{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:29Z","timestamp":1792789409038,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MSKCC Specialized Program of Research Excellence (SPORE) in Prostate Cancer","award":["5P50CA092629-23"],"award-info":[{"award-number":["5P50CA092629-23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [18F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms26157593","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:13:51Z","timestamp":1754475231000},"page":"7593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Two Decades of Disease Evolution and Biomarker-Guided Clinical Decision Making in Metastatic Prostate Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Tatiana","family":"Erazo","sequence":"first","affiliation":[{"name":"Translational Partnership Program, Memorial Sloan Kettering Cancer Center (MSK), New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Moiso","sequence":"additional","affiliation":[{"name":"Translational Partnership Program, Memorial Sloan Kettering Cancer Center (MSK), New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Aras","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard I.","family":"Scher","sequence":"additional","affiliation":[{"name":"Translational Partnership Program, Memorial Sloan Kettering Cancer Center (MSK), New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/s41571-024-00945-4","article-title":"Two decades of advances in clinical oncology-lessons learned and future directions","volume":"21","author":"Banerjee","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11864-025-01323-7","article-title":"Advances in Targeted Therapy for Metastatic Prostate Cancer","volume":"26","author":"Grewal","year":"2025","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_3","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41391-023-00725-8","article-title":"Real-world treatment patterns and overall survival among men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the US Medicare population","volume":"27","author":"Freedland","year":"2024","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s11523-018-0611-0","article-title":"Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment","volume":"13","author":"Shah","year":"2018","journal-title":"Target. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1758835920978134","DOI":"10.1177\/1758835920978134","article-title":"Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer","volume":"12","author":"Lavaud","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1126\/science.abn0478","article-title":"Lineage plasticity in prostate cancer depends on JAK\/STAT inflammatory signaling","volume":"377","author":"Chan","year":"2022","journal-title":"Science"},{"key":"ref_8","first-page":"5","article-title":"Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance","volume":"1","author":"Jamroze","year":"2024","journal-title":"Cancer Heterog. Plast."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aah4307","article-title":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","volume":"355","author":"Mu","year":"2017","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-020-00243-0","article-title":"Prostate cancer","volume":"7","author":"Rebello","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/s43018-020-00141-0","article-title":"Accelerating precision medicine in metastatic prostate cancer","volume":"1","author":"Mateo","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41585-020-00400-w","article-title":"Genomic and phenotypic heterogeneity in prostate cancer","volume":"18","author":"Haffner","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1200\/PO.20.00428","article-title":"Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing","volume":"5","author":"Chen","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41586-022-04975-9","article-title":"Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer","volume":"608","author":"Herberts","year":"2022","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1038\/s41467-024-45475-w","article-title":"Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer","volume":"15","author":"Fonseca","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13073-020-00770-1","article-title":"Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression","volume":"12","author":"Lau","year":"2020","journal-title":"Genome Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1158\/1078-0432.CCR-24-1096","article-title":"Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration Resistant Prostate Cancer","volume":"30","author":"Sweeney","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Combes, A.D., Palma, C.A., Calopedos, R., Wen, L., Woo, H., Fulham, M., and Leslie, S. (2022). PSMA PET-CT in the Diagnosis and Staging of Prostate Cancer. Diagnostics, 12.","DOI":"10.3390\/diagnostics12112594"},{"key":"ref_19","first-page":"494","article-title":"PSMA-targeted radiotherapy in metastatic castration-resistant prostate cancer","volume":"19","author":"Sartor","year":"2021","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Filippi, L., Urso, L., Schillaci, O., and Evangelista, L. (2023). [(18)F]-FDHT PET for the Imaging of Androgen Receptor in Prostate and Breast Cancer: A Systematic Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13152613"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13550-019-0531-8","article-title":"Sensitivity of (18)F-fluorodihydrotestosterone PET-CT to count statistics and reconstruction protocol in metastatic castration-resistant prostate cancer","volume":"9","author":"Cysouw","year":"2019","journal-title":"EJNMMI Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1200\/JCO.2015.64.2702","article-title":"Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3","volume":"34","author":"Scher","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40164-017-0067-4","article-title":"Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months","volume":"6","author":"Marconcini","year":"2017","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1158\/1078-0432.CCR-22-2875","article-title":"FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer","volume":"29","author":"Fallah","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e373","DOI":"10.1016\/S1470-2045(18)30534-5","article-title":"[(177)Lu]-PSMA-617 radionuclide therapy in patients with metastatic castration-resistant prostate cancer-Author\u2019s reply","volume":"19","author":"Hofman","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1097\/RLU.0000000000002210","article-title":"Therapeutic Responses and Survival Effects of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castrate-Resistant Prostate Cancer: A Meta-analysis","volume":"43","author":"Kim","year":"2018","journal-title":"Clin. Nucl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2967\/jnumed.116.183194","article-title":"German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients","volume":"58","author":"Rahbar","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2967\/jnumed.124.268640","article-title":"Therapy-Related