Paula M Wagner, Santiago J Fornasier, Mario E Guido
{"title":"Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.","authors":"Paula M Wagner, Santiago J Fornasier, Mario E Guido","doi":"10.1007/s10571-024-01485-2","DOIUrl":"10.1007/s10571-024-01485-2","url":null,"abstract":"<p><p>The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"51"},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440208","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}
Shu-Han Zhao, Xin-Yu Ji, Guo-Zhen Yuan, Tao Cheng, Hai-Yi Liang, Si-Qi Liu, Fu-Yi Yang, Yang Tang, Shuai Shi
{"title":"A Bibliometric Analysis of the Spatial Transcriptomics Literature from 2006 to 2023.","authors":"Shu-Han Zhao, Xin-Yu Ji, Guo-Zhen Yuan, Tao Cheng, Hai-Yi Liang, Si-Qi Liu, Fu-Yi Yang, Yang Tang, Shuai Shi","doi":"10.1007/s10571-024-01484-3","DOIUrl":"10.1007/s10571-024-01484-3","url":null,"abstract":"<p><p>In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"50"},"PeriodicalIF":4.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295606","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":"Urine Proteomic Signatures of Mild Hypothermia Treatment in Cerebral Ischemia-Reperfusion Injury in Rats.","authors":"Dandan Zhang, Dapeng Li, Xueting Wang, Yanyan Sui, Fuguo Ma, Yuting Dai, Mingshan Wang, Weiwei Qin","doi":"10.1007/s10571-024-01483-4","DOIUrl":"10.1007/s10571-024-01483-4","url":null,"abstract":"<p><p>Mild hypothermia (MH) is an effective measure to alleviate cerebral ischemia-reperfusion (I/R) injury. However, the underlying biological mechanisms remain unclear. This study set out to investigate dynamic changes in urinary proteome due to MH in rats with cerebral I/R injury and explore the neuroprotective mechanisms of MH. A Pulsinelli's four-vessel occlusion (4-VO) rat model was used to mimic global cerebral I/R injury. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to profile the urinary proteome of rats with/without MH (32 °C) treatment after I/R injury. Representative differentially expressed proteins (DEPs) associated with MH were validated by western blotting in hippocampus. A total of 597 urinary proteins were identified, among which 119 demonstrated significant changes associated with MH. Gene Ontology (GO) annotation of the DEPs revealed that MH significantly enriched in endopeptidase activity, inflammatory response, aging, response to oxidative stress and reactive oxygen species, blood coagulation, and cell adhesion. Notably, changes in 12 DEPs were significantly reversed by MH treatment. Among them, 8 differential urinary proteins were previously reported to be closely associated with brain disease, including NP, FZD1, B2M, EPCR, ATRN, MB, CA1and VPS4A. Two representative proteins (FZD1, B2M) were further validated by western blotting in the hippocampus and the results were shown to be consistent with urinary proteomic analysis. Overall, this study strengthens the idea that urinary proteome can sensitively reflect pathophysiological changes in the brain, and appears to be the first study to explore the neuroprotective effects of MH by urinary proteomic analysis. FZD1 and B2M may be involved in the most fundamental molecular biological mechanisms of MH neuroprotection.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"49"},"PeriodicalIF":4.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247091","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":"Astrocyte-Specific Inhibition of the Primary Cilium Suppresses C3 Expression in Reactive Astrocyte.","authors":"Nor Atiqah Muhamad, Kohei Masutani, Shota Furukawa, Shunsuke Yuri, Michinori Toriyama, Chuya Matsumoto, Seiya Itoh, Yuichiro Shinagawa, Ayako Isotani, Manami Toriyama, Hiroshi Itoh","doi":"10.1007/s10571-024-01482-5","DOIUrl":"10.1007/s10571-024-01482-5","url":null,"abstract":"<p><p>C3-positive reactive astrocytes play a neurotoxic role in various neurodegenerative diseases. However, the mechanisms controlling C3-positive reactive astrocyte induction are largely unknown. We found that the length of the primary cilium, a cellular organelle that receives extracellular signals was increased in C3-positive reactive astrocytes, and the loss or shortening of primary cilium decreased the count of C3-positive reactive astrocytes. Pharmacological experiments suggested that Ca<sup>2+</sup> signalling may synergistically promote C3 expression in reactive astrocytes. Conditional knockout (cKO) mice that specifically inhibit primary cilium formation in astrocytes upon drug stimulation exhibited a reduction in the proportions of C3-positive reactive astrocytes and apoptotic cells in the brain even after the injection of lipopolysaccharide (LPS). Additionally, the novel object recognition (NOR) score observed in the cKO mice was higher than that observed in the neuroinflammation model mice. These results suggest that the primary cilium in astrocytes positively regulates C3 expression. We propose that regulating astrocyte-specific primary cilium signalling may be a novel strategy for the suppression of neuroinflammation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"48"},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11144130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185670","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}
Kai-Uwe Lewandrowski, Alireza Sharafshah, John Elfar, Sergio Luis Schmidt, Kenneth Blum, Franklin Todd Wetzel
{"title":"A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy.","authors":"Kai-Uwe Lewandrowski, Alireza Sharafshah, John Elfar, Sergio Luis Schmidt, Kenneth Blum, Franklin Todd Wetzel","doi":"10.1007/s10571-024-01466-5","DOIUrl":"10.1007/s10571-024-01466-5","url":null,"abstract":"<p><p>Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"47"},"PeriodicalIF":4.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154631","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}
