Impact of intravenous iron or exogenous erythropoietin on hemoglobin mass, exercise performance, and acute mountain sickness during altitude acclimatization.

Chronic exposure to high altitude leads to increases in hemoglobin mass (Hbmass), which may improve exercise performance and decrease acute mountain sickness (AMS) symptoms. We evaluated the influence of intravenous iron or erythropoietin (EPO) treatment on Hbmass, exercise performance, and AMS during a 14-day exposure to 3094 m. Thirty-nine participants (12F) completed the study conducted in Eugene, Oregon (sea level (SL), 130 m) and Leadville, Colorado (3094 m).

Discovery, Optimization, and Evaluation of Non-Nucleoside SARS-CoV-2 NSP14 Inhibitors.

We recently reported the discovery of TDI-015051, a first-in-class small-molecule inhibitor of the SARS-CoV-2 guanine-N7 methyltransferase nonstructural protein 14 (NSP14). NSP14 plays a critical role in viral RNA cap synthesis and its inhibition represents a novel antiviral approach. Utilizing systematic structure-activity relationship studies, potent non-nucleoside-based inhibitors with single-digit nanomolar cellular activity were identified from an HTS hit lacking cellular activity.

Automated Deep Learning Pipeline for Callosal Angle Quantification.

Background And Purpose: Normal pressure hydrocephalus (NPH) is a potentially treatable neurodegenerative disorder that remains underdiagnosed due to its clinical overlap with other conditions and the labor-intensive nature of manual imaging analyses. Imaging biomarkers, such as the callosal angle (CA), Evans Index (EI), and Disproportionately Enlarged Subarachnoid Space Hydrocephalus (DESH), play a crucial role in NPH diagnosis but are often limited by subjective interpretations. To address these challenges, we developed a fully automated and robust deep learning framework for measuring the CA directly from raw T1 MPRAGE and non-MPRAGE MRI scans.

The Health, Aging, and Later-Life Outcomes Pilot Study: Design, recruitment, and participants' baseline characteristics.

Background: Multi-morbidity increases significantly with age, and obesity is a major risk factor for conditions like cardiovascular disease and diabetes, indicating a critical need for effective interventions.

Objective: We discuss the study design of the HALLO-Pilot Study that randomized older adults to in-person caloric restriction (CR), remotely delivered CR (RCR), or a time restricted eating (TRE) intervention. In addition, we emphasize inclusion/exclusion criteria, recruitment, and baseline characteristics of randomized participants.

Enhancing Predictive Modeling for Respiratory Support with LLM-Driven Guideline Adherence.

Background: Optimal respiratory support selection between high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) for intensive care units (ICU) patients at risk of invasive mechanical ventilation (IMV) remains unclear, particularly in cases not represented in prior clinical trials. We previously developed RepFlow-CFR, a deep counterfactual model estimating individualized treatment effects (ITE) of HFNC versus NIV. However, interpretability and guideline alignment remain challenges for clinical adoption.

Effects of Bacillus coagulans (GBI-30, 6086) supplementation on apparent total tract nutrient digestibility and the fecal characteristics and metabolites, immunity, and microbiota of healthy adult dogs.

Bacillus coagulans GBI-30, 6086 is a lactic acid-producing, spore-forming bacteria with diverse characteristics that lend it resiliency through commercial pet food processing, storage, and chemical and enzymatic digestion through the gastrointestinal tract. The objective of this study was to determine the effects of B. coagulans on dietary apparent total tract nutrient digestibility (ATTD) and the hematology, immunoglobulin concentrations, and fecal characteristics, metabolites, and microbiota populations of healthy adult dogs.

Addition of Intramuscular Epinephrine to Standard of Care by Paramedics to Decrease Time-to-Initial Epinephrine Dose in Pediatric Out-of-Hospital Cardiac Arrest: A Simulation Trial.

Objectives: Survival rates for pediatric out-of-hospital cardiac arrest (POHCA) are low at around 10%. Paramedic services administer critical interventions including epinephrine. While typically administered via intravenous (IV) or intraosseous (IO) routes, obtaining these access points in out-of-hospital emergencies is challenging.

