Mitochondrial fatty acid oxidation regulates monocytic type I interferon signaling via histone acetylation.

Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1.

What Are the Implications of Choosing a TAVR-First Strategy in the Lifetime Management of Aortic Stenosis?: A Critical Review of TAVR-Explant- and Redo-TAVR.

Some patients with aortic stenosis may require multiple valve interventions in their lifetime, and choosing transcatheter aortic valve replacement (TAVR) as the initial intervention may be appealing to many. If their transcatheter heart valve degenerates later in life, most will hope to undergo redo-TAVR. However, if redo-TAVR is not feasible, some may have to undergo surgical explantation of their transcatheter heart valve (TAVR-explant).

Cryo-electron tomography pipeline for plasma membranes.

Cryo-electron tomography (cryoET) provides sub-nanometer protein structure within the dense cellular environment. Existing sample preparation methods are insufficient at accessing the plasma membrane and its associated proteins. Here, we present a correlative cryo-electron tomography pipeline optimally suited to image large ultra-thin areas of isolated basal and apical plasma membranes.

Evaluation of Real-Time Cardiovascular Flow MRI Using Compressed Sensing in a Phantom and in Patients With Valvular Disease or Arrhythmia.

Background: Real-time (RT) phase contrast (PC) flow MRI can potentially be used to measure blood flow in arrhythmic patients. Undersampled RT PC has been combined with online compressed sensing (CS) reconstruction (CS RT) enabling clinical use. However, CS RT flow has not been validated in a clinical setting.

Individualized transfusion decisions to minimize adverse cardiovascular outcomes in patients with acute myocardial infarction and anemia.

Background: Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes.

Methods: This study analyzed 3,447 (98.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Relationship between left ventricular shape and cardiovascular risk factors: comparison between the Multi-Ethnic Study of Atherosclerosis and UK Biobank.

Background: Statistical shape atlases have been used in large-cohort studies to investigate relationships between heart shape and risk factors. The generalisability of these relationships between cohorts is unknown. The aims of this study were to compare left ventricular (LV) shapes in patients with differing cardiovascular risk factor profiles from two cohorts and to investigate whether LV shape scores generated with respect to a reference cohort can be directly used to study shape differences in another cohort.

Endothelial cell (EC)-specific CTGF/CCN2 Expression Increases EC Reprogramming and Atherosclerosis.

Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques.

Diabetes mellitus and glymphatic dysfunction: Roles for oxidative stress, mitochondria, circadian rhythm, artificial intelligence, and imaging.

Diabetes mellitus (DM) is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe. DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death. Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles, programmed cell death, and circadian rhythm impairments.

A Scoping Review of Electronic Health Records-Based Screening Algorithms for Familial Hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a common genetic disorder that is strongly associated with premature cardiovascular disease. Effective diagnosis and appropriate treatment of FH can reduce cardiovascular disease risk; however, FH is underdiagnosed. Electronic health record (EHR)-based FH screening tools have been previously described to enhance the detection of FH.

Focusing on antimicrobial resistant infections -are we missing the forest for the trees and the patients for pathogens?

Antimicrobial resistance (AMR) is a challenge because it is associated with worse patient outcomes. To solve the problem will take development of interventions and policies which improve patient outcomes by prolonging survival, improving patient symptoms, function and quality of life. Logically, we should look to focusing resources in areas that would have the greatest impact on public health.

Unraveling the dynamics of B7-H3-targeting therapeutic antibodies in cancer through PET imaging and antibody pharmacokinetics.

B7-H3, an immunomodulatory protein overexpressed in many cancers, is associated with tumor aggressiveness and poor prognosis, making it a crucial target for imaging to elucidate its role in cancer progression and guide therapeutic interventions. This study employed PET imaging to investigate the in vivo delivery and pharmacokinetics of two anti-B7-H3 antibodies, Ab-1 and Ab-2, in mouse xenograft models with varying B7-H3 expression levels. The antibodies were radiolabeled with [Zr]Zr and evaluated through PET imaging, biodistribution studies, and in vitro assays to assess binding, tumor uptake, and retention.

Comparing the Introduction and Implementation of Noninvasive Prenatal Testing (NIPT) in Japan, the Netherlands, and the United States: An Integrative Review.

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

HDL-associated vitamin D binding protein levels are inversely associated with necrotic plaque burden in psoriasis.

Background And Aims: Vitamin D binding protein (DBP) serves a dual function as a vitamin D carrier and actin scavenger. Free DBP is present in high concentrations in serum, while a smaller pool is bound to lipoproteins like HDL and VLDL. The role of DBP's interaction with lipoproteins remains unclear.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Heart-brain microvascular MRI study: protocol for a multicentre, observational, cohort study in the UK assessing associations between small vessel disease of the heart and brain.

Introduction: Ischaemic heart disease (IHD) and cerebrovascular disease are leading causes of morbidity and mortality worldwide. Cerebral small vessel disease (CSVD) is a leading cause of dementia and stroke. While coronary small vessel disease (coronary microvascular dysfunction) causes microvascular angina and is associated with increased morbidity and mortality.

Microbiota-derived proteins synergize with IL-23 to drive IL22 production in model type 3 innate lymphoid cells.

Microbiota-induced production of IL-22 by type 3 innate lymphoid cells (ILC3) plays an important role in maintaining intestinal health. Such IL-22 production is driven, in part, by IL-23 produced by gut myeloid cells that have sensed select microbial-derived mediators. The extent to which ILC3 can directly respond to microbial metabolites via IL-22 production is less clear, in part due to the difficulty of isolating and maintaining sufficient numbers of viable ILC3 ex vivo.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance.

The homolog of Sjögren's Syndrome Nuclear Antigen 1 is required for the structural integrity of the centriole and bipolar mitotic spindle assembly.

Centrioles play central roles in ciliogenesis and mitotic spindle assembly. Once assembled, centrioles exhibit long-term stability, a property essential for maintaining numerical control. How centriole stability is achieved and how it is lost in certain biological contexts are still not completely understood.