{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:23:49Z","timestamp":1792783429595,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Helsinki","id":[{"id":"https:\/\/ror.org\/040af2s02","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head and Neck Pathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mucosal melanoma is a rare disease with a poor prognosis, and its clinical signs and symptoms are nonspecific. This study aims to identify histopathological features and immunohistochemical markers of head and neck mucosal melanoma that characterize the tumor immunophenotype and are associated with patient survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study analysed head and neck mucosal melanoma diagnosed at Helsinki University hospital between January 1, 2011, and June 8, 2023. Samples were obtained from the Helsinki Biobank in Finland. New slides were prepared and stained for hematoxylin and eosin (H&amp;E), CD3, CD4, CD8, Granzyme B (GrzB), CD68, CD117, p16INK4a, p53, SOX10 and PRAME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study included 23 patients, 10 men and 13 women, aged 60\u201392 years (mean 75 years). The tumors were predominantly sinonasal. Ulceration was present in 15 cases, also 15 cases were amelanotic. Immunohistochemical staining SOX10 was positive in all tumors. PRAME was strongly positive in majority (20 cases, 87%). Strong p16 positivity was observed in 13 cases (57%), with a longer median survival compared to cases with weakened p16 expression (32.8 vs 13.8 months,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.176). The median survival was also longer in the cases with high score of tumor infiltrating CD3-, CD8- and CD68-positive immune cells, though not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Immunohistochemical markers routinely applied in cutaneous melanoma (SOX-10 and PRAME) are also expressed in head and neck mucosal melanoma. Tumour-infiltrating immune cells showed trend toward better survival, as has been previously found out in cutaneous melanoma. Strong p16 positivity may be an independent predictor of favorable prognosis in head and neck mucosal melanoma, irrespective of disease stage. Larger multicenter studies are warranted to validate these findings in this rare disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-026-01969-1","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:06:45Z","timestamp":1790071605000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical Predictors in Head and Neck Mucosal Melanoma"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4723-3779","authenticated-orcid":false,"given":"Sara C.","family":"Degerholm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-0088","authenticated-orcid":false,"given":"Tuula A.","family":"Salo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-2093","authenticated-orcid":false,"given":"Susanna","family":"Juteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-4939","authenticated-orcid":false,"given":"Matti O.","family":"Mauramo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"1969_CR1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-3-030-46227-7_6","volume-title":"Sunlight, vitamin D and skin cancer","author":"U Leiter","year":"2020","unstructured":"Leiter U, Keim U, Garbe C (2020) Epidemiology of skin cancer: update 2019. In: Reichrath J (ed) Sunlight, vitamin D and skin cancer. Springer International Publishing, Cham, pp 123\u2013139. https:\/\/doi.org\/10.1007\/978-3-030-46227-7_6"},{"key":"1969_CR2","volume-title":"Sy\u00f6p\u00e4 2023. Tilastoraportti Suomen sy\u00f6p\u00e4tilanteesta","author":"K Sepp\u00e4","year":"2025","unstructured":"Sepp\u00e4 K, Lappi-Heikkinen S, Johansson S, Malila N, Pitk\u00e4niemi