Molecular Pain最新文献

{"title":"Recruitment of cortical silent responses by forskolin in the anterior cingulate cortex of adult mice.","authors":"Yujie Ma, Jinjin Wan, Shun Hao, Qi-Yu Chen, Min Zhuo","doi":"10.1177/17448069241258110","DOIUrl":"10.1177/17448069241258110","url":null,"abstract":"<p><p>Recent studies using different experimental approaches demonstrate that silent synapses may exist in the adult cortex including the sensory cortex and anterior cingulate cortex (ACC). The postsynaptic form of long-term potentiation (LTP) in the ACC recruits some of these silent synapses and the activity of calcium-stimulated adenylyl cyclases (ACs) is required for such recruitment. It is unknown if the chemical activation of ACs may recruit silent synapses. In this study, we found that activation of ACs contributed to synaptic potentiation in the ACC of adult mice. Forskolin, a selective activator of ACs, recruited silent responses in the ACC of adult mice. The recruitment was long-lasting. Interestingly, the effect of forskolin was not universal, some silent synapses did not undergo potentiation or recruitment. These findings suggest that these adult cortical synapses are not homogenous. The application of a selective calcium-permeable AMPA receptor inhibitor 1-naphthyl acetyl spermine (NASPM) reversed the potentiation and the recruitment of silent responses, indicating that the AMPA receptor is required. Our results strongly suggest that the AC-dependent postsynaptic AMPA receptor contributes to the recruitment of silent responses at cortical LTP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241258110"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11119478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922882","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":"Mitochondrial dysfunction and disulfidptosis co-regulate neuronal cell in neuropathic pain based on bioinformatics analysis.","authors":"Hejia Ge, Hongmei Zhou, Liuyi Song, Yuqing Tao, Li Hu","doi":"10.1177/17448069241290114","DOIUrl":"10.1177/17448069241290114","url":null,"abstract":"<p><p>Neuropathic pain (NP) affects approximately 6.9-10% of the world's population and necessitates the development of novel treatments. Mitochondria are essential in the regulation of cell death. Neuroimmune mechanisms are implicated in various forms of cell death associated with NP. However, the specific involvement of mitochondrial dysfunction and disulfidptosis in NP remains uncertain. Further research is required to gain a better understanding of their combined contribution. Our comprehensive study employs a variety of bioinformatic analysis methods, including differential gene analysis, weighted gene co-expression network analysis, machine learning, functional enrichment analysis, immune infiltration, sub-cluster analysis, single-cell dimensionality reduction and cell-cell communication to gain insight into the molecular mechanisms behind these processes. Our study rationally defines a list of key gene sets for mitochondrial dysfunction and disulfidptosis. 6 hub mitochondrial genes and 3 disulfidptosis-related genes (DRGs) were found to be associated with NP. The key genes were predominantly expressed in neurons and were lowly expressed in the NP group compared to SHAM. In addition, our macrophages used the APP (Amyloid precursor protein)-CD74 (MHC class II invariant chain) pathway to interact with neurons. These results suggest that NP is interconnected with the mechanistic processes of mitochondrial dysfunction and disulfidptosis, which may contribute to clinically targeted therapies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"20 ","pages":"17448069241290114"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350551","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":"Association between migraine and mitochondria: A Mendelian randomization study.","authors":"Ming-Yang Hong, Yu-Xin Chen, Yi-Cheng Xiong, Yi-Han Sun, Abdullah Al Mamun, Jian Xiao","doi":"10.1177/17448069241298849","DOIUrl":"10.1177/17448069241298849","url":null,"abstract":"<p><strong>Background and objective: </strong>Mitochondria are important organelles functioning in metabolic processes, inflammatory response and neurological disorders. Migraines are chronic and paroxysmal neurological disorders characterized by recurrent episodes of severe headache and other neurological symptoms. We explored whether mitochondria may be genetically and/or causally associated with migraine.</p><p><strong>Methods: </strong>Summary-level statistics of mitochondrial DNA copy number (mtDNA-CN), 69 mitochondria related exposures and migraine with aura, migraine without aura, migraine with aura and triptan purchases, migraine with aura, drug-induced, migraine without aura and triptan purchases and migraine without aura, drug-induced, were collected from genome-wide association studies (GWAS). The analysis employed two-sample Mendelian randomization, utilizing various methods including MR-Egger, inverse-variance weighted (IVW), MR-PRESSO (MR-pleiotropy residual sum and outlier), maximum likelihood, and weighted median.</p><p><strong>Results: </strong>We observed a potential association with decreased levels of mtDNA-CN with the risk of migraine without aura (Odds ratio (OR) 1.517, 95% Confidence interval (CI) 1.072-2.147, <i>p</i> = 0.019). Besides, for every 1 unit in NAD-dependent protein deacylase sirtuin-5 (SIRT5), relative risk of migraine without aura increased by 16.4%. For every 1 unit increase in Phenylalanine-transfer RNA (tRNA) ligase, relative risk of migraine without aura increased by 13.5%. For every 1 unit increase in Apoptosis-inducing factor 1, relative risk of migraine without aura increased by 27.4%.</p><p><strong>Conclusion: </strong>This study indicates fresh evidence of association between mtDNA-CN, mitochondrial related exposures and migraine especially migraine without aura. The findings may shed light on developing interventions targeting on the causal pathway from mitochondria to migraine.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"20 ","pages":"17448069241298849"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882294","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":"Predicting long-term pain by combining brain imaging, genetics and health questionnaire data with Swedish national registries using a prospective superstruct design.","authors":"Filip Gedin, Sebastian Blomé, Granit Kastrati, Maria Lalouni, Fredrik Åhs, Peter Fransson, Jörgen Rosén, William Hedley Thompson, Karin Jensen","doi":"10.1177/17448069241301628","DOIUrl":"10.1177/17448069241301628","url":null,"abstract":"<p><strong>Background: </strong>Long-term pain is a common health problem that results in disability for patients of all ages, leading to an enormous economic burden. Over 20% of the population suffer from long-term pain. Unfortunately, there are no clinical tests that predicts who will develop long-term pain. The overall aim is to predict future pain incidence based on brain function, pain behavior, health status, and genetic variability.</p><p><strong>Method: </strong>PrePain utilizes a superstruct design, which involves recruiting participants from ongoing research projects. Eligible individuals for participation in PrePain were over 18 years old and free from long-term pain. During the baseline visit, participants provide pain and health-related questionnaires, undergo structural and functional MRI scans, and provide a saliva sample for DNA extraction. Individual baseline measures are then routinely followed-up via national registries.</p><p><strong>Result: </strong>We present quality-assessed data from over 300 participants. The average age was 34 years, and most participants were women (75%). Participants rated their pain sensitivity above average and reported low avoidance. Catastrophizing thoughts during painful episodes were rated as moderate. Assessments of (f)MRI data indicated generally good image quality. In this first follow-up, we found that 45 participants had a pain-related diagnoses.</p><p><strong>Conclusion: </strong>Results indicate that a superstruct design is feasible for collecting a large number of high-quality data. The incidence of long-term pain indicates that a sufficient number of participants have been recruited to complete the prediction analyses. PrePain is a unique prospective pain database with a fair prognosis to determine risk factors of long-term pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"20 ","pages":"17448069241301628"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751340","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":"Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model.","authors":"Ratan K Banik, Twan Sia, Malcolm E Johns, Phu V Tran, Andrew Y Cheng, Sudarshan Setty, Donald A Simone","doi":"10.1177/17448069241259535","DOIUrl":"10.1177/17448069241259535","url":null,"abstract":"<p><p>Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1β and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1β, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241259535"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076271","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":"Optotagging and characterization of GABAergic rostral ventromedial medulla (RVM) neurons.","authors":"Taylor Follansbee, Henry Le Chang, Mirela Iodi Carstens, Yun Guan, Earl Carstens, Xinzhong Dong","doi":"10.1177/17448069241270295","DOIUrl":"10.1177/17448069241270295","url":null,"abstract":"<p><p>The transmission of nociceptive and pruriceptive signals in the spinal cord is greatly influenced by descending modulation from brain areas such as the rostral ventromedial medulla (RVM). Within the RVM three classes of neurons have been discovered which are relevant to spinal pain modulation, the On, Off, and Neutral cells. These neurons were discovered due to their functional response to nociceptive stimulation. On cells are excited, Off cells are inhibited, and Neutral cells have no response to noxious stimulation. Since these neurons are identified by functional response characteristics it has been difficult to molecularly identify them. In the present study, we leverage our ability to perform optotagging within the RVM to determine whether RVM On, Off, and Neutral cells are GABAergic. We found that 27.27% of RVM On cells, 47.37% of RVM Off cells, and 42.6% of RVM Neutral cells were GABAergic. These results demonstrate that RVM On, Off, and Neutral cells represent a heterogeneous population of neurons and provide a reliable technique for the molecular identification of these neurons.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241270295"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759923","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":"Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms.","authors":"Hasan Golmakani, Amir Azimian, Ebrahim Golmakani","doi":"10.1177/17448069231225845","DOIUrl":"10.1177/17448069231225845","url":null,"abstract":"<p><p>Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA's functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain's pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069231225845"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040276","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":"Causal associations of immune cell phenotypes with migraine: A mendelian randomization study.","authors":"Weifang Chai, Weihao Chai, Fei Guo","doi":"10.1177/17448069241274679","DOIUrl":"10.1177/17448069241274679","url":null,"abstract":"<p><p>The interaction between the immune system and the brain, crucial for blood-brain barrier integrity, is a potential factor in migraine development. Although there's evidence of a connection between immune dysregulation and migraine, a clear causal link has been lacking. To bridge this knowledge gap, we performed a two-sample Mendelian randomization (MR) analysis of 731 immune cell phenotypes to determine their causality with migraine, of which parameters included fluorescence, cell abundance, count, and morphology. Sensitivity and pleiotropy checks validated our findings. After applying a false discovery rate correction, our MR study identified 35 of 731 immune phenotypes with a significant causal link to migraine (<i>p</i> < 0.05). Of these, 24 showed a protective effect (inverse variance weighting : <i>p</i> < 0.05, odds ratio <1), and 11 were risk factors (inverse variance weighting : <i>p</i> < 0.05, odds ratio >1). Although limited by population sample size and potential population-specific genetic variations, our study uncovers a significant genetic link between certain immune cell markers and migraine, providing new insights into the disorder's pathophysiology. These discoveries are crucial for developing targeted biomarkers and personalized treatments. The research enhances our understanding of immune cells' role in migraine and may substantially improve patient outcomes and lessen its socio-economic impact.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241274679"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860356","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":"Characteristics of immune cells and causal relationship with chondromalacia: A two-sample, bidirectional mendelian randomization study.","authors":"Weiwei Chai, Mengwei Zhang, Yan He, Weihao Chai","doi":"10.1177/17448069241289962","DOIUrl":"10.1177/17448069241289962","url":null,"abstract":"<p><p>Chondromalacia, characterized by the softening of cartilage, is a prevalent condition affecting joint health with complex etiology. The immune system's role in its pathogenesis has been implicated but remains to be fully elucidated. To address a critical knowledge gap, we conducted a two-sample Mendelian randomization analysis of 731 immune cell phenotypes, assessing parameters like fluorescence, cell count, and morphology. After sensitivity and pleiotropy checks, and applying a false discovery rate correction, our study linked 17 phenotypes to chondromalacia (<i>p</i> < .05). Among them, seven immune cell phenotypes were found to have a protective effect against chondromalacia (IVW: <i>p</i> < .05, OR <1), while 10 were considered risk factors (IVW:<i>p</i> < .05, OR >1). Despite the constraints of sample size and possible genetic differences among populations, our research has identified a notable genetic correlation between specific immune cell indicators and chondromalacia. This breakthrough sheds light on the pathophysiological mechanisms of the condition. The identification of protective and risk-associated immune cell phenotypes provides a foundation for further exploration of immunological mechanisms in chondromalacia and may pave the way for targeted interventions. Future research is warranted to validate these findings and explore their clinical implications.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241289962"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308165","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":"Kilohertz high-frequency electrical stimulation ameliorate hyperalgesia by modulating transient receptor potential vanilloid-1 and N-methyl-D-aspartate receptor-2B signaling pathways in chronic constriction injury of sciatic nerve mice.","authors":"Kexin Fang, Peixin Lu, Wen Cheng, Bin Yu","doi":"10.1177/17448069231225810","DOIUrl":"10.1177/17448069231225810","url":null,"abstract":"<p><p>The number of patients with neuropathic pain is increasing in recent years, but drug treatments for neuropathic pain have a low success rate and often come with significant side effects. Consequently, the development of innovative therapeutic strategies has become an urgent necessity. Kilohertz High Frequency Electrical Stimulation (KHES) offers pain relief without inducing paresthesia. However, the specific therapeutic effects of KHES on neuropathic pain and its underlying mechanisms remain ambiguous, warranting further investigation. In our previous study, we utilized the Gene Expression Omnibus (GEO) database to identify datasets related to neuropathic pain mice. The majority of the identified pathways were found to be associated with inflammatory responses. From these pathways, we selected the transient receptor potential vanilloid-1 (TRPV1) and N-methyl-D-aspartate receptor-2B (NMDAR2B) pathway for further exploration. Mice were randomly divided into four groups: a Sham group, a Sham/KHES group, a chronic constriction injury of the sciatic nerve (CCI) group, and a CCI/KHES stimulation group. KHES administered 30 min every day for 1 week. We evaluated the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL). The expression of TRPV1 and NMDAR2B in the spinal cord were analyzed using quantitative reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence assay. KHES significantly alleviated the mechanical and thermal allodynia in neuropathic pain mice. KHES effectively suppressed the expression of TRPV1 and NMDAR2B, consequently inhibiting the activation of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (IBA1) in the spinal cord. The administration of the TRPV1 pathway activator partially reversed the antinociceptive effects of KHES, while the TRPV1 pathway inhibitor achieved analgesic effects similar to KHES. KHES inhibited the activation of spinal dorsal horn glial cells, especially astrocytes and microglia, by inhibiting the activation of the TRPV1/NMDAR2B signaling pathway, ultimately alleviating neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069231225810"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040275","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}