Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.

Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

Consumer-grade wearable devices in arrhythmia diagnostics for clinicians: where we are and where we are going.

Atrial arrhythmias, including atrial fibrillation (AF), are a major contributor to cardiovascular morbidity and mortality. Early detection and effective management are critical to mitigating adverse outcomes such as stroke, heart failure, and overall mortality. Wearable devices have emerged as promising tools for monitoring, detecting, and managing atrial arrhythmias near-continuously.

Development and characterization of in vitro inducible immortalization of a murine microglia cell line for high throughput studies.

There are few in vitro models available to study microglial physiology in a homeostatic context. Recent approaches include the human induced pluripotent stem cell model, but these can be challenging for large-scale assays and may lead to batch variability. To advance our understanding of microglial biology while enabling scalability for high-throughput assays, we developed an inducible immortalized murine microglial cell line using a tetracycline expression system.

CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

Identifying proteomic prognostic markers for Alzheimer's disease with survival machine learning: The Framingham Heart Study.

Background: Protein abundance levels, sensitive to both physiological changes and external interventions, are useful for assessing the Alzheimer's disease (AD) risk and treatment efficacy. However, identifying proteomic prognostic markers for AD is challenging by their high dimensionality and inherent correlations.

Methods: Our study analyzed 1128 plasma proteins, measured by the SOMAscan platform, from 858 participants 55 years and older (mean age 63 years, 52.

Ultra-processed food consumption and risk of dementia and Alzheimer's disease: The Framingham Heart Study.

Background: Ultra-processed food consumption is emerging as a risk factor for various cardiometabolic diseases, however its association with dementia and Alzheimer's disease has rarely been explored.

Objectives: We sought to examine whether ultra-processed food consumption is associated with risk of all-cause dementia and Alzheimer's disease among middle-age and older adults.

Design: A prospective cohort study.

Differences in Postoperative Disposition by Kidney Disease Severity: A Population-Based Cohort Study.

Rationale & Objective: People with advanced kidney disease undergo more non-cardiac operations compared to the general population, with a higher risk of perioperative cardiac events and death. However, little is known about the associations between severity of preoperative kidney dysfunction with postoperative length of hospitalization and discharge disposition; these were the focus of this study.

Study Design: Population-based retrospective cohort.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a 2-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine to prognostic performance of this approach.

Methods: The VCTE-Prognosis Study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

Planetary Health Diet Index in relation to mortality in a prospective cohort study of U.S. Black females.

Background: To improve both human health and the health of our planet, the EAT-Lancet Commission proposed the planetary health diet (PHD).

Objective: We aimed to evaluate associations of PHD with all-cause, cardiovascular disease (CVD), and cancer-specific mortality among U.S.

Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries.

Objective: To assess variability among data elements collected among existing neonatal hypoxic-ischemic encephalopathy (HIE) data registries worldwide and to determine the need for future harmonization of standard common data elements.

Study Design: This was a cross-sectional study of data elements collected from current or recently employed HIE registry data forms. Registries were identified by literature search and email inquiries to investigators worldwide.

Prolonged length of stay among individuals presenting to the emergency department with psychosis: Associations with sociodemographic and visit-level characteristics.

Introduction: Individuals experiencing psychosis commonly initiate and engage in treatment within an emergency department (ED) setting. Understanding factors contributing to adverse ED experiences is critical for improving psychosis-related treatment. Prolonged ED length of stay (LOS), which can be conversely associated with treatment quality, is not well explored among individuals experiencing psychosis.

Isolated subsegmental pulmonary embolism identification based on international classification of diseases (ICD)-10 codes and imaging reports.

Background: Isolated subsegmental pulmonary embolism (issPE) is a commonly encountered diagnosis. Although the International Classification of Diseases (ICD)-10 codes are used for research, their validity for identifying issPE is unknown. Moreover, issPE diagnosis is challenging, and the findings from radiology reports may conflict with those from expert radiologists.

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.

Management of renal cell carcinoma with ablation in comparison to nephrectomy: A 5-year analysis of inpatient procedural data to evaluate utilization disparities in the United States.

Purpose: To perform a nationwide analysis of ablation compared to partial and total nephrectomy for the management of renal cell carcinoma (RCC) to evaluate utilization trends and disparities in the USA.

Materials And Methods: The 2016-2020 National Inpatient Sample was analyzed. Using ICD-10, we identified the diagnosis of RCC then analyzed the utilization trends of ablation and nephrectomies (both partial and complete).

Racial and ethnic disparities in post-acute care service utilization after stroke.

Evidence examining disparities in post-acute care (PAC) utilization among various racial and ethnic groups after stroke and the influence of social determinants of health (SDOH) in these decisions is lacking. Thus, we searched the literature from January 2000 to November 2023 regarding PAC among individuals after stroke through: 1) Pubmed, 2) Scopus, 3) Web of Science, 4) Embase, and 5) CINAHL. We found 14 studies.

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

Infection rate following mandibular distraction with internal and external devices in infants.

Background: Internal and external devices may be utilized in mandibular distraction osteogenesis (MDO) for the correction of symptomatic micrognathia in infants and children.

Purpose: To compare the rate and severity of infection between internal and external MDO devices.

Study Design, Setting, Sample: Retrospective cohort study utilizing an institutional database of patients who underwent MDO.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for assessing and visualizing cell microaggregate formation in whole blood by imaging flow cytometry.

Blood cell aggregates are clinically useful biomarkers in a number of medical disorders. This protocol provides accurate and quantitative analysis of cell aggregates using a small volume of whole blood and imaging flow cytometry. We describe steps for sample collection, staining, and measurement.

Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS.

Background: Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD.