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Recent years have seen growing interest in characterizing the properties of regional brain dynamics and their relationship to other features of brain structure and function. In particular, multiple studies have observed regional differences in the timescale over which activity fluctuates during periods of quiet rest. In the cerebral cortex, these timescales have been associated with both local circuit properties as well as patterns of inter-regional connectivity, including the extent to which each region exhibits widespread connectivity to other brain areas. In the current study, we build on prior observations of an association between connectivity and dynamics in the cerebral cortex by investigating the relationship between BOLD fMRI timescales and the modular organization of structural and functional brain networks. We characterize network community structure across multiple scales and find that longer timescales are associated with greater within-community functional connectivity and diverse structural connectivity. We also replicate prior observations of a positive correlation between timescales and structural connectivity degree. Finally, we find evidence for preferential functional connectivity between cortical areas with similar timescales. We replicate these findings in an independent dataset. These results contribute to our understanding of functional brain organization and structure-function relationships in the human brain, and support the notion that regional differences in cortical dynamics may in part reflect the topological role of each region within macroscale brain networks.

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and protein. Transcriptomic analyses of wild-type mouse DRGs suggested that SNI upregulates the expression of Rest transcripts and downregulates the transcripts of all four opioid receptor genes and the Cnr1 gene. Quantitative reverse transcription polymerase chain reaction analyses of these tissues validated these results. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of Oprm1 and Cnr1. Chromatin immunoprecipitation analyses indicated the presence of REST at these promoters. Full-length Rest conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of Oprd1 and Cnr1 in mouse DRG. Our results suggest that nerve injury represses the transcription of at least the Oprd1 and Cnr1 genes via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain. Thus, inhibiting REST activity could potentially reduce chronic neuropathic pain and augment opioid/cannabinoid analgesic actions by increasing the transcription of Oprd1 and Cnr1 genes in DRG neurons. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the acute effects of resistance exercise on muscle architecture and tissue organization at rest and during isometric maximum voluntary contraction (iMVC) of the gastrocnemius medialis muscle. In 16 healthy adults (25 ± 3 y), ultrasound scans were captured before (pre), immediately after (post), and 15 min after (post_15) single-leg calf raises during rest and iMVCs. Measurements included muscle thickness (MT), pennation angle (PA), and fascicle length (FL). Spatial frequency analysis (SFA) assessed tissue organization (e.g. peak spatial frequency radius (PSFR), quality factor (Q6)). MT increased significantly from pre to post (+5.7%) and post_15 (+5.6%) at rest. During iMVC, MT and FL increased significantly from pre to post (MT: +8.1%, FL: +14.9%) and post_15 (MT: +5.2%, FL: +10.5%), while PA decreased significantly from pre to post_15 (−10.2%). PSFR and Q6 decreased significantly from pre to post (−7.0-8.2%) and increased from post to post_15 (+10.3-10.6%) at rest, with no significant changes during iMVC. Resistance exercise led to altered muscle architecture for more than 15 min, while SFA parameters reverted to baseline within 15 min. Thus, SFA potentially enables early differentiation of potential physiological alterations in muscle micro-morphology. [ABSTRACT FROM AUTHOR]

Women's football has grown in popularity, competitiveness and professionalism, increasing the demands placed on players and their injury risk. This study aimed to identify differences in the match workload and international travel between injured and non‐injured professional women's footballers. The study was conducted as an observational, retrospective, case‐control study over two football seasons (2021/2022 and 2022/2023) in four top‐tier European women's football leagues. Fifty‐eight professional women football players (81 injuries) formed the injury group and were matched with 81 elite women football players (162 non‐injuries), from the same league, to form the control group. For each injury, cumulative match workload (minutes played, appearances, days between matches, rest) and international travel (distances, time, time zones crossed) were calculated over a 28‐day period preceding the injury, for both the injured players and matched controls. The injured group had a higher number of instances of less than 5 days between matches compared to the controls (p = 0.03, effect size = 0.3, small). The anterior cruciate ligament injury group made more appearances (p = 0.09, effect size = 0.8, moderate), had more instances of less than 5 days between matches (p = 0.09, effect size = 0.8, moderate) and had less rest time (p = 0.12, effect size = 0.8, moderate) than the control group. No meaningful differences were observed between the hamstring injury group and the control group. These findings underscore the importance of careful consideration when developing match fixture schedules in elite women's football, particularly concerning the number of matches scheduled in a short period. Strategies to increase rest and recovery are recommended to safeguard players against injuries. Highlights: Instances of less than 5 days between matches in elite women's football were significantly higher in the injured group compared to the non‐injured group.Elite female footballers who sustained anterior cruciate ligament (ACL) injuries made more appearances, had more instances of less than 5 days between matches and had less rest time in the 28 days prior to the injury than the non‐injured players.Elite female footballers who sustained ACL injuries also travelled further, for longer and crossed more time zones than the non‐injured players. [ABSTRACT FROM AUTHOR]

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Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC. [ABSTRACT FROM AUTHOR]

Study Design. Retrospective chart review. Objective. To determine the effect of conservative measures on radiographic outcomes in those with isolated spondylolysis. Summary of Background Data. Spondylolysis is a common cause of low back pain in pediatric patients, affecting between 4.4% and 4.7% of all pediatric patients. This rate is even higher in high-level athletes, with recent studies suggesting a rate of 47% in this population. Conservative measures are recommended for treating symptomatic spondylolysis and are effective in controlling symptoms, but there is little evidence regarding their effect on radiographic outcomes. Methods. A retrospective review was conducted of patients diagnosed with spondylolysis who were treated at a single academic institution between January 1, 2012, and January 1, 2022. Data collected included demographics, presentation characteristics, pretreatment and post-treatment radiologic findings, types of treatments employed, and final symptomatic status at follow-up. The Student t test and the Wilcoxon rank sum test were used to compare continuous variables. The χ² test was used to compare categorical variables. Results. A total of 119 patients were included in the study. There was an 81.5% rate of healing on advanced imaging for those treated with conservative measures. When comparing those with healing on advanced imaging to those without, those with healing were more likely to have an acute fracture (P= 0.04), have symptomatic improvement (P<0.01), and return-to-play (P= 0.02) compared with those without. Those with healing also had an odds ratio of 6.9 (P< 0.01) and 4.5 (P=0.02) to achieve symptomatic improvement and return to their sport, respectively, compared with those who did not. Conclusion. Our study found those with isolated spondylolysis who were treated with conservative measures had a high healing rate on advanced imaging and those with healing had significantly higher odds of having symptomatic improvement and returning to play compared with those without. [ABSTRACT FROM AUTHOR]

Abstract The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and protein. Transcriptomic analyses of wild-type mouse DRGs suggested that SNI upregulates the expression of Rest transcripts and downregulates the transcripts of all four opioid receptor genes and the Cnr1 gene. Quantitative reverse transcription polymerase chain reaction analyses of these tissues validated these results. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of Oprm1 and Cnr1. Chromatin immunoprecipitation analyses indicated the presence of REST at these promoters. Full-length Rest conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of Oprd1 and Cnr1 in mouse DRG. Our results suggest that nerve injury represses the transcription of at least the Oprd1 and Cnr1 genes via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain. Thus, inhibiting REST activity could potentially reduce chronic neuropathic pain and augment opioid/cannabinoid analgesic actions by increasing the transcription of Oprd1 and Cnr1 genes in DRG neurons.

Abstract Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

Background: The effect of some methods of time-restricted eating (TRE) on obesity has been investigated before, however its short term effect on obesity indices and physiological responses to exercise is not clear yet. This study aimed to evaluate the effect of TRE on anthropometric indices, as well as, resting and post-exercise responses of cortisol and erythrocyte sedimentation rate (ESR). Methods: Sixteen healthy men aged 17-29 years with body mass index (BMI) of 17.2-33.5 kg/m2 were voluntarily enrolled in this study. TRE was followed for two weeks; during this period of time, no food was consumed from 8 am to 4 pm, although water intake was allowed. Body weight, height, and waist were measured before and after TRE. Blood samples were provided before and after TRE following 10-11 hours of fasting, and after eating breakfast together with YoYo exercise test on the same day. Results: BMI and waist-to-height ratio (WHtR) decreased following two weeks of TRE. Also, a significant reduction in resting cortisol and an increase in resting ESR were noticed. After TRE, acute exercise and intake of breakfast, an increase in erythrocyte sedimentation rate (ESR) and reduction in cortisol were observed. Conclusion: Although two weeks TRE improved anthropometric indicators and resting cortisol as an anti-inflammatory response, ESR increased at rest and in response to acute exercise and intake of breakfast.

OBJECTIVE: Resting-state functional MRI (RS-fMRI) enables the mapping of function within the brain and is emerging as an efficient tool for the presurgical evaluation of eloquent cortex. Models capable of reliable and precise mapping of resting-state networks (RSNs) with a reduced scanning time would lead to improved patient comfort while reducing the cost per scan. The aims of the present study were to develop a deep 3D convolutional neural network (3DCNN) capable of voxel-wise mapping of language (LAN) and motor (MOT) RSNs with minimal quantities of RS-fMRI data. METHODS: Imaging data were gathered from multiple ongoing studies at Washington University School of Medicine and other thoroughly characterized, publicly available data sets. All study participants (n = 2252 healthy adults) were cognitively screened and completed structural neuroimaging and RS-fMRI. Random permutations of RS-fMRI regions of interest were used to train a 3DCNN. After training, model inferences were compared using varying amounts of RS-fMRI data from the control data set as well as 5 patients with glioblastoma multiforme. RESULTS: The trained model achieved 96% out-of-sample validation accuracy on data encompassing a large age range collected on multiple scanner types and varying sequence parameters. Testing on out-of-sample control data showed 97.9% similarity between results generated using either 50 or 200 RS-fMRI time points, corresponding to approximately 2.5 and 10 minutes, respectively (96.9% LAN, 96.3% MOT true-positive rate). In evaluating data from patients with brain tumors, the 3DCNN was able to accurately map LAN and MOT networks despite structural and functional alterations. CONCLUSIONS: Functional maps produced by the 3DCNN can inform surgical planning in patients with brain tumors in a time-efficient manner. The authors present a highly efficient method for presurgical functional mapping and thus improved functional preservation in patients with brain tumors.

Achieving chemical accuracy in describing reactions involving both main‐group elements and transition metals poses a substantial challenge for density functional approximations (DFAs), primarily due to the significantly different behaviors for electrons moving in the s,p‐orbitals or in the d,f‐orbitals. MOR41, a representative dataset of transition metal chemistry, has highlighted the PWPB95‐D3(BJ) functional, a B2PLYP‐type doubly hybrid (bDH) approximation equipped with an empirical dispersion correction, as the leading functional thus far (Dohm et al., J Chem Theory Comput 2018;14: 2596–2608). However, this functional is not among the top bDH methods for main‐group chemistry (Goerigk et al., Phys Chem Chem Phys. 2017;19: 32184). Conversely, bDH methods such as DSD‐BLYP‐D3, proficient in main‐group chemistry, often falter for transition metal chemistry. Herein, taking advantage of the home‐made Rust‐based Electronic‐Structure Toolkits, we examine a suite of XYG3‐type doubly hybrid (xDH) methods. We confirm that the trade‐off in descriptive accuracy between main‐group and transition metal systems persists within the realm of perturbation theory (PT2)‐based xDH methods. Notably, however, our study ushers in a pivotal advance with the recently proposed renormalized xDH method, R‐xDH7‐SCC15. This method not only distinguishes itself among the elite methods for main‐group chemistry, but also achieves an unprecedented accuracy for the MOR41 dataset, outperforming all other reported DFAs. The efficacy of R‐xDH7‐SCC15 stems from the successful integration of a renormalized PT2 correlation model (rPT2) and a machine‐learning strong‐correlation correction (SCC15), marking a significant step forward in the realm of computational chemistry. [ABSTRACT FROM AUTHOR]

Background. Immunological studies are impossible without long-term storage of cryopreserved biomaterial. There are no standard procedures for working with cryopreserved mononuclear leukocytes.The aim of the study. To optimize the protocol for culturing T lymphocytes thawed after cryopreservation by assessing their viability and proliferative capacity.Methods. Mononuclear leukocytes were isolated from the peripheral blood of relatively healthy volunteers (n = 18). Cells were subjected to controlled freezing down to –80 °C and were transferred to liquid nitrogen. First step: after thawing, the cells were stained with CFSE (carboxyfluorescein succinimidyl ester), were divided into two parts and cultured in the presence/absence of interleukin 2 (IL-2). Cell proliferation was stimulated with phytohemagglutinin (type P). Cells were incubated for 7 days. Sample analysis was performed using flow cytometry. Second stage: thawed cells were divided into three parts. Two parts were resuspended in a full growth medium with IL-2 and were placed in a thermostat (+37 °C) to “rest” for one hour or overnight. After “resting”, the cells were stained with CFSE. One third of the thawed leukocytes were stained with CFSE immediately after thawing. Cells were stimulated, cultured and analyzed the same way at both stages of the study.Results. It has been established that adding IL-2 to the culture medium contributes to a better cell survival. In the presence of IL-2, stimulated CD4+ and CD8+ T lymphocytes produced more daughter cell generations. At the end of the 7-day incubation “rested” samples had reduced leukocyte counts compared to the samples that were cultured immediately after thawing. The number of daughter cell generations formed by stimulated CD4+ and CD8+ T cells decreased when the “rest” stage was included into the study protocol.Conclusion. Adding IL-2 into culture medium can increase the viability and mitotic capacity of thawed T cells, making their state more similar to that of freshly isolated lymphocytes. Cell “rest” after thawing negatively affects the viability and proliferative activity of T lymphocytes during their weekly incubation.

The aim of this article is to justify the thesis that the right to be offline (the right to disconnect from digital tools) is not a redundant term. It is an original and autonomous right, distinct from the general right to rest. It is a right that arises in the new world of work, shaped by constant electronic and digital connectivity, designed with other needs in mind and exemplifying the increased legal protection required for rest and family time in the modern digital age.

Microservice architecture has become the design paradigm for creating scalable and maintainable software systems. Selecting the proper communication protocol in microservices is critical to achieving optimal system performance. This study compares the performance of three commonly used API protocols: REST, GraphQL, and gRPC, in microservices architecture. In this study, we established three microservices implemented in three containers and each microservice contained a Redis and MySQL database. We evaluated the performance of these API protocols using two key performance metrics: response time and CPU Utilization. This study performs two distinct data retrieval: fetching flat data and fetching nested data, with a number of requests ranging from 100 to 500 requests. The experimental results indicate that gRPC has a faster response time, followed by REST and GraphQL. Moreover, GraphQL shows higher CPU Utilization compared to gRPC and REST. The experimental results provide insight for developers and architects seeking to optimize their microservices communication protocols for specific use cases and workloads.

Abstract The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella. In SHH medulloblastoma tumor xenografts, REST elevation is strongly correlated with increased expression of the hypoxia-inducible factor 1-alpha (HIF1α)—a positive regulator of autophagy, and with reduced expression of the von Hippel-Lindau (VHL) tumor suppressor protein – a component of an E3 ligase complex that ubiquitinates HIF1α. Human SHH-medulloblastoma tumors with higher REST expression exhibit nuclear localization of HIF1α, in contrast to its cytoplasmic localization in low-REST tumors. In vitro, REST knockdown promotes an increase in VHL levels and a decrease in cytoplasmic HIF1α protein levels, and autophagy flux. In contrast, REST elevation causes a decline in VHL levels, as well as its interaction with HIF1α, resulting in a reduction in HIF1α ubiquitination and an increase in autophagy flux. These data suggest that REST elevation promotes autophagy in SHH medulloblastoma cells by modulating HIF1α ubiquitination and stability in a VHL-dependent manner. Thus, our study is one of the first to connect VHL to REST-dependent control of autophagy in a subset of medulloblastomas.

AbstractPurposeMaterials and MethodsResultsConclusions\nIMPLICATIONS FOR REHABILITATIONTo explore fatigue and physical activity behavior experiences and management, with an emphasis on activity pacing among adults with chronic conditions.Semi-structured interviews were conducted with 15 adults with chronic conditions and the symptoms of chronic fatigue who had either received or not received fatigue management advice. Interviews were audio-recorded and transcribed verbatim, then analyzed using reflexive thematic analysis.Participants reported barriers to fatigue management such as overactivity, mental health issues, and workplace challenges. Additionally, they highlighted rest, restful activities, and supportive social environment as facilitators of effective fatigue management, along with the importance of nutrition and physical activity. In some cases, there were conflicting experiences with social environment and physical activity. Activity pacing was identified as a promising solution and participants recommended several strategies for future consideration.Participants identified fatigue as a significant denominator in daily living and recognized the importance of activity pacing in fatigue management. Through reflective processes, they uncovered crucial factors for effective fatigue management, highlighting a multidimensional, interdisciplinary, and tailored approach to activity pacing as a promising solution. Further research should explore clinicians’ perspectives of a multidimensional fatigue management approach to further support optimal intervention design.Fatigue was perceived commonly across various chronic conditions, extending beyond mere tiredness and diminishing individuals’ capacity to perform daily activities.Rehabilitation professionals might incorporate activity pacing strategies tailored to each individual’s needs to effectively manage fatigue across chronic conditions.A multidimensional approach, including physical, psychological, and social interventions, is suggested for comprehensive fatigue management in rehabilitation.Facilitating rest and fostering a supportive social environment might be integral components of rehabilitation process to enhance the effectiveness of fatigue managementFatigue was perceived commonly across various chronic conditions, extending beyond mere tiredness and diminishing individuals’ capacity to perform daily activities.Rehabilitation professionals might incorporate activity pacing strategies tailored to each individual’s needs to effectively manage fatigue across chronic conditions.A multidimensional approach, including physical, psychological, and social interventions, is suggested for comprehensive fatigue management in rehabilitation.Facilitating rest and fostering a supportive social environment might be integral components of rehabilitation process to enhance the effectiveness of fatigue management [ABSTRACT FROM AUTHOR]

During sea‐level exercise, blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) in humans without a patent foramen ovale (PFO) is negatively correlated with pulmonary pressure. Yet, it is unknown whether the superior exercise capacity of Tibetans well adapted to living at high altitude is the result of lower pulmonary pressure during exercise in hypoxia, and whether their cardiopulmonary characteristics are significantly different from lowland natives of comparable ancestry (e.g. Han Chinese). We found a 47% PFO prevalence in male Tibetans (n = 19) and Han Chinese (n = 19) participants. In participants without a PFO (n = 10 each group), we measured heart structure and function at rest and peak oxygen uptake (V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$), peak power output (Ẇpeak${{\dot{W}}_{peak}}$), pulmonary artery systolic pressure (PASP), blood flow through IPAVA and cardiac output (Q̇T${{\dot{Q}}_{\mathrm{T}}} $) at rest and during recumbent cycle ergometer exercise at 760 Torr (SL) and at 410 Torr (ALT) barometric pressure in a pressure chamber. Tibetans achieved a higher Wpeak${W}_{\textit{peak}}$ than Han, and a higher V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ at ALT without differences in heart rate, stroke volume or Q̇T${{\dot{Q}}_{\mathrm{T}}} $. Blood flow through IPAVA was generally similar between groups. Increases in PASP and total pulmonary resistance at ALT were comparable between the groups. There were no differences in the slopes of PASP plotted as a function of Q̇T${{\dot{Q}}_{\mathrm{T}}} $ during exercise. In those without PFO, our data indicate that the superior aerobic exercise capacity of Tibetans over Han Chinese is independent of cardiopulmonary features and more probably linked to differences in local muscular oxygen extraction. Key points: Patent foramen ovale (PFO) prevalence was 47% in Tibetans and Han Chinese living at 2 275 m. Subjects with PFO were excluded from exercise studies.Compared to Han Chinese, Tibetans had a higher peak workload with acute compression to sea level barometric pressure (SL) and acute decompression to 5000 m altitude (ALT).Comprehensive cardiac structure and function at rest were not significantly different between Han Chinese and Tibetans.Tibetans and Han had similar blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) during exercise at SL.Peak pulmonary artery systolic pressure (PASP) and total pulmonary resistance were different between SL and ALT, with significantly increased PASP for Han compared to Tibetans at ALT. No differences were observed between groups at acute SL and ALT. [ABSTRACT FROM AUTHOR]

Introduction: Esports or competitive video gaming is a rapidly growing sector and an integral part of today's (youth) culture. Esports athletes are exposed to a variety of burdens, that can potentially impact an athlete's health and performance. Therefore, it is important that esports athletes are aware of (physical) burden and exertion associated with esports. For this purpose, a study was conducted to evaluate the influence of competitive video gaming on the perceived physical exertion and the perceived physical state (PEPS). Methods: Thirty-two healthy male esports athletes participated in two competitive video gaming sessions lasting 90-120 min, interrupted by a 10-minute passive sitting break. Repeated measures of perceived physical exertion (Borg Categorial Ratio-10 scale) and perceived physical state were recorded before, during, and after each video game session. Repeated measures ANOVA and Friedman's test were used for statistical analysis. Results: The results showed a significant difference in all dimensions of the PEPS (p < 0.05) as well as in Borg scale (p< 0.001). Post-hoc tests revealed significant increases in Borg scale between baseline measurements (T0: 1.0 ± 1.0) and after the first competitive video gaming session (T1: 2.4 ± 1.3, p < 0.001), as well as after the second competitive video gaming session (T3: 3.0 ± 1.7, p < 0.001). Furthermore, there was a significant reduction in perceived exertion between the measurement time after the first competitive video gaming session (T1) and the break (T2: 1.3 ± 1.2, p < 0.001). The PEPS dimensions activation, trained, and mobility showed similar significant changes in post-hoc analysis. Discussion: The results indicate that the perceived physical burden significantly increases during esports participation. As the duration of competitive video gaming extends, the perceived physical state decreases and perceived physical exertion increases. A passive break between two video game sessions can at least partially restore physical exertion and physical state. However, this break neither returns the scores to their baseline levels nor prevents a further decline in scores during the second video game session. Over time and with a lack of observation, this could result in health and performance limitations. [ABSTRACT FROM AUTHOR]

Background: Short-term (5 min) heart rate variability (HRV) analysis is widely used in assessing autonomic nervous system activity during exercise. While shortening the HRV measurement duration can help improve its application efficiency, its accuracy needs to be verified. This study investigated the agreement between ultra-short-term (UST) HRV (3 or 4 min) and standard 5 min HRV and explored the optimal recording duration under resting and post-exercise conditions. Methods: Fourteen participants exercised on a cycle ergometer at 60% of their maximum peak power. Data were collected during the rest condition (Pre-E) and three post-exercise conditions (Post-E1, Post-E2, and Post-E3), with indicators of the standard deviation (SDNN) of the ultra-short and short-term RR intervals and the root mean square (RMSSD) of the continuous difference between RR intervals. Repeated measures ANOVA, Cohen's d statistic, Bland–Altman analysis, and interclass correlation coefficients (ICC) assessed the agreement between UST-HRV and ST-HRV. Results: The consistency results of SDNN and RMSSD in resting and post-exercise were different. At the Pre-E, Post-E2, and Post-E3 phases, no statistical differences for SDNN and RMSSD were observed, with ICCs surpassing 0.9, indicating a high level of agreement. However, at Post-E2, there was a significant difference between 3 min RMSSD and 5 min RMSSD (p < 0.05), as well as between 3 min SDNN, 4 min SDNN, and 5 min SDNN (p < 0.05). Furthermore, the limits of agreement were observed to decrease as the time duration increased in Bland–Altman plots. Conclusions: UST-HRV analysis is a reliable substitute for standard 5 min HRV assessment, particularly during resting conditions. For post-exercise measurements, assessing the appropriateness of a 3- or 4 min duration based on the exercise's length is recommended to ensure accuracy and reliability. [ABSTRACT FROM AUTHOR]

Recent studies highlight the impact of circadian biology on cardiovascular health, leading to the rise of chronotherapy, an emerging field revolutionizing therapy timing for improved patient outcomes. Medication chronotherapy synchronizes drug treatments with the body's circadian rhythms, enhancing cardiovascular treatments. Light chronotherapy focuses on the influence of light timing on the circadian system, crucial for cardiovascular and metabolic well-being. Food chronotherapy harmonizes feeding/fasting patterns, microbiome, and gut physiology with the body's internal clock, shaping the circadian rhythm and health of the heart beyond the light–dark cycle. New frontiers in chronotherapy include the pioneering field of rest, new strategies for treating hypertension, managing pain through chronotherapy, and small molecules targeting the circadian mechanism. Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology. They optimize treatment schedules for better outcomes with fewer side effects by recognizing the profound influence of rhythmic body cycles. In this review, we focus on three chronotherapy areas (medication, light, and meal timing) with potential to enhance cardiovascular care. We also highlight pioneering research in the new field of rest, the gut microbiome, novel chronotherapies for hypertension, pain management, and small molecules that targeting the circadian mechanism. Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology. They optimize treatment schedules for better outcomes with fewer side effects by recognizing the profound influence of rhythmic body cycles. In this review, we focus on three chronotherapy areas (medication, light, and meal timing) with potential to enhance cardiovascular care. We also highlight pioneering research in the new field of rest, the gut microbiome, novel chronotherapies for hypertension, pain management, and small molecules that target the circadian mechanism. [ABSTRACT FROM AUTHOR]

