Machine Learning to Predict Individualized Treatment Effects of Sodium Bicarbonate for Patients With Out-of-Hospital Cardiac Arrest.

Objectives: Current evidence regarding the effect of sodium bicarbonate (SB) on patients with out-of-hospital cardiac arrest (OHCA) remains unclear. This study aimed to develop a machine-learning model to predict the individualized treatment effect (ITE) of SB use in OHCA patients.

Design: An eXtreme Gradient Boosting-based causal forest model was developed using an 8-year retrospective OHCA database after propensity score matching (PSM) for age, serum potassium, pH, bicarbonate, and Pco2 level.

Light-Activatable Nanotherapeutic Platform Synchronizing ROS-Mediated Antibacterial Action with Macrophage Polarization for Refractory Wound Infections.

The treatment of persistent drug-resistant bacterial infections in wounds poses a significant global medical challenge. Developing innovative antimicrobial strategies capable of simultaneously achieving bacterial eradication, inflammation resolution, and tissue regeneration has become imperative. Herein, a nanocomposite featuring plasma-enhanced enzymatic activity and immunoregulatory properties is engineered, designed to reprogram the wound microenvironment and expedite healing in drug-resistant bacterial infections.

Novel Self-Powered Biosensor Based on Highly Efficient Cosignal Accelerator and Multiple Signal Amplification Strategies toward Ultrasensitive miRNA-141 Assay.

A highly sensitive self-powered biosensor is designed based on gold-platinum nanorods (AuPt NRs) and the cascade reaction of catalytic hairpin assembly (CHA) and hybrid chain reaction (HCR) toward the miRNA-141 assay. As a cosignal accelerator, AuPt NRs enhance electrical conductivity between glucose oxidase (GOD) and a carbon paper (CP) electrode, thereby assisting in output signal enhancement. The cascade reaction of CHA-HCR is employed to efficiently amplify the detection signal and improve the sensitivity of the self-powered biosensor.

Titin-related familial dilated cardiomyopathy: factors associated with disease onset.

Background And Aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM.

Curcumin-loaded nanoscale coordination polymers for ROS scavenging and anti-inflammatory therapy in atherosclerosis.

The progression of atherosclerosis (AS) is marked by escalating chronic inflammation and oxidative stress within the arterial wall, which heightens the risk of plaque rupture and subsequent acute ischemic cardiovascular and cerebrovascular events. Conventional anti-inflammatory and antioxidant therapies, however, are often limited by modest efficacy and potential side effects. Here, we synthesized iron-curcumin coordination polymers (Fe-Cur CPs) coordinated by trivalent iron ions and the natural product curcumin (Cur).

Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer.

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation.

Multiple Hub Genes as Diagnostic and Therapeutic Targets Inducing Inflammation and Angiogenesis in Retinopathy of Prematurity.

Introduction: The pathogenesis of retinopathy of prematurity (ROP) is intricate and multifactorial. The current treatments for ROP include laser photocoagulation, cryotherapy, scleral buckling or vitrectomy and anti-VEGF drugs, yet which have numerous adverse effects. Consequently, the objective of this investigation was to mine new biomarkers of ROP and identify potential therapeutics that target these biomarkers.

Co-profiling of in situ RNA-protein interactions and transcriptome in single cells and tissues.

RNA-binding proteins (RBPs) are essential regulators of RNA fate and function. A long-standing challenge in studying RBP regulation has been mapping RNA interactomes within the dynamic transcriptomic landscape, especially in single-cell contexts and primary tissues. Here we introduce MAPIT-seq (modification added to RBP interacting transcript-sequencing), which uses an antibody-directed editing strategy to map genome-wide in situ RBP-RNA interactions and gene expression concurrently.

Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.

The current generation of highly successful atherosclerosis treatments, such as low-density lipoprotein (LDL)-cholesterol reduction, blood pressure management, and smoking cessation, has largely focused on ameliorating factors perceived to drive incident disease and its complications. The adverse contributions of these factors have typically been identified through epidemiological studies. The therapeutic strategies that arose in response focused on risk factors for disease development and tended to overlook the fact that patients already have established disease, by the time of presentation.

The interplay of hypoxia, inflammation, and microbiota as indicators of malignant transformation in oral potentially malignant disorders.

Oral Potentially Malignant Disorders (OPMDs), such as leukoplakia, erythroplakia, proliferative verrucous leukoplakia, and oral submucous fibrosis, carry a risk of malignant transformation, with reported rates ranging from 2.6 % to 7.9 %.

Positive-going hybrid indicators for voltage imaging in excitable cells and tissues.

Membrane potential dynamics are crucial to the physiology of electrically excitable cells, such as neurons, cardiomyocytes, and pancreatic islet cells. Fluorescence voltage indicators have enabled the visualization of electrical activities at the single-cell level across large cell populations. However, most existing indicators have a negative fluorescence-voltage response, resulting in a high background signal when cells are at their resting state.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Prediction of out-of-hospital cardiac arrest in older patients with insomnia: a longitudinal population study.

Background: The association of insomnia in older patients with out-of-hospital cardiac arrest (OHCA) is not completely elucidated. The current study developed and validated a predictive model for OHCA in older patients using population-based analysis.

Methods: This study used data from the National Health Insurance research database.

Mycobacterium tuberculosis PE5 stimulates anti-inflammatory cytokine production via innate immune toll-like receptor 4 signaling.

Mycobacterium tuberculosis possesses an intricate system of virulence factors that aid in providing resilience to the pathogen within the milieu of the host. M.tb expresses unique proteins, PE/PPE, that are conserved and play a crucial role in pathogenesis.

Sex differences in a murine model of infective endocarditis.

Infective endocarditis (IE) is a highly lethal disease with a notable male predominance, yet the biological basis for this sex disparity remains unclear. We established a murine IE model in C57BL6 mice in which aortic valve injury was induced via wire-injury and followed by intravenous injection of Staphylococcus aureus. Infection was confirmed by blood and valve cultures, and cardiac function was evaluated by echocardiography.

TGF-β1-mediated downregulation of L1CAM in pancreatic ductal adenocarcinoma drives upregulation of collagen 17A1 and MMP2, facilitating tumor invasiveness and metastasis.

The highly fibrotic microenvironment of pancreatic ductal adenocarcinoma (PDAC) poses significant challenges for effective treatment, particularly in drug delivery and tumor progression. Our study investigates the role of collagen dynamics in PDAC, revealing that TGF-β1 negatively regulates the expression of L1 cell adhesion molecule (L1CAM), leading to a more invasive tumor phenotype. We identify a subset of PDAC cells with low L1CAM expression (L1) that actively influences collagen deposition and remodeling, as evidenced by the upregulation of collagen 17A1 (COL17A1) and matrix metalloproteinase 2 (MMP2), both associated with poor prognosis.

External Validation of 3 Prediction Models for Mortality in Out-of-Hospital Cardiac Arrest Survivors: A Retrospective Multicenter Study.

Background: Predictive models such as the Cardiac Arrest Survival Score (CASS), FACTOR score, and Survival After ROSC in Cardiac Arrest (SARICA) have been developed to estimate in-hospital mortality in out-of-hospital cardiac arrest survivors. This study aims to externally validate and compare their predictive performance to determine their clinical utility upon emergency department admission.

Methods: This retrospective multicenter cohort study included out-of-hospital cardiac arrest patients admitted to the National Taiwan University Hospital and its branches between January 2016 and March 2024.

Butyrate preserves entorhinal-hippocampal spatial coding and blood brain barrier integrity in mice with depleted gut microbiome.

Given the widespread and increasing consumption of oral antibiotics globally, understanding their impact on cognition through the gut-brain axis is crucial. We investigated whether broad-spectrum antibiotics disrupt spatial cognition by altering behavior, neural dynamics, brain metabolism, and blood-brain barrier integrity. Here we show that male mice receiving antibiotic-treated water display significant impairments in spatial memory tasks and abnormal encoding of space by entorhinal grid cells and hippocampal place cells.

Cellular heterogeneity and therapeutic response profiling of human IDH+ glioma stem cell cultures.

Glioblastoma stem cell (GSC) cultures are initiated from glioblastoma (GBM) surgical resection tissue. They can capture and propagate key GBM primary tumor molecular and cellular features. We have deeply characterized four isocitrate dehydrogenase (IDH)-expressing (or IDH+) GSC cultures from unrelated adults to serve as cellular models for the majority of adult primary GBM.

Glucose Metabolism echoes Long-Range Temporal Correlations in the Human Brain.

Intrinsic brain activity is characterized by pervasive long-range temporal correlations. While these scale-invariant dynamics are a fundamental hallmark of brain function, their implications for individual-level metabolic regulation remain poorly understood. Here, we address this gap by integrating resting-state functional Magnetic Resonance Imaging (fMRI) and dynamic [F]FDG Positron Emission Tomography (PET) data acquired from the same cohort of participants.

A scalable platform for EPSC-Induced MSC extracellular vesicles with therapeutic potential.

Background: Extracellular Vesicles (EVs) derived from mesenchymal stem cells (MSCs) have gained recognition as promising therapeutic and drug delivery agents in regenerative medicine. However, their clinical application is limited by donor variability, low scalability, and inconsistent therapeutic quality. To overcome these challenges, a robust and standardized production platform is urgently needed.

DDX41 resolves G-quadruplexes to maintain erythroid genome integrity and prevent cGAS-mediated cell death.

Deleterious germline DDX41 variants constitute the most common inherited predisposition disorder linked to myeloid neoplasms (MNs), yet their role in MNs remains unclear. Here we show that DDX41 is essential for erythropoiesis but dispensable for other hematopoietic lineages. Ddx41 knockout in early erythropoiesis is embryonically lethal, while knockout in late-stage terminal erythropoiesis allows mice to survive with normal blood counts.