R3-Noria-methanesulfonate: A Molecular Cage with Superior Hyperpolarized Xenon-129 MRI Contrast.

Hyperpolarized (HP) xenon-129 (Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSOH).

Cucurbit[6]uril Hyperpolarized Chemical Exchange Saturation Transfer Pulse Sequence Parameter Optimization and Detectability Limit Assessment at 3.0T.

The front cover artwork is provided by Prof. Mitchell S. Albert's group at Lakehead University.

Cucurbit[6]uril Hyperpolarized Chemical Exchange Saturation Transfer Pulse Sequence Parameter Optimization and Detectability Limit Assessment at 3.0T.

Molecular imaging is the future of personalized medicine; however, it requires effective contrast agents. Hyperpolarized chemical exchange saturation transfer (HyperCEST) can boost the signal of Hyperpolarized Xe MRI and render it a molecular imaging modality of high efficiency. Cucurbit[6]uril (CB6) has been successfully employed in vivo as a contrast agent for HyperCEST MRI, however its performance in a clinical MRI scanner has yet to be optimized.

TransitionED: A protocol for Co-designing and implementing Canadian practice guidelines for transitions for youth with eating disorders.

Objective: Limited guidelines inform the transition from paediatric to adult healthcare for youth and young adults (YYA) with eating disorders (EDs). This study will develop, implement, and evaluate Canadian Clinical Practice Guidelines for ED transition, including identifying the relevant measurement and evaluation tools for transition readiness and continuity of care.

Methods: This study consists of three phases.

Changes in Children and Youth's Mental Health Presentations during COVID-19: A Study of Primary Care Practices in Northern Ontario, Canada.

Recent research suggests that children and youth are at increased risk of anxiety and depression due to the indirect effects of the COVID-19 pandemic. In Canada, children and youths may face additional hurdles in accessing mental health services in rural areas due to socioeconomic disadvantages and healthcare provider shortages worsened by the pandemic. Our study aimed to assess changes in primary healthcare utilization related to depression and anxiety among children and youth aged 10-25 years in Northern Ontario, Canada.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together.

Revealing a Third Dissolved-Phase Xenon-129 Resonance in Blood Caused by Hemoglobin Glycation.

Hyperpolarized (HP) xenon-129 (Xe), when dissolved in blood, has two NMR resonances: one in red blood cells (RBC) and one in plasma. The impact of numerous blood components on these resonances, however, has not yet been investigated. This study evaluates the effects of elevated glucose levels on the chemical shift (CS) and T2* relaxation times of HP Xe dissolved in sterile citrated sheep blood for the first time.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

Introduction: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.

Methods: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).

Bioinformatic assay reveal the potential mechanism of Guizhi-Shaoyao-Zhimu decoction against rheumatoid arthritis and mild-to-moderate COVID-19.

Background And Objective: Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population.

Comparison of a validated decision-support tool to a standard of care triage system for knee osteoarthritis assessment: a proof-of-concept study.

Background: Patients with knee osteoarthritis (OA) in northwestern Ontario are referred by their primary care provider (PCP) to a centralized assessment clinic for evaluation by an advanced practice physiotherapist (APP) to determine if they will require surgical management. However, many patients are found to not require surgical management, resulting in delays for patients who do. A decision-support tool was developed to address this issue and to guide treatment options by determining the need for surgical or nonsurgical approaches.

Aurora B Inhibitors as Cancer Therapeutics.

The Aurora kinases (A, B, and C) are a family of three isoform serine/threonine kinases that regulate mitosis and meiosis. The Chromosomal Passenger Complex (CPC), which contains Aurora B as an enzymatic component, plays a critical role in cell division. Aurora B in the CPC ensures faithful chromosome segregation and promotes the correct biorientation of chromosomes on the mitotic spindle.

A national-level examination of First Nations peoples' mental health data: Predicting mental well-being from social determinants of health using the 2017 Aboriginal Peoples Survey.

