Brain communications最新文献

{"title":"Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.","authors":"William J Scotton, Cameron Shand, Emily G Todd, Martina Bocchetta, Christopher Kobylecki, David M Cash, Lawren VandeVrede, Hilary W Heuer, Annelies Quaegebeur, Alexandra L Young, Neil Oxtoby, Daniel Alexander, James B Rowe, Huw R Morris, Adam L Boxer, Jonathan D Rohrer, Peter A Wijeratne","doi":"10.1093/braincomms/fcaf066","DOIUrl":"10.1093/braincomms/fcaf066","url":null,"abstract":"<p><p>Although the corticobasal syndrome was originally most closely linked with the pathology of corticobasal degeneration, the 2013 Armstrong clinical diagnostic criteria, without the addition of aetiology-specific biomarkers, have limited positive predictive value for identifying corticobasal degeneration pathology in life. Autopsy studies demonstrate considerable pathological heterogeneity in corticobasal syndrome, with corticobasal degeneration pathology accounting for only ∼50% of clinically diagnosed individuals. Individualized disease stage and progression modelling of brain changes in corticobasal syndrome may have utility in predicting this underlying pathological heterogeneity, and in turn improve the design of clinical trials for emerging disease-modifying therapies. The aim of this study was to jointly model the phenotypic and temporal heterogeneity of corticobasal syndrome, to identify unique imaging subtypes based solely on a data-driven assessment of MRI atrophy patterns and then investigate whether these subtypes provide information on the underlying pathology. We applied Subtype and Stage Inference, a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 individuals with corticobasal syndrome (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and then used to subtype and stage follow-up scans. The subtypes and stages at follow-up were used to validate the longitudinal consistency of the baseline subtype and stage assignments. We then investigated whether there were differences in associated pathology and clinical phenotype between the subtypes. Subtype and Stage Inference identified at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy progression in corticobasal syndrome; four-repeat-tauopathy confirmed cases were most commonly assigned to the <i>Subcortical</i> subtype (83% of individuals with progressive supranuclear palsy pathology and 75% of individuals with corticobasal-degeneration pathology), whilst those with Alzheimer's pathology were most commonly assigned to the <i>Fronto-parieto-occipital subtype</i> (81% of individuals). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in corticobasal syndrome that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with corticobasal syndrome at baseline has important implications for screening on entry into clinical trials, as well as f","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf066"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607582","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":"Frontotemporal dementia subtyping using machine learning, multivariate statistics and neuroimaging.","authors":"Amelie Metz, Yashar Zeighami, Simon Ducharme, Sylvia Villeneuve, Mahsa Dadar","doi":"10.1093/braincomms/fcaf065","DOIUrl":"10.1093/braincomms/fcaf065","url":null,"abstract":"<p><p>Frontotemporal dementia (FTD) is a prevalent form of early-onset dementia characterized by progressive neurodegeneration and encompasses a group of heterogeneous disorders. Due to overlapping symptoms, diagnosis of FTD and its subtypes still poses a challenge. Magnetic resonance imaging (MRI) is commonly used to support the diagnosis of FTD. Using machine learning and multivariate statistics, we tested whether brain atrophy patterns are associated with severity of cognitive impairment, whether this relationship differs between the phenotypic subtypes and whether we could use these brain patterns to classify patients according to their FTD variant. A total of 136 patients (70 behavioural variant FTD, 36 semantic variant primary progressive aphasia and 30 non-fluent variant primary progressive aphasia) from the frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) database underwent brain MRI and clinical and neuropsychological examination. Deformation-based morphometry, which offers increased sensitivity to subtle local differences in structural image contrasts, was used to estimate regional cortical and subcortical atrophy. Atlas-based associations between atrophy values and performance across different cognitive tests were assessed using partial least squares. We then applied linear regression models to discern the group differences regarding the relationship between atrophy and cognitive decline in the three FTD phenotypes. Lastly, we assessed whether the combination of atrophy and cognition patterns in the latent variables identified in the partial least squares analysis could be used as features in a machine learning model to predict FTD subtypes in patients. Results revealed four significant latent variables that combined accounted for 86% of the shared covariance between cognitive and brain atrophy measures. Partial least squares-based atrophy and cognitive patterns predicted the FTD phenotypes with a cross-validated accuracy of 89.12%, with high specificity (91.46-97.15%) and sensitivity (84.19-93.56%). When using only MRI measures and two behavioural tests in the partial least squares and classification algorithms, ensuring clinical feasibility, our model was equally precise in the same participant sample (87.18%, specificity 76.14-92.00%, sensitivity 86.93-98.26%). Here, including only atrophy or behaviour patterns in the analysis led to prediction accuracies of 69.76% and 76.54%, respectively, highlighting the increased value of combining MRI and clinical measures in subtype classification. We demonstrate that the combination of brain atrophy and clinical characteristics and multivariate statistical methods can serve as a biomarker for disease phenotyping in FTD, whereby the inclusion of deformation-based morphometry measures adds to the classification accuracy in the absence of extensive clinical testing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf065"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485050","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":"Tracking the neurophysiological effects of proteinopathy into the pre-clinical stage of Alzheimer's disease.","authors":"Alex I Wiesman, Santiago I Flores-Alonso","doi":"10.1093/braincomms/fcaf069","DOIUrl":"10.1093/braincomms/fcaf069","url":null,"abstract":"<p><p>This scientific commentary refers to 'Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults', by Scheijbeler <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf018).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf069"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506600","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":"Putaminal-cortical circuits predict response of bilateral deep brain stimulation of the subthalamic nucleus in the primary Meige syndrome after 5 years.","authors":"Ning Wang, Yifeng Wu, Chen Yao, Dawei Meng, Haoran Zhang, Qinxiu Cheng, Xiaodong Zhang, Hailiang Shen, Yingqi Lu, Lin Wang, Jinping Xu","doi":"10.1093/braincomms/fcaf042","DOIUrl":"10.1093/braincomms/fcaf042","url":null,"abstract":"<p><p>The deep brain stimulation (DBS) in the subthalamic nucleus (STN) has attracted more attention for primary Meige syndrome due to easier target location and lower power consumption. However, potential and reliable preoperative predictors of longitudinal outcomes of STN-DBS to guide therapeutic decisions remain largely unexplored. Herein, we used preoperative structural MRI and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) from 55 patients with primary Meige syndrome who finished STN-DBS after 5 years. They were further classified into response (<i>n</i> = 23) and super-response (<i>n</i> = 32) based on the improvement rates of BFMDRS. Voxel-based morphology, partial correlation analyses, receiver operating characteristic (ROC) analyses and support vector machine were performed. We identified that improved rates of BFMDRS were 63, 71.97, 76.64, 79.51, 81.02, 81.36, 81.16, 80.80 and 80.93% at 1, 3, 6, 12, 18, 24, 36, 48 and 60 months after STN-DBS, respectively, and remained steady across 1-5 years. Further voxel-based morphology analyses revealed significantly lower grey-matter volume in the right hippocampus, left putamen, right supramarginal gyrus and left superior frontal gyrus in response when compared with super-response. The grey-matter volumes in the left putamen, right supramarginal gyrus and left superior frontal gyrus were not only positively correlated with improvement rates of BFMDRS after STN-DBS for 5 years in the primary Meige syndrome, but also presented a reliable classification ability in distinguishing response and super-response (area under curve = 0.855). These results suggested that STN-DBS is an effective treatment for primary Meige syndrome, and preoperative grey-matter volume of putaminal-cortical circuits could be used as potential biomarkers to predict longitudinal outcomes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf042"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412004","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":"An open-label Phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis.","authors":"Ruben