{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T02:11:46Z","timestamp":1782180706987,"version":"3.54.5"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":11,"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":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Juvenile idiopathic arthritis (JIA) is among the most common autoimmune diseases in children, yet its pathophysiology remains incompletely understood. Reliable biomarkers are needed to assess disease activity and guide therapy. Bile salt-stimulated lipase (BSSL), originally identified as a lipolytic enzyme, has recently been implicated in inflammatory conditions such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in adults. Elevated serum BSSL levels correlate with markers of inflammation and decrease following positive response to anti-inflammatory treatments, suggesting potential utility as both a biomarker and a therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum BSSL concentrations were measured in children with JIA and compared with healthy controls. Correlations between BSSL and inflammatory markers (S100A8\/A9, HNL), blood cell counts (leukocytes, neutrophils, platelets), and clinical disease-activity indices (ESR, JADAS27, cJADAS27, CHAQ) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Children with JIA had significantly higher serum BSSL concentrations than healthy controls, and levels decreased following medical treatment. BSSL correlated positively with platelets, ESR, and S100A8\/A9, but not with JADAS27.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serum BSSL tracks systemic inflammatory activity and decreases with clinical improvement in JIA, supporting its further evaluation as a complementary inflammatory biomarker and potential pharmacodynamic read out in pediatric inflammatory arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12969-026-01191-x","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:33:33Z","timestamp":1770903213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum bile salt-stimulated lipase levels associates with systemic inflammation and declines with effect of treatment in juvenile idiopathic arthritis"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-0453","authenticated-orcid":false,"given":"Lillemor","family":"Berntson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8841-6200","authenticated-orcid":false,"given":"Olle","family":"Hernell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5604-8501","authenticated-orcid":false,"given":"Kajsa","family":"Linde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2396-0294","authenticated-orcid":false,"given":"Eva-Lotta","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-7343","authenticated-orcid":false,"given":"Susanne","family":"Lindquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"2","key":"1191_CR1","first-page":"390","volume":"31","author":"RE Petty","year":"2004","unstructured":"Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390\u20132. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14760812.","journal-title":"J Rheumatol"},{"issue":"9","key":"1191_CR2","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1002\/art.30426","volume":"63","author":"E Nordal","year":"2011","unstructured":"Nordal E, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Ongoing disease activity and changing categories in a long-term nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63(9):2809\u201318. https:\/\/doi.org\/10.1002\/art.30426.","journal-title":"Arthritis Rheum"},{"issue":"8","key":"1191_CR3","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.autrev.2011.02.001","volume":"10","author":"YT Lin","year":"2011","unstructured":"Lin YT, Wang CT, Gershwin ME, Chiang BL. The pathogenesis of oligoarticular\/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev. 2011;10(8):482\u20139. https:\/\/doi.org\/10.1016\/j.autrev.2011.02.001.","journal-title":"Autoimmun Rev"},{"key":"1191_CR4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez590","author":"AM Barendregt","year":"2020","unstructured":"Barendregt AM, Veldkamp SR, van de Hissink Muller PCE, Aarts C, van Gulik EC, et al. MRP8\/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis. Rheumatology (Oxford). 2020. https:\/\/doi.org\/10.1093\/rheumatology\/kez590.