Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Recent Advances in the Management of Patients with Relapsed/Refractory Follicular Lymphoma.","authors":"Georgios Pongas,&nbsp;Bruce Cheson","doi":"10.2147/BLCTT.S267569","DOIUrl":"https://doi.org/10.2147/BLCTT.S267569","url":null,"abstract":"<p><p>Advanced follicular lymphoma (FL) often relapses after front-line chemoimmunotherapy, and many patients will eventually require subsequent therapy. In 2021, two new therapies were granted approval by the Food and Drug Administration (FDA), including the PI3Kδ inhibitor umbralisib and the chimeric antigen receptor-T-cell therapy (CAR-T) axicabtagene ciloleucel. Herein, we present the latest advances in the management of FL, discussing the recently approved therapies in the relapsed and refractory (R/R) setting and various new therapeutic modalities that have the potential to change the treatment landscape and natural history of R/R FL.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 ","pages":"55-66"},"PeriodicalIF":2.8,"publicationDate":"2021-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/47/blctt-11-55.PMC8331102.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39279509","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":"Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence.","authors":"Galia Stemer,&nbsp;Jacob M Rowe,&nbsp;Yishai Ofran","doi":"10.2147/BLCTT.S236446","DOIUrl":"https://doi.org/10.2147/BLCTT.S236446","url":null,"abstract":"<p><p>The isocitrate dehydrogenase enzyme, catalyzing isocitrate conversion to α-ketoglutarate (αKG) in both the cell cytoplasm and mitochondria, contributes to the production of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) as a reductive potential in various cellular processes. <i>IDH1</i> gene mutations are revealed in up to 20% of the patients with acute myeloid leukemia (AML). A mutant IDH enzyme, existing in the cell cytoplasm and possessing neomorphic activity, converts αKG into oncometabolite R-2-hydroxyglutarate (R-2-HG) that accumulates in high amounts in the cell and inhibits αKG-dependent enzymes, including epigenetic regulators. The resultant alteration in gene expression and blockade of differentiation ultimately lead to leukemia development. Myeloid differentiation capacity can be restored by obstruction of the mutant enzyme, inducing substantial reduction in R-2-HG levels. Ivosidenib, a potent selective inhibitor of mutant <i>IDH1</i>, is a differentiating agent shown to be clinically effective in newly diagnosed AML (ND-AML) and relapsed/refractory (R/R) AML harboring this mutation. The drug is approved by the Food and Drug Administration (FDA) as a single-agent treatment for R/R AML. Significance of mutated <i>IDH1</i> targeting and a potential role of ivosidenib in AML management, when used either as a single agent or as part of combination therapies, will be reviewed herein.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 ","pages":"41-54"},"PeriodicalIF":2.8,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/94/blctt-11-41.PMC8235936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39053134","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 Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review.","authors":"Cynthia Bender, Luke Maese, Maria Carter-Febres, Anupam Verma","doi":"10.2147/BLCTT.S245210","DOIUrl":"10.2147/BLCTT.S245210","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from <i>Escherichia coli</i> and <i>Erwinia chrysanthemi</i>, have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts. Pegaspargase, a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase, has become an integral component of pediatric upfront and relapsed ALL protocols due to its longer half-life and improved immunogenicity profile compared to native asparaginase preparations. Over the past two decades great strides have been made in outcomes for pediatric ALL due to risk stratification, incorporation of multiagent chemotherapy protocols, and central nervous system prophylaxis with pegaspargase having played an important role in this success. However, adolescents and young adults (AYA) with ALL when treated on contemporaneous trials using adult ALL regimens, continue to have poor outcomes. There is increasing realization of adapting pediatric trial regimens for treating AYAs, especially those incorporating higher intensity of chemotherapeutic agents with pegaspargase being one such agent. Dose or treatment-limiting toxicity is observed in 25-30% of patients, most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis, and dyslipidemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival leading to higher risk of relapse, and in cases of relapse, a higher risk for remission failure. This article provides an overview of available evidence for use of pegaspargase in pediatric acute lymphoblastic leukemia.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 ","pages":"25-40"},"PeriodicalIF":2.8,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/e8/blctt-11-25.PMC8064615.