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This study is based on the "2014 the Schweitzer Program" in Taiwan which spanned for four weeks from the 2nd to 29th of August. The lessons included four classes of multimedia picture books and eight game-based lessons. The aim of this research is to describe how to integrate the theory of "Multiple Intelligence (MI)" by Howard Gardner as well as the theories of "Cooperative Learning", and "Game-Based Teaching" into summer intensive English classes among mixed-level and mixed-age students. There were 20 participants composed of 13 fifth graders and seven sixth graders with equal members of each gender. The study followed a qualitative action research methodology with the use of interviews, documents and observations. The students had two 60-minute English lessons and one 60-minute multimedia picture book session per week for four weeks with the researcher. This study provided a prototype of lesson plan designs for a group of mixed-level and mixed-age students. Results show that merging games into the teaching content and using 'Game-based Teaching' is significantly suitable for the mixed group. Based on the results, recommendations were provided for both EFL teachers and EFL schools. During lesson plan design, teachers could merge various games into their lessons especially when intended for students of mixed levels. For the schools, it is best to choose teaching materials that combine text with plenty of activities and classroom games.

Objective- The topographical distribution of atherosclerosis in vasculature underscores the importance of shear stress in regulating endothelium. With a systems approach integrating sequencing data, the current study aims to explore the link between shear stress-regulated master transcription factor and its regulation of endothelial cell (EC) function via epigenetic modifications. Approach and Results- H3K27ac (acetylation of histone 3 lysine 27)-ChIP-seq (chromatin immunoprecipitation followed by high throughput sequencing), ATAC-seq (an assay for transposase-accessible chromatin-sequencing), and RNA-seq (RNA-sequencing) were performed to investigate the genome-wide epigenetic regulations in ECs in response to atheroprotective pulsatile shear stress (PS). In silico prediction revealed that KLF4 binding motifs were enriched in the PS-enhanced H3K27ac regions. By integrating PS- and KLF4-modulated H3K27ac, we identified 18 novel PS-upregulated genes. The promoter regions of these genes showed an overlap between the KLF4-enhanced assay for transposase-accessible chromatin signals and the PS-induced H3K27ac peaks. Experiments using ECs isolated from mouse aorta, lung ECs from EC-KLF4-TG versus EC-KLF4-KO mice, and atorvastatin-treated ECs showed that ITPR3 (inositol 1,4,5-trisphosphate receptor 3) was robustly activated by KLF4 and statins. KLF4 ATAC-qPCR (quantitative polymerase chain reaction) and ChIP-qPCR further demonstrated that a specific locus in the promoter region of the ITPR3 gene was essential for KLF4 binding, H3K27ac enrichment, chromatin accessibility, RNA polymerase II recruitment, and ITPR3 transcriptional activation. Deletion of this KLF4 binding locus in ECs by using CRISPR-Cas9 resulted in blunted calcium influx, reduced expression of endothelial nitric oxide synthase, and diminished nitric oxide bioavailability. Conclusions- These results from a novel multiomics study suggest that KLF4 is crucial for PS-modulated H3K27ac that allow the transcriptional activation of ITPR3. This novel mechanism contributes to the Ca2+-dependent eNOS (endothelial nitric oxide synthase) activation and EC homeostasis.

AbstractPurposeMethodsResultsConclusionThe purpose of this study was to investigate the role and mechanism of caspase-8 in the development of choroidal neovascularization induced by age-related macular degeneration, with the aim of identifying a potential therapeutic target for neovascular age-related macular degeneration.Mouse models of laser photocoagulation-induced choroidal neovascularization and hypoxic human choroidal endothelial cells were utilized to examine the involvement of caspase-8 in choroidal neovascularization development. The toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was explored in hypoxic human choroidal endothelial cells to elucidate its contribution to pathological angiogenesis. Various experimental techniques, including inhibition assays and immunoblotting analysis, were employed to assess the effects and mechanisms of caspase-8 activation.Inhibition of caspase-8 demonstrated attenuated choroidal neovascularization development in mice subjected to laser photocoagulation. Activation of the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was observed in hypoxic human choroidal endothelial cells. Upon activation by the toll-like receptor 4/TIR domain-containing adaptor molecule 1 axis, caspase-8 directly cleaved caspase-1, leading to the cleavage of interleukin-1β and interleukin-18 by caspase-1. Consequently, activation of interleukin-1β and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway promoted the proliferative, migratory, and tube-forming abilities of hypoxic human choroidal endothelial cells.The findings of this study indicate that caspase-8 plays a crucial role in promoting choroidal neovascularization by activating interleukin-1β and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway in choroidal endothelial cells. Therefore, targeting caspase-8 may hold promise as a therapeutic approach for neovascular age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Introduction: Acromial stress fracture (ASF) is an uncommon but acknowledged complication of reverse total shoulder arthroplasty (RTSA). There is no standardised method to directly measure the bone mineral density of the acromion to allow a detailed analysis of the potential mechanism of ASF. The aim is to establish a reliable and reproducible technique for measurement of acromial density on computer tomography (CT). Methods: A retrospective review on CT scans obtained for three groups of patients: those planned for RTSA (n = 26); age and gender‐matched non‐operative (n = 26); and young non‐operative patients (n = 28) were performed. Standardised axial images of 1 mm thickness at 1 mm increments were created following horizontal straightening on the coronal and sagittal views. To assess inter‐rater reliability, two senior CT radiographers performed density measurements using standard region of interest (ROI) tool on the CTs with the ROI placed on the mid (ROI 1) and posterior (ROI 2) acromion. ROIs were selected as the most common locations for acromion fracture post RTSA. Measurements were repeated at least 6 weeks apart. Intra‐class coefficients (ICC) were used to determine intra‐ and inter‐rater reliability. Results: ICCs demonstrated good to high intra‐rater and inter‐rater reliability for both ROI 1 and ROI 2 across all three groups. The lower margin of 95% confidence intervals was more than 0 for all intra‐class coefficients. Conclusion: This study demonstrates a reliable method of measuring acromion density on CT. This method can be used to assess bone mineral density in the clinical setting and in future studies investigating ASF following RTSA. [ABSTRACT FROM AUTHOR]

Determining the accurate locations of interictal spikes has been fundamental in the presurgical evaluation of epilepsy surgery. Stereo-electroencephalography (SEEG) is able to directly record cortical activity and localize interictal spikes. However, the main caveat of SEEG techniques is that they have limited spatial sampling (covering

INTRODUCTION: Long‐term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. METHODS: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed‐effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity‐related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. RESULTS: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. DISCUSSION: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. Highlights: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL).The association between different components of BPV and brain structural changes may vary.BPV was associated with pNfL levels independent of average blood pressure.pNfL mediated the effects of BPV on comorbidity‐related brain structural changes and cognitive performance. [ABSTRACT FROM AUTHOR]

Background and Objective: Spinal muscular atrophy (SMA) is one of the most common monogenic neuromuscular diseases, and the pathogenesis mechanisms, especially the brain network topological properties, remain unknown. This study aimed to use individual‐level morphological brain network analysis to explore the brain neural network mechanisms in SMA. Methods: Individual‐level gray matter (GM) networks were constructed by estimating the interregional similarity of GM volume distribution using both Kullback–Leibler divergence‐based similarity (KLDs) and Jesen‐Shannon divergence‐based similarity (JSDs) measurements based on Automated Anatomical Labeling 116 and Hammersmith 83 atlases for 38 individuals with SMA types 2 and 3 and 38 age‐ and sex‐matched healthy controls (HCs). The topological properties were analyzed by the graph theory approach and compared between groups by a nonparametric permutation test. Additionally, correlation analysis was used to assess the associations between altered topological metrics and clinical characteristics. Results: Compared with HCs, although global network topology remained preserved in individuals with SMA, brain regions with altered nodal properties mainly involved the right olfactory gyrus, right insula, bilateral parahippocampal gyrus, right amygdala, right thalamus, left superior temporal gyrus, left cerebellar lobule IV–V, bilateral cerebellar lobule VI, right cerebellar lobule VII, and vermis VII and IX. Further correlation analysis showed that the nodal degree of the right cerebellar lobule VII was positively correlated with the disease duration, and the right amygdala was negatively correlated with the Hammersmith Functional Motor Scale Expanded (HFMSE) scores. Conclusions: Our findings demonstrated that topological reorganization may prioritize global properties over nodal properties, and disrupted topological properties in the cortical–limbic‐cerebellum circuit in SMA may help to further understand the network pathogenesis underlying SMA. [ABSTRACT FROM AUTHOR]