Personal Protective Equipment Portraits Canada (PPC)-Humanization and surveying mask-wearing nationally.

BACKGROUND: Personal Protective Equipment (PPE) Portraits is a hybridized art and medical intervention that lessens the alienating appearance of PPE through wearable, smiling headshot pictures. During the pandemic, the use of these portraits was expanded, but Canadian initiatives offered portraits only to immediate stakeholders. PPE Portraits Canada (PPC) aimed to provide PPE portraits to any Canadian healthcare institution and surveyed healthcare workers (HCW) regarding these portraits' impact. METHODS: University student volunteers founded PPC via online platforms and coast-to-coast collaborations that allowed any HCW nationwide to request a free portrait via an accessible online form. PPC has gathered feedback from participating HCWs directly via an anonymous and bilingual survey. RESULTS: 70% of HCWs wore their portraits "always" or "usually", 69% of HCWs "definitely would" recommend their portrait, 89.5% of HCWs found that the PPE portraits made a difference in their experiences with patients and 74% found the same for their colleagues. The pre- and post-effect of the portraits, led to a 37.5% greater likelihood that HCWs felt "connected" or "very connected" to patients/residents. For the thematic analysis, 70% or more of the comments were rated as positive, with less than 5% of comments being rated as negative. CONCLUSION: This model's logistical framework can be expanded beyond PPE portraits to other initiatives with limited resources, allowing them to reach and positively impact diverse populations. HCW feedback was predominantly positive. The optimal design and impact of PPE portraits on patients and HCWs should be studied further to improve portrait adoption.

The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer.

In triple-negative breast cancer (TNBC), stromal restriction of CD8+ T cells associates with poor clinical outcomes and lack of responsiveness to immune-checkpoint blockade (ICB). To identify mediators of T cell stromal restriction, we profiled murine breast tumors lacking the transcription factor Stat3, which is commonly hyperactive in breast cancers and promotes an immunosuppressive tumor microenvironment. Expression of the cytokine Chi3l1 was decreased in Stat3-/- tumors. CHI3L1 expression was elevated in human TNBCs and other solid tumors exhibiting T cell stromal restriction. Chi3l1 ablation in the polyoma virus middle T (PyMT) breast cancer model generated an anti-tumor immune response and delayed mammary tumor onset. These effects were associated with increased T cell tumor infiltration and improved response to ICB. Mechanistically, Chi3l1 promoted neutrophil recruitment and neutrophil extracellular trap formation, which blocked T cell infiltration. Our findings provide insight into the mechanism underlying stromal restriction of CD8+ T cells and suggest that targeting Chi3l1 may promote anti-tumor immunity in various tumor types.

HER2Δ16 Engages ENPP1 to Promote an Immune-Cold Microenvironment in Breast Cancer.

The tumor-immune microenvironment (TIME) is a critical determinant of therapeutic response. However, the mechanisms regulating its modulation are not fully understood. HER2Δ16, an oncogenic splice variant of the HER2, has been implicated in breast cancer and other tumor types as a driver of tumorigenesis and metastasis. Nevertheless, the underlying mechanisms of HER2Δ16-mediated oncogenicity remain poorly understood. Here, we show that HER2∆16 expression is not exclusive to the clinically HER2+ subtype and associates with a poor clinical outcome in breast cancer. To understand how HER2 variants modulated the tumor microenvironment, we generated transgenic mouse models expressing either proto-oncogenic HER2 or HER2Δ16 in the mammary epithelium. We found that HER2∆16 tumors were immune cold, characterized by low immune infiltrate and an altered cytokine profile. Using an epithelial cell surface proteomic approach, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) as a functional regulator of the immune cold microenvironment. We generated a knock-in model of HER2Δ16 under the endogenous promoter to understand the role of Enpp1 in aggressive HER2+ breast cancer. Knockdown of Enpp1 in HER2Δ16-derived tumor cells resulted in decreased tumor growth, which correlated with increased T-cell infiltration. These findings suggest that HER2Δ16-dependent Enpp1 activation associates with aggressive HER2+ breast cancer through its immune modulatory function. Our study provides a better understanding of the mechanisms underlying HER2Δ16-mediated oncogenicity and highlights ENPP1 as a potential therapeutic target in aggressive HER2+ breast cancer.

Tailoring therapies to counter the divergent immune landscapes of breast cancer.

Breast cancer remains a significant clinical concern affecting millions of women worldwide. Immunotherapy is a rapidly growing drug class that has revolutionized cancer treatment but remains marginally successful in breast cancer. The success of immunotherapy is dependent on the baseline immune responses as well as removing the brakes off pre-existing anti-tumor immunity. In this review, we summarize the different types of immune microenvironment observed in breast cancer as well as provide approaches to target these different immune subtypes. Such approaches have demonstrated pre-clinical success and are currently under clinical evaluation. The impact of combination of these approaches with already approved chemotherapies and immunotherapies may improve patient outcome and survival.

Five ways to get a grip on organizational logistics, backends, and workflows.

Organizational backends and logistics are often complex and many institutions set-up their workflows based on manual and tedious processes that negatively shape their interactions with stakeholders. Incorporating new technologies can be intimidating. However, a plethora of financially and technically accessible resources that do not require any coding knowledge, can be utilized by institutions to enhance their organizational workflow and stakeholder experience. Guided by our own learning experiences in optimal logistical set-up and user design, we wish to highlight five effective and easily implementable tricks to aid higher institutions and student groups in healthcare to accomplish their administrative duties.

Les backends et la logistique des organisations sont souvent complexes et de nombreuses institutions établissent leurs flux de travail sur la base de processus manuels et fastidieux qui influencent négativement leurs interactions avec les parties prenantes. L'intégration de nouvelles technologies peut être intimidante. Cependant, il existe une pléthore de ressources financièrement et techniquement accessibles, qui ne nécessitent aucune connaissance en codage, que les institutions peuvent utiliser pour améliorer leur flux de travail organisationnel et l'expérience des parties prenantes. Guidés par nos propres expériences d'apprentissage en matière de mise en place d'une logistique optimale et de conception pour l'utilisateur, nous souhaitons mettre en avant cinq astuces efficaces et faciles à mettre en œuvre pour aider les établissements supérieurs et les groupes d'étudiants en soins de santé à accomplir leurs tâches administratives.

Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo.

Breast cancer is associated with the second highest cancer-associated deaths worldwide. Therefore, understanding the key events that determine breast cancer progression, modulation of the tumor-microenvironment and metastasis, which is the main cause of cancer-associated death, are of great importance. The mammary specific polyomavirus middle T antigen overexpression mouse model (MMTV-PyMT), first published in 1992, is the most commonly used genetically engineered mouse model (GEMM) for cancer research. Mammary lesions arising in MMTV-PyMT mice follow similar molecular and histological progression as human breast tumors, making it an invaluable tool for cancer researchers and instrumental in understanding tumor biology. In this review, we will highlight key studies that demonstrate the utility of PyMT derived GEMMs in understanding the molecular basis of breast cancer progression, metastasis and highlight its use as a pre-clinical tool for therapeutic discovery.

Discovery of fifteen new geroprotective plant extracts and identification of cellular processes they affect to prolong the chronological lifespan of budding yeast.

In a quest for previously unknown geroprotective natural chemicals, we used a robust cell viability assay to search for commercially available plant extracts that can substantially prolong the chronological lifespan of budding yeast. Many of these plant extracts have been used in traditional Chinese and other herbal medicines or the Mediterranean and other customary diets. Our search led to a discovery of fifteen plant extracts that significantly extend the longevity of chronologically aging yeast not limited in calorie supply. We show that each of these longevity-extending plant extracts is a geroprotector that decreases the rate of yeast chronological aging and promotes a hormetic stress response. We also show that each of the fifteen geroprotective plant extracts mimics the longevity-extending, stress-protecting, metabolic and physiological effects of a caloric restriction diet but if added to yeast cultured under non-caloric restriction conditions. We provide evidence that the fifteen geroprotective plant extracts exhibit partially overlapping effects on a distinct set of longevity-defining cellular processes. These effects include a rise in coupled mitochondrial respiration, an altered age-related chronology of changes in reactive oxygen species abundance, protection of cellular macromolecules from oxidative damage, and an age-related increase in the resistance to long-term oxidative and thermal stresses.

Mechanisms by which PE21, an extract from the white willow Salix alba, delays chronological aging in budding yeast.

We have recently found that PE21, an extract from the white willow Salix alba, slows chronological aging and prolongs longevity of the yeast Saccharomyces cerevisiae more efficiently than any of the previously known pharmacological interventions. Here, we investigated mechanisms through which PE21 delays yeast chronological aging and extends yeast longevity. We show that PE21 causes a remodeling of lipid metabolism in chronologically aging yeast, thereby instigating changes in the concentrations of several lipid classes. We demonstrate that such changes in the cellular lipidome initiate three mechanisms of aging delay and longevity extension. The first mechanism through which PE21 slows aging and prolongs longevity consists in its ability to decrease the intracellular concentration of free fatty acids. This postpones an age-related onset of liponecrotic cell death promoted by excessive concentrations of free fatty acids. The second mechanism of aging delay and longevity extension by PE21 consists in its ability to decrease the concentrations of triacylglycerols and to increase the concentrations of glycerophospholipids within the endoplasmic reticulum membrane. This activates the unfolded protein response system in the endoplasmic reticulum, which then decelerates an age-related decline in protein and lipid homeostasis and slows down an aging-associated deterioration of cell resistance to stress. The third mechanisms underlying aging delay and longevity extension by PE21 consists in its ability to change lipid concentrations in the mitochondrial membranes. This alters certain catabolic and anabolic processes in mitochondria, thus amending the pattern of aging-associated changes in several key aspects of mitochondrial functionality.