Xenotransplantation最新文献

{"title":"Limited availability of methods for the detection of xenotransplantation-relevant viruses in veterinary laboratories.","authors":"Joachim Denner","doi":"10.1111/xen.12851","DOIUrl":"https://doi.org/10.1111/xen.12851","url":null,"abstract":"<p><strong>Background: </strong>The German Xenotransplantation Consortium is in the process to prepare a clinical trial application (CTA) on xenotransplantation of genetically modified pig hearts. In the CTA documents to the central and national regulatory authorities, that is, the European Medicines Agency (EMA) and the Paul Ehrlich Institute (PEI), respectively, it is required to list the potential zoonotic or xenozoonotic porcine microorganisms including porcine viruses as well as to describe methods of detection in order to prevent their transmission. The donor animals should be tested using highly sensitive detection systems. I would like to define a detection system as the complex including the actual detection methods, either PCR-based, cell-based, or immunological methods and their sensitivity, as well as sample generation, sample preparation, sample origin, time of sampling, and the necessary negative and positive controls. Lessons learned from the identification of porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) in the xenotransplanted heart in the recipient in the Baltimore study underline how important such systems are. The question is whether veterinary laboratories can supply such assays.</p><p><strong>Methods: </strong>A total of 35 veterinary laboratories in Germany were surveyed for their ability to test for selected xenotransplantation-relevant viruses, including PCMV/PRV, hepatitis E virus, and porcine endogenous retrovirus-C (PERV-C). As comparison, data from Swiss laboratories and a laboratory in the USA were analyzed. Furthermore, we assessed which viruses were screened for in clinical and preclinical trials performed until now and during screening of pig populations.</p><p><strong>Results: </strong>Of the nine laboratories that provided viral diagnostics, none of these included all potential viruses of concern, indeed, the most important assays confirmed in recent human trials, antibody detection of PCMV/PRV and screening for PERV-C were not available at all. The situation was similar in Swiss and US laboratories. Different viruses have been tested for in first clinical and preclinical trials performed in various countries.</p><p><strong>Conclusion: </strong>Based on these results it is necessary to establish special virological laboratories able to test for all xenotransplantation-relevant viruses using validated assays, optimally in the xenotransplantation centers.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 3","pages":"e12851"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam: Sir Roy Calne, FRCS, FRS, 1930-2024.","authors":"David K C Cooper","doi":"10.1111/xen.12849","DOIUrl":"https://doi.org/10.1111/xen.12849","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 3","pages":"e12849"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-pig antibodies in swine veterinarian serum: Implications for clinical xenotransplantation.","authors":"Guerard W Byrne, Christopher G A McGregor","doi":"10.1111/xen.12865","DOIUrl":"https://doi.org/10.1111/xen.12865","url":null,"abstract":"<p><p>Recent clinical xenotransplantation and human decedent studies demonstrate that clinical hyperacute rejection of genetically engineered porcine organs can be reliably avoided but that antibody mediated rejection (AMR) continues to limit graft survival. We previously identified porcine glycans and proteins which are immunogenic after cardiac xenotransplantation in non-human primates, but the clinical immune response to antigens present in glycan depleted triple knockout (TKO) donor pigs is poorly understood. In this study we use fluorescence barcoded human embryonic kidney cells (HEK) and HEK cell lines expressing porcine glycans (Gal and SDa) or proteins (tetraspanin-29 [CD9], membrane cofactor protein [CD46], protectin, membrane attack complex inhibition factor [CD59], endothelial cell protein C receptor, and Annexin A2) to screen antibody reactivity in human serum from 160 swine veterinarians, a serum source with potential occupational immune challenge from porcine tissues and pathogens. High levels of anti-Gal IgM were present in all samples and lower levels of anti-SDa IgM were present in 41% of samples. IgM binding to porcine proteins, primarily CD9 and CD46, previously identified as immunogenic in pig to non-human primate cardiac xenograft recipients, was detected in 28 of the 160 swine veterinarian samples. These results suggest that barcoded HEK cell lines expressing porcine protein antigens can be useful for screening human patient serum. A comprehensive analysis of sera from clinical xenotransplant recipients to define a panel of commonly immunogenic porcine antigens will likely be necessary to establish an array of porcine non-Gal antigens for effective monitoring of patient immune responses and allow earlier therapies to reverse AMR.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 3","pages":"e12865"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transthoracic echocardiography is a simple tool for size matching in cardiac xenotransplantation.","authors":"Maren Mokelke, Martin Bender, Bruno Reichart, Elisabeth Neumann, Julia Radan, Ines Buttgereit, David Ayares, Eckhard Wolf, Paolo Brenner, Jan-Michael Abicht, Matthias Längin","doi":"10.1111/xen.12861","DOIUrl":"https://doi.org/10.1111/xen.12861","url":null,"abstract":"<p><strong>Background: </strong>Preoperative size matching is essential for both allogeneic and xenogeneic heart transplantation. In preclinical pig-to-baboon xenotransplantation experiments, porcine donor organs are usually matched to recipients by using indirect parameters, such as age and total body weight. For clinical use of xenotransplantation, a more precise method of size measurement would be desirable to guarantee a \"perfect match.\" Here, we investigated the use of transthoracic echocardiography (TTE) and described a new method to estimate organ size prior to xenotransplantation.</p><p><strong>Methods: </strong>Hearts from n = 17 genetically modified piglets were analyzed by TTE and total heart weight (THW) was measured prior to xenotransplantation into baboons between March 2018 and April 2022. Left ventricular (LV) mass was calculated according to the previously published method by Devereux et al. and a newly adapted formula. Hearts from n = 5 sibling piglets served as controls for the determination of relative LV and right ventricular (RV) mass. After explantation, THW and LV and RV mass were measured.</p><p><strong>Results: </strong>THW correlated significantly with donor age and total body weight. The strongest correlation was found between THW and LV mass calculated by TTE. Compared to necropsy data of the control piglets, the Devereux formula underestimated both absolute and relative LV mass, whereas the adapted formula yielded better results. Combining the adapted formula and the relative LV mass data, THW can be predicted with TTE.</p><p><strong>Conclusions: </strong>We demonstrate reliable LV mass estimation by TTE for size matching prior to xenotransplantation. An adapted formula provides more accurate results of LV mass estimation than the generally used Devereux formula in the xenotransplantation setting. TTE measurement of LV mass is superior for the prediction of porcine heart sizes compared to conventional parameters such as age and total body weight.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 3","pages":"e12861"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity, growth and heart function of Auckland Island pigs, a potential source for organ xenotransplantation","authors":"Andreas Lange, Ivica Medugorac, Asghar Ali, Barbara Kessler, Mayuko Kurome, Valeri Zakhartchenko, Sabine E. Hammer, Andreas Hauser, Joachim Denner, Britta Dobenecker, Gerhard Wess, Paul L. J. Tan, Olga Garkavenko, Bruno Reichart, Eckhard Wolf, Elisabeth Kemter","doi":"10.1111/xen.12858","DOIUrl":"https://doi.org/10.1111/xen.12858","url":null,"abstract":"One of the prerequisites for successful organ xenotransplantation is a reasonable size match between the porcine organ and the recipient's organ to be replaced. Therefore, the selection of a suitable genetic background of source pigs is important. In this study, we investigated body and organ growth, cardiac function, and genetic diversity of a colony of Auckland Island pigs established at the Center for Innovative Medical Models (CiMM), LMU Munich. Male and female Auckland Island pig kidney cells (selected to be free of porcine endogenous retrovirus C) were imported from New Zealand, and founder animals were established by somatic cell nuclear transfer (SCNT). Morphologically, Auckland Island pigs have smaller body stature compared to many domestic pig breeds, rendering their organ dimensions well‐suited for human transplantation. Furthermore, echocardiography assessments of Auckland Island pig hearts indicated normal structure and functioning across various age groups throughout the study. Single nucleotide polymorphism (SNP) analysis revealed higher runs of homozygosity (ROH) in Auckland Island pigs compared to other domestic pig breeds and demonstrated that the entire locus coding the swine leukocyte antigens (SLAs) was homozygous. Based on these findings, Auckland Island pigs represent a promising genetic background for organ xenotransplantation.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"106 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel factors potentially initiating acute antibody‐mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen","authors":"Kohei Kinoshita, Akihiro Maenaka, Ivy A. Rosales, Ahmad Karadagi, Toshihide Tomosugi, David Ayares, Seth Lederman, Robert B. Colvin, Tatsuo Kawai, Richard N. Pierson, Takaaki Kobayashi, David K. C. Cooper","doi":"10.1111/xen.12859","DOIUrl":"https://doi.org/10.1111/xen.12859","url":null,"abstract":"Antibody‐mediated rejection (AMR) is a common cause of graft failure after pig‐to‐nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti‐CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti‐CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute‐onset AMR. The association of a urinary infection with graft rejection has been well‐documented in ABO‐incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"20 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Call for applications for the Dr. med. vet. Dr. med. Ernst von Wnuck Award 2024 for Cardiovascular Research","authors":"Eckhard Wolf","doi":"10.1111/xen.12856","DOIUrl":"https://doi.org/10.1111/xen.12856","url":null,"abstract":"<p>The call for applications for the Dr. med. vet. Dr. med. Ernst von Wnuck Award, endowed with 3000 EUR, is aimed at heads of research groups and young scientists working in the field of xenogeneic heart transplantation. The spectrum of relevant work includes basic research, development of suitable donor pigs, preclinical transplantation models, and innovative approaches to clinical translation. Applicants should have relevant, outstanding research and demonstrate a scientific focus in their career. Please send your application documents of maximum two pages on the current status of your scientific work, planned own projects in the field as well as five representative publications together with your CV by May 31, 2024 to Prof. Dr. Eckhard Wolf, Gene Center, LMU Munich, Germany (ewolf@genzentrum.lmu.de).</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenotransplantation clinical trials: Should patients with diminished capacity be permitted to enroll?","authors":"Daniel Rodger, James Mack, Christopher Bobier, Luz Padilla, Daniel J. Hurst","doi":"10.1111/xen.12857","DOIUrl":"https://doi.org/10.1111/xen.12857","url":null,"abstract":"&lt;h2&gt;1 INTRODUCTION&lt;/h2&gt;\u0000&lt;p&gt;Before xenotransplantation clinical trials begin, it is essential to establish clear and equitable participant selection criteria. Selection criteria have been suggested in the literature, as well as in a proposed kidney xenotransplantation phase 1 clinical trial.&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; In each, inclusion criteria is predicated on patients possessing clinical decision-making capacity. Ensuring informed consent for xenotransplantation clinical trials with patients who have decision-making capacity is recognized as complex for the following reasons: the possibility of therapeutic misconception, potential for xenozoonosis, and the potentially burdensome requirement for lifelong biosurveillance.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Informed consent for enrollment in a xenotransplantation trial with adult persons who have diminished capacity would involve additional complexities. By diminished capacity, we mean to describe someone who—for various medical reasons—does not have the ability to provide informed consent. To our knowledge, no xenotransplantation investigator, nor the proposed kidney xenotransplantation phase I clinical trial in the United States, currently proposes including persons with diminished capacity. Nonetheless, the topic has been broached, and we believe it requires additional independent scrutiny.&lt;/p&gt;\u0000&lt;h3&gt;1.1 Current recommendations for including persons with diminished capacity&lt;/h3&gt;\u0000&lt;p&gt;Xenotransplantation clinical trials with persons who lack decision-making capacity have not been considered at length and would likely be controversial. The Nuffield Council on Bioethics recommended that “the first xenotransplantation trials should not involve adults incapable of consenting to participation on their own behalf” (7.25).&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; It made an exception, however: “The Medical Research Council has recommended that the participation of incapacitated adults in therapeutic research may be justified if, in addition to evidence that the procedure will benefit the individual, it relates to their incapacitating condition and the relevant knowledge could not be gained by research in adults able to consent” (7.26).