{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:31:21Z","timestamp":1788003081910,"version":"build-2784847793"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The existence of transmissible amyloid fibril strains has long intrigued the scientific community. The strain theory originates from prion disorders, but here, we provide evidence of strains in systemic amyloidosis. Human AA amyloidosis manifests as two distinct clinical phenotypes called common AA and vascular AA. Glomerular amyloid deposition of the kidney defines the common form, while in the vascular type amyloid deposits are massive in the renal medulla and in arteries throughout the body, while glomeruli are spared. By electron microscopy the two types appeared morphologically different. The common type was composed of dispersed fibrils which tended to be clustered whereas the vascular type was composed of longer and more distinct less clustered fibrils. Staining with fluorescent amyloid binding ligands analyzed by hyperspectral microscopy showed differential staining patterns between the two groups supporting the notion of human AA amyloid strains. AA amyloid staining was significantly different from systemic AL amyloid. Both types of AA (common and vascular) and AL amyloid fibrils were isolated and used to seed mouse AA amyloid in groups of inflamed NMRI mice (<jats:italic>n<\/jats:italic>\u2009=\u20099\u201310 per group). All but two mice showed amyloid deposits in the spleen induced by the human seeds. Amyloid binding ligand analysis was applied on the splenic amyloid deposits and revealed no clear significant difference between mice seeded with AA fibrils from different donors being vascular or common, but the AA deposits of mice given AL fibrils showed significantly different amyloid fluorescent signals compared to all groups of mice receiving AA fibrils. The combined results support the hypothesis that AA amyloid fibril structures can vary depending on the seed and may manifest as amyloid strains.<\/jats:p>","DOI":"10.1038\/s41598-025-87239-6","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T15:54:21Z","timestamp":1738166061000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The question of strains in AA amyloidosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Gunilla T.","family":"Westermark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebba","family":"Nystr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Nystr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Peter R.","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Westermark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"87239_CR1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev.genet.31.1.139","volume":"31","author":"SB Prusiner","year":"1997","unstructured":"Prusiner, S. B. & Scott, M. R. Genetics of prions. Annu. Rev. Genet. 31, 139\u2013175 (1997).","journal-title":"Annu. Rev. Genet."},{"key":"87239_CR2","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1098\/rstb.2008.0069","volume":"363","author":"JDF Wadsworth","year":"2008","unstructured":"Wadsworth, J. D. F. et al. The origin of the prion agent of kuru: molecular and biological strain typing. Philos. Trans. R. Soc. B 363, 3747\u20133753 (2008).","journal-title":"Philos. Trans. R. Soc. B"},{"key":"87239_CR3","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1126\/science.1105850","volume":"307","author":"AT Petkova","year":"2005","unstructured":"Petkova, A. T. et al. Self-propagating, molecular-level polymorphism in Alzheimer\u2019s \u03b2-amyloid fibrils. Science 307, 262\u2013265 (2005).","journal-title":"Science"},{"key":"87239_CR4","doi-asserted-by":"publisher","first-page":"18349","DOI":"10.1073\/pnas.0806270105","volume":"105","author":"AK Paravastu","year":"2008","unstructured":"Paravastu, A. K., Leapman, R. D., Yau, W. M. & Tycko, R. Molecular structural basis for polymorphism in Alzheimer\u2019s \u03b2-amyloid fibrils. Proc. Natl. Acad. Sci. U. S.A. 105, 18349\u201318354 (2008).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR5","doi-asserted-by":"publisher","first-page":"7443","DOI":"10.1073\/pnas.0812033106","volume":"106","author":"AK Paravastu","year":"2009","unstructured":"Paravastu, A. K., Qahwash, I., Leapman, R. D., Meredith, S. C. & Tycko, R. Seeded growth of beta-amyloid fibrils from Alzheimer\u2019s brain-derived fibril produces a distinct fibril strructure. Proc. Natl. Acad. Sci. U. S. A. 106, 7443\u20137448 (2009).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR6","doi-asserted-by":"publisher","first-page":"E782","DOI":"10.1073\/pnas.1714966115","volume":"115","author":"C Condello","year":"2018","unstructured":"Condello, C. et al. Structural heterogeneity and intersubject variability of A\u03b2 in familial and sporadic Alzheimer\u2019s disease. Proc. Natl. Acad. Sci. U. S. A. 115, E782\u2013E791 (2018).