Simplifying clinical use of TCGA molecular subtypes through machine learning models.

In this issue of Cancer Cell, Ellrott et al. present machine learning models to classify samples into The Cancer Genome Atlas molecular subtypes using compact sets of genomic features. These validated, ready-to-use models are publicly available, although some clinical hurdles need to be cleared before they are fully implemented.

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.

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.

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.

Mucosal immunity elicited by a human-Fcγ receptor-I targeted intranasal vaccine platform enhances resistance against nasopharyngeal colonization of Streptococcus pneumoniae and induces broadly protective immunity against respiratory pathogens.

The development of safe and effective mucosal vaccines are hampered by safety concerns associated with adjuvants or live attenuated microbes. We previously demonstrated that targeting antigens to the human-Fc-gamma-receptor-I (hFcγRI) eliminates the need for adjuvants, thereby mitigating safety concerns associated with the mucosal delivery of adjuvant formulated vaccines. Here we evaluated the role of the route of immunization in the mucosal immunity elicited by the hFcγRI-targeted vaccine approach.

Association of experienced stigma in healthcare settings with health outcomes among Black women living with HIV: Mediating roles of internalized stigma, anticipated stigma, and trust in HIV care.

Background: Black women living with HIV (WLHIV) often have suboptimal ART adherence due to a multitude of social and structural barriers, including HIV-related stigma. Trust in healthcare providers plays a significant role in adhering to ART and is likely lower among Black WLHIV compared to their White counterparts. This study examined the relationship between experienced stigma in healthcare settings and ART adherence and viral suppression through anticipated stigma in healthcare settings, internalized stigma, and medical mistrust.

Cognitive and behavioral effects of perampanel 4 mg daily dose.

Objective: The neuropsychological adverse effects of antiseizure medications (ASMs) influence the tolerability, and in turn effectiveness of these medications, which can occur in a dose-dependent fashion. In this study, we examine the neuropsychological effects of perampanel (PER) at 4 mg daily as this dose has not been previously assessed with objective cognitive tests.

Methods: The study was originally designed to assess (1) effects of perampanel at 4 mg using different titration rates, and (2) habituation over time.

Vitamin D-related genetic variants and prostate cancer risk in Black men.

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Adjuvant radiation therapy is not associated with a survival benefit after R0 resection in non-metastatic adrenocortical carcinoma.

The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized for those who undergo initial R0 surgical resection. Patients in the NCDB who underwent R0 resection were placed into two cohorts - those who underwent adjuvant RT and those who did not. 388 patients were identified with 51 receiving RT.

Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial.

Background: Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches.

Characterizing Cardiac Adipose Tissue in Post-AMI Patients via CT Imaging: A Comparative Cross-sectional Study.

Aims: To identify differences in CT-derived perivascular (PVAT) and epicardial adipose tissue (EAT) characteristics that may indicate inflammatory status differences between post-treatment acute myocardial infarction (AMI) and stable coronary artery disease (CAD) patients.

Methods And Results: A cohort of 205 post-AMI patients (age 59.8±9.

Semi-supervised learning from small annotated data and large unlabeled data for fine-grained Participants, Intervention, Comparison, and Outcomes entity recognition.

Objective: Extracting PICO elements-Participants, Intervention, Comparison, and Outcomes-from clinical trial literature is essential for clinical evidence retrieval, appraisal, and synthesis. Existing approaches do not distinguish the attributes of PICO entities. This study aims to develop a named entity recognition (NER) model to extract PICO entities with fine granularities.

Nipple Position and Clinical Outcomes Following Nipple-Sparing Mastectomy: An Examination of Prepectoral and Subpectoral Implant-Based Reconstruction Using 3D Imaging.

Background: Nipple-sparing mastectomy (NSM) has become increasingly popular in recent years. However, the impact of prepectoral versus subpectoral implant reconstruction on nipple position, clinical outcomes, and patient-reported outcomes (PROs) after NSM remains unknown.

Objective: We hypothesized that prepectoral reconstruction would lead to a more anatomic nipple position and improved clinical outcomes and PROs as compared to subpectoral reconstruction following NSM.

Nitrous oxide production via enzymatic nitroxyl from the nitrifying archaeon .

Ammonia oxidizing archaea (AOA) are among the most abundant microorganisms on earth and are known to be a major source of nitrous oxide (NO) emissions, although biochemical origins of this NO remain unknown. Enzymological details of AOA nitrogen metabolism are broadly unavailable. We report the recombinant expression, purification, and characterization of a multicopper oxidase, Nmar_1354, from the AOA .

Collagen turnover during cervical remodeling involves both intracellular and extracellular collagen degradation pathways.

Reproductive success requires accurately timed remodeling of the cervix to orchestrate the maintenance of pregnancy, the process of labor, and birth. Prior work in mice established that a combination of continuous turnover of fibrillar collagen and reduced formation of collagen cross-links allows for the gradual increase in tissue compliance and delivery of the fetus during labor. However, the mechanism for continuous collagen degradation to ensure turnover during cervical remodeling is still unknown.

Measuring Talker Age Estimates Through Crowdsourced Listeners' Ratings: A Pilot Study for Voice Research.

Purpose: Most auditory-perceptual voice research utilizes the judgments of trained listeners rather than everyday listeners with no previous training in speech pathology. Online crowdsourcing of behavioral data from untrained participants is rapidly increasing in popularity but has yet to be a common procedure for auditory-perceptual studies of the voice. The objective of this pilot study was to assess the functionality of this model for judgments of voice by using an online experiment platform to replicate a lab-based, voice-specific age estimation study.

Psychology of Planning.

Planning has been studied in different fields of psychology, including cognitive, developmental, personality, social, and work and organizational research. This article looks at the planning process through the lens of motivation science, and asks the question, What kind of planning can help people reach their goals? We focus on the strategy of making if-then plans (also known as forming implementation intentions). We discuss what kinds of cognitive performance can be enhanced by if-then planning (e.

Cannabis vaping elicits transcriptomic and metabolomic changes in inflammatory, oxidative stress and cancer pathways in human bronchial epithelial cells.

The increasing shift from cannabis smoking to cannabis vaping is largely driven by the perception that vaping to form an aerosol represents a safer alternative to smoking and is a form of consumption appealing to youth. Herein, we compared the chemical composition and receptor-mediated activity of cannabis smoke extract (CaSE) to cannabis vaping extract (CaVE) along with the biological response in human bronchial epithelial cells. Chemical analysis using HPLC and GC/MS revealed that cannabis vaping aerosol contained fewer toxicants than smoke; CaSE and CaVE contained teratogens, carcinogens, and respiratory toxicants.

Rise of the beta-lactams: a retrospective, comparative cohort of oral beta-lactam antibiotics as step-down therapy for hospitalized adults with acute pyelonephritis.

Objective: The aim of this study was to determine if oral beta-lactam therapy is non-inferior to alternative therapy at discharge following inpatient treatment with an IV cephalosporin for acute pyelonephritis.

Design: Institutional Review Board (IRB)-approved, multicenter, retrospective, non-inferiority cohort (15% non-inferiority margin).

Setting: Six hospitals within two healthcare systems.