Zhen-Yuan Liu, Feng Tang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li
{"title":"The Role of Beta2-Microglobulin in Central Nervous System Disease.","authors":"Zhen-Yuan Liu, Feng Tang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li","doi":"10.1007/s10571-024-01481-6","DOIUrl":"10.1007/s10571-024-01481-6","url":null,"abstract":"<p><p>Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"46"},"PeriodicalIF":3.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921197","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":"Stem Cell-Derived Exosomal MicroRNAs as Novel Potential Approach for Multiple Sclerosis Treatment.","authors":"Fatemeh Tahmasebi, Elmira Roshani Asl, Zeinab Vahidinia, Shirin Barati","doi":"10.1007/s10571-024-01478-1","DOIUrl":"10.1007/s10571-024-01478-1","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation and demyelination of CNS neurons. Up to now, there are many therapeutic strategies for MS but they are only being able to reduce progression of diseases and have not got any effect on repair and remyelination. Stem cell therapy is an appropriate method for regeneration but has limitations and problems. So recently, researches were used of exosomes that facilitate intercellular communication and transfer cell-to-cell biological information. MicroRNAs (miRNAs) are a class of short non-coding RNAs that we can used to their dysregulation in order to diseases diagnosis. The miRNAs of microvesicles obtained stem cells may change the fate of transplanted cells based on received signals of injured regions. The miRNAs existing in MSCs may be displayed the cell type and their biological activities. Current studies show also that the miRNAs create communication between stem cells and tissue-injured cells. In the present review, firstly we discuss the role of miRNAs dysregulation in MS patients and miRNAs expression by stem cells. Finally, in this study was confirmed the relationship of microRNAs involved in MS and miRNAs expressed by stem cells and interaction between them in order to find appropriate treatment methods in future for limit to disability progression.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"44"},"PeriodicalIF":4.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11076329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849938","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}
Zhihua Wang, Jun Li, Tianqi Xu, Boyu Guo, Zhiping Xie, Meihua Li
{"title":"The Efficacy of Different Material Scaffold-Guided Cell Transplantation in the Treatment of Spinal Cord Injury in Rats: A Systematic Review and Network Meta-analysis.","authors":"Zhihua Wang, Jun Li, Tianqi Xu, Boyu Guo, Zhiping Xie, Meihua Li","doi":"10.1007/s10571-024-01465-6","DOIUrl":"10.1007/s10571-024-01465-6","url":null,"abstract":"<p><p>Cell transplantation is a promising treatment option for spinal cord injury (SCI). However, there is no consensus on the choice of carrier scaffolds to host the cells. This study aims to evaluate the efficacy of different material scaffold-mediated cell transplantation in treating SCI in rats. According to PRISMA's principle, Embase, PubMed, Web of Science, and Cochrane databases were searched, and relevant literature was referenced. Only original research on cell transplantation plus natural or synthetic scaffolds in SCI rats was included. Direct and indirect evidence for improving hind limb motor function was pooled through meta-analysis. A subgroup analysis of some factors that may affect the therapeutic effect was conducted to understand the results fully. In total, 25 studies met the inclusion criteria, in which 293 rats received sham surgery, 78 rats received synthetic material scaffolds, and 219 rats received natural materials scaffolds. The network meta-analysis demonstrated that although synthetic scaffolds were slightly inferior to natural scaffolds in terms of restoring motor function in cell transplantation of SCI rats, no statistical differences were observed between the two (MD: -0.35; 95% CI -2.6 to 1.9). Moreover, the subgroup analysis revealed that the type and number of cells may be important factors in therapeutic efficacy (P < 0.01). Natural scaffolds and synthetic scaffolds are equally effective in cell transplantation of SCI rats without significant differences. In the future, the findings need to be validated in multicenter, large-scale, randomized controlled trials in clinical practice. Trial registration: Registration ID CRD42024459674 (PROSPERO).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"43"},"PeriodicalIF":3.6,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847893","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}
Bingbing Li, Lixia Xu, Zhengang Wang, Qi Shi, Yang Cui, Weijia Fan, Qiaoli Wu, Xiaoguang Tong, Hua Yan
{"title":"Neutrophil Extracellular Traps Regulate Surgical Brain Injury by Activating the cGAS-STING Pathway","authors":"Bingbing Li, Lixia Xu, Zhengang Wang, Qi Shi, Yang Cui, Weijia Fan, Qiaoli Wu, Xiaoguang Tong, Hua Yan","doi":"10.1007/s10571-024-01470-9","DOIUrl":"https://doi.org/10.1007/s10571-024-01470-9","url":null,"abstract":"<p>Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate–adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate–adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><p>The schematic diagram shows the formation of NETs activated cGAS-STING pathway after SBI, leading to increased microglia activation, accompanied with elevation of inflammatory factors, which in turn aggravated brain injury.</p>\u0000","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"196 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623055","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}