Multiple sclerosis (Houndmills, Basingstoke, England)最新文献

{"title":"Rethinking the MS brain: Synaptic loss and computational modelling of brain networks.","authors":"Massimiliano Di Filippo, Andrea Mancini","doi":"10.1177/13524585221124307","DOIUrl":"https://doi.org/10.1177/13524585221124307","url":null,"abstract":"Extensive clinical and preclinical research over the past decades significantly improved our understanding of the immunopathogenesis of multiple sclerosis (MS) and highlighted how neuronal, axonal, and synaptic damage accompanies inflammatory processes since the earliest disease stages.1 It is still challenging, however, to decipher how such different factors interact and underpin the heterogeneity of MS clinical expression. Purely quantitative approaches, based on the evaluation of the extent of grey matter damage and demyelinating plaque burden, are sometimes contradicted by patterns of clinical-radiological dissociation, highlighting the relevance of individual coping mechanisms in each person with MS. Accordingly, new interpretative models are required to account for the heterogeneity of clinical phenotypes and manifestations in people with MS (PwMS). In this scenario, modern network science offers a different point of view. Brain networks can be considered as cost-efficient small-world networks, displaying high connectedness and efficient global integration, organized with hierarchical modularity and able to offer a proper balance between the segregation and integration of information.2 Structural or functional impairment of highly connected hubs may alter the function of the whole network, triggering compensatory changes in network activity that may represent maladaptive responses with progressive hub overload and hub failure.2 This interpretative model can be applied to different neurological disorders, with MS being a paradigmatic example, due to the presence of multifocal demyelinating lesions with a network ‘disconnecting’ effect3 and the more recent evidence of both functional and structural alterations of synaptic connections.4,5 In this issue, Huiskamp and colleagues6 provide a histological characterization of neuronal, excitatory and inhibitory synaptic densities in PwMS, testing through computational modelling how MS-related synaptic loss might affect brain network functioning. The authors found that excitatory and inhibitory synaptic densities were significantly reduced in the cortical layer VI of normal-appearing and demyelinated MS cortex, with respect to nonneurological controls. Interestingly, despite the fact that excitatory and inhibitory synapses were similarly reduced in normal-appearing MS cortex, the reduction was significantly larger for inhibitory synapses in demyelinated cortex. By testing such excitatory and inhibitory synaptic loss in a cortico-thalamic meanfield model that is thought to accurately mimic largescale brain dynamics, the authors show that inhibitory synapses impact network functioning more profoundly, leading to a disinhibitory increase in functional connectivity and neuronal activity. In this study, the authors translated histological findings on synaptic damage into macroscopic functional network analyses, showing that even slight changes in cortical excitatory and, especially, inhibitory synaptic de","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1999-2000"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33518559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bright spotty lesions as an imaging marker for neuromyelitis optica spectrum disorder.","authors":"Sara Salama,&nbsp;Michael Levy","doi":"10.1177/1352458521994259","DOIUrl":"https://doi.org/10.1177/1352458521994259","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory demyelinating disorder of the central nervous system (CNS). Aquaporin-4 (AQP4) antibodies in the serum are highly specific for the diagnosis of NMOSD, but the sensitivity remains under 90% allowing for diagnosis of AQP4 IgG seronegative disease. It remains of crucial importance to identify seronegative NMOSD myelitis as early as the first attack to initiate long-term treatment that will reduce future relapses and disability and to avoid potentially harmful treatments such as those of multiple sclerosis (MS). Over the years, many spinal imaging features have been reported to favour the diagnosis of NMOSD, but only longitudinally extensive transverse myelitis (LETM) was specific enough to make the diagnostic criteria in the AQP4 IgG seronegative cases. Bright spotty lesions (BSLs), which are defined as hyperintense lesions on axial T2-weighted images and sometimes associated with T1 low signal, are now reported to have a higher specificity and sensitivity compared to LETM in predicting a diagnosis of NMOSD against other causes of myelitis. In the review, we aim to highlight the position of BSLs in diagnosing NMOSD as well as its possible role as a prognostic factor for the clinical outcome.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1663-1666"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1352458521994259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25408506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All anti-CD20 monoclonal antibodies have similar efficacy and risks: No.","authors":"Finn Sellebjerg,&nbsp;Jeppe Romme Christensen","doi":"10.1177/13524585221103729","DOIUrl":"https://doi.org/10.1177/13524585221103729","url":null,"abstract":"Treatment with the B cell-depleting anti-CD20 monoclonal antibodies (mAb) ocrelizumab, ofatumumab, rituximab and ublituximab results in profound reductions in magnetic resonance imaging disease activity in multiple sclerosis (MS). Data on clinical and magnetic resonance imaging (MRI) efficacy from Phase 3 studies are in the same range for ocrelizumab and ofatumumab and data from Phase 2 studies also indicate similar effect and safety for rituximab and ublituximab.1,2 Although all four mAbs are highly efficacious in depleting circulating B cells and in reducing disease activity, they may differ in their safety profile and in their ability to prevent worsening of disability and disease progression.","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1845-1846"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40371106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial.","authors":"Bruce Ac Cree,&nbsp;Krzysztof W Selmaj,&nbsp;Lawrence Steinman,&nbsp;Giancarlo Comi,&nbsp;Amit Bar-Or,&nbsp;Douglas L Arnold,&nbsp;Hans-Peter Hartung,&nbsp;Xavier Montalbán,&nbsp;Eva K Havrdová,&nbsp;James K Sheffield,&nbsp;Neil Minton,&nbsp;Chun-Yen Cheng,&nbsp;Diego Silva,&nbsp;Ludwig Kappos,&nbsp;Jeffrey A Cohen","doi":"10.1177/13524585221102584","DOIUrl":"https://doi.org/10.1177/13524585221102584","url":null,"abstract":"<p><strong>Background: </strong>Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS.</p><p><strong>Objective: </strong>To characterize long-term safety and efficacy of ozanimod.</p><p><strong>Methods: </strong>Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021.</p><p><strong>Results: </strong>This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups.</p><p><strong>Conclusions: </strong>This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1944-1962"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/e0/10.1177_13524585221102584.PMC9493410.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40408128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early versus delayed treatment with glatiramer acetate: Analysis of up to 27 years of continuous follow-up in a US open-label extension study.","authors":"Corey C Ford,&nbsp;Jeffrey A Cohen,&nbsp;Andrew D Goodman,&nbsp;John W Lindsey,&nbsp;Robert P Lisak,&nbsp;Christopher Luzzio,&nbsp;Amy Pruitt,&nbsp;John Rose,&nbsp;Horea Rus,&nbsp;Jerry S Wolinsky,&nbsp;Shaul E Kadosh,&nbsp;Emily Bernstein-Hanlon,&nbsp;Yafit Stark,&nbsp;Jessica K Alexander","doi":"10.1177/13524585221094239","DOIUrl":"https://doi.org/10.1177/13524585221094239","url":null,"abstract":"<p><strong>Background: </strong>Glatiramer acetate (GA) is US-approved for relapsing multiple sclerosis.</p><p><strong>Objectives: </strong>To describe GA long-term clinical profile. To compare effectiveness of early start (ES) versus delayed start (DS; up to 3 years) with GA.</p><p><strong>Methods: </strong>Phase 3 trial participants entered a randomized placebo-controlled period then an open-label extension (OLE) with GA.</p><p><strong>Results: </strong>Overall, 208 out of 251 (82.9%) randomized participants entered the OLE; 24 out of 101 (23.8%, ES) and 28 out of 107 (26.2%, DS) participants completed the OLE. Median GA treatment was 9.8 (0.1-26.3) years. Annualized change in Expanded Disability Status Scale (EDSS) score was lower with ES versus DS (<i>p</i> = 0.0858: full study; <i>p</i> = 0.002; Year 5). Participants with improved/stable EDSS was consistently higher with ES versus DS: 40.3% versus 31.6% (<i>p</i> = 0.1590; full study); 70.8% versus 55.6% (<i>p</i> = 0.015; Year 5). ES prolonged time-to-6-month confirmed disease worsening (CDW) versus DS (9.8 vs 6.7 years), time-to-12-month CDW (18.9 vs 11.6 years), and significantly reduced time-to-second-6-month CDW (<i>p</i> = 0.0441). No new safety concerns arose.</p><p><strong>Conclusion: </strong>GA long-term treatment maintained clinical benefit with a similar safety profile to phase 3 results; a key limitation was that only 25% of participants completed the OLE. Early initiation of GA had sustained benefits versus delayed treatment.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1729-1743"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exoskeletons in MS rehabilitation are ready for widespread use in clinical practice: Commentary.","authors":"John DeLuca,&nbsp;Brian M Sandroff","doi":"10.1177/13524585221102923","DOIUrl":"https://doi.org/10.1177/13524585221102923","url":null,"abstract":"Rehabilitation has been recognized as the best, and perhaps only way to restore function in persons with MS.1 Recently, the application of robotic exoskeletons in MS rehabilitation has garnered much attention, as this approach is associated with a host of advantages relative to manual rehabilitation. Thus, the current controversy addresses whether or not robotic exoskeletons are ready for widespread use in clinical practice settings among persons with MS.","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1671-1672"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40565579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum neurofilament light chain predicts cognitive worsening in secondary progressive multiple sclerosis better than brain MRI measures.","authors":"Lorenzo Gaetani,&nbsp;Menno M Schoonheim","doi":"10.1177/13524585221122916","DOIUrl":"https://doi.org/10.1177/13524585221122916","url":null,"abstract":"fol-low-up of the study. Cross-sectionally, at baseline, CI was not related to sNfL levels, but did show effects for higher brain T2 lesion volume and lower normalized cortical deep grey matter and transverse temporal gyrus","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1831-1833"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40371105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients.","authors":"Gisella Guerrera,&nbsp;Alessandra Mandelli,&nbsp;Annamaria Finardi,&nbsp;Mario Orrico,&nbsp;Silvia D'Orso,&nbsp;Mario Picozza,&nbsp;Maddalena Noviello,&nbsp;Valeria Beretta,&nbsp;Bruno Bonetti,&nbsp;Massimiliano Calabrese,&nbsp;Damiano Marastoni,&nbsp;Nicola De Rossi,&nbsp;Ruggero Capra,&nbsp;Marco Salvetti,&nbsp;Maria Chiara Buscarinu,&nbsp;Matilde Inglese,&nbsp;Antonio Uccelli,&nbsp;Lucia Moiola,&nbsp;Catarina Raposo,&nbsp;Erwan Muros-Le Rouzic,&nbsp;Rosetta Pedotti,&nbsp;Massimo Filippi,&nbsp;Chiara Bonini,&nbsp;Luca Battistini,&nbsp;Giovanna Borsellino,&nbsp;Roberto Furlan","doi":"10.1177/13524585221102158","DOIUrl":"https://doi.org/10.1177/13524585221102158","url":null,"abstract":"<p><strong>Background: </strong>Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned.</p><p><strong>Objective: </strong>Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation.</p><p><strong>Results: </strong>ELISPOT assay against the spike and the <i>N</i> protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4⁺ and CD8⁺ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM⁺ CD4⁺ and CD8⁺ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory.</p><p><strong>Conclusions: </strong>B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1937-1943"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40058371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered functional brain states predict cognitive decline 5 years after a clinically isolated syndrome.","authors":"Ismail Koubiyr,&nbsp;Tommy Aa Broeders,&nbsp;Mathilde Deloire,&nbsp;Bruno Brochet,&nbsp;Thomas Tourdias,&nbsp;Jeroen Jg Geurts,&nbsp;Menno Michiel Schoonheim,&nbsp;Aurélie Ruet","doi":"10.1177/13524585221101470","DOIUrl":"https://doi.org/10.1177/13524585221101470","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment occurs in the earliest stages of multiple sclerosis (MS) together with altered functional connectivity (FC).</p><p><strong>Objective: </strong>The aim of this study was to investigate the evolution of dynamic FC states in early MS and their role in shaping cognitive decline.</p><p><strong>Methods: </strong>Overall, 32 patients were enrolled after their first neurological episode suggestive of MS and underwent cognitive evaluation and resting-state functional MRI (fMRI) over 5 years. In addition, 28 healthy controls were included at baseline.</p><p><strong>Results: </strong>Cognitive performance was stable during the first year and declined after 5 years.At baseline, the number of transitions between states was lower in MS compared to controls (<i>p</i> = 0.01). Over time, frequency of high FC states decreased in patients (<i>p</i> = 0.047) and increased in state with low FC (<i>p</i> = 0.035). Cognitive performance at Year 5 was best predicted by the mean connectivity of high FC state at Year 1.</p><p><strong>Conclusion: </strong>Patients with early MS showed reduced functional network dynamics at baseline. Longitudinal changes showed longer time spent in a state of low FC but less time spent and more connectivity disturbance in more integrative states with high within- and between-network FC. Disturbed FC within this more integrative state was predictive of future cognitive decline.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1973-1982"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40239982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemostatic factors in the pathogenesis of neuroinflammation in multiple sclerosis.","authors":"Gianmarco Abbadessa,&nbsp;Luigi Lavorgna,&nbsp;Constantina Andrada Treaba,&nbsp;Simona Bonavita,&nbsp;Caterina Mainero","doi":"10.1177/13524585211039111","DOIUrl":"https://doi.org/10.1177/13524585211039111","url":null,"abstract":"<p><strong>Background: </strong>A growing body of evidence has shed light on the role of the hemostatic pathway and its components in the pathogenesis of multiple sclerosis (MS), particularly in enhancing and sustaining neuroinflammation.</p><p><strong>Objective: </strong>To review the clinical, experimental, and neuroimaging evidence supporting the role of different components of the hemostatic pathway in the pathogenesis of neuroinflammation in MS and discuss their translational potential as disease biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>A literature search for most relevant articles from 1956 to 2020 was conducted in PubMed and Scopus.</p><p><strong>Results: </strong>Hemostasis components appear to be involved in different key events of neuroinflammation in MS including mononuclear cell diapedesis, microglia activation, and neuronal damage.</p><p><strong>Conclusion: </strong>The findings on the interplay between hemostatic and thrombotic molecular pathways in the pathogenesis of neuroinflammation in MS open new opportunities for developing novel biomarkers for disease monitoring and prognosis, as well as novel therapeutic targets.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1834-1842"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39326077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}