A non-conditioned bone marrow transplantation mouse model to study clonal hematopoiesis and myeloid malignancies.

Clonal hematopoiesis of indeterminate potential (CHIP) is a condition where blood or bone marrow cells carry mutations associated with hematological malignancies. Individuals with CHIP have an increased risk of developing hematological malignancies, atherosclerotic cardiovascular disease, and all-cause mortality. Bone marrow transplantation (BMT) of cells carrying CHIP mutations into irradiated mice are useful procedures to investigate the dynamics of clonal expansion and potential therapeutic strategies, but myeloablative conditioning can induce confounding effects.

Whole exome sequencing-based homologous recombination deficiency test for epithelial ovarian cancer.

Background: The homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score; however, the clinical value of WES-based HRD test was less validated in EOC.

Methods: We enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort.

Spatiotemporal Correlation Analysis for the Incidence of Esophageal and Gastric Cancer From 2010 to 2019: Ecological Study.

Background: Esophageal and gastric cancer were among the top 10 most common cancers worldwide. In addition, sex-specific differences were observed in the incidence. Due to their anatomic proximity, the 2 cancers have both different but also shared risk factors and epidemiological features.

Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells.

Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor "lymphocyte function-associated antigen-1" (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18).

KaRhab: an international online registry for cardiac rhabdomyomas.

Background: Cardiac rhabdomyoma (RHM) is considered one of the most frequent benign heart tumors in children. However, encounters with cardiac RHM in clinical practice remain rare. Clinical information is primarily available in the form of single case reports or smaller studies with a shortage of large-scale reviews encompassing a substantial number of cases.

Diagnosis and management of superficial arteriovenous malformations: French healthcare network's recommendations.

Superficial arteriovenous malformations are rare fast-flow lesions. They consist of arteriovenous shunts, without cellular hyperplasia or proliferation, which develop in the surrounding tissues (cutaneous, subcutaneous, muscular, bone). Although benign, they are among the most severe of superficial malformations.

Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2.

Background: The Immunoglobulin Heavy Chain (IGH) genomic region is responsible for the production of circulating antibodies and warrants careful investigation for its association with COVID-19 characteristics. Multiple allelic variants within and across different IGH gene segments form a limited set of haplotypes. Previous studies have shown associations between some of these haplotypes and clinical outcomes of COVID-19.

APOEε4 alters ApoE and Fabp7 in frontal cortex white matter in prodromal Alzheimer's disease.

The ApoE ε4 allele (APOEε4) is a major genetic risk factor for sporadic Alzheimer's disease (AD) and is linked to demyelination and cognitive decline. However, its effects on the lipid transporters apolipoprotein E (ApoE) and fatty acid-binding protein 7 (Fabp7), which are crucial for the maintenance of myelin in white matter (WM) during the progression of AD remain underexplored. To evaluate the effects of APOEε4 on ApoE, Fabp7 and myelin in the WM of the frontal cortex (FC), we examined individuals carrying one ε4 allele that came to autopsy with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and mild to moderate AD compared with non-carrier counterparts.

Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study.

Background: The DNA methylation-based epigenetic clocks are increasingly recognized for their precision in predicting aging and its health implications. Although prior research has identified connections between accelerated epigenetic aging and multiple sclerosis, the chronological and causative aspects of these relationships are yet to be elucidated. Our research seeks to clarify these potential causal links through a bidirectional Mendelian randomization study.

Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone.

Background: Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.

Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis.

Background: Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear.

Methods: Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls.

Exploring the impact of genetic factors and fatty acid quality on visceral and overall Fat levels in overweight and obese women: a genetic risk score study.

Background: Recent studies suggest a link between dietary fat quality and obesity. Genetic risk scores (GRS) can predict obesity risk based on genetic factors. This study investigates how GRS and fatty acid quality affect visceral adiposity index (VAI) and body adiposity index (BAI) in overweight and obese women.

Development and evaluation of patient-centred polygenic risk score reports for glaucoma screening.

Background: Polygenic risk scores (PRS), which provide an individual probabilistic estimate of genetic susceptibility to develop a disease, have shown effective risk stratification for glaucoma onset. However, there is limited best practice evidence for reporting PRS and patient-friendly reports for communicating PRS effectively are lacking. Here we developed patient-centred PRS reports for glaucoma screening based on the literature, and evaluated them with participants using a qualitative research approach.

Clinical integration of germline findings from a tumor testing precision medicine program.

Background: Integrating germline genetic testing (GGT) recommendations from tumor testing into hereditary cancer clinics and precision oncology trials presents challenges that require multidisciplinary expertise and infrastructure. While there have been advancements in standardizing molecular tumor boards, the implementation of tumor profiling for germline-focused assessments has only recently gained momentum. However, this progress remains inconsistent across institutions, largely owing to a lack of systematic approaches for managing these findings.

Identifying novel heterozygous PI4KA variants in fetal abnormalities.

Background: The clinical manifestations of PI4KA-related disorders are characterized by considerable variability, predominantly featuring neurological impairments, gastrointestinal symptoms, and a combined immunodeficiency. The aim of this study was to delineate the novel spectrum of PI4KA variants detected prenatally and to assess their influence on fetal development.

Methods: A thorough fetal ultrasound screening was conducted, supplemented by both antenatal and post-abortion magnetic resonance imaging (MRI) studies.

Polymorphisms and dental age in non-syndromic cleft lip and palate: a cross-sectional study.

Background: Children with non-syndromic cleft lip with or without palate (CL ± P) may present alterations in dental development. The purpose of this cross-sectional study was to compare the dental age (DA) between children with and without CL ± P, and whether single nucleotide polymorphisms (SNPs) in genes encoding growth factors are associated with DA variations.

Methods: Children aged between 5 and 14 years with and without CL ± P were recruited to participate in this study.

Relationship between mucin gene polymorphisms and different types of gallbladder stones.

Background: Gallstones, a common surgical condition globally, affect around 20% of patients. The development of gallstones is linked to abnormal cholesterol and bilirubin metabolism, reduced gallbladder function, insulin resistance, biliary infections, and genetic factors. In addition to these factors, research has shown that mucins play a role in gallstone formation.

A comprehensive allele specific expression resource for the equine transcriptome.

Background: Allele-specific expression (ASE) analysis provides a nuanced view of cis-regulatory mechanisms affecting gene expression.

Results: An equine ASE analysis was performed, using integrated Iso-seq and short-read RNA sequencing data from four healthy Thoroughbreds (2 mares and 2 stallions) across 9 tissues from the Functional Annotation of Animal Genomes (FAANG) project. Allele expression was quantified by haplotypes from long-read data, with 42,900 allele expression events compared.

Effects of proton pump inhibitor (PPI) use on migraine - a critical review.

Background: Proton pump inhibitor (PPI) drugs are widely used and are among the most significant achievements of modern pharmacology. Their primary purpose is treating and preventing gastric acid-related disorders. Migraine and PPI intake are prevalent, and many people are affected by both.

Assessment of cardiac iron deposition and genotypic classification in pediatric beta-thalassemia major: the role of cardiac MRI.

Background: Beta thalassemia major (β-TM) is a severe genetic anemia with considerable phenotypic heterogeneity. This study investigated whether genotype correlates with distinct myocardial iron overload patterns, assessed by cardiovascular magnetic resonance (CMR) T2* values.

Methods: CMR data for cardiac iron deposition evaluation, which recruited pediatric participants between January 2021 and December 2024, were analyzed with CVI42.

Comprehensive transcriptomic analysis reveals turnip mosaic virus infection and its aphid vector Myzus persicae cause large changes in gene regulatory networks and co-transcription of alternative spliced mRNAs in Arabidopsis thaliana.

Background: Virus infection and herbivory can alter the expression of stress-responsive genes in plants. This study employed high-throughput transcriptomic and alternative splicing analysis to understand the separate and combined impacts on host gene expression in Arabidopsis thaliana by Myzus persicae (green peach aphid), and turnip mosaic virus (TuMV).

Results: By investigating changes in transcript abundance, the data shows that aphids feeding on virus infected plants intensify the number of differentially expressed stress responsive genes compared to challenge by individual stressors.

Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives.

Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment.

Is maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children? Insights from individual participant data meta-analysis in ten birth cohorts.

Background: Growing evidence shows that dysregulated metabolic intrauterine environments can affect offspring's neurodevelopment and behaviour. However, the results of individual cohort studies have been inconsistent. We aimed to investigate the association between maternal diabetes before pregnancy and gestational diabetes mellitus (GDM) with neurodevelopmental, cognitive and behavioural outcomes in children.

Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis.

Background: The causes of breast cancer are poorly understood. A potential risk factor is Epstein-Barr virus (EBV), a lifelong infection nearly everyone acquires. EBV-transformed human mammary cells accelerate breast cancer when transplanted into immunosuppressed mice, but the virus can disappear as malignant cells reproduce.

Identifying Digital Markers of Attention-Deficit/Hyperactivity Disorder (ADHD) in a Remote Monitoring Setting: Prospective Observational Study.

Background: The symptoms and associated characteristics of attention-deficit/hyperactivity disorder (ADHD) are typically assessed in person at a clinic or in a research lab. Mobile health offers a new approach to obtaining additional passively and continuously measured real-world behavioral data. Using our new ADHD remote technology (ART) system, based on the Remote Assessment of Disease and Relapses (RADAR)-base platform, we explore novel digital markers for their potential to identify behavioral patterns associated with ADHD.