{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T15:11:18Z","timestamp":1726413078455},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Z Rheumatol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1007\/s00393-019-00708-y","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T08:05:57Z","timestamp":1568102757000},"page":"5-12","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pathogenese der Spondyloarthritiden","Pathogenesis of spondylarthritis"],"prefix":"10.1007","volume":"79","author":[{"given":"J.","family":"Sieper","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Poddubnyy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"708_CR1","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.semarthrit.2018.05.011","volume":"48","author":"EG Araujo","year":"2019","unstructured":"Araujo\u00a0EG, Englbrecht\u00a0M, Hoepken\u00a0S et\u00a0al (2019) Effects of ustekinumab versus tumor necrosis factor inhibition on enthesitis: results from the enthesial clearance in psoriatic arthritis (ECLIPSA) study. Semin Arthritis Rheum 48:632\u2013637","journal-title":"Semin Arthritis Rheum"},{"key":"708_CR2","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1136\/annrheumdis-2018-213328","volume":"77","author":"D Baeten","year":"2018","unstructured":"Baeten\u00a0D, Ostergaard\u00a0M, Wei\u00a0JC et al (2018) Risankizumab, an IL\u201123 inhibitor, for ankylosing spondylitis: results of a\u00a0randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis 77:1295\u20131302","journal-title":"Ann Rheum Dis"},{"key":"708_CR3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature04753","volume":"441","author":"E Bettelli","year":"2006","unstructured":"Bettelli\u00a0E, Carrier\u00a0Y, Gao\u00a0W et\u00a0al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235\u2013238","journal-title":"Nature"},{"key":"708_CR4","doi-asserted-by":"publisher","first-page":"e2095","DOI":"10.7717\/peerj.2095","volume":"4","author":"JE Bisanz","year":"2016","unstructured":"Bisanz\u00a0JE, Suppiah\u00a0P, Thomson\u00a0WM et\u00a0al (2016) The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals. Peer\u00a0J 4:e2095","journal-title":"Peer J"},{"key":"708_CR5","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key375","author":"J Braun","year":"2018","unstructured":"Braun\u00a0J, Baraliakos\u00a0X, Deodhar\u00a0A et al (2018) Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4\u2011year results from the MEASURE 1 study. Rheumatology (Oxford). \nhttps:\/\/doi.org\/10.1093\/rheumatology\/key375","journal-title":"Rheumatology (Oxford)"},{"key":"708_CR6","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/art.1780380407","volume":"38","author":"J Braun","year":"1995","unstructured":"Braun\u00a0J, Bollow\u00a0M, Neure\u00a0L et\u00a0al (1995) Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 38:499\u2013505","journal-title":"Arthritis Rheum"},{"key":"708_CR7","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1136\/annrheumdis-2016-211064","volume":"76","author":"M Breban","year":"2017","unstructured":"Breban\u00a0M, Tap\u00a0J, Leboime\u00a0A et\u00a0al (2017) Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis 76:1614\u20131622","journal-title":"Ann Rheum Dis"},{"key":"708_CR8","doi-asserted-by":"publisher","first-page":"4613","DOI":"10.1038\/s41467-018-06933-4","volume":"9","author":"I Cambre","year":"2018","unstructured":"Cambre\u00a0I, Gaublomme\u00a0D, Burssens\u00a0A et al (2018) Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nat Commun 9:4613","journal-title":"Nat Commun"},{"issue":"3","key":"708_CR9","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1002\/art.38967","volume":"67","author":"ME Costello","year":"2015","unstructured":"Costello\u00a0ME, Ciccia\u00a0F, Willner\u00a0D et\u00a0al (2015) Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol 67(3):686-691","journal-title":"Arthritis Rheumatol"},{"key":"708_CR10","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/art.40728","volume":"71","author":"A Deodhar","year":"2019","unstructured":"Deodhar\u00a0A, Gensler\u00a0LS, Sieper\u00a0J et al (2019) Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of Ustekinumab in axial Spondyloarthritis. Arthritis Rheumatol 71:258\u2013270","journal-title":"Arthritis Rheumatol"},{"key":"708_CR11","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/s41584-018-0091-8","volume":"14","author":"EM