Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain.

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.

Plasticity of Human Microglia and Brain Perivascular Macrophages in Aging and Alzheimer's Disease.

The complex roles of myeloid cells, including microglia and perivascular macrophages, are central to the neurobiology of Alzheimer's disease (AD), yet they remain incompletely understood. Here, we profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 unique donors covering the human lifespan and varying degrees of AD neuropathology. We delineated 13 transcriptionally distinct myeloid subtypes organized into 6 subclasses and identified AD-associated adaptive changes in myeloid cells over aging and disease progression.

Arthrodesis Versus Ligament Reconstruction and Tendon Interposition for Thumb Carpometacarpal Joint Arthritis: A Systematic Review and Meta-Analysis.

Purpose: Arthrodesis and ligament reconstruction and tendon interposition (LRTI) are commonly performed procedures for treatment of thumb carpometacarpal (CMC) osteoarthritis. Although LRTI is the most common surgical treatment, CMC arthrodesis has been performed because of its reported advantages. This systematic review and meta-analysis compared the differences between CMC arthrodesis and LRTI to better inform surgeons and patients when they are making treatment decisions.

Phenotype Scoring of Population Scale Single-Cell Data Dissects Alzheimer's Disease Complexity.

The complexity of Alzheimer's disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms (NPSs). However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-nucleus RNA-seq dataset comprising over 6 million nuclei from the prefrontal cortex of 1,494 individual brains, covering a variety of AD-related phenotypes that capture cognitive impairment, severity of pathological lesions, and the presence of NPSs.

Comparative Clinical Characteristics of Frail Older Adults in the Emergency Department: Long-Term Care Hospital versus Community Residence.

Background/objective: Older patients from long-term care hospitals (LTCHs) presenting to emergency departments (EDs) exhibit a higher prevalence of frailty than those from the community. However, no study has examined frailty in patients from LTCHs in the ED. This study compared frailty in older patients from LTCHs and the community.

Electrochemical kinetic energy harvesting mediated by ion solvation switching in two-immiscible liquid electrolyte.

Kinetic energy harvesting has significant potential, but current methods, such as friction and deformation-based systems, require high-frequency inputs and highly durable materials. We report an electrochemical system using a two-phase immiscible liquid electrolyte and Prussian blue analogue electrodes for harvesting low-frequency kinetic energy. This system converts translational kinetic energy from the displacement of electrodes between electrolyte phases into electrical energy, achieving a peak power of 6.

Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients.

Objective: Seizures can be triggered by a variety of endogenous or exogenous factors. We hypothesized that alterations in the gut microbiome may be a seizure precipitant and analyzed the composition and characteristics of the gut microbiome in epilepsy patients who experienced an abrupt seizure exacerbation without a clear seizure precipitant.

Methods: We prospectively enrolled 25 adult patients with epilepsy and collected fecal samples on the admission and after seizure recovery for next-generation sequencing analysis.

Biological Insights from Schizophrenia-associated Loci in Ancestral Populations.

Large-scale genome-wide association studies of schizophrenia have uncovered hundreds of associated loci but with extremely limited representation of African diaspora populations. We surveyed electronic health records of 200,000 individuals of African ancestry in the Million Veteran and All of Us Research Programs, and, coupled with genotype-level data from four case-control studies, realized a combined sample size of 13,012 affected and 54,266 unaffected persons. Three genome-wide significant signals - near , , and - are the first to be independently identified in populations of predominantly African ancestry.

Predictors of Patient-Reported Outcomes After Hyaluronic Acid Injections: Effect of Expectations and Psychological Stress.

Introduction: Hyaluronic acid (HA) injections are a common nonsurgical treatment of knee osteoarthritis (OA). Patient expectations and psychological stress are believed to affect outcomes after orthopaedic procedures.

Methods: This was a prospective cohort study seeking to identify factors predictive of greater patient-reported outcomes after HA injections, particularly expectations and psychological stress.

Determination of Sulfites in Dried Fruits by Paper Spray Ionization Tandem Mass Spectrometry.

Sulfite, a widely used food additive, is subject to regulated labeling. The extraction of sulfite as the stable hydroxymethylsulfonate (HMS) form and its quantitative analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized for their good sensitivity, selectivity, and versatility across various food materials. This study aimed to develop a cost-effective and simpler method for sulfite quantitation, while maintaining the superior sensitivity and selectivity of mass spectrometry (MS).

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.

Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data.

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used.

Validation of Enhancer Regions in Primary Human Neural Progenitor Cells using Capture STARR-seq.

Genome-wide association studies (GWAS) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. We performed capture STARR-sequencing of over 78,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We selected candidate regions by integrating data from NPCs, prefrontal cortex, developmental timepoints, and GWAS.

Projective light-sheet microscopy with flexible parameter selection.

Projection imaging accelerates volumetric interrogation in fluorescence microscopy, but for multi-cellular samples, the resulting images may lack contrast, as many structures and haze are summed up. Here, we demonstrate rapid projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle. This allows us to selectively image different sub-volumes of a sample, rapidly switch between them and exclude background fluorescence.

Genome-based taxonomic identification and safety assessment of an Enterococcus strain isolated from a homemade dairy product.

The aim of this study was to explore the taxonomic identification and evaluate the safety of a bacterium, Enterococcus lactis IDCC 2105, isolated from homemade cheese in Korea, using whole genome sequence (WGS) analysis. It sought to identify the species level of this Enterococcus spp., assess its antibiotic resistance, and evaluate its virulence potential.

Mapping Changes in Glutamate with Glutamate-Weighted MRI in Forced Swim Test Model of Depression in Rats.

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and H magnetic resonance spectroscopy (H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.

Alzheimer's disease transcriptional landscape in ex-vivo human microglia.

Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer's Disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present the transcriptional landscape of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, including 63 patients representing the full spectrum of clinical and pathological severity of AD.