Esophagectomy Trends and Postoperative Outcomes at Private Equity-Acquired Health Centers.

Importance: Growing trends in private equity acquisition of acute care hospitals in the US have motivated investigations into quality of care delivered at these health centers. While some studies have explored comparative outcomes for high-acuity medical conditions, care trends and outcomes of complex surgical procedures, such as esophagectomy, at private equity-acquired hospitals is unknown.

Objective: To compare structural characteristics and postoperative outcomes following esophagectomy between private equity-acquired and nonacquired health centers.

How community connection, homophobia, and racism shape gene expression in sexual minority men with and without HIV.

Objective: Although sexual minority men experience substantial discrimination, in addition to increased risk for several serious mental and somatic health problems, the biological mechanisms underlying these effects are unclear. To address this issue, we examined how experiences of social safety (i.e.

Lineage Analysis at Single-Cell Resolution by Twin-Spot MARCM with Lineage-Restricted Drivers.

Cell lineage analysis is primarily undertaken to understand cell fate specification and diversification along a cell lineage tree. Built with dual repressible markers, twin-spot mosaic analysis with repressible cell markers (MARCM) labels the two daughter cells made by a common precursor in distinct colors. The power of twin-spot MARCM to systematically subdivide complex lineages is exemplified in studies of Drosophila neural stem-cell lineages.

Role of mouse adenovirus type 1 E4orf6-induced degradation of protein kinase R in pathogenesis.

Protein kinase R (PKR) is an interferon-induced antiviral protein activated by autophosphorylation in response to double strand DNA (dsRNA) and other stimuli. Activated PKR causes translation inhibition and apoptosis, and it contributes to proinflammatory responses, cell growth, and differentiation. Mouse adenovirus type 1 (MAV-1) counteracts PKR by causing its degradation via a viral protein, early region 4 open reading frame 6 (E4orf6).

Dengue and Zika virus NS4B proteins differ in topology and in determinants of ER membrane protein complex dependency.

Flaviviruses utilize the cellular endoplasmic reticulum (ER) for all aspects of their lifecycle. Genome replication and other viral activities take place in structures called replication organelles (ROs), which are invaginations induced in the ER membrane. Among the required elements for RO formation is the biogenesis of viral nonstructural proteins NS4A and NS4B.

Systolic Blood Pressure and Pulse Pressure in Heart Failure: Pooled Participant-Level Analysis of 4 Trials.

Background: Hypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target <130 mm Hg. However, data supporting treatment to this target are limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.

Flaring of Protruding Coronary Stents Before Transcatheter Aortic Valve Replacement to Minimize Interaction-A Feasibility Study.

Background: Protruding coronary artery stents can adversely affect transcatheter aortic valve replacement (TAVR) procedure. Current evidence on the topic is limited.

Aims: We aim to study the clinical feasibility and safety of flaring of protruding coronary artery stents before TAVR to reduce interaction with transcatheter heart valves.

Discovery of SMD-3236: A Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers.

SMARCA2 is an attractive synthetic lethal target in human cancers with mutated, inactivated SMARCA4. We report herein the discovery of highly potent and selective SMARCA2 PROTAC degraders, as exemplified by SMD-3236, which was designed using a new, high-affinity SMARCA ligand and a potent VHL-1 ligand. SMD-3236 achieves DC < 1 nM and > 95% against SMARCA2 and >2000-fold degradation selectivity over SMARCA4.

Examining the Impact of Local Constraint Violations on Energy Computations in DFT.

This work examines the impact of locally imposed constraints in Density Functional Theory (DFT). Using a metric referred to as the extent of violation index (EVI), we quantify how well exchange-correlation functionals adhere to local constraints. Applying EVIs to a diverse set of molecules for GGA functionals reveals constraint violations, particularly for semi-empirical functionals.

Discovery of High-Affinity SMARCA2/4 Bromodomain Ligands and Development of Potent and Exceptionally Selective SMARCA2 PROTAC Degraders.

In the SWI/SNF chromatin-remodeling complex, the mutually exclusive catalytic ATPase subunits SMARCA2 and SMARCA4 proteins have a synthetic-lethal relationship. Selectively targeting SMARCA2 for degradation is a promising and new therapeutic strategy for human cancers harboring inactivated mutated SMARCA4. In this study, we report the design, synthesis, and biological evaluation of novel SMARCA2/4 ligands and our subsequent design of PROTAC degraders using high-affinity SMARCA ligands and VHL-1 ligands.

