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Abstract Background Health-system policy makers need timely access to synthesised research evidence to inform the policy-making process. No efforts to address this need have been evaluated using an experimental quantitative design. We developed an evidence service that draws inputs from Health Systems Evidence, which is a database of policy-relevant systematic reviews. The reviews have been (a) categorised by topic and type of review; (b) coded by the last year searches for studies were conducted and by the countries in which included studies were conducted; (c) rated for quality; and (d) linked to available user-friendly summaries, scientific abstracts, and full-text reports. Our goal is to evaluate whether a "full-serve" evidence service increases the use of synthesized research evidence by policy analysts and advisors in the Ontario Ministry of Health and Long-Term Care (MOHLTC) as compared to a "self-serve" evidence service. Methods/design We will conduct a two-arm randomized controlled trial (RCT), along with a follow-up qualitative process study in order to explore the findings in greater depth. For the RCT, all policy analysts and policy advisors (n = 168) in a single division of the MOHLTC will be invited to participate. Using a stratified randomized design, participants will be randomized to receive either the "full-serve" evidence service (database access, monthly e-mail alerts, and full-text article availability) or the "self-serve" evidence service (database access only). The trial duration will be ten months (two-month baseline period, six-month intervention period, and two month cross-over period). The primary outcome will be the mean number of site visits/month/user between baseline and the end of the intervention period. The secondary outcome will be participants' intention to use research evidence. For the qualitative study, 15 participants from each trial arm (n = 30) will be purposively sampled. One-on-one semi-structured interviews will be conducted by telephone on their views about and their experiences with the evidence service they received, how helpful it was in their work, why it was helpful (or not helpful), what aspects were most and least helpful and why, and recommendations for next steps. Discussion To our knowledge, this will be the first RCT to evaluate the effects of an evidence service specifically designed to support health-system policy makers in finding and using research evidence. Trial registration ClinicalTrials.gov: NCT01307228

Abstract Background The electronic health record (EHR) is an important application of information and communication technologies to the healthcare sector. EHR implementation is expected to produce benefits for patients, professionals, organisations, and the population as a whole. These benefits cannot be achieved without the adoption of EHR by healthcare professionals. Nevertheless, the influence of individual and organisational factors in determining EHR adoption is still unclear. This study aims to assess the unique contribution of individual and organisational factors on EHR adoption in healthcare settings, as well as possible interrelations between these factors. Methods A prospective study will be conducted. A stratified random sampling method will be used to select 50 healthcare organisations in the Quebec City Health Region (Canada). At the individual level, a sample of 15 to 30 health professionals will be chosen within each organisation depending on its size. A semi-structured questionnaire will be administered to two key informants in each organisation to collect organisational data. A composite adoption score of EHR adoption will be developed based on a Delphi process and will be used as the outcome variable. Twelve to eighteen months after the first contact, depending on the pace of EHR implementation, key informants and clinicians will be contacted once again to monitor the evolution of EHR adoption. A multilevel regression model will be applied to identify the organisational and individual determinants of EHR adoption in clinical settings. Alternative analytical models would be applied if necessary. Results The study will assess the contribution of organisational and individual factors, as well as their interactions, to the implementation of EHR in clinical settings. Conclusions These results will be very relevant for decision makers and managers who are facing the challenge of implementing EHR in the healthcare system. In addition, this research constitutes a major contribution to the field of knowledge transfer and implementation science.

Abstract Background While the evidence suggests that the way physicians provide information to patients is crucial in helping patients decide upon a course of action, the field of knowledge translation and exchange (KTE) is silent about how the physician and the patient influence each other during clinical interactions and decision-making. Consequently, based on a novel relationship-centered model, EXACKTE2 (EXploiting the clinicAl Consultation as a Knowledge Transfer and Exchange Environment), this study proposes to assess how patients and physicians influence each other in consultations. Methods We will employ a cross-sectional study design involving 300 pairs of patients and family physicians from two primary care practice-based research networks. The consultation between patient and physician will be audio-taped and transcribed. Following the consultation, patients and physicians will complete a set of questionnaires based on the EXACKTE2 model. All questionnaires will be similar for patients and physicians. These questionnaires will assess the key concepts of our proposed model based on the essential elements of shared decision-making (SDM): definition and explanation of problem; presentation of options; discussion of pros and cons; clarification of patient values and preferences; discussion of patient ability and self-efficacy; presentation of doctor knowledge and recommendation; and checking and clarifying understanding. Patients will be contacted by phone two weeks later and asked to complete questionnaires on decisional regret and quality of life. The analysis will be conducted to compare the key concepts in the EXACKTE2 model between patients and physicians. It will also allow the assessment of how patients and physicians influence each other in consultations. Discussion Our proposed model, EXACKTE2, is aimed at advancing the science of KTE based on a relationship process when decision-making has to take place. It fosters a new KTE paradigm by putting forward a relationship-centered perspective and has the potential to reveal unknown mechanisms that underline effective KTE in clinical contexts. This will result in better understanding of the mechanisms that may promote a new generation of knowledge transfer strategies.

Background: While the evidence suggests that the way physicians provide information to patients is crucial in helping patients decide upon a course of action, the field of knowledge translation and exchange (KTE) is silent about how the physician and the patient influence each other during clinical interactions and decision-making. Consequently, based on a novel relationship-centered model, EXACKTE(2) (EXploiting the clinicAl Consultation as a Knowledge Transfer and Exchange Environment), this study proposes to assess how patients and physicians influence each other in consultations.Methods: We will employ a cross-sectional study design involving 300 pairs of patients and family physicians from two primary care practice-based research networks. The consultation between patient and physician will be audio-taped and transcribed. Following the consultation, patients and physicians will complete a set of questionnaires based on the EXACKTE(2) model. All questionnaires will be similar for patients and physicians. These questionnaires will assess the key concepts of our proposed model based on the essential elements of shared decision-making (SDM): definition and explanation of problem; presentation of options; discussion of pros and cons; clarification of patient values and preferences; discussion of patient ability and self-efficacy; presentation of doctor knowledge and recommendation; and checking and clarifying understanding. Patients will be contacted by phone two weeks later and asked to complete questionnaires on decisional regret and quality of life. The analysis will be conducted to compare the key concepts in the EXACKTE(2) model between patients and physicians. It will also allow the assessment of how patients and physicians influence each other in consultations.Discussion: Our proposed model, EXACKTE(2), is aimed at advancing the science of KTE based on a relationship process when decision-making has to take place. It fosters a new KTE paradigm by putting forward a relationship-centered perspective and has the potential to reveal unknown mechanisms that underline effective KTE in clinical contexts. This will result in better understanding of the mechanisms that may promote a new generation of knowledge transfer strategies. [ABSTRACT FROM AUTHOR]

Background: Before the COVID-19 pandemic, it was already recognized that internet-based misinformation and disinformation could influence individuals to refuse or delay vaccination for themselves, their families, or their children. Reinformation, which refers to hyperpartisan and ideologically biased content, can propagate polarizing messages on vaccines, thereby contributing to vaccine hesitancy even if it is not outright disinformation., Objective: This study aimed to evaluate the impact of reinformation on vaccine hesitancy. Specifically, the goal was to investigate how misinformation presented in the style and layout of a news article could influence the perceived tentativeness (credibility) of COVID-19 vaccine information and confidence in COVID-19 vaccination., Methods: We conducted a web-based randomized controlled trial by recruiting English-speaking Canadians aged 18 years and older from across Canada through the Qualtrics (Silver Lake) paid opt-in panel system. Participants were randomly assigned to 1 of 4 distinct versions of a news article on COVID-19 vaccines, each featuring variations in writing style and presentation layout. After reading the news article, participants self-assessed the tentativeness of the information provided, their confidence in COVID-19 vaccines, and their attitude toward vaccination in general., Results: The survey included 537 participants, with 12 excluded for not meeting the task completion time. The final sample comprised 525 participants distributed about equally across the 4 news article versions. Chi-square analyses revealed a statistically significant association between general attitude toward vaccination and the perceived tentativeness of the information about COVID-19 vaccines included in the news article (χ 2 1 =37.8, P<.001). The effect size was small to moderate, with Cramer V=0.27. An interaction was found between vaccine attitude and writing style (χ 2 1 =6.2, P=.01), with a small effect size, Cramer V=0.11. In addition, a Pearson correlation revealed a significant moderate to strong correlation between perceived tentativeness and confidence in COVID-19 vaccination, r(523)=0.48, P<.001. The coefficient of determination (r 2 ) was 0.23, indicating that 23% of the variance in perceived tentativeness was explained by confidence in COVID-19 vaccines. In comparing participants exposed to a journalistic-style news article with those exposed to an ideologically biased article, Cohen d was calculated to be 0.38, indicating a small to medium effect size for the difference in the perceived tentativeness between these groups., Conclusions: Exposure to a news article conveying misinformation may not be sufficient to change an individual's level of vaccine hesitancy. The study reveals that the predominant factor in shaping individuals' perceptions of COVID-19 vaccines is their attitude toward vaccination in general. This attitude also moderates the influence of writing style on perceived tentativeness; the stronger one's opposition to vaccines, the less pronounced the impact of writing style on perceived tentativeness., International Registered Report Identifier (irrid): RR2-10.2196/41012., (©Benoît Béchard, Julie A Gramaccia, Dominique Gagnon, Elhadji Anassour Laouan-Sidi, Ève Dubé, Mathieu Ouimet, Delphine de Hemptinne, Sébastien Tremblay. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.12.2024.)

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality, with disparities observed between males and females. Psychosocial work exposures (PWE), including workload, job control, reward and long working hours, are associated with CVD development. Despite higher prevalence among females, the association with CVD is consistently observed in males, with limited explanations for these differences. This study aimed to examine the consideration of sex and gender in prospective studies within systematic reviews on PWE - specifically, the demand-control model, the effort-reward imbalance model, and long working hours - and CVD. Conducting a systematic review, we assessed sex and gender considerations using criteria from the Sex and Gender Equity in Research (SAGER) guidelines. While most studies recognized potential sex and gender differences in the associations between PWE and CVD, only about half of the 28 studies that included both sexes (15 studies) analyzed females and males separately. Moreover, few studies included criteria for sex- and gender-based analyses. Less than half of the studies (23 studies) incorporated a sex and/or gender perspective to discuss observed differences and similarities between men and women. Although there is a rising trend in integrating sex and gender considerations, significant gaps persist in methodologies and reporting, highlighting the need for comprehensive incorporation of sex and gender considerations to bolster CVD prevention strategies and policies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Evidence suggests that workers exposed to psychosocial stressors at work from the effort-reward imbalance (ERI) model are at increased risk for type 2 diabetes mellitus (T2DM). However, evidence about the effect of ERI on prediabetes is scarce. This study aimed to examine the association between effort-reward imbalance at work, glycated hemoglobin level and the prevalence of prediabetes in women and men from a prospective cohort study., Methods: This study was conducted among 1354 white-collar workers followed for an average of 18 years. Effort-reward imbalance at work was measured in 1999 to 2001 using a validated instrument. Glycated hemoglobin was assessed at follow-up (2015 to 2018). Differences in mean glycated hemoglobin levels were estimated with linear models. Prediabetes prevalence ratios (PRs) were computed using robust Poisson regression models., Results: In women, those exposed to effort-reward imbalance at work at baseline had a higher prevalence of prediabetes (PR = 1.60, 95% confidence interval: 1.02-2.49) at follow-up following adjustment for sociodemographic, lifestyle-related, clinical, and other occupational risk factors. There was no difference in mean glycated hemoglobin levels., Conclusion: Among women, effort-reward imbalance at work at midlife was associated with the prevalence of prediabetes, at older age. Preventive workplace interventions aiming to reduce the prevalence of effort-reward imbalance at work may be effective to reduce the prevalence of prediabetes among women., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Hypertension is the foremost risk factor for cardiovascular disease (CVD), which is the leading cause of death globally. In some countries, such as the US, the prevalence of hypertension and working-age CVD mortality are increasing. CVD is also the most common work-related disease worldwide. Long working hours and other psychosocial stressors at work are important modifiable risk factors for hypertension and CVD. However, there has been inadequate attention paid to the primary prevention of work-related hypertension and CVD. The state-of-the art method for blood pressure (BP) measurement is 24-hour ambulatory BP (ABP), necessary for accurate clinical decision making and to assess risk factors for BP elevation. Thus, ABP should be used in workplace screening and surveillance programs (along with surveys) to identify occupational risk factors, high-risk job titles, worksites and shifts, and evaluate programs designed to improve work organization. For example, after 30 months of an organizational intervention designed to lower psychosocial stressors at work among >2000 public sector white-collar workers in Quebec, Canada, BP and prevalence of hypertension significantly decreased in the intervention group, with no change in the control group, and a significant difference between the intervention and control groups. Further research is also needed on mechanisms linking work-related factors to hypertension and CVD, the cardiovascular effects of understudied work stressors, high-CVD risk worker groups, potential "upstream" intervention points, and country differences in working conditions, hypertension and CVD. Important organizational interventions, such as collective bargaining, worker cooperatives, or legislative and regulatory-level interventions, need to be evaluated.

Background: Healthcare workers (HCWs) can face situations that conflict with their moral beliefs, leading to moral injury, an adverse psychological consequence that was more frequent during the COVID-19 pandemic. Self-compassion is a potential coping mechanism for moral injury by encouraging acceptance of human limitations and suffering., Objectives: This study aimed to examine the associations between self-compassion components and moral injury prevalence among HCWs in Quebec, Canada, during the COVID-19 pandemic., Research Design: A cross-sectional study design was employed. Participants : and research context: The sample of this study consisted of HCWs and leaders from the Quebec province. Participants completed validated self-administered questionnaires assessing both positive and negative self-compassion components (self-kindness vs self-judgment; common humanity vs isolation; and mindfulness vs overidentification) and moral injury dimensions (self-oriented and other-oriented). Prevalence ratios (PRs) and 95% confidence intervals (CIs) for the associations between self-compassion components and moral injury dimensions were modeled using Poison robust regressions. The models were adjusted for various covariates, including sex, age, gender, and socio-demographic and lifestyle factors., Ethical Considerations: Ethical approval for this study was obtained from the ethics committee of the Centre intégré universitaire de santé et de services sociaux de la Capitale-Nationale in Quebec, Canada. All participants provided written informed consent prior to participating in the study. Additionally, permission was sought and obtained from the original authors of the tools used in this study, including the self-compassion and moral injury scales., Results: The study involved 572 HCWs (60.5% nurses) and leaders. Around half of the participants (50.70%) exhibited moderate levels of self-compassion, while the prevalence of low levels of self-compassion ranged from 21.68% to 48.08% for the positive subscales and from 23.78% to 44.41% for the negative subscales. Regarding moral injury, 10.14% of participants reported moderate to high self-oriented moral injury, 29.19% reported moderate to high other-oriented moral injury, and 13.81% demonstrated moderate to high total moral injury. Higher self-compassion levels were associated with lower moral injury prevalence. HCWs with high self-compassion had a 93% lower likelihood of experiencing moral injury (PR: 0.07, 95% CI: 0.03-0.19). Self-kindness demonstrated the strongest association with reduced moral injury (PR: 0.24, 95% CI: 0.11-0.52), followed by mindfulness (PR: 0.37, 95% CI: 0.18-0.75). However, common humanity did not show a statistically significant association with moral injury prevalence., Conclusion: These findings suggest a potential association between self-compassion and reduced prevalence of moral injury among HCWs, highlighting promising interventions to manage moral injury during crises. Such initiatives could promote the mental wellbeing of HCWs and preventing the negative consequences of moral injury, including anxiety, depression, and burnout., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Examining gender (socio-cultural) in addition to sex (biological) is required to untangle socio-cultural characteristics contributing to inequities within or between sexes. This study aimed to develop a gender measure including four gender dimensions and examine the association between this gender measure and CVD incidence, across sexes., Methods: A cohort of 9188 white-collar workers (49.9% females) in the Quebec region was recruited in 1991-1993 and follow-up was carried out 28 years later for CVD incidence. Data collection involved a self-administered questionnaire and extraction of medical-administrative CVD incident cases. Cox proportional models allowed calculations of hazard ratios (HR) and 95% confidence intervals (CI), stratified by sex., Results: Sex and gender were partly independent, as discordances were observed in the distribution of the gender score across sexes. Among males, being in the third tertile of the gender score (indicating a higher level of characteristics traditionally ascribed to women) was associated with a 50% CVD risk increase compared to those in the first tertile (HR = 1.50; 95% CI: 1.24 to 1.82). This association persisted after adjustment for several CVD risk factors (HR = 1.42; 95% CI: 1.16 to 1.73). Conversely, no statistically significant association between the third tertile of the gender score and CVD incidence was observed in females (HR = 0.79, 95% CI: 0.60-1.05)., Conclusions: The findings suggested that males within the third tertile of the gender score were more likely to develop CVD, while females with those characteristics did not exhibit an increased risk. These findings underline the necessity for clinical and population health research to integrate both sex and gender measures, to further evaluate disparities in cardiovascular health and enhance the inclusivity of prevention strategies., (© 2024. The Author(s).)

Introduction: The COVID-19 pandemic has had a major impact on nursing staff, resulting in alarming turnover rates. As part of the Quebec (Canada) government's response to the pandemic, nurses have been offered exceptional financial incentives. Considering the cost of these measures, the current article presents the research protocol of a study aiming to explore the impact of financial incentives on full-time equivalent, and retention rates among the nursing staff in two healthcare settings in Quebec., Methods and Analysis: A sequential mixed design (QUANT→QUAL) will be used. The quantitative phase will involve a quantitative descriptive analysis and the qualitative phase will consist of a qualitative descriptive study. Administrative data (working hours, employment status and retention rate) will be analysed over a 4.5-year follow-up (from 1 January 2019 to 30 June 2023) to explore the impact of the financial incentives. Focus groups will explore nurses' views on financial incentives. The results will inform the development of future interventions to mitigate attrition problems among nurses and ultimately improve access to and the continuity of public health services., Ethics and Dissemination: The study has been approved by ethics committees of the participating healthcare settings (Comité d'éthique de la recherche sectorial en santé des populations et première ligne du CIUSSS de la Capitale-Nationale; Comité d'éthique de la recherche du CISSS de Chaudière-Appalaches). The results will be disseminated mainly in scientific publications and at academic conferences in addition to presentations tailored to various non-academic audiences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Controlled substances (CS) are 'diverted' (stolen) from healthcare facilities via many integrated and diverse mechanisms due to a lack of safeguards. There remains a gap in understanding how healthcare workers (HCWs) leverage their social networks (e.g., their role/tasks and interactions with other roles/tasks) within the medication use process (MUP) that contribute to diversion. Social network analysis (SNA) is an analytic approach used to map and analyze social connections, which can help identify influential interdependence between HCWs and tasks susceptible to drug diversion., Objectives: To map the social network structures of MUP tasks vulnerable to CS diversion in two Inpatient pharmacies and compare diversion risks by identifying influential tasks and HCWs., Methods: This was an exploratory sequential mixed methods study conducted in the Inpatient pharmacies at two large hospitals in Toronto, Canada. Initial analysis used previously collected clinical observation data to identify key pharmacy roles and tasks vulnerable to CS diversion. Subsequently, a cross-sectional survey was conducted to collect demographic information on HCWs and assess their engagement in the identified vulnerable tasks. Clinical observations and survey data were used to perform two-mode SNA to identify connections between HCWs and tasks susceptible to drug diversion., Results: The analysis identified different network structures across both sites but highlighted the importance of strategic Pharmacist or Technician Supervisor oversight to moderate-high vulnerability tasks. Pharmacy technicians were found to be the network's most central actors, while Pharmacists had a more supportive role on the network's periphery, providing oversight. Across both sites, there was strong connectivity between HCWs and tasks, indicating a higher level of security against potential undetected diversion., Conclusion: By strategically involving Pharmacists or Technician Supervisors, diversion risk can be mitigated through cross-checking and quality control. Through identifying the network structure of each unit, hospitals can identify opportunities for future interventions to prevent diversion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The aim was to estimate direct medical costs of men and women patients by age group related to cardiovascular diseases (coronary heart disease, strokes) in the province of Quebec, Canada from the economic perspective of the healthcare public system, encompassing five cost components: physician fees, hospitalization (hospital stay, intensive care stay), emergency visits and medication costs., Methods: This matched case-control study involved secondary data from a longitudinal cohort study (1997-2018) of 4584 white-collar workers. Participants were followed for a four-year period. We used an incremental cost method of difference-in-difference. Descriptive analyses using frequency counts, arithmetic means, standardized differences, chi-squared tests, and Student's T-tests were performed. Direct medical costs were estimated using mean and 95% bootstrap confidence interval., Results: Direct medical costs per case were CAD $4970 [4344, 5595] for all in the first year after the event. For men patients, direct medical costs were $5351 [4649, 6053] and $4234 [2880, 5588] for women in the first year after the event, $221 [-229, 671] for men and $226 [-727, 1179] for women in the second year, and $11 [-356, 377] for men and $-24 [-612, 564] for women in the third year. This decrease was observed for both men and women, with higher costs for men. Within the first year, physician fees dominated CVD-associated costs among both men and women cases younger than 65. However, hospital stay represented the costliest component among cases aged 65 and older, incurring higher costs in women compared to men. In the subsequent years, the distribution of costs showed variations according to sex and age, with either medication costs or physician fees being the predominant components, depending on the specific subgroups., Conclusions: CVD-associated direct medical costs varied by components, sex, age, and follow-up years. Patients with CVD incurred more than twice the medical costs as compared to patients without CVD of same age and sex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gilbert-Ouimet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We estimated, for women and men (1) the associations between psychological distress and the prevalences of presenteeism and absenteeism, (2) average hours lost annually per person, and (3) costs from the employers' economic perspective., Methods: Participants were 1292 Canadian white-collar workers. Psychological distress, presenteeism, and absenteeism were assessed with validated questionnaires. The average annual hours of productivity loss and related costs were estimated using generalized linear models with a negative binomial distribution and a log link., Results: High psychological distress in women and men was associated with presenteeism costs ($6944 and $8432) and absenteeism costs ($2337 and $2796 per person). The association between psychological distress and annual hours lost to presenteeism was twice stronger for men than women., Conclusions: Productivity losses associated with psychological distress are high in women and men older workers., Competing Interests: Conflict of interest: M.G.-O. currently holds the Tier 2 Canada Research Chair in Sex and Gender in Occupational Health (CRC-2019-00255). J.R.G. is the recipient of a Chercheur-boursier Junior 2 career award from the Fonds de recherche du Québec-Santé (award no. 330678). The rest of the authors declare no conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background: Communication breakdowns among healthcare providers have been identified as a significant cause of preventable adverse events, including harm to patients. A large proportion of studies investigating communication in healthcare organizations lack the necessary understanding of social networks to make meaningful improvements. Process Improvement in healthcare (systematic approach of identifying, analyzing, and enhancing workflows) is needed to improve quality and patient safety. This review aimed to characterize the use of SNA methods in Process Improvement within healthcare organizations., Methods: Relevant studies were identified through a systematic search of seven databases from inception - October 2022. No limits were placed on study design or language. The reviewers independently charted data from eligible full-text studies using a standardized data abstraction form and resolved discrepancies by consensus. The abstracted information was synthesized quantitatively and narratively., Results: Upon full-text review, 38 unique articles were included. Most studies were published between 2015 and 2021 (26, 68%). Studies focused primarily on physicians and nursing staff. The majority of identified studies were descriptive and cross-sectional, with 5 studies using longitudinal experimental study designs. SNA studies in healthcare focusing on process improvement spanned three themes: Organizational structure (e.g., hierarchical structures, professional boundaries, geographical dispersion, technology limitations that impact communication and collaboration), team performance (e.g., communication patterns and information flow among providers., and influential actors (e.g., key individuals or roles within healthcare teams who serve as central connectors or influencers in communication and decision-making processes)., Conclusions: SNA methods can characterize Process Improvement through mapping, quantifying, and visualizing social relations, revealing inefficiencies, which can then be targeted to develop interventions to enhance communication, foster collaboration, and improve patient safety., (© 2024. The Author(s).)

Background: Psychosocial stressors at work, defined by the job strain and effort-reward imbalance at work (ERI) models, were shown to increase coronary heart disease risk. No previous study has examined the adverse effect of psychosocial stressors at work from both models on atrial fibrillation (AF) incidence. The objective of this study was to examine the separate and combined effect of psychosocial stressors at work from the job strain and ERI models on AF incidence in a prospective cohort study., Methods and Results: A total of 5926 white-collar workers (3021 women and 2905 men) free of cardiovascular disease at baseline were followed for an average of 18 years. Job strain (high psychological demands combined with low decision latitude) and ERI were assessed using validated instruments. AF events were identified in medical databases with universal coverage. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression models, controlling for socioeconomic characteristics and lifestyle-related and clinical risk factors. A total of 186 AF incident events were identified over 18 years. Workers exposed to job strain (HR, 1.83 [95% CI, 1.14-2.92]) and ERI (HR, 1.44 [95% CI, 1.05-1.98]) had a higher risk of AF in fully adjusted models. Combined exposure to job strain and ERI was associated with a 2-fold AF risk increase (HR, 1.97 [95% CI, 1.26-3.07])., Conclusions: Psychosocial stressors at work from the job strain and ERI models are associated with an increased risk of AF, separately and in combination. Workplace prevention strategies targeting these psychosocial stressors at work may be effective to reduce the burden associated with AF.

Dysregulation of the hematopoietic niche during hyperlipidemia facilitates pathologic leukocyte production, driving atherogenesis. Although definitive hematopoiesis occurs primarily in the bone marrow, during atherosclerosis this also occurs in the spleen. Cells of the bone marrow niche, particularly endothelial cells, have been studied in atherosclerosis, although little is known about how splenic endothelial cells respond to the atherogenic environment. Here we show unique dysregulated pathways in splenic compared to bone marrow endothelial cells during atherosclerosis, including perturbations of lipid metabolism and endocytic trafficking pathways. As part of this response, we identify the mixed lineage kinase domain-like (MLKL) protein as a repressor of splenic, but not bone marrow, myelopoiesis. Silencing MLKL in splenic endothelial cells results in inefficient endosomal trafficking and lipid accumulation, ultimately promoting the production of myeloid cells that participate in plaque development. These studies identify endocytic trafficking by MLKL as a key mechanism of splenic endothelial cell maintenance, splenic hematopoiesis and, subsequently, atherosclerosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Atherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression., Methods and Results: Atherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1β content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4 + T cells. Lastly, we found that autophagy flux in male mice was basally higher than in female mice during atherosclerosis progression., Conclusions: Our data demonstrate a sex-specific effect of trehalose in atherosclerosis regression, whereby trehalose reduced lipid content, inflammation, and increased collagen content in female mice but not in male mice. Furthermore, we discovered inherent differences in the autophagy flux capacities between the sexes: female mice exhibited lower plaque autophagy than males, which rendered the female mice more responsive to atherosclerosis regression. Our work highlights the importance of understanding sex differences in atherosclerosis to personalize the development of future therapies to treat cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Robichaud, Rochon, Emerton, Laval and Ouimet.)

Background: Alterations of FLT3 are among the most common driver events in acute leukaemia with important clinical implications, since it allows patient classification into prognostic groups and the possibility of personalising therapy thanks to the availability of FLT3 inhibitors. Most of the knowledge on FLT3 implications comes from the study of acute myeloid leukaemia and so far, few studies have been performed in other leukaemias., Methods: A comprehensive genomic (DNA-seq in 267 patients) and transcriptomic (RNA-seq in 160 patients) analysis of FLT3 in 342 childhood acute lymphoblastic leukaemia (ALL) patients was performed. Mutations were functionally characterised by in vitro experiments., Results: Point mutations (PM) and internal tandem duplications (ITD) were detected in 4.3% and 2.7% of the patients, respectively. A new activating mutation of the TKD, G846D, conferred oncogenic properties and sorafenib resistance. Moreover, a novel alteration involving the circularisation of read-through transcripts (rt-circRNAs) was observed in 10% of the cases. Patients presenting FLT3 alterations exhibited higher levels of the receptor. In addition, patients with ZNF384- and MLL/KMT2A-rearranged ALL, as well as hyperdiploid subtype, overexpressed FLT3., Discussion: Our results suggest that specific ALL subgroups may also benefit from a deeper understanding of the biology of FLT3 alterations and their clinical implications., (© 2023. The Author(s).)

The continuous improvement of expression platforms is necessary to respond to the increasing demand for recombinant proteins that are required to carry out structural or functional studies as well as for their characterization as biotherapeutics. While transient gene expression (TGE) in mammalian cells constitutes a rapid and well-established approach, non-clonal stably transfected cells, or "pools," represent another option, which is especially attractive when recurring productions of the same protein are required. From a culture volume of just a few liters, stable pools can provide hundreds of milligrams to gram quantities of high-quality secreted recombinant proteins.In this chapter, we describe a highly efficient and cost-effective procedure for the generation of Chinese Hamster Ovary cell stable pools expressing secreted recombinant proteins using commercially available serum-free media and polyethylenimine (PEI) as the transfection reagent. As a specific example of how this protocol can be applied, the production and downstream purification of recombinant His-tagged trimeric SARS-CoV-2 spike protein ectodomain (SmT1) are described., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The coronavirus 2019 (COVID-19) pandemic allowed for exceptional decision-making power to be placed in the hands of public health departments. Data and information were widely disseminated in the media and on websites. While the improvement of pandemic management is still a learning curve, the ecosystem perspective - that is, the interconnection of academic health research systems and decision-making spaces - has received little attention. In this commentary, we look at the mechanisms in place, or not, in Canada for ensuring decision-making spheres can "speak" to academic research systems. We look at the thick walls that are still in place between health research systems and decision-making spaces. More precisely, we discuss three organizational flaws that we identified in the evidence-informed decision-making ecosystem of Québec and, more broadly, Canada. We introduce some inspiring measures that other countries have implemented to better link evidence and public health decision-making during health crises. The observed flaws and options are related to the vitality of early information sharing relays, the cross-sectional capacity to issue opinions, and the collection and integration of hard and soft data., (© 2023. The Author(s).)

Objectives: There is evidence that both low socioeconomic status (SES) and psychosocial stressors at work (PSW) increase risk of depression, but prospective studies on the contribution of PSW to the socioeconomic gradient of depression are still limited., Methods: Using a prospective cohort of Quebec white-collar workers (n = 9188 participants, 50% women), we estimated randomized interventional analogues of the natural direct effect of SES indicators at baseline (education level, household income, occupation type and a combined measure) and of their natural indirect effects mediated through PSW (job strain and effort-reward imbalance (ERI) measured at the follow-up in 1999-2001) on incident physician-diagnosed depression., Results: During 3 years of follow-up, we identified 469 new cases (women: 33.1 per 1000 person-years; men: 16.8). Mainly in men, low SES was a risk factor for depression [education: hazard ratio 1.72 (1.08-2.73); family income: 1.67 (1.04-2.67); occupational type: 2.13 (1.08-4.19)]. In the entire population, exposure to psychosocial stressors at work was associated with increased risk of depression [job strain: 1.42 (1.14-1.78); effort-reward imbalance (ERI) 1.73 (1.41-2.12)]. The estimated indirect effects of socioeconomic indicators on depression mediated through job strain ranged from 1.01 (0.99-1.03) to 1.04 (0.98-1.10), 4-15% of total effects, and for low reward from 1.02 (1.00-1.03) to 1.06 (1.01-1.11), 10-15% of total effects., Discussion: Our study suggests that PSW only slightly mediate the socioeconomic gradient of depression, but that socioeconomic inequalities, especially among men, and PSW both increase the incidence of depression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pena-Gralle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Psychological distress and intention to leave school are highly prevalent among nursing students. Academic conditions, including psychosocial stressors and school-work-life conflicts, could contribute to psychological distress and intention to leave school., Objective: To explore the associations between academic conditions and 1) psychological distress and 2) intention to leave school., Design: Cross-sectional correlational design., Settings: Data collection was performed in February and October 2021 in two nursing schools in Canada: Cegep (publicly funded college, technical degree) and university (bachelor's degree)., Participants: 230 nursing students (Cegep 131, university 99)., Methods: A self-administered online questionnaire assessed academic conditions (psychosocial stressors (Demand-Control-Support, Effort-Reward Imbalance and Overcommitment scales) and school-work-life conflicts (single item)), psychological distress (Kessler-6 scale), intention to leave school, and several covariates. Poisson robust multivariate regression models were built to explore the associations between academic conditions and 1) psychological distress and 2) intention to leave school., Results: A large proportion of participants experienced high efforts, school-work-life conflicts, overcommitment, and psychological distress (49.5-84.7 %). One out of five participants had had intention to leave school "many times" (Cegep 20.61 %; university 22.22 %). In adjusted analysis, overcommitment and school-work-life conflicts were associated with a higher prevalence of psychological distress (Prevalence ratio = 2.10; 95 % Confidence Intervals = 1.15-3.84 and Prevalence ratio = 2.32; 95 % Confidence Intervals = 1.24-4.32, respectively). Adverse associations were observed between effort-reward imbalance (Prevalence ratio = 2.32; 95 % Confidence Intervals = 1.09-4.94) as well as school-work-life conflicts (Prevalence ratio = 2.40; 95 % Confidence Intervals = 1.05-5.45) and intention to leave school., Conclusions: Academic conditions might be risk factors for psychological distress and intention to leave school among nursing students. Interventions targeting modifiable academic conditions might improve nursing students' mental health and retention., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Psychosocial stressors at work, like job strain and effort-reward imbalance (ERI), can increase coronary heart disease (CHD) risk. ERI indicates an imbalance between the effort and received rewards. Evidence about the adverse effect of combined exposure to these work stressors on CHD risk is scarce. This study examines the separate and combined effect of job strain and ERI exposure on CHD incidence in a prospective cohort of white-collar workers in Quebec, Canada., Methods: Six thousand four hundred sixty-five white-collar workers without cardiovascular disease (mean age, 45.3±6.7) were followed for 18 years (from 2000 to 2018). Job strain and ERI were measured with validated questionnaires. CHD events were retrieved from medico-administrative databases using validated algorithms. Marginal Cox models were used to calculate hazard ratios (HR) stratified by sex. Multiple imputation and inverse probability weights were applied to minimize potential threats to internal validity., Results: Among 3118 men, 571 had a first CHD event. Exposure to either job strain or ERI was associated with an adjusted 49% CHD risk increase (HR, 1.49 [95% CI, 1.07-2.09]). Combined exposure to job strain and ERI was associated with an adjusted 103% CHD risk increase (HR, 2.03 [95% CI, 1.38-2.97]). Exclusion of early CHD cases and censoring at retirement did not alter these associations. Among 3347 women, 265 had a first CHD event. Findings were inconclusive (passive job HR, 1.24 [95% CI, 0.80-1.91]; active job HR, 1.16 [95% CI, 0.70-1.94]; job strain HR, 1.08 [95% CI, 0.66-1.77]; ERI HR, 1.02 [95% CI, 0.72-1.45])., Conclusions: In this prospective cohort study, men exposed to job strain or ERI, separately and in combination, were at increased risk of CHD. Early interventions on these psychosocial stressors at work in men may be effective prevention strategies to reduce CHD burden. Among women, further investigation is required., Competing Interests: Disclosures Drs Talbot, Gilbert-Ouimet, Vézina, Trudel, Milot, and Brisson reported receiving grants from the Canadian Institute of Health Research during the conduct of the study. M. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec en santé. Dr Talbot is supported by a research career award from the Fonds de Recherche du Québec en Santé. The other authors report no conflicts.

Objective: Arterial stiffness and exposure to psychosocial work-related factors increase the risk of developing cardiovascular disease. However, little is known about the relationship between psychosocial work-related factors and arterial stiffness. We aimed to examine this relationship., Design: Prospective cohort study., Setting: Public organisations in Quebec City, Canada., Participants: The study included 1736 white-collar workers (women 52%) from 19 public organisations., Primary and Secondary Outcome Measures: Association between psychosocial work-related factors from the job strain and effort-reward imbalance (ERI) models assessed at study baseline (1999-2001) with validated instruments and arterial stiffness assessed using carotid-femoral pulse wave velocity at follow-up, on average 16 years later (2015-2018). Generalised estimating equations were used to estimate differences in arterial stiffness between exposed and unexposed participants. Subgroup analyses according to sex, age, blood pressure (BP), cardiovascular risk score and employment status were conducted., Results: Among participants with high diastolic BP (≥90 mm Hg) at baseline, aged 47 on average, those exposed to high job strain had higher arterial stiffness (1.38 m/s (95% CI: 0.57 to 2.19)) at follow-up, 16 years later, following adjustment for a large set of potential confounders. The trend was similar in participants with high systolic BP (≥140 mm Hg) exposed to high job strain (0.84 m/s (95% CI: -0.35 to 2.03)). No association was observed for ERI in the total sample and counterintuitive associations were observed in subgroup analyses., Conclusions: Job strain may have a long-term deleterious effect on arterial stiffness in people with high BP. Interventions at midlife to reduce job strain may mitigate arterial stiffness progression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Protein expression from stably transfected Chinese hamster ovary (CHO) clones is an established but time-consuming method for manufacturing therapeutic recombinant proteins. The use of faster, alternative approaches, such as non-clonal stable pools, has been restricted due to lower productivity and longstanding regulatory guidelines. Recently, the performance of stable pools has improved dramatically, making them a viable option for quickly producing drug substance for GLP-toxicology and early-phase clinical trials in scenarios such as pandemics that demand rapid production timelines. Compared to stable CHO clones which can take several months to generate and characterize, stable pool development can be completed in only a few weeks. Here, we compared the productivity and product quality of trimeric SARS-CoV-2 spike protein ectodomains produced from stable CHO pools or clones. Using a set of biophysical and biochemical assays we show that product quality is very similar and that CHO pools demonstrate sufficient productivity to generate vaccine candidates for early clinical trials. Based on these data, we propose that regulatory guidelines should be updated to permit production of early clinical trial material from CHO pools to enable more rapid and cost-effective clinical evaluation of potentially life-saving vaccines., (© 2023 National Research Council Canada. Biotechnology and Bioengineering published by Wiley Periodicals LLC. Reproduced with the permission of the Minister of Innovation, Science, and Economic Development.)

The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers (51% female). Work-related psychosocial factors were evaluated according to the Demand-Control-Support and the Effort-Reward Imbalance (ERI) models. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment (MoCA). Telomere length and inflammatory biomarkers were measured using standardised protocols. The direct and indirect effects were estimated using a novel mediation analysis method developed for multiple correlated mediators. Associations were observed between passive work or low job control, and shorter telomeres among females, and between low social support at work, ERI or iso-strain, and a higher inflammatory index among males. An association was observed with higher cognitive performance for longer telomeres, but not for the inflammatory index. Passive work overall, and low reward were associated with lower cognitive performance in males; whereas, high psychological demand in both males and females and high job strain in females were associated with a higher cognitive performance. However, none of these associations were mediated by telomere length or the inflammatory index. This study suggests that some work-related psychosocial factors could be associated with shorter telomeres and low-grade inflammation, but these associations do not explain the relationship between work-related psychosocial factors and global cognitive function. A better understanding of the biological pathways, by which these factors affect cognitive function, could guide future preventive strategies to maintain cognitive function and promote healthy aging.

During the inflammatory response, macrophage phenotypes can be broadly classified as pro-inflammatory/classically activated "M1", or pro-resolving/alternatively "M2" macrophages. Although the classification of macrophages is general and assumes there are distinct phenotypes, in reality macrophages exist across a spectrum and must transform from a pro-inflammatory state to a proresolving state following an inflammatory insult. To adapt to changing metabolic needs of the cell, mitochondria undergo fusion and fission, which have important implications for cell fate and function. We hypothesized that mitochondrial fission and fusion directly contribute to macrophage function during the pro-inflammatory and proresolving phases. In the present study, we find that mitochondrial length directly contributes to macrophage phenotype, primarily during the transition from a pro-inflammatory to a proresolving state. Phenocopying the elongated mitochondrial network (by disabling the fission machinery using siRNA) leads to a baseline reduction in the inflammatory marker IL-1β, but a normal inflammatory response to LPS, similar to control macrophages. In contrast, in macrophages with a phenocopied fragmented phenotype (by disabling the fusion machinery using siRNA) there is a heightened inflammatory response to LPS and increased signaling through the ATF4/c-Jun transcriptional axis compared to control macrophages. Importantly, macrophages with a fragmented mitochondrial phenotype show increased expression of proresolving mediator arginase 1 and increased phagocytic capacity. Promoting mitochondrial fragmentation caused an increase in cellular lactate, and an increase in histone lactylation which caused an increase in arginase 1 expression. These studies demonstrate that a fragmented mitochondrial phenotype is critical for the proresolving response in macrophages and specifically drive epigenetic changes via lactylation of histones following an inflammatory insult.

Objective: Road traffic crash fatalities disproportionately affect young male drivers. Driver distraction is a leading contributor to crashes. Mind wandering (MW) is a prevalent form of driver distraction that is linked to certain unsafe driving behaviours that are associated with increased crash risk (e.g., faster driving). Negative mood can lead to MW, and thus may represent a causal pathway to MW-related unsafe driving. This preliminary pre-post (T1, T2), randomized, controlled, single-blinded experiment tested whether negative mood, compared to neutral mood, increases MW while driving as well as unsafe driving and emotional arousal during MW. It also tested the moderating contribution of trait rumination and inhibitory control to this proposed causal pathway., Methods: Forty healthy male drivers aged 20 to 24 were randomly allocated to a negative or neutral mood manipulation involving deception. Individual differences in trait rumination and inhibitory control were measured at T1. At T1 and T2, participants drove in a driving simulator measuring driving speed, headway distance, steering behaviour, and overtaking. Heart rate and thought probes during simulation measured emotional arousal and MW, respectively., Results: Negative mood exposure led to more MW while driving (Odds Ratio = 1.79, p = .022). Trait rumination positively moderated the relationship between negative mood and MW (Odds Ratio = 2.11, p = .002). Negative versus neutral mood exposure led to increases in headway variability (Cohen's d = 1.46, p = .026) and steering reversals (Rate Ratio = 1.33, p = .032) during MW relative to focused driving. Between-group differences in emotional arousal were not significant., Conclusion: Results support a causal pathway from negative mood to unsafe driving via MW, including the moderating contribution of trait rumination. If replicated, these preliminary findings may inform the development of interventions targeting this potential crash-risk pathway in vulnerable young driver subgroups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Moral injuries can occur when perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations. The COVID-19 crisis highlighted the fact that psychosocial stressors at work, such as high emotional demands, are placing Canadian healthcare workers at risk of moral injuries. Evidence linking psychosocial stressors at work to moral injuries are needed to better predict, prevent and manage moral injuries, as these stressors are frequent and modifiable occupational risk factors. This protocol presents a study aiming to: 1) understand workplace events having the potential to either cause or reduce moral injuries, 2) predict the risk and severity of moral injuries using a disease prevention model, 3) identify biological signatures (biomarkers) associated with psychosocial stressors at work and moral injuries and 4) elaborate preliminary guidelines of organizational practices for frontline healthcare workers to reduce and manage moral injuries. This study is a mixed methods research with three components: qualitative, quantitative and biological. The data collection has been completed and because of the COVID-19 pandemic, it was adjusted to allow for gathering qualitative and quantitative data remotely. Frontline healthcare workers and leaders were included. Through focus groups and individual interviews, and an online questionnaire, events and psychosocial working conditions that may increase the risk of moral injuries will be documented. In addition, blood samples which were collected from a sub-sample of volunteer participants will measure an innovative set of biomarkers associated with vulnerability to stress and mental health. Data analyses are ongoing. We anticipate to identify workplace events that may trigger moral injuries. We expect that potential predictors of moral injury risk occurrence and severity will be identified from psychosocial stressors at work that can be improved by implementing organizational practices. We also expect to observe a different mental health state and biological inflammation signature across workers exposed compared to workers not exposed to psychosocial stressors at work. Based on these future findings, we intend to develop preliminary recommendations of organizational practices for managers. This research will contribute to expand our knowledge of the events in the workplace likely to generate or lessen the impact moral injuries, to build a model for predicting the risk of moral injuries at work, all in the specific context of the COVID-19 health crisis among healthcare workers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Healthcare workers (HCWs) on the frontline of the COVID-19 pandemic exhibit a high prevalence of depression and psychological distress. Moral injury (MI) can lead to such mental health problems. MI occurs when perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations. Since the start of the pandemic, psychosocial stressors at work (PSWs) might have been exacerbated, which might in turn have led to an increased risk of MI in HCWs. However, research into the associations between PSWs and MI is lacking. Considering these stressors are frequent and most of them are modifiable occupational risk factors, they may constitute promising prevention targets. This study aims to evaluate the associations between a set of PSWs and MI in HCWs during the third wave of the COVID-19 pandemic in Quebec, Canada. Furthermore, our study aims to explore potential differences between urban and non-urban regions. The sample of this study consisted of 572 HCWs and leaders from the Quebec province. Prevalence ratios (PR) of MI and their 95% confidence intervals (CI) were modelled using robust Poisson regressions. Several covariates were considered, including age, sex, gender, socio-economic indicators, and lifestyle factors. Results indicated HCWs exposed to PSWs were 2.22-5.58 times more likely to experience MI. Low ethical culture had the strongest association (PR: 5.58, 95% CI: 1.34-23.27), followed by low reward (PR: 4.43, 95% CI: 2.14-9.16) and high emotional demands (PR: 4.32, 95% CI: 1.89-9.88). Identifying predictors of MI could contribute to the reduction of mental health problems and the implementation of targeted interventions in urban and non-urban areas., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetes Action Canada Strategy for Patient-Oriented Research (SPOR) Network in Chronic Disease was formed in 2016 and is funded primarily through the Canadian Institutes of Health Research (CIHR). We propose a novel mixed-methods approach to a network evaluation integrating the State of Network Evaluation framework and the Canadian Academy of Health Sciences (CAHS) preferred framework and indicators. We measure key network themes of connectivity, health and results, and impact and return on investment associated with health research networks. Our methods consist of a longitudinal cross-sectional network survey of members and social network analysis to examine Network Connectivity and assess the frequency of interactions, the topics discussed during them, and how networking effectively facilitates interactions and collaboration among members. Network Health will be evaluated through semistructured interviews, a membership survey inquiring about satisfaction and experience with the Network, and a review of documentary sources related to funding and infrastructure to evaluate Network Sustainability. Finally, we will examine Network Results and Impact using the CAHS preferred framework and indicators to measure returns on investment in health research across the five domains of the CAHS framework, which include: advancing knowledge, capacity building, informing decision making, health impact, and economic and social impact. Indicators will be assessed with various methods, including bibliometric analyses, review of relevant documentary sources (annual reports), member activities informing health and research policy, and Patient Partner involvement. The Network Evaluation will provide members and stakeholders with information for planning, improvements, and funding future Network endeavors., (© The Author(s) 2022. Published by Oxford University Press.)