P A van Eijk, Frederik J Steyn, Mark R Janse van Mantgem, Angela Schmidt, Myrte Meyjes, Sally Allen, Dara V Daygon, Jean-Philippe Loeffler, Ammar Al-Chalabi, Leonard H van den Berg, Robert D Henderson, Shyuan T Ngo","doi":"10.1093/braincomms/fcaf063","DOIUrl":"10.1093/braincomms/fcaf063","url":null,"abstract":"<p><p>Metabolic imbalance is associated with amyotrophic lateral sclerosis progression. Impaired glucose oxidation and increased reliance on fatty acid oxidation contribute to reduced metabolic flexibility and faster disease progression in amyotrophic lateral sclerosis. We sought to evaluate the safety and tolerability, and explore the pharmacodynamic response of trimetazidine, a partial fatty acid oxidation inhibitor, on oxidative stress markers and energy expenditure in amyotrophic lateral sclerosis. The study was conducted between June 29, 2021 and May 24, 2023. People living with amyotrophic lateral sclerosis, recruited in Australia and the Netherlands, received open-label oral trimetazidine for 12 weeks after an initial 4-week lead-in period. The primary outcome measures were safety and tolerability, as well as the change from baseline in oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Secondary outcome measures were change from baseline in energy expenditure, amyotrophic lateral sclerosis functional rating scale-revised, and slow vital capacity (SVC). Linear mixed effects were used to estimate the mean difference in MDA and 8-OHdG between the on- and off-treatment periods. This trial is registered under ClinicalTrial.gov National Clinical Trial (NCT) number NCT04788745 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2020-005018-17. Twenty-one participants received trimetazidine; 19 (90%) completed the treatment period. Trimetazidine was well tolerated; there were 57 adverse events reported, of which 7 (11%) were deemed potentially drug-related, including hot flushes (2), nausea (2), paraesthesia (2) and fatigue (1). MDA was numerically lower during treatment [-0.29 uM; 95% confidence interval (CI) -0.90 to 0.33, <i>P</i>  <i>=</i> 0.36]; 8-OHdG was significantly lower during treatment (-0.12 nM; 95% CI -0.23 to -0.01, <i>P</i> = 0.0245). The decrease in oxidative stress markers was accompanied by a reduction in resting energy expenditure (95 kcal, 95% CI 36.8-154, <i>P</i> = 0.0014). The absence of a placebo group prevented the interpretation of the clinical parameters. Oral trimetazidine was safe and well tolerated among patients with amyotrophic lateral sclerosis. This, combined with the significant reduction in markers of oxidative stress and resting energy expenditure, warrants a larger double-blind placebo-controlled efficacy study.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf063"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506056","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":"Navigating neural pathways: how stimulation polarity shapes deep brain stimulation efficacy.","authors":"Atefeh Asadi, Nabin Koirala, Muthuraman Muthuraman","doi":"10.1093/braincomms/fcaf061","DOIUrl":"10.1093/braincomms/fcaf061","url":null,"abstract":"<p><p>This scientific commentary refers to 'Neural pathway activation in the subthalamic region depends on stimulation polarity' by Borgheai <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf006).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf061"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470293","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":"Modulating nociception networks: the impact of low-intensity focused ultrasound on thalamocortical connectivity.","authors":"Arabinda Mishra, Pai-Feng Yang, Thomas J Manuel, Allen T Newton, M Anthony Phipps, Huiwen Luo, Michelle K Sigona, Allison Q Dockum, Jamie L Reed, John C Gore, William A Grissom, Charles F Caskey, Li Min Chen","doi":"10.1093/braincomms/fcaf062","DOIUrl":"10.1093/braincomms/fcaf062","url":null,"abstract":"<p><p>Pain engages multiple brain networks, with the thalamus serving as a critical subcortical hub. This study aims to explore the effects of low-intensity transcranial focused ultrasound-induced suppression on the organization of thalamocortical nociceptive networks. We employed MR-guided focused ultrasound, a potential non-invasive therapy, with real-time ultrasound beam localization feedback and fMRI monitoring. We first functionally identified the focused ultrasound target at the thalamic ventroposterior lateral nucleus by mapping the whole-brain blood oxygenation level-dependent responses to nociceptive heat stimulation of the hand using fMRI in each individual macaque monkey under light anaesthesia. The blood oxygenation level-dependent fMRI signals from the heat-responsive thalamic ventroposterior lateral nucleus were analysed to derive thalamocortical effective functional connectivity network using the psychophysical interaction method. Nineteen cortical regions across sensorimotor, cognitive, associative and limbic networks exhibited strong effective functional connectivity to the thalamic ventroposterior lateral during heat nociceptive processing. Focused ultrasound-induced suppression of heat activity in the thalamic ventroposterior lateral nucleus altered nociceptive responses in most of the 19 regions. Data-driven hierarchical clustering analyses of blood oxygenation level-dependent time courses across all thalamocortical region-of-interest pairs identified two effective functional connectivity subnetworks. The concurrent suppression of thalamic heat response with focused ultrasound reorganized these subnetworks and modified thalamocortical connection strength. Our findings suggest that the thalamic ventroposterior lateral nucleus has extensive and causal connections to a wide array of cortical areas during nociceptive processing. The combination of MR-guided focused ultrasound with fMRI enables precise dissection and modulation of nociceptive networks in the brain, a capability that no other device-based neuromodulation methods have achieved. This presents a promising non-invasive tool for modulating pain networks with profound clinical relevance. The robust modulation of nociceptive effective functional connectivity networks by focused ultrasound strongly supports the thalamic ventroposterior lateral as a viable target for pain management strategies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf062"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560394","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":"Correction to: Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.","authors":"","doi":"10.1093/braincomms/fcaf058","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf058","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/braincomms/fcae432.].</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf058"},"PeriodicalIF":4.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384481","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":"The inflammatory APRIL (a proliferation-inducing ligand) antagonizes chondroitin sulphate proteoglycans to promote axonal growth and myelination.","authors":"Mashal Claude Ahmed, Tejaswini Kakunuri, Leticia Peris, Delphine Meffre, Elif Nur Yilmaz, Laureen Grewing, Raquel Guerrero González, Benoit Manfroi, Evelyne Gout, Romain R Vivès, Una Fitzgerald, Pascal Schneider, Mehrnaz Jafarian-Tehrani, Tanja Kuhlmann, Bertrand Huard","doi":"10.1093/braincomms/fcae473","DOIUrl":"10.1093/braincomms/fcae473","url":null,"abstract":"<p><p>Lesions in the CNS are frequently associated to a detrimental inflammatory reaction. In autoimmune neurodegenerative diseases, a proliferation-inducing ligand (APRIL) produced by CNS-infiltrating inflammatory cells binds to chondroitin sulphate proteoglycans (CSPGs). The latter are well-established obstacles to neural regeneration and remyelination in the CNS by interacting with receptor protein tyrosine phosphatase (RPTP) and Nogo receptor (NgR) families. Here, we are showing that APRIL blocks the interactions of RPTP and NgR with all types of chondroitin sulphate (CS). Functionally, APRIL neutralized the inhibitory effects of CS on mouse and human neuronal process growth. APRIL also blocked the inhibition of CS on mouse and human oligodendrocyte differentiation. Finally, APRIL increased myelination in an <i>ex vivo</i> organotypic model of demyelination in the presence of endogenous CSPG upregulation. Our data demonstrate the potential value for a recombinant form of soluble APRIL to achieve repair in the CNS.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcae473"},"PeriodicalIF":4.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383707","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":"Decoding Alzheimer's disease: acetylcholine and dopamine pathway disruptions as early markers of cognitive decline.","authors":"Claudio Zaccone, Annalisa Nobili, Marcello D'Amelio","doi":"10.1093/braincomms/fcaf057","DOIUrl":"10.1093/braincomms/fcaf057","url":null,"abstract":"<p><p>This scientific commentary refers to 'Changes in neurotransmitter-related functional connectivity along the Alzheimer's disease continuum', by Manca <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf008).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf057"},"PeriodicalIF":4.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470263","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}