In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

Exploratory analysis of the variable response to an intensive lifestyle change program for metabolic syndrome.

Background: Substantial variability in response to lifestyle interventions has been recognized for many years, and researchers have begun to disentangle sources of error from inherent differences in individual responsiveness. The objective of this secondary analysis of an intensive lifestyle intervention (diet and exercise) for metabolic syndrome (MetS) was to identify potentially important differences among study completers grouped by treatment response as measured by change in a continuous metabolic syndrome score (Gurka/MetS).

Methods: All study completers from a 12-month primary care study were categorized into one of five groups according to change in the Gurka/MetS score.

Positive Trends in Racial Disparities for Head and Neck Microvascular Reconstructive Surgery.

Objective: To evaluate national trends in racial disparities for patients undergoing head and neck reconstructive surgery.

Methods: Retrospective analysis using the 2008 to 2021 American College of Surgeons National Surgical Quality Improvement Program database. Patients receiving microvascular free tissue transfer were eligible for inclusion.

Systematic multi-trait AAV capsid engineering for efficient gene delivery.

Broadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human knockin mice.

An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an AAV capsid, BI-hTFR1, that binds human Transferrin Receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human knock-in mice.

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence: Tumor Bed vs Resection Specimen Sampling.

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined.

Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC.

Campus food service users' support for nudge strategies for fruit and vegetable-rich items: findings from a large Canadian national sample.

Although customer support is critical to the wider uptake of nudging strategies to promote fruits and vegetables (FV) in institutional food service (FS) settings, empirical research is sparse and typically based on small convenience samples. An online survey was conducted to assess support, perceived effectiveness and intrusiveness of nine nudge types drawn from Münscher 's Taxonomy of Choice Architecture. We focused on the setting of campus FSs across Canada.

Meat reduction among post-secondary students: Exploration of motives, barriers, diets and preferences for meals with partial and full meat substitution.

Before developing new meat reduction interventions to support increased sustainability, it is important to understand the motives, diets and preferences of consumers who have already made efforts to reduce meat consumption. While self-declaration has been typically used to identify meat reducers, food frequency data suggests some reducers still identify as omnivores, here termed transitional meat reducers. We compared these "transitional" meat reducers to self-declared meat reducers, unrestricted omnivores and vegetarians/vegans for differences in diet, motives for reducing meat, and perceived barriers to consuming more legumes (dried beans, peas or lentils) and plant-based meat alternative products (PBMAs).

The Psyche Magnetometry Investigation.

The objective of the Psyche Magnetometry Investigation is to test the hypothesis that asteroid (16) Psyche formed from the core of a differentiated planetesimal. To address this, the Psyche Magnetometer will measure the magnetic field around the asteroid to search for evidence of remanent magnetization. Paleomagnetic measurements of meteorites and dynamo theory indicate that a diversity of planetesimals once generated dynamo magnetic fields in their metallic cores.

Rates of osteoradionecrosis in resected oral cavity cancer reconstructed with free tissue transfer in the intensity-modulated radiotherapy era.

Background: Resected oral cavity carcinoma defects are often reconstructed with osteocutaneous or soft-tissue free flaps, but risk of osteoradionecrosis (ORN) is unknown.

Methods: This retrospective study included oral cavity carcinoma treated with free-tissue reconstruction and postoperative IMRT between 2000 and 2019. Risk-regression assessed risk factors for grade ≥2 ORN.

Association of Treatment Strategies and Tumor Characteristics With Overall Survival Among Patients With Anaplastic Thyroid Cancer: A Single-Institution 21-Year Experience.

Importance: Survival outcomes for anaplastic thyroid cancer (ATC), the most aggressive subtype of thyroid cancers, have remained poor. However, targeted therapies and immunotherapies present new opportunities for treatment of this disease. Evaluations of survival outcomes over time with new multimodal therapies are needed for optimizing treatment plans.

Laryngology Outcomes Following Implantable Vagus Nerve Stimulation.

Importance: Vagus nerve stimulation (VNS) devices have gained widespread acceptance for treatment of resistant epilepsy and depression. The increasing number of procedures has resulted in an increasing number of iatrogenic injuries to the vagus nerve, which can have a significant effect on vocalization and quality of life.

Objective: To determine the relative frequency of laryngeal adverse effects reported to the US Food and Drug Administration (FDA) after VNS implantation and to analyze associated VNS device problems.

Induction of Human T Cell Development In Vitro with OP9-DL4-7FS Cells Expressing Human Cytokines.

For nearly a generation now, OP9-DL1 and OP9-DL4 cells have provided an efficient and reliable cell system to generate T cells from mouse and human hematopoietic stem cells (HSCs) and pluripotent stem cells. OP9-DL1 and OP9-DL4 were originally derived from the OP9 mouse bone marrow stromal cell line, which was transduced to ectopically express Delta-like 1 or 4 proteins, respectively. OP9-DL cells mimic the thymic microenvironment in that when cocultured with mouse or human (h) HSCs, they interact with and activate Notch receptors present on HSCs, required for T cell differentiation.

Relationship between Cardiometabolic Factors and the Response of Blood Pressure to a One-Year Primary Care Lifestyle Intervention in Metabolic Syndrome Patients.

Systemic hypertension has been recognized as a modifiable traditional cardiovascular risk factor and influenced by many factors such as eating habits, physical activity, diabetes, and obesity. The objective of this cross-sectional study was to identify factors that predict changes in blood pressure induced by a one-year lifestyle intervention in primary care settings involving a collaboration between family physicians, dietitians, and exercise specialists. Patients with metabolic syndrome diagnosis were recruited by family physicians participating in primary care lifestyle intervention among several family care clinics across Canada.

Differences in Practitioner Experience, Practice Type, and Profession in Attitudes Toward Growing Contact Lens Practice.

Objective: To investigate eye care practitioners' attitudes and perceptions toward potential interventions that can enhance contact lens (CL) practice across the world, and how this is influenced by their practice setting.

Methods: A self-administered, anonymized survey was constructed in English and then forward and backward translated into six more languages. The survey was distributed online via social media platforms and mailing lists involving reputed international professional bodies.

Key process features of personalized diet counselling in metabolic syndrome: secondary analysis of feasibility study in primary care.

Background: Personalized diet counselling, as part of lifestyle change programs for cardiometabolic risk conditions (combinations of prediabetes or type 2 diabetes, hypertension, dyslipidemia and high waist circumference) has been shown to reduce progression to type 2 diabetes overall. To identify key process of care measures that could be linked to changes in diet, we undertook a secondary analysis of a Canadian pre-post study of lifestyle treatment of metabolic syndrome (MetS). Diet counselling process measures were documented and association with diet quality changes after 3 months were assessed.

Modified Delphi Process to Identify Research Priorities and Measures for Adult Lifestyle Programs to Address Type 2 Diabetes and Other Cardiometabolic Risk Conditions.

Objectives: Clinical and community guidelines recommend lifestyle (i.e. diet and physical activity) interventions for cardiometabolic conditions (including type 2 diabetes), yet current evidence suggests limited and variable services in primary care and public health settings.

Customer support for nudge strategies to promote fruit and vegetable intake in a university food service.

Background: Diverse nudges, also known as choice architectural techniques, have been found to increase fruit and vegetable (FV) selection in both lab and field studies. Such strategies are unlikely to be adopted in mass eating settings without clear evidence of customer support; confirmation in specific contexts is needed. Inspired by the Taxonomy of Choice Architecture, we assessed support for eight types of nudging to increase the choice of FV-rich foods in a university food service.

Cancer Risk Associated with Continuous Positive Airway Pressure: A National Study.

Objective: In 2021 the U.S. FDA issued a Class 1 safety recall notice for specific devices due to a risk of carcinogen exposure.

Readmission Rates Following Major Head and Neck Surgery With Concurrent Tracheostomy.

Objectives: To determine the influence of major head and neck procedures on readmission and complication rates following tracheostomy.

Methods: A retrospective cohort study using the 2005 to 2017 National Surgical Quality Improvement Program (NSQIP) database. Current Procedural Terminology codes were used to identify tracheostomy patients and to define the underlying head and neck procedure.

Nudging food service users to choose fruit- and vegetable-rich items: Five field studies.

Although nudging has been found to promote the choice of healthy foods in lab studies and ad-hoc field studies, relatively little research is available regarding effectiveness in real food venues that operate for profit. The paucity of empirical studies providing "proof of implementation" reveals the difficulty of applying previous empirical findings on nudging to mass-eating food services contexts, which serve meals to a lot of individuals daily. Based on the typology of choice architecture in food choice contexts, we closely collaborated with the in-house food service operator to devise and implement five nudge interventions to promote fruits and vegetables (FV) in university cafeterias.