Designing strategies to support Implementation of iNtensive Therapy for Early Reach through PLAY (INTERPLAY) for young children with cerebral palsy: a study protocol.

Background: Intensive manual therapy is important for improving lifelong upper limb motor outcomes for infants and toddlers with cerebral palsy. This play-based therapy is delivered by caregivers who are coached by occupational therapists. However, access to this therapy is very limited for Canadian children with cerebral palsy younger than two years old.

Sterol-like drugs potentiate statin-triggered prostate cancer cell death by inhibiting SREBP2 nuclear translocation.

There is an urgent need to provide immediate and effective options for the treatment of prostate cancer (PCa) to prevent progression to lethal castration-resistant PCa (CRPC). The mevalonate (MVA) pathway is dysregulated in PCa, and statin drugs commonly prescribed for hypercholesterolemia, effectively target this pathway. Statins exhibit anti-PCa activity, however the resulting intracellular depletion of cholesterol triggers a feedback loop that restores MVA pathway activity, thus diminishing statin efficacy and contributing to resistance.

Disparities in diabetes processes of care among people experiencing homelessness: An opportunity for intervention.

Aims: To compare processes of diabetes care by homeless status.

Methods: A population-based propensity matched cohort study was conducted in Ontario, Canada. People with diabetes were identified in administrative healthcare data between April 2006 and March 2019.

Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer's dementia.

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention.

PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice, Leading to Decreased Synaptic Spine Density.

Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.

Pan-Canadian Analysis of Practice Patterns in Small Cell Carcinoma of the Cervix: Insights from a Multidisciplinary Survey.

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO).

Navigating the uncommon: challenges in applying evidence-based medicine to rare diseases and the prospects of artificial intelligence solutions.

The study of rare diseases has long been an area of challenge for medical researchers, with agonizingly slow movement towards improved understanding of pathophysiology and treatments compared with more common illnesses. The push towards evidence-based medicine (EBM), which prioritizes certain types of evidence over others, poses a particular issue when mapped onto rare diseases, which may not be feasibly investigated using the methodologies endorsed by EBM, due to a number of constraints. While other trial designs have been suggested to overcome these limitations (with varying success), perhaps the most recent and enthusiastically adopted is the application of artificial intelligence to rare disease data.

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs.

"Access to healthcare is a human right": a constructivist study exploring the impact and potential of a hospital-community partnered COVID-19 community response team for Toronto homeless services and congregate living settings.

Background: Individuals experiencing homelessness face unique physical and mental health challenges, increased morbidity, and premature mortality. COVID -19 creates a significant heightened risk for those living in congregate sheltering spaces. In March 2020, the COVID-19 Community Response Team formed at Women's College Hospital, to support Toronto shelters and congregate living sites to manage and prevent outbreaks of SARS-CoV-2 using a collaborative model of onsite mobile testing and infection prevention.

The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation.

Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including the microdeletion, bear no obvious connection to translation. Here, we use proteomics, genetics, and translation assays in cultured cells and mouse brain to reveal altered translation mediated by loss of the kinase TAOK2 in deletion models.

A novel in-bed body posture monitoring for decubitus ulcer prevention using body pressure distribution mapping.

Background: Decubitus ulcers are prevalent among the aging population due to a gradual decline in their overall health, such as nutrition, mental health, and mobility, resulting in injury to the skin and tissue. The most common technique to prevent these ulcers is through frequent repositioning to redistribute body pressures. Therefore, the main goal of this study is to facilitate the timely repositioning of patients through the use of a pressure mat to identify in-bed postures in various sleep environments.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure.

Mesenchymal cells support the early retention of primary alveolar type 2 cells on acellular mouse lung scaffolds.

Objectives: Tissue engineering approaches via repopulation of acellular biological grafts provide an exciting opportunity to generate lung grafts for transplantation. Alveolar type 2 (AT2) cells are a promising cell source for re-epithelialization. There are however inherent limitations with respect to their survival and growth, thus impeding their usability for tissue engineering applications.

The Fusion of Wide Field Optical Coherence Tomography and AI: Advancing Breast Cancer Surgical Margin Visualization.