Clonal hematopoiesis JAKs up plaque formation.

Clonal hematopoiesis (CH) is a condition in which hematopoietic stem cells (HSCs) acquire mutations seen in leukemia. While individuals with CH generally do not show signs of hematologic disease, the condition becomes more common with age and correlates with age-related diseases, especially cardiovascular disease (CVD). JAK2 mutations in HSCs can lead to CH and correlate with atherosclerosis, but the condition has been difficult to study because of challenges modeling the mutant cells at very low frequency.

Overlapping DNA methylation changes in enhancers in clonal cytopenia of undetermined significance and myelodysplastic neoplasm patients with , , or mutations.

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Detecting metastatic potential of cancer through longitudinal vasculature imaging of biomaterial scaffold using non-invasive photoacoustic microscopy and optical coherence tomography.

Metastasis represents a stage in which the therapeutic objective changes from curing disease to prolonging survival, as detection typically occurs at advanced stages. Technologies for the early identification of disease would enable treatment at a lower disease burden and heterogeneity. Herein, we investigate the vascular dynamics within a synthetic metastatic niche as a potential marker of disease progression.

Health care systems and policies for older adults in Nepal: new challenges for a low-middle income country.

Background: Nepal, like other low- and middle-income countries, is experiencing a rapid increase in the number of older adults and the rate of aging in the population. This has increased the number of older adults with age-associated chronic illnesses, which in turn will escalate the demand for specialized healthcare and long-term care in Nepal. However, very little is known regarding the current healthcare system and health policies for older adults in Nepal.

Common Variable Immunodeficiency Associated With Noninfectious Pulmonary Complications and Its Treatment: Beyond Immunoglobulin Therapy.

Common variable immunodeficiency (CVID) is a type of primary immunodeficiency that presents as a heterogenous disorder characterized by hypogammaglobinemia, poor response to vaccines, recurrent sinopulmonary infections, and can have noninfectious systemic manifestations. We performed a single-center, retrospective, observational study of five patients with noninfectious complications of CVID. All patients had CVID as defined by the European Society of Immunodeficiencies criteria and had received intravenous immunoglobulin therapy.

Serum fatty acid profiles in systemic lupus erythematosus and patient reported outcomes: The Michigan Lupus Epidemiology & Surveillance (MILES) Program.

Introduction: Despite progress in systemic lupus erythematosus (SLE) treatment, challenges persist in medication adherence due to side effects and costs. Precision nutrition, particularly adjusting fatty acid intake, offers a cost-effective strategy for enhancing SLE management. Prior research, including our own, indicates that increased consumption of omega-3 polyunsaturated fatty acids (PUFAs) correlates with improved outcomes in SLE patients.

Subjective Well-Being among African Americans: Findings from the National Survey of American Life.

Life satisfaction and happiness are related but distinct assessments of life quality with established links to sociodemographic and health factors. Despite a rich literature on quality of life, there remains a paucity of research on this topic among African Americans. This investigation explored (1) the sociodemographic correlates of life satisfaction and happiness and (2) how life satisfaction and happiness are related to health factors and adversity-relevant life circumstances.

Protein engineering in the deep learning era.

Advances in deep learning have significantly aided protein engineering in addressing challenges in industrial production, healthcare, and environmental sustainability. This review frames frequently researched problems in protein understanding and engineering from the perspective of deep learning. It provides a thorough discussion of representation methods for protein sequences and structures, along with general encoding pipelines that support both pre-training and supervised learning tasks.

Bacterial abundance and diversity in 64-74 Ma subseafloor igneous basement from the Louisville Seamount Chain.

The aquifer in the subseafloor igneous basement is a massive, continuous microbial substrate, yet sparingly little is known about life in this habitat. The work to date has focused largely on describing microbial diversity in the young basement (<10 Ma), where the basaltic crust is still porous and fluid flow through it is active. Here, we test the hypothesis that microbial life exists in subseafloor basement >65 Ma using samples collected from the Louisville Seamount Chain via seafloor drilling.

Plexiform Fibromyxoma.

Context.—: Plexiform fibromyxomas are uncommon gastrointestinal neoplasms that have histologic and molecular features that overlap with other gastrointestinal mesenchymal tumors and present a diagnostic challenge for surgical pathologists.

Objective.