Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohorts.

Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.

Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.

Cross-sectional relationships of circadian misalignment and rest-activity rhythms with occupational attainment in UK Biobank participants.

Circadian misalignment and disrupted rest-activity rhythms have been linked to adverse health and educational outcomes, yet few studies have considered their relationships with economic outcomes. We investigate associations between multiple accelerometer-measured circadian misalignment traits (Composite Phase Deviation and the Sleep Regularity Index) and rest-activity rhythm traits (Inter-daily Stability, Intra-daily variability and relative amplitude), with occupational attainment, measured using the average wage paid to an individual's occupation. We use data from 20 356 UK Biobank participants who wore an accelerometer (2013-16), provided employment data for the year they wore the accelerometer, and supplied covariate data at recruitment (2006-10).

Exploiting NRF2-ARE pathway activation in papillary renal cell carcinoma.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype but has no indicated targeted treatments. MET inhibition may be a treatment for MET-driven pRCC, but there is a large group of non-MET-driven pRCC without targeted therapy. Activation of NRF2-ARE pathway has been suggested to be involved in pRCC.

Etiology and correlates of alcohol misuse in early midlife.

Background: Early midlife individuals (ages 30-40) experience demographic shifts that may influence the remainder of adult life. Although new or persistent alcohol misuse is common during this period, early midlife is understudied in alcohol use literature. We examined the heritability of alcohol misuse; the associations between alcohol misuse and sociodemographic factors, physical health, and well-being; and whether these associations were robust in cotwin comparisons.

Accumulating evidence from meta-analyses of prognostic studies on oral cancer: towards biomarker-driven patient selection.

Background: Many histopathologic prognostic markers, identified by routine hematoxylin and eosin (HE) staining, have been proposed for predicting the survival of patients with oral squamous cell carcinoma (OSCC). Subsequently, several meta-analyses have been conducted on these prognostic markers. We sought to analyze the accumulated evidence from these meta-analyses.

Differential somatic coding variant landscapes between laser microdissected luminal epithelial cells from canine mammary invasive ductal solid carcinoma and comedocarcinoma.

Background: Breast cancer (BC) is the most common cancer in women. Likewise, canine mammary tumors (CMT) represent the most common cancer in intact female dogs and develop in the majority spontaneously. Similarities exist in clinical presentation, histopathology, biomarkers, and treatment.

Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.

Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins.

Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas.

The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAMs) and cytotoxic tumor-infiltrating T cells (TILs) were characteristic of ABC DLBCL TME.

Artificial intelligence aided serum protein electrophoresis analysis of Finnish patient samples: Retrospective validation.

Background And Aims: Serum protein electrophoresis interpretation requires a substantial amount of manual work. In 2020, Chabrun et al. created a machine learning method called SPECTR for the task.

Associations of body size and morphology with cardiometabolic health in children: the contribution of genetic factors.

Objective: We analyzed how anthropometric measures predict cardiometabolic health and how genetic and environmental factors contribute to these associations.

Methods: Data on 8 indicators of cardiometabolic health, 21 anthropometric measures, and 11 anthropometric indices were available for 216 twin pairs of individuals age 3 to 18 years living in the Autonomous Region of Madeira, Portugal (51% girls). Genetic twin modeling was used to estimate genetic and environmental correlations between the cardiometabolic and anthropometric indicators.

Molecular and functional profiling of primary normal ovarian cells defines insights into cancer development and drug responses.

Patients with ovarian cancer, especially the high-grade serous ovarian cancer (HGSOC) subtype, face poor prognosis due to late diagnosis and treatment resistance. Owing to the high heterogeneity of HGSOC, identifying the origin of the disease and optimal treatments is difficult. Here, we characterized two primary immortalized human ovarian cell lines, human ovarian surface epithelium (HOSE)1C and HOSE2C, comparing their molecular profiling with representative HGSOC cells.

Branched-chain amino acid supplementation and voluntary running have distinct effects on the serum metabolome of rats with high or low intrinsic aerobic capacity.

Introduction: A growing body of literature associates branched-chain amino acid (BCAA) catabolism to increased fatty acid oxidation and better metabolic health. Hence, BCAA-rich diets may improve body composition and muscle protein synthesis. However, the role of individual characteristics such as a low aerobic fitness, a well-established risk factor for cardio-metabolic diseases, has not been studied.

Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism.

Background: A large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.

Methods: By applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.

Results: Using gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D.

Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.

The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation.

Validation guidelines for drug-target prediction methods.

Introduction: Mapping the interactions between pharmaceutical compounds and their molecular targets is a fundamental aspect of drug discovery and repurposing. Drug-target interactions are important for elucidating mechanisms of action and optimizing drug efficacy and safety profiles. Several computational methods have been developed to systematically predict drug-target interactions.

Inherited infertility: Mapping loci associated with impaired female reproduction.

Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder.

PGxDB: an interactive web-platform for pharmacogenomics research.

Pharmacogenomics, the study of how an individual's genetic makeup influences their response to medications, is a rapidly evolving field with significant implications for personalized medicine. As researchers and healthcare professionals face challenges in exploring the intricate relationships between genetic profiles and therapeutic outcomes, the demand for effective and user-friendly tools to access and analyze genetic data related to drug responses continues to grow. To address these challenges, we have developed PGxDB, an interactive, web-based platform specifically designed for comprehensive pharmacogenomics research.

Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton.

Background: New biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.

Objective: We investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.

Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors.

Background: Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity.

Probe set selection for targeted spatial transcriptomics.

Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design).