Leukemia最新文献

{"title":"Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial","authors":"Carlo Gambacorti-Passerini, Tim H. Brümmendorf, Elisabetta Abruzzese, Kevin R. Kelly, Vivian G. Oehler, Valentín García-Gutiérrez, Henrik Hjorth-Hansen, Thomas Ernst, Eric Leip, Simon Purcell, Gerald Luscan, Andrea Viqueira, Francis J. Giles, Andreas Hochhaus","doi":"10.1038/s41375-024-02372-x","DOIUrl":"10.1038/s41375-024-02372-x","url":null,"abstract":"This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome–positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9–78.9) and 59.7% (95% CI, 51.4–67.7) attained or maintained major molecular response (MMR) and molecular response (MR)4, respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR4 at 36 months were 87.2% (78.0–92.7) and 80.7% (69.4–88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8–92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML. ClinicalTrials.gov, NCT02228382","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02372-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of metabolic comorbidities and viral co-infections in monoclonal gammopathy: a retrospective analysis","authors":"Tinatin Muradashvili, Mansen Yu, Sabrina L. Browning, Noffar Bar, Elan Gorshein, Terri L. Parker, Natalia Neparidze","doi":"10.1038/s41375-024-02380-x","DOIUrl":"10.1038/s41375-024-02380-x","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation","authors":"John Alan Gambril, Sanam M. Ghazi, Stephen Sansoterra, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Patrick Ruz, Adam S. Kittai, Kerry Rogers, Michael Grever, Seema Bhat, Tracy Wiczer, John C. Byrd, Jennifer Woyach, Daniel Addison","doi":"10.1038/s41375-024-02334-3","DOIUrl":"10.1038/s41375-024-02334-3","url":null,"abstract":"Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009–2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi’s were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi’s, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi’s. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02334-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials—a LYSA and GLA/ DSHNHL collaboration","authors":"Fabian Frontzek, Loïc Renaud, Ulrich Dührsen, Viola Poeschel, Sophie Bernard, Loïc Chartier, Nicolas Ketterer, Christian Récher, Olivier Fitoussi, Gerhard Held, Olivier Casasnovas, Corinne Haioun, Nicolas Mounier, Hervé Tilly, Franck Morschhauser, Steven Le Gouill, Imke E. Karsten, Gerben Duns, Christian Steidl, David W. Scott, Wolfram Klapper, Andreas Rosenwald, German Ott, Thierry Molina, Georg Lenz, Marita Ziepert, Bettina Altmann, Catherine Thieblemont, Norbert Schmitz","doi":"10.1038/s41375-024-02371-y","DOIUrl":"10.1038/s41375-024-02371-y","url":null,"abstract":"Progression or relapse in the central nervous system (CNS) remains a rare but mostly fatal event for patients with diffuse large B-cell lymphoma (DLBCL). In a retrospective analysis of 5189 patients treated within 19 prospective German and French phase 2/3 trials, we identified 159 patients experiencing a CNS event (relapse: 62%, progression: 38%). Intracerebral, meningeal, intraspinal, or combined involvement was reported in 44%, 31%, 3%, and 22% of patients, respectively. 62 of 155 evaluable patients (40%) showed concurrent systemic progression/ relapse. 82% of all CNS events occurred within two years after study inclusion or randomization. 87% of patients showed extranodal involvement outside the CNS. Patients generally had poor outcomes with a median overall survival (OS) of 3.4 months (95% CI 2.9–4.2) and a 2-year OS of 15% (10–22%). Outcomes did not differ depending on the site or time point of CNS events. Patients with isolated CNS events demonstrated significantly better OS (p = 0.023). Twenty-five patients were consolidated with autologous or allogeneic stem cell transplantation and achieved a 3-year OS of 36% (20–66%). This large study including more than 5000 DLBCL patients highlights the unmet medical need to improve the outcome of DLBCL patients suffering from CNS relapse.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in cancer resistance: New combinatorial strategy for cancer therapy","authors":"Eloïne Bestion, Régis Costello, Soraya Mezouar, Philippe Halfon","doi":"10.1038/s41375-024-02342-3","DOIUrl":"10.1038/s41375-024-02342-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The VLA-4 integrin is constitutively active in circulating chronic lymphocytic leukemia cells via BCR autonomous signaling: a novel anchor-independent mechanism exploiting soluble blood-borne ligands","authors":"Erika Tissino, Annalisa Gaglio, Antonella Nicolò, Federico Pozzo, Tamara Bittolo, Francesca Maria Rossi, Riccardo Bomben, Paola Nanni, Ilaria Cattarossi, Eva Zaina, Anna Maria Zimbo, Giulia Ianna, Guido Capasso, Gabriela Forestieri, Riccardo Moia, Moumita Datta, Andrea Härzschel, Jacopo Olivieri, Giovanni D’Arena, Luca Laurenti, Francesco Zaja, Annalisa Chiarenza, Giuseppe A. Palumbo, Enrica Antonia Martino, Massimo Gentile, Davide Rossi, Gianluca Gaidano, Giovanni Del Poeta, Roberta Laureana, Maria Ilaria Del Principe, Palash C. Maity, Hassan Jumaa, Tanja Nicole Hartmann, Antonella Zucchetto, Valter Gattei","doi":"10.1038/s41375-024-02376-7","DOIUrl":"10.1038/s41375-024-02376-7","url":null,"abstract":"In chronic lymphocytic leukemia (CLL), survival of neoplastic cells depends on microenvironmental signals at lymphoid sites where the crosstalk between the integrin VLA-4 (CD49d/CD29), expressed in ~40% of CLL, and the B-cell receptor (BCR) occurs. Here, BCR engagement inside–out activates VLA-4, thus enhancing VLA-4-mediated adhesion of CLL cells, which in turn obtain pro-survival signals from the surrounding microenvironment. We report that the BCR is also able to effectively inside–out activate the VLA-4 integrin in circulating CD49d-expressing CLL cells through an autonomous antigen-independent BCR signaling. As a consequence, circulating CLL cells exhibiting activated VLA-4 express markers of BCR pathway activation (phospho-BTK and phospho-PLC-γ2) along with higher levels of phospho-ERK and phospho-AKT indicating parallel activation of downstream pathways. Moreover, circulating CLL cells expressing activated VLA-4 bind soluble blood-borne VCAM-1 leading to increased VLA-4-dependent actin polymerization/re-organization and ERK phosphorylation. Finally, evidence is provided that ibrutinib treatment, by affecting autonomous BCR signaling, impairs the constitutive VLA-4 activation eventually decreasing soluble VCAM-1 binding and reducing downstream ERK phosphorylation by circulating CLL cells. This study describes a novel anchor-independent mechanism occurring in circulating CLL cells involving the BCR and the VLA-4 integrin, which help to unravel the peculiar biological and clinical features of CD49d+ CLL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02376-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish","authors":"Sarada Ketharnathan, Sujata Pokharel, Sergey V. Prykhozhij, Anna Cordeiro-Santanach, Kevin Ban, Serkan Dogan, Huy-Dung Hoang, Mira F. Liebman, Elaine Leung, Tommy Alain, Irina Alecu, Steffany A. L. Bennett, Miroslava Čuperlović-Culf, Yigal Dror, Jason N. Berman","doi":"10.1038/s41375-024-02367-8","DOIUrl":"10.1038/s41375-024-02367-8","url":null,"abstract":"Mutations in the DNAJC21 gene were recently described in Shwachman–Diamond syndrome (SDS), a bone marrow failure syndrome with high predisposition for myeloid malignancies. To study the underlying biology in hematopoiesis regulation and disease, we generated the first in vivo model of Dnajc21 deficiency using the zebrafish. Zebrafish dnajc21 mutants phenocopy key SDS patient phenotypes such as cytopenia, reduced growth, and defective protein synthesis. We show that cytopenia results from impaired hematopoietic differentiation, accumulation of DNA damage, and reduced cell proliferation. The introduction of a biallelic tp53 mutation in the dnajc21 mutants leads to the development of myelodysplastic neoplasia-like features defined by abnormal erythroid morphology and expansion of hematopoietic progenitors. Using transcriptomic and metabolomic analyses, we uncover a novel role for Dnajc21 in nucleotide metabolism. Exogenous nucleoside supplementation restores neutrophil counts, revealing an association between nucleotide imbalance and neutrophil differentiation, suggesting a novel mechanism in dnajc21-mutant SDS biology.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02367-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141973875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma","authors":"Michael Y. He, Kit I. Tong, Ting Liu, Ryder Whittaker Hawkins, Victoria Shelton, Yong Zeng, Mehran Bakhtiari, Yufeng Xiao, Guangrong Zheng, Ali Sakhdari, Lin Yang, Wenxi Xu, David G. Brooks, Rob C. Laister, Housheng Hansen He, Robert Kridel","doi":"10.1038/s41375-024-02325-4","DOIUrl":"10.1038/s41375-024-02325-4","url":null,"abstract":"Despite selective HDAC3 inhibition showing promise in a subset of lymphomas with CREBBP mutations, wild-type tumors generally exhibit resistance. Here, using unbiased genome-wide CRISPR screening, we identify GNAS knockout (KO) as a sensitizer of resistant lymphoma cells to HDAC3 inhibition. Mechanistically, GNAS KO-induced sensitization is independent of the canonical G-protein activities but unexpectedly mediated by viral mimicry-related interferon (IFN) responses, characterized by TBK1 and IRF3 activation, double-stranded RNA formation, and transposable element (TE) expression. GNAS KO additionally synergizes with HDAC3 inhibition to enhance CD8+ T cell-induced cytotoxicity. Moreover, we observe in human lymphoma patients that low GNAS expression is associated with high baseline TE expression and upregulated IFN signaling and shares common disrupted biological activities with GNAS KO in histone modification, mRNA processing, and transcriptional regulation. Collectively, our findings establish an unprecedented link between HDAC3 inhibition and viral mimicry in lymphoma. We suggest low GNAS expression as a potential biomarker that reflects viral mimicry priming for enhanced response to HDAC3 inhibition in the clinical treatment of lymphoma, especially the CREBBP wild-type cases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02325-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic neoplasm: a HARMONY Alliance study","authors":"Elena Crisà, Elvira Mora, Ulrich Germing, Cecile Bally, Maria Diez Campelo, Mikko Myllymäki, Martin Jädersten, Rami Komrokji, Uwe Platzbecker, Detlef Haase, Wolf-Karsten Hofmann, Najla H. Al Ali, Daniela Barraco, Juan José Bargay, Teresa Bernal, Felix López Cadenas, Anna Calvisi, Isabella Capodanno, Marco Cerrano, Rosanna Ciancia, Monica Crugnola, Andrea Kündgen, Carlo Finelli, Claudio Fozza, Chiara Frairia, Ebeling Freja, Christina Ganster, Anne Sophie Kubasch, Maria Jose Jimenez, Roberto Latagliata, Francisca Hernandez Mohedo, Antonieta Molero, Miriam Vara Pampliega, Clara Aparicio Perez, Giuseppe Pietrantuono, Antonella Poloni, Helena Pomares, Valle Recasens, Axel Rüfer, Alessio Signori, Eva Hellstrom-Lindberg, Pierre Fenaux, Guillermo Sanz, Valeria Santini","doi":"10.1038/s41375-024-02360-1","DOIUrl":"10.1038/s41375-024-02360-1","url":null,"abstract":"Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60–70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCR::ABL1 Proteolysis-targeting chimeras (PROTACs): The new frontier in the treatment of Ph+ leukemias?","authors":"Nataly Cruz-Rodriguez, Hua Tang, Benjamin Bateman, Weiping Tang, Michael Deininger","doi":"10.1038/s41375-024-02365-w","DOIUrl":"10.1038/s41375-024-02365-w","url":null,"abstract":"BCR::ABL1 tyrosine kinase inhibitors (TKIs) have turned chronic myeloid leukemia (CML) from a lethal condition into a chronic ailment. With optimal management, the survival of CML patients diagnosed in the chronic phase is approaching that of age-matched controls. However, only one-third of patients can discontinue TKIs and enter a state of functional cure termed treatment-free remission (TFR), while the remainder require life-long TKI therapy to avoid the recurrence of active leukemia. Approximately 10% of patients exhibit primary or acquired TKI resistance and eventually progress to the blast phase. It is thought that recurrence after attempted TFR originates from CML stem cells (LSCs) surviving despite continued suppression of BCR::ABL1 kinase. Although kinase activity is indispensable for induction of overt CML, kinase-independent scaffold functions of BCR::ABL1 are known to contribute to leukemogenesis, raising the intriguing but as yet hypothetical possibility, that degradation of BCR::ABL1 protein may accomplish what TKIs fail to achieve – eliminate residual LSCs to turn functional into real cures. The advent of BCR::ABL1 proteolysis targeting chimeras (PROTACs), heterobifunctional molecules linking a TKI-based warhead to an E3 ligase recruiter, has moved clinical protein degradation into the realm of the possible. Here we examine the molecular rationale as well as pros and cons of degrading BCR::ABL1 protein. We review reported BCR::ABL1 PROTACs, point out limitations of available data and compounds and suggest directions for future research. Ultimately, clinical testing of a potent and specific BCR::ABL1 degrader will be required to determine the efficacy and tolerability of this approach.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02365-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}