Introduction: A history of colonization and assimilation have resulted in social, economic, and political disparities for Indigenous people in Canada. Decades of discriminatory policies (e.g.

A Cytoplasm-Specific Fluorescent Ligand for Selective Imaging of RNA G-Quadruplexes in Live Cancer Cells.

The development of site-specific, target-selective and biocompatible small molecule ligands as a fluorescent tool for real-time study of cellular functions of RNA G-quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm-specific and RNA G4-selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA.

Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases.

Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases.

Intergenerational residential school attendance and increased substance use among First Nation adults living off-reserve: An analysis of the aboriginal peoples survey 2017.

Introduction: The Truth and Reconciliation Commission of Canada (TRCC) published 94 Calls to Action in 2015 to address long-term, intergenerational effects of the residential school system, highlighting the pervasive impact of colonialism on the wellbeing of Indigenous peoples in Canada. Indeed, research with Indigenous populations in Canada has captured that prior experiences of residential schools contributes to the intergenerational transmission of mental and physical health disparities. Despite these studies, further research is needed that contextualizes the influence of residential schools within broader frameworks that consider Indigenous social determinants of health in Canada.

Federated Learning via Augmented Knowledge Distillation for Heterogenous Deep Human Activity Recognition Systems.

Deep learning-based Human Activity Recognition (HAR) systems received a lot of interest for health monitoring and activity tracking on wearable devices. The availability of large and representative datasets is often a requirement for training accurate deep learning models. To keep private data on users' devices while utilizing them to train deep learning models on huge datasets, Federated Learning (FL) was introduced as an inherently private distributed training paradigm.

Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.

Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry.

Cultural adaptation considerations of a comprehensive housing outreach program for Indigenous youth exiting homelessness.

Generalist health interventions that aim to reduce chronic health disparities between Indigenous and non-Indigenous populations can be culturally adapted to better meet the needs of Indigenous people in Canada; however, little is known regarding best practices in implementing these adaptations. The present study first provides a review of the research process used to adapt a previous evidence-based housing initiative for Indigenous youth in Northwestern Ontario. Second, it includes an overview of the adaptations that were made and the associated rationale for such adaptations.

Can machine learning 'transform' peptides/peptidomimetics into small molecules? A case study with ghrelin receptor ligands.

There has been considerable interest in transforming peptides into small molecules as peptide-based molecules often present poorer bioavailability and lower metabolic stability. Our studies looked into building machine learning (ML) models to investigate if ML is able to identify the 'bioactive' features of peptides and use the features to accurately discriminate between binding and non-binding small molecules. The ghrelin receptor (GR), a receptor that is implicated in various diseases, was used as an example to demonstrate whether ML models derived from a peptide library can be used to predict small molecule binders.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

Introduction: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap.

Methods: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes.

Comparative Analysis of Multilayer Lead Oxide-Based X-ray Detector Prototypes.

Lead oxide (PbO) photoconductors are proposed as X-ray-to-charge transducers for the next generation of direct conversion digital X-ray detectors. Optimized PbO-based detectors have potential for utilization in high-energy and dynamic applications of medical X-ray imaging. Two polymorphs of PbO have been considered so far for imaging applications: polycrystalline lead oxide (poly-PbO) and amorphous lead oxide (a-PbO).

Dark Current Modeling for a Polyimide-Amorphous Lead Oxide-Based Direct Conversion X-ray Detector.

The reduction of the dark current (DC) to a tolerable level in amorphous selenium (a-Se) X-ray photoconductors was one of the key factors that led to the successful commercialization of a-Se-based direct conversion flat panel X-ray imagers (FPXIs) and their widespread clinical use. Here, we discuss the origin of DC in another X-ray photoconductive structure that utilizes amorphous lead oxide (a-PbO) as an X-ray-to-charge transducer and polyimide (PI) as a blocking layer. The transient DC in a PI/a-PbO detector is measured at different applied electric fields (5-20 V/μm).