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Item type: Item , Access status: Open Access , Mapping policies, regulations, and practice supports for medical office assistants in primary care: a scoping review(BMC, 2026-02-20) Shuldiner, Jennifer; Ragunathan, Apira; Mohammed, Jawairia; Katz, Alan; Andiappan, Meena; Barber, David; Condon, Amanda; Garber, Gary; Kiran, Tara; Hysong, Sylvia; Schoon, Jill; Martin, Danielle; Wong, Sabrina T.; Ivers, NoahImportance: Medical Office Assistants (MOAs) are non-clinicians who carry out critical tasks in primary care settings. Despite their central roles as the first point of contact for patients or at the front desk, there are no reviews of policies, supports or interventions that could help support MOAs within complex primary care clinics. Objective: We systematically scoped the literature to identify interventions, regulations, policies, practice supports, or resources targeting MOAs in primary care. Evidence review: Searches were conducted in Pubmed, EMBASE, Web of Science, and grey literature sources (Google, Google Scholar, and Duckduckgo), for items set in high-income countries and reported in English or French, from January 2000 to December 2024. We additionally searched for references for all articles through Scopus. Articles, reports, papers, or other online materials or articles were included if they reported anything about supporting MOAs in primary care clinics. Data analysis involved descriptive numerical summaries and content analysis. Findings: Sixty articles were included, covering team building or reconfiguration of the team (18/60; 30%), education/counselling/health coaching (15/60; 25%), navigator or care management of patients (10/60; 17%), training or credentials for MOAs (8/60; 13%), screening activities (6/60; 10%), and advanced rooming (3/60; 5%). Articles were primarily set in the United States (47/60; 78%). Workforce well-being was the most common positive outcome (26/60; 43%). Equity outcomes were rarely reported (5/60; 8%). Commonly identified barriers to implementing interventions included time and resource constraints, staffing challenges, inadequate training, and lack of provider buy-in. Involving MOAs in planning, offering role flexibility, and fostering leadership support were important for success. Furthermore, strong leadership, collaborative relationships, and fair compensation were key components of an environment conducive to change. Conclusion and relevance: This review reveals gaps in supporting MOAs as members of the primary care team. Most of the literature focuses on clinic-level changes, with limited evidence on MOA training and/or career growth. Given their strong impact on primary care access and experience for patients, more focus on MOAs in health system reform is warranted.Item type: Item , Access status: Open Access , Transferability of a 10-week remotely delivered Virtual Physical Activity Seated Exercise (V-PASE) program on post-stroke functional mobility: study protocol for a multisite randomized controlled trial(BMC, 2026-02-06) Mackie, Paul; Ashe, Maureen C.; Barclay, Ruth; Bayley, Mark T.; Donkers, Sarah J.; Fleet, Jamie L.; Mortenson, W. B.; Peters, Sue; Pollock, Courtney L.; Pooyania, Sepideh; Quigley, Adria; Sakakibara, Brodie M.; Schneeberg, Amy; Sheehy, Lisa; Stelling, Sally; Yao, Jennifer; Eng, Janice J.Background: Seated exercises may reduce the need for in-person support during home-based exercise programs in people with balance impairments. However, it is uncertain if these exercises can transfer to improved lower extremity function and mobility. Thus, the objective is to investigate the effects of a remotely delivered 10-week seated exercise intervention on functional mobility, compared with control, in individuals living with a chronic stroke who have balance impairments. Methods: The study is a multi-site, assessor blinded, randomized controlled trial that will recruit across five provinces in Canada using the CanStroke Recovery Trials platform. A total of 100 adults living with a chronic stroke (≥ 6 months post-stroke) and mobility impairment (using a walking aid) will be recruited. Participants will be randomized (1:1) to the 10-week Virtual Physical Activity Seated Exercise (V-PASE) or control group. All exercise sessions will be delivered one-on-one through videoconferencing by a trained instructor. Sessions will be 60 min in duration and completed 3 times/week at a moderate intensity (40%–60% Heart Rate Reserve). The primary outcome measure is the 30s Sit-To-Stand score at the end of the 10-week intervention. Secondary outcome measures will be mobility, balance, quality of life, stroke-related quality of life, cognition, fatigue, anxiety, depression, and blood profiles (glucose and lipids). Discussion: Exercises completed in a chair have the potential to transfer to improved functional mobility in people with balance impairments, such as individuals with stroke. The stability of the seated position may improve safety during home-based exercises and thus increase participation. Trial registration: ClinicalTrials.gov NCT05724823. Registered on February 13th, 2023.Item type: Item , Access status: Open Access , Based on the gut–heart axis: Polygonum capitatum improves atherosclerosis by modulating gut microbiota and TMAO, supporting MCPIP1/p53-associated endothelial protection(BMC, 2026-03-09) Wang, Yunpei; Tian, Weiyi; Ye, Zi; Liao, Yuanzhu; Huang, Chunhua; Qi, Dake; Wang, Yuhui; Chen, Yajie; Zhou, YixiaPolygonum capitatum (PC), known as “Tou Hua Liao” (Chinese name), is an essential source of Hmong medicinal plants, which has been used for treating various human diseases. This study examined whether PC has lipid-lowering and anti-atherosclerotic effects and explored the underlying mechanisms. We focused on PC’s influence on gut microbiota–derived metabolites. First, we analyzed animal-derived serum containing PC components and the botanical compounds of PC by UPLC-MS/MS to identify potential bioactive constituents. Second, we treated high-fat diet–fed hamsters with PC to determine whether the treatment improved plasma lipids and attenuated atherosclerosis progression. We then assessed PC’s effects on the gut microbiota by 16S rDNA sequencing and performed fecal microbiota transplantation in hamster models. Finally, we used human umbilical vein endothelial cells (HUVECs) to probe molecular mechanisms by which PC might inhibit oxidative stress and apoptosis. In a diet-induced atherosclerotic hamster model, PC treatment reduced atherosclerosis by decreasing lipid accumulation, oxidative stress, and apoptosis, and it restored gut microbiota balance while markedly lowering the abundance of TMAO-producing bacteria. PC also exerted antioxidant and anti-apoptotic effects and inhibited endothelial apoptosis via an MCPIP1-dependent mechanism. Together, these results indicate that PC suppresses atherosclerosis through two likely pathways: reduction of gut microbiota–derived TMAO production and inhibition of oxidative stress–driven endothelial apoptosis. Network pharmacology analysis of PC-specific blood-absorbed components supports these findings.Item type: Item , Access status: Open Access , Sex differences in disease severity and immune responses in murine and human inflammatory arthritis(BMC, 2026-02-07) Hemshekhar, Mahadevappa; O’Neil, Liam J; Kahia, Nyambura; Marshall, Courtney L.; Singh, Tamarah; Navarrete, Mario; El-Gabalawy, Hani; Mookherjee, Neeloffer; Arsenio, JanilynBackground: Rheumatoid Arthritis (RA), a systemic autoimmune disorder of unknown etiology, disproportionately affects females at a 3:1 ratio compared to males. While biological sex differences in the immune system exist, sex-related differences in inflammatory and immune mediators of RA disease severity are undefined. Our objective was to characterize sex-related differences in immune responses in a murine collagen-induced arthritis (CIA) model and in human RA patients. Methods: In CIA compared to saline control mice, inflammatory disease severity was assessed using standardized clinical scores. Anti-collagen antibodies, neutrophil elastase, calprotectin/ S100A8/A9 heterodimer, CRAMP, MMP3, and MMP9 were quantified by ELISA in the sera and joint tissues. Cytokine/chemokine levels in sera and joints were assessed using a Luminex based-44-Plex Discovery Assay® Array. Immunophenotyping of mouse splenic T cells analysis was performed by flow cytometry. Proteomic profiling of serum samples from an established RA cohort (72 female and 19 male that were at least 84% ACPA+) was performed using an aptamer-based SomaScan platform. Results: We identified distinct sex-related differences in disease severity and pro-inflammatory profiles in the sera and joint tissues of CIA mice, with inflammatory responses that were male-skewed in the sera and female-skewed in the joints. Furthermore, we demonstrated heightened neutrophil activation markers and CD4+ T cell-mediated inflammatory responses in female CIA mice. Similar sex-related differences in neutrophil activation and leucocyte migration were identified in RA patients. Conclusions: Our study demonstrates novel sex differences in pro-inflammatory mediators and activities of neutrophils and CD4+ T cells associated with disease severity in CIA mice, and in human RA patients. These findings provide new insights into sex-related differences in immunological pathways associated with inflammatory arthritis, which may contribute to the sex disparity in RA pathogenesis.Item type: Item , Access status: Open Access , Identifying the knowledge needs and preferences of parents of children with rare diseases regarding clinical trials: a scoping review protocol(BMC, 2026-02-05) Mabbott, Annie P.; Knisley, Lisa; Scott, Shannon D.Background: Rare diseases (i.e., incidence of <1/2000) are individually uncommon, but collectively these 10,000 conditions affect an estimated 473 million people globally, and approximately 70% of rare diseases manifest in childhood. Despite this global impact, 90% of rare diseases lack effective treatment. Treatments for rare diseases are often identified through clinical trials. Identifying parents’ knowledge needs and preferences regarding pediatric rare disease clinical trials is an important aspect of empowering parents, improving clinical research practices, and potentially improving recruitment to these vital trials. The aim of the scoping review is to determine the extent, range, and characteristics of the evidence on the knowledge needs and preferences of parents regarding pediatric rare disease clinical trials. Methods: A scoping review will be conducted to identify sources of literature on the topic. A systematic search strategy co-developed with a research librarian will be conducted in six databases (Medline, EMBASE, CINAHL, Scopus, Web of Science, and PsycINFO). Gray literature will be searched via Google, Perplexity AI, the ProQuest Dissertations & Theses Global database, and relevant rare disease organizational websites. Abstract and full-text screening will be conducted by two reviewers independently. Studies in English will be included regardless of study design, date of publication, or location of study/publication. Study quality will be appraised using the Mixed Methods Appraisal Tool. Data will be extracted including study characteristics, population, phenomena under investigation, and knowledge needs and preferences identified. Analysis will involve a descriptive numerical summary and qualitative content analysis. Findings will be presented in evidence tables, and patterns, themes, and gaps across the data will be reported using a narrative approach. Discussion: This review will provide an overview of the existing literature regarding parents’ knowledge needs and preferences about pediatric rare disease clinical trials. The findings of this review will inform future research and the development of knowledge translation resources for parents of children with rare diseases. Systematic review registration: This protocol has been registered in Open Science Framework (registration: https://doi.org/10.17605/OSF.IO/QXR8G ).Item type: Item , Access status: Open Access , Is Empagliflozin equivalent and/or synergistic with ACE inhibition in the treatment of chemotherapy mediated cardiotoxicity?(2026-03-25) Ali, Sumha; Ravandi, Amir (Internal Medicine); Dhingra, Sanjiv (Physiology and Pathophysiology); Wigle, Jeffrey (Biochemistry and Medical Genetics); Jassal, DavinderBackground: Doxorubicin and Trastuzumab (DOX+TRZ) are two of the most commonly used anti-cancer medications for treating breast cancer. Although these two drugs enhance overall survival rates in women with breast cancer, they are associated with an increased risk of cardiotoxicity. Various randomized controlled trials have demonstrated that sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as Empagliflozin (EMPA), reduce the risk of hospitalizations and mortality due to heart failure in patients with and without diabetes. However, little is known about the potential effects of SGLT2 inhibitors in treating DOX+TRZ mediated cardiotoxicity. Objective: The objective of this thesis is to assess whether the effectiveness of the SGLT2 inhibitor EMPA treatment is similar to and/or synergistic with the standard drug therapy using the RAS inhibitor perindopril (PER) in treating DOX+TRZ-induced cardiomyopathy. Methods: For the 6-week study, a total of 130 C57Bl/6 female mice were randomly assigned to receive weekly treatment with saline (n = 30) or DOX+TRZ (n = 100) intraperitoneally for 3 weeks to establish a chronic in vivo murine model of chemotherapy induced cardiotoxicity. Mice were treated with PER (3 mg/kg), EMPA (10 mg/kg) or EMPA+PER by oral gavage for an additional 3 weeks for a total of 6 weeks. Echocardiography was performed on a weekly basis and at the end of week 6, the mice were euthanized for histological and biochemical analyses. Results: In mice treated with DOX+TRZ (n=15), the left ventricular ejection fraction (LVEF) decreased from 74±4% at baseline to 37±6% at week 6. Mice treated with either PER, EMPA, or EMPA+PER via oral gavage demonstrated an improvement in LVEF of 62±4%, 63±3%, and 64±4%, respectively (p<0.05) (Figure 1). Histological analyses confirmed significant disruption of myofibrils, vacuolization, and loss of sarcomere integrity in the DOX+TRZ treated mice. Oral gavage with EMPA and EMPA+PER, however, improved myofibril integrity at week 6 in mice receiving DOX+TRZ. Finally, the Bax/Bcl-xL ratio, a marker of apoptotic signalling, was significantly increased by approximately 2-fold in mice receiving DOX+TRZ on Western analyses. This increase was attenuated by treatment with PER, EMPA, or the combination of EMPA+PER. Conclusion: EMPA was equivalent to PER in the treatment of DOX+TRZ mediated cardiotoxicity.Item type: Item , Access status: Open Access , Influence of comorbidity burden and senescence on patterns of DNA methylation in patients with Chronic Lymphocytic Leukemia(2026-01-05) Fauni, Maria Shenna; Marshall, Aaron (Immunology); Drögemöller, Britt (Biochemistry and Medical Genetics); Jones, MeaghanChronic lymphocytic leukemia (CLL) is characterized by a heterogeneous clinical course, with some patients showing slowly progressive disease and others progressing rapidly, requiring early intervention. This variability complicates treatment decision-making and highlights the need for reliable prognostic indicators. One emerging factor