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"1191_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12969-020-0398-2","volume":"18","author":"N Aljaberi","year":"2020","unstructured":"Aljaberi N, Tronconi E, Schulert G, Grom AA, Lovell DJ, Huggins JL, et al. The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis. Pediatr Rheumatol Online J. 2020;18(1):7. https:\/\/doi.org\/10.1186\/s12969-020-0398-2.","journal-title":"Pediatr Rheumatol Online J"},{"issue":"12","key":"1191_CR6","doi-asserted-by":"publisher","first-page":"7706","DOI":"10.1016\/S0021-9258(20)89506-4","volume":"266","author":"J Edgeworth","year":"1991","unstructured":"Edgeworth J, Gorman M, Bennett R, Freemont P, Hogg N. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem. 1991;266(12):7706\u201313.","journal-title":"J Biol Chem"},{"issue":"5","key":"1191_CR7","doi-asserted-by":"publisher","first-page":"R154","DOI":"10.1186\/ar2048","volume":"8","author":"JN Jarvis","year":"2006","unstructured":"Jarvis JN, Petty HR, Tang Y, Frank MB, Tessier PA, Dozmorov I, et al. Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheumatoid arthritis. Arthritis Res Ther. 2006;8(5):R154. https:\/\/doi.org\/10.1186\/ar2048.","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"1191_CR8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s12969-021-00600-7","volume":"19","author":"M Backlund","year":"2021","unstructured":"Backlund M, Venge P, Berntson L. A cross-sectional cohort study of the activity and turnover of neutrophil granulocytes in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2021;19(1):102. https:\/\/doi.org\/10.1186\/s12969-021-00600-7.","journal-title":"Pediatr Rheumatol Online J"},{"issue":"2","key":"1191_CR9","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/0005-2760(74)90254-9","volume":"369","author":"O Hernell","year":"1974","unstructured":"Hernell O, Olivecrona T. Human milk lipases. II. Bile salt-stimulated lipase. Biochim Biophys Acta. 1974;369(2):234\u201344. https:\/\/doi.org\/10.1016\/0005-2760(74)90254-9.","journal-title":"Biochim Biophys Acta"},{"issue":"11","key":"1191_CR10","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1194\/jlr.M015685","volume":"52","author":"EL Andersson","year":"2011","unstructured":"Andersson EL, Hernell O, Bl\u00e4ckberg L, F\u00e4lt H, Lindquist S. BSSL and PLRP2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line. J Lipid Res. 2011;52(11):1949\u201356. https:\/\/doi.org\/10.1194\/jlr.M015685.","journal-title":"J Lipid Res"},{"issue":"3","key":"1191_CR11","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1097\/MCO.0b013e328337bbf0","volume":"13","author":"S Lindquist","year":"2010","unstructured":"Lindquist S, Hernell O. Lipid digestion and absorption in early life: an update. Curr Opin Clin Nutr Metab Care. 2010;13(3):314\u201320. https:\/\/doi.org\/10.1097\/MCO.0b013e328337bbf0.","journal-title":"Curr Opin Clin Nutr Metab Care"},{"issue":"10","key":"1191_CR12","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.1128\/aac.00593-06","volume":"50","author":"MA Naarding","year":"2006","unstructured":"Naarding MA, Dirac AM, Ludwig IS, Speijer D, Lindquist S, Vestman EL, et al. Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4 + T cells. Antimicrob Agents Chemother. 2006;50(10):3367\u201374. https:\/\/doi.org\/10.1128\/aac.00593-06.","journal-title":"Antimicrob Agents Chemother"},{"issue":"Pt 3","key":"1191_CR13","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1042\/bj20050898","volume":"393","author":"N Ruvo\u00ebn-Clouet","year":"2006","unstructured":"Ruvo\u00ebn-Clouet N, Mas E, Marionneau S, Guillon P, Lombardo D, Le Pendu J. Bile-salt-stimulated lipase and mucins from milk of \u2018secretor\u2019 mothers inhibit the binding of Norwalk virus capsids to their carbohydrate ligands. Biochem J. 2006;393(Pt 3):627\u201334. https:\/\/doi.org\/10.1042\/bj20050898.","journal-title":"Biochem J"},{"issue":"2","key":"1191_CR14","doi-asserted-by":"publisher","first-page":"e17316","DOI":"10.1371\/journal.pone.0017316","volume":"6","author":"MJ Stax","year":"2011","unstructured":"Stax MJ, Naarding MA, Tanck MW, Lindquist S, Hernell O, Lyle R, et al. Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism. PLoS ONE. 2011;6(2):e17316. https:\/\/doi.org\/10.1371\/journal.pone.0017316.","journal-title":"PLoS ONE"},{"issue":"1","key":"1191_CR15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF02930225","volume":"8","author":"PJ Blind","year":"1991","unstructured":"Blind PJ, Buchler M, Blackberg L, Andersson Y, Uhl W, Beger HG, et al. Carboxylic ester hydrolase. A sensitive serum marker and indicator of severity of acute pancreatitis. Int J Pancreatol. 1991;8(1):65\u201373.","journal-title":"Int J Pancreatol"},{"issue":"5","key":"1191_CR16","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/00006676-199309000-00009","volume":"8","author":"D Lombardo","year":"1993","unstructured":"Lombardo D, Montalto G, Roudani S, Mas E, Laugier R, Sbarra V, et al. Is bile salt-dependent lipase concentration in serum of any help in pancreatic cancer diagnosis? Pancreas. 1993;8(5):581\u20138.","journal-title":"Pancreas"},{"issue":"8","key":"1191_CR17","doi-asserted-by":"publisher","first-page":"e0289980","DOI":"10.1371\/journal.pone.0289980","volume":"18","author":"S Lindquist","year":"2023","unstructured":"Lindquist S, Wang Y, Andersson EL, Tsuji Grebe S, Alenius GM, Rantap\u00e4\u00e4-Dahlqvist S, et al. Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders. PLoS ONE. 2023;18(8):e0289980. https:\/\/doi.org\/10.1371\/journal.pone.0289980.","journal-title":"PLoS ONE"},{"issue":"46","key":"1191_CR18","doi-asserted-by":"publisher","first-page":"38592","DOI":"10.1074\/jbc.M502266200","volume":"280","author":"A Kodvawala","year":"2005","unstructured":"Kodvawala A, Ghering AB, Davidson WS, Hui DY. Carboxyl ester lipase expression in macrophages increases cholesteryl ester accumulation and promotes atherosclerosis. J Biol Chem. 2005;280(46):38592\u20138. https:\/\/doi.org\/10.1074\/jbc.M502266200.","journal-title":"J Biol Chem"},{"issue":"Pt 3","key":"1191_CR19","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1042\/bj3290675","volume":"329","author":"F Li","year":"1998","unstructured":"Li F, Hui DY. Synthesis and secretion of the pancreatic-type carboxyl ester lipase by human endothelial cells. Biochem J. 1998;329(Pt 3):675\u20139. https:\/\/doi.org\/10.1042\/bj3290675.","journal-title":"Biochem J"},{"issue":"12","key":"1191_CR20","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1172\/jci32655","volume":"117","author":"L Panicot-Dubois","year":"2007","unstructured":"Panicot-Dubois L, Thomas GM, Furie BC, Furie B, Lombardo D, Dubois C. Bile salt-dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans. J Clin Invest. 2007;117(12):3708\u201319. https:\/\/doi.org\/10.1172\/jci32655.","journal-title":"J Clin Invest"},{"issue":"10","key":"1191_CR21","doi-asserted-by":"publisher","first-page":"e47006","DOI":"10.1371\/journal.pone.0047006","volume":"7","author":"S Lindquist","year":"2012","unstructured":"Lindquist S, Andersson EL, Lundberg L, Hernell O. Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents. PLoS ONE. 2012;7(10):e47006. https:\/\/doi.org\/10.1371\/journal.pone.0047006.","journal-title":"PLoS ONE"},{"issue":"1","key":"1191_CR22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12969-016-0085-5","volume":"14","author":"A Consolaro","year":"2016","unstructured":"Consolaro A, Giancane G, Schiappapietra B, Davi S, Calandra S, Lanni S, et al. Clinical outcome measures in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):23. https:\/\/doi.org\/10.1186\/s12969-016-0085-5.","journal-title":"Pediatr Rheumatol Online J"},{"issue":"11","key":"1191_CR23","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1002\/acr.22393","volume":"66","author":"A Consolaro","year":"2014","unstructured":"Consolaro A, Negro G, Chiara Gallo M, Bracciolini G, Ferrari C, Schiappapietra B, et al. Defining criteria for disease activity States in nonsystemic juvenile idiopathic arthritis based on a three-variable juvenile arthritis disease activity score. Arthritis Care Res (Hoboken). 2014;66(11):1703\u20139. https:\/\/doi.org\/10.1002\/acr.22393.","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"7","key":"1191_CR24","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1093\/rheumatology\/ket470","volume":"53","author":"G Horneff","year":"2014","unstructured":"Horneff G, Becker I. Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score. Rheumatology (Oxford). 