr-20-814","article-title":"EGFR variant allele frequency predicts EGFR-TKI efficacy in lung adenocarcinoma: A multicenter study","volume":"10","author":"Gieszer","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_26","first-page":"13136","article-title":"Comparison of EGFR mutation status between plasma and tumor tissue in non-small cell lung cancer using the Scorpion ARMS method and the possible prognostic significance of plasma EGFR mutation status","volume":"8","author":"Duan","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4143\/crt.2020.459","article-title":"A Phase II Trial of Osimertinib as the First-Line Treatment of Non-Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1","volume":"53","author":"Park","year":"2021","journal-title":"Cancer Res. Treat."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Watanabe, K., Saito, R., Miyauchi, E., Nagashima, H., Nakamura, A., Sugawara, S., Tanaka, N., Terasaki, H., Fukuhara, T., and Maemondo, M. (2023). Monitoring of Plasma EGFR Mutations during Osimertinib Treatment for NSCLC Patients with Acquired T790M Mutation. Cancers, 15.","DOI":"10.3390\/cancers15174231"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ang, Y.L.E., Zhao, X., Reungwetwattana, T., Cho, B.C., Liao, B.C., Yeung, R., Loong, H.H., Kim, D.W., Yang, J.C., and Lim, S.M. (2023). A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study). Cancers, 15.","DOI":"10.3390\/cancers15204999"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2500287","DOI":"10.1200\/PO-25-00287","article-title":"Variability of Circulating Tumor DNA Levels in Plasma Samples From Patients With Advanced Non-Small-Cell Lung Cancer in the Absence of Treatment","volume":"9","author":"Markovets","year":"2025","journal-title":"JCO Precis Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21037\/tlcr-20-371","article-title":"The prognostic value of longitudinal circulating tumor DNA profiling during osimertinib treatment","volume":"10","author":"Ma","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.annonc.2022.05.520","article-title":"ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: A report from the ESMO Precision Medicine Working Group","volume":"33","author":"Pascual","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"548","DOI":"10.3892\/ol.2024.14681","article-title":"Liquid biopsy: Comprehensive overview of circulating tumor DNA (Review)","volume":"28","author":"Ge","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.21037\/tlcr-20-1125","article-title":"Plasma pre-treatment T790M relative allelic frequency in patients with advanced EGFR-mutated non-small cell lung cancer predicts treatment response to subsequent-line osimertinib","volume":"10","author":"Ding","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.21037\/tcr-21-223","article-title":"The correlation between the abundance of EGFR T790M mutation and osimertinib response in advanced non-small cell lung cancer","volume":"10","author":"Pan","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"777","DOI":"10.4143\/crt.2018.387","article-title":"A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA: LiquidLung-O-Cohort 2","volume":"51","author":"Park","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.2147\/CMAR.S207170","article-title":"Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: A prospective observational study","volume":"11","author":"Igawa","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_38","first-page":"100636","article-title":"Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations","volume":"5","author":"Takeyasu","year":"2024","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s43018-021-00195-8","article-title":"Overcoming therapy resistance in EGFR-mutant lung cancer","volume":"2","author":"Passaro","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1158\/1078-0432.CCR-22-3497","article-title":"Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations","volume":"29","author":"Grant","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/s41467-023-35962-x","article-title":"Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial","volume":"14","author":"Chmielecki","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nm.3854","article-title":"Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M","volume":"21","author":"Thress","year":"2015","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1001\/jamaoncol.2018.2969","article-title":"Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib","volume":"4","author":"Oxnard","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gomatou, G., Syrigos, N., and Kotteas, E. (2023). Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options. Cancers, 15.","DOI":"10.3390\/cancers15030841"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1158\/1078-0432.CCR-18-2683","article-title":"Ultra-sensitive EGFRT790M Detection as an Independent Prognostic Marker for Lung Cancer Patients Harboring EGFRdel19 Mutations and Treated with First-generation TKIs","volume":"25","author":"Vendrell","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ho, H.Y., Chung, K.K., Kan, C.M., and Wong, S.C. (2024). Liquid Biopsy in the Clinical Management of Cancers. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168594"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jtho.2021.10.014","article-title":"Postoperative Chemotherapy Use and Outcomes From ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR-Mutated NSCLC","volume":"17","author":"Wu","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"200","DOI":"10.21037\/tlcr-22-899","article-title":"Molecular minimal residual disease in resected non-small cell lung cancer (NSCLC): Results of specifically designed interventional clinical trials eagerly awaited","volume":"12","author":"Denis","year":"2023","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kemper, M., Krekeler, C., Menck, K., Lenz, G., Evers, G., Schulze, A.B., and Bleckmann, A. (2023). Liquid Biopsies in Lung Cancer. Cancers, 15.","DOI":"10.3390\/cancers15051430"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shalata, W., Krayim, B., Miari, A., Agbarya, A., Peled, N., Dudnik, Y., Cohen, A.Y., Meirovitz, A., Maimon Rabinovich, N., and Yakobson, A. (2026). Variant allele frequency as a predictor of treatment response to osimertinib in EGFR-mutated NSCLC. Front. Mol. Biosci., 13.","DOI":"10.3389\/fmolb.2026.1822285"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:12:32Z","timestamp":1778818352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020233"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020233","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]}}}