{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:04:59Z","timestamp":1779689099138,"version":"3.53.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Trimodality therapy (TMT)\u2014maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy\u2014can offer oncologic outcomes comparable to radical cystectomy (RC) in carefully selected muscle-invasive bladder cancer (MIBC) patients while preserving the bladder and, possibly, the quality of life. Systematic reviews and long-term series support durable bladder-intact survival in responders, yet there is still a significant percentage of patients who exhibit incomplete response or invasive intravesical recurrence requiring salvage RC. This review covers computational genomics, transcriptomics, immune contexture, radiogenomics, and digital pathology approaches for predicting response in order to avoid preventable TMT failures. We discuss clinically relevant endpoints (complete response, invasive recurrence, bladder-intact survival, and salvage RC), patient selection (carcinoma in situ, hydronephrosis, debulking feasibility, and histology), and DNA damage response (DDR) biology\u2014highlighting ERCC2 and related pathways as determinants of chemo-radiation sensitivity. We then review reproducible transcriptomic subtype classifiers and immune deconvolution methods, emphasizing translational constraints and reporting standards. Finally, we propose an integrated hypothetical modeling framework (calibration, external validation, and decision-curve thresholds) to guide recommendations for upfront RC versus bladder preservation with intensified surveillance and timely salvage RC.<\/jats:p>","DOI":"10.3390\/life16050826","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systems Biology and Multi-Omics Determinants of Response to Bladder-Preserving Trimodality Therapy in Muscle-Invasive Bladder Cancer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-8889","authenticated-orcid":false,"given":"Vlad-Horia","family":"Schi\u021bcu","sequence":"first","affiliation":[{"name":"Department of Urology, Institute of Oncology \u201cProf. Dr. Ion Chiricuta\u201d Cluj-Napoca, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-2446","authenticated-orcid":false,"given":"Vlad Cristian","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Oncology \u201cProf. Dr. Ion Chiricuta\u201d Cluj-Napoca, 400015 Cluj-Napoca, Romania"},{"name":"Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-7031","authenticated-orcid":false,"given":"Mihnea Bogdan","family":"Borz","sequence":"additional","affiliation":[{"name":"Department of Urology, Targu Mures County Clinical Hospital, 540136 Targu Mures, Romania"},{"name":"Department of Anatomy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5107-614X","authenticated-orcid":false,"given":"Ion","family":"Cojocaru","sequence":"additional","affiliation":[{"name":"Department of Urology, Galati County Emergency Hospital, 800578 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavia","family":"Morari","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Oncology \u201cProf. Dr. Ion Chiricuta\u201d Cluj-Napoca, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mircea","family":"G\u00eerbovan","sequence":"additional","affiliation":[{"name":"Department of Urology, Targu Mures County Clinical Hospital, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9062-8593","authenticated-orcid":false,"given":"Andrei-Ionu\u021b","family":"Ti\u0219e","sequence":"additional","affiliation":[{"name":"Department of Urology, Alba County Emergency Hospital, 711325 Alba-Iulia, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"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":"300","DOI":"10.1016\/j.eururo.2015.08.037","article-title":"Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes","volume":"69","author":"Dobruch","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.eururo.2014.02.038","article-title":"Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: A systematic review","volume":"66","author":"Ploussard","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.eururo.2016.12.020","article-title":"Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: An updated analysis of the Massachusetts General Hospital experience","volume":"71","author":"Giacalone","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1200\/JCO.2014.57.5548","article-title":"Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: A pooled analysis of RTOG protocols 8802, 8903, 9506, 9706, 9906, and 0233","volume":"32","author":"Mak","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.urolonc.2017.10.002","article-title":"A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer","volume":"36","author":"Fahmy","year":"2018","journal-title":"Urol. Oncol."