Publications

CONCLUSIONS AND RELEVANCE: Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Migrant agricultural workers (MAWs), predominantly individuals from countries in the Global South, play a vital role in maintaining Canadian food security. Employed in low-income positions across the country, they often face workplace hazards and numerous occupational health and safety (OHS) challenges related to long working hours, limited access to OHS information, gaps in knowledge, structural power imbalances with employers, and language and cultural barriers. This pilot study explored the...

Self-fertilization reduces genetic diversity compared to outcrossing and hypothetically decreases the ability to adapt to diverse environments. Among Caenorhabditis nematodes, self-fertilization evolved three times independently in Caenorhabditis elegans, Caenorhabditis briggsae, and the more recently discovered Caenorhabditis tropicalis. To survey C. tropicalis genetic relatedness, the influence of geography and niche on species-wide variation, and the signatures of selection, we collected 785...

CONCLUSION: Using a rat model, our study demonstrates estrogen dependent ERE expression in pre-invasive ER^(+)FOXA1^(+) mammary tumor cells and in circulating immune cells, activation of innate immune responses, and the inhibitory effects of 3TC. ERE RNAs and proteins are also highly expressed in human ER^(+)FOXA1^(+) breast cancers, warranting further investigation into their functions and a potential use of 3TC as a preventive strategy for reducing a risk of cancer progression, especially in...

Spontaneous calcium (Ca^(2+)) waves play a critical role as internal stimuli in the early developing auditory system before the onset of sensory experiences. However, neither the spatiotemporal control of spontaneous Ca^(2+) waves nor their impacts on auditory development are well understood. Here we report that a lateral array of inner supporting cells (ISCs) beneath the inner hair cells displays a spontaneous ultra-long, ultra-fast, transient Ca^(2+) flash, termed "Ca^(2+) lightning", which...

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A combination of measurements of the CP properties of Higgs boson interactions with electroweak gauge bosons is presented, using 140 fb^{-1} of proton-proton collisions at sqrt[s]=13 TeV recorded by the ATLAS detector. Results from vector boson fusion H→ττ/WW^{*}/γγ, inclusive H→ZZ^{*}, and WH,H→bb[over ¯] channels are combined. No evidence of CP violation is observed, and constrains on the CP-violating operators in the Standard Model effective field theory framework (SMEFT) are set in the...

CONCLUSIONS: EEG differences between MRI-defined neuroanatomical profiles emerged in relation to clinical outcome. D1 was associated with electrophysiological patterns consistent with flexible, globally regulated cortical dynamics in SSRI responders, whereas D2 showed a distinct pattern in PLA responders, indicating partially separable neural mechanisms underlying pharmacological and PLA treatment effects.

DNA methylation (DNAm) episignatures are stable disorder-specific epigenetic patterns that serve as valuable biomarkers for assessing variant pathogenicity and phenotypic outcomes in neurodevelopmental disorders (NDDs). However, episignatures derived from whole blood are inherently tissue- and cell-type specific, limiting their applicability in prenatal diagnostics. To explore the feasibility of developing episignatures capable of informing variant pathogenicity across tissues and developmental...

Ewing sarcoma (EwS) is a childhood malignancy driven by oncogenic fusion proteins, most commonly EWS::FLI1, and is characterized by paradoxical co-occurrence of inflammation and immunosuppression. Our study shows that LINE, SINE, and LTR/HERV endogenous retroviral elements (EREs) may drive local and systemic inflammation in EwS, and their expression is linked to EWS::FLI1. EREs are not only highly expressed in EwS tumor cells but also disseminated in extracellular vesicles (EVs), selectively...

Defining vaccine-induced protection in children with humoral immunodeficiency is essential to guide SARS-CoV-2 vaccination strategies in this high-risk population. We conducted a longitudinal analysis of SARS-CoV-2 immunity at 1, 6 and 12 months after a primary Pfizer-BioNTech mRNA vaccine series in 27 children aged 5-11 years with primary or secondary antibody deficiencies and 48 matched healthy controls. Functional T-cell responses were quantified by IFN-γ and IL-2 ELISpot, and...

The incidence of disseminated gonococcal infection (DGI) has remained low since the advent of antibiotics; however, a recent surge in DGI has inexplicably emerged during the past decade. In an effort to understand whether Neisseria gonorrhoeae that cause disseminated disease can be differentiated from non-invasive strains, we have performed a phenotypic and genotypic analysis on a selection of isolates obtained from invasive and uncomplicated infections in Canada. The increase in DGI was...

The Human Reference Atlas (HRA) enables multiscale data exploration and visualization. We present "HRA: Powers of Ten," a virtual reality (VR) application for integrating, harmonizing, and visualizing data within the HRA Organ Gallery. It enables immersive navigation from a whole-body view of 81 organs to datasets across 5 organs, 5 assay types, and 4 spatial scales using a Multiscale Elevator System. The application, data, and code are available open-source.

Primary open-angle glaucoma (POAG) is a leading cause of blindness, yet the biochemical mechanisms underlying disease progression remain poorly understood. This study characterized aqueous humor (AH) across early and advanced stages of POAG using large-scale proteomics. AH samples were collected from patients with mild POAG, advanced POAG, and non-glaucomatous controls in this prospective cross-sectional study. Profiling of 8000 proteins was performed using an antibody array. Hierarchical...

CONCLUSIONS: These findings highlight the modest impact of sex on the cancer proteome, but the very limited power of existing proteomics cohorts for these analyses.

BACKGROUND: Engaging knowledge users, including patient partners and health-system partners, in embedded health services research is increasingly recognized as essential for strengthening the relevance of research and improving the quality and equity of health services and is foundational to the success of team science. Existing engagement frameworks, however, often capture experiences at single time points and do not fully reflect relational dimensions over time such as trust, reciprocity,...

Cellular processes are controlled by interconnected networks of protein-protein interactions that can be dynamically regulated by post-translational modifications such as phosphorylation. Dysregulation of signaling pathways can drive cellular transformation and contribute to cancer treatment resistance. Mass spectrometry (MS)-based approaches have emerged as key technologies to study both protein function and their dynamic regulation at a network level. Modern proteomics allows investigators to...

We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (viral transcriptional regulators [vTRs]) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale profiling of vTR binding, chromatin accessibility alterations, and gene expression impact reveals extensive EBV functional interactions with the human genome,...

Comprehensive exams are a standard component of doctoral-level training programs in epidemiology. In this manuscript, we describe current practices in the administration of comprehensive examinations across doctoral programs in epidemiology and discuss variation in the content, format, and structure of these exams. We present results from a survey about the comprehensive exam process at thirty-three different epidemiology programs. We also discuss a symposium focused on comprehensive exams that...

Amyloid beta (Aβ) oligomers are key mediators of synaptic dysfunction and neural circuit impairment in Alzheimer's disease (AD). While plasma Aβ oligomerization propensity (OAβ) correlates with cerebral amyloid pathology and cognitive decline, the systemic modulators of OAβ remain poorly understood. In this study, we identified the albumin interactome (albumin and its associated proteins) as a critical regulator of OAβ. Selective depletion of the albumin interactome from plasma eliminated the...