Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy.

Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma.

Purpose: In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.

Methods: ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL.

Domain Adversarial Convolutional Neural Network Improves the Accuracy and Generalizability of Wearable Sleep Assessment Technology.

Wearable accelerometers are widely used as an ecologically valid and scalable solution for long-term at-home sleep monitoring in both clinical research and care. In this study, we applied a deep learning domain adversarial convolutional neural network (DACNN) model to this task and demonstrated that this new model outperformed existing sleep algorithms in classifying sleep-wake and estimating sleep outcomes based on wrist-worn accelerometry. This model generalized well to another dataset based on different wearable devices and activity counts, achieving an accuracy of 80.

Time-Dependent ECG-AI Prediction of Fatal Coronary Heart Disease: A Retrospective Study.

: Fatal coronary heart disease (FCHD) affects ~650,000 people yearly in the US. Electrocardiographic artificial intelligence (ECG-AI) models can predict adverse coronary events, yet their application to FCHD is understudied. : The study aimed to develop ECG-AI models predicting FCHD risk from ECGs.

Changes in Waveguiding Cone Photoreceptors and Color Vision in Patients With Diabetes Mellitus.

Purpose: Although it is well known that photoreceptor damage and color vision loss occur in patients with diabetic retinopathy (DR), the relationship between structural and functional changes in diabetes mellitus (DM) remains unclear. Using highly sensitive measures of photoreceptor structure and function, we aim to determine whether early loss of color sensitivity in DM is also accompanied by decreased cone density.

Methods: Monocular data from 26 patients with DM and 25 healthy controls were examined to assess cone photoreceptor metrics, using confocal adaptive optics scanning light ophthalmoscopy, and red/green (RG) and yellow/blue (YB) color vision thresholds, using the Colour Assessment and Diagnosis test.

Intrinsic and environmental drivers of pairwise cohesion in wild Canis social groups.

Animals within social groups respond to costs and benefits of sociality by adjusting the proportion of time they spend in close proximity to other individuals in the group (cohesion). Variation in cohesion between individuals, in turn, shapes important group-level processes such as subgroup formation and fission-fusion dynamics. Although critical to animal sociality, a comprehensive understanding of the factors influencing cohesion remains a gap in our knowledge of cooperative behavior in animals.

Spatial resolution of a velocity-selected ion imaging microscope for surface reaction kinetics mapping.

Experimental validation of complex microkinetic models derived from quantum chemistry is crucial for the advancement of bottom-up approaches to heterogeneous catalysis. State-of-the-art velocity-resolved kinetics experiments have made tremendous progress in this arena but integrate reactivity over centimeter-scale single-crystal catalytic surfaces even when complex spatial phenomena may perturb the kinetic results. We report a new design, optimization, and analysis of an ion imaging microscope that can collect spatially resolved kinetic data from a catalytic surface.

Spatially Resolved CRISPR Screen Sequencing via Perturb-DBiT.

Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

CMS's Drug Price Negotiation Program 2023 Patient-Focused Listening Sessions: A Descriptive Analysis of Speaker Remarks.

Background: The US Centers for Medicare and Medicaid Services (CMS) held patient-focused listening sessions in Fall 2023 for each of the first ten drugs selected for the Inflation Reduction Act's (IRA) Drug Price Negotiation Program (DPNP). This study aimed to quantitatively describe speaker input at the sessions, including the absolute and relative time allocated to key areas of interest for the DPNP.

Methods: In this descriptive analysis of speaker remarks from ten CMS-hosted patient-focused listening sessions, speaker demographics were examined using video streams, time-stamped transcripts, public data, contextual clues, validated tools, and visual assessment when necessary.

Discrepancy in the Diagnosis of Heart Failure With Preserved Ejection Fraction Between Supine Versus Upright Exercise Hemodynamic Testing.

Background: Invasive exercise right heart catheterization is a gold standard in diagnosing heart failure with preserved ejection fraction (HFpEF). Body positions during the test influence hemodynamics. However, the discrepancy in HFpEF diagnosis between exercise testing in supine versus upright position is unknown.

A Mixed-Pure Planar Heterojunction Structure of Active Layers for Efficient Sequential Blade-Coating Organic Solar Cells.

Precise modulating the vertical structure of active layers to boost charge transfer is an effective way to achieve high power conversion efficiencies (PCEs) in organic solar cells (OSCs). Herein, efficient OSCs with a well-controlled vertical structure are realized by a rapid film-forming method combining low boiling point solvent and the sequential blade-coating (SBC) technology. The results of grazing incident wide-angle X-ray scattering measurement show that the vertical component distribution is varied by changing the processing solvent.

Early life adversity has sex-dependent effects on survival across the lifespan in rhesus macaques.

Exposure to early life adversity is linked to detrimental fitness outcomes across taxa. Owing to the challenges of collecting longitudinal data, direct evidence for long-term fitness effects of early life adversity from long-lived species remains relatively scarce. Here, we test the effects of early life adversity on male and female longevity in a free-ranging population of rhesus macaques () on Cayo Santiago, Puerto Rico.

Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension.

Background: Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis.

Plunge-diving into dynamic body acceleration and energy expenditure in the Peruvian booby.

Daily energy expenditure (DEE) is the result of decisions on how to allocate time among activities (resting, commuting and foraging) and the energy costs of those activities. Dynamic body acceleration (DBA), which measures acceleration associated with movement, can be used to estimate DEE. Previous studies of DBA-DEE correlations in birds were carried out on species foraging below their thermoneutral zone, potentially decoupling the DBA-DEE relationship.

Technology for fast-tracking high-risk head and neck cancer referrals: Co-designing with patients.

Background: Head and Neck Cancer (HNC) is the eighth most prevalent global cancer. Timely recognition of symptoms is crucial for reducing mortality rates. The EVolution of a patiEnt-REported symptom-based risk stratification sySTem to redesign the suspected Head and Neck cancer referral pathway (EVEREST-HN) study aims to develop and evaluate a risk stratification tool using patient reported symptoms, which will be populated remotely in the community before the patient is seen by the clinician to hasten HNC diagnosis.

Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.

Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways.

Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.

PD-1 is a key negative regulator of CD8 T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects.

Meaning and Joy at Work and Nurse Self-Care Practices: An Exploratory Study.

The Institute for Healthcare Improvement Framework for Improving Joy at Work includes self-care as a strategy to support happy, healthy, and productive people; however, this relationship has not previously been empirically demonstrated. The purpose of this study was to describe self-care practices and levels of meaning and joy in work (MJW) in a sample of registered nurses and to explore the relationship between self-care and MJW. Registered nurses (n = 122) from a regional health system completed a survey during a nursing recognition event.

SQUIRE-SIM (Standards for Quality Improvement Reporting Excellence for SIMulation): Publication Guidelines for Simulation-Based Quality Improvement Projects.

Introduction: With increased incorporation of simulation-based methodologies into quality improvement activities, standards for reporting on simulation-specific elements in healthcare improvement research are needed.

Methods: We followed established consensus process methodology to iteratively create simulation-based extensions for SQUIRE 2.0 reporting guidelines.

Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.

Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover.