Serum magnesium and outcomes in heart failure with reduced ejection fraction: the GALACTIC-HF trial.

Background And Aims: The frequency and prognostic significance of abnormalities in serum magnesium concentrations have not been described in a contemporary HF population. The authors evaluated the prognostic significance of magnesium concentrations in patients with HFrEF enrolled in GALACTIC-HF trial.

Methods: GALACTIC-HF was a randomized, double-blind, multicentre, event-driven trial that investigated the efficacy and safety of omecamtiv mecarbil compared to placebo in HF patients with LVEF ≤35%.

Dimer-Specific FokT-seq Reveals DNA-Binding Dimerization and Novel Genomic Targets of TDP-43.

In postmortem brain tissues of patients with sporadic amyotrophic lateral sclerosis (ALS), the dimerization ability of TAR DNA-binding protein 43 (TDP-43) is impaired, accompanied by an accumulation of insoluble TDP-43. Thus, the loss of TDP-43 dimerization may play a critical driving role in ALS pathogenesis, although its underlying mechanism remains unclear. In this study, the FokT (FokI-TDP-43) system is developed, which fuses TDP-43 protein with FokI nuclease.

Sacubitril/valsartan and Quality of Life Assessed Using the EuroQol 5-Dimension 3-Level Questionnaire Level Sum Score (EQ-5D-3L-LSS) in Patients with HFrEF and HFmrEF/HFpEF.

Objectives: To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials.

Methods: The LSS was calculated by summating the 3 levels (1-3) for each of the 5 domains (minimum sum score=5; maximum sum score=15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline.

Efficacy and Tolerability of Finerenone According to the Use and Dosage of Diuretics: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

Importance: Given their kidney actions, it is important to evaluate the efficacy and safety of mineralocorticoid receptor antagonists when combined with other diuretics and whether they have a so-called diuretic-sparing effect in patients with heart failure (HF).

Objective: To examine the efficacy and tolerability of finerenone related to background diuretic treatment in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Design, Setting, And Participants: This study is a prespecified secondary analysis of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) randomized clinical trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with HFmrEF/HFpEF, who were randomized between September 2020 and January 2023.

Cerebral ischemia-reperfusion injury: mechanisms and promising therapies.

Cerebral ischemia-reperfusion injury (Cerebral I/R injury) is a critical pathological process following ischemic stroke, closely associated with multiple mechanisms including oxidative stress, neuroinflammation, and neuronal apoptosis. It also involves the alteration and regulation of numerous key genes and non-coding RNAs. Due to its complex regulatory mechanisms, there are currently no Food and Drug Administration (FDA)-approved drugs specifically targeting Cerebral I/R injury.

Tetramethylpyrazine protects against myocardial ischemia/reperfusion injury via regulating Myl2-mediated NLRP3 signaling pathway inhibition.

The protective mechanism of tetramethylpyrazine (TMP), an alkaloid derived from the Chinese herbal remedy Ligusticum chuanxiong, in relation to myocardial ischemia/reperfusion injury (MIRI) is not yet fully understood. To investigate the therapeutic effects of TMP, we established an in vivo rat model of MIRI and an in vitro hypoxia and reoxygenation (H/R) model using H9c2 cells. First, TMP significantly reduced the infiltration of inflammatory cells in the myocardium, decreased serum levels of myocardial injury markers (CK-MB, cTnT and LDH), and alleviated myocardial infarct size in I/R rats.

Topographic associations of hyperreflective materials in diabetic retinopathy: a multimodal correlation with microvascular pathology, structural remodeling and systemic metabolic dysregulation.

Background: Hyperreflective materials (HRMs), enigmatic biomarkers observed in diabetic retinopathy (DR), exhibit poorly characterized pathophysiological origins and clinical implications.

Methods: This retrospective cross-sectional study investigates the spatial distribution patterns of HRMs subtypes and their integrative relationships with retinal microvascular architecture, structural remodeling, and systemic metabolic parameters in 205 DR eyes. HRMs were systematically classified via multimodal optical coherence tomography angiography (OCTA) analysis, incorporating topographic localization (inner vs.

