Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Cardiorenal outcomes associated with sodium-glucose co-transporter-2 inhibitors in chronic kidney disease stage 5 (CKD V): A propensity score-matched analysis.

Background: There remains a paucity of data regarding the cardio-renal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease stage 5 (CKD V) based on major clinical trials.

Objective: This retrospective study aimed to identify potential cardiovascular and renal outcomes associated with SGLT2i use in CKD V patients.

Methods: We queried the TriNetX Global collaborative network from Jan 2014 - Aug 2023 for patients ≥18 years diagnosed with CKD V but not on dialysis.

Newborn daughters get a fresh start through PI(3,5)P2-mediated vacuolar acidification.

Huda et al. (https://doi.org/10.

Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images.

Immune checkpoint inhibitors (ICI) have become integral to treatment of non-small cell lung cancer (NSCLC). However, reliable biomarkers predictive of immunotherapy efficacy are limited. Here, we introduce HistoTME, a novel weakly supervised deep learning approach to infer the tumor microenvironment (TME) composition directly from histopathology images of NSCLC patients.

A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques.

Eilat (EILV)/chikungunya virus (CHIKV), an insect-based chimeric alphavirus was previously reported to protect mice months after a single dose vaccination. The underlying mechanisms of host protection are not clearly defined. Here, we assessed the capacity of EILV/CHIKV to induce quick and durable protection in cynomolgus macaques.

Benefit of using an assistive listening device in a hospital setting.

High levels of noise in hospital settings can make communication difficult, especially for older adults. Assistive Listening Devices (ALDs) are personal amplifiers that can improve hearing in background noise. This study investigated the impact of providing ALDs to hospitalized patients 60 years of age and older without using hearing screenings to determine eligibility.

Psychometric evaluation of the Autism Symptom Dimensions Questionnaire.

Aim: To replicate and extend previous psychometric findings for the Autism Symptom Dimensions Questionnaire (ASDQ).

Method: Using a cross-sectional design in two samples, including a total of 3366 children and adolescents (aged 2-17 years; 1399 with autism spectrum disorder) and a small case series, factor structure, measurement invariance, reliability, construct validity, screening and diagnostic efficiency, and detection of reliable change were examined for the ASDQ.

Results: Strong psychometric properties were observed, including replicable factor structure, strong measurement invariance, adequate-to-excellent scale and conditional reliability, strong convergent and discriminant validity, and good screening efficiency.

Rewiring the disordered connectome with circuit-based paired stimulation after stroke-a randomized, double-blind and controlled Phase II trial.

The cortico-cortical paired associative stimulation, a combined stimulation based on two brain regions, may be an effective strategy for stroke rehabilitation. Our aim was to confirm that the cortico-cortical paired associative stimulation strengthens the connection between brain regions in the motor circuit and promotes improvements in motor function. This was a randomized double-blind, controlled Phase II trial.

Computational deconvolution of cell type-specific gene expression in COPD and IPF lungs reveals disease severity associations.

Background: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n > 1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity.

Simultaneous Traumatic Fractures of the Atlas and Axis: Presentation, Management, and Outcomes from a Series of 103 Consecutive Patients.

Background: Simultaneous C1 and C2 fractures are increasingly common, but contemporary series are limited.

Methods: All patients with traumatic fractures of both C1 and C2 admitted to an academic trauma center from 2012 to 2022 were retrospectively analyzed. Multivariable regression was used to identify characteristics relevant to management and outcomes.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Does the time between doses in an unintentional double dose bupropion exposure affect the incidence of adverse effects? A retrospective cohort study.

Introduction: Unintentional therapeutic errors with bupropion are common. The impact of the timing of the second dose in a double dose exposure on adverse effects is not well studied. This study aims to compare adverse effects between double doses separated by <720 min and ≥720 min.

Meta-Analysis of Transcriptomic Studies of Blood and Six Brain Regions Identifies a Consensus of 15 Cross-Tissue Mechanisms in Alzheimer's Disease and Suggests an Origin of Cross-Study Heterogeneity.

The comprehensive genome-wide nature of transcriptome studies in Alzheimer's disease (AD) should provide a reliable description of disease molecular states. However, the genes and molecular systems nominated by transcriptomic studies do not always overlap. Even when results do align, it is not clear if those observations represent true consensus across many studies.

Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder with psychosis. Two recently developed ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting.

Introduction: Brain metastases are difficult to treat due to the blood-brain barrier limiting the delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intra-axial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma.

Interleukin-13 Receptor Subunit Alpha 2 Induces Chemokine Expression and Macrophage Polarization to Promote Inflammation and Fibrosis.

Purpose: Interleukin-13 (IL-13) is a known mediator of radiation-induced lung injury (RILI). IL-13Rα2 has an accepted role in antagonizing IL-13 signaling by acting as a decoy receptor. We sought to understand the role of IL-13Rα2 in the progression of RILI.

Blood IL-1α and IL-6 predict specific breast cancer-induced increases in hippocampal pro-inflammatory cytokines in mice.

Neuroinflammation is a key factor in cognitive and behavioral changes seen in patients with non-CNS cancers, and cytokine levels in the blood are often used as a proxy for brain inflammation. However, this approach has yielded inconsistent results, and a common inflammatory signature remains elusive. To explore whether a blood-to-brain inflammatory signature exists across breast cancer types, we assessed cytokine and glial protein responses in the hippocampus, prefrontal cortex (PFC), and their relationship to serum cytokines in mice bearing three different mammary cancers (n = 40).

Validating social reinforcer classes for low-severity challenging behavior identified by sensitivity tests.

Behavior analysts typically assess and treat challenging behavior after it occurs regularly and at high severity. Although effective, this reactive approach is quite costly and resource intensive. A growing literature supports an alternative preventive approach; the first step involves conducting sensitivity tests to screen the topographies and functions of low-severity behavior evoked by establishing operations commonly included in challenging behavior research (e.

Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus.

The gene inositol polyphosphate-5-phosphatase D (INPP5D), which encodes the lipid phosphatase SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1), is associated with the risk of Alzheimer's disease (AD). How it influences microglial function and brain physiology is unclear. Here, we showed that SHIP1 was enriched in early stages of healthy brain development.

The effective multiplicity of infection for HCMV depends on the activity of the cellular 20S proteasome.

Human cytomegalovirus (HCMV) is a betaherpesvirus capable of infecting numerous cell types and persisting throughout an infected individual's life. Disease usually occurs in individuals with compromised or underdeveloped immune systems. Several antivirals exist but have limitations relating to toxicity and resistance.