Exploring patient perspectives on how they can and should be engaged in the development of artificial intelligence (AI) applications in health care.

BACKGROUND: Artificial intelligence (AI) is a rapidly evolving field which will have implications on both individual patient care and the health care system. There are many benefits to the integration of AI into health care, such as predicting acute conditions and enhancing diagnostic capabilities. Despite these benefits potential harms include algorithmic bias, inadequate consent processes, and implications on the patient-provider relationship. One tool to address patients' needs and prevent the negative implications of AI is through patient engagement. As it currently stands, patients have infrequently been involved in AI application development for patient care delivery. Furthermore, we are unaware of any frameworks or recommendations specifically addressing patient engagement within the field of AI in health care. METHODS: We conducted four virtual focus groups with thirty patient participants to understand of how patients can and should be meaningfully engaged within the field of AI development in health care. Participants completed an educational module on the fundamentals of AI prior to participating in this study. Focus groups were analyzed using qualitative content analysis. RESULTS: We found that participants in our study wanted to be engaged at the problem-identification stages using multiple methods such as surveys and interviews. Participants preferred that recruitment methodologies for patient engagement included both in-person and social media-based approaches with an emphasis on varying language modalities of recruitment to reflect diverse demographics. Patients prioritized the inclusion of underrepresented participant populations, longitudinal relationship building, accessibility, and interdisciplinary involvement of other stakeholders in AI development. We found that AI education is a critical step to enable meaningful patient engagement within this field. We have curated recommendations into a framework for the field to learn from and implement in future development. CONCLUSION: Given the novelty and speed at which AI innovation is progressing in health care, patient engagement should be the gold standard for application development. Our proposed recommendations seek to enable patient-centered AI application development in health care. Future research must be conducted to evaluate the effectiveness of patient engagement in AI application development to ensure that both AI application development and patient engagement are done rigorously, efficiently, and meaningfully.

Priorities for Artificial Intelligence Applications in Primary Care: A Canadian Deliberative Dialogue with Patients, Providers, and Health System Leaders.

BACKGROUND: Artificial intelligence (AI) implementation in primary care is limited. Those set to be most impacted by AI technology in this setting should guide it's application. We organized a national deliberative dialogue with primary care stakeholders from across Canada to explore how they thought AI should be applied in primary care. METHODS: We conducted 12 virtual deliberative dialogues with participants from 8 Canadian provinces to identify shared priorities for applying AI in primary care. Dialogue data were thematically analyzed using interpretive description approaches. RESULTS: Participants thought that AI should first be applied to documentation, practice operations, and triage tasks, in hopes of improving efficiency while maintaining person-centered delivery, relationships, and access. They viewed complex AI-driven clinical decision support and proactive care tools as impactful but recognized potential risks. Appropriate training and implementation support were the most important external enablers of safe, effective, and patient-centered use of AI in primary care settings. INTERPRETATION: Our findings offer an agenda for the future application of AI in primary care grounded in the shared values of patients and providers. We propose that, from conception, AI developers work with primary care stakeholders as codesign partners, developing tools that respond to shared priorities.

Implementing artificial intelligence in Canadian primary care: Barriers and strategies identified through a national deliberative dialogue.

BACKGROUND: With large volumes of longitudinal data in electronic medical records from diverse patients, primary care is primed for disruption by artificial intelligence (AI) technology. With AI applications in primary care still at an early stage in Canada and most countries, there is a unique opportunity to engage key stakeholders in exploring how AI would be used and what implementation would look like. OBJECTIVE: To identify the barriers that patients, providers, and health leaders perceive in relation to implementing AI in primary care and strategies to overcome them. DESIGN: 12 virtual deliberative dialogues. Dialogue data were thematically analyzed using a combination of rapid ethnographic assessment and interpretive description techniques. SETTING: Virtual sessions. PARTICIPANTS: Participants from eight provinces in Canada, including 22 primary care service users, 21 interprofessional providers, and 5 health system leaders. RESULTS: The barriers that emerged from the deliberative dialogue sessions were grouped into four themes: (1) system and data readiness, (2) the potential for bias and inequity, (3) the regulation of AI and big data, and (4) the importance of people as technology enablers. Strategies to overcome the barriers in each of these themes were highlighted, where participatory co-design and iterative implementation were voiced most strongly by participants. LIMITATIONS: Only five health system leaders were included in the study and no self-identifying Indigenous people. This is a limitation as both groups may have provided unique perspectives to the study objective. CONCLUSIONS: These findings provide insight into the barriers and facilitators associated with implementing AI in primary care settings from different perspectives. This will be vital as decisions regarding the future of AI in this space is shaped.

Overview Of The Canadian Clinician Investigator Trainees' Research Presented At The 2020 CSCI-CITAC Joint Meeting.

