Reporting of immune-related adverse events in US Food and Drug Administration approvals of immune checkpoint inhibitors.

Background: Predicting the occurrence of immune-related adverse events (irAEs) related to immune checkpoint inhibitors (ICI) is complex. Monitoring of irAEs is critical as toxicities cause morbidity and impact quality of life. Thus, we systematically evaluated the patterns and consistency of irAEs reporting in trials leading to US Food and Drug Administration (FDA) ICI approvals.

Pars plana vitrectomy with tissue plasminogen activator for traumatic submacular hemorrhage.

Aim: To evaluate visual outcomes of pars plana vitrectomy (PPV) combined with tissue plasminogen activator (tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage (SMH) in a cohort of closed-globe trauma patients.

Methods: A retrospective, multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted. The primary outcome measure was the change in Snellen visual acuity.

The dimerization domain of SARS-CoV-2 nucleocapsid protein is partially disordered and forms a dynamic high-affinity dimer.

The SARS-CoV-2 nucleocapsid (N) drives the compaction and packaging of the viral genome. Here, we focused on quantifying the mechanisms that control dimer formation utilizing single-molecule Förster resonance energy transfer to investigate the conformations and energetics of the dimerization domain in the context of the full-length protein. Under monomeric conditions, we observed significantly expanded configurations of the dimerization domain (compared to the folded dimer structure), which is consistent with a dynamic conformational ensemble.

Psychometric Properties of the Afrocentric Self-Regard Scale (ASRS): A Validation Study with Black Emerging Adults.

This study aimed to cross-validate the Afrocentric Self-Regard Scale (ASRS), which was previously developed and assessed in a sample of Black American adolescents. However, this study was conducted with a representative sample of 619 emerging Black adults aged 18-29 years. Participants completed a survey that included the ASRS and measured African heritage connections, Afro-cultural orientation norms, internalized negative stereotypes, career aspirations, anxiety, and depression.

Bayesian additive tree ensembles for composite quantile regressions.

In this paper, we introduce a novel approach that integrates Bayesian additive regression trees (BART) with the composite quantile regression (CQR) framework, creating a robust method for modeling complex relationships between predictors and outcomes under various error distributions. Unlike traditional quantile regression, which focuses on specific quantile levels, our proposed method, composite quantile BART, offers greater flexibility in capturing the entire conditional distribution of the response variable. By leveraging the strengths of BART and CQR, the proposed method provides enhanced predictive performance, especially in the presence of heavy-tailed errors and non-linear covariate effects.

Covalent Irreversible Inhibitors of Tetracycline Destructases.

Next-generation tetracycline antibiotics are threatened by an emerging resistance mechanism ─ enzymatic inactivation. The relevant enzymes ─ tetracycline destructases (TDases) ─ are structural homologues of class A flavin monooxygenase (FMO) that oxidize tetracycline antibiotics, leading to various inactive degradation products. Small molecule inhibitors of antibiotic-inactivating enzymes are critical clinical therapeutics used to manage bacterial resistance with combination therapy.

Trends in Surgical and Endoscopic Resection Intervention for Non-malignant Colorectal Polyps Over the Last Decade: A Nationwide Analysis.

Introduction: Surgery for non-malignant colorectal polyps is rarely performed and is considered if endoscopic removal is not feasible or unsuccessful, especially since the development of enhanced endoscopic mucosal resection (EMR) techniques and the advancements in endoscopic submucosal dissection (ESD). We aimed to evaluate the trend of surgery and endoscopic resection in patients with non-malignant colorectal polyps from 2014 to 2024.

Methods: We conducted a retrospective cohort study in the United States using the TriNetX research network to identify patients with non-malignant colorectal polyps who underwent surgery.

Direct aspiration versus stent retriever as First-line thrombectomy techniques for acute Basilar artery occlusions: an updated systematic review and Meta-Analysis.

Background: Endovascular thrombectomy is the primary treatment for acute basilar artery occlusion (BAO), with direct aspiration (DA) and stent retriever (SR) as the main techniques. This updated meta-analysis aims to compare these two techniques in terms of efficacy and safety outcomes.

Methods: A search was performed across PubMed, Embase, and Cochrane databases on December 23, 2024.

Uncertainty Quantification of Network Inference with Data Sufficiency.

Network inference, which involves reconstructing the connectivity structure of a network from recorded data, is essential for broadening our understanding of physical, biological, and chemical systems. Although data-driven network inference algorithms have made significant strides in recent years, determining how much data is required so that the inferred network topology faithfully mirrors the underlying network remains an essential but often overlooked subject. In this paper, we present a statistical method to determine whether the recorded data carries sufficient variability to ensure an accurate reconstruction of the true network topology.

Meaning maps predict reaction time in change detection.

To detect changes in our visual environments, the visual system compares pre-and post-change representations maintained in active working memory. Previous research has suggested that change detection is primarily informed by high-level semantics in naturalistic scenes. Here, across two experiments, we used meaning maps - a data driven method to measure the visual semantic information in naturalistic scenes - to investigate whether semantic features predicted visual change detection in a flicker paradigm.

Conventional versus advanced imaging selection for endovascular treatment of basilar artery occlusion strokes.

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

Patients And Methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry.

The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport.

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription.

Vagal Oxytocin Receptors as Molecular Targets in Gut-Brain Signaling: Implications for Appetite, Satiety, Obesity, and Esophageal Motility-A Narrative Review.

Oxytocin (OT), traditionally associated with reproduction and social bonding, has emerged as a key modulator of gastrointestinal (GI) physiology and appetite regulation behavior through its actions within the gut-brain axis. Central to this regulation are vagal oxytocin receptors (VORs), which are located along vagal afferent and efferent fibers and within brainstem nuclei such as the nucleus tractus solitarius and dorsal motor nucleus of the vagus. This review presents a comprehensive synthesis of current knowledge on the anatomical distribution, molecular signaling, developmental plasticity, and functional roles of VORs in the regulation of GI motility, satiety, and energy homeostasis.

Individual Differences in Student Learning: A Comparison Between the Student Approaches to Learning and Concept-Building Frameworks.

In cognitive science and education research, learning has been described to occur at surface and deep levels. Learners are thought to orient more toward one of these approaches to learning versus the other. In cognitive science, this has been assessed with a concept-building framework using objective function learning tasks to classify students as exemplar (surface) or abstraction (deep) learners.

Musical Distractions: Music-Based Rhythmic Auditory Stimulation Fails to Improve Gait in Huntington's Disease.

Background/objectives: Huntington's disease (HD) is a neurodegenerative disorder involving the basal ganglia and is characterized by psychiatric, cognitive, and movement dysfunction, including gait and balance impairment. Given the limited efficacy of pharmacological treatments for HD motor symptoms, nonpharmacological approaches like rhythmic auditory stimulation are being explored. This study aims to describe walking performance in people with HD during rhythmic auditory stimulation using external musical cues and internal singing cues.

Shoreline wave breaking strongly enhances the coastal sea spray aerosol population: Climate and air quality implications.

Sea spray aerosol (SSA) emission is a major source of atmospheric aerosols, influencing global climate and coastal air quality. Much of our knowledge about SSA derives from coastal observations near shorelines, but whether and when these observations accurately represent open oceans remain unclear. Here, we show that strong nearshore SSA production during high-wave periods greatly enhances downwind cloud condensation nuclei (CCN) and aerosol mass concentrations.

Ciliated cells promote high infectious potential of influenza A virus through the efficient intracellular activation of hemagglutinin.

Influenza viruses utilize host proteases to activate the viral fusion protein, hemagglutinin (HA), into its fusion-competent form. Although proteolytic activation of HA is essential for virus replication, the cell-type dependence of HA activation within the airway epithelium and the subcellular location(s) in which it occurs are not well established. To address these questions, we investigated the proteolytic activation of HA in differentiated human airway epithelial cells using contemporary and historical H1N1 and H3N2 strains.

