SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity.

Diagnostic performances of Claude 3 Opus and Claude 3.5 Sonnet from patient history and key images in Radiology's "Diagnosis Please" cases.

Purpose: The diagnostic performance of large language artificial intelligence (AI) models when utilizing radiological images has yet to be investigated. We employed Claude 3 Opus (released on March 4, 2024) and Claude 3.5 Sonnet (released on June 21, 2024) to investigate their diagnostic performances in response to the Radiology's Diagnosis Please quiz questions.

Drug-drug interactions between pemafibrate and statins on pharmacokinetics in healthy male volunteers: Open-label, randomized, 6-sequence, 3-period crossover studies.

Elevated triglyceride levels are associated with an increased risk of cardiovascular events despite guideline-based statin treatment of low-density lipoprotein cholesterol. Peroxisome proliferator-activated receptor α (PPARα) agonists exert a significant triglyceride-lowering effect. However, combination therapy of PPARα agonists with statins poses an increased risk of rhabdomyolysis, which is rare but a major concern of the combination therapy.

Prediction of Placental Abruption of Pregnant Women Drivers with Various Collision Velocities, Seatbelt Positions and Placental Positions-Analysis with Novel Pregnant Occupant Model.

The aims of this study were as follows: the (a) creation of a pregnant occupant finite element model based on pregnant uterine data from sonography, (b) development of the evaluation method for placental abruption using this model and (c) analysis of the effects of three factors (collision speed, seatbelt position and placental position) on the severity of placental abruption in simulations of vehicle collisions. The 30-week pregnant occupant model was developed with the uterine model including the placenta, uterine-placental interface, fetus, amniotic fluid and surrounding ligaments. A method for evaluating the severity of placental abruption on this pregnant model was established, and the effects of these factors on the severity of the injury were analyzed.

Evidence of γ-secretase complex involved in the regulation of intramembrane proteolysis in Entamoeba histolytica.

Presenilins (PSNs) are multifunctional membrane proteins involved in signal transduction, lysosomal acidification, and certain physiological processes related to mitochondria. The aspartic protease activity of PSN and the formation of a γ-secretase complex with other subunits such as nicastrin (NCT) are required for the biological functions. Although PSN is widely conserved in eukaryotes, most studies on PSN were conducted in metazoans.

Burosumab treatment of X-linked hypophosphatemia patients: interim analysis of the SUNFLOWER longitudinal, observational cohort study.

X-linked hypophosphatemia (XLH) is a genetic disease that results in excessive FGF23, chronic hypophosphatemia, and musculoskeletal abnormalities, with affected patients experiencing symptoms such as bone pain, bone deformity, fracture, and pseudofracture. Burosumab is a fully human monoclonal antibody that binds to FGF23, improving lowered serum 1,25(OH)D and phosphate levels in patients with XLH. There are insufficient data on the use of burosumab, its safety, and the outcomes of treated patients in a real-world setting.

Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study.

Objective: To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.

Design: A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

Setting: Twenty-five study centers in Japan.

Evaluation of the Effect of Thickeners in Enteral Formulas on the Gastric Emptying Rate of Proteins and Carbohydrates Using a Semi-Dynamic Gastric Model.

The emptying rate of specific nutrients in enteral formulas is poorly understood, despite the importance of controlling the emptying rate in tube-fed patients. Because of their viscosity, thickened formulas are widely used to avoid gastric reflux and reduce the burden on caregivers. This study examined how thickeners in enteral formulas affected the gastric emptying rates of proteins and carbohydrates.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees.

Objective: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function.

Methods: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64.

Proposed Clinical Algorithm for Pleuroparenchymal Fibroelastosis (PPFE).

Pleuroparenchymal fibroelastosis (PPFE) is characterized by fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes. As PPFE appears to occur in patients with heterogeneous etiologies, the disease course is thus also heterogenous, with some patients showing rapid progression while others have slow progression. Therefore, it is very difficult to predict prognosis with PPFE.

The Usefulness of Determining Plasma and Tissue Concentrations of Phosphorodiamidate Morpholino Oligonucleotides to Estimate Their Efficacy in Duchenne Muscular Dystrophy Patients.

Currently, four kinds of phosphorodiamidate morpholino oligomers (PMOs), such as viltolarsen, have been approved for the treatment of Duchenne muscular dystrophy (DMD); however, it is unclear whether human efficacy can be estimated using plasma concentrations. This study summarizes the tissue distribution of viltolarsen in mice and cynomolgus monkeys and evaluates the relationship between exposure and efficacy based on exon skipping. In the tissue distribution studies, all muscles in DMD-model mice showed higher concentrations of viltolarsen than those in wild-type mice and cynomolgus monkeys, and the concentrations in skeletal muscle were correlated with the exon-skipping efficiency in mice and cynomolgus monkeys.

Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7.

Background: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure.

Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

Background: Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce.

Objective: We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy.

Vascular Calcification Is Accelerated by Hyponatremia and Low Osmolality.

Background: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown.

Effects of an OX2R agonist on migration and removal of tau from mouse brain.

Pathological proteins including tau are produced in neurons and released into interstitial fluid (ISF) in a neural activity-dependent manner during wakefulness. Pathological proteins in ISF can be removed from the brain via the glymphatic pathway during nighttime. Thus, in individuals with Alzheimer's disease (AD) that have dysregulated sleep/wake rhythm, application of orexin receptor 2 (OX2R) agonists during daytime could recover the efflux of pathological proteins to ISF and indirectly promote the glymphatic pathway by improving the quality of nighttime sleep after proper daytime arousal, resulting in increased removal of these proteins from the brain.

High Tibial Osteotomy Alone Does Not Decrease Medial Meniscus Extrusion in the Setting of Medial Meniscus Posterior Root Tear: A Cadaveric Study.

Purpose: To investigate whether inducing valgus alignment and shifting the load laterally through high tibial osteotomy (HTO) alone decreases the extent of medial meniscus extrusion (MME) in the setting of medial meniscus posterior root tear (MMPRT) using ultrasound evaluation.

Methods: Eight fresh-frozen human cadaveric knee specimens were tested using a 6-degree-of-freedom robotic testing system and ultrasound. Each specimen was tested in 5 conditions: (1) intact, (2) MMPRT, (3) medial meniscus repair (MMR), (4) combined medial open-wedge HTO + MMR, and (5) HTO + MMPRT.

Investigation of Functional Cytochrome P450 4A Enzymes in Liver and Kidney of Pigs, Cats, Tree Shrews, and Dogs in Comparison with the Metabolic Capacity of Human P450 4A11.

Pigs are sometimes used in preclinical drug metabolism studies, with growing interest, and thus their drug-metabolizing enzymes, including the cytochromes P450 (P450 or CYP; EC 1.14.14.

Ultrasonographic Synovitis Is Associated with the Development of Joint Destruction in Patients with Psoriatic Arthritis.

Background: Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses.