A TROP2/Claudin Program Mediates Immune Exclusion to Impede Checkpoint Blockade in Breast Cancer.

Immune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. Here, we demonstrate that Trophoblast Cell-Surface Antigen 2 (TROP2), a key target of emerging anti-cancer Antibody Drug Conjugates (ADCs), controls barrier-mediated immune exclusion in Triple-Negative Breast Cancer (TNBC) through Claudin 7 association and tight junction regulation. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC.

Higher Body Mass Index is Associated with Increased Oxidative Stress in Patients of Type 2 Diabetes Mellitus.

Introduction: Type 2 diabetes mellitus (T2DM) is closely associated with the obesity; however, certain proportion of T2DM patients is non-obese or lean (BMI < 18.5 kg/m). Obesity has long been associated with oxidative stress; however, there are no studies available documenting levels of oxidative stress in the lean patients of T2DM.

Health-Economic Modelling of Improved Behavior in Insulin Injection Technique in Belgium.

Background: Adequate insulin injection technique (IIT) is crucial to optimize the efficacy of diabetes therapy. Widespread non-practice of injection-site rotation and frequent reuse of insulin pen needles (PN) promote high rates of lipohypertrophy (LH) among people living with diabetes (PwD). LH is associated with increased insulin requirement and suboptimal insulin absorption leading to worsened glycemic control and increased risk for hypoglycemia.

Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking.

Chronic kidney disease-associated pruritus: a comparison of instruments and associations with patient-reported outcomes using an electronic patient-reported outcome survey in Europe.

Background: The associations between self-reported chronic kidney disease-associated pruritus (CKD-aP) and patient-reported outcomes (PROs) have been reported using various instruments to assess itch. Data collection via multiple CKD-aP instruments allows the evaluation of different domains and measurements of CKD-aP burden and may help tailor data capture for future research or clinical care.

Methods: An electronic PRO (ePRO) survey was distributed to European hemodialysis (HD) patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2021-23.

Relaxed event-triggered tracking control of positive T-S fuzzy systems via a membership function method.

In this paper, the sampled-data-based event-triggered tracking control for the positive nonlinear system is discussed. The event-triggered mechanism naturally causes a mismatch between the membership functions of the system model and the fuzzy controller. Meanwhile, the positive constraint and tracking behavior increase the complexity of system analysis and bring conservative analysis results.

Clinical trials, challenges, and changes in TCR-based therapeutics for hematologic malignancies.

Introduction: T cells engineered to express antigen-specific T cell receptors (TCR; TCR-T) are a promising class of immunotherapeutic for patients with hematologic malignancies. Like chimeric antigen receptor-engineered T cells (CAR-T), TCR-T are cell products with defined specificity and composition. Unlike CAR-T, TCR-T can recognize targets arising both from intracellular and cell surface proteins and leverage the sensitivity of natural TCR signaling machinery.

Safe and effective anticoagulation use: case studies in anticoagulation stewardship.

Anticoagulant use is prevalent and associated with significant potential for harm. Anticoagulation stewardship practice has emerged to address care gaps and promote safe, effective, and cost-conscious anticoagulation use across health care systems. We present 4 patient cases describing common challenges in anticoagulation management: inappropriate dosing of direct oral anticoagulants, the diagnosis and management of heparin-induced thrombocytopenia, periprocedural anticoagulation management, and heavy menstrual bleeding on anticoagulation.

A proof-of-concept analysis of data from the first NHS clinic for young adults with comorbid cannabis use and psychotic disorders.

Background: Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.

Aims: Examine outcome data from the first 46 individuals to complete the CCP's intervention.

Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Diets and leisure activities are associated with curiosity.

Social connections are essential for human health. While curiosity and empathy are crucial psychological factors for a fulfilling life connected with others, it is unclear if acquired environmental factors influence them. In this cross-sectional observational study, 1,311 men and women aged 20-79 years living in Japan were observed to explore how lifestyle factors such as diet, sleep, and leisure activities (such as exercise and hobbies) impact curiosity and empathy.

Quality of Life Survey Using NEI VFQ-25 in Japanese Patients With Fuchs Endothelial Corneal Dystrophy.

Objectives: To assess the quality of life in Japanese patients with Fuchs endothelial corneal dystrophy (FECD) using The National Eye Institute Visual Function Questionnaire.

Methods: Here, 34 patients with FECD (FECD group) and 13 healthy individuals (control group) completed the National Eye Institute Visual Function Questionnaire Japanese version by interview format. The association between dominant eye corrected distance visual acuity and composite score (component 11) or subscales in the FECD group was evaluated using Spearman rank correlation coefficient.

Balloon aortic valvuloplasty with simultaneous aortic root injection: a case report of an adjunctive strategy to computed tomography for predicting coronary obstruction in transcatheter aortic valve-in-transcatheter aortic valve procedures.

Background: Computed tomography (CT) assessment is the standard for predicting coronary obstruction (CO) caused by sinus sequestration (SS) during transcatheter aortic valve (TAV) implantation in degenerated TAV (TAV-in-TAV) procedure, but it may not always be accurate. This report describes a prediction method for CO by using balloon aortic valvuloplasty (BAV) during TAV-in-TAV.

Case Summary: An 87-year-old woman with a history of balloon-expandable transcatheter heart valve (BE-THV) implantation 7 years prior was admitted with worsening dyspnoea.

Drug Interaction Studies of Cabamiquine:Ganaplacide Combination against Hepatic .

New antimalarial combination therapies with novel modes of action are required to counter the emergence and spread of drug resistance against existing therapeutics. Here, we present a study to evaluate the preventive activity of a combination of clinical antimalarial drug candidates, cabamiquine and ganaplacide, that have multistage activity against the liver and blood stages of infection. Cabamiquine (DDD107498, M5717) inhibits parasite protein synthesis, and ganaplacide (KAF156) inhibits protein trafficking, blocks the establishment of new permeation pathways, and causes endoplasmic reticulum expansion.

Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer.

Lurbinectedin is an approved second-line treatment for small-cell lung cancer (SCLC). SCLC clinical trials combining lurbinectedin with PD-L1 blockade are currently ongoing. However, the immunomodulatory effects of lurbinectedin remain largely unknown.

Effects of Diabetes and Attentional Focus on Learning of a Novel Balance Task.

Background And Purpose: Chronic diabetes is a prevalent systemic disease that impairs neuromotor functioning and often leads to increased risk of falls. Adopting an external focus of attention during motor skill practice has been shown to improve learning outcomes; however, it has not been examined in this population. We examined how attentional focus instructions (internal vs external) affect balance performance and learning in older adults with and without diabetes.

Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.

Background: Severe hemophilia A is managed with factor VIII replacement or hemostatic products that stop or prevent bleeding. Data on gene therapy with hematopoietic stem-cell (HSC)-based expression of factor VIII for the treatment of severe hemophilia A are lacking.

Methods: We conducted a single-center study involving five participants 22 to 41 years of age with severe hemophilia A without factor VIII inhibitors.

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Background: Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.

Preclinical and Clinical-Scale Magnetic Particle Imaging of Natural Killer Cells: in vitro and ex vivo Demonstration of Cellular Sensitivity, Resolution, and Quantification.

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation.