A phase 2 clinical trial of luspatercept in non-transfusion-dependent patients with myelodysplastic syndromes.

Luspatercept has shown durable clinical efficacy for the treatment of anemia in transfusion-dependent patients with lower-risk myelodysplastic syndromes (LR-MDS). We report the results of a prespecified primary analysis of a phase 2 trial of luspatercept in non-transfusion-dependent (NTD) Japanese patients with anemia due to LR-MDS. Luspatercept (starting dose 1.

Cell type-specific weighting-factors to solve solid organs-specific limitations of single cell RNA-sequencing.

While single-cell RNA-sequencing (scRNA-seq) is a popular method to analyze gene expression and cellular composition at single-cell resolution, it harbors shortcomings: The failure to account for cell-to-cell variations of transcriptome-size (i.e., the total number of transcripts per cell) and also cell dissociation/processing-induced cryptic gene expression.

Clinical characteristics of monoclonal immunoglobulin-associated renal disease: a retrospective cohort study.

Introduction: Clinical epidemiological data on monoclonal gammopathy of renal significance (MGRS) are lacking. In this retrospective observational study, MGRS was compared with B-cell or plasma cell malignancies (BCM/PCM) with renal involvement to clarify differences in their clinical features.

Methods: Among the 1408 renal biopsies performed at our hospital, 25 MGRS and 18 BCM/PCM patients were identified.

Predictors and clinical outcomes of true mitral stenosis in patients undergoing transcatheter aortic valve implantation.

Aims: Predictors of true degenerative mitral stenosis (MS) in patients with aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) remain unknown. This study aimed to investigate the predictors and prognostic value of true degenerative MS in this population.

Methods And Results: We retrospectively reviewed the records of 760 consecutive patients who underwent TAVI.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Context: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens.

Objective: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials.

The ADNI Administrative Core: Ensuring ADNI's success and informing future AD clinical trials.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Administrative Core oversees and coordinates all ADNI activities, to ensure the success and maximize the impact of ADNI in advancing Alzheimer's disease (AD) research and clinical trials. It manages finances and develops policies for data sharing, publications using ADNI data, and access to ADNI biospecimens. The Core develops and executes pilot projects to guide future ADNI activities and identifies key innovative methods for inclusion in ADNI.

Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.

Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first-in-human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS-0871), a highly selective, orally available, non-covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5-900 mg) and multiple ascending doses (MAD; 50-300 mg twice daily [b.

The Impact of Fermented Milk Products Containing BB536 on the Gut Environment: A Randomized Double-Blind Placebo-Controlled Trial.

Probiotics, particularly those native to the gut microbiota, have a profound influence on the gut environment. In this study, we conducted a randomized placebo-controlled, double-blind, parallel-group comparison trial to investigate the effects of BB536 ( BB536) on the fecal microbiota and metabolite compositions in healthy individuals. We compared the effects of fermented milk produced solely with and (placebo group) and fermented milk supplemented with BB536 (BY group).

Beyond Recycling Antibodies: Crovalimab's Molecular Design Enables Four-Weekly Subcutaneous Injections for PNH Treatment.

The advent of recycling antibodies, leveraging pH-dependent antigen binding and optimized FcRn interaction, has advanced the field of antibody therapies, enabling extended durability and reduced dosages. Eculizumab (Soliris) demonstrated the efficacy of C5 inhibitors for paroxysmal nocturnal hemoglobinuria (PNH), while its derivative, ravulizumab (Ultomiris), recognized as a recycling antibody, extended the dosing intervals. However, limitations including intravenous administration and inefficacy in patients with the R885H single-nucleotide polymorphism (SNP) in C5 could necessitate alternative solutions.

Bridging Gaps and Charting Future Directions in Vasculitis.

The field of vasculitis continues to evolve rapidly, driven by breakthroughs in both basic and clinical research [...

The Distress and Benefits of the Bereaved Family Survey: A Mortality Follow-Back Survey.

Context: The Bereaved Family Survey is an important method for evaluating the quality of palliative care.

Objectives: To examine the distress and benefits of bereaved families of patients with or without cancer, who participated in a Bereaved Family Survey, and identify factors associated with distress and benefits.

Methods: We conducted a nationwide cross-sectional, self-reported questionnaire mail survey among the bereaved families of patients who died of cancer, heart disease, cerebrovascular disease, pneumonia, or kidney failure.

Targeting Oxidative Phosphorylation with a Novel Thiophene Carboxamide Increases the Efficacy of Imatinib against Leukemic Stem Cells in Chronic Myeloid Leukemia.

Patients with chronic myeloid leukemia (CML) respond to tyrosine kinase inhibitors (TKIs); however, CML leukemic stem cells (LSCs) exhibit BCR::ABL kinase-independent growth and are insensitive to TKIs, leading to disease relapse. To prevent this, new therapies targeting CML-LSCs are needed. Rates of mitochondria-mediated oxidative phosphorylation (OXPHOS) in CD34CML cells within the primitive CML cell population are higher than those in normal undifferentiated hematopoietic cells; therefore, the inhibition of OXPHOS in CML-LSCs may be a potential cure for CML.

Preliminary study on the effects of boysenberry juice intake on brown adipose tissue activity in healthy adults.

Brown adipose tissue (BAT) plays an important role in energy metabolism because it uses fatty acids for thermogenesis during cold exposure. Preclinical studies found that boysenberry anthocyanins (BoyACs) activate BAT. Therefore, the aim of this preliminary study was to evaluate how BoyAC intake affects BAT in humans.

A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder.

Background And Objective: Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD.