Blood Neoplasia最新文献

{"title":"BIRC5 upregulation enhances DNMT3A-mutant T-ALL cell survival and pathogenesis","authors":"Wangisa Dunuwille ,&nbsp;William C. Wilson ,&nbsp;Hassan Bjeije ,&nbsp;Nancy Issa ,&nbsp;Wentao Han ,&nbsp;Tyler M. Parsons ,&nbsp;Andrew L. Young ,&nbsp;Infencia Xavier Raj ,&nbsp;Aishwarya Krishnan ,&nbsp;Tarang Gaur ,&nbsp;Eunice S. Wang ,&nbsp;Andrew P. Weng ,&nbsp;Matthew C. Stubbs ,&nbsp;Hamza Celik ,&nbsp;Amanda F. Cashen ,&nbsp;John R. Edwards ,&nbsp;Grant A. Challen","doi":"10.1016/j.bneo.2024.100040","DOIUrl":"10.1016/j.bneo.2024.100040","url":null,"abstract":"<div><h3>Abstract</h3><div>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm. Although the prognosis of pediatric T-ALL has improved with intensified chemotherapy regimens, this benefit has largely not translated to the adult T-ALL population. Development of new treatments requires understanding the mechanisms driven by specific mutations. <em>DNMT3A</em> mutations are identified in ∼10% to 18% of adult patients with T-ALL and are associated with poor clinical outcomes. Here, using primary human specimens, we show that cells from patients with T-ALL with <em>DNMT3A</em> mutations are resistant to apoptosis and certain chemotherapies. Elevated JAK/STAT signaling drove prosurvival programs in patients with mutant <em>DNMT3A</em>, and JAK/STAT inhibition restored sensitivity to chemotherapy. The prosurvival gene <em>BIRC5</em> was upregulated in patients with <em>DNMT3A</em>-mutant T-ALL, and these cells were specifically sensitive to the Baculoviral IAP Repeat Containing 5 (BIRC5) inhibitor YM155. Genetic inhibition of <em>BIRC5</em> in vivo lead to rapid depletion of <em>DNMT3A</em>-mutant T-ALL cells in patient-derived xenografts, positioning BIRC5 as a precision medicine target for these patients.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice","authors":"Natalia Timofeeva ,&nbsp;Nitin Jain ,&nbsp;Varsha Gandhi","doi":"10.1016/j.bneo.2024.100034","DOIUrl":"10.1016/j.bneo.2024.100034","url":null,"abstract":"<div><h3>Abstract</h3><p>The combination of ibrutinib and venetoclax has emerged as a promising therapeutic strategy for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations demonstrated a synergistic antitumor effect through multiple mechanisms, providing a robust foundation for translating this regimen into clinical trials. Beyond the dual inhibition by 2 small molecules, another innovative concept being tested with this combination is the use of measurable residual disease (MRD)–driven treatment vs fixed-duration treatment to meet the escalating demand for oral, convenient, cost-effective, and time-limited therapeutic approaches. The clinical translation of this combination has yielded remarkable outcomes with significant improvements in the progression-free survival and overall survival rates for both treatment-naïve patients and those with relapsed/refractory CLL. Notably, a substantial proportion of patients achieved undetectable MRD. Clinical trial updates following the initial published results have shown consistency and durability of responses over time. In this review, the initial investigator-initiated trial results for ibrutinib and venetoclax are discussed, several multicenter clinical trial designs and outcomes are examined, variables such as chromosome 17p deletion that influence treatment responses are addressed, and the safety of the regimen is discussed. In addition, we reviewed the usage of this combination in other B-cell malignancies and discussed how current knowledge can be used for shaping the future CLL treatment regimens.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000347/pdfft?md5=6d685af44e4971629738466491360299&pid=1-s2.0-S2950328024000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study","authors":"Koji Nagafuji ,&nbsp;Toshihiro Miyamoto ,&nbsp;Tetsuya Eto ,&nbsp;Tomohiko Kamimura ,&nbsp;Koji Kato ,&nbsp;Yasuhiko Miyazaki ,&nbsp;Atsushi Wake ,&nbsp;Kentaro Kohno ,&nbsp;Ken Takase ,&nbsp;Yutaka Imamura ,&nbsp;Naoyuki Uchida ,&nbsp;Kazuki Tanimoto ,&nbsp;Noriaki Kawano ,&nbsp;Toshiro Kurokawa ,&nbsp;Yukio Kondo ,&nbsp;Yoshikiyo Ito ,&nbsp;Tomoaki Fujisaki ,&nbsp;Junichi Tsukada ,&nbsp;Koji Yonemoto ,&nbsp;Toshinori Hori ,&nbsp;Koichi Akashi","doi":"10.1016/j.bneo.2024.100033","DOIUrl":"10.1016/j.bneo.2024.100033","url":null,"abstract":"<div><h3>Abstract</h3><p>The enhanced utilization of native L-asparaginase (L-Asp) aims to improve treatment outcomes for adult patients with non-Philadelphia chromosome (Ph) acute lymphoblastic leukemia (ALL). In this measurable residual disease 2014 (MRD2014) study, we modified our protocol to include an augmented dose of native L-Asp. Compared with former MRD2008, the total dose of L-Asp was raised from 36 000 U/m² to 232 000 U/m² in patients aged 16 to 35 and from 36 000 U/m² to 132 000 U/m² in patients aged 36 to 65 years. Adult patients with ALL were enrolled between January 2014 and December 2019 based on the following eligibility criteria: non-L3 ALL, age 16 to 65 years, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate liver and kidney functions (serum bilirubin ≤ 2.0 mg/dL; serum creatinine ≤ 2.0 mg/dL). The median follow-up time was 1128 days (range, 35-2400). A total of 81 patients with non-Ph ALL (40 males and 41 females; median age, 39 years [range, 16-64]) in whom MRD status was assessed were included. Complete remission was achieved in 72 patients (89%). The probability of 3-year event-free survival (EFS) and overall survival (OS) in these patients were 55% and 72%, respectively. The outcomes for patients aged 16 to 35 years demonstrated remarkable improvement. The 3-year EFS of MRD2008 at 45% significantly increased to 71% for MRD2014. Our study unequivocally demonstrated the beneficial effects of augmented use of L-Asp in this adolescent and young adult population. This trial was registered at UMIN Clinical Trials Registry as #UMIN000012382.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000335/pdfft?md5=bbf499ae9c9b69c23bb21aa6d69f4833&pid=1-s2.0-S2950328024000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell lymphoblastic lymphoma compared with T-cell acute lymphoblastic leukemia: similar subtypes and different fusions","authors":"Emma Kroeze ,&nbsp;Michelle M. Kleisman ,&nbsp;Rico Hagelaar ,&nbsp;Reno S. Bladergroen ,&nbsp;Lennart A. Kester ,&nbsp;Marijn A. Scheijde-Vermeulen ,&nbsp;Freerk van Dijk ,&nbsp;Jules P. P. Meijerink ,&nbsp;Roland P. Kuiper ∗ ,&nbsp;Jan L. C. Loeffen ∗","doi":"10.1016/j.bneo.2024.100029","DOIUrl":"10.1016/j.bneo.2024.100029","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000293/pdfft?md5=106dbe0b44388c3c2db4943f247d880b&pid=1-s2.0-S2950328024000293-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SLFN11-regulated pathways restores chemotherapy sensitivity in AML","authors":"Sara H. Small ,&nbsp;Ricardo E. Perez ,&nbsp;Elspeth M. Beauchamp ,&nbsp;Aneta H. Baran ,&nbsp;Stephen D. Willis ,&nbsp;Mariafausta Fischietti ,&nbsp;Michael Schieber ,&nbsp;Masha Kocherginsky ,&nbsp;Diana Saleiro ,&nbsp;Leonidas C. Platanias","doi":"10.1016/j.bneo.2024.100037","DOIUrl":"10.1016/j.bneo.2024.100037","url":null,"abstract":"<div><h3>Abstract</h3><div>Chemoresistance represents an ongoing challenge in treating patients with acute myeloid leukemia (AML), and a better understanding of the resistance mechanisms can lead to the development of novel AML therapies. Here, we demonstrated that low expression of the DNA damage response gene Schlafen 11 (<em>SLFN11</em>) correlates with poor overall survival and worse prognosis in patients with AML. Moreover, we showed that SLFN11 plays an essential role in regulating chemotherapy sensitivity in AML. AML cells with suppressed levels of SLFN11 do not undergo apoptosis in response to cytarabine because of aberrant activation of the Ataxia telangiectasia and Rad3-related protein (ATR)/Checkpoint kinase 1 (Chk1) pathway, allowing for DNA damage repair, whereas sensitivity to cytarabine can be restored by inhibiting the ATR pathway. Importantly, <em>SLFN11</em> knockout AML cells retain sensitivity to hypomethylating agents and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Altogether, these results reveal <em>SLFN11</em> as an important regulator and predictor of chemotherapy sensitivity in AML and suggest that targeting pathways suppressed by SLFN11 may offer potential combination therapies to enhance and optimize chemotherapy responses in AML.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and pathological features of pediatric peripheral T-cell lymphoma after solid organ transplantation","authors":"Jinjun Cheng ,&nbsp;Rachel Mariani ,&nbsp;Jyotinder Nain Punia ,&nbsp;Marimar de la Cruz Bonilla ,&nbsp;Pichayut Nithagon ,&nbsp;Metin Ozdemirli ,&nbsp;Wen Shuai ,&nbsp;Larry Wang ,&nbsp;Oussama Abla ,&nbsp;Shunyou Gong","doi":"10.1016/j.bneo.2024.100039","DOIUrl":"10.1016/j.bneo.2024.100039","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia","authors":"Kuo-Kai Chin ∗ ,&nbsp;Yannis Valtis ∗ ,&nbsp;Andriy Derkach ,&nbsp;Meira Yisraeli Salman ,&nbsp;Leora Boussi ,&nbsp;Jenna Ciervo ,&nbsp;Mark B. Geyer ,&nbsp;Jae H. Park ,&nbsp;Martin S. Tallman ,&nbsp;Jacob L. Glass ,&nbsp;Aaron D. Goldberg ,&nbsp;Eytan M. Stein","doi":"10.1016/j.bneo.2024.100038","DOIUrl":"10.1016/j.bneo.2024.100038","url":null,"abstract":"<div><h3>Abstract</h3><div>The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults aged &gt;75 years with newly diagnosed acute myeloid leukemia (AML) as well as those ineligible for intensive chemotherapy (IC). HMA/VEN is increasingly substituted for IC in adults with AML aged &lt;75 years, particularly in those with adverse cytogenetic and molecular features. When patients fail to respond or relapse after HMA/VEN, the utility of salvage IC is largely unknown. We performed a retrospective single-institution study and identified 46 patients who received IC after HMA/VEN, including 24 patients who received HMA/VEN as their first treatment for AML. This population had complete remission (CR)/CR with incomplete count recovery (CRi)/morphologic leukemia-free state rate of 37%, CR/CRi rate of 28%, and a median overall survival (mOS) of 7.2 months (95% confidence interval, 5.0-10.3). Patients who relapsed after an initial response to HMA/VEN and subsequently received IC were more likely to achieve a CR/CRi than those refractory to HMA/VEN (50% vs 19%; <em>P</em> = .04), although there was no statistically significant difference in survival (mOS, 8.8 vs 5.4 months; <em>P</em> = .64). Age &gt;65 years predicted poorer survival (mOS, 4.3 vs 10.6 months; <em>P</em> &lt; .001). IC after HMA/VEN should be further studied and chosen with caution.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1 study adding pitavastatin to venetoclax therapy in AML and CLL/SLL: a mechanism-based drug repurposing strategy","authors":"Elizabeth A. Brem ,&nbsp;Kevin Shieh ,&nbsp;Dennis Juarez ,&nbsp;Roberta Buono ,&nbsp;Deepa Jeyakumar ,&nbsp;Susan O’Brien ,&nbsp;Thomas H. Taylor ,&nbsp;David A. Fruman","doi":"10.1016/j.bneo.2024.100036","DOIUrl":"10.1016/j.bneo.2024.100036","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 vaccination in patients with classic and variant hairy cell leukemia","authors":"Robert J. Kreitman ,&nbsp;Lacey James ,&nbsp;Julie Feurtado ,&nbsp;Holly Eager ,&nbsp;Olena Sierra Ortiz ,&nbsp;Mory Gould ,&nbsp;Isaac Shpilman ,&nbsp;Hong Zhou ,&nbsp;Peter D. Burbelo ,&nbsp;Jeffrey I. Cohen ,&nbsp;Hao-Wei Wang ,&nbsp;Constance M. Yuan ,&nbsp;Evgeny Arons","doi":"10.1016/j.bneo.2024.100035","DOIUrl":"10.1016/j.bneo.2024.100035","url":null,"abstract":"<div><h3>Abstract</h3><div>Patients with the B-cell malignancy hairy cell leukemia (HCL) and the poorer-prognosis variant HCLv often receive anti-CD20 monoclonal antibodies (mAbs), which kill normal B cells, impairing humoral immunity. We measured COVID-19 antibodies after doses of COVID-19 vaccine in patients with HCL (n = 415) and HCLv (n = 32). After the second COVID-19 vaccine dose, spike antibody level most strongly correlated with normal B-cell levels (r = 0.365, <em>P</em> &lt; .0001), followed by CD4⁺ T-cell count (r = 0.244, <em>P</em> = .0002), and was less related to immunoglobulin G level (r = 0.101, <em>P</em> = .14). Spike antibody also correlated with normal B cells after the third to fifth vaccine doses and with CD4⁺ count after the third dose. Normal B-cells were undetectable in 87% of patients within 6 months after the last dose of anti-CD20 mAb and were lower than in patients at 6 to 12 months (<em>P</em> = .0003), which, in turn, were lower than at 12 to 18 months (<em>P</em> = .0002). Infection with COVID-19 became more common after use of the third vaccine dose; spike antibody levels were higher in patients with prior infection (positive vs negative nucleocapsid antibodies; <em>P</em> &lt; .0001). Spike antibodies decreased faster after ibrutinib or anti-CD20 mAb. We conclude that decreased levels of normal B cells in patients with HCL/HCLv, due to disease and/or anti-CD20 therapy, are associated with lower COVID-19 vaccination efficiency and such patients may not respond well to vaccines. The associated studies were registered at <span><span>www.ClinicalTrials.gov</span><svg><path></path></svg></span> as #NCT01087333 (HCL/HCLv) and #NCT04362865 (COVID-19).</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD5 expression in marginal zone lymphoma does not predict inferior outcome and has similarities to indolent lymphomas","authors":"Paola Ghione ,&nbsp;Kurt S. Bantilan ,&nbsp;Erel Joffe ,&nbsp;M. Lia Palomba ,&nbsp;Ariela Noy ,&nbsp;Philip Caron ,&nbsp;Paul Hamlin ,&nbsp;Anita Kumar ,&nbsp;Matthew Matasar ,&nbsp;Colette Owens ,&nbsp;Alison Moskowitz ,&nbsp;Lorenzo Falchi ,&nbsp;David Straus ,&nbsp;Steven Horwitz ,&nbsp;Gilles Salles ,&nbsp;Ahmet Dogan ∗ ,&nbsp;Andrew D. Zelenetz ∗","doi":"10.1016/j.bneo.2024.100031","DOIUrl":"10.1016/j.bneo.2024.100031","url":null,"abstract":"<div><h3>Abstract</h3><div>The prognostic relevance of CD5 expression in marginal zone lymphoma (MZL) remains poorly characterized. We aimed to compare baseline characteristics and outcomes of patients with CD5⁺ MZL and CD5^– historical matched controls. We hypothesized that patients with CD5⁺ MZL may have similarities to other CD5^– expressing B-cell lymphomas, which may be informative when considering alternative therapeutic approaches for this MZL subgroup. We retrospectively analyzed 64 patients with CD5⁺ MZL and 137 CD5^– MZL controls matched on age at diagnosis and sex. The CD5⁺ and CD5^– cases did not differ in terms of mucosa assiociated lymphoid tissue (MALT)–lymphoma International Prognostic Index or incidence of nodal involvement. Bone marrow involvement was significantly more frequent in CD5⁺ patients than in CD5^– patients (67.5% vs 47.2%; <em>P</em> = .048). Mutated immunoglobulin heavy chain variable region gene was more common in CD5⁺ patients (80.0%) than CD5^– patients (64.0%), but this association was not significant (<em>P</em> = .327). Overall survival was calculated until death from any cause, disease-specific survival until lymphoma-related death, and time from diagnosis to first treatment was calculated either considering all interventions or only systemic treatments. None of these outcomes were associated with CD5 expression.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 4","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}