Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

Examining the effectiveness of gamification as a tool promoting teaching and learning in educational settings: a meta-analysis.

The integration of gamification into educational settings has gained recognition for its potential to boost student motivation, engagement, interest, and learning outcomes. Despite its popularity, research on gamification has produced mixed results regarding student learning outcomes. This meta-analysis aims to synthesize the existing empirical evidence on the effectiveness of gamification as a tool for promoting teaching and learning in educational settings. Forty-one studies with 49 independent samples involving more than 5,071 participants were included in our analysis. Results from random effects models showed an overall significant large effect size (g = 0.822 [0.567 to 1.078]). The research performed the moderator analysis to scrutinize the effects of a number of factors on the relationship between gamification and student learning outcomes. The study uncovered significant moderating effects for user type, educational discipline, design principles for educational gamification, duration of "gameful" experience, and learning environment. However, measurement of student outcomes and publication type did not appear to have any significant moderating effect. Those findings hold important implications for improving and implementing gamification to promote teaching and learning in future research.

Neighborhood gentrification, wealth, and co-ethnic density associations with acculturation stressors among Chinese immigrants.

Objective: This study examined the cross-sectional relationships between neighborhood social composition and gentrification, and acculturation stressors. Methods: Person-level data came from first-generation Chinese immigrants enrolled in the Immigrant Enclaves Study (Philadelphia, Pennsylvania, baseline 2018-2020, N = 512). A validated scale was used to assess 22 stressors associated with migration or acculturation. Neighborhood characteristics from the American Community Survey 2015-2019 and 2008-2012 included: tract proportion of foreign born Chinese, neighborhood wealth, and past decade gentrification. Most neighborhood exposures were modeled as continuous as well as binary variables (intended to represent highest level of neighborhood exposure). Multivariable negative binomial regression adjusted for age, gender, income, education, employment, language, years in the U.S., and neighborhood variables (proportion co-ethnic, and neighborhood per capita income). Results: The majority of participants spoke Mandarin (68% vs Cantonese 32%), mean participant age was 52.7 years old, years in the US was 18, and nearly one-half of the sample had less than 8 years of education. Mean number of stressors was 5.9 with nearly 20% of participants reporting 11 or more stressors. Multivariable results found the number of acculturation stressors was 18% lower for residents in the highest co-ethnic density neighborhoods and 13% lower for residents in the highest wealth areas, compared to other areas (expß 0.82, 95% CI [CI] 0.69, 0.98; expß 0.87, CI 0.75, 1.01, respectively). Stressors were no different whether participants lived in gentrified areas or not. Conclusions: Among middle-aged Chinese immigrants, acculturation stress was lower for residents in neighborhoods with higher proportion of Chinese immigrants and for residents in neighborhoods with higher wealth, whereas gentrification had no influence on acculturation stress. More work on this topic is needed with vulnerable populations such as this one, informed by local context.

Cerebral Circulation Time Is a Potential Predictor of Disabling Ischemic Cerebrovascular Events in Patients With Non-disabling Middle Cerebral Artery Stenosis.

Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (-) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (-) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (-) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.