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR7","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.nbd.2017.07.018","volume":"109","author":"C Peng","year":"2018","unstructured":"Peng, C., Gathagan, R. J. & Lee, V. M. Distinct \u03b1-synuclein strains and implications for heterogeneity among \u03b1-synucleinopathies. Neurobiol. Dis. 109, 209\u2013218 (2018).","journal-title":"Neurobiol. Dis."},{"key":"87239_CR8","doi-asserted-by":"publisher","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","volume":"47","author":"S Narasimhan","year":"2017","unstructured":"Narasimhan, S. et al. Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J. Neurosci. 47, 11406\u201311423 (2017).","journal-title":"J. Neurosci."},{"key":"87239_CR9","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/13506129.2024.2405948","volume":"31","author":"JN Buxbaum","year":"2024","unstructured":"Buxbaum, J. N. et al. Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) nomenclature Committee. Amyloid 31, 249\u2013256 (2024).","journal-title":"Amyloid"},{"key":"87239_CR10","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev-pathol-020712-163913","volume":"10","author":"GT Westermark","year":"2015","unstructured":"Westermark, G. T., F\u00e4ndrich, M. & Westermark, P. AA amyloidosis: Pathogenesis and targeted therapy. Annu. Rev. Pathol. Mech. Dis. 10, 321\u2013344 (2015).","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"87239_CR11","first-page":"427","volume":"41","author":"P Westermark","year":"1979","unstructured":"Westermark, P., Sletten, K. & Eriksson, M. Morphologic and chemical variation of the kidney lesions in amyloidosis secondary to rheumatoid arthritis. Lab. Investig. 41, 427\u2013431 (1979).","journal-title":"Lab. Investig."},{"key":"87239_CR12","first-page":"137","volume":"19","author":"HM Falck","year":"1983","unstructured":"Falck, H. M., T\u00f6rnroth, T. & Wegelius, O. Predominantly vascular amyloid deposition in the kidney in patients with minimal or no proteinuria. Clin. Nephrol. 19, 137\u2013142 (1983).","journal-title":"Clin. Nephrol."},{"key":"87239_CR13","first-page":"57","volume":"57","author":"GT Westermark","year":"1987","unstructured":"Westermark, G. T., Westermark, P. & Sletten, K. Amyloid fibril protein AA. Characterization of uncommon subspecies from a patient with rheumatoid arthritis. Lab. Investig. 57, 57\u201364 (1987).","journal-title":"Lab. Investig."},{"key":"87239_CR14","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/j.1365-3083.1989.tb02468.x","volume":"30","author":"GT Westermark","year":"1989","unstructured":"Westermark, G. T., Sletten, K. & Westermark, P. Massive vascular AA-amyloidosis: a histologically and biochemically distinctive subtype of reactive systemic amyloidosis. Scand. J. Immunol. 30, 605\u2013613 (1989).","journal-title":"Scand. J. Immunol."},{"key":"87239_CR15","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3109\/13506129409148635","volume":"1","author":"G Husby","year":"1994","unstructured":"Husby, G., Marhaug, G., Dowton, B., Sletten, K. & Sipe, J. D. Serum amyloid A (SAA): biochemistry, genetics and the pathogenesis of AA amyloidosis. Amyloid 1, 119\u2013137 (1994).","journal-title":"Amyloid"},{"key":"87239_CR16","doi-asserted-by":"crossref","unstructured":"Kluve-Beckerman, B. in High-density Lipoprotein Amyloid Proteins in Amyloid Proteins the beta Sheet Conformation and Disease, 589\u2013623 (eds Sipe, J. D.) (Wiley, 2005).","DOI":"10.1002\/9783527619344.ch22"},{"key":"87239_CR17","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/s41467-019-09033-z","volume":"10","author":"F Liberta","year":"2019","unstructured":"Liberta, F. et al. Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids. Nat. Commun. 10, 1104 (2019).","journal-title":"Nat. Commun."},{"key":"87239_CR18","doi-asserted-by":"publisher","first-page":"7261","DOI":"10.1038\/s41467-022-34636-4","volume":"13","author":"S Banerjee","year":"2022","unstructured":"Banerjee, S. et al. Amyloid fibril structure from the vascular variant of systemic AA amyloidosis. Nat. Commun. 13, 7261 (2022).","journal-title":"Nat. Commun."},{"key":"87239_CR19","doi-asserted-by":"publisher","first-page":"6979","DOI":"10.1073\/pnas.092205999","volume":"99","author":"K Lundmark","year":"2002","unstructured":"Lundmark, K. et al. Transmissibility of systemic amyloidosis by a prion-like mechanism. Proc. Natl. Acad. Sci. U. S. A. 99, 6979\u20136984 (2002).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3109\/13506120009146825","volume":"7","author":"T Nilsen","year":"2000","unstructured":"Nilsen, T., Sletten, K. & Westermark, P. AL 612, a glycosylated lambda light chain of subgroup I. Amyloid 7, 51\u201353 (2000).","journal-title":"Amyloid"},{"key":"87239_CR21","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/path.1759","volume":"206","author":"J Bergstr\u00f6m","year":"2005","unstructured":"Bergstr\u00f6m, J. et al. Amyloid deposits in transthyretin-derived amyloidosis: cleaved transthyretin is associated with distinct amyloid morphology. J. Pathol. 206, 224\u2013232 (2005).","journal-title":"J. Pathol."},{"key":"87239_CR22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3109\/13506129.2011.630761","volume":"18","author":"A Larsson","year":"2011","unstructured":"Larsson, A., Malmstr\u00f6m, S. & Westermark, P. Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition. Amyloid 18, 229\u2013234 (2011).","journal-title":"Amyloid"},{"key":"87239_CR23","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3109\/13506129.2012.711391","volume":"19","author":"SN Nystr\u00f6m","year":"2012","unstructured":"Nystr\u00f6m, S. N. & Westermark, G. T. AA-amyloid is cleared by endogenous immunological mechanisms. Amyloid 19, 138\u2013145 (2012).","journal-title":"Amyloid"},{"key":"87239_CR24","first-page":"1301","volume":"144","author":"\u00c5 Gustavsson","year":"1994","unstructured":"Gustavsson, \u00c5., Engstr\u00f6m, U. & Westermark, P. Mechanisms of transthyretin (TTR) amyloidogenesis: antigenic mapping of transthyretin purified from plasma and amyloid fibrils and within in situ tissue localizations. Am. J. Path. 144, 1301\u20131311 (1994).","journal-title":"Am. J. Path"},{"key":"87239_CR25","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1016\/j.ajpath.2012.12.035","volume":"182","author":"J Sponarova","year":"2013","unstructured":"Sponarova, J. et al. Efficient amyloid a clearance in the absence of immunoglobulins and complement factors. Am. J. Path 182, 1297\u20131307 (2013).","journal-title":"Am. J. Path"},{"key":"87239_CR26","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1073\/pnas.95.5.2558","volume":"95","author":"K Johan","year":"1998","unstructured":"Johan, K. et al. Acceleration of AA-amyloidosis by amyloid-like synthetic fibrils. Proc. Natl. Acad. Sci. U. S. A. 95, 2558\u20132563 (1998).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR27","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/978-1-61779-551-0_24","volume":"849","author":"P Westermark","year":"2012","unstructured":"Westermark, P. Subcutaneous adipose tissue biopsy for amyloid protein studies. Methods Mol. Biol. 849, 363\u2013371 (2012).","journal-title":"Methods Mol. Biol."},{"key":"87239_CR28","doi-asserted-by":"publisher","first-page":"e6041","DOI":"10.1371\/journal.pone.0006041","volume":"4","author":"P Westermark","year":"2009","unstructured":"Westermark, P., Lundmark, K. & Westermark, G. T. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model. PLoS One 4, e6041 (2009).","journal-title":"PLoS One"},{"key":"87239_CR29","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1177\/002215540004800906","volume":"48","author":"SD Styren","year":"2000","unstructured":"Styren, S. D., Hamilton, R. L., Styren, G. C. & Klunk, W. E. X-34, a fluorescent derivative of Congo red: a novel histochemical stain for Alzheimer\u2019s disease pathology. J. Histochem. Cytochem. 48, 1223\u20131232 (2000).","journal-title":"J. Histochem. Cytochem."},{"key":"87239_CR30","doi-asserted-by":"publisher","first-page":"7210","DOI":"10.1002\/chem.201800501","volume":"24","author":"J Zhang","year":"2018","unstructured":"Zhang, J. et al. Detection and imaging of A\u00df1\u201342 and tau fibrils by redesigned fluorescent X-34 analogues. Chemistry 24, 7210\u20137216 (2018).","journal-title":"Chemistry"},{"key":"87239_CR31","doi-asserted-by":"publisher","first-page":"e202100684","DOI":"10.1002\/cbic.202100684","volume":"23","author":"K Butina","year":"2022","unstructured":"Butina, K. et al. Structural properties dictating selective optotracer detection of Staphylococcus aureus. Chembiochem 23, e202100684 (2022).","journal-title":"Chembiochem"},{"key":"87239_CR32","doi-asserted-by":"publisher","first-page":"e202300044","DOI":"10.1002\/cbic.202300044","volume":"24","author":"L Bj\u00f6rk","year":"2023","unstructured":"Bj\u00f6rk, L., Klingstedt, T. & Nilsson, K. P. R. Thiophene-based ligands: design, synthesis and their utilization for optical assignment of polymorphic-disease-associated protein aggregates. Chembiochem 24, e202300044 (2023).","journal-title":"Chembiochem"},{"key":"87239_CR33","doi-asserted-by":"publisher","first-page":"5956","DOI":"10.1002\/anie.201008276","volume":"50","author":"AK Sch\u00fctz","year":"2011","unstructured":"Sch\u00fctz, A. K. et al. The amyloid-Congo red interface at atomic resolution. Angew Chem. Int. Ed. Engl. 50, 5956\u20135960 (2011).","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"87239_CR34","doi-asserted-by":"publisher","first-page":"299ra123","DOI":"10.1126\/scitranslmed.aab1923","volume":"7","author":"US Herrmann","year":"2015","unstructured":"Herrmann, U. S. et al. Structure-based drug design identifies polythiophenes as antiprion compounds. Sci. Transl. Med. 7, 299ra123 (2015).","journal-title":"Sci. Transl. Med."