Critical Care Management of Acute Venous Thromboembolism: Integrating Pharmacotherapy, Thrombectomy, and Temporary Mechanical Support.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, carries significant morbidity and mortality risks, and is conventionally managed with anticoagulation. In recent years, notable progress has been made in the therapeutic options available for the acute treatment of VTE. The heterogeneity within pulmonary embolism, spanning a wide spectrum of risks, underscores the critical need for precise risk stratification, particularly in identifying individuals prone to right heart failure and increased mortality.

Obesity and the development of Parkinson's disease within the Framingham Heart study cohort.

Objective: To determine the role of obesity in the development of Parkinson's disease (PD).

Background: Obesity has been reported to be both a risk factor for PD, as well as potentially protective. The Framingham Heart Study (FHS) is a multigenerational longitudinal cohort study that was started in 1948, which is well-known for its cardiovascular health studies.

A Scoping Review on Sex and Gender Differences in the Adverse Health Outcomes of Individuals with Sickle Cell Trait.

Although there is an emerging body of evidence that addresses the adverse health outcomes of individuals with sickle cell trait (SCT), it is not clear if the findings are generalizable from a sex and gender perspective. The purpose of this scoping review was to complete an assessment of main concepts, identify knowledge gaps, and determine the potential value of conducting an eventual systematic review. The research question guiding this scoping review is: In SCT individuals with adverse health outcomes, what is known about sex and gender differences? We conducted a scoping review of research on SCT from 2016 to 2022 across five databases, with 36 research studies included in the review.

Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.

In recent years, advances in artificial intelligence (AI) have transformed structural biology, particularly protein structure prediction. Though AI-based methods, such as AlphaFold (AF), often predict single conformations of proteins with high accuracy and confidence, predictions of alternative folds are often inaccurate, low-confidence, or simply not predicted at all. Here, we review three blind spots that alternative conformations reveal about AF-based protein structure prediction.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Endonuclease G promotes hepatic mitochondrial respiration by selectively increasing mitochondrial tRNA production.

Mitochondrial endonuclease G (EndoG) contributes to chromosomal degradation when it is released from mitochondria during apoptosis. It is presumed to also have a mitochondrial function because EndoG deficiency causes mitochondrial dysfunction. However, the mechanism by which EndoG regulates mitochondrial function is not known.

Association of Mycobacterium tuberculosis aerosolization and HIV coinfection in the index case with T cell responses in household contacts.

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.

Effects of seven days' fasting on physical performance and metabolic adaptation during exercise in humans.

Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.

Deep learning-based aberration compensation improves contrast and resolution in fluorescence microscopy.

Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations.

Baseline Smartphone App Survey Return in the Electronic Framingham Heart Study Offspring and Omni 1 Study: eCohort Study.

Background: Smartphone apps can be used to monitor chronic conditions and offer opportunities for self-assessment conveniently at home. However, few digital studies include older adults.

Objective: We aim to describe a new electronic cohort of older adults embedded in the Framingham Heart Study including baseline smartphone survey return rates and survey completion rates by smartphone type (iPhone [Apple Inc] and Android [Google LLC] users).

Tsg101 mimicry of canonical E2 enzymes underlies its role in ubiquitin signaling.

Tsg101 is a highly conserved protein best known as an early-functioning component of cellular ESCRT machinery participating in recognition, sorting, and trafficking of cellular cargo to various intracellular destinations. It shares sequence and structural homology to canonical ubiquitin-conjugating (E2) enzymes and is linked to diverse events regulated by Ub signaling. How it might fulfill these roles is unclear.

Insights into the renal pathophysiology in Hermansky-Pudlak syndrome-1 from urinary extracellular vesicle proteomics and a new mouse model.

Hermansky-Pudlak syndrome type 1 (HPS-1) is a rare, autosomal recessive disorder caused by defects in the biogenesis of lysosome-related organelles complex-3 (BLOC-3). Impaired kidney function is among its clinical manifestations. To investigate HPS-1 renal involvement, we employed 1D-gel-LC-MS/MS and compared the protein composition of urinary extracellular vesicles (uEVs) from HPS-1 patients to normal control individuals.

Modeling predicts facile release of nitrite but not nitric oxide from the thionitrate CHSNO with relevance to nitroglycerin bioactivation.

Nitroglycerin is a potent vasodilator in clinical use since the late 1800s. It functions as a prodrug that is bioactivated by formation of an enzyme-based thionitrate, E-Cys-NO. This intermediate reportedly decomposes to release NO and NO but their relative yields remain controversial.

Orthologs of and impact sleep in mice.

Model organisms such as are powerful tools to study the genetic basis of sleep. Previously, we identified the genes and using selective breeding for long and short sleep duration in an outbred population of . is a transcription factor that is part of the epidermal growth factor receptor signaling pathway, while is involved in proline and arginine metabolism.

Gene therapy for sickle cell disease: recent advances, clinical trials and future directions.

Sickle cell disease (SCD) is the most common inherited blood disorder worldwide, impacting millions and imposing severe healthcare challenges, particularly in resource-limited regions. Current treatments have variable efficacy and require lifelong adherence. Allogeneic Hematopoietic Stem Cell Transplantation can be curative but comes with significant side effects and limited donor availability limits its widespread applicability.

A transcription network underlies the dual genomic coordination of mitochondrial biogenesis.

Mitochondrial biogenesis requires the expression of genes encoded by both the nuclear and mitochondrial genomes. However, aside from a handful transcription factors regulating specific subsets of mitochondrial genes, the overall architecture of the transcriptional control of mitochondrial biogenesis remains to be elucidated. The mechanisms coordinating these two genomes are largely unknown.

Haemodynamic and hyperaemic effects of adenosine in patients with atrial fibrillation undergoing quantitative myocardial perfusion cardiovascular magnetic resonance.

Aims: Patients with atrial fibrillation (AF) are thought to have an attenuated response to adenosine during vasodilator stress testing. We sought to investigate the haemodynamic and hyperaemic effects of adenosine in patients with AF undergoing adenosine-stress cardiovascular magnetic resonance (CMR) assessment.

Methods And Results: We retrospectively examined 318 patients referred for clinical adenosine-stress CMR (AF = 158, sinus rhythm [SR] = 160).

Generation of induced pluripotent stem cell lines TRNDi037-A and TRNDi038-A from two patients with Alagille syndrome carrying heterozygous JAG1 mutations.

Human induced pluripotent stem cell (iPSC) lines TRNDi037-A and TRNDi038-A were generated from the lymphoblastoid cell lines (LCL) of two patients with different heterozygous JAG1 variants resulting in Alagille syndrome (ALGS). ALGS is a rare genetic disease of haploinsufficiency that affects the formation of the bile duct, in addition to other symptoms. These ALGS iPSC lines can be used to model ALGS and aid in the identification of therapeutics to treat patients with ALGS.

Obesity modulates NK cell activity via LDL and DUSP1 signaling for populations with adverse social determinants.

African American (AA) women are disproportionately affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) that contribute to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair NK cells. As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK cell dysfunction related to obesity and hyperlipidemia in AA women from underresourced neighborhoods.

Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.

Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.

Multimorbidity in patients with atrial fibrillation and community controls: A population-based study.

Background: Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented.

Methods: The prevalence of 18 chronic conditions (6 cardiometabolic, 7 other somatic, 5 mental health) was obtained in patients with new-onset AF from 2013-2017 from a 27-county region and controls matched 1:1 on age, sex, and county of residence. For AF patients and controls separately, clustering of conditions and co-occurrence beyond chance was estimated (using the asymmetric Somers' D statistic), overall and for ages <65, 65-74, 75-84, and ≥85 years.

Multilevel Mediators on the Associations of Neighborhood Social Environmental Factors and Severity of Metabolic Syndrome: The Jackson Heart Study.

Background: Neighborhood characteristics serve as risk factors for metabolic syndrome (MetS). However, the intermediary factors linking this relationship remain understudied. Thus, we investigated the sex-specific mediating role of C-reactive protein, physical activity (PA), and perceived stress in the associations of perceived neighborhood social environment (PNSE) with MetS severity among Black adults.