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...

Loss of skeletal muscle mass and strength is a debilitating consequence of various chronic diseases, inflammatory myopathies, and neuromuscular disorders. Inflammation plays a major role in the perpetuation of myopathy in degenerative muscle diseases. TGF-β-activated kinase 1 (TAK1) is a major signaling protein that mediates the activation of multiple signaling pathways in response to inflammatory cytokines and microbial products. Recent studies have demonstrated that TAK1 is essential for th...

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...

Metabolic dysfunction-associated steatohepatitis (MASH), an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), is characterized by significant hepatic fibrosis and inflammation. The pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist IVA337 (lanifibranor) has demonstrated potential as an anti-MASH therapeutic, although its mechanisms of action remain incompletely understood. This study explores the effects and mechanisms of IVA337 using two disti...

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...

Accurate detection of EBV in tumors is essential for refining diagnosis and guiding management of EBV-associated cancers. This validation study evaluated the performance of the FoundationOne CDx (F1CDx) and FoundationOne Heme (F1H) next-generation sequencing (NGS) assays for detecting EBV compared to the reference standard EBV-encoded RNA (EBER) in situ hybridization (ISH). A total of 413 samples of gastric carcinoma, squamous cell carcinoma (predominantly nasopharyngeal carcinoma), and diffu...

Preterm prelabor rupture of membrane (pPROM) is a risk factor for preterm birth. However, spontaneous healing of ruptured fetal membranes is occasionally clinically observed. Prostaglandins (PGs) are involved in the wound healing process in various tissues. Here, the roles of prostacyclin (PGI2) in the repair of fetal membranes were investigated in a mouse model. Ptgs1, Ptgs2, Ptgis mRNA, and PGI2 were increased in the ruptured murine fetal membranes. Compared with those at the intact site, t...

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 testing has proven utility in disease diagnostics, guiding clinical management and improving outcomes. Use of high throughput sequencing by clinical laboratories has generated opportunities and challenges in data analysis resulting in the emergence of a laboratory role termed Variant Scientist. The aim of this study was to characterize this laboratory role. We developed a thirty-item survey to collect information describing the current demographic landscape, salary ranges, work enviro...

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...

Cerebrospinal fluid (CSF) drains along the perivascular space, known as the glymphatic system, to the meninges, where meningeal lymphatic vessels (MLVs) remove toxic products with excess CSF from the brain. Macrophages are widely present in the leptomeninges and dura mater of meninges. However, whether leptomeningeal and dural macrophages play the same or distinct roles in maintaining optimal CSF drainage remains unclear. By intra-cisterna magna (i.c.m.) injection of clodronate liposomes (CLL...

Perilipin 2 expression is related to poor prognosis of patients with various malignant tumors. Perilipin 2 exists on the surface of lipid droplets (LDs), which store lipids that can be used as an energy source during cancer progression. However, the underlying mechanism of lipid metabolism involving LDs in the progression of lung adenocarcinoma is unclear. Herein, this study investigated the role of perilipin 2 in the regulation of lipid metabolism in lung adenocarcinoma, as well as patient p...

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...