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Abstract Background Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. Methods By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. Results We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. Conclusions This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

Abstract The brain-computer interface (BCI) is a technology that involves direct communication with parts of the brain and has evolved rapidly in recent years; it has begun to be used in clinical practice, such as for patient rehabilitation. Patient electroencephalography (EEG) datasets are critical for algorithm optimization and clinical applications of BCIs but are rare at present. We collected data from 50 acute stroke patients with wireless portable saline EEG devices during the performance of two tasks: 1) imagining right-handed movements and 2) imagining left-handed movements. The dataset consists of four types of data: 1) the motor imagery instructions, 2) raw recording data, 3) pre-processed data after removing artefacts and other manipulations, and 4) patient characteristics. This is the first open dataset to address left- and right-handed motor imagery in acute stroke patients. We believe that the dataset will be very helpful for analysing brain activation and designing decoding methods that are more applicable for acute stroke patients, which will greatly facilitate research in the field of motor imagery-BCI.

Abstract Limited knowledge exists regarding the ramifications of climate warming on death burden from neurodegenerative diseases. Here, we conducted a nationwide, individual-level, case-crossover study between 2013 and 2019 to investigate the effects of non-optimal temperatures on various neurodegenerative diseases and to predict the potential death burden under different climate change scenarios. Our findings reveal that both low and high temperatures are linked to increased risks of neurodegenerative diseases death. We project that heat-related neurodegenerative disease deaths would increase, while cold-related deaths would decrease. This is characterized by a steeper slope in the high-emission scenario, but a less pronounced trend in the scenarios involving mitigation strategies. Furthermore, we predict that the net changes in attributable death would increase after the mid-21st century, especially under the unrestricted-emission scenario. These results highlight the urgent need for effective climate and public health policies to address the growing challenges of neurodegenerative diseases associated with global warming.

Abstract Objective As a potentially life‐threatening condition, myasthenia gravis (MG) has limited epidemiological studies on mortality. We aim to provide demographic distribution, geographical variation, and temporal trend of MG‐related mortality in China. Methods The national population‐based analysis was conducted based on records derived from the National Mortality Surveillance System of China. All deaths related to MG were identified from 2013 to 2020, and MG‐related mortality was evaluated by sex, age, location, and year. Results A total of 4224 deaths were related to MG during 2013–2020, and the median age at death of MG was 59.45 years, significantly lower than that in the general population (75.47 years, P

Summary: Background: Stroke and dementia are the leading causes of neurological disease burden. Detrimental effects of air pollution on both conditions are increasingly recognised, while the impacts on the dynamic transitions have not yet been explored, and whether critical time intervals exist is unknown. Methods: This prospective study was conducted based on the UK Biobank. Annual average air pollution concentrations at baseline year 2010 estimated by land-use regression models were used as a proxy for long-term air pollution exposure. Associations between multiple air pollutants (PM2.5, PM2.5-10, and NO2) indicated by air pollution score and the dynamic transitions of stroke and dementia were estimated, and the impacts during critical time intervals were explored. The date cutoff of this study was February 29, 2020. Findings: During a median follow-up of 10.9 years in 413,372 participants, 6484, 3813, and 376 participants developed incident stroke, dementia, and comorbidity of stroke and dementia. For the overall transition from stroke to comorbid dementia, the hazard ratio (HR) for each interquartile range (IQR) increase in air pollution score was 1.38 (95% CI, 1.15, 1.65), and the risks were limited to two time intervals (within 1 year and over 5 years after stroke). As for the transition from dementia to comorbid stroke, increased risk was only observed during 2–3 years after dementia. Interpretation: Our findings suggested that air pollution played an important role in the dynamic transition of stroke and dementia even at concentrations below the current criteria. The findings provided new evidence for alleviating the disease burden of neurological disorders related to air pollution during critical time intervals. Funding: The State Scholarship Fund of China Scholarship Council.

Abstract Vitamin D deficiency is associated with worse clinical outcomes after ischemic stroke; nevertheless, the pathophysiological mechanisms remain largely unexplored. In this study, we characterized the molecular mechanisms of how vitamin D signaling modulated stroke progression in male mouse ischemia–reperfusion stroke models. We found that vitamin D receptor (VDR) exhibited a predominant upregulation in peri-infarct microglia/macrophages following cerebral ischemia. Conditional Vdr inactivation in microglia/macrophages markedly augmented infarct volumes and neurological deficits. VDR-deficient microglia/macrophages exhibited a more primed proinflammatory phenotype with substantial secretion of TNF-α and IFN-γ. These inflammatory cytokines further enhanced CXCL10 release from endothelial cells and blood–brain barrier disruption, and ultimately infiltration of peripheral T lymphocytes. Notably, blocking TNF-α and IFN-γ significantly ameliorated stroke phenotypes in Vdr conditional knockout mice. Collectively, VDR signaling in microglia/macrophages plays a crucial role in restraining ischemia-elicited neuroinflammation and stroke progression. Our findings delineate a novel mechanism underlying the association between vitamin D deficiency and poor stroke outcomes, and underline the significance of maintaining a functional vitamin D signaling in the management of acute ischemic stroke.