Patients with established coronary artery disease remain at elevated risk of major adverse cardiac events. The goal of this study was to evaluate the utility of plasminogen activator inhibitor-1-positive platelet-derived extracellular vesicles as a biomarker for major adverse cardiac events and to explore potential underlying mechanisms. Our study suggests these extracellular vesicles as a potential biomarker to identify and a therapeutic target to ameliorate neointimal formation of high-risk patients., Competing Interests: This project was supported by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario and the Canadian Foundation of Innovation. Dr Jung was funded by the Vanier Canadian Institutes of Health Research Canada Graduate Scholarship for his graduate studies. Dr Duchez was supported by the Cardiac Endowment Fund at the University of Ottawa Heart Institute. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Lipid droplet (LD) autophagy (lipophagy) is a recently discovered selective form of autophagy and is a pathway for LD catabolism. This ubiquitous process has been an ongoing area of research within the budding yeast, Saccharomyces cerevisiae. Yeast lipophagy phenotypically resembles microautophagy, although it has a distinct set of genetic requirements depending on the mode of induction. This review highlights the similarities and differences between different forms of yeast lipophagy and offers perspectives on how our knowledge of lipophagy in yeast may guide our understanding of this process within mammalian cells to ultimately inform future applications of lipophagy., (© 2022 John Wiley & Sons Ltd.)

Background: Efforts have been made by health research granting agencies to bring research closer to patients' concerns. In Canada, such efforts were formalized in 2011 with the funding of the Strategy for Patient-Oriented Research (SPOR)'s research networks to address research priorities identified by patients and accelerate the translation of research findings into patient care and health care policy. Among these networks, SPOR Diabetes Action Canada (DAC) has created patient-partner circles to facilitate their integration within the network. The nature of the relationships within this atypical patient-oriented research network is systematically explored in this paper., Methods: A cross-sectional social network study was conducted among the SPOR DAC's network members to examine inter-individual interactions, and the topics discussed the most between members. Descriptive data analyses were conducted to explore which discussion topics were discussed most among members whose primary roles were research, administration, governance, and patient representation., Results: The response rate was 51.9%, providing data on 76.5% of the maximum number of connections in the network. The survey captured 2763 inter-individual relationships. Responses to a sub-question inserted in the survey show that 482 of these relationships (17,4%) existed before joining the network in collaboration on a research project. Most ties captured in the survey were yearly or quarterly, while few relationships were monthly, weekly, or daily. In measured relationships, members discussed several topics, the most frequent being scientific research, patient engagement, network coordination and governance, and operations and management. The topics associated with the most significant proportion of relationships captured in the survey were scientific research (45.4%) and patient engagement (40.7%). Management & operations and governance & coordination follow, corresponding to 24.3 and 23.9% of the captured relationships. All discussion topic subnetworks were either somewhat or highly centralized, meaning that relationships were not equally distributed among members involved in these discussions. Of the 1256 relationships involving exchanges about scientific research, 647 (51.5%) involved a researcher, 419 (33.3%) an administrator, 182 (14.5%) a patient partner, and 82 (6.5%) a member whose primary role is network governance., Conclusions: Scientific research and patient engagement were the most common topics discussed, consistent with the patient-centered research at the heart of the SPOR Diabetes Action Canada network. The study identified several relationships where a patient partner has discussed scientific research with a researcher. However, relationships involving research discussions were three times more common between a researcher and an administrator than between a researcher and a patient partner, although twice as many patient partners as administrators participated in the survey. The institutionalization of patient-partner involvement in large research networks is an evolving practice for which optimal engagement methods are still being explored., (© 2022. The Author(s).)

Objective: Recent research identified that workplace factors play a role in the development of diabetes mellitus (DM). This study examines the longitudinal association of work-related overqualification with the incidence of DM over a 14-year follow-up period., Methods: We used data from the 2003 Canadian Community Health Survey linked to the Ontario Health Insurance Plan and the Canadian Institute for Health Information Discharge Abstract databases. Cox proportional hazards regression models were performed to evaluate the relationship between overqualification and the incidence of DM., Results: Over the study period, there were 91,835 person-years of follow-up (median follow-up = 13.7 years). The final sample included 7026 respondents (mean [standard deviation] age at baseline = 47.1 [8.2]; 47% female). An elevated risk of DM was associated with substantial overqualification (hazard ratio = 1.58, 95% confidence interval = 1.01-2.49) after adjustment for sociodemographic, health, and work variables. Additional adjustment for body mass index and health behaviors attenuated this risk (hazard ratio = 1.30, 95% confidence interval = 0.81-2.08). Underqualification was not associated with the incidence of DM in adjusted regression models. We did not observe any statistical difference in the effects of overqualification on DM risk across sex or education groups., Conclusions: This study adds to the growing body of research literature uncovering the relationships between work exposures and DM risk. The results from the study suggest that higher body mass index and, to a lesser extent, health behaviors may be mediating factors in the association between overqualification and incident DM. Further research on the association of overqualification with DM is warranted., (Copyright © 2022 by the American Psychosomatic Society.)

