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Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality

People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person's degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic d

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and e

Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain

Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neuroge

S100A6 is a critical regulator of hematopoietic stem cells.

The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell

Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes

Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatme

Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness

OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortalit

Methodology to simulate temporal changes in breast tumors and parenchyma using Perlin noise

Simulating temporal changes in breast tissue has been challenging, despite advancement in virtual clinical trials. This study aims to enable virtual trials over time, motivated by interest in the effect of tissue involution on tumor visibility. We present a framework for creating 3D voxel-based breast phantoms and lesions using in-house Perlin Noise-based algorithm. The framework consists of three

Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability

Hexavalent chromium (Cr(VI)) can induce oxidative stress, genomic instability, and epigenetic modifications. In occupational settings, Cr(VI)-exposed workers may also be exposed to other toxicants, such as elements besides Cr, and per- and polyfluoroalkyl substances (PFAS). However, research on the extent of these co-exposures and their combined effects remains limited. The objective of this study

Time-resolved analysis of nanoparticle composition from alloyed feedstocks

Since its development in the 1980s, spark ablation has been widely used to produce nanoparticles (NPs) in the aerosol phase, effectively eliminating surface contamination common in other generation methods (Schmitt-Ott, 2019). This is a significant advantage, as the surface of NPs plays a crucial role in applications such as sensing and catalysis. Additionally, spark ablation enables the productio

Structure and morphology of vesicular dispersions based on novel glycophospholipids with various monosaccharide head groups

Glycophospholipids combine the structural versatility of phospholipids and carbohydrates, but their potential as excipients and performance in other related applications remains largely unexplored due to their low natural abundance. We have synthesized four novel phosphatidyl saccharide conjugates with different carbohydrate head groups; glucose, galactose, fructose and xylose by using a Phospholi

A framework for simulation of temporal evolution and longitudinal studies of breast anatomy in radiology

Background: Virtual imaging trials (VITs) are in silico studies that simulate medical imaging and disease processes, offering a cost-effective and reproducible addition to traditional imaging trials. While VITs are well established in breast imaging, most existing implementations simulate imaging based on static anatomical models, capturing only a single time point. This limits their ability to st

Spatial transcriptomics reveals a key role of fibroblast-like vascular smooth muscle cells in human atherosclerotic cell crosstalk and stability

BACKGROUND AND AIMS: Atherosclerotic plaques are the leading cause of cardiovascular events. Single-cell approaches have identified diverse human plaque cell phenotypes but their spatial distribution and interactions remain unclear. Here, intercellular communication patterns in human plaque microenvironments were mapped to reveal novel targets to prevent atherosclerotic events.METHODS: Spatial tra

Single-cell mass-density measurements using microchannel gradient centrifugation

We present a microchannel-based adaptation of mass density-gradient centrifugation for the mass density measurement of cells or microparticles. The workflow consists of three basic steps: Microchannel filling, centrifugation, and microscopy. Microchannel filling and subsequent centrifugation of two liquids with different densities allows the instantaneous, precise, and repeatable generation of a o

Metformin and incident osteoarthritis : Causal insights from a co-twin control study

Aims: In a co-twin control design, we aimed to examine whether individuals who initiate metformin treatment have an altered risk of incident diagnosis of osteoarthritis (OA), for up to 11 years after starting the treatment, compared with their non-treated co-twin. Methods: In all twin pairs different for metformin treatment (N=1 261 pairs) and all eligible twins/singletons (N=52 341) aged 35–75 ye

Circulating HER2/ErbB2 Levels Are Associated With Increased Incidence of Diabetes : A Population-Based Cohort Study

OBJECTIVE: HER2/ErbB2 is a member of the epidermal growth factor receptor family. It is widely used as a tumor marker, but it also has recently been associated with insulin resistance. Both ErbB2 and diabetes have been associated with cancer; however, the relationship between ErbB2 and diabetes has not been well explored. The aim of this population-based cohort study was to assess the association

Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes

Epigenome-wide studies of pancreatic islets provide valuable insights into type 2 diabetes (T2D) but lack methylomes from individual cell types. Here we show changes to alpha and beta cell-specific methylomes and transcriptomes from people with or without T2D, using whole-genome bisulfite sequencing and RNA sequencing. We discover 22,544 differentially methylated regions annotated to 7,975 genes i

Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals

Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods: Participa

Exploring the Functional Landscape of the p53 Regulatory Domain : The Stabilizing Role of Post-Translational Modifications

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the