{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:44:54Z","timestamp":1790315094128,"version":"4.1.0"},"reference-count":34,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:p>The NOTCH ligand, JAG2, was found to be overexpressed in malignant plasma cells from multiple myeloma (MM) patients and cell lines but not in nonmalignant plasma cells from tonsils, bone marrow from healthy individuals, or patients with other malignancies. In addition, JAG2 overexpression was detected in 5 of 5 patients with monoclonal gammopathy of undetermined significance (MGUS), an early phase of myeloma disease progression. This overexpression appears to be a consequence of hypomethylation of the JAG2 promoter in malignant plasma cells. An in vitro coculture assay was used to demonstrate that JAG2 induced the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) in stromal cells. Further, the induction of IL-6 secretion was blocked in vitro by interference with anti\u2013Notch-1 monoclonal antibodies raised against the binding sequence of Notch-1 with JAG2. Taken together, these results indicate that JAG2 overexpression may be an early event in the pathogenesis of multiple myeloma involving IL-6 production.<\/jats:p>","DOI":"10.1182\/blood-2003-12-4114","type":"journal-article","created":{"date-parts":[[2004,8,4]],"date-time":"2004-08-04T01:08:45Z","timestamp":1091581725000},"page":"3697-3704","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":142,"title":["Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines"],"prefix":"10.1182","volume":"104","author":[{"given":"Christiane","family":"Houde","sequence":"first","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Song","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Barton","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Godwin","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucha","family":"Nand","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Toor","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serhan","family":"Alkan","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Veronique","family":"Smadja","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herve\u0301","family":"Avet-Loiseau","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen S.","family":"Lima","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Miele","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel J.","family":"Coignet","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL; Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY; Cytogenetic Laboratory, Hopital St-Antoine, Paris, France; Laboratoire d'He\u0301matologie, Institut de Biologie, Nantes, France; and Hematology and Hemotherapy Center, State University of Campinas, Cidade Universita\u0301ria \u201cZeferino Vaz,\u201d Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217544246800_REF1","doi-asserted-by":"crossref","unstructured":"Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998;91: 3-21.","DOI":"10.1182\/blood.V91.1.3"},{"key":"2020021217544246800_REF2","doi-asserted-by":"crossref","unstructured":"Kyle RA. \u201cBenign\u201d monoclonal gammopathy\u2014 after 20 to 35 years of follow-up. Mayo Clin Proc. 1993;68: 26-36.","DOI":"10.1016\/S0025-6196(12)60015-9"},{"key":"2020021217544246800_REF3","doi-asserted-by":"crossref","unstructured":"Vescio RA, Cao J, Hong CH, et al. Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity. J Immunol. 1995;155: 2487-2497.","DOI":"10.4049\/jimmunol.155.5.2487"},{"key":"2020021217544246800_REF4","doi-asserted-by":"crossref","unstructured":"Klein B, Zhang XG, Lu ZY, Bataille R. Interleukin-6 in human multiple myeloma. Blood. 1995; 85: 863-872.","DOI":"10.1182\/blood.V85.4.863.bloodjournal854863"},{"key":"2020021217544246800_REF5","doi-asserted-by":"crossref","unstructured":"Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2\/IL-6 for human multiple myelomas. Nature. 1988;332: 83-85.","DOI":"10.1038\/332083a0"},{"key":"2020021217544246800_REF6","doi-asserted-by":"crossref","unstructured":"Zhang XG, Bataille R, Widjenes J, Klein B. Interleukin-6 dependence of advanced malignant plasma cell dyscrasias. Cancer. 1992;69: 1373-1376.","DOI":"10.1002\/1097-0142(19920315)69:6<1373::AID-CNCR2820690612>3.0.CO;2-1"},{"key":"2020021217544246800_REF7","doi-asserted-by":"crossref","unstructured":"Vidriales MB, Anderson KC. Adhesion of multiple myeloma cells to the bone marrow microenvironment: implications for future therapeutic strategies. Mol Med Today. 1996;2: 425-431.","DOI":"10.1016\/1357-4310(96)84846-5"},{"key":"2020021217544246800_REF8","doi-asserted-by":"crossref","unstructured":"Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284: 770-776.","DOI":"10.1126\/science.284.5415.770"},{"key":"2020021217544246800_REF9","doi-asserted-by":"crossref","unstructured":"Miele L, Osborne B. Arbiter of differentiation and death: Notch signaling meets apoptosis. J Cell Physiol. 1999;181: 393-409.","DOI":"10.1002\/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6"},{"key":"2020021217544246800_","doi-asserted-by":"crossref","unstructured":"Osborne B, Miele L. Notch and the immune system. Immunity. 1999;11: 653-663.","DOI":"10.1016\/S1074-7613(00)80140-5"},{"key":"2020021217544246800_REF11","doi-asserted-by":"crossref","unstructured":"Nickoloff BJ, Osborne B, Miele L. Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene. 2003;22: 6598-6608.","DOI":"10.1038\/sj.onc.1206758"},{"key":"2020021217544246800_REF12","doi-asserted-by":"crossref","unstructured":"Tamura K, Taniguchi Y, Minoguchi S, et al. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa\/Su(H). Curr Biol. 1995;5: 1416-1423.","DOI":"10.1016\/S0960-9822(95)00279-X"},{"key":"2020021217544246800_REF13","doi-asserted-by":"crossref","unstructured":"Hsieh JJ, Hayward SD. Masking of the CBF1\/RBPJ kappa transcriptional repression domain by Epstein-Barr virus EBNA2. Science. 1995;268: 560-563.","DOI":"10.1126\/science.7725102"},{"key":"2020021217544246800_REF14","doi-asserted-by":"crossref","unstructured":"Oswald F, Liptay S, Adler G, Schmid RM. NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa. Mol Cell Biol. 1998;18: 2077-2088.","DOI":"10.1128\/MCB.18.4.2077"},{"key":"2020021217544246800_REF15","doi-asserted-by":"crossref","unstructured":"Palmieri M, Sasso MP, Monese R, et al. Interaction of the nuclear protein CBF1 with the kappaB site of the IL-6 gene promoter. Nucleic Acids Res. 1999;27: 2785-2791.","DOI":"10.1093\/nar\/27.13.2785"},{"key":"2020021217544246800_REF16","doi-asserted-by":"crossref","unstructured":"Kao HY, Ordentlich P, Koyano-Nakagawa N, et al. A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev. 1998;12: 2269-2277.","DOI":"10.1101\/gad.12.15.2269"},{"key":"2020021217544246800_REF17","doi-asserted-by":"crossref","unstructured":"Hsieh JJ, Nofziger DE, Weinmaster G, Hayward SD. Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks differentiation. J Virol. 1997;71: 1938-1945.","DOI":"10.1128\/JVI.71.3.1938-1945.1997"},{"key":"2020021217544246800_REF18","doi-asserted-by":"crossref","unstructured":"Deng Y, Madan A, Banta AB, et al. Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene. Genomics. 2000;63: 133-138.","DOI":"10.1006\/geno.1999.6045"},{"key":"2020021217544246800_REF19","doi-asserted-by":"crossref","unstructured":"Tsai S, Fero J, Bartelmez S. Mouse Jagged2 is differentially expressed in hematopoietic progenitors and endothelial cells and promotes the survival and proliferation of hematopoietic progenitors by direct cell-to-cell contact. Blood. 2000;96: 950-957.","DOI":"10.1182\/blood.V96.3.950"},{"key":"2020021217544246800_REF20","doi-asserted-by":"crossref","unstructured":"Cereseto A, Tsai S. Jagged2 induces cell cycling in confluent fibroblasts susceptible to density-dependent inhibition of cell division. J Cell Physiol. 2000;185: 425-431.","DOI":"10.1002\/1097-4652(200012)185:3<425::AID-JCP13>3.0.CO;2-U"},{"key":"2020021217544246800_REF21","doi-asserted-by":"crossref","unstructured":"Jelinek DF. Mechanisms of myeloma cell growth control. Hematol Oncol Clin North Am. 1999;13: 1145-1159.","DOI":"10.1016\/S0889-8588(05)70117-9"},{"key":"2020021217544246800_REF22","doi-asserted-by":"crossref","unstructured":"Nacheva E, Fischer PE, Sherrington PD, et al. A new human plasma cell line, Karpas 620, with translocations involving chromosomes 1, 11 and 14 Br J Haematol. 