Background: A significant burden of atherosclerotic disease is driven by inflammation. Recently, microRNAs (miRNAs) have emerged as important factors driving and protecting from atherosclerosis. miR-223 regulates cholesterol metabolism and inflammation via targeting both cholesterol biosynthesis pathway and NF k B signaling pathways; however, its role in atherosclerosis has not been investigated. We hypothesize that miR-223 globally regulates core inflammatory pathways in macrophages in response to inflammatory and atherogenic stimuli thus limiting the progression of atherosclerosis., Methods and Results: Loss of miR-223 in macrophages decreases Abca1 gene and protein expression as well as cholesterol efflux to apoA1 (Apolipoprotein A1) and enhances proinflammatory gene expression. In contrast, overexpression of miR-223 promotes the efflux of cholesterol and macrophage polarization toward an anti-inflammatory phenotype. These beneficial effects of miR-223 are dependent on its target gene, the transcription factor Sp3 . Consistent with the antiatherogenic effects of miR-223 in vitro, mice receiving miR223 -/- bone marrow exhibit increased plaque size, lipid content, and circulating inflammatory cytokines (ie, IL-1β). Deficiency of miR-223 in bone marrow-derived cells also results in an increase in circulating pro-atherogenic cells (total monocytes and neutrophils) compared with control mice. Furthermore, the expression of miR-223 target gene ( Sp3 ) and pro-inflammatory marker ( Il-6 ) are enhanced whereas the expression of Abca1 and anti-inflammatory marker ( Retnla ) are reduced in aortic arches from mice lacking miR-223 in bone marrow-derived cells. In mice fed a high-cholesterol diet and in humans with unstable carotid atherosclerosis, the expression of miR-223 is increased. To further understand the molecular mechanisms underlying the effect of miR-223 on atherosclerosis in vivo, we characterized global RNA translation profile of macrophages isolated from mice receiving wild-type or miR223 -/- bone marrow. Using ribosome profiling, we reveal a notable upregulation of inflammatory signaling and lipid metabolism at the translation level but less significant at the transcription level. Analysis of upregulated genes at the translation level reveal an enrichment of miR-223-binding sites, confirming that miR-223 exerts significant changes in target genes in atherogenic macrophages via altering their translation., Conclusions: Our study demonstrates that miR-223 can protect against atherosclerosis by acting as a global regulator of RNA translation of cholesterol efflux and inflammation pathways.

Background : Summaries of systematic reviews are a reference method for the dissemination of research evidence on the effectiveness of public health interventions beyond the scientific community. Motivated reasoning and cognitive dissonance may interfere with readers' ability to process the information included in such summaries. Methods : We conducted a web experiment on a panel of university-educated North Americans ( N = 259) using a systematic review of the effectiveness of bicycle helmet legislation as a test case. The outcome variables were the perceived tentativeness of review findings and attitude toward bicycle helmet legislation. We manipulated two types of uncertainty: (i) deficient uncertainty (inclusion vs. non-inclusion of information on limitations of the studies included in the review) and (ii) consensus uncertainty (consensual findings showing legislation effectiveness vs. no evidence of effectiveness). We also examined whether reported expertise in helmet legislation and the frequency of wearing a helmet while cycling interact with the experimental factors. Results : None of the experimental manipulations had a main effect on the perceived tentativeness. The presentation of consensual efficacy findings had a positive main effect on the attitude toward the legislation. Self-reported expertise had a significant main effect on the perceived tentativeness, and exposing participants with reported expertise to results showing a lack of evidence of efficacy increased their favorable attitude toward the legislation. Participants' helmet use was positively associated with their attitude toward the legislation (but not with perceived tentativeness). Helmet use did not interact with the experimental manipulations. Conclusions : Motivated reasoning and cognitive dissonance influence a reader's ability to process information contained in a systematic review summary.

Lay Abstract: What is already known about the topic? Quality of life refers to how people perceive aspects of their life such as physical health, material security, and interpersonal relationships. Studies have reported lower quality of life among autistic individuals than in the general population. What does this article contribute? This article contributes to a better understanding of quality of life and its measures from the point of view of autistic adults. By comparing two groups of French-speaking autistic adults from two different places (France and Québec-Canada), this research shows that the perception of quality of life and its determining factors differ for autistic adults living in each country. The Québec group reported a superior quality of life, and some quality of life predictors were different in each group. The social experience of autism-related stigmatization, however, was a powerful predictor of quality of life for all. Implications for practice, research, and policy To promote a higher quality of life for autistic people, it is important to consider the sociocultural context and implement awareness programs and public campaigns aimed at identifying and countering stigmatization processes.

Fragile X Mental Retardation protein (FMRP), widely known for its role in hereditary intellectual disability, is an RNA-binding protein (RBP) that controls translation of select mRNAs. We discovered that endoplasmic reticulum (ER) stress induces phosphorylation of FMRP on a site that is known to enhance translation inhibition of FMRP-bound mRNAs. We show ER stress-induced activation of Inositol requiring enzyme-1 (IRE1), an ER-resident stress-sensing kinase/endoribonuclease, leads to FMRP phosphorylation and to suppression of macrophage cholesterol efflux and apoptotic cell clearance (efferocytosis). Conversely, FMRP deficiency and pharmacological inhibition of IRE1 kinase activity enhances cholesterol efflux and efferocytosis, reducing atherosclerosis in mice. Our results provide mechanistic insights into how ER stress-induced IRE1 kinase activity contributes to macrophage cholesterol homeostasis and suggests IRE1 inhibition as a promising new way to counteract atherosclerosis., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Rationale: Atherosclerosis is characterized by an accumulation of foam cells within the arterial wall, resulting from excess cholesterol uptake and buildup of cytosolic lipid droplets (LDs). Autophagy promotes LD clearance by freeing stored cholesterol for efflux, a process that has been shown to be atheroprotective. While the role of autophagy in LD catabolism has been studied in macrophage-derived foam cells, this has remained unexplored in vascular smooth muscle cell (VSMC)-derived foam cells that constitute a large fraction of foam cells within atherosclerotic lesions., Objective: We performed a comparative analysis of autophagy flux in lipid-rich aortic intimal populations to determine whether VSMC-derived foam cells metabolize LDs similarly to their macrophage counterparts., Methods and Results: Atherosclerosis was induced in GFP-LC3 (microtubule-associated proteins 1A/1B light chain 3) transgenic mice by PCSK9 (proprotein convertase subtilisin/kexin type 9)-adeno-associated viral injection and Western diet feeding. Using flow cytometry of aortic digests, we observed a significant increase in dysfunctional autophagy of VSMC-derived foam cells during atherogenesis relative to macrophage-derived foam cells. Using cell culture models of lipid-loaded VSMCs and macrophages, we show that autophagy-mediated cholesterol efflux from VSMC foam cells was poor relative to macrophage foam cells, and largely occurs when HDL (high-density lipoprotein) was used as a cholesterol acceptor, as opposed to apoA-1 (apolipoproteinA-1). This was associated with the predominant expression of ABCG1 in VSMC foam cells. Using metformin, an autophagy activator, cholesterol efflux to HDL was significantly increased in VSMC, but not in macrophage, foam cells., Conclusions: These data demonstrate that VSMC and macrophage foam cells perform cholesterol efflux by distinct mechanisms, and that autophagy flux is highly impaired in VSMC foam cells, but can be induced by pharmacological means. Further investigation is warranted into targeting autophagy specifically in VSMC foam cells, the predominant foam cell subtype of advanced atherosclerotic plaques, to promote reverse cholesterol transport and resolution of the atherosclerotic plaque.

Objectives: Previous studies on the effect of low social support at work on blood pressure showed mixed results. Few previous studies have used ambulatory blood pressure and examined whether the effect of low social support at work vary among men and women. The aim of this study was to examine the association between low social support at work, ambulatory blood pressure means and hypertension prevalence, in a sample of white-collar workers men and women., Methods: A repeated cross-sectional design was used. Data were collected three times during a 5-year period, among 3919 white-collar women and men. At each time, coworker and supervisor social support at work were measured using validated scales. Ambulatory blood pressure was measured every 15 min during a working day. General estimating equations were used., Results: In adjusted models, women exposed to low coworker (+0.6 mmHg) and low supervisor social support at work (+0.7 mmHg) had slightly higher diastolic blood pressure means when compared to unexposed women. In men, those with low coworker social support at work had higher diastolic (+0.7 mmHg) blood pressure while those with low supervisor social support had a higher prevalence of hypertension (prevalence ratio = 1.14, 95% CI: 1.04-1.24)., Conclusions: Men with low supervisor social support at work had a higher prevalence of hypertension. Low social support at work was associated with modest increases in diastolic blood pressure among men and women. Workplace prevention strategies aiming to increase social support at work could lead to beneficial effects on worker's cardiovascular health., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Population-based strategies targeting modifiable risk factors are needed to improve the prevention of hypertension. Long working hours have been linked to high blood pressure (BP), but more longitudinal research is required. The objective of this study was to examine the effect of long working hours (≥41 h/week) on ambulatory BP mean over a 2.5-year follow-up. The effect modification of family responsibilities was also investigated. A repeated longitudinal design was used. Data collection was performed at three-time points over a 2.5-year follow-up among over 2000 white-collar workers. Working hours were self-reported assessed by questionnaire. BP was measured using Spacelabs 90207. The outcomes were systolic and diastolic BP mean. Cross-lagged GEE linear regressions were used to examine whether working hours were associated with BP means at the next measurement time. Women working long hours had a higher diastolic BP mean at follow-up compared to women working regular hours (+1.8 mm Hg (95% CI: 0.5-3.1)). In men, those working long hours had both higher systolic and diastolic BP means increases (systolic: +2.5 mm Hg (95% CI: 0.5-4.4)) and diastolic: +2.3 mm Hg (95% CI: 1.0-3.7)). This association was greater among workers having high family responsibilities. This longitudinal study showed that women and men working long hours had higher BP means when compared those working 35-40 h per week. These findings suggest that strategies that promote work weeks not exceeding 40 h might contribute to the primary prevention of hypertension, especially for workers with high family responsibilities., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Objectives: This systematic review and meta-analysis aimed to synthesize the available data on prospective associations between work-related stressors and the risk of type 2 diabetes mellitus (T2DM) among adult workers, according to the demand-control-support (DCS) and the effort-reward imbalance (ERI) models., Method: We searched for prospective studies in PubMed, EMBASE, Web of Science, Scopus, CINHAL and PsychInfo. After screening and extraction, quality of evidence was assessed using the ROBINS-I tool adapted for observational studies. The effect estimates extracted for each cohort were synthesized using random effect models., Results: We included 18 studies (reporting data on 25 cohorts) in meta-analyses for job strain, job demands, job control, social support at work and ERI. Workers exposed to job strain had a higher risk of developing T2DM when compared to unexposed workers [pooled rate ratio (RR) 1.16, 95% confidence interval (CI) 1.07-1.26]. This association was robust in several supplementary analyses. For exposed women relative to unexposed women, the RR was 1.35 (95% CI 1.12-1.64). The RR of workers exposed to ERI was 1.24 (95% CI 1.08-1.42) compared to unexposed workers., Conclusions: This is the first meta-analysis to find an effect of ERI on the onset of T2DM incidence. It also confirms that job strain increases the incidence of T2DM, especially among women.