The importance of mental health of children has gained considerable recognition in present days. The right to rest and leisure of students at educational institutions is one such right which has remained in the limelight recently. Education not only means improving the cognitive abilities of the child, but also flourishing the affective and psychomotor domain, which can be boosted only when the child is given needed time to rest and rejuvenate the energy to facilitate their cognitive capacity. The Universal Declaration of Human Rights (UDHR) in article 24 states-'Everyone has the right to rest and leisure, including reasonable limitation of working hours and periodic holidays with pay.' The right to rest and leisure is not only a sheer fundamental right of the working people, but also of students who spend more than half of their day at educational institutions. A student can only proof their worth to the best of their ability when they are given the opportunity to think in solitude. [ABSTRACT FROM AUTHOR]

The conceptual metaphor DEATH IS REST is a metaphor that appears with great frequency in discourse expressing the concept of "death" in Vietnamese and English. Its basic structure is a partial mapping schema with the characteristic of “rest” activated in association with the abstract idea of “death”. Through analyzing the two languages used, Vietnamese and English, the results of this study aim to point out similarities and differences as well as provide some insights into the mechanism of perceiving "death" in Vietnamese and English through the mindset of “rest”. The conclusions of the study can be used as a reference source for other studies on conceptual metaphors and applied language teaching relating to cultural factors. [ABSTRACT FROM AUTHOR]

Due to its importance and widespread use in industry, automated testing of REST APIs has attracted major interest from the research community in the last few years. However, most of the work in the literature has been focused on black-box fuzzing. Although existing fuzzers have been used to automatically find many faults in existing APIs, there are still several open research challenges that hinder the achievement of better results (e.g., in terms of code coverage and fault finding). For example, under-specified schemas are a major issue for black-box fuzzers. Currently, EvoMaster is the only existing tool that supports white-box fuzzing of REST APIs. In this paper, we provide a series of novel white-box heuristics, including for example how to deal with under-specified constrains in API schemas, as well as under-specified schemas in SQL databases. Our novel techniques are implemented as an extension to our open-source, search-based fuzzer EvoMaster. An empirical study on 14 APIs from the EMB corpus, plus one industrial API, shows clear improvements of the results in some of these APIs. [ABSTRACT FROM AUTHOR]

Background: In schizophrenia patients, spontaneous speech production has been hypothesized as correlating with right hemispheric activation, including the inferior frontal and superior temporal gyri as speech-relevant areas. However, robust evidence for this association is still missing. The aim of the present fMRI study is to examine BOLD signal changes during natural, fluent speech production in patients with schizophrenia in the chronic phase of their disease. Methods: Using a case-control design, the study included 15 right-handed patients with schizophrenia spectrum disorders as well as 15 healthy controls. The participants described eight pictures from the Thematic Apperception Test for 1 min each, while BOLD signal changes were measured with 3T fMRI. The occurrence of positive and negative formal thought disorders was determined using standardized psychopathological assessments. Results: We found significant BOLD signal changes during spontaneous speech production in schizophrenia patients compared to healthy controls, particularly in the right hemispheric network. A post-hoc analysis showed that this righthemispheric lateralization was mainly driven by activation during experimental rests. Furthermore, the TLI sum value in patients correlated negatively with BOLD signal changes in the right Rolandic operculum. Conclusions: Possible underlying factors for this inverse right-hemispheric lateralization of speech-associated areas are structural changes and transmitter system alterations, as well as a lack of neural downregulation in schizophrenia patients during rest periods due to dysfunctional executive functions. When examining spontaneous speech as the most natural form of language, other influencing factors, such as social cognition or emotional processing, should be considered. Our results indicate that future studies should consider group differences during rest, which might provide additional information typically covered in differential contrasts. [ABSTRACT FROM AUTHOR]

Introduction: Sleep is vital for health in older adulthood. Ethnic disparities have been noted with regards to sleep health. However, culturally appropriate approaches to sleep as a broader social experience are lacking. Methods: Here, sleep-related group interviews were conducted in the form of hui (group meetings and discussions) with eleven participants of a health service intervention for older Māori (the Indigenous people of New Zealand) and their whanau (extended family). Notes were collated and analyzed thematically. Results: Four key themes were constructed that represent the key conversations and ideas. These concerned the conceptualizing of sleep--including appreciation for its somatic role but also the spiritual properties of sleep states; the changing obligations around sleep and wake--including individual and communal time use and changing cultural and familial obligations with advancing age; and the barriers and facilitators for supporting sleep--including the social and spiritual nature of communal sleeping, the schedules and sleep of others, as well as holistic and environmental methods for relaxation. Findings demonstrate themultifaceted nature of sleep and aging among Māori. Culturally relevant interpretations of sleep practices and disturbances were offered and are beyond typical Western models which are predominantly medicalized. Discussion: This work aids the understanding and representation of sleep as a social and cultural perspective within the New Zealand context. This provides foundations for future participatory research to design culturally appropriate approaches to assessing and supporting sleep health in forms that aremeaningful for aging well across cultures. [ABSTRACT FROM AUTHOR]

Repressor element-1 silencing transcription factor (REST) is required for the formation of mature neurons. REST dysregulation underlies a key mechanism of neurodegeneration associated with neurological disorders. However, the mechanisms leading to alterations of REST-mediated silencing of key neurogenesis genes are not known. Here, we show that BRCA1 Associated ATM Activator 1 (BRAT1), a gene linked to neurodegenerative diseases, is required for the activation of REST-responsive genes during neuronal differentiation. We find that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 as a distinct trimeric complex to activate critical neuronal genes during differentiation. BRAT1 depletion results in persistence of REST residence on critical neuronal genes disrupting the differentiation of NT2 cells into astrocytes and neuronal cells. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations in BRAT1 diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex. Finally, loss of Brat1 in mouse embryonic stem cells leads to a defect in neuronal differentiation assay. Importantly, while reconstitution with wild-type BRAT1 restores neuronal differentiation, the addition of a BRAT1 mutant is unable to associate with INTS11/INTS9 and fails to rescue the neuronal phenotype. Taken together, our study highlights the importance of BRAT1 association with INTS11 and INTS9 in the development of the nervous system. [ABSTRACT FROM AUTHOR]

Professional literature shows that certain modifiable behaviors in lifestyle, such as diet, physical activity, leisure time, and rest, are risk factors for decreased quality of life. In other words, neglecting these vital aspects of life leads, in chain, to the impairment of physical and mental health. Self-care behaviors, management of physical and mental resources are affected by personal psychological characteristics, with locus of control playing a central role. Research has been marked by the idea that dietary behavior (nutrition), alongside its specific existential roles (roles of growth and development, maturation, and survival), is significantly linked to other important dimensions of physical and mental life (locus of control, self-attitude, professional activity, physical and emotional regulation activities - such as engaging in physical activities and rest). To collect data in support of the formulated hypothesis, we administered two questionnaires (lifestyle questionnaire and locus of control questionnaire) to a sample of 219 teachers from pre-university education. [ABSTRACT FROM AUTHOR]

Female domestic workers (FDWs) experience space–time constraints and mobility challenges corresponding to their demanding daily work responsibilities. Studies have shown that FDWs' mobility and activities are primarily dictated by their employers through work tasks. It is unclear, though, how FDWs' activity and mobility patterns outside their employers' homes are shaped by individual and contextual factors, including government policies that mandate that FDWs be granted a rest day. Using an activity space approach combined with multilevel modeling, I evaluated mobility and activity patterns on work and rest days for a sample of Indonesian FDWs in Hong Kong. Data were collected using innovative online activity diaries and were triangulated with qualitative data from WhatsApp follow-up conversations. This research uncovers that FDWs' activity patterns differ significantly between work and rest days. FDWs rarely go outside on workdays except to perform work-related tasks. On the rest day, FDWs' activity spaces are much more expansive as they conduct social and personal activities that are essential for maintaining their well-being. By comparing work and rest days, this research deepens our understanding of geographical, social, and temporal aspects of FDWs' space–time constraints and (im)mobility experiences that encompass and go beyond employer-assigned tasks. Furthermore, the findings demonstrate the benefits of rest day policies for enhancing the visibility of marginalized women in public spaces, particularly in the context of FDWs' restrictive space–time constraints. [ABSTRACT FROM AUTHOR]

Understanding the behaviour of a system's API can be hard. Giving users access to relevant examples of how an API behaves has been shown to make this easier for them. In addition, such examples can be used to verify expected behaviour or identify unwanted behaviours. Methods for automatically generating examples have existed for a long time. However, state-of-the-art methods rely on either white-box information, such as source code, or on formal specifications of the system behaviour. But what if you do not have access to either? This may be the case, for example, when interacting with a third-party API. In this paper, we present an approach to automatically generate relevant examples of behaviours of an API, without requiring either source code or a formal specification of behaviour. Evaluation on an industry-grade REST API shows that our method can produce small and relevant examples that can help engineers to understand the system under exploration. [ABSTRACT FROM AUTHOR]

Background: γ-Glutamylcyclotransferase (GGCT), an enzyme crucial in glutathione metabolism, has emerged as a participant in tumorigenesis. The present study is designed to elucidate the biological role and molecular mechanisms underlying GGCT in glioma. Methods: Gene Expression Profiling Interactive Analysis (GEPIA), Chinese Glioma Genome Atlas (CGGA), and PrognoScan online databases were utilized to examine the expressions and clinical prognosis of GGCT and REST in glioma. Cell Counting Kit-8 (CCK-8), Transwell, Wound healing, and Flow cytometric assays, and RNA-sequencing analysis were employed to uncover the molecular role of GGCT and REST. Prediction of Differentially expressed microRNA (DE-miRNAs) and miRNAs targeting GGCT 3′ Untranslated Region (UTR) was performed using miRanda online datasets. Finally, Real time-quantitative Polymerase Chain Reaction (RT-qPCR), western blot and dual luciferase reporter gene activity analysis were employed to confirm a positive feedback loop involving GGCT/REST/miR-34a-5p in glioma cells. Results: High expression of GGCT was correlated with poor prognosis in glioma. GGCT silencing demonstrated inhibitory effects on the proliferation, migration, and induction of apoptosis in T98G and U251 cells. Mechanistically, GGCT downregulated REST expression and modulated cancer-associated pathways in glioma cells. High expression of REST was associated with poor prognosis in glioma. In vitro and in vivo experiments showed that REST overexpression restored the repression of proliferation, invasion, migration, and xenograft tumor formation induced by GGCT knockdown. Furthermore, the study uncovered that REST inhibited miR-34a-5p mRNA expression, and miR-34a-5p suppressed GGCT expression by targeting its 3′UTR, forming a positive regulatory loop in glioma. Notably, the inhibitor of miR-34a-5p restored the role of REST silencing in decreasing GGCT expression in glioma cells. Conclusions: GGCT/REST/miR-34a-5p axis holds promising potential as a therapeutic target, offering a potential breakthrough in the treatment of glioma.

Objective: The diversity of electrode placement systems brought the problem of channel location harmonization in large-scale electroencephalography (EEG) applications to the forefront. Therefore, our goal was to resolve this problem by introducing and assessing the reference electrode standardization technique (REST) to transform EEGs into a common electrode distribution with computational zero reference at infinity offline. Methods: Simulation and eye-closed resting-state EEG datasets were used to investigate the performance of REST for EEG signals and power configurations. Results: REST produced small errors (the root mean square error (RMSE): 0.2936–0.4583; absolute errors: 0.2343–0.3657) and high correlations (>0.9) between the estimated signals and true ones. The comparison of configuration similarities in power among various electrode distributions revealed that REST induced infinity reference could maintain a perfect performance similar (>0.9) to that of true one. Conclusion: These results demonstrated that REST transformation could be adopted to resolve the channel location harmonization problem in large-scale EEG applications.

This article uses a feminist cultural studies of sport framework to explore dominant storytelling about sleep in the Women's National Basketball Association. In a historical moment when rest is understood as a vital component in athlete performance, being denied full access to the conditions and resources that are imagined to be conducive to sleep is problematic. However, the Women's National Basketball Association's embrace of a commercial, technoscientific promotional sleep culture often comes at the expense of understanding the impact of structural forces on recovery. By exploring a variety of stories about sleep and performance, it is possible to understand the limitations and possibilities of using sleep enhancement frameworks to foster healthier and more humane sport settings and societies. [ABSTRACT FROM AUTHOR]

Abstract The RE1-silencing transcription factor (REST) acts either as a repressor or activator of transcription depending on the genomic and cellular context. REST is a key player in brain cell differentiation by inducing chromatin modifications, including DNA methylation, in a proximity of its binding sites. Its dysfunction may contribute to oncogenesis. Mutations in IDH1/2 significantly change the epigenome contributing to blockade of cell differentiation and glioma development. We aimed at defining how REST modulates gene activation and repression in the context of the IDH mutation-related phenotype in gliomas. We studied the effects of REST knockdown, genome wide occurrence of REST binding sites, and DNA methylation of REST motifs in IDH wild type and IDH mutant gliomas. We found that REST target genes, REST binding patterns, and TF motif occurrence proximal to REST binding sites differed in IDH wild-type and mutant gliomas. Among differentially expressed REST targets were genes involved in glial cell differentiation and extracellular matrix organization, some of which were differentially methylated at promoters or gene bodies. REST knockdown differently impacted invasion of the parental or IDH1 mutant glioma cells. The canonical REST-repressed gene targets showed significant correlation with the GBM NPC-like cellular state. Interestingly, results of REST or KAISO silencing suggested the interplay between these TFs in regulation of REST-activated and repressed targets. The identified gene regulatory networks and putative REST cooperativity with other TFs, such as KAISO, show distinct REST target regulatory networks in IDH-WT and IDH-MUT gliomas, without concomitant DNA methylation changes. We conclude that REST could be an important therapeutic target in gliomas.

STUDY OBJECTIVES: Sleep duration and intraindividual variability in sleep duration undergo substantial changes in adolescence and impact brain and behavioral functioning. Although experimental work has linked acute sleep deprivation to heightened limbic responding and reduced regulatory control, there is limited understanding of how variability in sleep patterns might interact with sleep duration to influence adolescent functioning. This is important for optimal balancing of length and consistency of sleep. Here, we investigated how objective indices of sleep duration and variability relate to stress, restfulness, and intrinsic limbic network functioning in adolescents. METHODS: A sample of 101 adolescents ages 14-18 reported their stressors, after which they wore wrist actigraph watches to monitor their sleep and rated their restfulness every morning over a 2-week period. They also completed a resting-state fMRI scan. RESULTS: Adolescents reporting more stress experienced shorter sleep duration and greater sleep variability over the 2-week period. Longer nightly sleep duration was linked to feeling more rested the next morning, but this effect was reduced in adolescents with high cumulative sleep variability. Sleep variability showed both linear and quadratic effects on limbic connectivity: adolescents with high sleep variability exhibited more connectivity within the limbic network and less connectivity between the limbic and frontoparietal networks than their peers, effects which became stronger once variability exceeded an hour. CONCLUSIONS: Results suggest that cumulative sleep variability is related to stress and limbic network connectivity and shows interactive effects with sleep duration, highlighting the importance of balancing length and consistency of sleep for optimal functioning in adolescence.

BACKGROUND: While Alzheimers disease (AD) pathology is associated with altered brain structure, it is not clear whether gene expression changes mirror the onset and evolution of pathology in distinct brain regions. Deciphering the mechanisms which cause the differential manifestation of the disease across different regions has the potential to help early diagnosis. OBJECTIVE: We aimed to identify common and unique endotypes and their regulation in tangle-free neurons in sporadic AD (SAD) across six brain regions: entorhinal cortex (EC), hippocampus (HC), medial temporal gyrus (MTG), posterior cingulate (PC), superior frontal gyrus (SFG), and visual cortex (VCX). METHODS: To decipher the states of tangle-free neurons across different brain regions in human subjects afflicted with AD, we performed analysis of the neural transcriptome. We explored changes in differential gene expression, functional and transcription factor target enrichment, and co-expression gene module detection analysis to discern disease-state transcriptomic variances and characterize endotypes. Additionally, we compared our results to tangled AD neuron microarray-based study and the Allen Brain Atlas. RESULTS: We identified impaired neuron function in EC, MTG, PC, and VCX resulting from REST activation and reversal of mature neurons to a precursor-like state in EC, MTG, and SFG linked to SOX2 activation. Additionally, decreased neuron function and increased dedifferentiation were linked to the activation of SUZ12. Energetic deficit connected to NRF1 inactivation was found in HC, PC, and VCX. CONCLUSIONS: Our findings suggest that SAD manifestation varies in scale and severity in different brain regions. We identify endotypes, such as energetic shortfalls, impaired neuronal function, and dedifferentiation.

The RE1-silencing transcription factor (REST) acts either as a repressor or activator of transcription depending on the genomic and cellular context. REST is a key player in brain cell differentiation by inducing chromatin modifications, including DNA methylation, in a proximity of its binding sites. Its dysfunction may contribute to oncogenesis. Mutations in IDH1/2 significantly change the epigenome contributing to blockade of cell differentiation and glioma development. We aimed at defining how REST modulates gene activation and repression in the context of the IDH mutation-related phenotype in gliomas. We studied the effects of REST knockdown, genome wide occurrence of REST binding sites, and DNA methylation of REST motifs in IDH wild type and IDH mutant gliomas. We found that REST target genes, REST binding patterns, and TF motif occurrence proximal to REST binding sites differed in IDH wild-type and mutant gliomas. Among differentially expressed REST targets were genes involved in glial cell differentiation and extracellular matrix organization, some of which were differentially methylated at promoters or gene bodies. REST knockdown differently impacted invasion of the parental or IDH1 mutant glioma cells. The canonical REST-repressed gene targets showed significant correlation with the GBM NPC-like cellular state. Interestingly, results of REST or KAISO silencing suggested the interplay between these TFs in regulation of REST-activated and repressed targets. The identified gene regulatory networks and putative REST cooperativity with other TFs, such as KAISO, show distinct REST target regulatory networks in IDH-WT and IDH-MUT gliomas, without concomitant DNA methylation changes. We conclude that REST could be an important therapeutic target in gliomas. [ABSTRACT FROM AUTHOR]

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Introduction: Monitoring overnight behavior is important in assessing the overall wellbeing of ex-situ elephant populations, with recumbent rest and stereotypy as key indicators of welfare. However, there have been few studies that address the overnight behavior of singly housed male elephants with a history of stereotypy. We conducted an opportunistic case study of the overnight behavior (i.e., rest and stereotypy) of a singly housed geriatric male Asian elephant at the Oklahoma City Zoo to identify his overnight behavioral rhythms in response to physiological (musth) and environmental changes (habitat access, automatic timed feeders) and guide management strategies. Methods: Infrared cameras were utilized to conduct continuous focal-animal sampling of the elephant's behavior between 20:00 and 08:00 in indoor and outdoor habitats. Sampling occurred from January 2023 to October 2023, with a total of 179 overnight observations. Results: The elephant exhibited recumbent rest for 175.66 ± 6.80 (mean ± SE) minutes per night and was engaged in stereotypy for 175.88 ± 9.68 minutes per night. While there was no significant relationship between stereotypy and the sexual state of musth, musth was associated with reduced durations of recumbent rest. Access to both indoor and outdoor habitats was significantly related to decreased stereotypy compared to indoor-only treatments. Recumbent rest occurred most frequently between 02:00 and 05:00, and stereotypic behavior was most common between 06:00 and 08:00. Contrary to our expectations, automatic feeders did not significantly reduce stereotypy. Discussion: The results of this study provide insight into the behavioral patterns of a geriatric male Asian elephant, demonstrating the importance of implementing an animal-centered approach to enhance animal wellbeing. As the zoo-housed Asian elephant population grows and continues to age, this case study emphasizes the importance of developing comprehensive welfare strategies for the elephants in our care. [ABSTRACT FROM AUTHOR]

Microservice architecture has become the design paradigm for creating scalable and maintainable software systems. Selecting the proper communication protocol in microservices is critical to achieving optimal system performance. This study compares the performance of three commonly used API protocols: REST, GraphQL, and gRPC, in microservices architecture. In this study, we established three microservices implemented in three containers and each microservice contained a Redis and MySQL database. We evaluated the performance of these API protocols using two key performance metrics: response time and CPU Utilization. This study performs two distinct data retrieval: fetching flat data and fetching nested data, with a number of requests ranging from 100 to 500 requests. The experimental results indicate that gRPC has a faster response time, followed by REST and GraphQL. Moreover, GraphQL shows higher CPU Utilization compared to gRPC and REST. The experimental results provide insight for developers and architects seeking to optimize their microservices communication protocols for specific use cases and workloads. [ABSTRACT FROM AUTHOR]

An important tool for improving the productive characteristics of pigs, including boars, is a thorough study of their behavioural patterns and reactions to compliance with housing conditions, which serves as an indicator of the protocol for assessing the welfare of this sex group in commercial pig farms. The purpose of the experiment was to identify the influence of age, season of the year, and type of ventilation on the duration of behavioural acts of boars by breeds to establish their behavioural patterns in industrial technology. The experiment involved 18 boars of the Large White, Landrace, and Duroc breeds. The boars selected for the experiments were clinically healthy and divided into two groups of 9 animals each. The control group of boars was kept in a room with a transverse ventilation system, and the animals of the experimental group were kept in geothermal air supply conditions for a year. In the process of visualising the behaviour parameters of boars of different breeds, it was found that: the duration of rest was significant (P < 0.001) affected by 49.1-67.6% - age, 10.9-23.2% - season of the year, 0.1-3.0% - type of ventilation; the duration of movement during the day was significant (P < 0.001) affected by 44.7-68.0% - age, 9.1-28.5% - season of the year, 0.5-3.2% - type of ventilation; the duration of admission feed and water were significant affected (P < 0.001) by 49.7-71.9% - age, 7.9-25.9% - season of the year, 0.1-2.4% - type of ventilation. A behavioural act that prevailed in duration and frequency (P < 0.001), especially in the summer-autumn period, was rest, which increased in time with age from 72.3% to 76.4%, regardless of the breed, season of the year, and type of ventilation. In summer and autumn, the transverse air supply system visualised abnormal apathetic behaviour during rest in animals (lying on their sides, stomach, eyes closed, without any reactions to indifferent stimuli, and the time that boars spent on stereotypical behaviour (head banging, jumping and licking the bars of the cage) increased by 3% (P < 0.95) and in the "position of sitting dog" by 2% (P < 0.95). The results obtained allow introducing the use of ethological factors in industrial pig production to increase boar sperm production, and identify individuals with behavioural deviations to develop ways to assess welfare and integrate them into production. [ABSTRACT FROM AUTHOR]

The brain often switches freely between focused attention and divergent thinking, and the Default Mode Network (DMN) is activated during brain rest. Since its discovery, the DMN, together with its function and characteristics, indicates that learning does not stop when the brain "rests". Therefore, DMN plays an important role in learning. Neural activities such as beta wave rhythm regulation, "subconscious" divergence thinking mode initiation, hippocampal function, and neural replay occur during default mode, all of which explains that "rest" promotes learning. This paper summarized the function and neural mechanism of DMN in learning and proposed that the DMN plays an essential role in learning, which is that it enables rest to promote learning. [ABSTRACT FROM AUTHOR]

Introduction. Agility, an essential aspect of various sports, has attracted increasing interest and has become a popular subject of research due to its direct influence on athletic performance. Aim of Study. The aim of this study was to analyze an acute effect of training with VertiMax and inertial devices as mechanisms for post-activation performance enhancement (PAPE) in physically active individuals. Material and Methods. A sample consisted of 27 participants with an average age of 24.33 ± 2.89 years. Participants were randomly assigned to three groups: An inertial RSP-squat device group, a VertiMax device group, and a control group. Results. Frequentist analyses revealed a significant interaction between pretest and posttest conditions, although no significant differences were found between the study groups. These findings were confirmed by Bayesian analyses. Both experimental groups and the control group showed reductions in race times, although a percentage of change was higher for a VertiMax training protocol. Additionally, it was observed that rest periods of approximately five minutes between measurements were more effective in improving athletic performance. Conclusions. Integration of PAPE-based training strategies with the use of devices can be crucial in optimizing athletic performance, although ongoing research is needed to inform practical and theoretical decisions in a field of physical conditioning. [ABSTRACT FROM AUTHOR]