Islets最新文献

{"title":"Reconstructing human pancreatic islet architectures using computational optimization.","authors":"Gerardo J Félix-Martínez,&nbsp;Aurelio N Mata,&nbsp;J Rafael Godínez-Fernández","doi":"10.1080/19382014.2020.1823178","DOIUrl":"https://doi.org/10.1080/19382014.2020.1823178","url":null,"abstract":"<p><p>We outline a general methodology based on computational optimization and experimental data to reconstruct human pancreatic islet architectures. By using the nuclei coordinates of islet cells obtained through DAPI staining, cell types identified by immunostaining, and cell size distributions estimated from capacitance measurements, reconstructed islets composed of non-overlapping spherical cells were obtained through an iterative optimization procedure. In all cases, the reconstructed architectures included >99% of the experimental identified cells, each of them having a radius within the experimentally reported ranges. Given the wide use of mathematical modeling for the study of pancreatic cells, and recently, of cell-cell interactions within the pancreatic islets, the methodology here proposed, also capable of identifying cell-to-cell contacts, is aimed to provide with a framework for modeling and analyzing experimentally-based pancreatic islet architectures.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 6","pages":"121-133"},"PeriodicalIF":2.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1823178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38519884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.","authors":"M Hoang,&nbsp;J W Joseph","doi":"10.1080/19382014.2020.1802183","DOIUrl":"https://doi.org/10.1080/19382014.2020.1802183","url":null,"abstract":"<p><p>Anaplerosis and the associated mitochondrial metabolite transporters generate unique cytosolic metabolic signaling molecules that can regulate insulin release from pancreatic β-cells. It has been shown that mitochondrial metabolites, transported by the citrate carrier (CIC), dicarboxylate carrier (DIC), oxoglutarate carrier (OGC), and mitochondrial pyruvate carrier (MPC) play a vital role in the regulation of glucose-stimulated insulin secretion (GSIS). Metabolomic studies on static and biphasic insulin secretion, suggests that several anaplerotic derived metabolites, including α-ketoglutarate (αKG), are strongly associated with nutrient regulated insulin secretion. Support for a role of αKG in the regulation of insulin secretion comes from studies looking at αKG dependent enzymes, including hypoxia-inducible factor-prolyl hydroxylases (PHDs) in clonal β-cells, and rodent and human islets. This review will focus on the possible link between defective anaplerotic-derived αKG, PHDs, and the development of type 2 diabetes (T2D).</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 5","pages":"108-119"},"PeriodicalIF":2.2,"publicationDate":"2020-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1802183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38336250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish.","authors":"Morgan A Robertson,&nbsp;Leah R Padgett,&nbsp;Jonathan A Fine,&nbsp;Gaurav Chopra,&nbsp;Teresa L Mastracci","doi":"10.1080/19382014.2020.1791530","DOIUrl":"https://doi.org/10.1080/19382014.2020.1791530","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a disease characterized by destruction of the insulin-producing beta cells. Currently, there remains a critical gap in our understanding of how to reverse or prevent beta cell loss in individuals with T1D. Previous studies in mice discovered that pharmacologically inhibiting polyamine biosynthesis using difluoromethylornithine (DFMO) resulted in preserved beta cell function and mass. Similarly, treatment of non-obese diabetic mice with the tyrosine kinase inhibitor Imatinib mesylate reversed diabetes. The promising findings from these animal studies resulted in the initiation of two separate clinical trials that would repurpose either DFMO (NCT02384889) or Imatinib (NCT01781975) and determine effects on diabetes outcomes; however, whether these drugs directly stimulated beta cell growth remained unknown. To address this, we used the zebrafish model system to determine pharmacological impact on beta cell regeneration. After induction of beta cell death, zebrafish embryos were treated with either DFMO or Imatinib. Neither drug altered whole-body growth or exocrine pancreas length. Embryos treated with Imatinib showed no effect on beta cell regeneration; however, excitingly, DFMO enhanced beta cell regeneration. These data suggest that pharmacological inhibition of polyamine biosynthesis may be a promising therapeutic option to stimulate beta cell regeneration in the setting of diabetes.