Large-scale brainstem neuroimaging and genetic analyses provide new insights into the neuronal mechanisms of hypertension.

While brainstem regions are central regulators of blood pressure, the neuronal mechanisms underlying their role in hypertension remain poorly understood. Here, we investigated the structural and genetic relationships between global and regional brainstem volumes and blood pressure. We used magnetic resonance imaging data from n = 32,666 UK Biobank participants, and assessed the association of volumes of the whole brainstem and its main regions with blood pressure.

Correction: Flow and clogging of capillary droplets.

Correction for 'Flow and clogging of capillary droplets' by Yuxuan Cheng , , 2024, https://doi.org/10.1039/D4SM00752B.

Flow and clogging of capillary droplets.

Capillary droplets form due to surface tension when two immiscible fluids are mixed. We describe the motion of gravity-driven capillary droplets flowing through narrow constrictions and obstacle arrays in both simulations and experiments. Our new capillary deformable particle model recapitulates the shape and velocity of single oil droplets in water as they pass through narrow constrictions in microfluidic chambers.

Flucloxacillin instantly decreases serum levels of valproic acid: A case report.

Valproic acid (VPA) is used for epilepsy and bipolar disorder. It has near-complete bioavailability and is primarily metabolized by glucuronosyltransferases and mitochondrial oxidation. This case highlights a 79-year-old male with bipolar disorder on VPA therapy that started with flucloxacillin for Staphylococcus aureus bacteraemia and exhibited significantly reduced VPA serum levels.

Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer's Disease in the UK Biobank.

Background: During the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging.

Estimating random close packing density from circle radius distributions.

Circles of a single size can pack together densely in a hexagonal lattice, but adding in size variety disrupts the order of those packings. We conduct simulations which generate dense random packings of circles with specified size distributions and measure the area fraction in each case. While the size distributions can be arbitrary, we find that for a wide range of size distributions the random close-packing area fraction ϕ_{rcp} under this general protocol is determined to high accuracy by the polydispersity and skewness of the size distribution.

Discharge of rice-shaped particles from a monolayer flat-bottom silo.

In this work, we performed experiments regarding the outflow of spheres and two different types of rice-shaped particles in a quasi-two-dimensional monolayer silo with a flat bottom. We investigate the velocity and solid fraction profiles at the orifice and test whether the profiles for nonspherical particles have similar self-similar properties as in the spherical case. We find that the magnitude and shape of the velocity profiles for all three particle types are in a similar range.

Spreading of volatile droplets in a humidity-controlled environment.

When a pure ethanol droplet is deposited on a dry, wettable and conductive substrate, it is expected to spread into a thin, uniform film. Here, we demonstrate that this uniform spreading behaviour can be altered significantly by controlling the ambient relative humidity. We show that higher relative humidity not only promotes faster spreading of the droplet, it also destabilizes the moving contact line, resulting in a fingering instability.

Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets.

While genome-wide association studies are increasingly successful in discovering genomic loci associated with complex human traits and disorders, the biological interpretation of these findings remains challenging. Here we developed the GSA-MiXeR analytical tool for gene set analysis (GSA), which fits a model for the heritability of individual genes, accounting for linkage disequilibrium across variants and allowing the quantification of partitioned heritability and fold enrichment for small gene sets. We validated the method using extensive simulations and sensitivity analyses.

Dissecting the Shared Genetic Architecture of Common Epilepsies With Cortical Brain Morphology.

Background And Objectives: Epilepsies are associated with differences in cortical thickness (TH) and surface area (SA). However, the mechanisms underlying these relationships remain elusive. We investigated the extent to which these phenotypes share genetic influences.

Deformable vector fields warping for modelling of irregular breathing.

Purpose 4D computed tomography (4DCT) is the clinical standard to image organ motion in radiotherapy, although it is limited in imaging breathing variability. We propose a method to transfer breathing motion across longitudinal imaging datasets to include intra-patient variability and verify its performance in lung cancer patients. Methods Five repeated control 4DCTs for 6 non-small cell lung cancer patients were combined into multi-breath datasets (m4DCT) by merging stages of deformable image registration to isolate respiratory motion.

Comparison of the performance of two targeted metagenomic virus capture probe-based methods using reference control materials and clinical samples.

Unlabelled: Viral enrichment by probe hybridization has been reported to significantly increase the sensitivity of viral metagenomics. This study compares the analytical performance of two targeted metagenomic virus capture probe-based methods: (i) SeqCap EZ HyperCap by Roche (ViroCap) and (ii) Twist Comprehensive Viral Research Panel workflow, for diagnostic use. Sensitivity, specificity, and limit of detection were analyzed using 25 synthetic viral sequences spiked in increasing proportions of human background DNA, eight clinical samples, and American Type Culture Collection (ATCC) Virome Virus Mix.

Dissecting unique and common variance across body and brain health indicators using age prediction.

Ageing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter-individual heterogeneity in the multisystem ageing process. Using machine-learning regression models on the UK Biobank data set (N = 32,593, age range 44.

An evolutionary timeline of the oxytocin signaling pathway.

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution.

Unraveling the shared genetics of common epilepsies and general cognitive ability.

Objective: Cognitive impairment is prevalent among individuals with epilepsy, and it is possible that genetic factors can underlie this relationship. Here, we investigated the potential shared genetic basis of common epilepsies and general cognitive ability (COG).

Methods: We applied linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR) to analyze different aspects of genetic overlap between COG and epilepsies.

Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study.

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]).

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance.

Dissecting the genetic overlap between three complex phenotypes with trivariate MiXeR.

Comorbidities are an increasing global health challenge. Accumulating evidence suggests overlapping genetic architectures underlying comorbid complex human traits and disorders. The bivariate causal mixture model (MiXeR) can quantify the polygenic overlap between complex phenotypes beyond global genetic correlation.

Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.

Unlabelled: Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes.