RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC.

Introduction: RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.

Lung contusion complicated by pneumonia worsens lung injury via the inflammatory effect of alveolar small extracellular vesicles on macrophages and epithelial cells.

Background: Lung contusion (LC) complicated by pneumonia is associated with a higher risk of acute lung injury (ALI) mediated by activation of immune cells and injury to the lung epithelium. Small extracellular vesicles (sEVs) are essential mediators of cellular crosstalk; however, their role in the development of postinjury ALI remains unclear. We hypothesized that LC complicated by pneumonia increases the pro-inflammatory effect of alveolar sEVs on macrophages and the cytotoxicity of alveolar sEVs to pulmonary epithelial cells, worsening the severity of ALI.

Structural Analysis of Interfacial Films of Oil/Water Emulsions Prepared by Emulsification via Lamellar Gels.

An effective approach to stabilize emulsions is to increase the rigidity of oil-water (O/W) interfacial films by adsorbing molecular assemblies such as lamellar phases around the emulsion particles. In this study, we aimed to analyze the structure of a lamellar phase adsorbed at an O/W interface and to clarify the effect of the structure and physicochemical properties of the lamellar phase on the dispersion stability of emulsions. The adsorption of the lamellar phase at the O/W interface of the emulsions was confirmed by freeze-fracture transmission electron microscopy of O/W emulsions prepared by diluting and dispersing gels formed with polyglycerol fatty acid esters, water, and cetyl isooctanoate (CIO).

Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan.

Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions worldwide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds. More than 5 years have passed since tisagenlecleucel was approved in Japan.

Progression and risk factors of hallux valgus angle in elite adolescent dancers: a cohort study.

Introduction: To the best of our knowledge, no previous studies have linked the progression of hallux valgus (HV) with plantar pressure distribution. Therefore, this study aimed to determine the progression of HV angle in elite adolescent dancers and evaluate the risk factors associated with foot plantar pressure during demi-pointe movement.

Methods: For this cohort study, 40 adolescent dancesport dancers (age: 14.

Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial.

In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial (NCT00490139), we identify and characterize five molecular subtypes associated with the risk of distant recurrence: immune-enriched, proliferative/metabolic-enriched, mesenchymal/stroma-enriched, luminal, and ERBB2-dependent.

Safety, reactogenicity, and immunogenicity of a novel 24-valent pneumococcal vaccine candidate in healthy, pneumococcal vaccine-naïve Japanese adults: A phase 1 randomized dose-escalation trial.

Background: The burden of pneumococcal diseases remains high in Japan. Pn-MAPS24v is a novel MAPS-based vaccine containing complexes of 24 serotype-specific polysaccharides (PS), non-covalently coupled with fusion protein 1 (CP1). This study evaluated the safety and immunogenicity of different dose levels of Pn-MAPS24v, administered in Japanese adults either subcutaneously (SC) or intramuscularly (IM).

Platelet dysfunction in heatstroke-induced coagulopathy: A retrospective observational study.

Purpose: Severe heatstroke is often complicated by disseminated intravascular coagulation (DIC). The aim of this study was to evaluate platelet function assessed through thromboelastography (TEG) at the emergency department (ED) and DIC severity among patients with heatstroke.

Materials And Methods: We performed a retrospective single-tertiary hospital cohort study.

Inhibition of amyloid β aggregation and BACE1, and protective effect on SH-SY5Y cells, by p-terphenyl compounds from mushroom Thelephora aurantiotincta.

The number of patients with Alzheimer's disease (AD) is expected to increase as the population ages. The amyloid cascade hypothesis is proposed as the pathogenic mechanism of AD. We report the isolation and structural determination of three new p-terphenyl compounds, thelephantin P (1), thelephantin Q (2), and thelephantin R (3), with four known compounds (4-7), from the fruiting bodies of Thelephora aurantiotincta Corner.

Delirium assessment, management and barriers to effective care across Scotland: A secondary analysis of survey data from World Delirium Awareness Day 2023.

Introduction: Delirium is a common, severe neuropsychiatric syndrome in hospitalised older adults. We evaluated use of validated delirium assessment tools, adherence to national guidelines and prevalence and management of delirium across Scotland, identifying barriers to effective care.

Methods: Secondary analysis of national survey data, collected by participating clinicians on World Delirium Awareness Day (15 March 2023).

Moral gradients based on social boundaries: Children prioritize themselves and their ingroup when resources are limited.

In an ideal world, there would be sufficient resources to be fairly allocated to everyone. The reality, however, is that resources are often limited. How do children navigate resource distribution decisions in the face of scarcity and sufficiency? Our study consisted of two experiments with 4- to 12-year-olds (N = 96), where children were required to distribute resources among themselves, a gender ingroup member, and a gender outgroup member when there was a limited number of resources (Experiment 1) and when there were sufficient resources for an equitable distribution (Experiment 2).

Pathogenic variants in the fibronectin type III domain of leptin receptor: Molecular dynamics simulation and structural analysis.

Several case reports have identified leptin receptor (LEPR) variants associated with severe obesity in humans. However, the structure of LEPR has only been partially understood until recently, and few studies have investigated the detrimental effects of these variants on the protein's three-dimensional structure. Notably, fibronectin type III (FnIII) domains play a crucial role in signal transduction.

Psychometric property of the Japanese version of self-efficacy for managing chronic disease scale in individuals with chronic diseases.

Background: Although accurately assessing self-efficacy for self-management is crucial in chronic illness care, important, there is a scarcity of validated psychometric properties in Japan. This study aimed to validate a Japanese version of the Self-Efficacy for Managing Chronic Disease (SEMCD-J) scale.

Methods: Individuals with self-reported chronic diseases, symptoms, or conditions for over one year were recruited online.

Dual Responsive Magnetic DCR3 Nanoparticles: A New Strategy for Efficiently Targeting Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer deaths globally. Unlike traditional molecularly targeted drugs, magnetically controlled drug delivery to micro/nanorobots enhances precision in targeting tumors, improving drug efficiency and minimizing side effects. This study develops a dual-responsive, magnetically controlled drug delivery system using PEGylated paramagnetic nanoparticles conjugated with decoy receptor 3 (DCR3) antibodies.

[National Survey on Procedure Dose of Endovascular Treatment for Lower Extremity Artery Disease].

Purpose: The objective of this study is to elucidate the current status of procedural radiation doses for endovascular treatment (EVT) of lower extremity artery disease (LEAD) in Japan and to validate the diagnostic reference level (DRL) quantity.

Methods: Survey requests were mailed to 493 facilities across Japan. The study targeted cases of EVT for LEAD performed between April 1, 2020, and March 31, 2022, with a maximum of 10 cases collected per facility.

GMP-Compliant Automated Radiolabeling and Quality Controls of [Ga]Ga-FAPI-46 for Fibroblast Activation Protein-Targeted PET Imaging in Clinical Settings.

In nuclear medicine, molecular imaging of the tumor microenvironment using radiopharmaceuticals (RPs) targeting cancer-associated fibroblasts is gaining significant interest. Among these RPs, [Ga]Ga-FAPI-46 for positron emission tomography (PET) imaging is frequently used in clinical research protocols. To ensure that the production of this RP complies with good manufacturing practices, process automation is widely adopted.

Development of an automated tool for the estimation of histological remission in ulcerative colitis using single wavelength endoscopy technology.

Introduction: Ulcerative colitis (UC) management employs a strategy targeting histological and endoscopic remission. Correlation of white-light endoscopy (WLE) scores with histological activity is limited. Single-wavelength endoscopy (SWE) addressing microvascular changes reflecting histological disease activity, may better assess histological remission.

The index of maximum sweat ion reabsorption rates of sweat glands does not correlate to whole body sweat sodium concentration in exercising young healthy men.

Factors explaining individual variations in whole body sweat sodium ion concentration ([Na]) during exercise are not fully understood. Galvanic skin conductance (GSC) reflects the electrical properties of the skin influenced by sweat rate (SR) and the presence of ions. Initiation of increases in this response to elevating sweating may reflect exceeding the maximal capacity of sweat ion reabsorption in sweat glands.

Clinical Phenotypes Associated with the Gut Microbiome in Older Japanese People with Care Needs in a Nursing Home.

Background: Frailty increases the risk of needing nursing care and significantly affects the life and functional prognosis of older individuals. Early detection and tailored interventions are crucial for maintaining and enhancing their life functions. Recognizing distinct clinical phenotypes is essential for devising appropriate interventions.