J (2025) Sy\u00f6p\u00e4 2023. Tilastoraportti Suomen sy\u00f6p\u00e4tilanteesta. Suomen Sy\u00f6p\u00e4yhdistys, Helsinki"},{"key":"1969_CR3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.semcancer.2019.09.013","volume":"61","author":"KW Nassar","year":"2020","unstructured":"Nassar KW, Tan AC (2020) The mutational landscape of mucosal melanoma. Semin Cancer Biol 61:139\u2013148. https:\/\/doi.org\/10.1016\/j.semcancer.2019.09.013","journal-title":"Semin Cancer Biol"},{"key":"1969_CR4","doi-asserted-by":"publisher","DOI":"10.1111\/jop.70129","author":"S Degerholm","year":"2026","unstructured":"Degerholm S, Salo T, Mauramo M (2026) Mucosal melanoma of head and neck: a rare and aggressive disease\u2014a register-based cohort study. J Oral Pathol Med. https:\/\/doi.org\/10.1111\/jop.70129 (in press)","journal-title":"J Oral Pathol Med"},{"issue":"7","key":"1969_CR5","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00262-019-02351-7","volume":"68","author":"A Moya-Plana","year":"2019","unstructured":"Moya-Plana A, Herrera G\u00f3mez RG, Rossoni C, Dercle L, Ammari S, Girault I et al (2019) Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma. Cancer Immunol Immunother 68(7):1171\u20131178. https:\/\/doi.org\/10.1007\/s00262-019-02351-7","journal-title":"Cancer Immunol Immunother"},{"key":"1969_CR6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.critrevonc.2017.01.019","volume":"112","author":"PA Ascierto","year":"2017","unstructured":"Ascierto PA, Accorona R, Botti G, Farina D, Fossati P, Gatta G et al (2017) Mucosal melanoma of the head and neck. Crit Rev Oncol Hematol 112:136\u2013152. https:\/\/doi.org\/10.1016\/j.critrevonc.2017.01.019","journal-title":"Crit Rev Oncol Hematol"},{"key":"1969_CR7","unstructured":"WHO Classification of Tumours Editorial Board (2023) Head and neck tumours. Lyon (France): International Agency for Research on Cancer, 5th edn; vol. 9. WHO classification of tumours series. https:\/\/publications.iarc.who.int\/629"},{"key":"1969_CR8","doi-asserted-by":"publisher","unstructured":"American Joint Committee on Cancer (2002) AJCC Cancer Staging Manual [Internet]. In: Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, et al (eds) Springer, New York. https:\/\/doi.org\/10.1007\/978-1-4757-3656-4","DOI":"10.1007\/978-1-4757-3656-4"},{"key":"1969_CR9","unstructured":"Regezi J, Sciubba J, Jordan R (2016) Oral pathology: clinical pathologic correlations, 7th edn, pp. 141\u2013144. Available from: https:\/\/www.elsevier.com\/books\/oral-pathology\/regezi\/978-0-323-29768-4"},{"issue":"6","key":"1969_CR10","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1097\/PAI.0b013e318279bc0a","volume":"21","author":"A Mohamed","year":"2013","unstructured":"Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C (2013) SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol 21(6):506\u2013510. https:\/\/doi.org\/10.1097\/PAI.0b013e318279bc0a","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"1969_CR11","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-022-01515-9","author":"WFJ Scheurleer","year":"2022","unstructured":"Scheurleer WFJ, Braunius WW, Tijink BM, Suijkerbuijk KPM, Dierselhuis MP, Meijers RWJ et al (2022) PRAME staining in sinonasal mucosal melanoma: a single-center experience. Head Neck Pathol. https:\/\/doi.org\/10.1007\/s12105-022-01515-9","journal-title":"Head Neck Pathol"},{"issue":"20","key":"1969_CR12","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1056\/NEJMoa050092","volume":"353","author":"JA Curtin","year":"2005","unstructured":"Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353(20):2135\u20132147. https:\/\/doi.org\/10.1056\/NEJMoa050092","journal-title":"N Engl J Med"},{"issue":"8","key":"1969_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081133","volume":"11","author":"N Dumaz","year":"2019","unstructured":"Dumaz N, Jouenne F, Delyon J, Mourah S, Bensussan A, Lebb\u00e9 C (2019) Atypical BRAF and NRAS mutations in mucosal melanoma. Cancers 11(8):1133. https:\/\/doi.org\/10.3390\/cancers11081133","journal-title":"Cancers"},{"issue":"16","key":"1969_CR14","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1101\/gad.1437206","volume":"20","author":"L Chin","year":"2006","unstructured":"Chin L, Garraway LA, Fisher DE (2006) Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev 20(16):2149\u20132182. https:\/\/doi.org\/10.1101\/gad.1437206","journal-title":"Genes Dev"},{"issue":"5","key":"1969_CR15","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1097\/00008390-200209000-00007","volume":"12","author":"BK Ragnarsson-Olding","year":"2002","unstructured":"Ragnarsson-Olding BK, Karsberg S, Platz A, Ringborg UK (2002) Mutations in the TP53 gene in human malignant melanomas derived from sun-exposed skin and unexposed mucosal membranes. Melanoma Res 12(5):453\u2013463. https:\/\/doi.org\/10.1097\/00008390-200209000-00007","journal-title":"Melanoma Res"},{"issue":"11","key":"1969_CR16","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1007\/s11912-023-01453-x","volume":"25","author":"MC Sergi","year":"2023","unstructured":"Sergi MC, Filoni E, Triggiano G, Cazzato G, Intern\u00f2 V, Porta C et al (2023) Mucosal melanoma: epidemiology, clinical features, and treatment. Curr Oncol Rep 25(11):1247\u20131258. https:\/\/doi.org\/10.1007\/s11912-023-01453-x","journal-title":"Curr Oncol Rep"},{"issue":"5","key":"1969_CR17","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/j.1755-148X.2008.00495.x","volume":"21","author":"NF Box","year":"2008","unstructured":"Box NF, Terzian T (2008) The role of p53 in pigmentation, tanning and melanoma. Pigment Cell Melanoma Res 21(5):525\u2013533. https:\/\/doi.org\/10.1111\/j.1755-148X.2008.00495.x","journal-title":"Pigment Cell Melanoma Res"},{"issue":"6456","key":"1969_CR18","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/366704a0","volume":"366","author":"M Serrano","year":"1993","unstructured":"Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D\/CDK4. Nature 366(6456):704\u2013707. https:\/\/doi.org\/10.1038\/366704a0","journal-title":"Nature"},{"issue":"12","key":"1969_CR19","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1111\/cup.14717","volume":"51","author":"SS Chinchanikar","year":"2024","unstructured":"Chinchanikar SS, Fraga GR (2024) Ancillary immunohistochemistry testing for loss of p16 in melanoma: a systematic review and meta-analysis of diagnostic accuracy studies. J Cutan Pathol 51(12):971\u2013979. https:\/\/doi.org\/10.1111\/cup.14717","journal-title":"J Cutan Pathol"},{"issue":"3","key":"1969_CR20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/CMR.0b013e32831993f3","volume":"19","author":"BC Soares De S\u00e1","year":"2009","unstructured":"Soares De S\u00e1 BC, Fugimori ML, Braga Ribeiro KDC, Duprat Neto JP, Neves RI, Landman G (2009) Proteins involved in pRb and p53 pathways are differentially expressed in thin and thick superficial spreading melanomas. Melanoma Res 19(3):135\u2013141. https:\/\/doi.org\/10.1097\/CMR.0b013e32831993f3","journal-title":"Melanoma Res"},{"issue":"6","key":"1969_CR21","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/apm.12529","volume":"124","author":"LH Mikkelsen","year":"2016","unstructured":"Mikkelsen LH, Larsen A, Von Buchwald C, Drzewiecki KT, Prause JU, Heegaard S (2016) Mucosal malignant melanoma\u2014a clinical, oncological, pathological and genetic survey. APMIS 124(6):475\u2013486. https:\/\/doi.org\/10.1111\/apm.12529","journal-title":"APMIS"},{"key":"1969_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02105","volume":"11","author":"F Maibach","year":"2020","unstructured":"Maibach F, Sadozai H, Seyed Jafari SM, Hunger RE, Schenk M (2020) Tumor-infiltrating lymphocytes and their prognostic value in cutaneous melanoma. Front Immunol 11:2105. https:\/\/doi.org\/10.3389\/fimmu.2020.02105","journal-title":"Front Immunol"},{"key":"1969_CR23","unstructured":"Oble DA, Loewe R, Yu P, Mihm MC (2009) Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun 9:3. PMID: 19338264; PubMed Central PMCID: PMC2935762."},{"issue":"12","key":"1969_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10123209","volume":"10","author":"S Salmi","year":"2022","unstructured":"Salmi S, H\u00e4linen K, Lin A, Suikkanen S, Jokelainen O, Rahunen E et al (2022) The association of CD8+ cytotoxic T cells and Granzyme B+ lymphocytes with immunosuppressive factors, tumor stage and prognosis in cutaneous melanoma. Biomedicines 10(12):3209. https:\/\/doi.org\/10.3390\/biomedicines10123209","journal-title":"Biomedicines"},{"issue":"1","key":"1969_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28944-3","volume":"8","author":"H Halse","year":"2018","unstructured":"Halse H, Colebatch AJ, Petrone P, Henderson MA, Mills JK, Snow H et al (2018) Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma. Sci Rep 8(1):11158. https:\/\/doi.org\/10.1038\/s41598-018-28944-3","journal-title":"Sci Rep"},{"issue":"7","key":"1969_CR26","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1593806","volume":"8","author":"Q Fu","year":"2019","unstructured":"Fu Q, Chen N, Ge C, Li R, Li Z, Zeng B et al (2019) Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis. Oncoimmunology 8(7):e1593806. https:\/\/doi.org\/10.1080\/2162402X.2019.1593806","journal-title":"Oncoimmunology"},{"issue":"11","key":"1969_CR27","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1097\/PAS.0000000000001134","volume":"42","author":"C Lezcano","year":"2018","unstructured":"Lezcano C, Jungbluth AA, Nehal KS, Hollmann TJ, Busam KJ (2018) PRAME expression in melanocytic tumors. Am J Surg Pathol 42(11):1456\u20131465. https:\/\/doi.org\/10.1097\/PAS.0000000000001134","journal-title":"Am J Surg Pathol"},{"issue":"1","key":"1969_CR28","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.9510","volume":"21","author":"A Radu","year":"2020","unstructured":"Radu A, Bejenaru C, \u0162olea I, Maranduca M, Br\u0103ni\u015fteanu D, Bejenaru L et al (2020) Immunohistochemical study of CD117 in various cutaneous melanocytic lesions. Exp Ther Med 21(1):78. https:\/\/doi.org\/10.3892\/etm.2020.9510","journal-title":"Exp Ther Med"},{"issue":"6","key":"1969_CR29","doi-asserted-by":"publisher","first-page":"588","DOI":"10.32074\/1591-951X-1659","volume":"117","author":"F Fortarezza","year":"2026","unstructured":"Fortarezza F, Zarrilli G, Munari G, Angerilli V, Balistreri M, Piccin L et al (2026) Immunohistochemical and molecular profiling of uveal melanoma: clinicopathological correlations from an Italian cohort. Pathologica 117(6):588\u2013597. https:\/\/doi.org\/10.32074\/1591-951X-1659","journal-title":"Pathologica"},{"issue":"3","key":"1969_CR30","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S1368-8375(00)00107-X","volume":"37","author":"N Tanaka","year":"2001","unstructured":"Tanaka N (2001) Expression of Rb, pRb2\/p130, p53, and p16 proteins in malignant melanoma of oral mucosa. Oral Oncol 37(3):308\u2013314. https:\/\/doi.org\/10.1016\/S1368-8375(00)00107-X","journal-title":"Oral Oncol"},{"key":"1969_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2022.154289","volume":"241","author":"S Ledderose","year":"2023","unstructured":"Ledderose S, Schulz H, Paul T, Ledderose C, Ledderose GJ (2023) Characterization of the tumor-infiltrating