Activity

In vitro, a significant increase of Chd8 and β-catenin expression was observed in HT22 cells after lipopolysaccharide (lps) treatment or mechanical injury, respectively. Chd8 knockdown inhibited wnt signaling pathway and increased apoptosis and autophagy activation in lps-stimulated HT22 cells. But activation of wnt signaling inverted the effects of Chd8-siRNA. Our results demonstrated that Chd8 exerted neuroprotection and promoted cognitive recovery through inhibiting apoptosis and autophagy activation following TBI, at least partially by wnt signaling pathway.PURPOSE Segmentation of organs from chest X-ray images is an essential task for an accurate and reliable diagnosis of lung diseases and chest organ morphometry. In this study, we investigated the benefits of augmenting state-of-the-art deep convolutional neural networks (CNNs) for image segmentation with organ contour information and evaluated the performance of such augmentation on segmentation of lung fields, heart, and clavicles from chest X-ray images. METHODS Three state-of-the-art CNNs were augmented, namely the UNet and LinkNet architecture with the ResNeXt feature extraction backbone, and the Tiramisu architecture with the DenseNet. All CNN architectures were trained on ground-truth segmentation masks and additionally on the corresponding contours. The contribution of such contour-based augmentation was evaluated against the contour-free architectures, and 20 existing algorithms for lung field segmentation. RESULTS The proposed contour-aware segmentation improved the segmentation performance, and when compared against existing algorithms on the same publicly available database of 247 chest X-ray images, the UNet architecture with the ResNeXt50 encoder combined with the contour-aware approach resulted in the best overall segmentation performance, achieving a Jaccard overlap coefficient of 0.971, 0.933, and 0.903 for the lung fields, heart, and clavicles, respectively. CONCLUSION In this study, we proposed to augment CNN architectures for CXR segmentation with organ contour information and were able to significantly improve segmentation accuracy and outperform all existing solution using a public chest X-ray database.Increased levels of psychological stress during adolescence have been associated with a decline in academic performance, school dropout and increased risk of mental health problems. Intervening during this developmental period may prevent these problems. The school environment seems particularly suitable for interventions and over the past decade, various school-based stress reduction programs have been developed. The present study aims to evaluate the results of (quasi-)experimental studies on the effectiveness of school-based intervention programs targeting adolescent psychological stress and to investigate moderators of effectiveness. A three-level random effects meta-analytic model was conducted. The search resulted in the inclusion of k = 54 studies, reporting on analyses in 61 independent samples, yielding 123 effect sizes (N = 16,475 individuals). The results indicated a moderate overall effect on psychological stress. Talabostat cost Yet, significant effects were only found in selected student samples. School-based intervention programs targeting selected adolescents have the potential to reduce psychological stress. Recommendations for practice, policy and future research are discussed.Although there are theoretical reasons to expect an association between ethnic minority status and popularity, research on this topic is scarce. Therefore, this association was investigated including the moderating role of the ethnic classroom composition and the mediating role of aggression. Data from the longitudinal Dutch SNARE (Social Network Analysis of Risk behavior in Early adolescence) project were used among first-year students (comparable to 5th grade) (N = 1134, Nclassrooms = 51, M = 12.5 years, 137 non-Western ethnic minority students). Popularity and aggression were assessed with peer nominations. Multi-level Structural Equation Models showed that ethnic minority status was indirectly associated with higher popularity, through higher aggression. Moreover, with increasing numbers of ethnic minority students in the classroom, popularity levels of both ethnic majority and ethnic minority students decreased. Only when differences in aggression between ethnic minority and majority students were included in the analyses, while the ethnic classroom composition was not included, lower popularity levels were found for ethnic minority than ethnic majority students. Scientific and practical implications of this study were addressed in the discussion.BACKGROUND The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. OBJECTIVE This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. PATIENTS AND METHODS Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combination with carboplatin (AUC 5) alone or paclitaxel (175 mg/m2) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. Preliminary safety and dose-limiting toxicity analyses were performed and dose escalation/de-escalation conducted as appropriate. RESULTS Adavosertib 175 mg bid for 2.5 days with carboplatin alone or paclitaxel plus carboplatin was considered tolerable. Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable. Grade ≥ 3 adverse events reported most commonly in any cohort included anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia. Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients. A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose. CONCLUSIONS Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients.