Leveraging Model Master Files for Long-Acting Injectables.

The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on May 2-3, 2024, titled "Considerations and Potential Regulatory Applications for a Model Master File (Lachaine et al Can J Psychiatry.

Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).

Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH.

Hilbert transform analysis of the mouse scotopic electroretinogram reveals two distinct bursts of oscillatory potentials with progressively dimmer flashes.

Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG).

Methods: Scotopic ERGs [Intensity: - 6.3 to 0.

Effects of 24-h sleep deprivation on whole-body heat exchange in young men during exercise in the heat.

Sleep deprivation has been associated with impaired thermoregulatory function. However, whether these impairments translate to changes in whole-body heat exchange during exercise-heat stress remains unknown. Therefore, following either a night of normal sleep or 24 h of sleep deprivation, 10 young men (mean (SD): 23 (3) years) completed three 30-min bouts of semi-recumbent cycling at increasing fixed rates of metabolic heat production (150, 200, 250 W/m), each separated by a 15-min rest in dry heat (40 °C, ~ 13% relative humidity).

Molecular Therapeutics in Development to Treat Hyperlipoproteinemia.

Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them.

Description of STRIVE-ON Study Protocol: Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Phase III Trial (STRIVE-ON).

Oral nimodipine is the only drug approved in North America for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow.

Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.

Objective: Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs.

Who drives weight stigma? A multinational exploration of clustering characteristics behind weight bias against preconception, pregnant, and postpartum women.

Background: Weight bias is a global health challenge and community members are endorsed as the most common source of weight bias. The nature of weight biases specifically against preconception, pregnant, and postpartum (PPP) women from the perspective of community members is not known, especially in terms of cross-cultural trends. We investigated the magnitude of explicit and implicit weight bias and profiles of characteristics associated with harbouring weight bias.

fMRI data acquisition and analysis for task-free, anesthetized rats.

Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies.

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing.

Assessment of Opuntia ficus-indica supplementation on enhancing antioxidant levels.

Opuntia ficus-indica (OFi) is a major fruit source prevalent in semiarid and arid regions across various countries worldwide. It is widely recognised for its potential health benefits; however, most studies investigating its effects have been limited to pre-clinical models, highlighting the need for further validation through clinical trials. This study aimed to evaluate the effectiveness of OFi supplementation in enhancing antioxidant levels.

A cross sectional investigation of the development of rhythmic preferences with motor and perceptual tests.

The preferred period hypothesis posits a slowing down of motor and perceptual rhythmic preferences with age, both reflecting an increase in the common internal oscillation period. This study further investigates the preferred period hypothesis by improving the measurement of perceptual rhythmic preferences through two tasks, tempo adjustment and tempo judgment, conducted in auditory and visual modalities. The study was conducted with three groups of children (5-6, 8-9, and 11-12 years old), and a group of young adults (21 to 30 years old) during the same time of the day.

Machine learning models for predicting interaction affinity energy between human serum proteins and hemodialysis membrane materials.

Membrane incompatibility poses significant health risks, including severe complications and potential fatality. Surface modification of membranes has emerged as a pivotal technology in the membrane industry, aiming to improve the hemocompatibility and performance of dialysis membranes by mitigating undesired membrane-protein interactions, which can lead to fouling and subsequent protein adsorption. Affinity energy, defined as the strength of interaction between membranes and human serum proteins, plays a crucial role in assessing membrane-protein interactions.

Identifying factors that contribute to collision avoidance behaviours while walking in a natural environment.

Busy walking paths, like in a park, city centre, or shopping mall, frequently necessitate collision avoidance behaviour. Lab-based research has shown how different situation- and person-specific factors, typically studied independently, affect avoidance behaviour. What happens in the real world is unclear.

Comparative analysis of salivary cytokine profiles in newly diagnosed pediatric patients with cancer and healthy children.

Salivary cytokines have the potential to serve as biomarkers for evaluating cancer progression and treatment response in specific cancer types. This study explored salivary cytokine profiles in pediatric cancer patients and healthy controls, examining changes during chemotherapy. We conducted a prospective study involving newly diagnosed cancer patients and healthy controls under 19 years old.

Dilated SE-DenseNet for brain tumor MRI classification.

In the field of medical imaging, particularly MRI-based brain tumor classification, we propose an advanced convolutional neural network (CNN) leveraging the DenseNet-121 architecture, enhanced with dilated convolutional layers and Squeeze-and-Excitation (SE) networks' attention mechanisms. This novel approach aims to improve upon state-of-the-art methods of tumor identification. Our model, trained and evaluated on a comprehensive Kaggle brain tumor dataset, demonstrated superior performance over established convolution-based and transformer-based models: ResNet-101, VGG-19, original DenseNet-121, MobileNet-V2, ViT-L/16, and Swin-B across key metrics: F1-score, accuracy, precision, and recall.

Exploring when to exploit: the cognitive underpinnings of foraging-type decisions in relation to psychopathy.

Impairments in reinforcement learning (RL) might underlie the tendency of individuals with elevated psychopathic traits to behave exploitatively, as they fail to learn from their mistakes. Most studies on the topic have focused on binary choices, while everyday functioning requires us to learn the value of multiple options. In this study, we evaluated the cognitive correlates of naturalistic foraging-type decision-making and their electrophysiological signatures in a community sample (n = 108) with varying degrees of psychopathic traits.

Bias-Induced Ga-O-Ir Interface Breaks the Limits of Adsorption-Energy Scaling Relationships for High-Performing Proton Exchange Membrane Electrolyzers.

Rationally manipulating the in-situ formed catalytically active surface of catalysts remains a significant challenge for achieving highly efficient water electrolysis. Herein, we present a bias-induced activation strategy to modulate in-situ Ga leaching and trigger the dynamic surface restructuring of lamellar Ir@Ga2O3 for the electrochemical oxygen evolution reaction. The in-situ reconstructed Ga-O-Ir interface sustains high water oxidation rates at OER overpotentials.

Enantioselective Borylcupration/Cyclization of Alkene-Tethered Oxime Esters.

A copper-catalyzed enantioselective synthesis of borylated 1-pyrrolines from γ,δ-unsaturated oxime esters is reported. Twenty-four novel 1-pyrroline derivatives are reported in yields ranging from 26% to 96% and enantioselectivities from 74.5:25.

Examining Long-Haul Truck Driver Needs and Preferences to Improve the Truck Stop Environment.

Objective: This study examined and compared the truck stop needs and preferences of long-haul truck drivers (LHTD) based on gender.

Methods: LHTD were recruited from various provincial and federal trucking associations and trucking companies across Canada. A sample of 406 drivers completed an online survey that consisted of questions on demographics, health conditions and behaviours, and preferences for truck stop amenities.

A retrospective analysis of medical student authorship in highest impact radiology journal publications.

Objectives: To assess medical student authorship in radiology research, focusing on the prevalence and impact of student articles, demographic trends, and potential barriers and opportunities for involvement.

Methods: We retrospectively assessed original research and review papers from 2018 to 2022 in the top five radiology journals based on their 2022 Impact Factor. Three reviewers manually validated and classified articles by medical student (MS) and non-MS authorship.