People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. BMS-1 inhibitor chemical structure DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson's disease (and none with Alzheimer's disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predition differences. Our previous studies showed that GV1001 has various protective effects against β-amyloid and other stressors. Based on these findings, we hypothesized that GV1001 might have beneficial effects in patients with Alzheimer's disease (AD). A phase 2, double-blind, parallel-group, placebo-controlled, 6-month randomized clinical trial was performed to evaluate the safety and efficacy of subcutaneously administered GV1001. Between September 2017 and September 2019, 13 centers in South Korea recruited participants. A total of 106 patients were screened, and 96 patients with moderate-to-severe AD were randomized 111 to the placebo (group 1, n = 31), GV1001 0.56 mg (group 2, n = 33), and 1.12 mg (group 3, n = 32) groups. GV1001 was administered every week for 4 weeks (4 times), followed by every 2 weeks until week 24 (10 times). The primary endpoint was the change in the Severe Impairment Battery (SIB) score from baseline to week 24. The key secondary efficacy endpoints were the change in the Clinical Dementia Ratited without safety concerns. This study warrants a larger clinical trial. ClinicalTrials.gov NCT03184467 . Registered on June 12, 2017.ClinicalTrials.gov NCT03184467 . Registered on June 12, 2017. Foot characteristics and mechanics are hypothesized to affect aetiology of several lower extremity musculoskeletal conditions, including knee osteoarthritis (KOA). The purpose of this systematic review was to identify the foot characteristics and mechanics of individuals with KOA. Five databases were searched to identify relevant studies on foot characteristics and mechanics in people with KOA. Meta-analyses were performed where common measures were found across included studies. Included studies were evaluated for data reporting quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist. Thirty-nine studies were included in this systematic review. Two studies reported participants with KOA had statistically significantly (P < 0.05) more pronated foot postures than those without. Meta-analyses for foot progression angle (FPA) and peak rearfoot eversion angle found no difference between those with and without KOA (FPA mean difference-1.50 [95% confidence interval - 4.20-1.21]; peak rearfoot eversion mean difference 0.71 [1.55-2.97]). A more pronated foot posture was noticed in those with KOA. However, it was not possible to establish a relationship between other foot characteristics or mechanics in people with KOA due to heterogeneity between the included study and limited number of studies with similar measurements. There is need for identifying common measurement techniques and reporting metrics when studying the foot in those with KOA.A more pronated foot posture was noticed in those with KOA. However, it was not possible to establish a relationship between other foot characteristics or mechanics in people with KOA due to heterogeneity between the included study and limited number of studies with similar measurements. There is need for identifying common measurement techniques and reporting metrics when studying the foot in those with KOA. Sjogren's syndrome (SS) is a chronic autoimmune rheumatic disease with an incidence of 0.03 to 0.3%. In recent years, there are an increasing number of randomized controlled trials of traditional Chinese medicine (TCM) for SS. However, there are generally some problems in these published clinical trials lack of reporting primary or long-term outcomes and the heterogeneous in different clinical trials' outcome. Our study aims to determine the priority outcomes and standard TCM syndromes for all stakeholders and reach agreement on the COS and syndromes to be measured and reported in all future TCM trials in patients with SS. A phase-wise refinement approach will be used, consisting of three phases, yet complementary, sub-work phases, whereby each phase will inform the next coming phases. The following are the three phases (I-a) identifying of a long initial list of outcomes through systematic literature review and semi-structured qualitative interviews and (I-b) identifying an initial list of TCM syndromes through (1) systematic literature review, (2) referencing ancient Chinese medical books, and (3) retrospective studies of medical records; (II) prioritization of outcomes using Delphi survey with different stakeholders, such as health professionals and patients; and (III) through consensus meetings with patients and professionals to agree on the final COS and TCM syndromes. We summarized the actions of COS into three points direct action, indirect action, and final action. After the final COSs is completed, we will publish this research in a journal to promote communication. Core Outcome Measures in Effectiveness Trials Initiative (COMET) number 1429 . Registered on 01 December 2019.Core Outcome Measures in Effectiveness Trials Initiative (COMET) number 1429 . Registered on 01 December 2019. T cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated. We applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat. By applying unsupervised clustering, we defined thymocyte subtypes and validated DP cell subtypes by flow cytometry. We classified the cell cycle phases of each cell according to expression of cell cycle phase-specific genes. For immune synapse detection, we used immunofluorescent staining and ImageStream-based flow cytometry. We studied and integrated human thymocyte data to verify the conservation of our findings and also performed cross-species comparisons to examine species-specific gene regulation. We classified blast, rearrangement, and selection subtypes of DP thymocytes and used the surface markers CD2 and Ly6d to identify these subtypes by flow cytometry.