{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:52:02Z","timestamp":1786121522211,"version":"build-2736575974"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extranodal involvement (ENI) is incorporated into routine risk assessment for diffuse large B-cell lymphoma (DLBCL), but treating ENI as a single binary adverse feature may conceal clinically relevant heterogeneity in extranodal burden, anatomical distribution, treatment feasibility, and immune-molecular context. We evaluated ENI as a burden- and site-aware phenotype rather than as a uniform descriptor. We retrospectively studied 710 adults with newly diagnosed DLBCL treated with first-line immunochemotherapy between June 2011 and December 2024. Outcomes were analyzed according to ENI status, number of extranodal sites, and involved organs. Targeted sequencing was available in 176 tumors, and RNA sequencing was performed in 107 quality-controlled tumor samples. Clinical models were interpreted as adjustment models because ENI burden overlaps with established risk factors; site-specific and molecular analyses were prespecified as exploratory and were interpreted with attention to available-case denominators, treatment heterogeneity, sparse subgroups, and multiplicity. ENI was associated with inferior overall survival (OS) and progression-free survival (PFS) in unadjusted analyses. Multisite ENI was enriched for adverse baseline features, including advanced Ann Arbor stage, elevated lactate dehydrogenase (LDH), higher International Prognostic Index (IPI), and impaired performance status. After multivariable adjustment, the independent prognostic contribution of ENI burden was attenuated, indicating substantial clinical overlap with systemic disease burden and host fitness. Several anatomical sites showed candidate adverse signals, but rare-site estimates were limited by small subgroup sizes, wide confidence intervals, and multiple testing. Targeted sequencing and RNA-seq suggested heterogeneous genomic and immune-transcriptional patterns across ENI categories; these results should be regarded as hypothesis-generating because of tissue availability, tumor-only sequencing in many cases, modest molecular sample sizes, and lack of orthogonal immune validation. ENI in DLBCL is best interpreted as a clinically heterogeneous disease descriptor rather than a single uniform prognostic category. ENI burden and anatomical distribution provide useful descriptive and prognostic context, but they should be interpreted alongside established clinical risk, treatment intensity, censoring patterns, tissue-sampling constraints, and molecular ascertainment limitations. Exploratory genomic and immune-transcriptional correlates identified in this study require prospective multicenter validation with harmonized staging, treatment-intensity annotation, matched-normal sequencing, and spatial or cellular immune profiling before ENI-informed biological or therapeutic stratification can be applied clinically.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>Study design, ENI boundary definitions, statistical safeguards, and multi-omics integration<\/jats:p>","DOI":"10.1007\/s10238-026-02268-3","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:04:21Z","timestamp":1785038661000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extranodal involvement defines distinct immune-molecular phenotypes and clinical outcomes in diffuse large b-cell lymphoma"],"prefix":"10.1007","volume":"26","author":[{"given":"Yiliya","family":"Ahongjiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biwen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"2268_CR1","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","volume":"127","author":"SH Swerdlow","year":"2016","unstructured":"Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375\u201390. https:\/\/doi.org\/10.1182\/blood-2016-01-643569.","journal-title":"Blood"},{"key":"2268_CR2","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1056\/NEJMra2027612","volume":"384","author":"LH Sehn","year":"2021","unstructured":"Sehn LH, Salles G. Diffuse large B-cell lymphoma. N Engl J Med. 2021;384:842\u201358. https:\/\/doi.org\/10.1056\/NEJMra2027612.","journal-title":"N Engl J Med"},{"key":"2268_CR3","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/35000501","volume":"403","author":"AA Alizadeh","year":"2000","unstructured":"Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503\u201311. https:\/\/doi.org\/10.1038\/35000501.","journal-title":"Nature"},{"key":"2268_CR4","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa1801445","volume":"378","author":"R Schmitz","year":"2018","unstructured":"Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378:1396\u2013407. https:\/\/doi.org\/10.1056\/NEJMoa1801445.","journal-title":"N Engl J Med"},{"key":"2268_CR5","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41591-018-0016-8","volume":"24","author":"B Chapuy","year":"2018","unstructured":"Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24:679\u201390. https:\/\/doi.org\/10.1038\/s41591-018-0016-8.","journal-title":"Nat Med"},{"key":"2268_CR6","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.cell.2017.09.027","volume":"171","author":"A Reddy","year":"2017","unstructured":"Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, et al. Genetic and functional drivers of diffuse large B cell lymphoma. Cell. 2017;171:481-494.e15. https:\/\/doi.org\/10.1016\/j.cell.2017.09.027.","journal-title":"Cell"},{"key":"2268_CR7","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.ccell.2020.03.015","volume":"37","author":"GW Wright","year":"2020","unstructured":"Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell. 2020;37:551-568.e14. https:\/\/doi.org\/10.1016\/j.ccell.2020.03.015.","journal-title":"Cancer Cell"},{"key":"2268_CR8","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1182\/blood-2017-11-764332","volume":"131","author":"L Pasqualucci","year":"2018","unstructured":"Pasqualucci L, Dalla-Favera R. Genetics of diffuse large B-cell lymphoma. Blood. 2018;131:2307\u201319. https:\/\/doi.org\/10.1182\/blood-2017-11-764332.","journal-title":"Blood"},{"key":"2268_CR9","doi-asserted-by":"publisher","unstructured":"The International Non-Hodgkin\u2019s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin\u2019s lymphoma. N Engl J Med. 1993;329:987\u2013994. https:\/\/doi.org\/10.1056\/NEJM199309303291402.","DOI":"10.1056\/NEJM199309303291402"},{"key":"2268_CR10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1182\/blood-2013-09-524108","volume":"123","author":"Z Zhou","year":"2014","unstructured":"Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123:837\u201342. https:\/\/doi.org\/10.1182\/blood-2013-09-524108.","journal-title":"Blood"},{"key":"2268_CR11","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.ccr.2011.11.006","volume":"20","author":"M Challa-Malladi","year":"2011","unstructured":"Challa-Malladi M, Lieu YK, Califano O, Holmes A, Bhagat G, Murty VV, et al. Combined genetic inactivation of \u03b22-microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B-cell lymphoma. Cancer Cell. 2011;20:728\u201340. https:\/\/doi.org\/10.1016\/j.ccr.2011.11.006.","journal-title":"Cancer Cell"},{"key":"2268_CR12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2104504118","volume":"118","author":"M Fangazio","year":"2021","unstructured":"Fangazio M, Ladewig E, Gomez K, Garcia-Ibanez L, Kumar R, Teruya-Feldstein J, et al. Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2021;118:e2104504118. https:\/\/doi.org\/10.1073\/pnas.2104504118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2268_CR13","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1158\/2159-8290.CD-20-0839","volume":"11","author":"N Kotlov","year":"2021","unstructured":"Kotlov N, Bagaev A, Revuelta MV, Phillip JM, Cacciapuoti MT, Antysheva Z, et al. Clinical and biological subtypes of B-cell lymphoma revealed by microenvironmental signatures. Cancer Discov. 2021;11:1468\u201389. https:\/\/doi.org\/10.1158\/2159-8290.CD-20-0839.","journal-title":"Cancer Discov"},{"key":"2268_CR14","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/hon.2905","volume":"39","author":"H Yu","year":"2021","unstructured":"Yu H, Fu D, Xu PP, Cheng S, Wang L, Zhang YZ, et al. Implication of immune cell signature of tumor microenvironment in diffuse large B-cell lymphoma. Hematol Oncol. 2021;39:616\u201324. https:\/\/doi.org\/10.1002\/hon.2905.","journal-title":"Hematol Oncol"},{"key":"2268_CR15","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1056\/NEJMoa011795","volume":"346","author":"B Coiffier","year":"2002","unstructured":"Coiffier B, Lepage E, Bri\u00e8re J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235\u201342. https:\/\/doi.org\/10.1056\/NEJMoa011795.","journal-title":"N Engl J Med"},{"key":"2268_CR16","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","volume":"32","author":"BD Cheson","year":"2014","unstructured":"Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059\u201368. https:\/\/doi.org\/10.1200\/JCO.2013.54.8800.","journal-title":"J Clin Oncol"},{"key":"2268_CR17","unstructured":"Andrews S FastQC: a quality control tool for high throughput sequence data. Babraham Bioinformatics. 2010. Available from: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"2268_CR18","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114\u201320. https:\/\/doi.org\/10.1093\/bioinformatics\/btu170.","journal-title":"Bioinformatics"},{"key":"2268_CR19","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics. 2009;25:1754\u201360. https:\/\/doi.org\/10.1093\/bioinformatics\/btp324.","journal-title":"Bioinformatics"},{"key":"2268_CR20","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, et al. Twelve years of SAMtools and BCFtools. Gigascience. 2021;10:giab008. https:\/\/doi.org\/10.1093\/gigascience\/giab008.","journal-title":"Gigascience"},{"key":"2268_CR21","volume-title":"Genomics in the cloud: using Docker, GATK, and WDL in Terra","author":"GA Van der Auwera","year":"2020","unstructured":"Van der Auwera GA, O\u2019Connor BD. Genomics in the cloud: using Docker, GATK, and WDL in Terra. Sebastopol, CA: O\u2019Reilly Media; 2020."},{"key":"2268_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The Ensembl variant effect predictor. Genome Biol. 2016;17:122. https:\/\/doi.org\/10.1186\/s13059-016-0974-4.","journal-title":"Genome Biol"},{"key":"2268_CR23","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47. https:\/\/doi.org\/10.1093\/nar\/gkv007.","journal-title":"Nucleic Acids Res"},{"key":"2268_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. https:\/\/doi.org\/10.1186\/1471-2105-9-559.","journal-title":"BMC Bioinformatics"},{"key":"2268_CR25","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY. ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16:284\u20137. https:\/\/doi.org\/10.1089\/omi.2011.0118.","journal-title":"OMICS"},{"key":"2268_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7. https:\/\/doi.org\/10.1186\/1471-2105-14-7.","journal-title":"BMC Bioinformatics"},{"key":"2268_CR27","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman AM, Steen CB, Liu CL, Gentles AJ, Chaudhuri AA, Scherer F, et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol. 2019;37:773\u201382. https:\/\/doi.org\/10.1038\/s41587-019-0114-2.","journal-title":"Nat Biotechnol"},{"key":"2268_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1","volume":"18","author":"D Aran","year":"2017","unstructured":"Aran D, Hu Z, Butte AJ. XCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017;18:220. https:\/\/doi.org\/10.1186\/s13059-017-1349-1.","journal-title":"Genome Biol"},{"key":"2268_CR29","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289\u2013300. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x.","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"2268_CR30","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1101\/gr.239244.118","volume":"28","author":"A Mayakonda","year":"2018","unstructured":"Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018;28:1747\u201356. https:\/\/doi.org\/10.1101\/gr.239244.118.","journal-title":"Genome Res"},{"key":"2268_CR31","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1002\/ajh.23638","volume":"89","author":"JJ Castillo","year":"2014","unstructured":"Castillo JJ, Winer ES, Olszewski AJ. Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol. 2014;89:310\u20134. https:\/\/doi.org\/10.1002\/ajh.23638.","journal-title":"Am J Hematol"},{"key":"2268_CR32","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.3109\/10428194.2014.982636","volume":"56","author":"CS Lu","year":"2015","unstructured":"Lu CS, Chen JH, Huang TC, Wu YY, Chang PY, Dai MS, et al. Diffuse large B-cell lymphoma: sites of extranodal involvement are a stronger prognostic indicator than number of extranodal sites in the rituximab era. Leuk Lymphoma. 2015;56:2047\u201355. https:\/\/doi.org\/10.3109\/10428194.2014.982636.","journal-title":"Leuk Lymphoma"},{"key":"2268_CR33","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1182\/blood.2020005112","volume":"137","author":"S Bobillo","year":"2021","unstructured":"Bobillo S, Joffe E, Lavery JA, Sermer D, Ghione P, Noy A, et al. Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era. Blood. 2021;137:39\u201348. https:\/\/doi.org\/10.1182\/blood.2020005112.","journal-title":"Blood"},{"key":"2268_CR34","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3904\/kjim.2010.25.3.301","volume":"25","author":"C Yoo","year":"2010","unstructured":"Yoo C, Kim S, Sohn BS, Kim JE, Yoon DH, Huh J, et al. Modified number of extranodal involved sites as a prognosticator in R-CHOP-treated patients with disseminated diffuse large B-cell lymphoma. Korean J Intern Med. 2010;25:301\u20138. https:\/\/doi.org\/10.3904\/kjim.2010.25.3.301.","journal-title":"Korean J Intern Med"},{"key":"2268_CR35","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1007\/s00277-023-05165-x","volume":"102","author":"K Oiwa","year":"2023","unstructured":"Oiwa K, Fujita K, Lee S, Morishita T, Tsujikawa T, Negoro E, et al. Prognostic value of metabolic tumor volume of extranodal involvement in diffuse large B cell lymphoma. Ann Hematol. 2023;102:1141\u20138. https:\/\/doi.org\/10.1007\/s00277-023-05165-x.","journal-title":"Ann Hematol"},{"key":"2268_CR36","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.pathol.2017.09.006","volume":"50","author":"S Li","year":"2018","unstructured":"Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50:74\u201387. https:\/\/doi.org\/10.1016\/j.pathol.2017.09.006.","journal-title":"Pathology"},{"key":"2268_CR37","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-018-0555-8","volume":"19","author":"TA Ollila","year":"2018","unstructured":"Ollila TA, Olszewski AJ. Extranodal diffuse large B cell lymphoma: molecular features, prognosis, and risk of central nervous system recurrence. Curr Treat Options Oncol. 2018;19:38. https:\/\/doi.org\/10.1007\/s11864-018-0555-8.","journal-title":"Curr Treat Options Oncol"},{"key":"2268_CR38","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1002\/cac2.70033","volume":"45","author":"SY Chen","year":"2025","unstructured":"Chen SY, Xu PP, Feng R, Cui GH, Wang L, Cheng S, et al. Extranodal diffuse large B-cell lymphoma: clinical and molecular insights with survival outcomes from the multicenter EXPECT study. Cancer Commun. 2025;45:919\u201335. https:\/\/doi.org\/10.1002\/cac2.70033.","journal-title":"Cancer Commun"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-026-02268-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02268-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02268-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:45:43Z","timestamp":1786077943000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-026-02268-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,26]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2268"],"URL":"https:\/\/doi.org\/10.1007\/s10238-026-02268-3","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,26]]},"assertion":[{"value":"25 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"293"}}