Myeloid Neoplasms After [(177)Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series","volume":"66","author":"Eifer","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2400143","DOI":"10.1200\/PO.24.00143","article-title":"Clonal Hematopoiesis in Patients With Neuroendocrine Tumor Treated With Lutetium-177 and the Risk of Thrombocytopenia: A Prospective Study","volume":"8","author":"Kusne","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1038\/s41467-021-24109-5","article-title":"Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS","volume":"12","author":"Jayakumaran","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1001\/jamaoncol.2018.5801","article-title":"Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade","volume":"5","author":"Abida","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2019.02.012","article-title":"Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis","volume":"176","author":"Petljak","year":"2019","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/pros.24328","article-title":"Bipolar androgen therapy (BAT): A patient\u2019s guide","volume":"82","author":"Denmeade","year":"2022","journal-title":"Prostate"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1158\/1078-0432.CCR-14-2666","article-title":"Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer","volume":"21","author":"Azad","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00029","article-title":"Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making","volume":"1","author":"Abida","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/oncolo\/oyad055","article-title":"Bipolar Androgen Therapy Followed by Androgen Receptor Inhibition as Sequential Therapy for Prostate Cancer","volume":"28","author":"Denmeade","year":"2023","journal-title":"Oncologist"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.eururo.2020.06.042","article-title":"A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts","volume":"79","author":"Markowski","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1200\/JCO.20.02759","article-title":"TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer","volume":"39","author":"Denmeade","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41467-023-44514-2","article-title":"Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: The COMBAT phase II trial","volume":"15","author":"Markowski","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.eururo.2016.09.020","article-title":"Extreme Response to High-dose Testosterone in BRCA2- and ATM-mutated Prostate Cancer","volume":"71","author":"Teply","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.eururo.2019.05.042","article-title":"Durable Response of Enzalutamide-resistant Prostate Cancer to Supraphysiological Testosterone Is Associated with a Multifaceted Growth Suppression and Impaired DNA Damage Response Transcriptomic Program in Patient-derived Xenografts","volume":"77","author":"Lam","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.clgc.2021.08.001","article-title":"Molecular and Clinical Characterization of Patients With Metastatic Castration Resistant Prostate Cancer Achieving Deep Responses to Bipolar Androgen Therapy","volume":"20","author":"Markowski","year":"2022","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41391-022-00636-0","article-title":"Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer","volume":"26","author":"Schweizer","year":"2023","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Prosz, A., Duan, H., Tisza, V., Sahgal, P., Topka, S., Klus, G.T., Borcsok, J., Sztupinszki, Z., Hanlon, T., and Diossy, M. (2023). Nucleotide excision repair deficiency is a targetable therapeutic vulnerability in clear cell renal cell carcinoma. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-47946-4"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nishiyama, A., Sato, S., Sakaguchi, H., Kotani, H., Yamashita, K., Ohtsubo, K., Nanjo, S., Yano, S., Mizuguchi, K., and Ikeda, H. (2024). Challenges in the treatment of BRAF K601E-mutated lung carcinoma: A case report of rapid response and resistance to dabrafenib and trametinib. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1374594"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1158\/1078-0432.CCR-19-3443","article-title":"Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131)","volume":"26","author":"Johnson","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"CT247","DOI":"10.1158\/1538-7445.AM2025-CT247","article-title":"FORTE: A Phase II master protocol assessing plixorafenib for BRAF-altered cancers","volume":"85","author":"Schreck","year":"2025","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1200\/JCO.23.00433","article-title":"Targeting the Androgen Signaling Axis in Prostate Cancer","volume":"41","author":"Dai","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1200\/JCO.2023.41.16_suppl.5005","article-title":"LuPARP: Phase 1 trial of 177Lu-PSMA-617 and olaparib in patients with metastatic castration resistant prostate cancer (mCRPC)","volume":"41","author":"Sandhu","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2967\/jnumed.124.268902","article-title":"(177)Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial","volume":"66","author":"Hallqvist","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1158\/1078-0432.CCR-15-1050","article-title":"Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis","volume":"22","author":"Corcoran","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"805","DOI":"10.20892\/j.issn.2095-3941.2020.0177","article-title":"Evolving insights: How DNA repair pathways impact cancer evolution","volume":"17","author":"Zhou","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jmoldx.2014.12.006","article-title":"Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A Hybridization Capture-Based Next-Generation Sequencing Clinical Assay for Solid Tumor Molecular Oncology","volume":"17","author":"Cheng","year":"2015","journal-title":"J. Mol. Diagn."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Barzi, A., Weipert, C.M., Espenschied, C.R., Raymond, V.M., Wang-Gillam, A., Nezami, M.A., Gordon, E.J., Mahadevan, D., and Mody, K. (2024). ERBB2 (HER2) amplifications and co-occurring KRAS alterations in the circulating cell-free DNA of pancreatic ductal adenocarcinoma patients and response to HER2 inhibition. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1339302"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:24:21Z","timestamp":1760034261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":58,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157593"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157593","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]}}}