This study explores the integration of Wide Field Optical Coherence Tomography (WF-OCT) with an AI-driven clinical decision support system, with the goal of enhancing productivity and decision making in breast cancer surgery margin assessment. A computationally efficient convolutional neural network (CNN)-based binary classifier is developed using 585 WF-OCT margin scans from 151 subjects. The CNN model swiftly identifies suspicious areas within margins with an on-device inference time of approximately 10 ms for a 420 × 2400 image.

Small-molecule targeting AMPA-mediated excitotoxicity has therapeutic effects in mouse models for multiple sclerosis.

While most research and treatments for multiple sclerosis (MS) focus on autoimmune reactions causing demyelination, it is possible that neurodegeneration precedes the autoimmune response. Hence, glutamate receptor antagonists preventing excitotoxicity showed promise in MS animal models, though blocking glutamate signaling prevents critical neuronal functions. This study reports the discovery of a small molecule that prevents AMPA-mediated excitotoxicity by targeting an allosteric binding site.

Enhancing the value of digital health tools for mental health help-seeking in Canadian transitional aged youth during the pandemic: Qualitative study.

While the COVID-19 pandemic has greatly exacerbated the mental health challenges of transition-aged youth (TAY) between 17 and 29 years old, it has also led to the rapid adoption of digital tools for mental health help-seeking and treatment. However, to date, there has been limited work focusing on how this shift has impacted perceptions, needs and challenges of this population in using digital tools. The current study aims to understand their perspectives on mental health help-seeking during the pandemic and emerging issues related to digital tools (e.

Exploiting redundancy in large materials datasets for efficient machine learning with less data.

Extensive efforts to gather materials data have largely overlooked potential data redundancy. In this study, we present evidence of a significant degree of redundancy across multiple large datasets for various material properties, by revealing that up to 95% of data can be safely removed from machine learning training with little impact on in-distribution prediction performance. The redundant data is related to over-represented material types and does not mitigate the severe performance degradation on out-of-distribution samples.

Pseudomonas aeruginosa biofilm exopolysaccharides: assembly, function, and degradation.

The biofilm matrix is a fortress; sheltering bacteria in a protective and nourishing barrier that allows for growth and adaptation to various surroundings. A variety of different components are found within the matrix including water, lipids, proteins, extracellular DNA, RNA, membrane vesicles, phages, and exopolysaccharides. As part of its biofilm matrix, Pseudomonas aeruginosa is genetically capable of producing three chemically distinct exopolysaccharides - alginate, Pel, and Psl - each of which has a distinct role in biofilm formation and immune evasion during infection.

Understanding the Unmet Accommodation Needs of People Working with Mental or Cognitive Conditions: The Importance of Gender, Gendered Work, and Employment Factors.

Purpose: Workplace support needs for women and men living with mental health conditions are not well understood. This study examined workplace accommodation and support needs among women and men with and without mental health or cognitive conditions and individual and workplace factors associated with having unmet needs.

Methods: A cross-sectional survey of 3068 Canadian workers collected information on disability, gender, gendered occupations, job conditions, work contexts, and workplace accommodations.

Cutaneous mucormycosis in the immunocompromised host: An important cause of persistent post traumatic skin lesions.

We describe a case of a 31-year-old man with a history of ocular non-Hodgkin's lymphoma who presented with a large 12-cm non-resolving traumatic skin lesion on his back. Biopsy showed fungal elements, and on fungal culture, (formerly ) was isolated. Cutaneous mucormycosis is an important diagnostic consideration for a non-resolving skin lesion in an immunocompromised host.

"It just made me feel better": qualitative examination of the implementation of a novel virtual psychosocial support program for adolescents with cancer.

Purpose: Adolescents with cancer routinely report feelings of isolation and exclusion, including from medical decision-making. To address this problem and support adolescents, we designed and implemented the novel, virtual, weekly Teens4Teens peer support group and patient education program. We examined the views of participating adolescents, program guest speakers, and program moderators as they pertained to the need for the program, its feasibility, acceptability, and perceived impact.