Annals of Neurology最新文献

{"title":"Annals of Neurology: Volume 97, Number 3, March 2025","authors":"","doi":"10.1002/ana.26977","DOIUrl":"https://doi.org/10.1002/ana.26977","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 3","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Precision Medicine and Stroke Rehabilitation in Atrial Fibrillation: Exploring the Multidimensional Impacts of Vessel Occlusion, Age, and Treatment\".","authors":"Alexander P Benz, David Seiffge","doi":"10.1002/ana.27212","DOIUrl":"https://doi.org/10.1002/ana.27212","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychoses of Epilepsy: Unravelling the Phenotypic and Genotypic Features.","authors":"Genevieve Rayner, Eliza Honybun, Melanie Bahlo, Karen L Oliver, Ingrid E Scheffer","doi":"10.1002/ana.27209","DOIUrl":"https://doi.org/10.1002/ana.27209","url":null,"abstract":"<p><strong>Objectives: </strong>We analyzed the genotypic and phenotypic features of patients with psychosis of epilepsy (POE).</p><p><strong>Methods: </strong>Patients with POE recruited to an epilepsy genetics research program underwent phenotyping and genetic analysis. The latter included screening for rare pathogenic variants in epilepsy genes, and polygenic risk score (PRS) calculation for common risk variants associated with schizophrenia.</p><p><strong>Results: </strong>One hundred twenty-two individuals with POE were identified. Eighty-six of 122 of the individuals (70%) had interictal psychosis, with schizophrenia the most common interictal phenotype (36/86, 42%). Twenty-eight of 122 of the individuals (23%) had postictal psychosis (PIP), 2 of 122 of the individuals (2%) had antiseizure medication-induced psychosis, and 6 of 122 of the individuals (5%) had substance-induced psychosis. Focal epilepsies were more frequently associated with PIP (24/28, 86%) compared to interictal psychosis (39/86, 45%; p < 0.05). Twenty-nine percent of the patients with POE with genetic data had a rare pathogenic variant: 19 in an epilepsy gene (PCDH19, SCN1A, DEPDC5, KCNT1, CHD2, SLC2A1, NPRL3, CLN3, NPRL3, ATP1A3, and CACNA1A) and 4 had a chromosomal anomaly. Fifty-seven percent of the patients with a rare pathogenic variant had interictal schizophrenia/schizophreniform disorder rather than PIP (9%; p < 0.05). PRSs showed that schizophrenia-related common risk variants were enriched in patients with POE compared to population controls (p = 0.0007), however, among the POE phenotypes, a raised PRS was only observed in interictal schizophrenia (p = 0.015) and not in those with PIP or other interictal POEs.</p><p><strong>Interpretation: </strong>Interictal POE is threefold more common than PIP, and more likely to be associated with both rare pathogenic variants for epilepsy and common risk variants for schizophrenia. Distinguishing between different POE phenotypes enhances clinical practice and our understanding of etiology, paving the way for precision medicine. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Molecular Pathways of Multiple Sclerosis: A Gene Prioritization and Network Analysis of White Matter Pathology Transcriptomics.","authors":"Gianmarco Abbadessa, Ai Nagano, Simon Hametner, Owain Howell, David Owen, Artemis Papadaki, Prashant Srivastava, Simona Bonavita, Roberta Magliozzi, Richard Reynolds, Mie Rizig, Richard Nicholas","doi":"10.1002/ana.27216","DOIUrl":"https://doi.org/10.1002/ana.27216","url":null,"abstract":"<p><strong>Objectives: </strong>Rapid advances in transcriptomics have driven efforts to identify deregulated pathways in multiple sclerosis (MS) tissues, though many detected differentially expressed genes are likely false positives, with only a small fraction reflecting actual pathological events. Robust, integrative methods are essential for accurately understanding the molecular mechanisms underlying MS pathology.</p><p><strong>Methods: </strong>We conducted a gene prioritization analysis of MS white matter pathology transcriptomic studies. Articles were sought in Scopus and PubMed up to July 31, 2024. Potentially eligible publications were those that provided either transcriptomics datasets (deposited in GEO) or lists of differentially expressed genes comparing MS white matter to control white matter.</p><p><strong>Results: </strong>Applying a vote-count strategy to search for the intersection of genes reported in multiple independent studies with a consistent fold-change direction, followed by a Monte Carlo simulation, we identified 528 highly significant differentially expressed multi-study genes (p < 0.0001; 10,000 simulations). Functional enrichment analysis revealed deregulation of the folate pathway in MS normal-appearing white matter, and tumor necrosis factor (TNF) -related and complement-related pathways in active and chronic active lesions, respectively. Network analysis identified 6 key signaling hubs: PTPRC, HLA-B, MYC, MMP2, COL11A2, MAG. The major nodes identified revealed mechanistic concordance with published in vivo MS models, supporting their value as potential therapeutic targets.</p><p><strong>Interpretation: </strong>Our strategy provides a robust framework for integrating gene expression data, effectively identifying the intricate pathways altered in human diseased tissues. This method holds potential for translating findings into drug development strategies. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine and Stroke Rehabilitation in Atrial Fibrillation: Exploring the Multidimensional Impacts of Vessel Occlusion, Age, and Treatment.","authors":"Xueneng Yang, Ruijuan Li, Jun Shu","doi":"10.1002/ana.27211","DOIUrl":"https://doi.org/10.1002/ana.27211","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Dual Antiplatelet Treatment up to 72 Hours in Acute Ischemic Stroke Stratified by Glycemic Status.","authors":"Qi Zhou, Ying Gao, Weiqi Chen, S Claiborne Johnston, Pierre Amarenco, Philip M Bath, Xuan Wang, Hongyi Yan, Tingting Wang, Yingying Yang, Yanli Zhang, Qingwu Yang, Mengxing Wang, Jing Jing, Chunjuan Wang, Yongjun Wang, Yilong Wang, Yuesong Pan","doi":"10.1002/ana.27207","DOIUrl":"https://doi.org/10.1002/ana.27207","url":null,"abstract":"<p><strong>Objective: </strong>The objective was to investigate the efficacy and safety of clopidogrel-aspirin versus aspirin alone in patients after ischemic stroke by glycemic status using data from the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial.</p><p><strong>Methods: </strong>Patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) were randomized to clopidogrel-aspirin or aspirin alone. They were categorized into 3 subgroups according to glycemic status based on medical history and diagnosis by a clinician during hospitalization: without type 2 diabetes mellitus, with newly diagnosed type 2 diabetes, and with a history of type 2 diabetes mellitus. The primary efficacy and safety outcomes were new stroke and moderate-to-severe bleeding risk within 90-day follow-up.</p><p><strong>Results: </strong>A total of 6,100 patients were enrolled (3,050 in each arm), with a median age of 65 years (interquartile range [IQR], 57-71) and 2,185 female (35.8%). Clopidogrel-aspirin treatment was associated with a reduction in recurrent stroke compared with aspirin alone in patients without type 2 diabetes mellitus (6.3% vs 8.4%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59-0.94; p = 0.01) and those with newly diagnosed type 2 diabetes mellitus (5.8% vs 13.0%; HR, 0.30; 95% CI, 0.14-0.66; p = 0.002), but not in those with a history of type 2 diabetes mellitus (10.0% vs 9.9%; HR, 0.98; 95% CI, 0.72-1.33; p = 0.88) (p for interaction = 0.03). Moderate-to-severe bleeding events did not differ significantly by treatment across glycemic subgroups.</p><p><strong>Interpretation: </strong>In the INSPIRES trial, patients without or with type 2 diabetes mellitus derived greater benefit from clopidogrel-aspirin than those with a history of type 2 diabetes mellitus after mild ischemic stroke or high-risk TIA.</p><p><strong>Trial registration: </strong>INSPIRES, NCT03635749. Registered 15 August 2018, https://clinicaltrials.gov/search?cond=NCT03635749. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults.","authors":"Alexandra Beaudry-Richard, Ahmed Abdelhak, Rowan Saloner, Simone Sacco, Shivany C Montes, Frederike C Oertel, Christian Cordano, Nour Jabassini, Kirtana Ananth, Apraham Gomez, Azeen Keihani, Makenna Chapman, Sree Javvadi, Shikha Saha, Adam Staffaroni, Christopher Songster, Martin Warren, John W Boscardin, Joel Kramer, Bruce Miller, Joshua W Miller, Ralph Green, Ari J Green","doi":"10.1002/ana.27200","DOIUrl":"10.1002/ana.27200","url":null,"abstract":"<p><strong>Objective: </strong>Vitamin B12 (B12) plays a critical role in fatty- and amino-acid metabolism and nucleotide synthesis. While the association between B12 deficiency and neurological dysfunction is well-known, the exact threshold for adequacy remains undefined in terms of functional impairment and evidence of injury. The objective was to assess whether B12 levels within the current normal range in a cohort of healthy older adults may be associated with measurable evidence of neurological injury or dysfunction.</p><p><strong>Methods: </strong>We enrolled 231 healthy elderly volunteers (median age 71.2 years old) with a median B12 blood concentration of 414.8 pmol/L (as measured by automated chemiluminescence assay). We performed multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. Moreover, we measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology.</p><p><strong>Results: </strong>Low (log-transformed) B12, especially decreased holo-transcobalamin, was associated with visual evoked potential latency delay (estimate = -0.04; p = 0.023), processing speed impairment (in an age-dependent manner; standardized β = -2.39; p = 0.006), and larger volumes of white matter hyperintensities on MRI (β = -0.21; p = 0.039). Remarkably, high levels of holo-haptocorrin (biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration (β = 0.22, p = 0.015).</p><p><strong>Interpretation: </strong>Healthy older subjects exhibit neurological changes at both ends of the measurable \"normal\" B12 spectrum. These findings challenge our current understanding of optimal serum B12 levels and suggest revisiting how we establish appropriate nutritional recommendations. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nigral Neuroinflammation and Dopaminergic Neurons in Parkinson's Disease and Atypical Parkinsonisms.","authors":"Emmilotta A Backman, Maria Gardberg, Laura Luntamo, Markus Peurla, Tero Vahlberg, Per Borghammer, Nadia Stefanova, Gregor Wenning, Valtteri Kaasinen","doi":"10.1002/ana.27202","DOIUrl":"https://doi.org/10.1002/ana.27202","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of neuroinflammation in the substantia nigra pars compacta (SNc) across different parkinsonian disorders-Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA)-by examining SNc dopaminergic neuron counts, neuroinflammatory T cells, and microglial activity.</p><p><strong>Methods: </strong>Postmortem neuropathological samples were collected from 79 individuals (PD, n = 38; PSP, n = 15; MSA, n = 14; controls, n = 12). The density of SNc tyrosine hydroxylase (TH)-positive neurons, T cells (CD3+, CD4+, and CD8+), and Iba1 expression (Iba1-positive microglia/macrophages) were examined in the SNc and crus cerebri. Demographic and clinical data were gathered from patient histories.</p><p><strong>Results: </strong>PSP patients had 89 to 212% more nigral CD3+, CD4+, and CD8+ T cells compared to MSA patients (p < 0.04), 125 to 178% more CD3+ and CD4+ T cells than healthy controls (p < 0.002), and 95% more CD4+ T cells than PD patients (p = 0.001). Iba1 expression in the SNc was higher in PD patients than in MSA patients (p = 0.004), with no significant differences observed across other conditions. There was a negative association between disease duration and SNc CD3+ T cell density (p = 0.002), and a positive correlation between nigral dopaminergic neuron density and CD3+ density, CD8+ density, and Iba1 expression in PD patients.</p><p><strong>Interpretation: </strong>The study reveals distinctive neuroinflammatory patterns in the SNc, with T cell-mediated inflammation prominent in PSP and microglia-mediated inflammation in PD. PSP and MSA show greater SNc dopaminergic neuron loss compared to PD. Increased neuroinflammatory response is seen in earlier disease stages, diminishing with greater neuron loss, which may inform disease progression understanding and therapeutic strategies. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Plasma Biomarker Profiles Predict Neurological Outcome in Traumatic Spinal Cord Injury.","authors":"Judith Fraussen, Sjors G J G In't Veld, Charlotte C M van Laake-Geelen, Bart Depreitere, Jens Deckers, Dieter Peuskens, Erwin M J Cornips, Sven Bamps, Charlotte E Teunissen, Veerle Somers","doi":"10.1002/ana.27198","DOIUrl":"https://doi.org/10.1002/ana.27198","url":null,"abstract":"<p><strong>Objective: </strong>Traumatic spinal cord injury (SCI) is diagnosed by imaging and clinical scoring using the American Spinal Injury Association Impairment Scale (AIS). These methods have limited value for prognosis. Here, the prognostic value of plasma neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and contactin-1 (CNTN-1) was analyzed.</p><p><strong>Methods: </strong>Biomarker levels were determined in the plasma of traumatic SCI patients (n = 37) and healthy controls (n = 22). SCI samples (n = 112) were collected at different time points from 0 to 4 days to 18 weeks post-injury. NfL and GFAP were measured by single molecule array (Simoa) technology, CNTN-1 by Luminex. Baseline and outcome AIS and motor scores were collected as a measure of injury severity.</p><p><strong>Results: </strong>NfL, GFAP, and CNTN-1 showed different kinetics in SCI patients over time. Baseline biomarker levels could identify AIS-A SCI patients (NfL + GFAP) and discriminate between patients with a motor score change <5 and those with a change ≥5 (NfL + GFAP+CNTN-1). Longitudinally, NfL could identify AIS-A patients up to 12 weeks post-SCI and discriminate between patients with a motor score change <5 and those with a change ≥5 up to 18 weeks post-SCI. Further, baseline biomarker levels positively (NfL + GFAP) or negatively (CNTN-1) correlated with outcome injury severity and together could accurately predict AIS conversion (AUC 0.863) and motor score change (AUC 0.857). This predictive ability was maintained in subacute/chronic SCI stages.</p><p><strong>Interpretation: </strong>In conclusion, plasma NfL, GFAP, and CNTN-1 are potential prognostic biomarkers in SCI. This is important for patient stratification in clinical trials, prediction of neurological outcome and informed decision-making in SCI treatment and rehabilitation. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous Thrombolysis in Patients Taking Direct Oral Anticoagulation Treatment Before Stroke Onset: Results from the Safe Implementations of Treatments in Stroke International Stroke Registry.","authors":"Marius Matusevicius, Malin Säflund, Maurizio Balestrino, Manuel Cappellari, Delfina Ferrandi, Abdoreza Ghoreishi, André Peeters, Viiu-Marika Rand, Manuela De Michele, Aleksandras Vilionskis, Andrea Zini, Niaz Ahmed","doi":"10.1002/ana.27189","DOIUrl":"https://doi.org/10.1002/ana.27189","url":null,"abstract":"<p><strong>Objectives: </strong>Intravenous thrombolysis (IVT) is contraindicated for acute ischemic stroke (AIS) patients taking direct oral anticoagulants (DOACs) within 48 hours before index stroke. Limited data exist on off-label use of IVT for these patients. We compared the safety and outcomes of IVT in AIS patients with DOAC treatment and patients with no OAC before index stroke.</p><p><strong>Methods: </strong>We analyzed data from the Safe Implementations of Treatments in Stroke (SITS) International Stroke Thrombolysis Registry during 2013-2024. Outcomes were symptomatic intracerebral hemorrhage (SICH) by the SITS Monitoring Study and European Cooperative Acute Stroke Study II definitions, functional independency (modified Rankin Scale score 0-2), and death by 3 months. Propensity score matching with a nearest neighbor matching algorithm with a ratio of 1:2 was used for relevant clinical variables. We also analyzed the time from last DOAC dose to IVT treatment.</p><p><strong>Results: </strong>A total of 1,311 DOAC and 129,384 no OAC patients were included. We matched 894 patients with DOAC to 1,788 with no OAC. The mean age was 75 years versus 76 years, and the median National Institutes of Health Stroke Scale score 11 versus 12, respectively. Patients with DOAC had a similar proportion of outcomes compared with patients with no OAC: SICH per SITS Monitoring Study (1.1 vs 1.5%, p = 0.50), SICH per European Cooperative Acute Stroke Study II (4.0 vs 4.3%, p = 0.82), any parenchymal hematoma (6.3 vs 7.8, p = 0.22), and functional independency (47.9 vs 46.4%, p = 0.59) and death (25.1 vs 24.0%, p = 0.65) at 3-month follow-up. The time from last DOAC dose to IVT did not affect outcomes.</p><p><strong>Interpretation: </strong>In this observational study, we did not find any difference in outcomes after IVT therapy in AIS patients with DOAC compared with no OAC treatment before index stroke. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}