is frailty, a multidimensional syndrome reflecting cumulative physiological decline across organ systems. In oncology, frailty is often estimated using the Cumulative Illness Rating Scale (CIRS), a weighted comorbidity index with prognostic value. However, the biological basis of CIRS and its relationship to molecular aging remain poorly understood. Because frailty shares physiological features with aging, biological aging markers, particularly epigenetic age derived from DNA methylation (DNAm) patterns, may offer mechanistic insight. Epigenetic age acceleration, where biological age exceeds chronological age, has been proposed as a predictor of frailty and disease risk. However, the accuracy of epigenetic clocks varies by tissue type, population, and training data. Cellular senescence, a hallmark of aging associated with a pro-inflammatory secretory phenotype, may also reshape the epigenetic landscape and influence these clocks. Yet whether senescence contributes to epigenetic age acceleration and clinical frailty in CLL remains unclear. To investigate this, we profiled DNAm in both malignant B cells and non-malignant immune cells from CLL patients aged 52–98 years, examining associations between epigenetic aging, CIRS scores, and known prognostic markers, including IGHV mutation status and CD38 expression. We also analyzed T cell subsets to determine whether cellular senescence affected epigenetic age estimates or their predictive accuracy. Our findings show that epigenetic age acceleration does not correlate with CIRS scores or poor prognostic markers in CLL. Epigenome-wide association studies (EWAS) identified no significant CpG sites associated with high CIRS scores. In addition, cellular senescence markers did not influence epigenetic clock accuracy or affect estimates of cell composition. These results suggest that DNAm-based epigenetic clocks, while valuable for studying aging, may have limited utility in capturing clinical frailty, at least as defined by CIRS, in CLL. Overall, this study highlights the complexity of aging and frailty in hematological malignancies and underscores the importance of integrating molecular, clinical, and immunological data when developing biomarkers for risk stratification and planning.Item type: Item , Access status: Open Access , Livelihood vulnerability, and the role of agency in adaptation: evidence from the Sundarbans fishing communities of Bangladesh(2026-03-19) Ahmed, Rukhser; Rahman, Mokhlesur (Natural Resources Institute); Wilson, Nicole (Environment and Geography); Haque, C. Emdad; Nayak, PrateepClimate change-induced disasters disproportionately impact livelihoods, particularly among coastal small-scale fishing communities in Bangladesh. Climatic hazards intersect deep-rooted socio-economic inequalities, marginalization, gender norms, and other triggers that create differential vulnerability among diverse groups. These issues highlight the importance of assessing and understanding the dynamic patterns of vulnerability and adaptation for effective policy interventions. Using a mixed-method approach, this thesis research assesses the dynamics of intersectional livelihood vulnerability among small-scale fishing communities in the Sundarbans region of Bangladesh and examines how they mobilize individual and collective agency to craft locally grounded adaptation responses in the face of recurring climatic, environmental, and socio-political stressors. Field data were collected from April 2024 to June 2024 in two coastal Unions of Shyamnagar Upazila, Satkhira District, using multiple Participatory Rural Appraisal (PRA) tools. The study integrates numerical household survey data with qualitative insights from key informant interviews, focus group discussions, and participant observation conducted in the study area. The results reveal that the interaction between spatial features and socio-economic processes generates uneven vulnerability of coastal fishing communities to extreme climate-related events. However, people demonstrate proactivity in addressing and adapting to these vulnerabilities, even amid constraints, by exercising their agency. Here, agency is largely deliberate and proactive rather than reactive; it evolves from past triggers and lived experiences and is typically reflected in adaptive actions to sustain livelihoods. The research findings underscore the need to integrate household heterogeneity and intersectionality perspectives into vulnerability assessments. By exploring adaptation actions in connection to various forms of agency, we infer that resilience outcomes depend not only on local adaptive capacities but also on enabling governance conditions that recognize and support meaningful application of agency. Finally, the need for locally grounded adaptation policies, stronger institutional arrangements targeting marginalized groups, and greater investment in women’s capacities to support community resilience in hazard-prone coastal settings is emphasized.Item type: Item , Access status: Open Access , Optimal designs for linear models: balancing efficiency and independence among parameter estimators(2026-03-26) Bae, Gun Ho; Thulasiram, Ruppa (Computer Science); Yang, Po (Statistics); Paul, Sudhir (University of Windsor); Mandal, SaumenOptimal design theory provides a systematic method for selecting experimental conditions that yield efficient and unbiased parameter estimates. While classical design criteria such as D-, A-, and L-optimality have been extensively studied, they often focus on minimizing generalized variance or average variance without considering specific aspects of estimator behaviour. This dissertation develops methods for constructing optimal designs based on the variances, covariances, and correlations among parameter estimators in linear models. It also develops methods for constrained optimal designs by maximizing compound criteria formed by combining classical optimality criteria (D- or A-optimality) with correlation constraints. Beyond classical variance-based objectives, special attention is given to minimizing covariances and correlations among parameter estimators. Criteria are proposed to enforce balance among estimators, such as equalizing variances of specific parameters and reducing correlation structures, thereby improving interpretability and stability of inference. A further contribution is the study of constrained optimal designs. Many practical experiments must satisfy resource, ethical, or operational constraints that restrict the design space or impose conditions on the design measure. This work introduces a general constrained optimization methodology, formulates first-order Lagrangian conditions, and implements iterative algorithms for constrained probability distributions. Numerical studies demonstrate that these constrained designs maintain efficiency while satisfying feasibility requirements, thereby extending the applicability of optimal design methodology to realistic experimental contexts. Applications include polynomial regression models, chemistry-inspired regression models, and a radiation-dosage model examining the effect of treatment levels on tumor shrinkage in breast cancer patients. Across these examples, the proposed designs achieve lower estimator variance, reduced parameter correlation, and improved balance compared to standard optimal designs. Overall, this research contributes to the theory and practice of optimal experimental design by (i) generalizing classical criteria to variance-, covariance-, and correlation-based objectives, (ii) establishing rigorous optimality conditions and algorithmic construction methods, and (iii) extending the methodology to constrained optimization with correlation constraints.Item type: Item , Access status: Open Access , Salmonella Enteritidis (SE) multispecies biofilm formation and its persistence in the poultry environment(2026-03-17) Ebosa, Oritsetimeyin; Bandara, Nandika (Food and Human Nutritional Sciences); Yang, Chengbo (Animal Science); Narváez-Bravo, ClaudiaIntroduction: Salmonella Enteritidis (SE) is a major food-borne pathogen that forms biofilms which attach to processing surfaces in the laying barns and poultry facilities thereby contaminating eggs and poultry products. Methods: The aim was to evaluate SE biofilm formation abilities and SE interactions with selected bacteria associated with eggshells (BAE) and Lactic Acid Bacteria (LAB) in multispecies biofilms formed at 10 and 20 °C in 96-well microplates. In the second study, two multispecies combinations M1: E. coli + P. aeruginosa and M2: B. cereus + P. aeruginosa were assessed for multispecies biofilm formation with 36SusP a strong biofilm former on galvanized steel (GS) and Plastic (PLA) surfaces under dry (20-30% relative humidity; RH) and wet (50-60% RH) conditions at 20 °C for 6 days. Single-species biofilms were used as control positives, and SE recovery from multispecies biofilms was achieved by enrichment. Results: It was found that SE biofilm formation increased significantly at 20 °C (P<0.001), forming strong biofilms in comparison to the weak biofilms formed at 10 °C. At 10 oC SE counts were low (between 4.4 to 5.5 log10 CFU/mL) with all multispecies combinations with E. coli + E. faecalis, P. aeruginosa + E. coli and P. aeruginosa + B. cereus showing a slight increase in bacterial counts that was not statistically significant (P>0.05). At 20 °C however, SE counts reduced with the lowest counts recovered from the combination with P. aeruginosa + E. coli (P<0.05). Regarding the type of surface, SE bacterial growth differed between GS and PLA surfaces under both wet and dry conditions, with PLA having significantly more bacterial retention than GS (P>0.0001). SE recovery was consistent in multispecies biofilms with M1, with enrichment improving recovery in both dry (from 16.7 to 60%) and wet (from 16.7 to 33.3%) conditions, while M2 showed low recovery overall and dropped to 0% even after enrichment in dry and wet conditions. Conclusion: SE biofilm formation is largely temperature-driven, and species-specific traits determine the extent to which cooperative or competitive interactions develop, controlling which species can occupy and persist within the multispecies biofilm, highlighting that biofilm formation relies on ecological relationships.