Gravallese","year":"2018","unstructured":"Gravallese\u00a0EM, Schett\u00a0G (2018) Effects of the IL\u201123-IL\u201117 pathway on bone in spondyloarthritis. Nat Rev Rheumatol 14:631\u2013640","journal-title":"Nat Rev Rheumatol"},{"key":"708_CR12","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1136\/gutjnl-2011-301668","volume":"61","author":"W Hueber","year":"2012","unstructured":"Hueber\u00a0W, Sands\u00a0BE, Lewitzky\u00a0S et al (2012) Secukinumab, a\u00a0human anti-IL\u201117A monoclonal antibody, for moderate to severe Crohn\u2019s disease: unexpected results of a\u00a0randomised, double-blind placebo-controlled trial. Gut 61:1693\u20131700","journal-title":"Gut"},{"key":"708_CR13","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.immuni.2015.09.003","volume":"43","author":"JS Lee","year":"2015","unstructured":"Lee\u00a0JS, Tato\u00a0CM, Joyce-Shaikh\u00a0B et al (2015) Interleukin-23-independent IL\u201117 production regulates intestinal epithelial permeability. Immunity 43:727\u2013738","journal-title":"Immunity"},{"key":"708_CR14","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1124\/jpet.115.224246","volume":"354","author":"PR Mangan","year":"2015","unstructured":"Mangan\u00a0PR, Su\u00a0LJ, Jenny\u00a0V et al (2015) Dual inhibition of Interleukin-23 and Interleukin-17 offers superior efficacy in mouse models of autoimmunity. J\u00a0Pharmacol Exp Ther 354:152\u2013165","journal-title":"J Pharmacol Exp Ther"},{"key":"708_CR15","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/S0140-6736(97)12004-9","volume":"352","author":"D Mcgonagle","year":"1998","unstructured":"Mcgonagle\u00a0D, Gibbon\u00a0W, Emery\u00a0P (1998) Classification of inflammatory arthritis by enthesitis. Lancet 352:1137\u20131140","journal-title":"Lancet"},{"key":"708_CR16","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/S0140-6736(13)60594-2","volume":"382","author":"IB Mcinnes","year":"2013","unstructured":"Mcinnes\u00a0IB, Kavanaugh\u00a0A, Gottlieb\u00a0AB et al (2013) Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 382:780\u2013789","journal-title":"Lancet"},{"key":"708_CR17","first-page":"2279","volume":"22","author":"H Mielants","year":"1995","unstructured":"Mielants\u00a0H, Veys\u00a0EM, Cuvelier\u00a0C et\u00a0al (1995) The evolution of spondyloarthropathies in relation to gut histology. III. Relation between gut and joint. J\u00a0Rheumatol 22:2279\u20132284","journal-title":"J Rheumatol"},{"key":"708_CR18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1136\/annrheumdis-2017-211544","volume":"77","author":"C Molnar","year":"2018","unstructured":"Molnar\u00a0C, Scherer\u00a0A, Baraliakos\u00a0X et\u00a0al (2018) TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort. Ann Rheum Dis 77:63\u201369","journal-title":"Ann Rheum Dis"},{"key":"708_CR19","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/cei.12830","volume":"186","author":"M Noack","year":"2016","unstructured":"Noack\u00a0M, Ndongo-Thiam\u00a0N, Miossec\u00a0P (2016) Role of podoplanin in the high interleukin-17A secretion resulting from interactions between activated lymphocytes and psoriatic skin-derived mesenchymal cells. Clin Exp Immunol 186:64\u201374","journal-title":"Clin Exp Immunol"},{"key":"708_CR20","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1189\/jlb.3HI1215-542R","volume":"100","author":"T Noordenbos","year":"2016","unstructured":"Noordenbos\u00a0T, Blijdorp\u00a0I, Chen\u00a0S et al (2016) Human mast cells capture, store, and release bioactive, exogenous IL\u201117A. J\u00a0Leukoc Biol 100:453\u2013462","journal-title":"J Leukoc Biol"},{"key":"708_CR21","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.berh.2010.05.001","volume":"24","author":"D Poddubnyy","year":"2010","unstructured":"Poddubnyy\u00a0D, Appel\u00a0H, Sieper\u00a0J (2010) Investigation of involved tissue in axial spondyloarthritis\u2014what have we learnt from immunohistochemical studies? Best Pract Res Clin Rheumatol 24:715\u2013719","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"708_CR22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s11926-017-0681-5","volume":"19","author":"D Poddubnyy","year":"2017","unstructured":"Poddubnyy\u00a0D, Sieper\u00a0J (2017) Mechanism of new bone formation