2014;53(7):1229\u201334. https:\/\/doi.org\/10.1093\/rheumatology\/ket470.","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"1191_CR25","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1002\/art.1780371209","volume":"37","author":"G Singh","year":"1994","unstructured":"Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1994;37(12):1761\u20139.","journal-title":"Arthritis Rheum"},{"issue":"35","key":"1191_CR26","doi-asserted-by":"publisher","first-page":"26692","DOI":"10.1016\/S0021-9258(19)74368-3","volume":"268","author":"L Hansson","year":"1993","unstructured":"Hansson L, Bl\u00e4ckberg L, Edlund M, Lundberg L, Str\u00f6mqvist M, Hernell O. Recombinant human milk bile salt-stimulated lipase. Catalytic activity is retained in the absence of glycosylation and the unique proline-rich repeats. J Biol Chem. 1993;268(35):26692\u20138.","journal-title":"J Biol Chem"},{"issue":"3","key":"1191_CR27","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/rheumatology\/kex441","volume":"57","author":"K Ramanathan","year":"2018","unstructured":"Ramanathan K, Glaser A, Lythgoe H, Ong J, Beresford MW, Midgley A, et al. Neutrophil activation signature in juvenile idiopathic arthritis indicates the presence of low-density granulocytes. Rheumatology (Oxford). 2018;57(3):488\u201398. https:\/\/doi.org\/10.1093\/rheumatology\/kex441.","journal-title":"Rheumatology (Oxford)"},{"issue":"4","key":"1191_CR28","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3109\/03009747709095457","volume":"6","author":"GK Endresen","year":"1977","unstructured":"Endresen GK, H\u00f8yeraal HM. K\u00e5ss. Platelet count and disease activity in juvenile rheumatoid arthritis. Scand J Rheumatol. 1977;6(4):237\u201340. https:\/\/doi.org\/10.3109\/03009747709095457.","journal-title":"Scand J Rheumatol"},{"issue":"4","key":"1191_CR29","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1002\/art.41561","volume":"73","author":"S Luo","year":"2021","unstructured":"Luo S, Clarke SLN, Ramanan AV, Thompson SD, Langefeld CD, Marion MC, et al. Platelet glycoprotein Ib \u03b1-Chain as a putative therapeutic target for juvenile idiopathic arthritis: A Mendelian randomization study. Arthritis Rheumatol. 2021;73(4):693\u2013701. https:\/\/doi.org\/10.1002\/art.41561.","journal-title":"Arthritis Rheumatol"},{"key":"1191_CR30","doi-asserted-by":"publisher","first-page":"109170","DOI":"10.1016\/j.clim.2022.109170","volume":"245","author":"Z Parackova","year":"2022","unstructured":"Parackova Z, Zentsova I, Horvath R, Malcova H, Cebecauerova D, Sediva A, et al. Immunomodulation of neutrophils and platelets by TNF blockage in patients with juvenile idiopathic arthritis. Clin Immunol. 2022;245:109170. https:\/\/doi.org\/10.1016\/j.clim.2022.109170.","journal-title":"Clin Immunol"},{"key":"1191_CR31","doi-asserted-by":"publisher","first-page":"650619","DOI":"10.3389\/fmed.2021.650619","volume":"8","author":"L Lamot","year":"2021","unstructured":"Lamot L, Miler M, Vukojevi\u0107 R, Vidovi\u0107 M, Lamot M, Trutin I, et al. The increased levels of fecal calprotectin in children with active enthesitis related arthritis and MRI signs of sacroiliitis: the results of a single center Cross-Sectional exploratory study in juvenile idiopathic arthritis patients. Front Med (Lausanne). 2021;8:650619. https:\/\/doi.org\/10.3389\/fmed.2021.650619.","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"1191_CR32","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12969-016-0104-6","volume":"14","author":"M Arvonen","year":"2016","unstructured":"Arvonen M, Berntson L, Pokka T, Karttunen TJ, Vahasalo P, Stoll ML. Gut microbiota-host interactions and juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):44. https:\/\/doi.org\/10.1186\/s12969-016-0104-6.","journal-title":"Pediatr Rheumatol Online J"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-026-01191-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-026-01191-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-026-01191-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:10:55Z","timestamp":1781633455000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12969-026-01191-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1191"],"URL":"https:\/\/doi.org\/10.1186\/s12969-026-01191-x","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]},"assertion":[{"value":"12 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2026","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 study was approved by the Regional Ethics Committee in Uppsala County (reference numbers: 2006\/327; 2006\/327\/1; 2006\/327\/3; 2014\/335; 2021\u2009\u2212\u200901614; 2022-05356-02). Verbal informed consent was obtained from parents and children and written informed consent was obtained from parents and patients older than 12 years. All procedures were conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11"}}