{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:46:36Z","timestamp":1789019196113,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2009,2,16]],"date-time":"2009-02-16T00:00:00Z","timestamp":1234742400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2009,2,16]],"date-time":"2009-02-16T00:00:00Z","timestamp":1234742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Anti-PM\/Scl antibodies are present in sera from patients with polymyositis (PM), systemic sclerosis (SSc), and PM\/SSc overlap syndromes. The prevalence of antibodies against the 75- and 100-kDa PM\/Scl proteins and their clinical associations have not been studied in SSc patients in detail so far but could provide a valuable tool for risk assessment in these patients. Furthermore, it remains speculative whether commercially available test systems detecting only anti-PM\/Scl-100 antibodies are sufficient in SSc patients.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Two hundred eighty sera from SSc patients, patients with other connective tissue diseases (n = 209), and healthy blood donors (n = 50) were analyzed for the presence of anti-PM\/Scl-75 and anti-PM\/Scl-100 antibodies by means of line immunoblot assay. For the SSc patients, possible associations between both subsets of anti-PM\/Scl antibodies with clinical and laboratory findings were studied.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>The determination of anti-PM\/Scl reactivity revealed a diagnostic sensitivity of 12.5% and a specificity of 96.9% for SSc. Among anti-PM\/Scl-positive SSc patients, 10.4% and 7.1% were positive for anti-PM\/Scl-75 and anti-PM\/Scl-100 antibodies, respectively. The highest prevalences of reactivity to PM\/Scl were detected in diffuse SSc (19.8%) and overlap syndromes (17.6%). Patients with diffuse SSc showed mainly an anti-PM\/Scl-75 response, whereas most cases of overlap syndromes were characterized by reactivity to both PM\/Scl antigens. The presence of anti-PM\/Scl-75\/100 antibodies was associated with muscular and lung involvements as well as with digital ulcers; pulmonary arterial hypertension was found less frequently. Anti-PM\/Scl-75 antibodies were detected more frequently in younger and more active patients with joint contractures. Anti-PM\/Scl-100 antibodies were associated with creatine kinase elevation; however, gastrointestinal involvements were observed less frequently.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Anti-PM\/Scl antibodies are common in distinct SSc subsets and are associated with several clinical symptoms. They are directed mainly to the PM\/Scl-75 antigen. Consequently, the detection of anti-PM\/Scl antibodies by tests based only on PM\/Scl-100 as an antigen source may miss a relevant number of SSc patients positive for these antibodies.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2614","type":"journal-article","created":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T07:14:10Z","timestamp":1234854850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Antibodies against PM\/Scl-75 and PM\/Scl-100 are independent markers for different subsets of systemic sclerosis patients"],"prefix":"10.1186","volume":"11","author":[{"given":"Katharina","family":"Hanke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia S","family":"Br\u00fcckner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"D\u00e4hnrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f6rte","family":"Huscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Komorowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthonia","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Backhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Kill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Egerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd R","family":"Burmester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Hiepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schlumberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Riemekasten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,2,16]]},"reference":[{"key":"2461_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/BF00915286","volume":"4","author":"M Reichlin","year":"1984","unstructured":"Reichlin M, Maddison PJ, Targoff I, Bunch T, Arnett F, Sharp G, Treadwell E, Tan EM: Antibodies to a nuclear\/nucleolar antigen in patients with polymyositis overlap syndromes. J Clin Immunol. 1984, 4: 40-44. 10.1007\/BF00915286.","journal-title":"J Clin Immunol"},{"key":"2461_CR2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.semarthrit.2005.03.005","volume":"35","author":"VD Steen","year":"2005","unstructured":"Steen VD: Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005, 35: 35-42. 10.1016\/j.semarthrit.2005.03.005.","journal-title":"Semin Arthritis Rheum"},{"key":"2461_CR3","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.autrev.2007.01.013","volume":"6","author":"M Mahler","year":"2007","unstructured":"Mahler M, Raijmakers R: Novel aspects of autoantibodies to the PM\/Scl complex: clinical, genetic and diagnostic insights. Autoimmun Rev. 2007, 6: 432-437. 10.1016\/j.autrev.2007.01.013.","journal-title":"Autoimmun Rev"},{"key":"2461_CR4","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1002\/art.1780351014","volume":"35","author":"CV Oddis","year":"1992","unstructured":"Oddis CV, Okano Y, Rudert WA, Trucco M, Duquesnoy RJ, Medsger TA: Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations. Arthritis Rheum. 1992, 35: 1211-1217. 10.1002\/art.1780351014.","journal-title":"Arthritis Rheum"},{"key":"2461_CR5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1097\/00005792-199211000-00001","volume":"71","author":"C Marguerie","year":"1992","unstructured":"Marguerie C, Bunn CC, Copier J, Bernstein RM, Gilroy JM, Black CM, So AK, Walport MJ: The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. Medicine (Baltimore). 1992, 71: 327-336. 10.1097\/00005792-199211000-00001.","journal-title":"Medicine (Baltimore)"},{"key":"2461_CR6","first-page":"129","volume":"24","author":"F Vandergheynst","year":"2006","unstructured":"Vandergheynst F, Ocmant A, Sordet C, Humbel RL, Goetz J, Roufosse F, Cogan E, Sibilia J: Anti-pm\/scl antibodies in connective tissue disease: clinical and biological assessment of 14 patients. Clin Exp Rheumatol. 2006, 24: 129-133.","journal-title":"Clin Exp Rheumatol"},{"key":"2461_CR7","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1084\/jem.173.4.941","volume":"173","author":"F Alderuccio","year":"1991","unstructured":"Alderuccio F, Chan EK, Tan EM: Molecular characterization of an autoantigen of PM-Scl in the polymyositis\/scleroderma overlap syndrome: a unique and complete human cDNA encoding an apparent 75-kD acidic protein of the nucleolar complex. J Exp Med. 1991, 173: 941-952. 10.1084\/jem.173.4.941.","journal-title":"J Exp Med"},{"key":"2461_CR8","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1084\/jem.176.4.973","volume":"176","author":"M Bl\u00fcthner","year":"1992","unstructured":"Bl\u00fcthner M, Bautz FA: Cloning and characterization of the cDNA coding for a polymyositis-scleroderma overlap syndrome-related nucleolar 100-kD protein. J Exp Med. 1992, 176: 973-980. 10.1084\/jem.176.4.973.","journal-title":"J Exp Med"},{"key":"2461_CR9","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/art.20056","volume":"50","author":"R Raijmakers","year":"2004","unstructured":"Raijmakers R, Renz M, Wiemann C, Egberts WV, Seelig HP, van Venrooij WJ, Pruijn GJ: PM-Scl-75 is the main autoantigen in patients with the polymyositis\/scleroderma overlap syndrome. Arthritis Rheum. 2004, 50: 565-569. 10.1002\/art.20056.","journal-title":"Arthritis Rheum"},{"key":"2461_CR10","doi-asserted-by":"publisher","first-page":"30698","DOI":"10.1074\/jbc.M302488200","volume":"278","author":"R Raijmakers","year":"2003","unstructured":"Raijmakers R, Egberts WV, van Venrooij WJ, Pruijn GJ: The association of the human PM\/Scl-75 autoantigen with the exosome is dependent on a newly identified N terminus. J Biol Chem. 2003, 278: 30698-30704. 10.1074\/jbc.M302488200.","journal-title":"J Biol Chem"},{"key":"2461_CR11","doi-asserted-by":"publisher","first-page":"R704","DOI":"10.1186\/ar1729","volume":"7","author":"M Mahler","year":"2005","unstructured":"Mahler M, Raijmakers R, D\u00e4hnrich C, Bl\u00fcthner M, Fritzler MJ: Clinical evaluation of autoantibodies to a novel PM\/Scl peptide antigen. Arthritis Res Ther. 2005, 7: R704-713. 10.1186\/ar1729.","journal-title":"Arthritis Res Ther"},{"key":"2461_CR12","doi-asserted-by":"publisher","first-page":"R28","DOI":"10.1186\/ar2622","volume":"11","author":"K Hanke","year":"2009","unstructured":"Hanke K, Dahnrich C, Bruckner C, Huscher D, Becker M, Janssen A, Meyer W, Egerer K, Hiepe F, Burmester G R, Schlumberger W, Riemekasten G: Diagnostic value of anti-topoisomerase I antibodies in a large monocentric cohort. Arthritis Res Ther. 2009, 11: R28-10.1186\/ar2622.","journal-title":"Arthritis Res Ther"},{"key":"2461_CR13","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1136\/ard.2006.062901","volume":"66","author":"UA Walker","year":"2007","unstructured":"Walker UA, Tyndall A, Czirj\u00e1k L, Denton C, Farge-Bancel D, Kowal-Bielecka O, M\u00fcller-Ladner U, Bocelli-Tyndall C, Matucci-Cerinic M: Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis. 2007, 66: 754-763. 10.1136\/ard.2006.062901.","journal-title":"Ann Rheum Dis"},{"key":"2461_CR14","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1093\/rheumatology\/ken179","volume":"47","author":"N Hunzelmann","year":"2008","unstructured":"Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M, Moinzadeh P, M\u00fcller-Ladner U, Pfeiffer C, Riemekasten G, Schulze-Lohoff E, Sunderkoetter C, Weber M, Worm M, Klaus P, Rubbert A, Steinbrink K, Grundt B, Hein R, Scharffetter-Kochanek K, Hinrichs R, Walker K, Szeimies RM, Karrer S, M\u00fcller A, Seitz C, Schmidt E, Lehmann P, Foeldv\u00e1ri I, Reichenberger F, et al: Registry of the German Network for Systemic Scleroderma. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford). 2008, 47: 1185-1192. 10.1093\/rheumatology\/ken179.","journal-title":"Rheumatology (Oxford)"},{"key":"2461_CR15","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1136\/ard.2006.066530","volume":"66","author":"L Czirj\u00e1k","year":"2007","unstructured":"Czirj\u00e1k L, Nagy Z, Aringer M, Riemekasten G, Matucci-Cerinic M, Furst DE, EUSTAR: The EUSTAR model for teaching and implementing the modified Rodnan skin score in systemic sclerosis. Ann Rheum Dis. 2007, 66: 966-969. 10.1136\/ard.2006.066530.","journal-title":"Ann Rheum Dis"},{"key":"2461_CR16","first-page":"202","volume":"15","author":"EC LeRoy","year":"1988","unstructured":"LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988, 15: 202-205.","journal-title":"J Rheumatol"},{"key":"2461_CR17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0889-857X(21)01048-6","volume":"16","author":"RM Bennett","year":"1990","unstructured":"Bennett RM: Scleroderma overlap syndrome. Rheum Dis Clin North Am. 1990, 16: 185-198.","journal-title":"Rheum Dis Clin North Am"},{"key":"2461_CR18","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1001\/jama.1962.03050210027006","volume":"180","author":"GP Rodnan","year":"1962","unstructured":"Rodnan GP, Fennel RH: Progressive systemic sclerosis sine scleroderma. JAMA. 1962, 180: 665-670.","journal-title":"JAMA"},{"key":"2461_CR19","first-page":"615","volume":"17","author":"M Mosca","year":"1999","unstructured":"Mosca M, Neri R, Bombardieri S: Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol. 1999, 17: 615-620.","journal-title":"Clin Exp Rheumatol"},{"key":"2461_CR20","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/art.1780360309","volume":"36","author":"C Vitali","year":"1993","unstructured":"Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB, Braga S, Coll J, de Vita S, Drosos AA, Ehrenfeld M, Hatron PY, Hay EM, Isenberg DA, Janin A, Kalden JR, Kater L, Konttinen YT, Maddison PJ, Maini RN, Manthorpe R, Meyer O, Ostuni P, Pennec Y, Prause JU, Richards A, Sauvezie B, Schi\u00f8dt M, Sciuto M, et al: Preliminary criteria for the classification of Sj\u00f6gren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993, 36: 340-347. 10.1002\/art.1780360309.","journal-title":"Arthritis Rheum"},{"key":"2461_CR21","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1002\/art.1780251101","volume":"25","author":"EM Tan","year":"1982","unstructured":"Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277. 