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 5","pages":"99-107"},"PeriodicalIF":2.2,"publicationDate":"2020-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1791530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity.","authors":"Yu Hee Lee,&nbsp;Hye Sook Jung,&nbsp;Min Jeong Kwon,&nbsp;Jung Eun Jang,&nbsp;Tae Nyun Kim,&nbsp;Soon Hee Lee,&nbsp;Mi-Kyung Kim,&nbsp;Jeong Hyun Park","doi":"10.1080/19382014.2020.1783162","DOIUrl":"https://doi.org/10.1080/19382014.2020.1783162","url":null,"abstract":"<p><strong>Introduction: </strong>Melatonin is a hormone known as having very strong anti-oxidant property. Senescence is a biological state characterized by the loss of cell replication and the changes consisting of a pro-inflammatory phenotype, leading to Senescence Associated Secretory Phenotype (SASP) which is now regarded as one of the fundamental processes of many degenerative diseases. Increased cell division count induces cell senescence via DNA damage in response to elevated Reactive Oxygen Species (ROS). We wanted to test whether melatonin could reduce apoptosis and stress induced premature pancreatic β-cell senescence induced by glucotoxicity and glucolipotoxicity.</p><p><strong>Materials and method: </strong>Cultured rodent pancreatic β-cell line (INS-1 cell) was used. Glucotoxicity (HG: hyperglycemia) and glucolipotoxicity (HGP: hyperglycemia with palmitate) were induced by hyperglycemia and the addition of palmitate. The degrees of the senescence were measured by SA-β-Gal and P16^lnk4A staining along with the changes of cell viabilities, cell cycle-related protein and gene expressions, endogenous anti-oxidant defense enzymes, and Glucose Stimulated Insulin Secretion (GSIS), before and after melatonin treatment.</p><p><strong>Results: </strong>Cultured INS-1 cells in HG and HGP conditions revealed accelerated senescence, increased apoptosis, cell cycle arrest, compromised endogenous anti-oxidant defense, and impaired glucose-stimulated insulin secretion. Melatonin decreased apoptosis and expressions of proteins related to senescence, increase the endogenous anti-oxidant defense, and improved glucose-stimulated insulin secretion.</p><p><strong>Conclusion: </strong>Melatonin protected pancreatic β-cell from apoptosis, decreased expressions of the markers related to the accelerated senescence, and improved the biological deteriorations induced by glucotoxicity and glucolipotoxicity.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 4","pages":"87-98"},"PeriodicalIF":2.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1783162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38158802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a mouse model of islet transplantation using MIN-6 cells.","authors":"Douglas O Sobel,&nbsp;Barath Ramasubramanian,&nbsp;Larry Mitnaul","doi":"10.1080/19382014.2020.1763719","DOIUrl":"https://doi.org/10.1080/19382014.2020.1763719","url":null,"abstract":"<p><p>Immortalized beta cells are an abundant source of insulin-producing cells. Although MIN-6 cells have similar characteristics as normal islets <i>in vitro</i>, the <i>in vivo</i> use of MIN-6 cells has not been fully described. This study characterizes <i>in vivo</i> mouse models of MIN-6 transplantation and rejection. Subcutaneous (<i>sc</i>) transplantation of MIN-6 cells in either Matrigel or HyStem-C hydrogels reduced blood sugars in nude mice and thus are good matrices for MIN-6 cells <i>in vivo</i>. NOD mice are good transplant recipients since they best rejected MIN-6 cells. MLR responses from BalbC, Black Webster, Swiss Black, C3H, and NOD mice correlated with mean blood glucose response suggesting the importance of allogeneic differences in the rejection of cells. Three days of cyclosporine administration caused no inhibition of MIN-6 cell rejection and 6 days resulted in a transient decrease in blood glucose, while daily administration inhibited rejection long term. Kinetic glucose tolerance (GTT) studies in nude mice demonstrated transplanted MIN-6 cells are close but not as effective as normal islets in controlling blood glucose and blood glucose set point for insulin release in MIN-6 cells decreases to hypoglycemic levels over time. To avoid hypoglycemia, the effect of MIN-6 cell irradiation was assessed. However, irradiation only delayed the development of hypoglycemia, not altering the final glucose set point for insulin release. In conclusion, we have characterized a mouse model for beta-cell transplantation using subcutaneous MIN-6 cells that can be used as a tool to study approaches to mitigate immune rejection.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 4","pages":"71-86"},"PeriodicalIF":2.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1763719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38070305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An islet maturation media to improve the development of young porcine islets during in vitro culture.","authors":"Hien Lau,&nbsp;Nicole Corrales,&nbsp;Samuel Rodriguez,&nbsp;Colleen Luong,&nbsp;Frank Zaldivar,&nbsp;Michael Alexander,&nbsp;Jonathan R T Lakey","doi":"10.1080/19382014.2020.1750933","DOIUrl":"https://doi.org/10.1080/19382014.2020.1750933","url":null,"abstract":"<p><strong>Background: </strong>The use of pancreata from pre-weaned piglets has the potential to serve as an unlimited alternative source of islets for clinical xenotransplantation. As pre-weaned porcine islets (PPIs) are immature and require prolonged culture, we developed an islet maturation media (IMM) and evaluated its effect on improving the quantity and quality of PPIs over 14 days of culture.</p><p><strong>Methods: </strong>PPIs were isolated from the pancreata of pre-weaned Yorkshire piglets (8-15 days old). Each independent islet isolation was divided for culture in either control Ham's F-10 media (n = 5) or IMM (n = 5) for 14 days. On day 3, 7 and 14 of culture, islets were assessed for islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of beta cells, and insulin secretion during glucose stimulation.</p><p><strong>Results: </strong>In comparison to control islets, culturing PPIs in IMM significantly increased islet yield. PPIs cultured in IMM also maintained a stable isolation index and viability throughout 14 days of culture. The insulin content, endocrine cellular composition, and differentiation of beta cells were significantly improved in PPIs cultured in IMM, which subsequently augmented their insulin secretory capacity in response to glucose challenge compared to control islets.</p><p><strong>Conclusions: </strong>Culturing PPIs in IMM increases islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of endocrine progenitor cells toward beta cells, and insulin secretion. Due to the improved islet quantity and quality after <i>in vitro</i> culture, the use of IMM in the culture of PPIs will assist to advance the outcomes of clinical islet xenotransplantation.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 3","pages":"41-58"},"PeriodicalIF":2.2,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1750933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37981103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective monitoring of insulin secretion after CRISPR interference in intact pancreatic islets despite submaximal infection.","authors":"Kaavian Shariati,&nbsp;Zachary Pappalardo,&nbsp;Deeksha G Chopra,&nbsp;Nicholas Yiv,&nbsp;Robin Sheen,&nbsp;Gregory Ku","doi":"10.1080/19382014.2020.1752072","DOIUrl":"https://doi.org/10.1080/19382014.2020.1752072","url":null,"abstract":"<p><p>Virus-mediated gene knockdown in intact pancreatic islets is technically challenging due to poor infection of the center of the islet. Because the cells that do not have knockdown have normal insulin secretion, measuring changes in insulin secretion after gene knockdown is challenging. We describe a method to monitor insulin secretion from only the beta cells with knockdown of a gene of interest in intact islets using a single lentivirus containing a guide RNA, a luciferase insulin secretion reporter and a dCas9-KRAB cassette. This method allows rapid and inexpensive monitoring of insulin secretion from only those beta cells with knockdown, circumventing the problem of incomplete islet infection.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 3","pages":"59-69"},"PeriodicalIF":2.2,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1752072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38078821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of pre-transplant psychosocial burden in an integrated national islet transplant program.","authors":"Aaron Yl Liew,&nbsp;Elizabeth Holmes-Truscott,&nbsp;Anneliese Js Flatt,&nbsp;Denise Bennett,&nbsp;Robert Crookston,&nbsp;Mirka Pimkova,&nbsp;Linda Birtles,&nbsp;John Casey,&nbsp;Andrew Pernet,&nbsp;Ruth C Wood,&nbsp;Pratik Choudhary,&nbsp;Shareen Forbes,&nbsp;Martin K Rutter,&nbsp;Miranda Rosenthal,&nbsp;Paul Johnson,&nbsp;James Am Shaw,&nbsp;Jane Speight","doi":"10.1080/19382014.2020.1736740","DOIUrl":"https://doi.org/10.1080/19382014.2020.1736740","url":null,"abstract":"<p><p>The psychological burden experienced by people with diabetes prior to islet transplantation is recognized but has not been studied comprehensively, especially in relation to glycemia. Therefore, we conducted a rigorous pre-operative psychosocial profile of UK islet transplant recipients, and compared groups with higher/lower HbA1 c to test the null hypothesis that pre-transplant hypoglycemia awareness and psychosocial burden would not be related to baseline HbA1 c in this high-risk cohort. Pre-transplant, recipients (n = 44) completed validated hypoglycemia awareness questionnaires and generic/diabetes-specific measures of psychological traits and states. Scores were compared in groups, dichotomized by HbA1 c (≤8% versus >8%). Participants were aged (mean±SD) 53 ± 10 years; 64% were women; with HbA1 c 8.3 ± 1.7%. Median rate of severe hypoglycemia over the preceding 12 months was 13 events/person-year and 90% had impaired awareness of hypoglycemia (Gold/Clarke score ≥4). Participants had elevated fear of hypoglycemia (HFS-II Worry), impaired diabetes-specific quality of life (DQoL) and low generic health status (SF-36; EQ-5D). One quarter reported scores indicating likely anxiety/depression (HAD). Dispositional optimism (LOT-R) and generalized self-efficacy (GSE) were within published 'norms.' Despite negative perceptions of diabetes (including low personal control), participants were confident that islet transplantation would help (BIPQ). Hypoglycemia awareness and psychosocial profile were comparable in lower (n = 24) and higher (n = 20) HbA1 c groups. Islet transplant candidates report sub-optimal generic psychological states (anxiety/depressive symptoms), health status and diabetes-specific psychological states (fear of hypoglycemia, diabetes-specific quality of life). While their generic psychological traits (optimism, self-efficacy) are comparable with the general population, they are highly optimistic about forthcoming transplant. HbA1 c is not a proxy measure of psychosocial burden, which requires the use of validated questionnaires to systematically identify those who may benefit most from psychological assessment and support.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 2","pages":"21-31"},"PeriodicalIF":2.2,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1736740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38279081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway.","authors":"Mark Anthony Jara,&nbsp;Joao Pedro Werneck-De-Castro,&nbsp;Camila Lubaczeuski,&nbsp;James D Johnson,&nbsp;Ernesto Bernal-Mizrachi","doi":"10.1080/19382014.2020.1762471","DOIUrl":"https://doi.org/10.1080/19382014.2020.1762471","url":null,"abstract":"<p><p>Maintenance of pancreatic β-cell mass and function is fundamental to glucose homeostasis and to prevent diabetes. The PI3 K-Akt-mTORC1 pathway is critical for β-cells mass and function, while PDX1 has been implicated in β-cell development, maturation, and function. Here we tested whether Akt signaling requires PDX1 expression to regulate β-cell mass, proliferation, and glucose homeostasis. In order to address that, we crossed a mouse model overexpressing constitutively active Akt mutant in β-cells (<i>β-caAkt</i>) with mice lacking one allele of PDX1gene (<i>β-caAkt/pdx1^+/-)</i>. While the <i>β-caAkt</i> mice exhibit higher plasma insulin levels, greater β-cell mass and improved glucose tolerance compared to control mice, the <i>β-caAkt/pdx1^+/-</i> mice are hyperglycemic and intolerant to glucose. The changes in glucose homeostasis in <i>β-caAkt/pdx1^+/-</i> were associated with a 60% reduction in β-cell mass compared to <i>β-caAkt</i> mice. The impaired β-cell mass in the <i>β-caAkt/pdx1^+/-</i> mice can be explained by a lesser β-cell proliferation measured by the number of Ki67 positive β-cells. We did not observe any differences in apoptosis between <i>β-caAkt/pdx1^+/-</i> and <i>β-caAkt</i> mice. In conclusion, PDX1 contributes to β-cell mass expansion and glucose metabolism induced by activation of Akt signaling.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 2","pages":"32-40"},"PeriodicalIF":2.2,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1762471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38336301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of preexisting HMGB1 within fetal bovine serum on murine pancreatic beta cell biology.","authors":"Hyunwoo Chung,&nbsp;Sung Ji Hong,&nbsp;So Won Choi,&nbsp;Chung-Gyu Park","doi":"10.1080/19382014.2019.1696128","DOIUrl":"https://doi.org/10.1080/19382014.2019.1696128","url":null,"abstract":"<p><p>High-mobility group box 1 (HMGB1) can act as a structural protein of the chromatin and at the same time as a mediator of the immune system. Its high correlation with the graft acceptance in pancreatic islet recipients makes it a biomarker in islet transplantation. With the suspicion that preexisting HMGB1 in the fetal bovine serum (FBS) would be detrimental to the viability and function of murine beta cells, HMGB1 was removed from FBS and its impact was investigated. Interestingly, the elimination of HMGB1 from FBS seemed unfavorable to the viability and function of cultured murine beta cells, suggesting that the preexisting HMGB1 in the FBS may be an indispensable component of islet cell culture.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 1","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1696128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37540515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}