Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.

Celecoxib, a selective COX-2 inhibitor, has demonstrated anti-liver cancer effects in various preclinical models and clinical traits. However, prolonged use of celecoxib can lead to drug resistance, necessitating higher doses to maintain efficacy, which often results in severe side effects, limiting its clinical application. This study aimed to identify strategies to overcome celecoxib resistance in liver cancer.

Sex Identification and Species Confirmation in Modern and Archeological Caprine Enamel.

Proteomics has become a transformative tool for species and sex determination. This study introduces a novel methodology that integrates amelogenin (Amel) and enamelin (Enam) proteins extracted from the tooth enamel of caprines. Since morphologically, osteological remains of sheep and goats often cannot be easily discriminated, we developed our method on both modern domestic sheep () and goats () to establish unique proteomic signatures for each species for sex and species identification.

Long-term experience with lomitapide treatment in patients with homozygous familial hypercholesterolemia: Over 10 years of efficacy and safety data.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by loss of low-density lipoprotein receptor (LDLR) function, an extreme elevation of circulating low-density lipoprotein cholesterol (LDL-C) from birth and substantially reduced life expectancy, if untreated. Patients with HoFH are frequently diagnosed late and have a markedly elevated risk of premature atherosclerotic cardiovascular disease (ASCVD).

Sources Of Material: The current European Atherosclerosis Society consensus statement on the treatment of HoFH recommends an LDL-C goal of <55 mg/dL for adults with ASCVD or major ASCVD risk factors, <70 mg/dL for adults without ASCVD risk factors, and <115 mg/dL for pediatric patients without ASCVD.

A universal point-of-care immunochromatographic test for the serodiagnosis of hepatitis D.

Hepatitis D is estimated to affect 12 million people worldwide and is caused by the hepatitis D virus (HDV), a defective virus that requires the presence of the hepatitis B virus (HBV) for infection. Here, we report a new recombinant antigen (DTH10.1) to detect anti-HDV IgG antibodies, designed to include a consensus sequence of the HDV antigen, based on bioinformatic analysis of the eight HDV genotypes.

Characterization of Visual Field Loss Over 4 Years in the Rate of Progression in USH2A-Related Retinal Degeneration (RUSH2A) Study.

Purpose: To report visual field loss using static perimetry (SP) and kinetic perimetry (KP) over 4 years in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Prospective, observational cohort study.

Subjects, Participants, And/or Controls: Participants had USH2A-related rod-cone degeneration, visual acuity ≥20/80, and KP III4e ≥10° at baseline in the study eye.

Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa: Molecular Genetics and Clinical Characteristics.

Purpose: To describe in detail the genetic profile, clinical features, and genotype-phenotype correlation of retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (RP) in Koreans.

Design: A retrospective multicenter case series.

Methods: This study recruited genetically confirmed RPGR-associated X-linked RP patients from nine tertiary hospitals and clinics across Korea.

Performance evaluation of a fully automated deep sequencing platform for hepatitis B genotyping and resistance testing.

Background: Treatment of chronic hepatitis B infection requires lifelong administration of nucleos(t)ide analogues with a high barrier to resistance and effective viral suppression. The major limitation of lifelong therapy is the possible selection of drug-resistant hepatitis B virus (HBV) strains. International Liver Society guidelines recommend that hepatitis B resistance testing must be performed by a reference laboratory.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Nicotine Metabolism-Related Genetic Polymorphisms Associated with Smoking Cessation in Korean Men: A Candidate Gene Association Study in a Korean Cohort.

Introduction: Smoking cessation is influenced by genetic and environmental factors, particularly genetic polymorphisms influencing nicotine metabolism. This study investigated the association between specific nicotine metabolism-related genetic variants and smoking cessation among Korean men.

Methods: A candidate gene association study was performed targeting single nucleotide polymorphisms (SNPs) within nicotine metabolism-related genes.

Profiling low-mRNA content cells in complex human tissues using BD Rhapsody single-cell analysis.

The successful recovery of immune cells, particularly those with low mRNA content, by single-cell RNA sequencing (scRNA-seq) remains a significant challenge. Tissue dissociation and selection of the appropriate scRNA-seq technology are crucial. Our protocol efficiently recovers low-mRNA content immune cells using the BD Rhapsody scRNA-seq platform.

Effects of a Protease Inhibitor Camostat Mesilate on Gut Microbial Function in Patients with Irritable Bowel Syndrome: A Pilot Randomized Placebo-Controlled Study.

Introduction: Increased fecal protease activity, which may induce visceral hypersensitivity, has been observed in patients with irritable bowel syndrome (IBS). Serine proteases modulate FK506 binding protein (FKBP)-type peptidylprolyl cis-trans isomerase (PPIase) activity associated with immune and glucocorticoid receptor functions. The aim was to investigate whether camostat mesilate (CM), a serine protease inhibitor, modifies fecal bacterial function related to FKBP-type PPIases in patients with IBS.

Enhancing bone regeneration: Unleashing the potential of magnetic nanoparticles in a microtissue model.

Bone tissue engineering addresses the limitations of autologous resources and the risk of allograft disease transmission in bone diseases. In this regard, engineered three-dimensional (3D) models emerge as biomimetic alternatives to natural tissues, replicating intracellular communication. Moreover, the unique properties of super-paramagnetic iron oxide nanoparticles (SPIONs) were shown to promote bone regeneration via enhanced osteogenesis and angiogenesis in bone models.

The diagnostic cascade for patients with hepatitis delta infection in France, 2018-2022: A cross-sectional study.

Background And Aims: Chronic hepatitis D infection is the most severe form of viral hepatitis and can rapidly progress to cirrhosis or hepatocellular carcinoma. Despite recommendations for systematic screening of hepatitis B surface antigen (HBsAg)-positive individuals, data from real-world studies have reported a low frequency of hepatitis D (or delta) virus (HDV) screening. Our cross-sectional analysis evaluated the diagnostic cascade for hepatitis D infection in tertiary centres and described the characteristics of HDV-positive patients.

'Unusual' HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment.

The high genetic diversity of hepatitis C virus (HCV) has led to the emergence of eight genotypes and a large number of subtypes in limited geographical areas. Currently approved pangenotypic DAA regimens have been designed and developed to be effective against the most common subtypes (1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a and 6a). However, large populations living in Africa and Asia, or who have migrated from these regions to industrialised countries, are infected with 'unusual', non-epidemic HCV subtypes, including some that are inherently resistant to currently available direct-acting antiviral (DAA) drugs due to the presence of natural polymorphisms at resistance-associated substitution positions.

Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.

Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes.

A novel mutation in EROS (CYBC1) causes chronic granulomatous disease.

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD.

Rapid leaf xylem acclimation diminishes the chances of embolism in grapevines.

Under most conditions tight stomatal regulation in grapevines (Vitis vinifera) avoids xylem embolism. The current study evaluated grapevine responses to challenging scenarios that might lead to leaf embolism and consequential leaf damage. We hypothesized that embolism would occur if the vines experienced low xylem water potential (Ψx) shortly after bud break or later in the season under a combination of extreme drought and heat.

A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D.

Background: Coinfection with hepatitis D virus (HDV) accelerates the progression of liver disease associated with chronic hepatitis B. Bulevirtide inhibits the entry of HDV into hepatocytes.

Methods: In this ongoing phase 3 trial, patients with chronic hepatitis D, with or without compensated cirrhosis, were randomly assigned, in a 1:1:1 ratio, to receive bulevirtide subcutaneously at 2 mg per day (2-mg group) or 10 mg per day (10-mg group) for 144 weeks or to receive no treatment for 48 weeks followed by bulevirtide subcutaneously at 10 mg per day for 96 weeks (control group).

An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury.

Objective: To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI).

Settings: Acute and subacute beds.

Participants: Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.

A TMT-based shotgun proteomics uncovers overexpression of thrombospondin 1 as a contributor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Hepatic sinusoidal obstruction disease (HSOS) is a rare but life-threatening vascular liver disease. However, its underlying mechanism and molecular changes in HSOS are largely unknown, thus greatly hindering the development of its effective treatment. Hepatic sinusoidal endothelial cells (HSECs) are the primary and essential target for HSOS.