Clinical implementation of whole genome and whole exome sequencing by next generation sequencing (NGS) allows for comprehensive detection of genomic alterations. However, with the growing number of clinically relevant genes and variants there is an urgent and growing need for reference materials to optimize, validate, and quality control NGS tests. This pilot study documents the paucity of physical reference materials for widely tested genes and demonstrates the utility of in silico mutageniz...

Dysregulation of nucleus pulposus cells (NPCs) is a critical contributor to intervertebral disc degeneration (IDD). One characteristic of degenerated discs is the increased apoptosis of NPCs and the substantial degradation of the extracellular matrix (ECM). This study identified significantly reduced miR-204-5p levels in IDD tissues. Using lipopolysaccharide (LPS)-treated rat NPCs, miR-204-5p overexpression was found to suppress apoptosis, reduce ECM degradation, and enhance ECM synthesis. Me...

Chlamydia species are responsible for significant diseases in both humans and animals, with their infection processes involving complex interactions with host cells. Protein post-translational modifications (PTMs) have emerged as a critical focus in understanding the complex interplay between Chlamydia and its host. PTMs, including phosphorylation, glycosylation, ubiquitination, acetylation, and methylation, play pivotal roles in regulating key processes during Chlamydia infection, such as ba...

Tumor necrosis factor α (TNFα) is a highly pleiotropic cytokine with a variety of biological functions such as cell proliferation, metabolic activation, inflammatory response and cell death. TNFα can induce a variety of mechanisms to initiate hepatocyte apoptosis, resulting in subsequent liver damage. HBsAg is the most abundant HBV protein in the hepatocyte during chronic virus infection. However, its role in TNFα-mediated apoptosis of hepatocytes has not been revealed. We report here that HB...

Homologous recombination deficiency (HRD) affects 50% of ovarian cancers (OC) and influences PARP inhibitors efficacy. While one-third of HRD tumours harbour a deleterious BRCA1/2 mutation, these mutations are not the sole cause of HRD. Promoter methylation of BRCA1 and RAD51C contributes to 19% and 2% of cases, respectively.A cohort of 224 ovarian cancer (OC) patients tested for HRD validated our droplet digital PCR (ddPCR) technique. DNA was extracted from FFPE tissue, and the Genomic Insta...

Enterreno: el archivo fotográfico histórico colaborativo más grande de Chile. Más de 10.000 fotografías desde 1854 hasta 2005, aportadas por la comunidad.

Accurate prognosis represents a critical component in oncology research, enabling personalized treatment planning, and optimized healthcare resource utilization. While existing prognostic models demonstrate promising performance on restricted datasets, they remain constrained by two limitations: modality-specific architectural designs and cancer type-specific training paradigms that hinder cross-domain generalization. To address these challenges, the Unified Multi-modal Pan-cancer Survival Ne...

Diagnostic analysis of messenger RNA is essential as altered splicing is a frequent cause of genetic diseases. High throughput splicing studies remain difficult to implement in routine diagnostics. This is why we developed SEALigHTS (splice and expression analyses by ligation and high throughput sequencing), a cost-effective and easy-to-implement technique designed for simultaneous analysis of RNA from multiple patients on a panel of genes, using probes designed at exon extremities. Following...

Genomic profiling of cancers informs diagnostic and prognostic classification and aids in selection of targeted therapeutics. Targeted, next-generation sequencing of cancer-specific genes is clinically feasible and enables comprehensive somatic reporting; without a matched germline specimen, germline alterations can confound analyses of the somatic profile and create uncertainty in interpretation. We report the validation and implementation of optional matched tumor/germline sequencing in our...

Retinitis pigmentosa (RP) is a group of sight-threatening genetic diseases characterized by progressive degeneration of photoreceptors, leading to severe vision loss from childhood to adulthood. With limited treatment options, understanding the molecular mechanisms underlying RP is crucial. Evidence points to increased DNA methylation, especially in degenerating photoreceptors, as a contributing factor to retinal damage in RP. To exploit the molecular insights into methylation-driven pathways...

Cancer treatment costs pose a significant global economic burden. By facilitating treatment plans tailored to the genomic profile of patients’ cancer, genomic testing has the potential to reduce healthcare costs. Using real-world evidence, this study compared the cost-effectiveness of comprehensive genomic profiling (CGP) versus small panel (SP) testing in patients with advanced non-small cell lung cancer (aNSCLC) in the US and Germany. A partitioned survival model was developed to estimate t...

Molecular syndromic assays have improved respiratory diagnostics by enabling the simultaneous detection of multiple pathogens from a single sample. However, fixed-panel designs may not align with age-specific prevalence patterns or evolving epidemiologic trends, limiting clinical utility and reimbursement viability. In this study, 1520 positive nasopharyngeal swabs from symptomatic individuals collected during the 2022 to 2023 respiratory season were analyzed by using the LIAISON PLEX Respira...

Protein S-palmitoylation, a reversible posttranslational modification, is crucial for tumor progression. However, the palmitoylation landscape in tumor cells and its variability within different tumor cell populations remain underexplored. We analyzed protein palmitoylation using 23 palmitoyl-acyltransferases and 7 de-palmitoyl-acyltransferases. Through copy number variation, pseudotime, enrichment, and cell-cell communication analyses, we explored heterogeneity among epithelial cells in lung...

Genetic testing, as part of the medico-legal autopsy in cases of suspected sudden cardiac death, has been recommended for several years, however, are rarely performed. The aim was to assess the value of postmortem genetic testing in unexplained sudden death in the young. This is a prospective study including all cases with unexplained natural sudden death cases in individuals ≤50 years old undergoing a legal autopsy. Postmortem genetic testing was routinely performed in cases under 35 and aft...

Accurate genomic characterization of respiratory syncytial virus (RSV) is crucial for studies of epidemiology and viral evolution, including monitoring potential escape from newly authorized vaccines and prophylactic monoclonal antibodies. We adapted a viral genome tiling amplicon panel (UW-ARTIC) and developed a custom bioinformatic pipeline for high-throughput, cost-effective sequencing of both RSV-A and RSV-B subgroups. We established genome acceptability criteria and determined the perfor...

Who Could Ever Love You is an intimate, heartbreaking memoir of a father, a mother, and a family’s exile.Mary Trump grew up in a family divided by its patriarch’s relentless drive for money and power....

myeloMATCH is a National Cancer Institute (NCI) precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a leukemia’s diagno...

Osteonecrosis of the femoral head (ONFH) is an orthopaedic disease with multifaceted pathogenesis. The role of long noncoding RNA (lncRNA) taurine-up-regulated gene 1 (TUG1) in ONFH remains unexplored. Thus, lncRNA expression profiles in subchondral bone from patients with ONFH and healthy controls were analyzed using microarray analysis, RT-qPCR, and bioinformatics. To evaluate the effect of TUG1 on osteogenic differentiation, TUG1 was overexpressed or knocked down in human bone marrow mesen...