Evaluating the generalizability of graph neural networks for predicting collision cross section.

Ion Mobility coupled with Mass Spectrometry (IM-MS) is a promising analytical technique that enhances molecular characterization by measuring collision cross-section (CCS) values, which are indicative of the molecular size and shape. However, the effective application of CCS values in structural analysis is still constrained by the limited availability of experimental data, necessitating the development of accurate machine learning (ML) models for in silico predictions. In this study, we evaluated state-of-the-art Graph Neural Networks (GNNs), trained to predict CCS values using the largest publicly available dataset to date.

Natural Products Have Increased Rates of Clinical Trial Success throughout the Drug Development Process.

Natural products (NPs) or their derivatives represent a large proportion of drugs that successfully progress through clinical trials to approval. This study explores the presence of NPs in both early- and late-stage drug discovery to determine their success rate, and the factors or features of natural products that contribute to such success. As a proxy for early drug development stages, we analyzed patent applications over several decades, finding a consistent proportion of NP, NP-derived, and synthetic-compound-based patent documents, with the latter group outnumbering NP and NP-derived ones (approximately 77% vs 23%).

Cleft Laterality Dental Arch Relationship Outcomes for Children with Unilateral Cleft Lip and Palate in New Zealand.

Objectives: To investigate cleft laterality dental arch relationship outcomes of children with non-syndromic complete unilateral cleft lip and palate (UCLP) in New Zealand.

Design: A retrospective nationwide study.

Settings: Virtual 3D orthodontic study models collected prior to undertaking secondary alveolar bone grafting.

Weighting Low-Intensity MS/MS Ions and / Frequency for Spectral Library Annotation.

Calculating spectral similarity is a fundamental step in MS/MS data analysis in untargeted metabolomics experiments, as it facilitates the identification of related spectra and the annotation of compounds. To improve matching accuracy when querying an experimental mass spectrum against a spectral library, previous approaches have proposed increasing peak intensities for high / ranges. These high / values tend to be smaller in magnitude, yet they offer more crucial information for identifying the chemical structure.

Exploring the known chemical space of the plant kingdom: insights into taxonomic patterns, knowledge gaps, and bioactive regions.

Plants are one of the primary sources of natural products for drug development. However, despite centuries of research, only a limited region of the phytochemical space has been studied. To understand the scope of what is explored versus unexplored in the phytochemical space, we begin by reconstructing the known chemical space of the plant kingdom, mapping the distribution of secondary metabolites, chemical classes, and plants traditionally used for medicinal purposes (i.

MRI and amino acid PET detection of whole-brain tumor burden.

Background: [F]fluciclovine amino acid PET has shown promise for detecting brain tumor regions undetected on conventional anatomic MRI scans. However, it remains unclear which of these modalities provides a better assessment of the whole brain tumor burden. This study quantifies the performance of [F]fluciclovine PET and MRI for detecting the whole brain tumor burden.

Dissociative episodes characterised by hair-pulling in a late adolescent woman.

A woman in late adolescence with a history of sickle cell disease, moyamoya disease, cerebrovascular accident, mild intellectual disability, post-traumatic stress disorder, functional seizures, generalised anxiety disorder and transient psychosis was referred for a psychiatry consultation. She presented with worsening episodes of dissociation characterised by compulsory hair-pulling. Limited research exists regarding patients engaging in activities of automated behaviour during episodes of dissociation.

Modern drug discovery using ethnobotany: A large-scale cross-cultural analysis of traditional medicine reveals common therapeutic uses.

For millennia, numerous cultures and civilizations have relied on traditional remedies derived from plants to treat a wide range of conditions and ailments. Here, we systematically analyzed ethnobotanical patterns across taxonomically related plants, demonstrating that congeneric medicinal plants are more likely to be used for treating similar indications. Next, we reconstructed the phytochemical space covered by medicinal plants to reveal that (i) taxonomically related medicinal plants cover a similar phytochemical space, and (ii) chemical similarity correlates with similar therapeutic usage.

Editorial: The Untapped Potential of Partial Hospitalization Programs.

The prevalence of mental health conditions in adolescents has been increasing worldwide. With the increasing demand, access to effective mental health care has struggled to keep pace. More adolescents are requiring intensive inpatient hospitalizations for high-risk conditions and often lack adequate resources for sub-acute care following discharge.

5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades.

Introduction: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

On the correspondence between the transcriptomic response of a compound and its effects on its targets.

Better understanding the transcriptomic response produced by a compound perturbing its targets can shed light on the underlying biological processes regulated by the compound. However, establishing the relationship between the induced transcriptomic response and the target of a compound is non-trivial, partly because targets are rarely differentially expressed. Therefore, connecting both modalities requires orthogonal information (e.

Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.

Chemical genetic approaches have had a transformative impact on discovery of drug targets for malaria but have primarily been used for parasite targets. To identify human pathways required for intrahepatic development of parasite, we implemented multiplex cytological profiling of malaria infected hepatocytes treated with liver stage active compounds. Some compounds, including MMV1088447 and MMV1346624, exhibited profiles similar to cells treated with nuclear hormone receptor (NHR) agonist/antagonists.

Assessment of complementary white matter microstructural changes and grey matter atrophy in a preclinical model of Alzheimer's disease.

Alzheimer's disease (AD) has been associated with amyloid and tau pathology, as well as neurodegeneration. Beyond these hallmark features, white matter microstructural abnormalities have been observed using MRI. The objective of this study was to assess grey matter atrophy and white matter microstructural changes in a preclinical mouse model of AD (3xTg-AD) using voxel-based morphometry (VBM) and free-water (FW) diffusion tensor imaging (FW-DTI).

Optimal Use of Advanced Practice Providers at an Academic Medical Center: A First-Year Retrospective Review.

Background Physician assistants/associates (PAs) and nurse practitioners (NPs), together known as advanced practice providers (APPs), practice with a high degree of clinical autonomy and professional respect, and play a critical role in team-based care. Aligning APP care delivery models to promote top-of-license practice is essential to improving ambulatory capacity and bottom-line expectations at academic medical centers (AMCs) in the 21 century and beyond. This administrative quality improvement study assesses the downstream impact of restructuring our APP care models to promote independent practice sessions.

Effectiveness of ENGAGE in reducing difficulties in everyday executive functions among Finnish preschoolers: a randomized controlled trial.

Effective interventions applicable for young preschool-age children are needed to reduce the risk of widespread and sustained adversities that are linked to early executive function (EF) difficulties. This randomized controlled trial (RCT) examined the effectiveness of the play-based ENGAGE intervention in improving behavioral outcomes related to EFs among Finnish preschool-age children with hyperactivity and/or inattention problems. 95 children between 4 and 5 years of age and their parents were randomly assigned to the ENGAGE intervention or a waitlist control group.

Adaption and implementation of the engage programme within the early childhood curriculum.

Poor self-regulation has been associated with an array of adverse outcomes including difficulties with school transition, educational attainment, and social functioning in childhood, and employment, mental health, physical health, relationships, and criminal activity in adulthood. Enhancing Neurobehavioural Gains with the Aid of Games and Exercises (ENGAGE) is a play-based intervention fostering the development of self-regulation in pre-schoolers and has led to improvements within the home setting. The aim for this study was to ascertain whether ENGAGE can be implemented within an Early Childhood Education (ECE) group setting and whether this leads to improved self-regulation.

Ensembles of knowledge graph embedding models improve predictions for drug discovery.

Recent advances in Knowledge Graphs (KGs) and Knowledge Graph Embedding Models (KGEMs) have led to their adoption in a broad range of fields and applications. The current publishing system in machine learning requires newly introduced KGEMs to achieve state-of-the-art performance, surpassing at least one benchmark in order to be published. Despite this, dozens of novel architectures are published every year, making it challenging for users, even within the field, to deduce the most suitable configuration for a given application.

Investigating the moderators and mediators of an effective sleep intervention in the Prevention of Overweight in Infancy (POI) randomized controlled trial: Exploratory analyses.

The Prevention of Overweight in Infancy (POI) sleep intervention halved obesity risk at 2 years of age. However, the intervention mechanisms are unclear. Consequently, the objective of the current work was to use exploratory analyses to investigate potential moderators and mediators of the sleep intervention on obesity outcomes at age 2 years.

Causal reasoning over knowledge graphs leveraging drug-perturbed and disease-specific transcriptomic signatures for drug discovery.

Network-based approaches are becoming increasingly popular for drug discovery as they provide a systems-level overview of the mechanisms underlying disease pathophysiology. They have demonstrated significant early promise over other methods of biological data representation, such as in target discovery, side effect prediction and drug repurposing. In parallel, an explosion of -omics data for the deep characterization of biological systems routinely uncovers molecular signatures of disease for similar applications.

Imaging Glioblastoma With F-Fluciclovine Amino Acid Positron Emission Tomography.

Introduction: Conventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with F-fluciclovine (fluciclovine) provides regional assessment of amino acid uptake in tumors that could overcome some of the limitations of conventional imaging. However, the biological basis of enhanced fluciclovine uptake is insufficiently characterized in brain tumors, which confounds clinical interpretation and application.

Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors.

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity.

Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study.

T relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease.

Adherence to 24-h movement behavior guidelines and psychosocial functioning in young children: a longitudinal analysis.

Background: A recent paradigm shift has highlighted the importance of considering how sleep, physical activity and sedentary behaviour work together to influence health, rather than examining each behaviour individually. We aimed to determine how adherence to 24-h movement behavior guidelines from infancy to the preschool years influences mental health and self-regulation at 5 years of age.

Methods: Twenty-four hour movement behaviors were measured by 7-day actigraphy (physical activity, sleep) or questionnaires (screen time) in 528 children at 1, 2, 3.

Designing Video Games for Nutrition Education: A Participatory Approach.

Objective: To describe the participatory approach used to inform the development of a video game designed to increase children's nutrition knowledge. The objectives were to (1) assess children's nutrition areas of focus, (2) explore parents' and children's perceptions of video games for nutrition education, and (3) collect information on children's video game preferences.

Design: Qualitative research design using 10 focus group interviews and 5 workshops.