Journal of neuroimmunology最新文献

{"title":"Influence of cocaine use reduction on markers of immune function","authors":"William W. Stoops ,&nbsp;Thomas P. Shellenberg ,&nbsp;Sean D. Regnier ,&nbsp;David H. Cox ,&nbsp;Reuben Adatorwovor ,&nbsp;Lon R. Hays ,&nbsp;Danielle M. Anderson ,&nbsp;Joshua A. Lile ,&nbsp;Joy M. Schmitz ,&nbsp;Jennifer R. Havens ,&nbsp;Suzanne C. Segerstrom","doi":"10.1016/j.jneuroim.2024.578470","DOIUrl":"10.1016/j.jneuroim.2024.578470","url":null,"abstract":"<div><div>This study determined the effects of reduced cocaine use on immune function. Treatment seeking participants with Cocaine Use Disorder enrolled in a 12-week contingency management trial to reduce cocaine use. Participants were randomly assigned 1:1:1 to High Value Reinforcers (i.e., $55/negative urine sample) for cocaine abstinence (<em>n</em> = 41), Low Value Reinforcers (i.e., $13/negative urine sample) for cocaine abstinence (<em>n</em> = 33) or Non-Contingent Control (n = 33). Immune measures were collected at 6-week intervals. The High Value group had greatest use reductions, increased erythema and IL-6 and decreased IL-10 and CCL5, suggesting an activated immune response. Cocaine use reduction may promote changes in immune health.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578470"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590665","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":"Kidney injury: An overlooked manifestation in autoimmune encephalitis","authors":"Zhirong Fan ,&nbsp;Jing Li ,&nbsp;Yingchi Zhang ,&nbsp;Juan Kang ,&nbsp;Di Wang ,&nbsp;Lijuan Liu ,&nbsp;Min Li ,&nbsp;Xiaodan Shi ,&nbsp;Na Yuan ,&nbsp;Yuanli Zhang ,&nbsp;Fang Du ,&nbsp;Wen Jiang","doi":"10.1016/j.jneuroim.2024.578472","DOIUrl":"10.1016/j.jneuroim.2024.578472","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the prevalence and clinical features of kidney injury in patients with autoimmune encephalitis (AE).</div></div><div><h3>Methods</h3><div>Kidney injury was suspected in kidney-involving group due to persistent abnormal in urinary protein and serum albumin. Data on demographics and clinical features were compared between kidney-involving group and kidney-sparing group (patients without kidney injury) using Wilcoxon rank-sum test or chi-square test. Renal biopsy was conducted to identify the type of kidney injury.</div></div><div><h3>Results</h3><div>Approximate 30 % (32 of 108) patients with AE were suspicious of kidney injury. Nine patients further tested 24 h urine total protein, and seven of them had an elevated urine protein higher than 150 mg. The predominantly patterns of kidney injury were elevated urine protein, decreased serum albumin and normal kidney function. Compared to kidney-sparing group, the spectrum of AE antibodies in kidney-involving group was different, manifested as less anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor antibodies (50 % vs. 72.4 %, <em>p</em> = 0.025) and more anti-contactin-associated protein like 2 antibodies (18.8 % vs. 1.3 %, <em>p</em> = 0.003). Definite pathological changes indicative of IgA nephropathy and membranous nephropathy in renal biopsy of two cases provided evidence of autoimmune attacks.</div></div><div><h3>Discussion</h3><div>Kidney injury occurred in considerable proportion of patients with AE. An in-depth screening for nephropathy could be essential for AE.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578472"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561070","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":"Corrigendum to “Clinical features and outcomes of patients with muscle-specific kinase antibody-positive myasthenia gravis in Japan” [Journal of Neuroimmunology 385 (2023) 578241].","authors":"Manato Yasuda ,&nbsp;Akiyuki Uzawa ,&nbsp;Satoshi Kuwabara ,&nbsp;Shigeaki Suzuki ,&nbsp;Hiroyuki Akamine ,&nbsp;Yosuke Onishi ,&nbsp;Yukiko Ozawa ,&nbsp;Naoki Kawaguchi ,&nbsp;Tomoya Kubota ,&nbsp;Masanori P. Takahashi ,&nbsp;Yasushi Suzuki ,&nbsp;Genya Watanabe ,&nbsp;Takashi Kimura ,&nbsp;Takamichi Sugimoto ,&nbsp;Makoto Samukawa ,&nbsp;Naoya Minami ,&nbsp;Masayuki Masuda ,&nbsp;Shingo Konno ,&nbsp;Yuriko Nagane ,&nbsp;Kimiaki Utsugisawa","doi":"10.1016/j.jneuroim.2024.578465","DOIUrl":"10.1016/j.jneuroim.2024.578465","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578465"},"PeriodicalIF":2.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502427","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":"Modulating sonic hedgehog (SHH) pathway to create a rapid CNS-TB model: Facilitating drug discovery","authors":"Mohamad Mosa Mubarak ,&nbsp;Shahnawaz Majeed ,&nbsp;Zubair Ahmad Wani ,&nbsp;Hadiya Amin Kantroo ,&nbsp;Abbass Malik ,&nbsp;Ishfaq Ahmad Baba ,&nbsp;Radhika Mhatre ,&nbsp;Zahoor Ahmad","doi":"10.1016/j.jneuroim.2024.578471","DOIUrl":"10.1016/j.jneuroim.2024.578471","url":null,"abstract":"<div><div>Tuberculous meningitis, a severe complication of <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) infection, involves the dissemination of bacilli in the brain. This study explored the role of the sonic hedgehog (SHH) signaling pathway in regulating blood-brain barrier (BBB) integrity, <em>M. tb</em> invasion into the central nervous system (CNS), and disease progression of Central Nervous System Tuberculosis (CNS-TB) in a Balb/c mouse model. The modulation of the SHH pathway using agonist Purmorphamine (PUR) and antagonist Cyclopamine (CYC) revealed that CYC treatment led to a rapid and extensive invasion of <em>M. tb</em> in the brain, with bacterial loads increasing by 99 % compared to the untreated-infected group. In contrast, PUR reduced <em>M. tb</em> loads by 50 % and delayed disease progression. Histopathological analysis showed that CYC exacerbated inflammation and immune cell infiltration, while PUR mitigated these responses. Immunohistochemistry demonstrated that CYC caused severe BBB breakdown and reactive gliosis, while PUR partially attenuated this response. Further analysis revealed that CYC upregulated Matrix Metalloproteinase-9 (MMP-9) secretion, a key contributor to BBB disruption. These findings highlight the critical role of the SHH pathway in maintaining BBB integrity and regulating the immunopathological response during CNS-TB, opening up future scope for drug discovery. This Cyclopamine-induced model of rapid <em>M. tb</em> invasion and chronic inflammation provides a new tool for studying CNS-TB pathogenesis and evaluating potential therapeutic interventions targeting the SHH signaling axis.</div></div><div><h3>Significance statement</h3><div>Understanding how tuberculosis (TB) infection can spread to the brain is crucial, as this “central nervous system TB” (CNS-TB) is a serious and potentially life-threatening health complication. However, studying CNS-TB in humans is very difficult. Animal models are needed to better understand how TB gets into the brain and the resulting damage. This study in mice showed that blocking a signaling pathway called Sonic Hedgehog (SHH) allowed TB to rapidly spread to the brain, damaging the blood-brain barrier and causing severe inflammation. In contrast, activating the SHH pathway helped protect the brain from TB. These findings provide important insights that could lead to new ways to prevent or treat this dangerous form of TB.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578471"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622542","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":"NAD+ supplement relieved chronic sleep restriction (CSR)-induced microglial proinflammation in vivo and in vitro","authors":"Qiqiang Chen ,&nbsp;Jinrong Xiao ,&nbsp;Zhenya Lin ,&nbsp;Xin Xu ,&nbsp;Jinlan Chen","doi":"10.1016/j.jneuroim.2024.578469","DOIUrl":"10.1016/j.jneuroim.2024.578469","url":null,"abstract":"<div><div>Sleep insufficiency is a significant health problem worldwide and can induce multiple neurodevelopmental disorders in the central nervous system (CNS). Sleep deprivation (SD), especially chronic SD, leads to cognition and memory loss and worsens neurodegenerative disease liability. Microglia are the main inflammation-dominant glia and play a crucial role in SD-induced neurological impairments. Nicotinamide adenine dinucleotide (NAD+) is a redox reaction coenzyme that exerts anti-inflammatory and mitochondria-protective effects in microglia. Whether NAD+ mitigated SD-induced neurological disorders by regulating microglial functions is still unknown. In the current study, we designed an <em>in vivo</em> and <em>in vitro</em> model to evaluate the neuroprotective effect of NAD+ on chronic sleep restriction (CSR) and further investigate the underlying mechanisms. Behavioral tests and immunofluorescence staining were applied to investigate the cognition impairments and microglial activation. Biochemical experiments were tested to analyze the oxidative status and possible mechanism. <em>In vitro</em> data were used to verify the <em>in vivo</em> data. Our results displayed that NAD+ supplement mitigated CSR-induced cognitive decline and microglial activation response by suppressing the expression of pro-inflammatory cytokines <em>in vivo</em>. NAD+ administration also decreased oxidative stress and mitochondrial impairments in microglia. <em>In vitro</em> results showed that NAD+ treatment inhibited ROS production and prompted M1 conversion to M2 phenotype. cGAS-STING/NF-κB pathways were significantly activated but down-regulated by NAD+ administration. H151, a STING antagonist, was applied to validate that NAD+ treatment alleviates neuroinflammation partially by regulating cGAS-STING pathways in microglia. Our findings suggest that NAD+ supplement is a promising therapy for sleep disorders-induced neurological problems, and cGAS-STING pathway may act as a critical regulator in microglial proinflammation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578469"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622544","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":"Nicotine is an Immunosuppressant: Implications for Women's Health and Disease","authors":"Ashley M. White ,&nbsp;Ashley J. Craig ,&nbsp;Daryl L. Richie ,&nbsp;Christa Corley ,&nbsp;Safiyah M. Sadek ,&nbsp;Heather N. Barton ,&nbsp;Cassandra D. Gipson","doi":"10.1016/j.jneuroim.2024.578468","DOIUrl":"10.1016/j.jneuroim.2024.578468","url":null,"abstract":"<div><div>A plethora of evidence supports that nicotine, the primary alkaloid in tobacco products that is generally accepted for maintaining use, is immunoregulatory and may function as an immunosuppressant. Women have unique experiences with use of nicotine-containing products and also undergo significant reproductive transitions throughout their lifespan which may be impacted by nicotine use. Within the extant literature, there is conflicting evidence that nicotine may confer beneficial health effects in specific disease states (e.g., in ulcerative colitis). Use prevalence of nicotine-containing products is exceptionally high in individuals presenting with some comorbid disease states that impact immune system health and can be a risk factor for the development of diseases which disproportionately impact women; however, the mechanisms underlying these relationships are largely unclear. Further, little is known regarding the impacts of nicotine's immunosuppressive effects on women's health during the menopausal transition, which is arguably an inflammatory event characterized by a pro-inflammatory peri-menopause period. Given that post-menopausal women are at a higher risk than men for the development of neurodegenerative diseases such as Alzheimer's disease and are also more vulnerable to negative health effects associated with diseases such as HIV-1 infection, it is important to understand how use of nicotine-containing products may impact the immune milieu in women. In this review, we define instances in which nicotine use confers immunosuppressive, anti-inflammatory, or pro-inflammatory effects in the context of comorbid disease states, and focus on how nicotine impacts neuroimmune signaling to maintain use. We posit that regardless of potential health benefits, nicotine use cessation should be a priority in the clinical care of women. The synthesis of this review demonstrates the importance of systematically defining the relationships between volitional nicotine use, immune system function, and comorbid disease states in women to better understand how nicotine impacts women's health and disease.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578468"},"PeriodicalIF":2.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502428","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":"Myelin oligodendrocyte glycoprotein antibody–associated disease with histopathologic features of primary CNS angiitis without demyelination: Case report and literature review","authors":"Seongmi Kim ,&nbsp;Suin Lee ,&nbsp;Yeon Hak Chung ,&nbsp;Hyunjin Ju ,&nbsp;Yeon-Lim Suh ,&nbsp;Ju-Hong Min","doi":"10.1016/j.jneuroim.2024.578467","DOIUrl":"10.1016/j.jneuroim.2024.578467","url":null,"abstract":"<div><div>Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease that affects both small- and medium-sized vessels of the CNS, while myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) is a novel antibody-mediated inflammatory demyelinating disorder that causes damage to the myelin in CNS. We report a case diagnosed as MOGAD due to a history of recurrent myelitis, brain lesions, and positive anti-MOG, but the brain biopsy showed vasculitis without demyelination.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"396 ","pages":"Article 578467"},"PeriodicalIF":2.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502426","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":"May high mobility group box protein-1 be a biomarker for major depressive disorder?","authors":"Ali Emre Köse ,&nbsp;Tayfun Turan ,&nbsp;Eser Kilic","doi":"10.1016/j.jneuroim.2024.578466","DOIUrl":"10.1016/j.jneuroim.2024.578466","url":null,"abstract":"<div><div>High Mobility Group Box Protein-1 (HMGB1), which has proinflammatory properties, is known to be involved in psychiatric disorders as far as we know, there are only one clinical studies investigating the role of HMGB1 in major depressive disorder (MDD). In this study, we aimed to investigate the role of HMGB1 in the etiopathogenesis of MDD and whether HMGB1 can be used as a biomarker in MDD by measuring the serum HMGB1 levels of depressed patients in the episode and remission periods. This study included 30 patients diagnosed with MDD in episode, 30 patients in remission and 30 healthy controls. Each group comprised 20 female and 10 male participants. In this study, serum HMGB1 levels were found to be lower in the patient group in the episode compared to the patient group in the remission period and the healthy control group. There was no significant difference between the patient group in remission and the healthy control group in terms of serum HMGB1 levels. The fact that serum HMGB1 levels were lower in the patient group in the episode compared to the patient group in the remission period and the control group may be related to the neuroprotective effects of HMGB1. HMGB1 may be used as a biomarker for MDD.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"396 ","pages":"Article 578466"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468198","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":"Pathogenic Th17 cells are a potential therapeutic target for tacrolimus in AChR-myasthenia gravis patients","authors":"Yingkai Li ,&nbsp;Pei Chen ,&nbsp;Xin Huang ,&nbsp;Hao Huang ,&nbsp;Qian Ma ,&nbsp;Zhongqiang Lin ,&nbsp;Li Qiu ,&nbsp;Changyi Ou ,&nbsp;Weibin Liu","doi":"10.1016/j.jneuroim.2024.578464","DOIUrl":"10.1016/j.jneuroim.2024.578464","url":null,"abstract":"<div><div>In our study, we investigated the impact of tacrolimus (TAC) on CD4+ T cell subsets in 41 AChR-MG patients over 12 weeks. Twenty-seven patients were classified as the response group (RG) (improved myasthenia gravis composite scores ≥3), while 14 were non-response. We found that TAC treatment significantly reduced Th17 and pathogenic Th17 cells, along with IL-17 levels in RG, while Th1 and Tfh cells slightly decreased without affecting Th2 or Treg subsets. This indicates that TAC's clinical benefits may be due to its inhibitory effect on the Th17 response, enhancing our insight into its immunomodulatory mechanisms in MG management.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"396 ","pages":"Article 578464"},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406495","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":"Effectiveness of double-filtration plasmapheresis in reducing immunoglobulin and culprit antibody levels in neuroimmune disorders: A single-center retrospective analysis from China","authors":"Yan Lin ,&nbsp;Xiajun Zhou ,&nbsp;Jun Wu,&nbsp;Yufang Mei,&nbsp;Liping Ni,&nbsp;Huiying Qiu,&nbsp;Yan Zhou,&nbsp;Ying Chen,&nbsp;Wenbin Wan","doi":"10.1016/j.jneuroim.2024.578463","DOIUrl":"10.1016/j.jneuroim.2024.578463","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales.</div></div><div><h3>Results</h3><div>The cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by ∼70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2–3) to 1 (IQR 1–2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events.</div></div><div><h3>Conclusions</h3><div>DFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"396 ","pages":"Article 578463"},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422735","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}