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38914100","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":"BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma.","authors":"Vikas A Gupta,&nbsp;James Ackley,&nbsp;Jonathan L Kaufman,&nbsp;Lawrence H Boise","doi":"10.2147/BLCTT.S245191","DOIUrl":"https://doi.org/10.2147/BLCTT.S245191","url":null,"abstract":"<p><p>Although much progress has been made in the treatment of multiple myeloma, the majority of patients fail to be cured and require numerous lines of therapy. Inhibitors of the BCL2 family represent an exciting new class of drugs with a novel mechanism of action that are likely to have activity as single agents and in combination with existing myeloma therapies. The BCL2 proteins are oncogenes that promote cell survival and are frequently upregulated in multiple myeloma, making them attractive targets. Venetoclax, a BCL2 specific inhibitor, is furthest along in development and has shown promising results in a subset of myeloma characterized by the t(11;14) translocation. Combining venetoclax with proteasome inhibitors and monoclonal antibodies has improved responses in a broader group of patients, but has come at the expense of a toxicity safety signal that requires additional follow-up. MCL1 inhibitors are likely to be effective in a broader range of patients and are currently in early clinical trials. This review will cover much of what is known about the biology of these drugs, biomarkers that predict response, mechanisms of resistance, and unanswered questions as they pertain to multiple myeloma.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 ","pages":"11-24"},"PeriodicalIF":2.8,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/d0/blctt-11-11.PMC7965688.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25493024","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":"The Impact of Obesity on the Outcomes of Adult Patients with Acute Lymphoblastic Leukemia - A Single Center Retrospective Study.","authors":"Qiuju Liu,&nbsp;Brittny Major,&nbsp;Jennifer Le-Rademacher,&nbsp;Aref A Al-Kali,&nbsp;Hassan Alkhateeb,&nbsp;Kebede Begna,&nbsp;Michelle A Elliott,&nbsp;Naseema Gangat,&nbsp;William J Hogan,&nbsp;C Christopher Hook,&nbsp;Scott H Kaufmann,&nbsp;Animesh Pardanani,&nbsp;Mrinal S Patnaik,&nbsp;Ayalew Tefferi,&nbsp;Alexandra P Wolanskyj-Spinner,&nbsp;Wei Wei,&nbsp;Mark R Litzow","doi":"10.2147/BLCTT.S269748","DOIUrl":"https://doi.org/10.2147/BLCTT.S269748","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients.</p><p><strong>Methods: </strong>We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification.</p><p><strong>Results: </strong>The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03-2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84-15.98) p<0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population.</p><p><strong>Discussion: </strong>In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2021-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/76/blctt-11-1.PMC7837742.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25314927","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":"Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy.","authors":"Audrey M Sigmund,&nbsp;Kieran D Sahasrabudhe,&nbsp;Bhavana Bhatnagar","doi":"10.2147/BLCTT.S223894","DOIUrl":"https://doi.org/10.2147/BLCTT.S223894","url":null,"abstract":"<p><p>Although adults with B-cell acute lymphoblastic leukemia (B-ALL) achieve high complete remission (CR) rates following treatment with intensive multi-agent chemotherapy regimens, up to two-thirds of these patients eventually relapse. Unfortunately, adults with relapsed or refractory (R/R) B-ALL have a poor prognosis, with variable responses to salvage chemotherapy regimens and allogeneic stem cell transplant. As such, the need to develop effective and well-tolerated treatments for this patient population has been of paramount importance over the past decade. In this regard, treatment options for R/R B-ALL patients have expanded considerably over a relatively short period of time, with the approvals of blinatumomab, inotuzumab ozogamicin and tisagenlecleucel occurring within only the past six years. Blinatumomab, a CD19 x CD3 bispecific T-cell engager (BiTE) was the first of these immune therapies to receive approval, and for many patients, is used as first-line salvage therapy. A number of large clinical trials have demonstrated improved progression-free survival and overall survival for R/R B-ALL patients receiving blinatumomab as compared to those receiving conventional salvage chemotherapy. In addition to being approved for both Philadelphia chromosome-negative and Philadelphia chromosome-positive R/R B-ALL, blinatumomab is also the only ALL therapy that carries approval for the treatment of measurable residual disease (MRD). Although blinatumomab has changed the therapeutic landscape for adults with R/R B-ALL, a number of important clinical considerations and questions remain, including the potential role of blinatumomab in the frontline setting, mechanisms of resistance, optimal goal MRD level, the role of transplant following MRD clearance, the optimal place for blinatumomab in the context of other recently approved immune-mediated therapies, and real world outcomes for patients treated outside the context of clinical trials. These issues are the focus of ongoing studies, which will hopefully inform future clinical practice regarding the utility of blinatumomab in the treatment of B-ALL patients.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"10 ","pages":"7-20"},"PeriodicalIF":2.8,"publicationDate":"2020-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S223894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38595620","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":"The Impact of Age on Survival in CLL Patients Receiving Ibrutinib as Initial Therapy.","authors":"Chaitra Ujjani,&nbsp;Anthony Mato,&nbsp;Brian T Hill,&nbsp;John N Allan,&nbsp;Frederick Lansigan,&nbsp;Ryan Jacobs,&nbsp;Alan Skarbnik,&nbsp;Hande Tuncer,&nbsp;John Pagel,&nbsp;Danielle Brander,&nbsp;Bruce Cheson,&nbsp;Paul Barr,&nbsp;Lindsey E Roeker,&nbsp;Jeffrey Pu,&nbsp;Nirav N Shah,&nbsp;Andre Goy,&nbsp;Stephen J Schuster,&nbsp;Nicole Lamanna,&nbsp;Alison Sehgal,&nbsp;Constantine S Tam,&nbsp;Mazyar Shadman","doi":"10.2147/BLCTT.S262592","DOIUrl":"https://doi.org/10.2147/BLCTT.S262592","url":null,"abstract":"<p><strong>Introduction: </strong>Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to 70 years of age.