Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) and other neurodegenerative diseases (NDs) cause substantial health-related and economic burdens, but progress towards preventative or ameliorative treatments has been limited. Genome-wide association studies have identified hundreds of risk loci containing single nucleotide polymorphisms (SNPs) that alter risk for these diseases, but >90% of these SNPs are in noncoding regions, which are cell type-specific and difficult to study. To address this gap, we have characterized the epigenomes of iPSC-derived neuronal and glial cells and performed CRISPRi single cell screening to dissect the molecular and cellular mechanisms underlying 10 ND risk loci.

CD47 predominates over CD24 as a macrophage immune checkpoint in cancer.

Macrophages hold tremendous promise as effectors of cancer immunotherapy, but the best strategies to provoke these cells to attack tumors remain unknown. Here, we evaluated the therapeutic potential of targeting two distinct macrophage immune checkpoints: CD47 and CD24. We found that antibodies targeting these antigens could elicit maximal levels of phagocytosis when combined together in vitro.

Ciliopathy interacts with neonatal anesthesia to cause non-apoptotic caspase-mediated motor deficits.

Increasing evidence suggests that anesthesia may induce developmental neurotoxicity, yet the influence of genetic predispositions associated with congenital anomalies on this toxicity remains largely unknown. Children with congenital heart disease often exhibit mutations in cilia-related genes and ciliary dysfunction, requiring sedation for their catheter or surgical interventions during the neonatal period. Here we demonstrate that briefly exposing ciliopathic neonatal mice to ketamine causes motor skill impairments, which are associated with a baseline deficit in neocortical layer V neuron apical spine density and their altered dynamics during motor learning.

Virtual individual cognitive stimulation therapy (V-iCST): Mixed methods feasibility randomised controlled trial.

Objective: Cognitive Stimulation Therapy (CST) is a dementia intervention shown to improve cognition and quality of life (QoL). Previous research on individual CST delivered by family carers showed no significant improvements in people with dementia. We aimed to evaluate the feasibility and acceptability of Virtual Individual Cognitive Stimulation Therapy (V-iCST) delivered by healthcare personnel.

Use of in situ simulation to improve team performance and utilization of a rapid sequence intubation checklist.

Background: Intubation checklists have emerged as tools to reduce adverse events and improve efficiency during rapid sequence intubation (RSI) in pediatric emergency departments (PEDs). This study aimed to use multidisciplinary simulation (SIM) training as an educational tool to improve PED team performance during RSI scenarios through utilization of an RSI checklist.

Methods: We created a checklist modeled after previously published PED checklists.