Psychosocial risks and mental health of preschool care providers in Kuala Lumpur, Malaysia: a cross-sectional study.

Background: Child maltreatment in daycare is a public health issue. As childcare is stressful, high care provider negativity independently predicts more internalizing behaviour problems, affecting children's psycho-neurological development. This study aimed to determine psychosocial factors associated with the mental health of preschool care providers in Kuala Lumpur.

Sarcolemma resilience and skeletal muscle health require O-mannosylation of dystroglycan.

Background: Maintaining the connection between skeletal muscle fibers and the surrounding basement membrane is essential for muscle function. Dystroglycan (DG) serves as a basement membrane extracellular matrix (ECM) receptor in many cells, and is also expressed in the outward-facing membrane, or sarcolemma, of skeletal muscle fibers. DG is a transmembrane protein comprised of two subunits: alpha-DG (α-DG), which resides in the peripheral membrane, and beta-DG (β-DG), which spans the membrane to intracellular regions.

Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.

Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.

Simulated retail food environments: A literature review of systems science approaches to advance equity in access to healthy diets.

As researchers increasingly utilize systems science simulation modeling (SSSM), little is known about how and by whom SSSMs are being leveraged to address inequities in access to healthy diets. We evaluated the extent to which studies (n = 66) employing SSSM to examine retail food environments (RFEs): included three pillars of equity (social position, human capital, socioeconomic and political context) that shape RFEs and access to healthy diets; grounded model design and development in theory; engaged with diverse stakeholders and lived experiences related to RFEs; and translated model findings towards addressing inequities in RFEs. Most studies (n = 58) included some model characteristics related to social position (e.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Commutability assessment of new standard reference materials (SRMs) for determining serum total 25-hydroxyvitamin D using ligand binding and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.

Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyvitamin D [25(OH)D], was assessed through an interlaboratory study.

IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.

Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.

Conditional Deletion of Gremlin-1 in Cathepsin K-expressing Mature Osteoclasts Altered the Skeletal Response to Calcium Depletion in Sex-Dependent Manner.

This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover.

Interpretable identification of cancer genes across biological networks via transformer-powered graph representation learning.

Graph representation learning has been leveraged to identify cancer genes from biological networks. However, its applicability is limited by insufficient interpretability and generalizability under integrative network analysis. Here we report the development of an interpretable and generalizable transformer-based model that accurately predicts cancer genes by leveraging graph representation learning and the integration of multi-omics data with the topologies of homogeneous and heterogeneous networks of biological interactions.

Advancing brain immunotherapy through functional nanomaterials.

Glioblastoma (GBM), a highly aggressive brain tumor, poses significant treatment challenges due to its highly immunosuppressive microenvironment and the brain immune privilege. Immunotherapy activating the immune system and T lymphocyte infiltration holds great promise against GBM. However, the brain's low immunogenicity and the difficulty of crossing the blood-brain barrier (BBB) hinder therapeutic efficacy.

Standardized patient profile review using large language models for case adjudication in observational research.

Using administrative claims and electronic health records for observational studies is common but challenging due to data limitations. Researchers rely on phenotype algorithms, requiring labor-intensive chart reviews for validation. This study investigates whether case adjudication using the previously introduced Knowledge-Enhanced Electronic Profile Review (KEEPER) system with large language models (LLMs) is feasible and could serve as a viable alternative to manual chart review.

Transcription factor networks in cellular quiescence.

Many of the cells in mammalian tissues are in a reversible quiescent state; they are not dividing, but retain the ability to proliferate in response to extracellular signals. Quiescence relies on the activities of transcription factors (TFs) that orchestrate the repression of genes that promote proliferation and establish a quiescence-specific gene expression program. Here we discuss how the coordinated activities of TFs in different quiescent stem cells and differentiated cells maintain reversible cell cycle arrest and establish cell-protective signalling pathways.

G-SET-DCL: a guided sequential episodic training with dual contrastive learning approach for colon segmentation.

Purpose: This article introduces a novel deep learning approach to substantially improve the accuracy of colon segmentation even with limited data annotation, which enhances the overall effectiveness of the CT colonography pipeline in clinical settings.

Methods: The proposed approach integrates 3D contextual information via guided sequential episodic training in which a query CT slice is segmented by exploiting its previous labeled CT slice (i.e.

UW supplementation with AP39 improves liver viability following static cold storage.

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.

Sugemule-7 alleviates oxidative stress, neuroinflammation, and cell death, promoting synaptic plasticity recovery in mice with postpartum depression.

Postpartum depression (PPD) profoundly impacts the mental and physical health of women globally and is an incurable psychological disorder. Traditional pharmacological treatments often have strong side effects and may adversely affect infant health through breastfeeding, underscoring the critical need for natural and gentle treatment strategies. Sugemule-7, a traditional Chinese medicine comprising multiple natural plant ingredients, represents a potentially safer and more effective alternative.

The Psu protein of phage satellite P4 inhibits transcription termination factor ρ by forced hyper-oligomerization.

Many bacteriophages modulate host transcription to favor expression of their own genomes. Phage satellite P4 polarity suppression protein, Psu, a building block of the viral capsid, inhibits hexameric transcription termination factor, ρ, by presently unknown mechanisms. Our cryogenic electron microscopy structures of ρ-Psu complexes show that Psu dimers clamp two inactive, open ρ rings and promote their expansion to higher-oligomeric states.

Divergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.

N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.

Enhancing immunotherapy efficacy in colorectal cancer: targeting the FGR-AKT-SP1-DKK1 axis with DCC-2036 (Rebastinib).

This research demonstrates that DCC-2036 (Rebastinib), a potent third-generation tyrosine kinase inhibitor (TKI), effectively suppresses tumor growth in colorectal cancer (CRC) models with functional immune systems. The findings underscore the capacity of DCC-2036 to enhance both the activation and cytotoxic functionality of CD8 T cells, which are crucial for facilitating anti-tumor immune responses. Through comprehensive multi-omics investigations, significant shifts in both gene and protein expression profiles were detected, notably a marked decrease in DKK1 levels.

Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.

Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.

Performance evaluation of a machine learning-based methodology using dynamical features to detect nonwear intervals in actigraphy data in a free-living setting.

Goal And Aims: One challenge using wearable sensors is nonwear time. Without a nonwear (e.g.

Importance of infarct topography in determination of stroke mechanism and recurrence risk: a post-hoc analysis of the dabigatran acute treatment of stroke trial.

Objective: To evaluate the relationship between infarct pattern, inferred stroke mechanism and risk of recurrence in patients with ischaemic stroke. The question is clinically relevant to optimise secondary stroke prevention investigations and treatment.

Design: We conducted a retrospective analysis of the dabigatran treatment of acute stroke II (DATAS II) trial (ClinicalTrials.

Single-Cell Heterogeneity of EGFR Pathway Is Linked to Unique Signatures of Drug Response and Malignancy in Patient Derived Glioblastoma Stem Cells.

Purpose: In glioblastoma, the therapeutically intractable and resistant phenotypes can be derived from glioma stem cells, which often have different underlying mechanisms from non-stem glioma cells. Aberrant signaling across the EGFR-PTEN-AKT-mTOR pathways have been shown as common drivers of glioblastoma. Revealing the inter and intra-cellular heterogeneity within glioma stem cell populations in relations to signaling patterns through these pathways may be key to precision diagnostic and therapeutic targeting of these cells.