Cytotherapy最新文献

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(25)00009-X","DOIUrl":"10.1016/S1465-3249(25)00009-X","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Page A4"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143336728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders","authors":"Dimitrios Mougiakakos ,&nbsp;Ranjita Sengupta ,&nbsp;Ralf Gold ,&nbsp;Roland Schroers ,&nbsp;Aiden Haghikia ,&nbsp;Mario Lorente ,&nbsp;Michael Pendleton ,&nbsp;Ames Register ,&nbsp;Christoph Heesen ,&nbsp;Nicolaus Kröger ,&nbsp;Georg Schett ,&nbsp;Andreas Mackensen ,&nbsp;Amber Podoll ,&nbsp;Jonathan Gutman ,&nbsp;Richard Furie ,&nbsp;Ruthee Bayer ,&nbsp;Jörg H.W. Distler ,&nbsp;Sascha Dietrich ,&nbsp;Gerhard Krönke ,&nbsp;Lars Bullinger ,&nbsp;Karen Walker","doi":"10.1016/j.jcyt.2024.09.008","DOIUrl":"10.1016/j.jcyt.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>B-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases.</div></div><div><h3>Methods</h3><div>KYV-101 was manufactured from peripheral blood-derived mononuclear cells of 20 patients across seven autoimmune disease types (neurological autoimmune diseases, n = 13; rheumatological autoimmune diseases, n = 7). Patients ranged from 18 to 75 years of age. Duration of disease ranged from &lt;1 to 23 years since diagnosis. Patients were heavily pretreated, and most were refractory to prior immunosuppressive treatments. Apheresis was collected across nine sites, cryopreserved, and shipped to the manufacturing facility. Healthy donor apheresis samples were collected for manufacturing comparison. Manufacturing was performed using the CliniMACS Prodigy system. Cells were enriched for CD4⁺/CD8⁺ T cells, transduced with a third generation lentiviral vector encoding the CAR, expanded in vitro, and harvested. Percent cell viability, T-cell purity, cellular expansion, and transduction efficiency were assessed. Activity was assessed using cytokine release assays for KYV-101 CAR T cells co-cultured with different CD19^+/– target cell lines.</div></div><div><h3>Results</h3><div>KYV-101 was successfully manufactured for 100% of patients. Transduced cell populations were highly viable, with expansion ranging from 11 to 66 fold at Day 8, and were comparable across disease types. Healthy donor-derived controls displayed similar expansion ranges. High CAR expression and transduction rates were observed, ranging between 37 and 77% with low variation in transgene copy number (two to four per cell). Cell viability of the final KYV-101 drug product ranged from 87 to 97%. KYV-101 displayed robust CD19-dependent and effector dose-related release of the pro-inflammatory cytokine IFN-γ.</div></div><div><h3>Conclusions</h3><div>KYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results support the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 236-246"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell multiomics to advance cell therapy","authors":"Kyndal Goss ,&nbsp;Edwin M. Horwitz","doi":"10.1016/j.jcyt.2024.10.009","DOIUrl":"10.1016/j.jcyt.2024.10.009","url":null,"abstract":"<div><div>Single-cell RNA-sequencing (scRNAseq) was first introduced in 2009 and has evolved with many technological advancements over the last decade. Not only are there several scRNAseq platforms differing in many aspects, but there are also a large number of computational pipelines available for downstream analyses which are being developed at an exponential rate. Such computational data appear in many scientific publications in virtually every field of study; thus, investigators should be able to understand and interpret data in this rapidly evolving field. Here, we discuss key differences in scRNAseq platforms, crucial steps in scRNAseq experiments, standard downstream analyses and introduce newly developed multimodal approaches. We then discuss how single-cell omics has been applied to advance the field of cell therapy.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 137-145"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female-to-male allogeneic transplantation affects outcomes differently according to the type of haplo-transplantation","authors":"Masaharu Tamaki ,&nbsp;Shunto Kawamura ,&nbsp;Kosuke Takano ,&nbsp;Hirohisa Nakamae ,&nbsp;Noriko Doki ,&nbsp;Hiroyuki Ohigashi ,&nbsp;Yumiko Maruyama ,&nbsp;Shuichi Ota ,&nbsp;Nobuhiro Hiramoto ,&nbsp;Tetsuya Eto ,&nbsp;Satoshi Yoshihara ,&nbsp;Ken-ichi Matsuoka ,&nbsp;Masayoshi Masuko ,&nbsp;Makoto Onizuka ,&nbsp;Yoshinobu Kanda ,&nbsp;Takahiro Fukuda ,&nbsp;Yoshiko Atsuta ,&nbsp;Ryu Yanagisawa ,&nbsp;Kimikazu Yakushijin ,&nbsp;Hideki Nakasone","doi":"10.1016/j.jcyt.2024.09.007","DOIUrl":"10.1016/j.jcyt.2024.09.007","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49–0.99], <em>P</em> = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68–1.16], <em>P</em> = 0.40; NRM 0.98 [95% CI: 0.68–1.41], <em>P</em> = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 213-221"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the procedure for manufacturing clinical-grade genetically manipulated natural killer cells for adoptive immunotherapy","authors":"Haolong Lin ,&nbsp;Shanwei Ye ,&nbsp;Shujia Zhang ,&nbsp;Tong Ge ,&nbsp;Dengju Li ,&nbsp;Liang Huang ,&nbsp;Li Zhu ,&nbsp;Wei Mu","doi":"10.1016/j.jcyt.2024.10.006","DOIUrl":"10.1016/j.jcyt.2024.10.006","url":null,"abstract":"<div><h3>Background aims</h3><div><em>Ex vivo−</em>expanded natural killer (NK) cells hold significant potential as antitumor effector cells for adoptive immunotherapy. However, producing clinical-grade, genetically modified NK cells in sufficient quantities presents a considerable challenge.</div></div><div><h3>Methods</h3><div>We tested RPMI 1640, KBM581, SCGM, NK MACS, X-VIVO 15 and AIM-V, each supplemented with fetal bovine serum, human AB serum, human platelet lysate or Immune Cell Serum Replacement (SR) combined with feeder cells, to produce cytotoxic NK cells. Subsequent analyses were conducted to assess cell viability, expansion folds, cytotoxicity, immunophenotype and transcriptome profile of NK cells under certain conditions. Furthermore, transfer plasmids varying in transgene size, promoter elements, backbones and packaging plasmids with different envelopes were used to transduce NK cells, and differences in transduction efficiency were compared. Nucleofection was performed every 2 days from day 0 to day 12 to determine the optimal time window for gene editing.</div></div><div><h3>Results</h3><div>NK cells cultured in KBM581 medium supplemented with serum replacement exhibited the best expansion, achieving greater than 5000-fold increase within 2 weeks and exceeding 25 000-fold expansion within 3 weeks. In addition, NK cells cultured in KBM581 medium with human AB serum demonstrated the greatest cytolytic activities and exhibited greater expression of NKp30, 2B4, PRF1, granzyme B and IL2RG. Baboon envelope pseudotyped lentivirus outperformed baboon envelope-vesicular stomatitis virus type G hybrid envelope lentivirus, achieving robust NK-cell transduction. In addition, efficient gene knockout efficiency was achieved in NK cells on day 4 to day 6 post feeder cell activation using the LONZA DN-100 program, which can strike a balance between editing efficiency and cell expansion.</div></div><div><h3>Conclusions</h3><div>This research presents a Good Manufacturing Practice−compliant protocol using a feeder cell expansion system for the large-scale production of highly cytotoxic NK cells. The protocol facilitates genetic modification of these cells, positioning them as promising candidates for universal therapeutic applications in immunotherapy.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 247-257"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delphi-driven consensus definition for mesenchymal stromal cells and clinical reporting guidelines for mesenchymal stromal cell–based therapeutics","authors":"Laurent Renesme ,&nbsp;Kelly D. Cobey ,&nbsp;Manoj M. Lalu ,&nbsp;Tania Bubela ,&nbsp;Raghavan Chinnadurai ,&nbsp;John De Vos ,&nbsp;Rod Dunbar ,&nbsp;Dean Fergusson ,&nbsp;Daniel Freund ,&nbsp;Jacques Galipeau ,&nbsp;Edwin Horwitz ,&nbsp;Maxime Lê ,&nbsp;Michael Matthay ,&nbsp;David Moher ,&nbsp;Jan Nolta ,&nbsp;Graham Parker ,&nbsp;Donald G. Phinney ,&nbsp;Mahendra Rao ,&nbsp;John E.J. Rasko ,&nbsp;Patricia R.M. Rocco ,&nbsp;Bernard Thébaud","doi":"10.1016/j.jcyt.2024.10.008","DOIUrl":"10.1016/j.jcyt.2024.10.008","url":null,"abstract":"<div><h3>Background aims</h3><div>Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies.</div></div><div><h3>Methods</h3><div>A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. For the first round, to obtain a broad perspective, additional investigators recommended by the steering committee were invited to participate. The first two rounds consisted of online surveys, whereas the third round took the form of a virtual meeting. Participants were asked to rate a series of potential defining characteristics of MSCs and items for reporting guidelines. Consensus was defined as at least 80% of the participants rating the item in the same category of importance.</div></div><div><h3>Results</h3><div>Eighty-seven international participants participated in the first round survey (spring 2023), 17 participants participated in the second online survey (fall 2023) and 15 participants participated in the final virtual consensus meeting (January 2024). For the MSC definition, 20 items were considered and nine reached consensus. Items included terminology (one item), cell marker expression (five items), tissue origin (one item), stemness (one item) and description of critical quality attributes (one item). For the reporting guidelines, with the 28 initial items and the additional items suggested during round 1, a total of 33 items to report were included. This included items on MSC intervention group and control (e.g., MSC product, dose and administration), MSC characteristics (e.g., MSC provenance, “fitness,” viability and immune compatibility) and MSC culture conditions (e.g., oxygen environment, culture medium and use of serum).</div></div><div><h3>Conclusions</h3><div>By applying a Delphi method to establish a consensus definition for MSCs and reporting guidelines for MSC-based clinical trials, this work represents a significant advance in improving transparency and reproducibility in the conduct and reporting of MSC research.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 146-168"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enumeration and gentle sorting of immune cells on chip, key to next generation advanced therapies in outpatient setting","authors":"Sarah Libbrecht ,&nbsp;Koen de Wijs ,&nbsp;Chengxun Liu ,&nbsp;Liesbet Lagae","doi":"10.1016/j.jcyt.2024.10.002","DOIUrl":"10.1016/j.jcyt.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>A thorough understanding of immune-oncology and molecular medicine has been vital in the development of cell therapeutics. At the basis of this translational research and its future implementation into a medicinal product, lies the availability of pure and viable cell populations. Currently, FACS and magnetic bead isolation are successfully used but suffer to fulfill all requirements. FACS is costly and difficult to upscale due to the limitation of shear stress, especially fragile, cells can handle. Therefore, magnetic bead isolation is often used as it is gentler, but it lacks the multiparametric aspect to isolate more complex cellular profiles.</div></div><div><h3>Aims</h3><div>We aim to develop a versatile technology able of multi marker detection and isolation of complex cell types with high purity, viability and throughput.</div></div><div><h3>Methods</h3><div>We have developed a gentle sorting mechanism based on a jet flow created by micro vapor bubbles, enabling a closed microfluidic cell isolation platform capable of multiparametric sorting with high viability, purity and throughput. In this work we compared the purity, recovery and viability of sorted CD4+ CD14- cells to magnetic isolation, most often used for other cell manufacturing approaches. Futhermore, we cultured the sorted cells of both isolation strategies and compared their growth curve and expression of activation-induced IL2 and IFN-γ.</div></div><div><h3>Results</h3><div>We demonstrate that this tool can achieve a pure population of CD4+ CD14- cells with high viability after sorting without compromising the recovery. On top of the viability also the growth and activation potential of sorted cells is unhampered by comparison to the benchmark gentle magnetic isolation.</div></div><div><h3>Conclusions</h3><div>Our technology allows for the development of a compact system which sets it apart from other efforts intended to create automated cell therapeutic solutions.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 229-235"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-based cell replacement therapy: from basic research to clinical application.","authors":"Jun Takahashi","doi":"10.1016/j.jcyt.2025.01.015","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.015","url":null,"abstract":"<p><p>The advancement of induced pluripotent stem cell (iPSC) technology has revolutionized regenerative medicine, enabling breakthroughs in disease modeling, drug discovery, and cell replacement therapies. This review examines the progression of iPSC-based regenerative medicine, focusing on cell replacement therapy and mechanisms like the Replacement Effect, which is crucial for long-term tissue regeneration. Using Parkinson's disease as a key example, it discusses the induction of midbrain dopaminergic neurons from iPSCs and the importance of precise signaling for safety and efficacy. By demonstrating the integration and safety of these cells, animal studies have paved the way for clinical trials. This review highlights the need for strategic collaboration among stakeholders-regulatory authorities, research and medical staff, and industry-to ensure successful clinical applications. iPSC technology's ongoing evolution holds significant promise for broader therapeutic applications and improved patient outcomes.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(25)00007-6","DOIUrl":"10.1016/S1465-3249(25)00007-6","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143336965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal cells can block palmitate training of macrophages via cyclooxygenase-2 and interleukin-1 receptor antagonist","authors":"Laura M. Bitterlich ,&nbsp;Courteney Tunstead ,&nbsp;Andrew E. Hogan ,&nbsp;James A. Ankrum ,&nbsp;Karen English","doi":"10.1016/j.jcyt.2024.10.011","DOIUrl":"10.1016/j.jcyt.2024.10.011","url":null,"abstract":"<div><div>Innate training of macrophages can be beneficial for the clearance of pathogens. However, for certain chronic conditions, innate training can have detrimental effects due to an excessive production of pro-inflammatory cytokines. Obesity is a condition that is associated with a range of increased pro-inflammatory training stimuli including the free fatty acid palmitate. Mesenchymal stromal cells (MSCs) are powerful immunomodulators and known to suppress inflammatory macrophages via a range of soluble factors. We show that palmitate training of murine bone-marrow-derived macrophages and human monocyte-derived macrophages (MDMs) results in an increased production of TNFα and IL-6 upon stimulation with lipopolysaccharide and is associated with epigenetic remodeling. Palmitate training led to metabolic changes, however, MSCs did not alter the metabolic profile of human MDMs. Using a transwell system, we demonstrated that human bone marrow MSCs block palmitate training in both murine and human macrophages suggesting the involvement of secreted factors. MSC disruption of the training process occurs through more than one pathway. Suppression of palmitate-enhanced TNFα production is associated with cyclooxygenase-2 activity in MSCs, while secretion of interleukin-1 receptor antagonist by MSCs is required to suppress palmitate-enhanced IL-6 production in MDMs.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 169-180"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}