Objectives: Psychosocial stressors at work have been proposed as modifiable risk factors for mild cognitive impairment (MCI). This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on cognitive function., Methods: This study was conducted among 9188 white-collar workers recruited in 1991-1993 (T1), with follow-ups 8 (T2) and 24 years later (T3). After excluding death, losses to follow-up and retirees at T2, 5728 participants were included. Psychosocial stressors at work were measured according to the Karasek's questionnaire. Global cognitive function was measured with the Montreal Cognitive Assessment. Cumulative exposures to low psychological demand, low job control, passive job and high strain job were evaluated using marginal structural models including multiple imputation and inverse probability of censoring weighting., Results: In men, cumulative exposures (T1 and T2) to low psychological demand, low job control or passive job were associated with higher prevalences of more severe presentation of MCI (MSMCI) at T3 (Prevalence ratios (PRs) and 95% CIs of 1.50 (1.16 to 1.94); 1.38 (1.07 to 1.79) and 1.55 (1.20 to 2.00), respectively), but not with milder presentation of MCI. In women, only exposure to low psychological demand or passive job at T2 was associated with higher prevalences of MSMCI at T3 (PRs and 95% CI of 1.39 (0.97 to 1.99) and 1.29 (0.94 to 1.76), respectively)., Conclusions: These results support the deleterious effect of a low stimulating job on cognitive function and the cognitive reserve theory. Psychosocial stressors at work could be part of the effort for the primary prevention of cognitive decline., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic low-grade inflammation has been associated with high risk of several chronic diseases such as cardiovascular diseases, diabetes, depression, and dementia. As low-grade inflammation could be present long before the apparition of the disease, identifying modifiable risk factors could allow to act upstream. Psychosocial stressors at work have been suggested as modifiable risk factors of low-grade inflammation, but few longitudinal studies have evaluated the association between these stressors and inflammatory biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6)., Objective: This longitudinal study evaluate the associations between exposure to psychosocial stressors at work and CRP and IL-6, separately and combined into an inflammatory index., Methods: Data came from a cohort of 9188 white-collar workers recruited in 1991-1993 (T1) and followed-up after 8 (T2, 1999-2000) and 24 (T3, 2015-2018) years. Participants included in this study were randomly selected at T3 for serum biomarkers studies (n = 2557). CRP and IL-6 were measured using standardized protocols. Psychosocial stressors at work were assessed at T2 according to recognized models: Karasek's Demand-Control-Support model and Siegrist's Effort-Reward Imbalance (ERI) model, using validated questionnaires. High job strain was defined by an exposure to high psychological demand combined with low job control, and iso-strain was defined by an exposure to high job strain combined with low social support at work. ERI was defined by an imbalance between psychological demand and social, economic, and organizational reward. Several covariates were considered including sociodemographic, anthropometric, and lifestyle characteristics, and comorbidities. Prevalence ratios (PRs) and 95% confidence interval (CI) for the highest quartile of CRP, IL-6 and inflammatory index at T3 according to psychosocial stressors at work measured at T2 were calculated using generalized estimating equations. Multiple imputation and inverse probability of censoring weighting were done., Results: In men, an association was observed between exposure to iso-strain and the inflammatory index (PR of 1.42 (95% CI: 1.06;1.90)), mainly among men aged less than 65 years (PR of 2.00 (95% CI: 1.37;2.92)). In this same age group, associations with inflammatory biomarkers were also observed among men with exposure to ERI, and among women with exposure to low reward at work or moderate social support at work., Conclusion: These results suggest that psychosocial stressors at work may increase low-grade inflammation. However, further studies are needed to corroborate these results and to clarify the potential differences between men and women. As these stressors are frequent and modifiable, their reduction is important for public health and could play a role in the primary prevention of chronic diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Macrophage autophagy is a highly anti-atherogenic process that promotes the catabolism of cytosolic lipid droplets (LDs) to maintain cellular lipid homeostasis. Selective autophagy relies on tags such as ubiquitin and a set of selectivity factors including selective autophagy receptors (SARs) to label specific cargo for degradation. Originally described in yeast cells, "lipophagy" refers to the degradation of LDs by autophagy. Yet, how LDs are targeted for autophagy is poorly defined. Here, we employed mass spectrometry to identify lipophagy factors within the macrophage foam cell LD proteome. In addition to structural proteins (e.g., PLIN2), metabolic enzymes (e.g., ACSL) and neutral lipases (e.g., PNPLA2), we found the association of proteins related to the ubiquitination machinery (e.g., AUP1) and autophagy (e.g., HMGB, YWHA/14-3-3 proteins). The functional role of candidate lipophagy factors (a total of 91) was tested using a custom siRNA array combined with high-content cholesterol efflux assays. We observed that knocking down several of these genes, including Hmgb1, Hmgb2, Hspa5 , and Scarb2 , significantly reduced cholesterol efflux, and SARs SQSTM1/p62, NBR1 and OPTN localized to LDs, suggesting a role for these in lipophagy. Using yeast lipophagy assays, we established a genetic requirement for several candidate lipophagy factors in lipophagy, including HSPA5, UBE2G2 and AUP1. Our study is the first to systematically identify several LD-associated proteins of the lipophagy machinery, a finding with important biological and therapeutic implications. Targeting these to selectively enhance lipophagy to promote cholesterol efflux in foam cells may represent a novel strategy to treat atherosclerosis. Abbreviations: ADGRL3: adhesion G protein-coupled receptor L3; agLDL: aggregated low density lipoprotein; AMPK: AMP-activated protein kinase; APOA1: apolipoprotein A1; ATG: autophagy related; AUP1: AUP1 lipid droplet regulating VLDL assembly factor; BMDM: bone-marrow derived macrophages; BNIP3L: BCL2/adenovirus E1B interacting protein 3-like; BSA: bovine serum albumin; CALCOCO2: calcium binding and coiled-coil domain 2; CIRBP: cold inducible RNA binding protein; COLGALT1: collagen beta(1-O)galactosyltransferase 1; CORO1A: coronin 1A; DMA: deletion mutant array; Faa4: long chain fatty acyl-CoA synthetase; FBS: fetal bovine serum; FUS: fused in sarcoma; HMGB1: high mobility group box 1; HMGB2: high mobility group box 2: HSP90AA1: heat shock protein 90: alpha (cytosolic): class A member 1; HSPA5: heat shock protein family A (Hsp70) member 5; HSPA8: heat shock protein 8; HSPB1: heat shock protein 1; HSPH1: heat shock 105kDa/110kDa protein 1; LDAH: lipid droplet associated hydrolase; LIPA: lysosomal acid lipase A; LIR: LC3-interacting region; MACROH2A1: macroH2A.1 histone; MAP1LC3: microtubule-associated protein 1 light chain 3; MCOLN1: mucolipin 1; NBR1: NBR1, autophagy cargo receptor; NPC2: NPC intracellular cholesterol transporter 2; OPTN: optineurin; P/S: penicillin-streptomycin; PLIN2: perilipin 2; PLIN3: perilipin 3; PNPLA2: patatin like phospholipase domain containing 2; RAB: RAB, member RAS oncogene family; RBBP7, retinoblastoma binding protein 7, chromatin remodeling factor; SAR: selective autophagy receptor; SCARB2: scavenger receptor class B, member 2; SGA: synthetic genetic array; SQSTM1: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; TFEB: transcription factor EB; TOLLIP: toll interacting protein; UBE2G2: ubiquitin conjugating enzyme E2 G2; UVRAG: UV radiation resistance associated gene; VDAC2: voltage dependent anion channel 2; VIM: vimentin.