Mitochondrial ROS and HIF-1α signaling mediate synaptic plasticity in the critical period.

As developing networks transition from spontaneous irregular to patterned activity, they undergo plastic tuning phases, termed "critical periods"; "critical" because disturbances during these phases can lead to lasting changes in network development and output. Critical periods are common to developing nervous systems, with analogous features shared from insects to mammals, yet the core signaling mechanisms that underlie cellular critical period plasticity have remained elusive. To identify these, we exploited the Drosophila larval locomotor network as an advantageous model system.

Comparing High-Flow Nasal Cannula and Non-Invasive Ventilation in Critical Care: Insights from Deep Counterfactual Inference.

Randomized trials comparing high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIV) for acute respiratory failure (ARF) offer population-level guidance but often fail to capture individual variability in treatment response. In this retrospective study, we identified intensive care units (ICU) patients at risk of invasive mechanical ventilation (IMV) using a previously published risk prediction model. Patients who first received HFNC or NIV after crossing the high-risk threshold formed the early treatment cohort.

Artificial intelligence-driven decision support for patients with acute respiratory failure: a scoping review.

Background: Artificial intelligence (AI) has emerged as a promising tool for decision support in managing acute respiratory failure, yet its real-world clinical impact remains unclear. This scoping review identifies clinically validated AI-driven tools in this domain, focusing on the reporting of key evaluation quality measures that are a prerequisite for broader deployment.

Eligibility Criteria: Studies were included if they compared a clinical, human factors, or health systems-related outcome of an AI-driven intervention to a control group in adult patients with acute respiratory failure.

Improving paediatric clinical teaching unit handover: A quality improvement project.

Background: Handover is an integral part of patient care and is dependent on effective communication between physicians. Poor quality handover can lead to patient harm, with up to 75% of patients in whom there are handover failures sustaining preventable adverse events. Paediatric Clinical Teaching Unit (CTU) Morbidity and Mortality rounds identified multiple handover-related adverse events.

Home-based phototherapy for neonatal hyperbilirubinemia: A one-time Canadian Paediatric Surveillance Program Survey.

Objectives: Home-based phototherapy (HP) has gained traction as an alternative to hospital-based treatment for neonatal hyperbilirubinemia, but the safety of this practice remains unclear. This study aimed to identify adverse events (AEs) associated with HP in Canada.

Methods: A one-time survey, distributed through the Canadian Paediatric Surveillance Program, collected retrospective data from paediatricians.

Change points for dynamic biomarkers in the Alzheimer's disease pathological cascade: A 30-year cohort study.

Introduction: This study aimed to delineate trajectories of biomarkers-amyloid beta (Aβ), phosphorylated tau, neurodegeneration, and inflammation-and to identify change points along these trajectories.

Methods: Longitudinal data were collected over 30 years from 349 cognitively unimpaired individuals enrolled in the Biomarkers for Older Controls at Risk for Dementia study. Piecewise regression models were used to identify change points in cerebrospinal fluid biomarkers, brain magnetic resonance imaging volumes, and a composite measure of global cognition.

Radiographic Findings in the Lower Extremity Joints of Long-Term Users of Implanted Standing Neuroprostheses with Spinal Cord Injuries.

Objective: To assess whether lower extremity degenerative joint changes developed in long-term users of implantable neuromuscular prostheses.

Design: Before-after radiographic assessment.

Setting: Tertiary care center.

Performance change while learning novel cognitive tasks as a potential identifier of preclinical Alzheimer's disease.

Background: In healthy older adults (OA), the effects of amyloid-β (Aβ) deposition on cognitive functions involved in learning are unclear.

Objective: This study aimed to determine how age, practice, and neuropsychological test performance are associated with performance change during the learning of three cognitive tasks, and if Aβ deposition impacts performance change in OA.

Methods: Fifty-five OA and 28 young adults completed neuropsychological tests, and Aβ deposition was assessed in OA.

Utilization Patterns and Clinical Factors Associated With Hospitalization in Early-Stage Dementia With Lewy Bodies.

Objectives: Characterize patterns of hospitalization and emergency department (ED) visits in early-stage dementia with Lewy bodies (DLB).

Methods: We analyzed electronic health records and claims data from a U.S.

A Randomized-Controlled Trial Using Point of Care Ultrasound to Evaluate Volunteer Patients in the Emergency Department Versus a Manikin Simulator for Improving Knowledge and Confidence of Hypotension and Shock in Medicine Sub-Internship Students.

Aim: Point of Care Ultrasound (POCUS) excels in the assessment of patients with hypotension and shock. Whether using real patients or a manikin simulator to teach POCUS skills is preferable is not completely clear. We designed a randomized-controlled trial to compare these two different teaching methods of POCUS.

Infantile epileptic spasm syndrome: predictors of short- and long-term outcomes.

Introduction: Infantile epileptic spasm syndrome (IESS) has significant impact on affected children that affects their future seizure control and neurodevelopmental outcomes. The aim of this study is to identify potential short- and long-term predictors of outcomes in children diagnosed IESS.

Method: This retrospective study evaluated outcomes of seizure control and developmental status in a historical cohort of 60 children with IESS.

Underlying Diagnosis of Food Bolus Obstruction Acute Admissions to Otorhinolaryngology: A Shift to Provide the Best Care as per the Current Guidelines.

In the United Kingdom, some patients with food bolus obstruction (FBO) are admitted under the care of ear, nose, and throat (ENT) doctors. In the literature, eosinophilic oesophagitis (EoE) is the most common cause of FBO. We analysed ENT FBO admissions and interventions used in our hospital to investigate for EoE.

Relationship of Visual Impairment and Poor Mobility With Mortality.

Background: Older adults with visual impairment (VI) have a greater risk of mortality, but the reasons are poorly understood. We have shown that older adults with VI are more likely to have poor mobility performance on the short physical performance battery (SPPB). In this analysis, we examined whether VI predicted mortality over 10 years and if this was related to poor baseline mobility (SPPB < 9).

Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection.

Emerging RNA virus outbreaks, including Zika virus, highlight the urgent need for novel antiviral strategies. Zika virus, a positive-strand RNA virus, causes congenital Zika syndrome, and to date, there are no approved vaccines or antiviral treatments. In this context, microRNAs are small non-coding RNAs that regulate gene expression and show potential as antiviral agents due to their ability to target viral RNA, making them a promising therapeutic approach against Zika syndrome.

Neurons accumulate disease-specific somatic genomic changes across tau pathologic states in Alzheimer's disease.

Tau deposition within neurons marks Alzheimer's disease (AD) neuropathology, suggesting that tau may contribute to cellular dysfunction and death. In AD, somatic mutations accumulate in neurons, with features that suggest deleterious effects on cellular function. To examine the relationship between tau and somatic mutation, we isolated neurons according to tau pathology and performed single-cell whole-genome sequencing on tau+, tau-, and tau-agnostic neurons from 13 individuals with AD, as well as neurons from 15 control individuals.

Butorphanol-azaperone-medetomidine and ketamine-butorphanol-azaperone-medetomidine chemical immobilization in habituated subadult female giraffe (Giraffa camelopardalis).

Objective: To describe the effects of butorphanol-azaperone-medetomidine (BAM) and ketamine-butorphanol-azaperone-medetomidine (KBAM) used for the chemical immobilization of giraffes.

Study Design: Quasi-experimental trial.

Animals: A group of 10 habituated subadult female giraffes.

Anti-amyloid antibody equilibrium binding to Aβ aggregates from human Alzheimer disease brain.

Importance: Anti-amyloid immunotherapy is used to treat Alzheimer disease (AD) with moderate benefits and potentially serious side effects due to amyloid related imaging abnormality with effusions/edema (ARIA-E). Different anti-amyloid antibodies have different binding characteristics to different synthetic Aβ aggregates, leading to the assumption that they bind different species in the human brain. Lecanemab is hypothesized to bind "protofibrils," but these are not well-characterized in human brain.