Repeat Procedures After Pulsed Field Ablation for Atrial Fibrillation: MANIFEST-REDO Study.

Background: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centers and involved a limited number of operators. The electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF are incompletely understood.

Nucleic acid recognition during prokaryotic immunity.

Parasitic elements often spread to hosts through the delivery of their nucleic acids to the recipient. This is particularly true for the primary parasites of bacteria, bacteriophages (phages) and plasmids. Although bacterial immune systems can sense a diverse set of infection signals, such as a protein unique to the invader or the disruption of natural host processes, phage and plasmid nucleic acids represent some of the most common molecules that are recognized as foreign to initiate defense.

Molecular determinants of condensate composition.

Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces.

Metabolism-driven chromatin dynamics: Molecular principles and technological advances.

Cells integrate metabolic information into core molecular processes such as transcription to adapt to environmental changes. Chromatin, the physiological template of the eukaryotic genome, has emerged as a sensor and rheostat for fluctuating intracellular metabolites. In this review, we highlight the growing list of chromatin-associated metabolites that are derived from diverse sources.

A tale of two strands: Decoding chromatin replication through strand-specific sequencing.

DNA replication, a fundamental process in all living organisms, proceeds with continuous synthesis of the leading strand by DNA polymerase ε (Pol ε) and discontinuous synthesis of the lagging strand by polymerase δ (Pol δ). This inherent asymmetry at each replication fork necessitates the development of methods to distinguish between these two nascent strands in vivo. Over the past decade, strand-specific sequencing strategies, such as enrichment and sequencing of protein-associated nascent DNA (eSPAN) and Okazaki fragment sequencing (OK-seq), have become essential tools for studying chromatin replication in eukaryotic cells.

Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens.

A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential.

Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome.

The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood.

Ligand-based cheminformatics and free energy-inspired molecular simulations for prioritizing and optimizing G-protein coupled receptor kinase-6 (GRK6) inhibitors in multiple myeloma treatment.

Multiple myeloma (MM) is the second most frequently diagnosed hematological malignancy, presenting limited treatment options with no curative potential and significant drug resistance. Recent studies involving genetic knockdown established the crucial role of GRK6 in upholding the viability of MM cells, emphasizing the need to identify potential inhibitors. Computational exploration of GRK6 inhibitors has not been attempted previously.

Dissemination of genes associated with antibiotic resistance and bacterial virulence during ecosystem succession in two Tibetan glacier forefields.

The release of pathogens and DNA from the cryosphere (glacier, permafrost, and, sea ice) has become a new threat to society and environment. Due to enhanced glacier retreat, the size of glacier forefields has greatly expanded. Herein, we used a combination of metagenomic and metatranscriptomic methods and adopted a sequence-based approach to investigate the distribution and changing patterns of virulence factor genes (VFGs) and antibiotic resistance genes (ARGs) in two glacier forefields.

Evaluating sources of mercury in Canada's Mackenzie River.

Arctic rivers may be the largest net sources of mercury (Hg) to the Arctic Ocean, yet riverine sources of Hg remain poorly characterized compared to atmospheric processes. This article reviews the current state of knowledge on Hg inputs to the Mackenzie River and Valley in Northern Canada from six point and non-point sources. Point sources include the locations of mines, fossil fuel extraction facilities, and retrogressive permafrost thaw slumps.

Molecular-level exploration of spatiotemporal dynamics of fluvial particulate organic carbon sources during storm events: Using a high-temporal resolution multi-biomarker approach.

Identifying the origins of storm fluvial particulate organic carbon (POC) provides information about the hydrological connectivity within the river corridor and the roles of the land-stream interface in the carbon cycle. However, current understanding of storm-induced POC source dynamics is constrained by observations limited in space and time. This study presents a unique approach integrating higher spatial and temporal resolution sampling with a multi-biomarker analysis to better understand POC source dynamics across scales.

Combining steric exclusion with anion exchange - development of a universal and scalable adeno-associated virus downstream process.

Adeno-associated viruses (AAV) are among the leading vectors for in vivo gene therapy. The purification of AAV remains a bottleneck as it typically requires multiple individual process steps, often resulting in product loss and high costs. Current downstream processes are usually serotype-specific and rely primarily on expensive affinity resins.

Influence of positive consequences on subsequent incentive ratings and drinking quantity.

Alcohol use is prevalent among young adults, with significant rates of binge drinking and frequent reports of both positive and negative consequences. The current study investigates how positive drinking consequences influence subsequent incentives ratings and drinking behavior. Utilizing mobile daily diary data from 104 young adults over two weeks (event N = 507), we assessed the impact of event-specific positive consequences on future incentive ratings and drinking quantity.

An Examination of predictors of prospective changes in self-reported drinker identity and changes in drinker identity as a predictor of changes in alcohol use and associated consequences.

Purpose: Self-reported drinker identity, the extent to which one views oneself as a drinker, is associated with alcohol consumption and related harms in young adults. The current study examined changes in self-reported drinker identity, theoretically relevant factors associated with drinker identity development, and drinker identity's association with changes in drinking and alcohol-related consequences. We hypothesized that drinker identity would increase over time; theoretically relevant factors would be significantly and positively associated with that increase, and increases in drinking identity would be associated with elevated drinking and related consequences.

Phase angle between dim light melatonin onset and sleep timing during residential treatment prospectively predicts obsessive-compulsive symptoms.

The relation between obsessive-compulsive disorder (OCD) and circadian rhythm disturbance has been increasingly acknowledged in recent years. While prior clinical studies have utilized patients' self-reported sleep behaviors, there is a need to also explore the measurable, biological aspects of circadian rhythms. The current study has two aims: first, to describe the biological circadian rhythms of individuals with OCD seeking intensive residential treatment, including their relationship with self-reported measures of sleep and OCD symptoms; and second, to examine longitudinal associations between biological circadian rhythms and OCD symptom severity during the course of residential treatment.

Novel c.221+1dup pathogenic variant in AGK gene linked to Sengers syndrome.

Sengers Syndrome (SS) is a rare autosomal recessive mitochondrial disorder caused by mutations in the acylglycerol kinase (AGK) gene on chromosome 7, also known as cardiomyopathic mitochondrial DNA depletion syndrome (MTDPS10). This disorder disrupts mitochondrial DNA function and energy metabolism, presenting with symptoms such as congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Previous research has shown SS affects oxidative phosphorylation and mitochondrial respiration, implicating the TIM22 complex and carrier import.

The effect of the foreign body response on drug elution from subdermal delivery systems.

Contrasting findings are presented in the literature regarding the influence of foreign body response (FBR) on drug release from implantable drug delivery systems. To this end, here we sought direct evidence of the effect of the fibrotic tissue on subcutaneous drug release from long-acting drug delivery implants. Specifically, we investigated the pharmacokinetic impact of fibrotic encapsulation on a small molecule drug, islatravir (293 Da), and a large protein, IgG (150 kDa), administered via biocompatible implants.

Protecting monoclonal antibodies via competitive interfacial adsorption of nonionic surfactants.

Hypothesis: Bioengineered monoclonal antibodies (mAbs) have gained significant recognition as medical therapies. However, during processing, storage and use, mAbs are susceptible to interfacial adsorption and desorption, leading to structural deformation and aggregation, and undermining their bioactivity. To suppress antibody surface adsorption, nonionic surfactants are commonly used in formulation.

A systematic review of participant diversity in psychedelic-assisted psychotherapy trials.

A lack of diverse and representative participant samples in mental health intervention research perpetuates mental health disparities. This issue has become a salient concern in studies of psychedelic-assisted psychotherapy (PAT), which is emerging as a promising mental health intervention. This systematic review evaluates the reporting, representation, and analysis of participant sociodemographic characteristics in randomized controlled trials (RCTs) of PAT.

Demographic trends of boxing-associated fractures over 10 years.

Background: Boxing is a sport well-known for the risk of injury. However, the epidemiology of boxing-associated fractures has not been well studied. This study aims to report the characteristics of boxing fractures that lead to presentation to the emergency room and evaluate the demographics and practices of the patients to prevent these injuries.

Generation of induced pluripotent stem cell line from a patient with long COVID.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection, leads to vascular dysfunction, which contributes to the chronic multi-organ damage often seen in affected patients. Long COVID, a global health concern is associated with increased thrombotic risk, also known as COVID-19-associated coagulopathy (CAC). Here, we derived an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a long COVID patient.

Gamma knife versus linear accelerator thalamotomy for essential tremor and Parkinson's disease: A systematic review and meta-analysis.

Background: Tremor, either in patients with Essential Tremor (ET) or Parkinson's disease (PD), constitutes the most common movement disorder. Stereotactic radiosurgery using Gamma Knife (GK) and linear accelerator (LINAC) systems, is an effective, incisionless treatment modality for ET and PD. Although these technologies have been used clinically since the 1990's, most studies have focused on GK, and efficacy, safety and time to treatment effect (latency) of GK and LINAC have not been compared.

Catching the glucocorticoid receptor in the act: Lessons from fluorescence fluctuation methods.

Technological innovation can drive scientific inquiry by allowing researchers to answer questions that were once out of reach. Eukaryotic mRNA synthesis was not so long ago thought of as a deterministic, sequential process in which transcriptional regulators and general transcription factors assemble in an orderly fashion into chromatin to, ultimately, activate RNA polymerase II. Advances in fluorescence microscopy techniques have revealed a much more complex scenario, wherein transcriptional regulators dynamically engage with chromatin in a more stochastic, probabilistic way.