</p><p><strong>Methods: </strong>Therefore, we conducted a retrospective analysis to investigate whether ibrutinib was associated with a greater mortality in older patients outside of a clinical trial setting. This multicenter analysis was performed by investigators at 20 academic and community practices.</p><p><strong>Results: </strong>Amongst the 391 patients included, there was no correlation between age and response rate, PFS, or OS. However, there was a trend to higher rate of deaths in patients >65-years-old (8.7% vs 3.8%, p=0.097), with an increased number of early deaths (13 vs 4, p=0.3).</p><p><strong>Conclusion: </strong>These data suggest greater intolerance, and possibly mortality, with ibrutinib in an older population. Patients should be educated regarding the potential complications related to ibrutinib and symptoms of concern to report.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"10 ","pages":"1-5"},"PeriodicalIF":2.8,"publicationDate":"2020-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S262592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38391486","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":"The Evolving Role of Brentuximab Vedotin in Classical Hodgkin Lymphoma.","authors":"Catherine Lai,&nbsp;Adrese Michael Kandahari,&nbsp;Chaitra Ujjani","doi":"10.2147/BLCTT.S231821","DOIUrl":"https://doi.org/10.2147/BLCTT.S231821","url":null,"abstract":"<p><p>The arrival of the CD30 directed antibody-drug conjugate, brentuximab vedotin (BV), has altered the approach to patients with classical Hodgkin lymphoma. Since initial approval in 2011, BV has been extensively studied in previously untreated and relapsed/refractory patients. Treatment indications for the antibody-drug conjugate have been expanded from the previously treated population to include maintenance therapy after autologous stem cell transplantation and recently, combination with chemotherapy in newly diagnosed advanced stage patients. This article will review the evolution of BV in classical Hodgkin lymphoma, detailing the studies that led to the approved indications and discussion of recent trials in combination with chemotherapy and immunotherapy.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"9 ","pages":"63-71"},"PeriodicalIF":2.8,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S231821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37468005","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":"Knockout Of <i>BIRC5</i> Gene By CRISPR/Cas9 Induces Apoptosis And Inhibits Cell Proliferation In Leukemic Cell Lines, HL60 And KG1.","authors":"Manizheh Narimani,&nbsp;Mohammadreza Sharifi,&nbsp;Ali Jalili","doi":"10.2147/BLCTT.S230383","DOIUrl":"https://doi.org/10.2147/BLCTT.S230383","url":null,"abstract":"<p><strong>Introduction: </strong>Human Baculoviral inhibitor of apoptosis repeat-containing 5 (<i>BIRC5</i>) which encodes survivin exhibits multiple biological activities, such as cell proliferation and apoptosis. Survivin is overexpressed in numerous malignant diseases including acute myeloid leukemia (AML). Recent studies have shown that the CRISPR/Cas9 nuclease-mediated gene-editing systems are suitable approach's for editing or knocking out various genes including oncogenes.</p><p><strong>Methods and materials: </strong>We used CRISPR-Cas9 to knockout the <i>BIRC5</i> in the human leukemic cell line, HL60, and KG1, and these cell lines were transfected with either the Cas9- and three sgRNAs expressing plasmids or negative control (scramble) using Lipofectamine 3000. The efficacy of the transfection was determined by quantitative reverse transcription-polymerase chain (RT-qPCR) and surveyor mutation assays. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively.</p><p><strong>Results: </strong>We have successfully knocked out the <i>BIRC</i>5 gene in these leukemic cells and observed that the <i>BIRC5</i>-knocked out cells by CRISPR/Cas9 showed a significant decrease (30 folds) of survivin at mRNA levels. Moreover, cell death and apoptosis were significantly induced in <i>BIRC5</i>-CRISPR/Cas9-transfected cells compared to the scramble vector.</p><p><strong>Conclusion: </strong>We demonstrated for the first time that targeting <i>BIRC5</i> by CRISPR/Cas9 technology is a suitable approach for the induction of apoptosis in leukemic cells. However, further studies targeting this gene in primary leukemic cells are required.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"9 ","pages":"53-61"},"PeriodicalIF":2.8,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S230383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683328","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":"Strategies For Targeting Chronic Myeloid Leukaemia Stem Cells","authors":"Giovanna Carrá, A. Cartellà, B. Maffeo, A. Morotti","doi":"10.2147/BLCTT.S228815","DOIUrl":"https://doi.org/10.2147/BLCTT.S228815","url":null,"abstract":"Abstract Chronic Myeloid Leukaemia is a myeloproliferative disorder driven by the t(9;22) chromosomal translocation coding for the chimeric protein BCR-ABL. CML treatment represents the paradigm of molecular therapy of cancer. Since the development of the tyrosine kinase inhibitor of the BCR-ABL kinase, the clinical approach to CML has dramatically changed, with a stunning improvement in the quality of life and response rates of patients. However, it remains clear that tyrosine kinase inhibitors (TKIs) are unable to target the most immature cellular component of CML, the CML stem cell. This review summarizes new insights into the mechanisms of resistance to TKIs.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"11 1","pages":"45 - 52"},"PeriodicalIF":2.8,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82820013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}