lymphocyte landscape in sinonasal mucosal melanoma. Pathol Res Pract 241:154289. https:\/\/doi.org\/10.1016\/j.prp.2022.154289","journal-title":"Pathol Res Pract"},{"issue":"12","key":"1969_CR32","doi-asserted-by":"publisher","first-page":"4048","DOI":"10.1111\/cas.15437","volume":"113","author":"T Yusa","year":"2022","unstructured":"Yusa T, Yamashita Y, Okabe H, Nakao Y, Itoyama R, Kitano Y et al (2022) Survival impact of immune cells infiltrating peritumoral area of hepatocellular carcinoma. Cancer Sci 113(12):4048\u20134058. https:\/\/doi.org\/10.1111\/cas.15437","journal-title":"Cancer Sci"},{"key":"1969_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.561390","volume":"11","author":"F Sabbatino","year":"2020","unstructured":"Sabbatino F, Scognamiglio G, Liguori L, Marra A, Anniciello AM, Polcaro G et al (2020) Peritumoral immune infiltrate as a prognostic biomarker in thin melanoma. Front Immunol 11:561390. https:\/\/doi.org\/10.3389\/fimmu.2020.561390","journal-title":"Front Immunol"},{"issue":"2","key":"1969_CR34","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ijom.2015.08.987","volume":"45","author":"ALN Francisco","year":"2016","unstructured":"Francisco ALN, Furlan MV, Peresi PM, Nishimoto IN, Louren\u00e7o SV, Pinto CAL et al (2016) Head and neck mucosal melanoma: clinicopathological analysis of 51 cases treated in a single cancer centre and review of the literature. Int J Oral Maxillofac Surg 45(2):135\u2013140. https:\/\/doi.org\/10.1016\/j.ijom.2015.08.987","journal-title":"Int J Oral Maxillofac Surg"},{"issue":"1","key":"1969_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16010227","volume":"16","author":"L Clavero-Rovira","year":"2024","unstructured":"Clavero-Rovira L, G\u00f3mez-Tom\u00e1s \u00c1, Bassas-Freixas P, Bodet D, Ferrer B, Hern\u00e1ndez-Losa J et al (2024) Mucosal melanoma clinical management and prognostic implications: a retrospective cohort study. Cancers 16(1):227. https:\/\/doi.org\/10.3390\/cancers16010227","journal-title":"Cancers"},{"issue":"4","key":"1969_CR36","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1097\/CMR.0b013e3283470ffd","volume":"21","author":"H Gavriel","year":"2011","unstructured":"Gavriel H, McArthur G, Sizeland A, Henderson M (2011) Review: mucosal melanoma of the head and neck. Melanoma Res 21(4):257\u2013266. https:\/\/doi.org\/10.1097\/CMR.0b013e3283470ffd","journal-title":"Melanoma Res"},{"key":"1969_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.702287","volume":"11","author":"Y Ma","year":"2021","unstructured":"Ma Y, Xia R, Ma X, Judson-Torres RL, Zeng H (2021) Mucosal melanoma: pathological evolution, pathway dependency and targeted therapy. Front Oncol 11:702287. https:\/\/doi.org\/10.3389\/fonc.2021.702287","journal-title":"Front Oncol"}],"container-title":["Head and Neck Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-026-01969-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12105-026-01969-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-026-01969-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:06:49Z","timestamp":1790071609000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12105-026-01969-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1969"],"URL":"https:\/\/doi.org\/10.1007\/s12105-026-01969-1","relation":{},"ISSN":["1936-0568"],"issn-type":[{"value":"1936-0568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"14 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Northern Ostrobothnia Hospital District PPSHP EETTMK: 101\/2020 \u00a7 20 and Helsinki University Hospital: HUS\/150\/2022 \u00a7 25, HUS\/124\/023 \u00a7 21.","order":2,"name":"Ethics","label":"Compliance with Ethical Standards","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"99"}}