Basic Science and Pathogenesis.

Background: Late Onset Alzheimer's Disease (LOAD) is the most common neurodegenerative disorder. Carriers of an ɛ4 allele of the apolipoprotein E gene (APOE) have significantly increased risk of developing LOAD. LOAD is also strongly sex biased.

Senolysis by ABT-263 is associated with inherent apoptotic dependence of cancer cells derived from the non-senescent state.

Cellular senescence is a stress response that cells can employ to resist cell death. Senescent cells rely on anti-apoptotic signaling for their survival, which can be targeted by senolytic agents, like the BCL-XL, BCL-2, BCL-W inhibitor ABT-263. However, the response to ABT-263 of senescent cancer cells ranges from highly sensitive to refractory.

Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.

Cultural transmission, networks, and clusters among Austronesian-speaking peoples.

With its linguistic and cultural diversity, Austronesia is important in the study of evolutionary forces that generate and maintain cultural variation. By analysing publicly available datasets, we have identified four classes of cultural features in Austronesia and distinct clusters within each class. We hypothesized that there are differing modes of transmission and patterns of variation in these cultural classes and that geography alone would be insufficient to explain some of these patterns of variation.

Exploring How the Kidney BEAM Physical Activity Digital Health Intervention Improved Mental Health-Related Quality of Life for People Living With Kidney Disease.

Introduction: The Kidney BEAM randomized controlled trial reported clinically meaningful and statistically significant improvements in mental health-related quality of life (HRQoL), physical function (sit-to-stand-60, but not the physical component of HRQoL) and patient activation after a 12-week physical activity digital health intervention (DHI). This study explores factors that contributed to the effectiveness of Kidney BEAM through mixed methods analyses.

Methods: Quantitative data analysis was obtained from the recently published primary manuscript.

The impact of the COVID-19 pandemic on the antimicrobial stewardship workforce in Scottish acute care hospitals-a qualitative study.

Background: Antimicrobial stewardship (AMS) programmes seek to reduce the risk of antimicrobial resistance by minimizing inappropriate antimicrobial use. The SARS-CoV-2 coronavirus (COVID-19) pandemic was characterized by initial widespread use of antimicrobials in patients with COVID-19, with potential negative effects on AMS efforts.

Objective: To explore the impact of the pandemic on the AMS workforce in Scottish acute care hospitals.

A transcriptomic comparison of in vitro models of the human placenta.

Introduction: Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. The aim of this research was to compare the transcriptomes of common in vitro models of the human placenta compared to bulk human placental tissue.

Methods: We performed differential gene expression analysis on publicly available transcriptomic data from 7 in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, Villous Explants, and Trophoblast Stem Cells) and compared to bulk placental tissue from 2 cohort studies (CANDLE and GAPPS) or individual trophoblast cell types derived from bulk placental tissue.

Structural insights into the ATP-dependent activation of NOD-like receptor with pyrin 3 (NLRP3) protein by molecular dynamics simulation.

The inflammasome-forming NOD-like receptor containing pyrin-3 (NLRP3) protein is a critical player in the innate immune responses to cellular danger signals. New structural data of NLRP3 provide a framework to probe the conformational impact of nucleotide binding. In this study, microsecond molecular dynamics (MD) simulations were used to detail information on the unique structural conformations adopted by NLRP3 with ATP or ADP binding.

Combating Emerging Respiratory Viruses: Lessons and Future Antiviral Strategies.

Emerging viral diseases, including seasonal illnesses and pandemics, pose significant global public health risks. Respiratory viruses, particularly coronaviruses and influenza viruses, are associated with high morbidity and mortality, imposing substantial socioeconomic burdens. This review focuses on the current landscape of respiratory viruses, particularly influenza and SARS-CoV-2, and their antiviral treatments.

Partial Enteral Nutrition in the Management of Crohn's Disease: A Systematic Review and Meta-Analysis.

Background: Exclusive enteral nutrition is an established treatment for active Crohn's disease (CD) but the role of partial enteral nutrition (PEN) in the broader management of the disease is less clear. This systematic review and meta-analysis reviewed the literature on the role of PEN in CD management.

Methods: This review was conducted following Cochrane recommendations.

C2-Arylated Indoles and Benzofurans through Formal (4 + 1) Annulation of -Sulfonyl-2-aminobenzaldehydes and Salicylaldehyde Derivatives with Electron-Deficient Benzyl Chlorides.

A two-step formal (4 + 1) annulation-dehydration reaction offers a convenient route to C2-arylated indoles and benzofurans. This reaction exploits the bifunctional reactivity of electron-deficient benzyl chlorides with -sulfonyl-2-aminobenzaldehydes or salicylaldehyde derivatives. The reaction tolerates both electron-withdrawing and donating groups on the substituted aldehydes, as well as variation of electron-withdrawing groups at the position of the benzyl chloride reagent.

Integrating Compassion and Collaboration into the Care of Intensive Care Unit Survivors: A Modest Proposal.

The number of intensive care unit (ICU) survivors continues to grow, largely due to the emergence of more sophisticated treatment options. Yet despite this remarkable life-saving progress, far too little attention is paid to the survivor's long-term quality of life after discharge. Post-Intensive Care Syndrome continues to impact many survivors' physical, cognitive, and mental health, as well as their social functioning related to these new impairments.

Kidney Beam-A Cost-Effective Digital Intervention to Improve Mental Health.

Introduction: There is inequity in the provision of physical rehabilitation services for people living with chronic kidney disease (CKD). The Kidney BEAM trial evaluated the clinical value and cost effectiveness of a physical activity digital health intervention (DHI) in CKD.

Methods: In a single-blind, 11 center, randomized controlled trial, 340 adult participants with CKD were randomly assigned to either the Kidney BEAM physical activity DHI or a waitlist control.

Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.

Mutations in GBA (glucosylceramidase beta), which encodes the lysosomal enzyme glucocerebrosidase (GCase), are the strongest genetic risk factor for the neurodegenerative disorders Parkinson's disease (PD) and Lewy body dementia. Recent work has suggested that neuroinflammation may be an important factor in the risk conferred by GBA mutations. We therefore systematically tested the contributions of immune-related genes to neuropathology in a Drosophila model of GCase deficiency.

Centre-level fluid management practices in the BISTRO trial and their lack of association with participant fluid status and blood pressure in non-anuric haemodialysis patients.

Introduction: Fluid assessment and management is a key aspect of good dialysis care and is affected by patient-level characteristics and potentially centre-level practices. In this secondary analysis of the BISTRO trial we wished to establish whether centre-level practices with the potential to affect fluid status were stable over the course of the trial and explore if they had any residual associations with participant's fluid status.

Methods: Two surveys (S) of fluid management practices were conducted in 32 participating centres during the trial, (S1: 2017-18 and S2: 2021-22).

Flagellar motility and the mucus environment influence aggregation mediated antibiotic tolerance of in chronic lung infection.

frequently causes chronic lung infection in individuals with muco-obstructive airway diseases (MADs). Chronic infections are difficult to treat, primarily owing to antibiotic treatment failure, which is often observed in the absence of antimicrobial resistance. In MADs, forms biofilm-like aggregates within the luminal mucus.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Rigor and Reproducibility of Digital Spatial Profiling on Clinically Sourced Human Tissues.

Spatial transcriptomic profiling enables precise quantification of gene expression with simultaneous localization of expression profiles onto tissue structures. This new technology promises to improve our understanding of the disease mechanisms. Therefore, there is intense interest in applying these methods in clinical trials or as laboratory developed tests to aid in diagnosis of disease.

Cystic fibrosis-related diabetes is associated with reduced islet protein expression of GLP-1 receptor and perturbation of cell-specific transcriptional programs.

Insulin secretion is impaired in individuals with cystic fibrosis (CF), contributing to high rates of CF-related diabetes (CFRD) and substantially increasing disease burden. To develop improved therapies for CFRD, better knowledge of pancreatic pathology in CF is needed. Glucagon like peptide-1 (GLP-1) from islet α cells potentiates insulin secretion by binding GLP-1 receptors (GLP-1Rs) on β cells.

Sharing the motherload: A review and development of the CO-Parent conceptual model for early childhood obesity prevention.

Fathers remain under-represented in early childhood obesity prevention research and interventions, despite growing evidence that paternal biopsychosocial factors and behaviors from pre- and post-conception can influence lifelong offspring health. Informed by a literature review of high-quality evidence, "CO-Parent" (childhood obesity-Parent) is a new conceptual model underpinned by couple interdependence theory and a socioecological framework. Literature was searched for the concepts parental AND weight-related behaviors AND child weight or weight-related behaviors, in databases including MEDLINE, PsycINFO, Global Health, Scopus, and SocINDEX.

Associations Between Prenatal Vitamin D and Placental Gene Expression.

Background: Vitamin D is a hormone that regulates gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D.