},{"key":"87239_CR35","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1021\/acschemneuro.7b00397","volume":"9","author":"AK Sch\u00fctz","year":"2018","unstructured":"Sch\u00fctz, A. K. et al. Binding of polythiophenes to amyloids: structural mapping of the pharmacophore. ACS Chem. Neurosci. 9, 475\u2013481 (2018).","journal-title":"ACS Chem. Neurosci."},{"key":"87239_CR36","doi-asserted-by":"crossref","unstructured":"Tycko, R. \u03b2-amyloid fibrils structures, in vitro and in vivo. In:  Proteopathic Seeds and Neuro Degenerative Disases, 19\u201331 (Jucker M, Christen Y, eds)  (Springer, 2013).","DOI":"10.1007\/978-3-642-35491-5_2"},{"key":"87239_CR37","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.cell.2012.02.022","volume":"148","author":"D Eisenberg","year":"2012","unstructured":"Eisenberg, D. & Jucker, M. The amyloid state of protein in human diseases. Cell 148, 1188\u20131203 (2012).","journal-title":"Cell"},{"key":"87239_CR38","doi-asserted-by":"publisher","first-page":"6098","DOI":"10.1073\/pnas.0501814102","volume":"102","author":"K Lundmark","year":"2005","unstructured":"Lundmark, K., Westermark, G. T., Ols\u00e9n, A. & Westermark, P. Protein fibrils in nature can enhance AA amyloidosis in mice: cross-seeding as a disease mechanism. Proc. Natl. Acad. Sci. U. S. A. 102, 6098\u20136102 (2005).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR39","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/j.1365-3083.2007.02005.x","volume":"66","author":"Y Liu","year":"2007","unstructured":"Liu, Y. et al. Induction of murine AA amyloidosis by various homogeneous amyloid fibrils and amyloid-like synthetic peptides. Scand. J. Immunol. 66, 495\u2013500 (2007).","journal-title":"Scand. J. Immunol."},{"key":"87239_CR40","doi-asserted-by":"publisher","first-page":"8691","DOI":"10.1073\/pnas.0701250104","volume":"104","author":"S Linse","year":"2007","unstructured":"Linse, S. et al. Nucleation of protein fibrillation by nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 104, 8691\u20138696 (2007).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"87239_CR41","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.molmed.2010.08.004","volume":"16","author":"GT Westermark","year":"2010","unstructured":"Westermark, G. T. & Westermark, P. Prion-like aggregates: infectious agents in human disease. Trends Mol. Med. 16, 501\u2013507 (2010).","journal-title":"Trends Mol. Med."},{"key":"87239_CR42","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1080\/13506129.2017.1290599","volume":"24","author":"S Nystr\u00f6m","year":"2017","unstructured":"Nystr\u00f6m, S. et al. Seed-dependent templating of murine AA amyloidosis. Amyloid 24, 140\u2013141 (2017).","journal-title":"Amyloid"},{"key":"87239_CR43","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0006-291X(05)80107-X","volume":"182","author":"GT Westermark","year":"1992","unstructured":"Westermark, G. T., Engstr\u00f6m, U. & Westermark, P. The N-terminal segment of protein AA determines its fibrillogenic property. Biochem. Biophys. Res. Commun. 182, 27\u201333 (1992).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"87239_CR44","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1021\/cb900112v","volume":"4","author":"A Aslund","year":"2009","unstructured":"Aslund, A. et al. Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chem. Biol. 4, 673\u2013684 (2009).","journal-title":"ACS Chem. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-87239-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-87239-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-87239-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T15:55:45Z","timestamp":1738166145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-87239-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["87239"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-87239-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]},"assertion":[{"value":"14 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3684"}}