},{"key":"ref_7","first-page":"E197","article-title":"Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: A Markov microsimulation model","volume":"16","author":"Magee","year":"2022","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1007\/s00345-020-03436-0","article-title":"Incidence and outcome of salvage cystectomy after bladder sparing therapy for muscle invasive bladder cancer: A systematic review and meta-analysis","volume":"39","author":"Schuettfort","year":"2021","journal-title":"World J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.ijrobp.2014.01.001","article-title":"Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: Results from the national cancer data base","volume":"88","author":"Gray","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_10","unstructured":"De Jong, J.J., van der Heijden, A.G., Boormans, J.L., Aben, K.K.H., Meijer, R.P., and Richters, A. (2025, January 21\u201324). Discrepancy between clinical and pathological stage in patients with muscle-invasive bladder cancer: A population-based study. Proceedings of the 40th Annual EAU Congress (EAU25), Madrid, Spain. Available online: https:\/\/urosource.uroweb.org\/resource-centres\/EAU25\/262783\/abstract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.eururo.2011.11.010","article-title":"Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: The MGH experience","volume":"61","author":"Efstathiou","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Miyajima, K., Matsukawa, A., Yanagisawa, T., Miszczyk, M., Roessler, N., Inoue, S., Nishimura, S., Alqahtani, A.S., Alfarhan, A.R., and Urabe, F. (2025). Prognostic factors of trimodal therapy for muscle-invasive bladder cancer: A systematic review and meta-analysis. Eur. Urol. Focus, preprint.","DOI":"10.1016\/j.euf.2025.12.010"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.eururo.2025.02.019","article-title":"European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2025 guidelines","volume":"87","author":"Bruins","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3233\/BLC-150025","article-title":"Bladder preservation for muscle invasive bladder cancer","volume":"2","author":"Mirza","year":"2016","journal-title":"Bladder Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1200\/JCO.2005.05.516","article-title":"Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy","volume":"23","author":"Lotan","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1158\/1078-0432.CCR-18-2512","article-title":"DNA damage response gene alterations in urothelial cancer: Ready for practice?","volume":"25","author":"Grivas","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1158\/2159-8290.CD-14-0623","article-title":"Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma","volume":"4","author":"Mouw","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1158\/1078-0432.CCR-18-1001","article-title":"ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer","volume":"25","author":"Li","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7017","DOI":"10.1158\/0008-5472.CAN-10-1202","article-title":"MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer","volume":"70","author":"Choudhury","year":"2010","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2242378","DOI":"10.1001\/jamanetworkopen.2022.42378","article-title":"Analysis of MRE11 and mortality among adults with muscle-invasive bladder cancer managed with trimodality therapy","volume":"5","author":"Magliocco","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1200\/JCO.2017.75.7740","article-title":"Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1\/PD-L1 blockade in advanced urothelial cancers","volume":"36","author":"Teo","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s41591-019-0628-7","article-title":"Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial","volume":"25","author":"Powles","year":"2019","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrurol.2014.129","article-title":"Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer","volume":"11","author":"Choi","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1200\/JCO.2017.35.6_suppl.287","article-title":"Subtyping muscle-invasive bladder cancer to assess clinical response to trimodality therapy","volume":"35","author":"Efstathiou","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2017.09.007","article-title":"Comprehensive molecular characterization of muscle-invasive bladder cancer","volume":"171","author":"Robertson","year":"2017","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.eururo.2019.09.006","article-title":"A consensus molecular classification of muscle-invasive bladder cancer","volume":"77","author":"Kamoun","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.euo.2022.01.008","article-title":"Immune contexture and differentiation features predict outcome in bladder cancer","volume":"5","author":"Taber","year":"2022","journal-title":"Eur. Urol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19352","DOI":"10.18632\/aging.203333","article-title":"Identification of immune-related genes that predict prognosis and risk of bladder cancer: Bioinformatics analysis of TCGA database","volume":"13","author":"Guo","year":"2021","journal-title":"Aging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"H\u00e4nzelmann, S., Castelo, R., and Guinney, J. (2013). GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-7"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sj\u00f6dahl, G., Eriksson, P., Liedberg, F., and H\u00f6glund, M. (2022). Molecular subtypes as a basis for stratified use of neoadjuvant chemotherapy for muscle-invasive bladder cancer\u2014A narrative review. Cancers, 14.","DOI":"10.3390\/cancers14071692"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S325","DOI":"10.21037\/tau.2019.05.12","article-title":"Molecular subtyping, tumor infiltration, and trimodal therapy for muscle-invasive bladder cancer: More questions than answers","volume":"8","author":"Kool","year":"2019","journal-title":"Transl. Androl. Urol."