Blood最新文献

{"title":"Pancreatitis-associated thrombotic microangiopathic hematolytic anemia with thrombocytopenia in a child.","authors":"Colleen Kelly, Riten Kumar","doi":"10.1182/blood.2024026629","DOIUrl":"https://doi.org/10.1182/blood.2024026629","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 21","pages":"2270"},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680859","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 Aza/Ven reshuffle.","authors":"Mark Levis","doi":"10.1182/blood.2024026429","DOIUrl":"https://doi.org/10.1182/blood.2024026429","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 21","pages":"2159-2160"},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680860","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":"Serum free light chains in a racially diverse population including African Americans and populations from South Africa.","authors":"Luca Bertamini, Jean-Baptiste Alberge, David Jungpa Lee, Habib El-Khoury, Sungjae Kim, Grace Fleming, Ciara Suen Marie Murphy, Julia Colchie, Maya I Davis, Jacqueline Perry, Elizabeth D Lightbody, Sabine Allam, Lindokuhle N Goqwana, Vinitha Philip, Natalie Anne Smyth, Dhananjay Sakrikar, Mark C Perkins, Stephen Harding, Derek Troske, Gad Getz, Elizabeth W Karlson, Nikhil C Munshi, Kenneth C Anderson, Lorenzo Trippa, Catherine R Marinac, Wenlong Carl Chen, Maureen Joffe, Irene M Ghobrial","doi":"10.1182/blood.2024026078","DOIUrl":"https://doi.org/10.1182/blood.2024026078","url":null,"abstract":"<p><p>Detection of light chain (LC) monoclonal gammopathies (MG) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10,035 individuals for heavy chain MG, identifying 9,028 negative cases whose FLC were measured. Participants included 4,149 from the PROMISE Study (US, n=2,383; South Africa, n=1,766) and 4,879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1,074 out of 10,035 individuals (10.7%) were diagnosed with LC-MGUS, with 99% being κ-restricted. In the US, 14.8% of Black and 4% of White individuals were diagnosed (p<0.01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (p<0.01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of African descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs. 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685962","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":"Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine.","authors":"Hartmut Döhner, Keith W Pratz, Courtney D DiNardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea","doi":"10.1182/blood.2024024944","DOIUrl":"10.1182/blood.2024024944","url":null,"abstract":"<p><strong>Abstract: </strong>The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2211-2222"},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970592","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":"CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML.","authors":"Harrison Silva, Grace Martin, Filippo Birocchi, Marc Wehrli, Michael C Kann, Valentina M Supper, Aiyana Parker, Charlotte E Graham, Alexandra Grace Bratt, Amanda A Bouffard, Hannah Donner, Giulia Escobar, Hana N Takei, Alexander Armstrong, Sadie Goncalves, Trisha R Berger, Bryan D Choi, Marcela V Maus, Mark B Leick","doi":"10.1182/blood.2023023210","DOIUrl":"https://doi.org/10.1182/blood.2023023210","url":null,"abstract":"<p><p>CD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based CAR. However, here, we identify in vivo CD70 antigen escape as a limitation of single antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity. We hypothesized that modifying our CD70 CAR platform to secrete a bispecific T cell engaging antibody molecule (\"TEAM\") targeting CD33 (7033) would create a therapeutic window whereby AML heterogeneity could be addressed without increasing tissue toxicity. We found that CD33 TEAMs mediated specific cytotoxicity across AML cell lines, including CD33 or CD70 single-antigen knockout tumors. 7033 CAR-T cells eradicated tumor in an in vivo mixed tumor model of CD70 antigen escape and outperformed the previously optimized CD70 CAR in a patient-derived xenograft. In vivo gene expression profiling of CAR-T cells revealed enhanced 7033 CAR-T cell pathway scoring for persistence, activation, and TCR signaling. Additionally, CD33 TEAMs successfully redirected T cells isolated from AML patients to activate, secrete cytokines, and kill tumor targets despite exposure to substantial prior cytotoxic therapies. In summary, our findings demonstrate the feasibility of our 7033 CAR to overcome AML heterogeneity and leverage the bystander T cells of patients; this approach warrants further study in patients with this dire clinical need.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685955","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":"Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study.","authors":"Teena Bhatla, Laura E Hogan, David T Teachey, Francisco Bautista, John Moppett, Pablo Velasco Puyó, Concetta Micalizzi, Claudia Rossig, Neerav Shukla, Gil Gilad, Franco Locatelli, André Baruchel, C Michel Zwaan, Natalie S Bezler, Alba Rubio-San-Simón, David C Taussig, Elizabeth A Raetz, Zhengwei J Mao, Brent L Wood, Diana Alvarez Arias, Maria Krevvata, Ivo Nnane, Nibedita Bandyopadhyay, Lorena Lopez Solano, Robyn M Dennis, Robin Carson, Ajay Vora","doi":"10.1182/blood.2024024493","DOIUrl":"10.1182/blood.2024024493","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) have poor outcomes compared with newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children with relapsed/refractory B-cell ALL (n = 7) after ≥2 relapses, and children and young adults with T-cell ALL (children, n = 24; young adults, n = 5) or LL (n = 10) after first relapse. The primary end point was complete response (CR) in the B-cell ALL (end of cycle 2) and T-cell ALL (end of cycle 1) cohorts, after which patients could proceed off study to allogeneic hematopoietic stem cell transplant (HSCT). Seven patients with advanced B-cell ALL received daratumumab with no CRs achieved; this cohort was closed because of futility. For the childhood T-cell ALL, young adult T-cell ALL, and T-cell LL cohorts, the CR (end of cycle 1) rates were 41.7%, 60.0%, and 30.0%, respectively; overall response rates (any time point) were 83.3% (CR + CR with incomplete count recovery [CRi]), 80.0% (CR + CRi), and 50.0% (CR + partial response), respectively; minimal residual disease negativity (<0.01%) rates were 45.8%, 20.0%, and 50.0%, respectively; observed 24-month event-free survival rates were 36.1%, 20.0%, and 20.0%, respectively; observed 24-month overall survival rates were 41.3%, 25.0%, and 20.0%, respectively; and allogeneic HSCT rates were 75.0%, 60.0%, and 30.0%, respectively. No new safety concerns with daratumumab were observed. In conclusion, daratumumab was safely combined with backbone chemotherapy in children and young adults with T-cell ALL/LL and contributed to successful bridging to HSCT. This trial was registered at www.clinicaltrials.gov as NCT03384654.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2237-2247"},"PeriodicalIF":21.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999336","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":"Methylation sequencing enhances interpretation of clonal hematopoiesis dynamics.","authors":"Alyssa C Parker, Joseph Van Amburg, J Brett Heimlich, Yash Pershad, Nicole Angelina Mickels, Taralynn Mack, Paul Brent Ferrell, Michael R Savona, Angela Jones, Alexander G Bick","doi":"10.1182/blood.2024026555","DOIUrl":"https://doi.org/10.1182/blood.2024026555","url":null,"abstract":"<p><p>We have developed a cost-effective DNA methylation sequencing assay to improve monitoring of clonal hematopoiesis. By inferring cell-type proportions, this method enhances interpretation of clonal trajectories compared to interpretation based on variant allele fraction only.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680841","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":"Nanobody-based Naturally Selected CD7-Targeted CAR-T Therapy for Acute Myeloid Leukemia.","authors":"Peihua Lu, Xian Zhang, Junfang Yang, Jingjing Li, Liyuan Qiu, Meiwei Gong, Hui Wang, Jiaqi Chen, Hongxing Liu, Min Xiong, Ying Liu, Lin Wang","doi":"10.1182/blood.2024024861","DOIUrl":"https://doi.org/10.1182/blood.2024024861","url":null,"abstract":"<p><p>Approximately 30% of acute myeloid leukemia (AML) patients express CD7 on their myeloblasts. We have previously demonstrated that scFv-based \"naturally selected\" CD7 CAR-T (NS7CAR-T) therapy shows significant efficacy with a favorable safety profile in T-cell lymphoid malignancies. Here we derived dual nanobody-based dVHH NS7CAR-T cells that have superior CD7 binding specificity, affinity to their scFv-based counterparts and improved proliferative capability. In this phase I clinical trial, we evaluated the efficacy and safety of dVHH NS7CAR-T cells in patients with CD7-positive refractory/relapsed (r/r) AML. A cohort of ten patients received dVHH NS7CAR-T cells across two dosage levels of 5×105/kg and 1×106/kg. Before enrollment, patients had undergone a median of 8 (range: 3-17) prior lines of therapy. Seven patients had prior transplants. Following NS7CAR-T cell infusion, 7/10 (70%) patients achieved complete remission (CR). The median observation time was 178 days (28-776 days). Among the seven patients who achieved CR, 3 who relapsed from prior transplants underwent a second allogeneic hematopoietic stem cell transplant (allo-HSCT). One patient remained leukemia-free on day 401, and the other two died on day 241 and day 776 from non-relapse-related causes. Three CR patients without consolidative allo-HSCT relapsed within 90 days. All the nonresponders and relapsed patients had CD7 loss. The treatment was well-tolerated, with 80% experiencing mild cytokine release syndrome and none had neurotoxicity. This trial underscores the potential promising treatment of dVHH NS7CAR-T in providing clinical benefits with a manageable safety profile to CD7-positive AML patients, warranting further investigation. NCT04938115.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674721","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":"Development of ALL-Hematotox (ALL-HT): Predicting post CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia.","authors":"Monica S Nair, Sara K Silbert, Kai Rejeski, Karilynn A Wilson, Adam Joseph Lamble, Yannis K Valtis, Bonnie Yates, Alexa Morales Arana, Roni Shouval, Kevin J Curran, Rebecca A Gardner, Haneen Shalabi, Colleen Annesley, Jae H Park, Marion Subklewe, Nirali N Shah","doi":"10.1182/blood.2024025910","DOIUrl":"https://doi.org/10.1182/blood.2024025910","url":null,"abstract":"<p><p>Immune effector cell-associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. While ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (>14 days of ANC <500/µl), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/µl) was 13 days (95% CI 10-16), with 83 (53%) experiencing grade >3 ICAHT. Applying CAR-HT, nearly 90% were classified as high-risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and post-infusion neutropenia (r=0.64, p<0.0001), we developed the ALL-Hematotox (ALL-HT) score which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve=0.84, p<0.0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days, p<0.0001), fewer rates of complete response (88% vs 98%, p=0.03), and shorter median overall survival (9.8 vs 24 months, logrank p=0.0002). ALL-HT was also validated in two independent cohorts. The ALL-HT score refines a widely accepted predictive model of post-infusion hematotoxicity, applicable in B-ALL.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674796","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":"Bivalent CD47 Immunotoxin for Targeted Therapy of T-Cell Acute Lymphoblastic Leukemia.","authors":"Jihong Ma, Zhaohui Wang, Danielle Mintzlaff, Huiping Zhang, Rashmi Ramakrishna, Eduardo Davila, Matthew T Witkowski, M Scott Lucia, Marc S Schwartz, Elizabeth A Pomfret, David W Mathes, Zhirui Wang","doi":"10.1182/blood.2024025277","DOIUrl":"https://doi.org/10.1182/blood.2024025277","url":null,"abstract":"<p><p>CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin-based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique diphtheria toxin-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for ~4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the \"optimal\" binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674708","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}