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Rspo2+ cells may contribute to tendon/ligament homeostasis under pathogenic conditions.Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 20 whole transcriptomes, 5 single-cell transcriptomes, and 4 whole genomes from primary Rb tumors to identify previously unknown Rb dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in Rb pathogenesis. RB1 directly interacts with and inhibits ESRRG, and RB1 loss uncouples ESRRG from negative regulation. ESRRG regulates genes involved in retinogenesis and oxygen metabolism in Rb cells. ESRRG is preferentially expressed in hypoxic Rb cells in vivo. Depletion or inhibition of ESRRG causes marked Rb cell death, which is exacerbated in hypoxia. These findings reveal a previously unidentified dependency of Rb cells on ESRRG, and they implicate ESRRG as a potential therapeutic vulnerability in Rb.This paper aims to examine the key factors influencing young drivers' hazard avoidance in Iran. In this study, a hazard avoidance index is defined and calculated for investigating the effect of impulsiveness, behavioral, and psychological characteristics on driving hazard avoidance. A questionnaire and go-no-go and flanker computer tests as well as a driving simulator are used for collecting data from 173 Iranian drivers under the age of 30. For this purpose, different scenarios were used, such as pedestrian crossing, the presence of fixed obstacles, and animals crossing the road, whose various characteristics are also changed. GDC-0973 nmr Structural equation modeling and the partial least squares method are applied for investigating the relationship between different variables and the hazard avoidance index. The results show that the driver hazard avoidance index is mostly affected by variables such as inhibitory control, opposite directional response, attentional impulsiveness, motion impulsiveness, non-planning impulsiveness, disregarding the law, and lapses and error. The results could help policymakers to assess diving hazard avoidance and improve training programs related to traffic safety based on the variables that are more effective on inexperienced and novice drivers' hazard avoidance.The purpose of this study was to examine the impact of ashwagandha (ASH) (Withania somnifera) on sleep, perceived stress, and cravings in a college student population. Sixty healthy students were screened/enrolled into a 30-day double-blinded placebo (PLA)-controlled intervention (700 mg daily, full spectrum extract of ASH root). Anthropometrics, demographics, and validated questionnaires assessing physical activity, restorative sleep, perceived stress, and food cravings were assessed before and after the study. Descriptive statistics, Pearson's correlations, and point biserial correlations were used to screen the data. For sleep and stress, a nonsignificant mixed (group × time) multivariate analysis of variance (MANOVA) was followed by one-way MANOVA (time on sleep/stress) and one-way multivariate analysis of covariance (MANCOVA) (group on sleep/stress, using initial sleep as a covariate) as follow-up tests. Further follow-up tests for this MANCOVA showed group membership affected final sleep (58.4 ± 12.4 vs. 48.2 ± 15.0 ASH vs. PLA respectively, P less then .05) using initial sleep as a covariate. Initial sleep (confounder) affected final stress, but not final sleep. Mixed analysis of variance (group × time) showed an interaction effect on food cravings, where the ASH group experienced lower cravings than the PLA group over time at end of study. The 30-day intervention was shorter than most other studies where more pronounced stress differences were seen at six weeks, indicating ASH may need the longer time period to show more pronounced stress relieving differences. ASH can be an effective safe intervention in young adult populations to help manage stress and its detrimental impacts on sleep and satiety in as little as 30 days. Clinical Trial Registration number-NCT05430685.Stress, anxiety, and depression, along with feeling overwhelmed and exhausted have been widely reported by college students as factors that negatively impact their academic performance, and overall well-being. Ashwagandha is an Ayurvedic herb that has been used historically to support healthy responses to stressors, but has recently gained popularity in the United States for its ability to support well-being for populations who experience chronic stress. To our knowledge, there have not been any human trials evaluating the efficacy of ashwagandha on stress in the United States. No studies to date have used qualitative research methods to consider the experiential impact of ashwagandha supplementation. Our purpose was to explore the lived experiences of college students participating in a double-blind randomized control trial evaluating the impact of ashwagandha as an intervention to support college students' well-being. Participants were college students (N = 60) age 18-50 years, who were randomized to either intervention or placebo group to take one capsule twice a day for 30 days. Intervention group participants took 700 mg of full spectrum extract of ashwagandha root per day, whereas those in the placebo group took glycerol capsules. Qualitative data included daily affect check-ins and focus groups. Data were analyzed using Dedoose qualitative coding software and thematic analysis. Four themes resulted regarding energy levels, mental clarity, sleep dynamics, and stress. Our findings demonstrated that ashwagandha increased college students' perceived well-being through supporting sustained energy, heightened mental clarity, and enhanced sleep quality, through a moderate dose of ashwagandha for the course of 30 days. Clinical Trial Registration number NCT05430685.Heat dissipation is necessary for the safer operation of high-power electronic devices and high-capacity batteries. Thermal meta-materials can efficiently manipulate heat flow by molding natural materials into specific structures. In this study, we construct a three-dimensional-printed meta-material structure with efficient and deterministic heat conduction through combining the 2D boron nitride (BN) with nano-diamond (DM) bridging. A research of thermal conductivity and dielectric properties exhibits that the nanosized diamond-bridged and oriented 2D boron nitride endows efficient heat transfer and maintains low dielectric loss with low filler loading. The composites loaded with 19 wt% BN platelets and 1 wt% DM have the highest thermal conductivity of 3.687 W/(m·K) in the heat flow orientation, while the thermal conductivity is only 0.632 W/(m·K) in the vertical heading of heat flow. The thermal conductive networks with thermal meta-materials based on the structural characteristics have been designed to secure critical device components from the heat source and dissipate heat flow in a definite way. The infrared images show that the temperature difference of monitoring points in different directions on the BN-oriented composite substrate is 9 °C, which realizes the protection of the heat source and key components. This study shows the latent capacity of 3D-printed structured materials for critical device component protection and heat administration applications in electronic devices and electric equipment.The rising prevalence of metabolic diseases represents a major challenge to public health worldwide. Therefore, there is a strong need to conduct research on the effectiveness of complementary and alternative therapies for metabolic disorders. Fucoidan is a fucose-enriched and sulfated polysaccharide extracted from ubiquitous brown seaweed. The antihypertensive, antidiabetic, antiobesity, and hypolipidemic effects of fucoidan have been reported in preclinical research and clinical trials. This study aims to review the mechanisms of action and the experimental and clinical use of different types of fucoidan for the treatment of metabolic diseases.Epigenetic clocks allow us to accurately predict the age and future health of individuals based on the methylation status of specific CpG sites in the genome and are a powerful tool to measure the effectiveness of longevity interventions. There is a growing need for methods to efficiently construct epigenetic clocks. The most common approach is to create clocks using elastic net regression modelling of all measured CpG sites, without first identifying specific features or CpGs of interest. The addition of feature selection approaches provides the opportunity to optimise the identification of predictive CpG sites. Here, we apply novel feature selection methods and combinatorial approaches including newly adapted neural networks, genetic algorithms, and 'chained' combinations. Human whole blood methylation data of ~470,000 CpGs was used to develop clocks that predict age with R2 correlation scores of greater than 0.73, the most predictive of which uses 35 CpG sites for a R2 correlation score of 0.87. The five most frequent sites across all clocks were modelled to build a clock with a R2 correlation score of 0.83. These two clocks are validated on two external datasets where they maintain excellent predictive accuracy. When compared with three published epigenetic clocks (Hannum, Horvath, Weidner) also applied to these validation datasets, our clocks outperformed all three models. We identified gene regulatory regions associated with selected CpGs as possible targets for future aging studies. Thus, our feature selection algorithms build accurate, generalizable clocks with a low number of CpG sites, providing important tools for the field.Fetal phonocardiography is a non-invasive, completely passive and low-cost method based on sensing acoustic signals from the maternal abdomen. However, different types of interference are sensed along with the desired fetal phonocardiography. This study focuses on the comparison of fetal phonocardiography filtering using eight algorithms Savitzky-Golay filter, finite impulse response filter, adaptive wavelet transform, maximal overlap discrete wavelet transform, variational mode decomposition, empirical mode decomposition, ensemble empirical mode decomposition, and complete ensemble empirical mode decomposition with adaptive noise. The effectiveness of those methods was tested on four types of interference (maternal sounds, movement artifacts, Gaussian noise, and ambient noise) and eleven combinations of these disturbances. The dataset was created using two synthetic records r01 and r02, where the record r02 was loaded with higher levels of interference than the record r01. The evaluation was performed using the objective parameters such as accuracy of the detection of S1 and S2 sounds, signal-to-noise ratio improvement, and mean error of heart interval measurement. According to all parameters, the best results were achieved using the complete ensemble empirical mode decomposition with adaptive noise method with average values of accuracy = 91.53% in the detection of S1 and accuracy = 68.89% in the detection of S2. The average value of signal-to-noise ratio improvement achieved by complete ensemble empirical mode decomposition with adaptive noise method was 9.75 dB and the average value of the mean error of heart interval measurement was 3.27 ms.
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