Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors.

The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC-NA signals by increasing intracellular calcium in an integrative manner ('flares').

Novel Injectable Collagen/Glycerol/Pullulan Gel Promotes Osteogenic Differentiation of Mesenchymal Stem Cells and the Repair of Rat Cranial Defects.

Bone tissue engineering is a technique that simulates the bone tissue microenvironment by utilizing cells, tissue scaffolds, and growth factors. The collagen hydrogel is a three-dimensional network bionic material that has properties and structures comparable to those of the extracellular matrix (ECM), making it an ideal scaffold and drug delivery system for tissue engineering. The clinical applications of this material are restricted due to its low mechanical strength.

WEE1 confers resistance to KRAS inhibitors in non-small cell lung cancer.

KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

Decoding Brain Development and Aging: Pioneering Insights From MRI Techniques.

The aging process induces a variety of changes in the brain detectable by magnetic resonance imaging (MRI). These changes include alterations in brain volume, fluid-attenuated inversion recovery (FLAIR) white matter hyperintense lesions, and variations in tissue properties such as relaxivity, myelin, iron content, neurite density, and other microstructures. Each MRI technique offers unique insights into the structural and compositional changes occurring in the brain due to normal aging or neurodegenerative diseases.

RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Association of Baseline Mitral Valve Area With Procedural and Clinical Outcomes of Mitral Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry.

Background: A small mitral valve area (MVA) is one of the challenging anatomies for transcatheter edge-to-edge repair (TEER) for mitral regurgitation, but the relationship between baseline MVA and clinical outcomes remains unknown. This study aimed to evaluate the association of baseline MVA with procedural and clinical outcomes in patients undergoing TEER with MitraClip from the OCEAN-Mitral registry (Optimized Catheter Valvular Intervention-Mitral).

Methods: A total of 1768 patients undergoing TEER were divided into 3 groups according to baseline MVA: group 1: <4.

combined with L858R mutation reduced afatinib sensitivity and associated to early recurrence in lung cancer.

Background: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for -mutated non-small cell lung cancer (NSCLC). However, there is no established treatment for osimertinib resistance, so second-generation afatinib is an alternative treatment option. The purpose of this study was to elucidate gene alterations associated with afatinib efficacy and resistance by analyzing cell-free DNA (cfDNA) obtained from patients with -mutated NSCLC.

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.

The burden of diseases, injuries, and risk factors by state in the USA, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states.

Methods: GBD 2021 analysed trends in mortality, morbidity, and disability for 371 diseases and injuries and 88 risk factors in the USA between 1990 and 2021.

Staphylococcus aureus enterotoxin sensitization is associated with declined capsaicin cough sensitivity in chronic obstructive pulmonary disease.

Sensitization to Staphylococcus aureus (S. aureus) enterotoxins (SEs) A (SEA) and B (SEB) is associated with the pathogenesis of several chronic airway diseases, including asthma and chronic rhinosinusitis, but its role in chronic obstructive pulmonary disease (COPD) remains unclear. This cohort study aimed to investigate the impact of sensitization to SEs on total IgE levels, and capsaicin cough reflex sensitivity (C-CS) in COPD.

Collagen I Microfiber Promotes Brain Capillary Network Formation in Three-Dimensional Blood-Brain Barrier Microphysiological Systems.

Background: The blood-brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous system (CNS). Moreover, BBB functional proteins show species differences; therefore, humanized in vitro BBB models are urgently needed to improve the predictability of preclinical studies. Recently, international trends in the 3Rs in animal experiments and the approval of the FDA Modernization Act 2.

Vegetable Salad Improves Lipid and Glucose Metabolism and Enhances Absorption of Specific Nutrients in Vegetables.

Vegetables are low in energy and rich in vitamins, minerals, and dietary fiber; various health benefits associated with their intake have been reported. Salads are one of the most convenient ways to consume vegetables and can be made simply by pouring mayonnaise, dressing, olive oil, or other condiments over a selection of vegetables. There are also many reports on the ways in which vegetable intake can improve health.

Quantitative in toto live imaging analysis of apical nuclear migration in the mouse telencephalic neuroepithelium.

In the embryonic neuroepithelium (NE), neural progenitor cells undergo cell cycle-dependent interkinetic nuclear migration (IKNM) along the apicobasal axis. Extensive IKNM supports increasing cell production rates per unit apical surface, as typically observed in the mammalian telencephalic NE. Apical nucleokinesis during the G2 phase is an essential premitotic event, but its occurrence has not yet been quantitatively analyzed at a large 3D-scale with sufficient spatiotemporal resolution.

GLP-1 receptor signaling restores aquaporin 4 subcellular polarization in reactive astrocytes and promotes amyloid β clearance in a mouse model of Alzheimer's disease.

The physiological actions of a gut hormone, glucagon-like peptide-1 (GLP-1), in Alzheimer's disease (AD) brain remain poorly understood, although GLP-1 receptor (GLP-1R) expression in this organ has been shown in several experimental studies. Therefore, we explored whether the GLP-1R signaling promotes the clearance of amyloid β (Aβ) (1-42) which is a core pathological hallmark of AD, focusing on the water channel protein aquaporin 4 (AQP4) localized to astrocyte endfeet perivascular membranes in intact brain. First, we confirmed that Glp1r mRNA is predominantly expressed at perivascular site of astrocytes in normal mouse cerebral cortex through in situ hybridization analysis.

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.