{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:47:50Z","timestamp":1790293670233,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39\/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition<jats:italic>in vivo<\/jats:italic>via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Normal and malignant lymphocytes were isolated from whole blood from patients with CLL and healthy volunteers. Enzyme activity was measured via radio-TLC assay and expression via FACS. Semi-quantititative RT-PCR for CD39 splice variants and platelet function tests were performed on several samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Functional assays demonstrated that ADPase and ATPase activities were much higher in CLL cells than in total lymphocytes from the normal population on a per cell basis (p-value &lt; 0.00001). CD39 activity was elevated in stage 0\u20132 CLL compared to stage 3\u20134 (p &lt; 0.01). FACS of lymphocytes demonstrated CD39 expression on &gt; 90% of normal and malignant B-lymphocytes and ~8% of normal T-lymphocytes. RT-PCR showed increased full length CD39 and splice variant 1.5, but decreased variant 1.3 in CLL cells. Platelet function tests showed inhibition of platelet activation and recruitment to ADP by CLL cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD39 is expressed and active on CLL cells. Enzyme activity is higher in earlier stages of CLL and decreased enzyme activity may be associated with worsening disease. These results suggest that CD39 may play a role in the pathogenesis of malignancy and protect CLL patients from thrombotic events.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1479-5876-5-23","type":"journal-article","created":{"date-parts":[[2007,5,4]],"date-time":"2007-05-04T19:00:33Z","timestamp":1178305233000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia"],"prefix":"10.1186","volume":"5","author":[{"given":"Dianne","family":"Pulte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim E","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Johan","family":"Broekman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naziba","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold S","family":"Ballard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R","family":"Furman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,5,4]]},"reference":[{"key":"183_CR1","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1056\/NEJM199510193331606","volume":"333","author":"C Rozman","year":"1995","unstructured":"Rozman C, Montserrat E: Chronic lymphocytic leukemia. N Engl J Med. 1995, 333: 1052-1057. 10.1056\/NEJM199510193331606.","journal-title":"N Engl J Med"},{"key":"183_CR2","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3322\/canjclin.56.2.106","volume":"56","author":"A Jemal","year":"2006","unstructured":"Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ: Cancer statistics, 2006. CA Cancer J Clin. 2006, 56: 106-130.","journal-title":"CA Cancer J Clin"},{"key":"183_CR3","doi-asserted-by":"crossref","first-page":"4990","DOI":"10.1182\/blood.V87.12.4990.bloodjournal87124990","volume":"87","author":"BD Cheson","year":"1996","unstructured":"Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996, 87: 4990-4997.","journal-title":"Blood"},{"key":"183_CR4","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1080\/1042819021000006367","volume":"43","author":"T Cukierman","year":"2002","unstructured":"Cukierman T, Gatt ME, Libster D, Goldschmidt N, Matzner Y: Chronic lymphocytic leukemia presenting with extreme hyperleukocytosis and thrombosis of the common femoral vein. Leuk Lymphoma. 2002, 43: 1865-1868. 10.1080\/1042819021000006367.","journal-title":"Leuk Lymphoma"},{"key":"183_CR5","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1002\/1097-0142(19890401)63:7<1398::AID-CNCR2820630727>3.0.CO;2-F","volume":"63","author":"MG Conlan","year":"1989","unstructured":"Conlan MG, Mosher DF: Concomitant chronic lymphocytic leukemia, acute myeloid leukemia, and thrombosis with protein C deficiency. Case report and review of the literature. Cancer. 1989, 63: 1398-1401. 10.1002\/1097-0142(19890401)63:7<1398::AID-CNCR2820630727>3.0.CO;2-F.","journal-title":"Cancer"},{"key":"183_CR6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1163\/15685590051129896","volume":"30","author":"P Miljic","year":"2000","unstructured":"Miljic P, Milosevic-Jovicic N, Antunovic P, Boskovic D, Basara N, Rolovic Z: Recurrent venous thrombosis in a patient with chronic lymphocytic leukemia and acquired protein S deficiency. Haematologia (Budap ). 2000, 30: 51-54. 10.1163\/15685590051129896.","journal-title":"Haematologia (Budap )"},{"key":"183_CR7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1080\/02688699844934","volume":"12","author":"JE Bromberg","year":"1998","unstructured":"Bromberg JE, Vandertop WP, Jansen GH: Recurrent subdural haematoma as the primary and sole manifestation of chronic lymphocytic leukaemia. Br J Neurosurg. 1998, 12: 373-376. 10.1080\/02688699844934.","journal-title":"Br J Neurosurg"},{"key":"183_CR8","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/ajh.2830420215","volume":"42","author":"M Dhodapkar","year":"1993","unstructured":"Dhodapkar M, Yale SH, Hoagland HC: Hemorrhagic pleural effusion and pleural thickening as a complication of chronic lymphocytic leukemia. Am J Hematol. 1993, 42: 221-224. 10.1002\/ajh.2830420215.","journal-title":"Am J Hematol"},{"key":"183_CR9","first-page":"635","volume":"90","author":"DO Faigel","year":"1995","unstructured":"Faigel DO, Vaughn DJ, Furth EE, Metz DC: Chronic lymphocytic leukemia: an unusual cause of upper gastrointestinal hemorrhage. Am J Gastroenterol. 1995, 90: 635-637.","journal-title":"Am J Gastroenterol"},{"key":"183_CR10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00277-003-0723-0","volume":"83","author":"R Ali","year":"2004","unstructured":"Ali R, Ozkalemkas F, Ozkocaman V, Bulbul-Baskan E, Ozcelik T, Ozan U, Kimya Y, Tunali A: Successful labor in the course of chronic lymphocytic leukemia (CLL) and management of CLL during pregnancy with leukapheresis. Ann Hematol. 2004, 83: 61-63. 10.1007\/s00277-003-0723-0.","journal-title":"Ann Hematol"},{"key":"183_CR11","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/ajh.10216","volume":"71","author":"G Gurman","year":"2002","unstructured":"Gurman G: Pregnancy and successful labor in the course of chronic lymphocytic leukemia. Am J Hematol. 2002, 71: 208-210. 10.1002\/ajh.10216.","journal-title":"Am J Hematol"},{"key":"183_CR12","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.1182\/blood.V99.11.4087","volume":"99","author":"RN Damle","year":"2002","unstructured":"Damle RN, Ghiotto F, Valetto A, Albesiano E, Fais F, Yan XJ, Sison CP, Allen SL, Kolitz J, Schulman P, Vinciguerra VP, Budde P, Frey J, Rai KR, Ferrarini M, Chiorazzi N: B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. Blood. 2002, 99: 4087-4093. 10.1182\/blood.V99.11.4087.","journal-title":"Blood"},{"key":"183_CR13","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1182\/blood.V93.2.624","volume":"93","author":"S Sembries","year":"1999","unstructured":"Sembries S, Pahl H, Stilgenbauer S, Dohner H, Schriever F: Reduced expression of adhesion molecules and cell signaling receptors by chronic lymphocytic leukemia cells with 11q deletion. Blood. 1999, 93: 624-631.","journal-title":"Blood"},{"key":"183_CR14","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.4049\/jimmunol.146.7.2235","volume":"146","author":"GS Kansas","year":"1991","unstructured":"Kansas GS, Wood GS, Tedder TF: Expression, distribution, and biochemistry of human CD39. Role in activation-associated homotypic adhesion of lymphocytes. J Immunol. 1991, 146: 2235-2244.","journal-title":"J Immunol"},{"key":"183_CR15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1124\/jpet.102.043729","volume":"305","author":"AJ Marcus","year":"2003","unstructured":"Marcus AJ, Broekman MJ, Drosopoulos JHF, Islam N, Pinsky DJ, Sesti C, Levi R: Metabolic control of excessive extracellular nucleotide accumulation by CD39\/ecto-nucleotidase-1: Implications for ischemic vascular diseases. J Pharmacol Exp Ther. 2003, 305: 9-16. 10.1124\/jpet.102.043729.","journal-title":"J Pharmacol Exp Ther"},{"key":"183_CR16","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1093\/intimm\/11.5.739","volume":"11","author":"S Ingvarsson","year":"1999","unstructured":"Ingvarsson S, Dahlenborg K, Carlsson R, Borrebaeck CA: Co-ligation of CD44 on naive human tonsillar B cells induces progression towards a germinal center phenotype. Int Immunol. 1999, 11: 739-744. 10.1093\/intimm\/11.5.739.","journal-title":"Int Immunol"},{"key":"183_CR17","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1182\/blood.V89.3.919","volume":"89","author":"JD Pound","year":"1997","unstructured":"Pound JD, Gordon J: Maintenance of human germinal center B cells in vitro. Blood. 1997, 89: 919-928.","journal-title":"Blood"},{"key":"183_CR18","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/nm0402-358","volume":"8","author":"N Mizumoto","year":"2002","unstructured":"Mizumoto N, Kumamoto T, Robson SC, Sevigny J, Matsue H, Enjyoji K, Takashima A: CD39 is the dominant Langerhans cell-associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness. Nat Med. 2002, 8: 358-365. 10.1038\/nm0402-358.","journal-title":"Nat Med"},{"key":"183_CR19","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.4049\/jimmunol.170.6.2962","volume":"170","author":"HP Langston","year":"2003","unstructured":"Langston HP, Ke Y, Gewirtz AT, Dombrowski KE, Kapp JA: Secretion of IL-2 and IFN-gamma, but not IL-4, by antigen-specific T cells requires extracellular ATP. J Immunol. 2003, 170: 2962-2970.","journal-title":"J Immunol"},{"key":"183_CR20","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1172\/JCI1753","volume":"101","author":"RB Gayle III","year":"1998","unstructured":"Gayle RB, Maliszewski CR, Gimpel SD, Schoenborn MA, Caspary RG, Richards C, Brasel K, Price V, Drosopoulos JH, Islam N, Alyonycheva TN, Broekman MJ, Marcus AJ: Inhibition of platelet function by recombinant soluble ecto-ADPase\/CD39. J Clin Invest. 1998, 101: 1851-1859.","journal-title":"J Clin Invest"},{"key":"183_CR21","doi-asserted-by":"publisher","first-page":"6936","DOI":"10.1021\/bi992581e","volume":"39","author":"JH Drosopoulos","year":"2000","unstructured":"Drosopoulos JH, Broekman MJ, Islam N, Maliszewski CR, Gayle RB, Marcus AJ: Site-directed mutagenesis of human endothelial cell ecto-ADPase\/soluble CD39: requirement of glutamate 174 and serine 218 for enzyme activity and inhibition of platelet recruitment. Biochemistry. 2000, 39: 6936-6943. 10.1021\/bi992581e.","journal-title":"Biochemistry"},{"key":"183_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.thromres.2004.11.024","volume":"116","author":"MM El-Omar","year":"2005","unstructured":"El-Omar MM, Islam N, Broekman MJ, Drosopoulos JH, Roa DC, Lorin JD, Sedlis SP, Olson KE, Pulte ED, Marcus AJ: The ratio of ADP- to ATP-ectonucleotidase activity is reduced in patients with coronary artery disease. Thromb Res. 2005, 116: 199-206. 10.1016\/j.thromres.2004.11.024.","journal-title":"Thromb Res"},{"key":"183_CR23","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1172\/JCI19560","volume":"113","author":"KM Dwyer","year":"2004","unstructured":"Dwyer KM, Robson SC, Nandurkar HH, Campbell DJ, Gock H, Murray-Segal LJ, Fisicaro N, Mysore TB, Kaczmarek E, Cowan PJ, d'Apice AJ: Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation. J Clin Invest. 2004, 113: 1440-1446. 10.1172\/JCI200419560.","journal-title":"J Clin Invest"},{"key":"183_CR24","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1152\/japplphysiol.00315.2004","volume":"98","author":"A Coppola","year":"2005","unstructured":"Coppola A, Coppola L, dalla ML, Limongelli FM, Grassia A, Mastrolorenzo L, Gombos G, Lucivero G: Vigorous exercise acutely changes platelet and B-lymphocyte CD39 expression. J Appl Physiol. 2005, 98: 1414-1419. 10.1152\/japplphysiol.00315.2004.","journal-title":"J Appl Physiol"},{"key":"183_CR25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11239-005-1381-y","volume":"19","author":"JM Buergler","year":"2005","unstructured":"Buergler JM, Maliszewski CR, Broekman MJ, Kaluza GL, Schulz DG, Marcus AJ, Raizner AE, Kleiman NS, Ali NM: Effects of SolCD39, a novel inhibitor of Platelet Aggregation, on Platelet Deposition and Aggregation after PTCA in a Porcine Model. J Thromb Thrombolysis. 2005, 19: 115-122. 10.1007\/s11239-005-1381-y.","journal-title":"J Thromb Thrombolysis"},{"key":"183_CR26","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/S0014-5793(98)00603-6","volume":"430","author":"KN Dzhandzhugazyan","year":"1998","unstructured":"Dzhandzhugazyan KN, Kirkin AF, thor SP, Zeuthen J: Ecto-ATP diphosphohydrolase\/CD39 is overexpressed in differentiated human melanomas. FEBS Lett. 1998, 430: 227-230. 10.1016\/S0014-5793(98)00603-6.","journal-title":"FEBS Lett"},{"key":"183_CR27","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1177\/002215540205000412","volume":"50","author":"A Kittel","year":"2002","unstructured":"Kittel A, Garrido M, Varga G: Localization of NTPDase1\/CD39 in normal and transformed human pancreas. J Histochem Cytochem. 2002, 50: 549-556.","journal-title":"J Histochem Cytochem"},{"key":"183_CR28","doi-asserted-by":"crossref","first-page":"C973","DOI":"10.1152\/ajpcell.1997.273.3.C973","volume":"273","author":"EE Clifford","year":"1997","unstructured":"Clifford EE, Martin KA, Dalal P, Thomas R, Dubyak GR: Stage-specific expression of P2Y receptors, ecto-apyrase, and ecto-5'-nucleotidase in myeloid leukocytes. Am J Physiol. 1997, 273: C973-C987.","journal-title":"Am J Physiol"},{"key":"183_CR29","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.thromres.2004.07.016","volume":"115","author":"S Ziegler","year":"2005","unstructured":"Ziegler S, Sperr WR, Knobl P, Lehr S, Weltermann A, Jager U, Valent P, Lechner K: Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors, and impact on prognosis. Thromb Res. 2005, 115: 59-64. 10.1016\/j.thromres.2004.07.016.","journal-title":"Thromb Res"},{"key":"183_CR30","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1046\/j.1365-2141.1997.d01-1982.x","volume":"96","author":"DG Savage","year":"1997","unstructured":"Savage DG, Szydlo RM, Goldman JM: Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period. Br J Haematol. 1997, 96: 111-116. 10.1046\/j.1365-2141.1997.d01-1982.x.","journal-title":"Br J Haematol"},{"key":"183_CR31","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1172\/JCI115485","volume":"88","author":"AJ Marcus","year":"1991","unstructured":"Marcus AJ, Safier LB, Hajjar KA, Ullman HL, Islam N, Broekman MJ, Eiroa AM: Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells. J Clin Invest. 1991, 88: 1690-1696.","journal-title":"J Clin Invest"},{"key":"183_CR32","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1055\/s-2005-869528","volume":"31","author":"AJ Marcus","year":"2005","unstructured":"Marcus AJ, Broekman MJ, Drosopoulos JH, Olson KE, Islam N, Pinsky DJ, Levi R: Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection. Semin Thromb Hemost. 2005, 31: 234-246. 10.1055\/s-2005-869528.","journal-title":"Semin Thromb Hemost"},{"key":"183_CR33","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1172\/JCI109967","volume":"66","author":"AJ Marcus","year":"1980","unstructured":"Marcus AJ, Weksler BB, Jaffe EA, Broekman MJ: Synthesis of prostacyclin from platelet-derived endoperoxides by cultured human endothelial cells. J Clin Invest. 1980, 66: 979-986.","journal-title":"J Clin Invest"},{"key":"183_CR34","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1182\/blood.V106.11.3088.3088","volume":"106","author":"KE Olson","year":"2005","unstructured":"Olson KE, Pulte ED, Broekman MJ, A.E. O, Drosopoulos JH, Islam N, Musi E, Marcus AJ: CD39\/NTPDase1 Variants Identified in Human Neutrophils Regulate Antithrombotic Activity(abstract). Blood. 2005, 106: 3088-","journal-title":"Blood"},{"key":"183_CR35","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1172\/JCI119294","volume":"99","author":"AJ Marcus","year":"1997","unstructured":"Marcus AJ, Broekman MJ, Drosopoulos JH, Islam N, Alyonycheva TN, Safier LB, Hajjar KA, Posnett DN, Schoenborn MA, Schooley KA, Gayle RB, Maliszewski CR: The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39. J Clin Invest. 1997, 99: 1351-1360.","journal-title":"J Clin Invest"},{"key":"183_CR36","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/BF03401797","volume":"6","author":"C Goepfert","year":"2000","unstructured":"Goepfert C, Imai M, Brouard S, Csizmadia E, Kaczmarek E, Robson SC: CD39 modulates endothelial cell activation and apoptosis. Mol Med. 2000, 6: 591-603.","journal-title":"Mol Med"},{"key":"183_CR37","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1182\/blood.V94.2.448","volume":"94","author":"FR Mauro","year":"1999","unstructured":"Mauro FR, Foa R, Giannarelli D, Cordone I, Crescenzi S, Pescarmona E, Sala R, Cerretti R, Mandelli F: Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood. 1999, 94: 448-454.","journal-title":"Blood"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-5876-5-23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T03:29:32Z","timestamp":1707881372000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/1479-5876-5-23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,4]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["183"],"URL":"https:\/\/doi.org\/10.1186\/1479-5876-5-23","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,4]]},"assertion":[{"value":"16 January 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2007","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"23"}}