User-Centered Design and Usability of a Culturally Adapted Virtual Survivorship Care App for Chinese Canadian Prostate Cancer Survivors: Qualitative Descriptive Study.

BACKGROUND: Cultural adaptations of digital health innovations are a growing field. However, digital health innovations can increase health inequities. While completing exploratory work for the cultural adaptation of the Ned Clinic virtual survivorship app, we identified structural considerations that provided a space to design digitally connected and collective care. OBJECTIVE: This study used a community-based participatory research and user-centered design process to develop a cultural adaptation of the Ned Clinic app while designing to intervene in structural inequities. METHODS: The design process included primary data collection and qualitative analysis to explore and distill design principles, an iterative design phase with a multidisciplinary team, and a final evaluation phase with participants throughout the design process as a form of member checking and validation. RESULTS: Participants indicated that they found the final adapted prototype to be acceptable, appropriate, and feasible for their use. The changes made to adapt the prototype were not specifically culturally Chinese. Instead, we identified ways to strengthen connections between the survivor and their providers; improve accessibility to resources; and honor participants' desires for relationality, accountability, and care. CONCLUSIONS: We grounded the use of user-centered design to develop a prototype design that supports the acts of caring through digital technology by identifying and designing to resist structures that create health inequities in the lives of this community of survivors. By designing for collective justice, we can provide accessible, feasible, and relational care with digital health through the application of Indigenous and Black feminist ways of being and knowing.

Beyond the Body: Using Photovoice to Explore Social Determinants of Diabetes With South Asian Adolescents in the Peel Region of Ontario, Canada.

OBJECTIVES: The higher prevalence of diabetes in the South Asian (SA) population living in Canada spans across generations and is often associated with individual risk factors while undermining the social determinants of health (SDOH). There is a scarcity of studies on the perspectives of SA adolescents with a family history of type 2 diabetes mellitus (T2DM). Learning directly from these adolescents can fill a major gap by providing insight on how the SDOH contribute to disproportionate rates of T2DM in SA immigrant communities. METHODS: In this study, we used Photovoice, which is a community-based participatory research (CBPR) method that involves the use of photography to visually capture the challenges of diabetes prevention from the perspective of those with lived experiences. A group of 15 SA youth were recruited from an adolescent diabetes education program in the Peel Region of Ontario. The youth discussed their images and accompanied written narratives during focus groups. RESULTS: Four themes emerged from the thematic analysis of the photographs and participant narratives that influence the manifestation of T2DM in SA communities: 1) immigration and resettlement stressors; 2) food insecurity; 3) unhealthy school environments; and 4) academic pressures. CONCLUSIONS: Findings suggest the need to address T2DM as a response to unjust conditions and environments rather than as an epidemic entrenched in genetic predisposition, culture, and poor lifestyle choices.

Assessing Support for Policy Actions With Co-Benefits for Climate Change and Physical Activity in Canada.

BACKGROUND: Calls to action addressing the interconnections between physical (in)activity and the climate crisis are increasing. The current study aimed to investigate public support for policy actions that potentially have co-benefits for physical activity promotion and climate change mitigation. METHODS: In 2023, a survey through the Angus Reid Forum was completed by 2507 adults living in Canada. Binary logistic regressions were conducted. Separate models were created to reflect support or opposition to the 8 included policy items. Several covariates were included in the models including age, gender, political orientation, physical activity levels, income, urbanicity climate anxiety, and attitudes surrounding physical activity and climate change. The data were weighted to reflect the gender, age, and regional composition of the country. RESULTS: Most individuals living in Canada strongly or moderately supported all actions (ranging from 71% to 85%). Meeting the physical activity guidelines, higher self-reported income, and scoring high on personal experience of climate change were associated with higher odds of supporting the policy actions related to climate actions. CONCLUSIONS: Most adults living in Canada support policies that align with the recommended policy actions related to physical activity and climate change. National campaigns enhancing awareness and understanding of the bidirectional relationship between physical activity and climate change are warranted, and these should consider the consistent demographic differences (eg, gender, age, and political orientation) seen in public support for physical activity-related policies.

Re-assessing the social climate of physical (in)activity in Canada.

Social-ecological models suggest that a strategy for increasing population physical activity participation is to reconstruct the "social climate" through changing social norms and beliefs about physical activity (PA). In this study, we assessed whether the PA social climate in Canada has changed over a five-year period after controlling for sociodemographic factors and PA levels. Replicating a survey administered in 2018, a sample of adults in Canada (n = 2,507) completed an online survey assessing social climate dimensions, including but not limited to descriptive and injunctive norms. Descriptive statistics were calculated, and binary logistic regressions were conducted to assess the associations of sociodemographic factors and year of the survey with social climate dimensions. Results suggest some social climate constructs are trending in a positive direction between 2018 and 2023. Physical inactivity was considered a serious public health concern by 49% of respondents, second to unhealthy diets (52%). Compared to those who participated in the 2018 survey, participants in 2023 were less likely to see others walking or wheeling in their neighbourhood (OR = 1.58, 95% CI: 1.41, 1.78), but more likely to see people exercising (OR = 0.82, 95% CI: 0.73, 0.92) and kids playing in their neighbourhood (OR = 0.75, 95% CI: 0.66, 0.85). No changes were reported between 2018 and 2023 in individuals' perceptions of whether physical inactivity is due to individual versus external factors (OR = 0.99, 95% CI: 0.87, 1.13). The findings of this work indicate a modest positive shift in some measured components of the social climate surrounding PA although attributing causes for these changes remain speculative.

Honoring the Care Experiences of Chinese Canadian Survivors of Prostate Cancer to Cultivate Cultural Safety and Relationality in Digital Health: Exploratory-Descriptive Qualitative Study.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed nonskin cancer for Canadian men and has one of the highest 5-year survival rates, straining systems to provide care. Virtual care can be one way to relieve this strain, but survivors' care needs and technology use are influenced by intersecting social and cultural structures. Cultural adaptation has been posited as an effective method to tailor existing interventions to better serve racialized communities, including Chinese men. However, cultural adaptations may inadvertently draw attention away from addressing structural inequities. OBJECTIVE: This study used qualitative methods to (1) explore the perceptions and experiences of Chinese Canadian PCa survivors with follow-up and virtual care, and (2) identify implications for the cultural adaptation of a PCa follow-up care app, the Ned (no evidence of disease) Clinic. METHODS: An axiology of relational accountability and a relational paradigm underpinned our phenomenologically informed exploratory-descriptive qualitative study design. A community-based participatory approach was used, informed by cultural safety and user-centered design principles, to invite Chinese Canadian PCa survivors and their caregivers to share their stories. Data were inductively analyzed to explore their unmet needs, common experiences, and levels of digital literacy. RESULTS: Unmet needs and technology preferences were similar to broader trends within the wider community of PCa survivors. However, participants indicated that they felt uncomfortable, unable to, or ignored when expressing their needs. Responses spoke to a sense of isolation and reflected a reliance on culturally informed coping mechanisms, such as "eating bitterness," and familial assistance to overcome systemic barriers and gaps in care. Moreover, virtual care was viewed as "better than nothing;" it did not change a perceived lack of focus on improving quality of life or care continuity in survivorship care. Systemic changes were identified as likely to be more effective in improving care delivery and well-being rather than the cultural adaptation of Ned for Chinese Canadians. Participants' desires for care reflected accessibility issues that were not culturally specific to Chinese Canadians. CONCLUSIONS: Chinese Canadian survivors are seeking to strengthen their connections in a health care system that provides privacy and accessibility, protects relationality, and promotes transparency, accountability, and responsibility. Designing "trickle-up" adaptations that address structural inequities and emphasize accessibility, relationality, and privacy may be more effective and efficient at improving care than creating cultural adaptations of interventions.

Social Media Interventions for Nutrition Education Among Adolescents: Scoping Review.

BACKGROUND: Adolescence is a critical period for reinforcing healthy dietary behaviors and supporting the development of cooking skills. Social media may be an avenue for supporting these behaviors, as it is popular among adolescents and can improve access to nutrition education interventions. This study sought to understand the optimal implementation of effective social media-based nutrition education interventions to inform the implementation of future social media-based nutrition education interventions. OBJECTIVE: A scoping review of the characteristics, feasibility, effectiveness, and factors influencing social media-based nutrition education interventions for adolescents was conducted. METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science, and PsycINFO databases using a predefined search strategy. Primary research articles were independently screened and included if they involved adolescent populations (10-18 years old) and delivered nutrition education through social media. The information on intervention characteristics, feasibility, effectiveness, and factors influencing social media-based nutrition education interventions was extracted. RESULTS: A total of 28 publications out of 20,557 met the eligibility criteria. Twenty-five nutrition interventions were examined by 28 studies. Fourteen interventions used homegrown social media platforms, 8 used Facebook, and 2 used Instagram. Feasibility outcomes were infrequently reported, and the cost of intervention delivery was not reported. Engagement with interventions was variable; high engagement was not required to elicit significant improvements in dietary behaviors. Tailoring interventions, offering practical content, meaningful peer support, and involving families and communities facilitated successful interventions. Strategies to address engagement and technical issues were varied. CONCLUSIONS: Emerging evidence demonstrates that social media interventions for adolescent nutrition are acceptable and improve nutrition outcomes. Future interventions should strengthen peer support components and tailor delivery to specific populations. Further research should examine engagement, adherence, and the impact of interventions on behavioral and physical outcomes. This review is the first to examine the use of social media as the primary medium for nutrition education for adolescent populations. The analysis used in this review argues the importance of peer support in social media-based nutrition interventions and the need for user-centered design of the interventions.

ALDH1A1 promotes PARP inhibitor resistance by enhancing retinoic acid receptor-mediated DNA polymerase θ expression.

Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi) have been approved for both frontline and recurrent setting in ovarian cancer with homologous recombination (HR) repair deficiency. However, more than 40% of BRCA1/2-mutated ovarian cancer lack the initial response to PARPi treatment, and the majority of those that initially respond eventually develop resistance. Our previous study has demonstrated that increased expression of aldehyde dehydrogenase 1A1 (ALDH1A1) contributes to PARPi resistance in BRCA2-mutated ovarian cancer cells by enhancing microhomology-mediated end joining (MMEJ) but the mechanism remains unknown. Here, we find that ALDH1A1 enhances the expression of DNA polymerase θ (Polθ, encoded by the POLQ gene) in ovarian cancer cells. Furthermore, we demonstrate that the retinoic acid (RA) pathway is involved in the transcription activation of the POLQ gene. The RA receptor (RAR) can bind to the retinoic acid response element (RARE) located in the promoter of the POLQ gene, promoting transcription activation-related histone modification in the presence of RA. Given that ALDH1A1 catalyzes the biosynthesis of RA, we conclude that ALDH1A1 promotes POLQ expression via the activation of the RA signaling pathway. Finally, using a clinically-relevant patient-derived organoid (PDO) model, we find that ALDH1A1 inhibition by the pharmacological inhibitor NCT-505 in combination with the PARP inhibitor olaparib synergistically reduce the cell viability of PDOs carrying BRCA1/2 mutation and positive ALDH1A1 expression. In summary, our study elucidates a new mechanism contributing to PARPi resistance in HR-deficient ovarian cancer and shows the therapeutic potential of combining PARPi and ALDH1A1 inhibition in treating these patients.

Embedding anti-racism in Schools of Public Health: a pathway to accountability for progress towards equity.

The importance of seeing race as a socially constructed idea continues to produce unfair differences between humans and establishes power relations that lead to injustice and exposure to death. Since the racial justice movement in early 2020, there has been a heightened awareness of, and increased interest in, addressing historic racial disparities across Schools of Public Health (SPH) in Canada. Steps have been taken to recognize systemic racism and increase diversity through structural reforms to advance equity and inclusion; however, addressing racism demands collectively uprooting racist institutional designs still inherent in learning, teaching, research, service, and community engagement. This commentary highlights the need for sustained commitment to establishing longitudinal benchmarks for greater racial equity among students, staff, and faculty; revising curricula to include historic and contemporary narratives of colonialism and slavery; and providing community-engaged learning opportunities as instrumental to dismantle systemic drivers of racial health inequities locally and globally. We also advocate for intersectoral collaboration, mutual learning, and sharing of resources across SPH and partner agencies to accomplish a continual collective agenda for racial health equity and inclusion that is intersectional in Canada, while being held accountable to Indigenous and racialized communities.

RéSUMé: L'importance de voir la race comme une idée socialement construite continue de produire des différences inéquitables entre les gens et d'établir des relations de pouvoir qui mènent à l'injustice et à l'exposition à la mort. Depuis que le mouvement pour la justice raciale s'est enclenché au début de 2020, il existe une conscience aiguë des disparités raciales historiques entre les écoles de santé publique (ESP) du Canada et un intérêt accru pour le redressement de ces disparités. Des mesures ont été prises pour reconnaître le racisme systémique et accroître la diversité par des réformes structurelles visant à promouvoir l'équité et l'inclusion; cependant, pour aborder le racisme, il faut collectivement arracher les modèles institutionnels racistes qui font encore partie intégrante de l'apprentissage, de l'enseignement, de la recherche, des services et de la participation de la communauté. Dans notre commentaire, nous soulignons le besoin d'un engagement soutenu à établir des repères longitudinaux pour une plus grande équité raciale dans la population étudiante, au sein du personnel et dans le corps professoral, à revoir les programmes d'études pour y inclure les discours historiques et contemporains du colonialisme et de l'esclavage, et à offrir des possibilités d'enseignement faisant appel aux communautés, car elles contribueront à démanteler les moteurs systémiques des iniquités raciales en santé à l'échelle locale et mondiale. Nous promulguons aussi la collaboration intersectorielle, l'apprentissage mutuel et le partage des ressources entre les ESP et les organismes partenaires afin de concrétiser un plan d'action collective continue en faveur de l'équité raciale en santé et de l'inclusion ­ un plan qui sera intersectionnel au Canada et qui rendra des comptes aux communautés autochtones et racisées.

ERK inactivation enhances stemness of NSCLC cells via promoting Slug-mediated epithelial-to-mesenchymal transition.

Rationale: The mitogen-activated protein kinase pathway (MAPK) is one of the major cancer-driving pathways found in non-small cell lung cancer (NSCLC) patients. ERK inhibitors (ERKi) have been shown to be effective in NSCLC patients with MAPK pathway mutations. However, like other MAPK inhibitors, ERKi rarely confers complete and durable responses. The mechanism of tumor relapse after ERKi treatment is yet defined. Methods: To best study the mechanism of tumor relapse after ERK inhibitor treatment in NSCLC patients, we treated various NSCLC cell lines and patient-derived xenograft (PDX) with ERK inhibitors and evaluated the enrichment of cancer stem cell (CSC) population. We then performed a Next-generation sequencing (NGS) to identify potential pathways that are responsible for the CSC enrichment. Further, the involvement of specific pathways was examined using molecular and cellular methods. Finally, we investigated the therapeutic benefits of ERKi treatment combined with JAK/STAT pathway inhibitor using cellular and xenograft NSCLC models. Results: We found that ERKi treatment expands the CSC population in NSCLC cells through enhanced epithelial-to-mesenchymal transition (EMT)-mediated cancer cell dedifferentiation. Mechanistically, ERK inactivation induces EMT via pSTAT3-mediated upregulation of Slug, in which, upregulation of miR-204 and downregulation of SPDEF, a transcription repressor of Slug, are involved. Finally, the JAK/STAT pathway inhibitor Ruxolitinib blocks the ERK inactivation-induced EMT and CSC expansion, as well as the tumor progression in xenograft models after ERKi treatment. Conclusions: This study revealed a potential tumor relapse mechanism of NSCLC after ERK inhibition through the unintended activation of the EMT program, ascertained the pSTAT-miR-204-SPDEF-Slug axis, and provided a promising combination inhibitor approach to prevent tumor relapse in patients.

PDE4 inhibitor eliminates breast cancer stem cells via noncanonical activation of mTOR.

Ineffective cancer treatment is implicated in metastasis, recurrence, resistance to chemotherapy and radiotherapy, and evasion of immune surveillance. All these failures occur due to the persistence of cancer stem cells (CSCs) even after rigorous therapy, thereby rendering them as essential targets for cancer management. Contrary to the quiescent nature of CSCs, a gene profiler array disclosed that phosphatidylinositol-3-kinase (PI3K), which is known to be crucial for cell proliferation, differentiation, and survival, was significantly upregulated in CSCs. Since PI3K is modulated by cyclic adenosine 3',5' monophosphate (cAMP), analyses of cAMP regulation revealed that breast CSCs expressed increased levels of phosphodiesterase 4 (PDE4) in contrast to normal stem cells. In accordance, the effects of rolipram, a PDE4 inhibitor, were evaluated on PI3K regulators and signaling. The efficacy of rolipram was compared with paclitaxel, an anticancer drug that is ineffective in obliterating breast CSCs. Analyses of downstream signaling components revealed a switch between cell survival and death, in response to rolipram, specifically of the CSCs. Rolipram-mediated downregulation of PDE4A levels in breast CSCs led to an increase in cAMP levels and protein kinase A (PKA) expression. Subsequently, PKA-mediated upregulation of phosphatase and tensin homolog antagonized the PI3K/AKT/mTOR pathway and led to cell cycle arrest. Interestingly, direct yet noncanonical activation of mTOR by PKA, circumventing the influence of PI3K and AKT, temporally shifted the fate of CSCs toward apoptosis. Rolipram in combination with paclitaxel indicated synergistic consequences, which effectively obliterated CSCs within a tumor, thereby suggesting combinatorial therapy as a sustainable and effective strategy to abrogate breast CSCs for better patient prognosis.

Service Provider Perspectives on Exploring Social Determinants of Health Impacting Type 2 Diabetes Management for South Asian Adults in Peel Region, Canada.

OBJECTIVES: Individuals from South Asian communities are known to have a higher likelihood of developing type 2 diabetes (T2D), which is often attributed to individual lifestyle and behavioural factors. This focus on individual responsibility can position communities as complicit in their illness, compounding stigmatization and systemic discrimination. In this article, we explore the social determinants of health (SDOH) that influence health behaviours among South Asian adults with T2D from a service provider's perspective. METHODS: Using a qualitative descriptive design, we conducted semistructured interviews with 12 community, social and health-care service providers. We used thematic analysis and the analytical concept of intersectionality to explore how different social locations and SDOH impact T2D management for South Asian adults. RESULTS: Three themes were identified: 1) managing challenges with settlement process, labour policies and job market disparities take priority over T2D management; 2) poor working conditions and low socioeconomic status reduce access to health care and medication; and 3) there are social, economic and cultural barriers to implementing diet and exercise recommendations. CONCLUSIONS: Service providers identified social, economic and systemic factors as influencing the higher prevalence of T2D among South Asian individuals. They also identified their important roles in providing culturally appropriate supports to address SDOH and described advocacy for changes to policies and practices that reinforce systemic racism. The providers further suggested that more equitable employment policies and practices are needed to address the systemic factors that contribute to the higher risk of T2D among South Asian adults in the Peel Region.

A Novel Estrogen Receptor ß Agonist Diminishes Ovarian Cancer Stem Cells via Suppressing the Epithelial-to-Mesenchymal Transition.

Epithelial ovarian cancer is the most lethal malignancy of the female reproductive tract. A healthy ovary expresses both Estrogen Receptor α (ERα) and ß (ERß). Given that ERα is generally considered to promote cell survival and proliferation, thereby, enhancing tumor growth, while ERß shows a protective effect against the development and progression of tumors, the activation of ERß by its agonists could be therapeutically beneficial for ovarian cancer. Here, we demonstrate that the activation of ERß using a newly developed ERß agonist, OSU-ERb-12, can impede ovarian cancer cell expansion and tumor growth in an ERα-independent manner. More interestingly, we found that OSU-ERb-12 also reduces the cancer stem cell (CSC) population in ovarian cancer by compromising non-CSC-to-CSC conversion. Mechanistically, we revealed that OSU-ERb-12 decreased the expression of Snail, a master regulator of the epithelial-to-mesenchymal transition (EMT), which is associated with de novo CSC generation. Given that ERα can mediate EMT and facilitate maintenance of the CSC subpopulation and that OSU-ERb-12 can block the transactivity of ERα, we conclude that OSU-ERb-12 reduces the CSC subpopulation by inhibiting EMT in an ERα-dependent manner. Taken together, our data indicate that the ERß agonist OSU-ERb-12 could be used to hinder tumor progression and limit the CSC subpopulation with the potential to prevent tumor relapse and metastasis in patients with ovarian cancer.

Antiproliferative and apoptotic potential of methotrexate lipid nanoparticles in a murine breast cancer model.

Aim: To evaluate the efficacy of novel methotrexate-loaded nanoparticles (MTX-NPs) in vitro and in vivo in the treatment of breast cancer. Materials & methods: MTX-NPs were tested for cellular uptake, cell viability, cell cycle, cellular wound migration and changes in tumor volume using characterized NPs. Results: The solid lipid NPs (SLNPs) showed strong cellular uptake, increased apoptosis, controlled cytotoxicity at lower IC50 of methotrexate and a sizable reduction in tumor burden. Conclusion: MTX-NP oral formulation can be a promising candidate in breast cancer treatment with improved cellular uptake and in vivo efficacy.

Poor health disparities among racialized students in a Canadian university.

OBJECTIVE: The short report aims to examine differences in self-rated general health across racialized post-secondary students at a university in Ontario, Canada. METHODS: Binary logistic regression analysis was used to examine poor health as an outcome among racialized students as whole, as well as across Asian, South Asian, Afro-Caribbean and Middle Eastern student groups in comparison to white Caucasian post-secondary students. RESULTS: After adjusting for several covariates, racialized students as a whole had 2.43 times the odds of reporting poor general health compared to white Caucasian students. Asian (OR = 2.77; CI = 1.84-4.18; p < 0.05) and South Asian (OR = 2.52; CI = 1.56-4.08; p < 0.05) students were significantly more likely to report poor health compared to white Caucasian students. CONCLUSION: The findings call for further attention to the health needs of racialized post-secondary students living in Canada and creating campuses where diverse student populations feel safe and systemically included.

Determination of DNA lesion bypass using a ChIP-based assay.

DNA lesion bypass facilitates DNA synthesis across bulky DNA lesions, playing a critical role in DNA damage tolerance and cell survival after DNA damage. Assessing lesion bypass efficiency in the cell is important to better understanding of the mechanism of carcinogenesis and chemoresistance. Here we developed a chromatin immunoprecipitation (ChIP)-based method to measure lesion bypass activity across cisplatin-induced intrastrand crosslinks in cancer cells. DNA lesion bypass enables the replication to continue in the presence of replication blocks. Thus, the successful lesion bypass should result in the coexistence of DNA lesions and the newly synthesized DNA fragment opposite to this lesion. Using ChIP, we precipitated the cisplatin-induced intrastrand crosslinks, and quantitated the precipitated newly synthesized DNA that was labeled with BrdU. We validated this method on ovarian cancer cells with inhibited TLS activity. We then applied this method to show that ovarian cancer stem cells exhibit high lesion bypass activity relative to bulk cancer cells from the same cell line. In conclusion, this novel ChIP-based lesion bypass assay can detect the extent to which cisplatin-induced DNA lesions are bypassed in live cells. Our study may be applied more broadly to the study of other DNA lesions, as specific antibodies to these specific lesions are available.