10.1002\/art.1780251101.","journal-title":"Arthritis Rheum"},{"key":"2461_CR22","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002\/art.1780310302.","journal-title":"Arthritis Rheum"},{"key":"2461_CR23","first-page":"84","volume":"25","author":"DE Furst","year":"1998","unstructured":"Furst DE, Clements PJ, Steen VD, Medsger TA, Masi AT, D'Angelo WA, Lachenbruch PA, Grau RG, Seibold JR: The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol. 1998, 25: 84-88.","journal-title":"J Rheumatol"},{"key":"2461_CR24","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1136\/ard.62.9.901","volume":"62","author":"G Valentini","year":"2003","unstructured":"Valentini G, Bencivelli W, Bombardieri S, D'Angelo S, Della Rossa A, Silman AJ, Black CM, Czirjak L, Nielsen H, Vlachoyiannopoulos PG: European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria. Ann Rheum Dis. 2003, 62: 901-903. 10.1136\/ard.62.9.901.","journal-title":"Ann Rheum Dis"},{"key":"2461_CR25","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s001099900072","volume":"78","author":"M Bl\u00fcthner","year":"2000","unstructured":"Bl\u00fcthner M, Mahler M, M\u00fcller DB, D\u00fcnzl H, Bautz FA: Identification of an alpha-helical epitope region on the PM\/Scl-100 autoantigen with structural homology to a region on the heterochromatin p25beta autoantigen using immobilized overlapping synthetic peptides. J Mol Med. 2000, 78: 47-54. 10.1007\/s001090050381.","journal-title":"J Mol Med"},{"key":"2461_CR26","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1002\/art.22237","volume":"55","author":"A Selva-O'Callaghan","year":"2006","unstructured":"Selva-O'Callaghan A, Labrador-Horrillo M, Solans-Laque R, Simeon-Aznar CP, Mart\u00ednez-G\u00f3mez X, Vilardell-Tarr\u00e9s M: Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy. Arthritis Rheum. 2006, 55: 791-798. 10.1002\/art.22237.","journal-title":"Arthritis Rheum"},{"key":"2461_CR27","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/ar389","volume":"4","author":"R Brouwer","year":"2002","unstructured":"Brouwer R, Vree Egberts WT, Hengstman GJ, Raijmakers R, van Engelen BG, Seelig HP, Renz M, Mierau R, Genth E, Pruijn GJ, van Venrooij WJ: Autoantibodies directed to novel components of the PM\/Scl complex, the human exosome. Arthritis Res. 2002, 4: 134-138. 10.1186\/ar389.","journal-title":"Arthritis Res"},{"key":"2461_CR28","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1136\/ard.60.2.116","volume":"60","author":"R Brouwer","year":"2001","unstructured":"Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, Gr\u00f8ndal G, Hietarinta M, Isenberg D, Kalden JR, Lundberg I, Moutsopoulos H, Roux-Lombard P, Vencovsky J, Wikman A, Seelig HP, van Engelen BG, van Venrooij WJ: Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001, 60: 116-123. 10.1136\/ard.60.2.116.","journal-title":"Ann Rheum Dis"},{"key":"2461_CR29","unstructured":"Mahler M, Mierau R, Humbel RL, Fritzler MJ: Anti-PM1-alpha antibodies: analytical evaluation in two centers. Paper presented at: 6th International Congress on Autoimmunity; 10\u201314 September 2008; Porto, Portugal"},{"key":"2461_CR30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1159\/000063865","volume":"128","author":"M Schmidt","year":"2002","unstructured":"Schmidt M, Hoffman DR: Expression systems for production of recombinant allergens. Int Arch Allergy Immunol. 2002, 128: 264-270. 10.1159\/000063865.","journal-title":"Int Arch Allergy Immunol"},{"key":"2461_CR31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/j.1745-7254.2005.00078.x","volume":"26","author":"YC Hu","year":"2005","unstructured":"Hu YC: Baculovirus as a highly efficient expression vector in insect and mammalian cells. Acta Pharmacol Sin. 2005, 26: 405-416. 10.1111\/j.1745-7254.2005.00078.x. Review","journal-title":"Acta Pharmacol Sin"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar2614\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T11:09:17Z","timestamp":1728385757000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar2614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,16]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2009,2]]}},"alternative-id":["2461"],"URL":"https:\/\/doi.org\/10.1186\/ar2614","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,16]]},"assertion":[{"value":"23 October 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2009","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2009","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2009","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R22"}}