in axial spondyloarthritis. Curr Rheumatol Rep 19:55","journal-title":"Curr Rheumatol Rep"},{"issue":"7","key":"708_CR23","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1093\/rheumatology\/kex361","volume":"57","author":"D Poddubnyy","year":"2018","unstructured":"Poddubnyy\u00a0D, Sieper\u00a0J (2018) What is the best treatment target in axial spondyloarthritis: tumour necrosis factor alpha, interleukin 17, or both? Rheumatology (Oxford) 57(7):1145\u20131150","journal-title":"Rheumatology (Oxford)"},{"key":"708_CR24","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nrrheum.2017.56","volume":"13","author":"V Ranganathan","year":"2017","unstructured":"Ranganathan\u00a0V, Gracey\u00a0E, Brown\u00a0MA et\u00a0al (2017) Pathogenesis of ankylosing spondylitis\u2014recent advances and future directions. Nat Rev Rheumatol 13:359\u2013367","journal-title":"Nat Rev Rheumatol"},{"key":"708_CR25","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1093\/rheumatology\/keu356","volume":"54","author":"T Ratz","year":"2015","unstructured":"Ratz\u00a0T, Dean\u00a0LE, Atzeni\u00a0F et al (2015) A possible link between ankylosing spondylitis and periodontitis: a\u00a0systematic review and meta-analysis. Rheumatology (Oxford) 54:500\u2013510","journal-title":"Rheumatology (Oxford)"},{"key":"708_CR26","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13075-018-1639-3","volume":"20","author":"EH Regner","year":"2018","unstructured":"Regner\u00a0EH, Ohri\u00a0N, Stahly\u00a0A et\u00a0al (2018) Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota. Arthritis Res Ther 20:149","journal-title":"Arthritis Res Ther"},{"key":"708_CR27","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s11926-016-0614-8","volume":"18","author":"JT Rosenbaum","year":"2016","unstructured":"Rosenbaum\u00a0JT, Asquith\u00a0MJ (2016) The Microbiome: a\u00a0revolution in treatment for rheumatic diseases? Curr Rheumatol Rep 18:62","journal-title":"Curr Rheumatol Rep"},{"key":"708_CR28","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nm.2817","volume":"18","author":"JP Sherlock","year":"2012","unstructured":"Sherlock\u00a0JP, Joyce-Shaikh\u00a0B, Turner\u00a0SP et al (2012) IL\u201123 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med 18:1069\u20131076","journal-title":"Nat Med"},{"key":"708_CR29","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1136\/annrheumdis-2015-207897","volume":"75","author":"J Sieper","year":"2016","unstructured":"Sieper\u00a0J, Listing\u00a0J, Poddubnyy\u00a0D et al (2016) Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a\u00a0randomised multicentre trial (ENRADAS). Ann Rheum Dis 75:1438\u20131443","journal-title":"Ann Rheum Dis"},{"key":"708_CR30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","volume":"390","author":"J Sieper","year":"2017","unstructured":"Sieper\u00a0J, Poddubnyy\u00a0D (2017) Axial spondyloarthritis. Lancet 390:73\u201384","journal-title":"Lancet"},{"key":"708_CR31","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/nrrheum.2016.42","volume":"12","author":"J Sieper","year":"2016","unstructured":"Sieper\u00a0J, Poddubnyy\u00a0D (2016) New evidence on the management of spondyloarthritis. Nat Rev Rheumatol 12:282\u2013295","journal-title":"Nat Rev Rheumatol"},{"key":"708_CR32","doi-asserted-by":"publisher","first-page":"795","DOI":"10.3389\/fimmu.2018.00795","volume":"9","author":"N Tamassia","year":"2018","unstructured":"Tamassia\u00a0N, Arruda-Silva\u00a0F, Calzetti\u00a0F et al (2018) A reappraisal on the potential ability of human neutrophils to express and produce IL\u201117 family members in vitro: failure to reproducibly detect it. Front Immunol 9:795","journal-title":"Front Immunol"},{"key":"708_CR33","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1084\/jem.180.6.2359","volume":"180","author":"JD Taurog","year":"1994","unstructured":"Taurog\u00a0JD, Richardson\u00a0JA, Croft\u00a0JT et al (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J\u00a0Exp Med 180:2359\u20132364","journal-title":"J Exp Med"},{"key":"708_CR34","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/art.39802","volume":"69","author":"RY Tito","year":"2017","unstructured":"Tito\u00a0RY, Cypers\u00a0H, Joossens\u00a0M et\u00a0al (2017) Brief report: Dialister as a\u00a0microbial marker of disease activity in Spondyloarthritis. Arthritis Rheumatol 69:114\u2013121","journal-title":"Arthritis Rheumatol"},{"issue":"7","key":"708_CR35","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1080\/14712598.2019.1605352","volume":"19","author":"M Torgutalp","year":"2019","unstructured":"Torgutalp\u00a0M, Poddubnyy\u00a0D (2019) IL\u201117 inhibition in axial spondyloarthritis: current and future perspectives. Expert Opin Biol Ther 19(7):631\u2013641","journal-title":"Expert Opin Biol Ther"},{"key":"708_CR36","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1136\/annrheumdis-2017-212377","volume":"77","author":"D Van Der Heijde","year":"2018","unstructured":"Van Der Heijde\u00a0D, Baraliakos\u00a0X, Hermann\u00a0KA et al (2018) Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4\u2011year imaging outcomes from the RAPID-axSpA phase III randomised trial. Ann Rheum Dis 77:699\u2013705","journal-title":"Ann Rheum Dis"},{"key":"708_CR37","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1136\/annrheumdis-2013-203854","volume":"73","author":"L Van Praet","year":"2014","unstructured":"Van Praet\u00a0L, Jans\u00a0L, Carron\u00a0P et\u00a0al (2014) Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann Rheum Dis 73:1186\u20131189","journal-title":"Ann Rheum Dis"},{"key":"708_CR38","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1002\/art.21054","volume":"52","author":"A Wanders","year":"2005","unstructured":"Wanders\u00a0A, Heijde\u00a0D, Landewe\u00a0R et\u00a0al (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a\u00a0randomized clinical trial. Arthritis Rheum 52:1756\u20131765","journal-title":"Arthritis Rheum"},{"key":"708_CR39","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1038\/ng.2007.17","volume":"39","author":"PR Burton","year":"2007","unstructured":"Wellcome Trust Case Control C, Australo-Anglo-American Spondylitis C, Burton\u00a0PR et al (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 39:1329\u20131337","journal-title":"Nat Genet"},{"key":"708_CR40","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13059-017-1271-6","volume":"18","author":"C Wen","year":"2017","unstructured":"Wen\u00a0C, Zheng\u00a0Z, Shao\u00a0T et\u00a0al (2017) Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 18:142","journal-title":"Genome Biol"},{"key":"708_CR41","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00296-018-4012-6","volume":"38","author":"D Ziebolz","year":"2018","unstructured":"Ziebolz\u00a0D, Douglas\u00a0D, Douglas\u00a0D et al (2018) Periodontal condition is associated with disease duration and motoric disabilities in patients with ankylosing spondylitis: results of a\u00a0cross-sectional study. Rheumatol Int 38:855\u2013863","journal-title":"Rheumatol Int"}],"container-title":["Zeitschrift f\u00fcr Rheumatologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00393-019-00708-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00393-019-00708-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00393-019-00708-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T10:52:15Z","timestamp":1599735135000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00393-019-00708-y"}},"subtitle":["Relevanz f\u00fcr die Therapie","Relevance for treatment"],"short-title":[],"issued":{"date-parts":[[2019,9,10]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["708"],"URL":"https:\/\/doi.org\/10.1007\/s00393-019-00708-y","relation":{},"ISSN":["0340-1855","1435-1250"],"issn-type":[{"type":"print","value":"0340-1855"},{"type":"electronic","value":"1435-1250"}],"subject":[],"published":{"date-parts":[[2019,9,10]]},"assertion":[{"value":"10 September 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Einhaltung ethischer Richtlinien"}},{"value":"J.\u00a0Sieper: Forschungsf\u00f6rderung durch: AbbVie, BMS, MSD, Novartis, Pfizer, Roche; Referenten\u2011\/Beratert\u00e4tigkeit f\u00fcr: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. D.\u00a0Poddubnyy: Forschungsf\u00f6rderung durch: AbbVie, Lilly, MSD, Novartis, Pfizer; Referenten\u2011\/Beratert\u00e4tigkeit f\u00fcr: AbbVie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Interessenkonflikt"}},{"value":"F\u00fcr diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgef\u00fchrt. F\u00fcr die aufgef\u00fchrten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Interessenkonflikt"}}]}}