},{"key":"ref_36","first-page":"43","article-title":"Current role of radiomics and radiogenomics in predicting oncological outcomes in bladder cancer","volume":"19","author":"Temperley","year":"2024","journal-title":"Curr. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, X., Wang, X., Lan, X., Deng, J., Lei, Y., and Lin, F. (2022). The role of radiomics with machine learning in the prediction of muscle-invasive bladder cancer: A mini review. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.990176"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1200\/JCO.2025.43.16_suppl.1567","article-title":"Magnetic resonance imaging (MRI) radiomics as predictor of clinical outcomes to neoadjuvant immunotherapy in patients with muscle invasive bladder cancer undergoing radical cystectomy","volume":"43","author":"Necchi","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8738","DOI":"10.1038\/s41598-017-09315-w","article-title":"Bladder cancer treatment response assessment in CT using radiomics with deep-learning","volume":"7","author":"Cha","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ucl.2023.07.002","article-title":"Bladder cancer and artificial intelligence","volume":"51","author":"Laurie","year":"2024","journal-title":"Urol. Clin. N. Am."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/JU.0000000000001696","article-title":"Complications and outcomes of salvage cystectomy after trimodality therapy","volume":"206","author":"Pieretti","year":"2021","journal-title":"J. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1056\/NEJMoa1106106","article-title":"Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer","volume":"366","author":"James","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41746-025-01560-y","article-title":"Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning","volume":"8","author":"Bai","year":"2025","journal-title":"npj Digit. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41586-021-03642-9","article-title":"ctDNA guiding adjuvant immunotherapy in urothelial carcinoma","volume":"595","author":"Powles","year":"2021","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3233\/BLC-220055","article-title":"Predicting recurrence and progression in patients with non-muscle-invasive bladder cancer: Systematic review on the performance of risk stratification models","volume":"8","author":"Subiela","year":"2022","journal-title":"Bladder Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"LBA632","DOI":"10.1200\/JCO.2026.44.7_suppl.LBA632","article-title":"Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle-invasive bladder cancer (MIBC): Integrated analysis of the RETAIN trials","volume":"44","author":"Ghatalia","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1200\/JCO.2025.43.5_suppl.815","article-title":"A phase 2 trial of risk enabled therapy after neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer (RETAIN-2)","volume":"43","author":"Ross","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1200\/JCO-25-01608","article-title":"End points for the next-generation bladder-sparing perioperative trials for patients with muscle-invasive bladder cancer","volume":"43","author":"Necchi","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.euf.2025.06.009","article-title":"Urinary tumor DNA-based liquid biopsy in bladder cancer management: A systematic review","volume":"11","author":"Lee","year":"2025","journal-title":"Eur. Urol. Focus"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e271","DOI":"10.1016\/j.clgc.2022.03.009","article-title":"The role of Bladder EpiCheck test in follow-up of patients with non-muscle invasive bladder cancer","volume":"20","author":"Ragonese","year":"2022","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41585-023-00725-2","article-title":"Circulating and urinary tumour DNA in urothelial carcinoma\u2014upper tract, lower tract and metastatic disease","volume":"20","author":"Rose","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/JU.0000000000004849","article-title":"Early detection of metastatic progression by circulating tumor DNA in patients undergoing bladder-preserving trimodality therapy","volume":"215","author":"Zhao","year":"2026","journal-title":"J. Urol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S1603","DOI":"10.1016\/j.annonc.2025.08.3705","article-title":"Artificial intelligence predicts molecular subtypes and outcomes in muscle-invasive bladder cancer from whole slide images","volume":"36","author":"Blondel","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_54","unstructured":"(2026, April 21). SWOG\/NRG S1806. Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer. SWOG Clinical Trials. Available online: https:\/\/www.swog.org\/clinical-trials\/s1806."},{"key":"ref_55","unstructured":"(2026, April 21). ECOG-ACRIN\/NRG EA8185 (INSPIRE). Bladder Cancer Treatment Trial EA8185\/INSPIRE. ECOG-ACRIN Cancer Research Group. Available online: https:\/\/ecog-acrin.org\/clinical-trials\/ea8185."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:51:59Z","timestamp":1779688319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,16]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["life16050826"],"URL":"https:\/\/doi.org\/10.3390\/life16050826","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,16]]}}}