1990;74: 70-76.","DOI":"10.1111\/j.1365-2141.1990.tb02540.x"},{"key":"2020021217544246800_REF23","unstructured":"Kluin-Nelemans HC, Limpens J, Meerabux J, et al. A new non-Hodgkin's B-cell line (DoHH2) with a chromosomal translocation t(14;18)(q32;q21). Leukemia. 1991;5: 221-224."},{"key":"2020021217544246800_REF24","doi-asserted-by":"crossref","unstructured":"Meyer C, MacLeod RA, Quentmeier H, et al. Establishment of the B cell precursor acute lymphoblastic leukemia cell line MUTZ-5 carrying a (12: 13) translocation. Leukemia. 2001;15: 1471-1474.","DOI":"10.1038\/sj.leu.2402212"},{"key":"2020021217544246800_REF25","doi-asserted-by":"crossref","unstructured":"Tarte K, De Vos J, Thykjaer T, et al. Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts. Blood. 2002;100: 1113-1122.","DOI":"10.1182\/blood.V100.4.1113.h81602001113_1113_1122"},{"key":"2020021217544246800_REF26","doi-asserted-by":"crossref","unstructured":"Coignet LJ, Lima CS, Min T, et al. Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia. Genes Chromosomes Cancer. 1999;25: 222-229.","DOI":"10.1002\/(SICI)1098-2264(199907)25:3<222::AID-GCC4>3.0.CO;2-C"},{"key":"2020021217544246800_REF27","doi-asserted-by":"crossref","unstructured":"Jiang Q, Galiegue-Zouitina S, Roumier C, Hildebrand MP, Thomas S, Coignet LJ. Genomic organization and refined mapping of the human nuclear corepressor 2 (NCOR2)\/silencing mediator of retinoid and thyroid hormone receptor (SMRT) gene on chromosome 12q24.3. Cytogene. Cell Genet. 2001;92: 217-220.","DOI":"10.1159\/000056906"},{"key":"2020021217544246800_REF28","doi-asserted-by":"crossref","unstructured":"Yuille MA, Coignet LJ, Abraham SM, et al. ATM is usually rearranged in T-cell prolymphocytic leukaemia. Oncogene. 1998;16: 789-796.","DOI":"10.1038\/sj.onc.1201603"},{"key":"2020021217544246800_REF29","unstructured":"Yuille MA, Coignet LJ. The ataxia telangiectasia gene in familial and sporadic cancer. Recent Results Cancer Res. 1998;154: 155-173."},{"key":"2020021217544246800_REF30","doi-asserted-by":"crossref","unstructured":"Yasutomo K, Doyle C, Fuchs C, Miele L, Germain RN. The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature. 2000;404: 506-510.","DOI":"10.1038\/35006664"},{"key":"2020021217544246800_REF31","doi-asserted-by":"crossref","unstructured":"De Vos J, Thykjaer T, Tarte K, et al. Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays. Oncogene. 2002;44: 6848-6857.","DOI":"10.1038\/sj.onc.1205868"},{"key":"2020021217544246800_REF32","doi-asserted-by":"crossref","unstructured":"Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken B. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood. 2002;99: 3398-3403.","DOI":"10.1182\/blood.V99.9.3398"},{"key":"2020021217544246800_REF33","doi-asserted-by":"crossref","unstructured":"Jundt F, Probsting KS, Anagnostopoulos I, et al. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood. 2004;103: 3511-3515.","DOI":"10.1182\/blood-2003-07-2254"},{"key":"2020021217544246800_REF34","doi-asserted-by":"crossref","unstructured":"Nefedova Y, Cheng P, Alsina M, Dalton WS, Gabrilovich DI. Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood. 2004;103: 3503-3510.","DOI":"10.1182\/blood-2003-07-2340"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/104\/12\/3697\/1703473\/zh802304003697.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/104\/12\/3697\/1703473\/zh802304003697.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T03:56:44Z","timestamp":1682740604000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/104\/12\/3697\/89034\/Overexpression-of-the-NOTCH-ligand-JAG2-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,1]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2004,12,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2003-12-4114","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,1]]}}}