Lactate Metabolism in Health and Disease.

Lactate (La) is a ubiquitous carbohydrate-derived metabolite and a major player in the coordination of whole-body metabolism. As the redox-balanced end-product of glycolysis, La forms the conceptual node linking glycolysis, a process that does not require oxygen, and which occurs in the cytosol, to the TCA cycle and aerobic bioenergetics in the mitochondria. Through rapid multisystem exchange involving membrane monocarboxylate transporters, lactate concentration ([La]) in the blood offers a "snapshot" of relative rates of glycolytic La production and its mitochondrial consumption.

Biophysical Characterization of Protein-Protein Interactions in Respiratory Syncytial Virus Infections.

Human respiratory syncytial virus (RSV) encodes multifunctional viral proteins that form interactions with each other and with host proteins during different stages of the viral replication cycle to facilitate viral replication and pathogenesis. Biochemical and biophysical characterization of protein-protein interactions is important for validation and for providing insights into the regulatory mechanisms used by viral proteins during RSV infections. In this chapter, we describe a process that can be used to validate direct protein-protein interactions by in vitro pulldown assay and biophysical characterization using size-exclusion chromatography-multiangle light scattering (SEC-MALS) and hydrogen-deuterium exchange-mass spectrometry (HDX-MS).

Severe Hemolytic Phenotype in Children With Sickle Cell Anemia and Co-Inherited Red Blood Cell Variants.

Remarkable phenotypic variability exists among individuals with sickle cell anemia (SCA), which may be explained by co-inheritance of traits affecting red blood cell (RBC) biology, such as genes affecting globin expression or glucose-6-phosphate dehydrogenase enzyme activity. Here, we describe three children with severe SCA who have co-inherited variants in genes for membrane proteins (SPTA1 and EPB1) and PIEZO1. These cases suggest that variants in RBC membrane proteins may contribute to SCA severity and phenotypic variation.

Maternal separation disrupts noradrenergic control of adult coping behaviors.

Early life stress (ELS) profoundly impacts the brain and correlates with negative affective behaviors in adulthood. The locus coeruleus (LC), a stress-responsive brainstem nucleus that supplies most of the brain with norepinephrine (NE), is known to modulate negative affect. Using repeated maternal separation stress (MSS), we investigated the impact of ELS on the LC and stress-related behaviors in adulthood.

Feedback Control of Coupled Nonlinear Oscillators with Uncertain Parameters.

The effective control of synchronization patterns in an oscillator ensemble is essential for optimal functioning of natural and engineered systems, with applications across diverse domains, including power systems, robotics, and medical device development. In this work, we address the problem of designing a feedback law to establish a desired synchronization structure in a pair of oscillators with model uncertainties. These oscillators are modeled using phase models with uncertainties in their phase response curves and oscillation frequencies.

CoRRECT: A Deep Unfolding Framework for Motion-Corrected Quantitative R2* Mapping.

Quantitative MRI (qMRI) refers to a class of MRI methods for quantifying the spatial distribution of biological tissue parameters. Traditional qMRI methods usually deal separately with artifacts arising from accelerated data acquisition, involuntary physical motion, and magnetic field inhomogeneities, leading to sub-optimal end-to-end performance. This paper presents CoRRECT, a unified deep unfolding (DU) framework for qMRI consisting of a model-based end-to-end neural network, a method for motion artifact reduction, and a self-supervised learning scheme.

Nicotinamide and Pyridoxine in Muscle Aging: Nutritional Regulation of Redox, Inflammation, and Regeneration.

Sarcopenia, the progressive loss of muscle mass, strength, and regenerative capacity with age, is driven by interconnected processes such as oxidative stress, chronic inflammation, mitochondrial dysfunction, and reduced activity of muscle stem cells. As the population ages, nutritional strategies that target these mechanisms are becoming increasingly important. This review focuses on nicotinamide (vitamin B3) and pyridoxine (vitamin B6), two essential micronutrients found in functional foods, which play complementary roles in redox regulation, immune balance, and muscle repair.