Most neuropsychiatric disease risk variants are in noncoding sequences and lack functional interpretation. Because regulatory sequences often reside in open chromatin, we reasoned that neuropsychiatric disease risk variants may affect chromatin accessibility during neurodevelopment. Using human induced pluripotent stem cell (iPSC)–derived neurons that model developing brains, we identified thousands of genetic variants exhibiting allele-specific open chromatin (ASoC). These neuronal ASoCs were partially driven by altered transcription factor binding, overrepresented in brain gene enhancers and expression quantitative trait loci, and frequently associated with distal genes through chromatin contacts. ASoCs were enriched for genetic variants associated with brain disorders, enabling identification of functional schizophrenia risk variants and their cis-target genes. This study highlights ASoC as a functional mechanism of noncoding neuropsychiatric risk variants, providing a powerful framework for identifying disease causal variants and genes.

Objective A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS). Methods From a single‐center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12‐year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion. Results Patients who developed SPMS showed faster cord atrophy rates (−2.19%/yr) at least 4 years before conversion compared to their RRMS matches (−0.88%/yr, p < 0.001). Spinal cord atrophy rates decelerated after conversion (−1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (−1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p < 0.0001) and 53% (p < 0.0001) shorter time to silent progression and SPMS conversion, respectively. Interpretation Silent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268–281

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Herein, we report a new and facile method for fabricating TiO 2 @mesoporous carbon hybrid materials. Uniform polydopamine (PDA) layers were coated onto the surface of titanate nanotubes (TNTs) and TiO 2 nanorods (TNDs) through the spontaneous adhesion and self-polymerization of dopamine during the dipping process. Core-shell mesoporous carbon nanotubes with TiO 2 nanorods or nanoparticles encapsulated inside (TiO 2 @MC) were then obtained by transforming PDA layers into carbonaceous ones through calcination in nitrogen at 800 • C. The thickness of the mesoporous carbon layers is tens of nanometers and can be controlled by adjusting the coated PDA layers through the self-polymerization reaction time. In addition, three-layered nanocomposites of TiO 2 @MC@MO (MO, metal oxide) can be readily prepared by utilizing PDA layers in TNTs@PDA or TNDs@PDA to adsorb the metal ions, followed by the calcination process.

BackgroundAs coronavirus disease 2019 (COVID-19) vaccination campaign underway, little is known about the vaccination coverage and the underlying barriers of the vaccination campaign in patients with Parkinson's disease (PD).ObjectiveTo investigate the vaccination status and reasons for COVID-19 vaccine acceptance and hesitancy among PD patients.MethodsIn concordance with the CHERRIES guideline, a web-based, single-center survey was promoted to patients with PD via an online platform from April 2022 and May 2022. Logistic regression models were used to identify factors related to COVID-19 vaccine hesitancy.ResultsA total of 187 PD cases participated in this online survey (response rate of 23%). COVID-19 vaccination rate was 54.0%. Most participants had a fear of COVID-19 (77.5%) and trusted the efficacy (82.9%) and safety (66.8%) of COVID-19 vaccine. Trust in government (70.3%) and concerns about the impact of vaccine on their disease (67.4%) were the most common reasons for COVID-19 vaccine acceptance and hesitancy, respectively. COVID-19 vaccine hesitancy was independently associated with the history of flu vaccination (OR: 0.09, p &lt; 0.05), trust in vaccine efficacy (OR: 0.15, p &lt; 0.01), male gender (OR: 0.47, p &lt; 0.05), disease duration of PD (OR: 1.08, p &lt; 0.05), and geographic factor (living in Shanghai or not) (OR: 2.87, p &lt; 0.01).ConclusionsThe COVID-19 vaccination rate remained low in PD patients, however, most individuals understood benefits of vaccination. COVID-19 vaccine hesitancy was affected by multiple factors such as geographic factor, history of flu vaccination, disease duration and trust in efficacy of vaccine. These findings could help government and public health authorities to overcome the barrier to COVID-19 vaccination and improve vaccine roll-out in PD patients.