Results of ICE-Guided Isolation of the Superior Vena Cava With Pulsed Field Ablation.

Background: Earlier studies have documented the risk for sinoatrial node injury and phrenic nerve paralysis as complications following radiofrequency catheter ablation for electrical isolation of the superior vena cava (SVCI).

Objectives: The aim of this study was to assess the safety and feasibility of SVCI in patients with atrial fibrillation undergoing pulsed field ablation (PFA) METHODS: Six hundred sixteen consecutive patients undergoing PFA for pulmonary vein isolation plus SVCI were included in this multicenter analysis. Superior vena cava (SVC) ablation was performed under the continuous guidance of intracardiac echocardiography.

A nuanced scrutiny of the segmental renal artery spectral Doppler in "Pickering" the right diagnosis.

Approximately 5-10% of patients with hypertension have secondary hypertension. We describe a case of secondary hypertension from bilateral renal artery stenosis (RAS): "Pickering syndrome." This is a case of hypertension secondary to bilateral RAS which provides an opportunity to review secondary hypertension with a specific focus on RAS, in terms of when to consider work up, causes of secondary hypertension, diagnostic testing, and treatment.

Evidence-based Diagnosis and Treatment of Vasa Previa.

Vasa previa is an abnormality of the umbilical cord and fetal membranes that affects ∼1 in 1300 pregnancies. The diagnosis is made by visualization of velamentous fetal vessels coursing within the membranes over the cervix unprotected by Wharton jelly or placenta. When it is not diagnosed prenatally, it is associated with a high risk of fetal death.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Crystallographic Spin Torque Conductivity Tensor of Epitaxial IrO Thin Films for Oxide Spintronics.

Unconventional spin-orbit torques arising from electric-field-generated spin currents in anisotropic materials have promising potential for spintronic applications, including for perpendicular magnetic switching in high-density memory applications. Here, all the independent elements of the spin torque conductivity tensor allowed by bulk crystal symmetries for the tetragonal conductor IrO are determined via measurements of conventional (in-plane) anti-damping torques for IrO thin films in the high-symmetry (001) and (100) orientations. It is then tested whether rotational transformations of this same tensor can predict both the conventional and unconventional anti-damping torques for IrO thin films in the lower-symmetry (101), (110), and (111) orientations, finding good agreement.

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

Theoretical Study on the Kinetics of Secondary Oxygen Addition Reactions for N-Butyl Radicals.

Chemical kinetics for second oxygen addition reactions (·QOOH + O) of long-chain alkanes are of great importance in low-temperature combustion technologies. However, kinetic data for key reactions of ·QOOH + O systems are often difficult to obtain experimentally and are primarily estimated or calculated by using theoretical methods. In this work, barrier heights (BHs), reaction energies (Δs), and relative energies (REs) of stationary points for key reactions of two representative ·QOOH + O systems in the low-temperature oxidation of -butyl as well as pressure-dependent rate constants for the involved reactions are calculated with the high-level quantum chemical method CCSD(T)-F12b/CBS.

LD-transpeptidase-mediated cell envelope remodeling enables developmental transitions and survival in and .

and are two phylogenetically related bacterial pathogens that exhibit extreme intrinsic resistance when they enter into a dormancy-like state. This enables both pathogens to survive extended periods in growth-limited environments. Survival is dependent upon their ability to undergo developmental transitions into two phenotypically distinct variants, one specialized for intracellular replication and another for prolonged survival in the environment and host.

The Cutaneous Pathology of Erythromelalgia and Its Role in Establishing Critical Clues Regarding Pathogenesis.

Erythromelalgia, a rare cutaneous pain syndrome, is characterized by acral burning pain and flushing, often alleviated by cold and rest. Primary erythromelalgia is caused by gain-of-function mutations of genes encoding for sodium channels, resulting in hyperexcitability of pain signaling neurons. Autoimmunity and hematologic dyscrasias such as thrombocythemia have been implicated in secondary erythromelalgia.

Benefits of Cilostazol's Effect on Vascular and Neuropathic Complications Caused by Diabetes.

Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients' quality of life.

The Evolution of Match Running Performance in the Top Two Spanish Soccer Leagues: A Comparative Four-Season Study.

: This study uniquely examines the evolution of match running performance in official matches over four consecutive seasons (2019/2020-2022/23) within Spain's top two professional soccer leagues (LaLiga). By analyzing differences between competitive league standards (First Division vs. Second Division), this research provides critical insights into how competition levels influence physical performance trends over time.

Coupling high-throughput and modeling approaches to streamline early-stage process development for biologics.

Platforms have long been implemented for downstream process development of monoclonal antibodies (mAbs) to streamline development and reduce timelines. These platforms are also increasingly being used for other complex biologics modalities. While development has traditionally been conducted at the lab bench scale in a sequential manner, automated miniaturized and parallelized approaches like RoboColumns and resin plates have also been implemented for chromatographic screening.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Stipulations of cell and gene therapy and the ties to biomanufacturing.

Cell and gene therapy (CGT) products are emerging and innovative biopharmaceuticals that hold promise for treating diseases that are otherwise beyond the scope of conventional medicines. The evolution of CGT from a research idea to a promising therapeutic product is due to the complementary advancements across various scientific disciplines. First, the innovations and advancements in gene editing and delivery technology have provided fundamental tools to manipulate genes and cells for therapeutic pursuits.

Structural Characterization of the Platinum Nanoparticle Hydrogen-Evolving Catalyst Assembled on Photosystem I by Light-Driven Chemistry.

Directed assembly of abiotic catalysts onto biological redox protein frameworks is of interest as an approach for the synthesis of biohybrid catalysts that combine features of both synthetic and biological materials. In this report, we provide a multiscale characterization of the platinum nanoparticle (NP) hydrogen-evolving catalysts that are assembled by light-driven reductive precipitation of platinum from an aqueous salt solution onto the photosystem I protein (PSI), isolated from cyanobacteria as trimeric PSI. The resulting PSI-NP assemblies were analyzed using a combination of X-ray energy-dispersive spectroscopy (XEDS), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), small-angle X-ray scattering (SAXS), and high-energy X-ray scattering with atomic pair distribution function (PDF) analyses.

Interest in Injectable and Oral PrEP for HIV Prevention Among Women and Men Who Inject Drugs.

Background: People who inject drugs (PWID) are at increased risk for human immunodeficiency virus (HIV). Women who inject are a particularly vulnerable group. Preexposure prophylaxis (PrEP) is effective, but access and uptake has been limited.

Prescribing Psychostimulants for the Treatment of Stimulant Use Disorder: Navigating the Federal Legal Landscape.

Stimulant use disorder (StUD) is a rapidly growing concern in the United States, with escalating rates of death attributed to amphetamines and cocaine. No medications are currently approved for StUD treatment, leaving clinicians to navigate off-label medication options. Recent studies suggest that controlled prescription psychostimulants such as dextroamphetamine, methylphenidate, and modafinil are associated with reductions in self-reported stimulant use, craving, and depressive symptoms.

Tangential Versus Segmental Portomesenteric Venous Resection During Pancreatoduodenectomy for Pancreatic Cancer: An International Multicenter Cohort Study on Surgical and Oncological Outcome.

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement.

Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer include all degrees of PMV involvement, including cases where tangential PVR may not be a feasible approach, limiting the clinical applicability.

Methods: International retrospective study in 10 centers from 5 countries, including all consecutive patients after pancreatoduodenectomy with PVR for pancreatic cancer with ≤180° PMV involvement on cross-sectional imaging at diagnosis (2014-2020).

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Directed Acyclic Graphs in Decision-Analytic Modeling: Bridging Causal Inference and Effective Model Design in Medical Decision Making.

Our commentary proposes the application of directed acyclic graphs (DAGs) in the design of decision-analytic models, offering researchers a valuable and structured tool to enhance transparency and accuracy by bridging the gap between causal inference and model design in medical decision making.The practical examples in this article showcase the transformative effect DAGs can have on model structure, parameter selection, and the resulting conclusions on effectiveness and cost-effectiveness.This methodological article invites a broader conversation on decision-modeling choices grounded in causal assumptions.

Measuring the effects of motion corruption in fetal fMRI.

Irregular and unpredictable fetal movement is the most common cause of artifacts in in utero functional magnetic resonance imaging (fMRI), affecting analysis and limiting our understanding of early functional brain development. The accurate detection of corrupted functional connectivity (FC) resulting from motion artifacts or preprocessing, instead of neural activity, is a prerequisite for reliable and valid analysis of FC and early brain development. Approaches to address this problem in adult data are of limited utility in fetal fMRI.