Burden of macular complications in Japanese patients aged 75 years and over with sarcoid uveitis.

Purpose: To investigate the epidemiology and complications of sarcoid uveitis in older Japanese patients.

Methods: A single-center, retrospective cohort study. Medical records of patients aged ≥ 65 years with sarcoid uveitis at the Institute of Science Tokyo Hospital between 2012 and 2022 were analyzed.

Teprotumumab for Thyroid Eye Disease: Mechanism, Clinical Efficacy, and Current Challenges.

Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management.

Disruption of Spore Coat Integrity in Enhances Macrophage Immune Activation.

Probiotics play a pivotal role in animal production by promoting growth, enhancing gut health, and modulating immune responses. , a widely utilized probiotic, forms robust spores that exhibit exceptional resistance, making it ideal for feed applications. While spores have been shown to stimulate innate immune signaling, the specific contributions of spore coat proteins to immune modulation remain poorly characterized.

Associations of serum neurofilament and asthma: evidence from the NHANES 2013-2014.

Background: Neural mechanisms are important in asthma, and serum neurofilament light chain (sNfL) is a biomarker of neuronal damage. This study investigated the correlation between sNfL and asthma.

Methods: This cross-sectional study was based on NHANES data and used multiple logistic regression analysis, subgroup analysis, and smoothed curve fitting to explore the relationship between sNfL and asthma.

The role of nursing interventions in the management and outcomes of gynecological tumors: a systematic review and meta-analysis.

Purpose: This meta-analysis evaluates the effectiveness of nurse-led interventions in improving quality of life (QoL), mental health, sexual function, marital satisfaction, postoperative recovery, and symptom distress in gynecological cancer patients.

Methods: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO identified randomized controlled trials (RCTs) and quasi-experimental studies. A random-effects meta-analysis was conducted, assessing heterogeneity (I), publication bias, and evidence certainty using the GRADE framework.

A global perspective on autoinducer-2-mediated cell communication in prokaryotes.

Animal communication within a community is essential for their survival and reproduction. This phenomenon is not restricted to animals but is also prevalent in prokaryotes, which employ quorum sensing (QS) mechanisms for communication and behavior. Despite their importance, cell-cell communication in prokaryotes has not been cataloged in detail.

Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP-43-Associated ALS and AD.

Cytoplasmic aggregation of transactive response DNA-binding protein 43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and occurs in 57% of Alzheimer's disease (AD) cases. TDP-43 regulates RNA processing, including cryptic exon splicing. Here, we demonstrate that TDP-43 directly controls growth-associated protein (GAP43) expression by binding to its pre-mRNA.

The transcription factor REM16a promotes flowering time in soybean by activating flowering-related genes.

The flowering time of soybean [Glycine max (L.) Merr.] is extremely sensitive to photoperiod, which importantly influences its yield potential and restricts the geographical range of soybean cultivars to specific latitudes.

Race and Ethnicity in Heart Failure Trials: Time to Update Recommended Categories for Global Relevance.

Background: The collection of race and ethnicity data in clinical trials using standardized categories is recommended by the US Food and Drug Administration, although this is primarily for domestic reasons. The applicability and understanding of the categories in multinational trials are uncertain.

Methods: We analyzed patient-level data from 13 major heart failure trials, examining race and ethnicity data recorded by country, as recommended by the Food and Drug Administration: "American Indian or Alaska Native," "Asian," "Black or African American," "Native Hawaiian or Other Pacific Islander," and "White" for race and "Hispanic or Latino" as a minimum for ethnicity (with an expanded list of ethnicities available).

Mapping the role of cytokine signaling at single-cell and structural resolution in uveal melanoma.

To better understand the complexity of the tumor microenvironment and to identify novel treatment strategies for uveal melanoma (UVM), we analyzed single-cell RNA sequencing (scRNA-seq) data from eight primary UVM eye tissues and three metastatic UVMs in the liver (GSE139829). We integrated this with bulk RNA-seq data from UVM patients derived from TCGA-UVM and GSE84976 cohorts. Our study focused on cytokine signaling in immune-related genes (CSIRGs), revealing distinct cellular compositions, intercellular interactions, and prognostic implications in UVM.

Sestrin2 alleviates cognitive impairment via inhibiting hippocampus ferroptosis in cigarette smoke-induced chronic obstructive pulmonary disease.

Cognitive dysfunction is an essential comorbidity that contributing to the whole disease process of the individual of chronic obstructive pulmonary disease (COPD), yet its specific mechanism remains controversial due to a lack of cellular and molecular evidence. Our clinical data revealed a significant reduction in total hippocampal volume in patients with COPD, with the CA1 subfield notably smaller and associated with lung function. Long-term CS exposure caused hippocampus impairment, leading to spatial and working memory impairments in COPD model mice.

Glycaemic level and glycaemic variability in acute ischaemic stroke and functional outcome: An observational continuous glucose monitoring study.

Introduction: Glycaemic variability has been associated with poor outcomes in critically ill patients. We aimed to study the association between glycaemic variability and functional outcome in patients with acute ischaemic stroke using continuous glucose monitoring to ensure all episodes of hyper- and hypoglycaemia were captured.

Research Design And Methods: Participants with acute ischaemic stroke were enrolled and started blinded continuous glucose monitoring (Dexcom G6) between November 2020 and December 2022.

Ocular Manifestations of Mpox and Other Poxvirus Infections: Clinical Insights and Emerging Therapeutic and Preventive Strategies.

Poxvirus infections, particularly those caused by the monkeypox virus, have emerged as significant public health threats. Ocular manifestations constitute a severe potential clinical complication associated with these infections, potentially resulting in permanent visual impairment in afflicted patients. This review aimed to examine the clinical spectrum of ocular manifestations associated with mpox and other poxvirus infections and to evaluate current management strategies alongside emerging therapeutic interventions and prevention strategies.

Correlation between binocular vision function and visual fatigue in school-age children with myopic anisometropia.

We investigated the differences in binocular vision function and visual fatigue between school-aged children with myopic anisometropia and those with myopic isometropia. It also examined the correlation between myopic anisometropia and binocular vision parameters. One hundred school-aged (ages 6-13 years) children (43 boys and 57 girls) were divided into two groups: the myopic anisometropia group (interocular spherical equivalent difference ≥ 1.

Anaemia in patients with heart failure and mildly reduced or preserved ejection fraction: A prespecified analysis of the FINEARTS-HF trial.

Aims: Anaemia is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and associated with poor clinical outcomes. While renin-angiotensin system blockers reduce haemoglobin, little is known about the effect of mineralocorticoid receptor antagonists on haemoglobin and in patients with anaemia. We evaluated the effects of finerenone according to anaemia status in patients with HFmrEF/HFpEF enrolled in FINEARTS-HF.

Associations of weight-adjusted-waist index and systemic immune-inflammatory index with sKlotho: evidence from the NHANES 2007-2016.

Background: Klotho is an anti-aging protein, and obesity and inflammation have been identified as having a relationship with Klotho. This study investigated the correlation between weight-adjusted-waist index(WWI), systemic inflammation index(SII) and soluble Klotho (sKlotho) and explored the potential mediating role of SII.

Methods: The association between WWI, SII, and sKlotho was investigated using weighted multivariate linear regression, subgroup analysis, and smoothed curve fitting in this cross-sectional study, which was based on NHANES data.

An optimal water distribution model for canal systems based on water level.

This paper presents an optimal water distribution model for canals that focuses on canal flow capacity as a foundational premise. The model aims to optimize the flow rate and timing of irrigation to satisfy the water demands necessary for crop growth. Traditionally, the flow rate in the upper-level canal is viewed as the sum of the flow rates in the lower-level canals, with the distribution of water based solely on this flow rate.