&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Similarly, the United States Department of Health and Human Services (DHHS) stated: “enrollment of mentally impaired individuals into xenotransplantation protocols should be limited to those in whom mental capacity is likely to be restored by the procedure.”&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Additionally, in the DHHS guidelines, a surrogate must confirm that the clinical trial aligns with the person's preferences or would promote their best interests and that they are “likely to adhere to lifelong follow-up requirements.”&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;In 2012, the American Medical Association (AMA) Council on Ethical and Judicial Affairs posited that it “would be ethical to include children and incompetent adults in xenotransplantation research protocols only when the patients ar","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"8 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human ST3Gal II and ST6GalNAc IV genes increase human serum‐mediated cytotoxicity to xenogeneic cells","authors":"Hyunju Choi, Kwon‐Ho Song, Hee‐Do Kim, Jun‐Young Park, Young‐Choon Lee, Hee‐Jung Choi, Cheorl‐Ho Kim","doi":"10.1111/xen.12855","DOIUrl":"https://doi.org/10.1111/xen.12855","url":null,"abstract":"Carbohydrate‐antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self‐defense and immunity. Xeno‐reactive antibodies included in natural human sera play a protecting role in an acute phase‐rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation‐pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV‐transfected PK15 cells, as compared to the control. In the hST6Gal I‐carrying cells, the cytotoxicity to human serum was rather decreased. Moreover, flow cytometry analysis revealed that an alteration of pig glycosylation‐pattern by hST3Gal II or hST6GalNAc IV influences on a binding of human IgM or IgG, respectively, in pig kidney cells, regardless of Gal antigen alteration. Finally, we found that hST6GalNAc IV contributed to increase of terminal disialylated tetrasaccharide structure, disialyl T antigen, as evidenced by increase of the MAL II lectin binding capacity in the hST6GalNAc IV‐transfected PK15 cells, compared with control. Therefore, our results suggest that carbohydrate antigens, such as disialyl T antigen, newly synthesized by the ST3Gal II‐ and ST6GalNAc IV are potentially believed to be new xeno‐reactive elements.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"25 4 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of novel circoviruses in humans and pigs and their possible importance for xenotransplantation and blood transfusions.","authors":"Tanja Opriessnig, Chao-Ting Xiao, Nicolas J Mueller, Joachim Denner","doi":"10.1111/xen.12842","DOIUrl":"10.1111/xen.12842","url":null,"abstract":"<p><strong>Background: </strong>As sequencing is becoming more broadly available, virus discovery continues. Small DNA viruses contribute to up to 60% of the overall virus load in pigs. Porcine circoviruses (PCVs) are small DNA viruses with a single-stranded circular genome. They are common in pig breeds and have not been properly addressed for their potential risk in xenotransplantation. Whereas PCV1 is non-pathogenic in pigs, PCV2 has been associated with various disease manifestations. Recently two new circoviruses have been described, PCV3 and PCV4. While PCV4 is currently present mainly in Asia, PCV3 is widely distributed, and has been identified in commercial pigs, wild boars, and pigs generated for xenotransplantation. In one case PCV3 was transmitted by pigs to baboons via heart transplantation. PCV3 pathogenicity in pigs was controversial initially, however, the virus was found to be associated with porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure, and multisystemic inflammation. Inoculation studies with PCV3 infectious clones confirmed that PCV3 is pathogenic. Most importantly, recently discovered human circoviruses (CV) are closely related to PCV3.</p><p><strong>Methods: </strong>Literature was evaluated and summarized. A dendrogram of existing circoviruses in pigs, humans, and other animal species was created and assessed at the species level.</p><p><strong>Results: </strong>We found that human circoviruses can be divided into three species, human CV1, CV2, and CV3. Human CV2 and CV3 are closest to PCV3.</p><p><strong>Conclusions: </strong>Circoviruses are ubiquitous. This communication should create awareness of PCV3 and the newly discovered human circoviruses, which may be a problem for blood transfusions and xenotransplantation in immune suppressed individuals.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 2","pages":"e12842"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}