The 2020 Annual General Meeting (AGM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was the first meeting to be hosted virtually. The theme was "Navigating Uncertainty, Embracing Change and Empowering the Next Generation of Clinician-Scientists", and the meeting featured lectures and workshops that were designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Jason Berman (President of CSCI/SCRC), Tina Marvasti (President of CITAC/ACCFC) and Nicola Jones (University of Toronto Clinician Investigator Program Symposium Chair). Dr. Michael Strong, President of the Canadian Institutes of Health Research, delivered the keynote presentation titled "CIHR's COVID-19 Response and Strategic Planning". Dr. John Bell (University of Ottawa) received the CSCI Distinguished Scientist Award, Dr. Stanley Nattel (Université de Montréal) received the CSCI-RCPSC Henry Friesen Award (RCPSC; Royal College of Physicians and Surgeons of Canada) and Dr. Meghan Azad (University of Manitoba) received the CSCI Joe Doupe Young Investigator Award. Each scientist delivered talks on their award-winning research. The interactive workshops were "Developing Strategies to Maintain Wellness", "Understanding the Hidden Curriculum: Power and Privilege in Science and Medicine", "Hiring a Clinician Scientist Trainee: What Leaders Are Looking For" and "COVID-19: A Case Study for Pivoting Your Research". The AGM included presentations from clinician investigator trainees nationwide. Over 70 abstracts were showcased, most are summarized in this review, and six were selected for oral presentations.

Overview of the Canadian Clinician Investigator Trainees' research presented at the 2019 CSCI-CITAC Joint Meeting.

The 2019 Annual General Meeting and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherche Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada / Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was held in Banff, Alberta on November 8-10th, 2019. The theme was "Positioning Early Career Investigators for Success: Strategy and Resilience". Lectures and workshops provided knowledge and tools to facilitate the attendees' development as clinician investigators. Dr. Jason Berman (President of CSCI/SCRC), Elina Cook (President of CITAC/ACCFC) and Drs. Doreen Rabi and Zelma Kiss (University of Calgary Organizing Co-Chairs) gave opening presentations. The keynote speakers were Dr. William Foulkes (McGill University) (Distinguished Scientist Award winner) and Dr. Andrés Finzi (Université de Montréal) (Joe Doupe Young Investigator Award winner). Dr. Robert Bortolussi (Dalhousie University) received the Distinguished Service Award for his work as the Editor-in-Chief of Clinical and Investigative Medicine and for being instrumental in the development of the Canadian Child Health Clinician Scientist Program. This meeting was the first to host a panel discussion with Drs. Stephen Robbins and Marcello Tonelli from the Canadian Institutes of Health Research. Workshops on communication, career planning and work-life balance were hosted by André Picard and Drs. Todd Anderson, Karen Tang, William Ghali, May Lynn Quan, Alicia Polachek and Shannon Ruzycki. The AGM showcased 90 presentations from clinician investigator trainees from across Canada. Most of the abstracts are summarized in this review. Eight outstanding abstracts were selected for oral presentation at the President's Forum.

Newsletter Fall 2020: Clinician Investigator Trainee Association of Canada (CITAC).

Message from the CITAC president To say that 2020 has been an unprecedented year is an understatement. The coronavirus disease 2019 (COVID-19) global pandemic and the major societal awakening on racial equity and justice have led us to reflect on our direction, goals and mission. Thanks to our talented and dedicated executive team, we were able to pivot our efforts and adapt to the changing landscape of research and advocacy. In April, we provided our members with a list of resources to help facilitate a smooth transition to working from home. In June, we published Clinician Investigator Trainee Association of Canada's (CITAC) press release on our role in combating anti-Black discrimination and racial injustice and have outlined specific advocacy efforts that we will be committing to over the next years (the full statement can be found on our website, https://www.citac-accfc.org).

Publisher Correction: Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction.

In the version of this article initially published, the equal contribution of the third author was omitted. The footnote links for that author should be "Sara Nejat1,11" and the correct statement is as follows: "11These authors contributed equally: Sarah A. Dick, Jillian A. Macklin, Sara Nejat." The error has been corrected in the HTML and PDF versions of the article.

A subset of calcium-binding S100 proteins show preferential heterodimerization.

The assembly of proteins into dimers and oligomers is a necessary step for the proper function of transcription factors, muscle proteins, and proteases. In uncontrolled states, oligomerization can also contribute to illnesses such as Alzheimer's disease. The S100 protein family is a group of dimeric proteins that have important roles in enzyme regulation, cell membrane repair, and cell growth. Most S100 proteins have been examined in their homodimeric state, yet some of these important proteins are found in similar tissues implying that heterodimeric molecules can also be formed from the combination of two different S100 members. In this work, we have established co-expression methods in order to identify and quantify the distribution of homo- and heterodimers for four specific pairs of S100 proteins in their calcium-free states. The split GFP trap methodology was used in combination with other GFP variants to simultaneously quantify homo- and heterodimeric S100 proteins in vitro and in living cells. For the specific S100 proteins examined, NMR, mass spectrometry, and GFP trap experiments consistently show that S100A1:S100B, S100A1:S100P, and S100A11:S100B heterodimers are the predominant species formed compared to their corresponding homodimers. We expect the tools developed here will help establish the roles of S100 heterodimeric proteins and identify how heterodimerization might alter the specificity for S100 protein action in cells.

Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction.

Macrophages promote both injury and repair after myocardial infarction, but discriminating functions within mixed populations remains challenging. Here we used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4+LYVE1+MHC-IIloCCR2- resident cardiac macrophages self-renew with negligible blood monocyte input. Monocytes partially replaced resident TIMD4-LYVE1-MHC-IIhiCCR2- macrophages and fully replaced TIMD4-LYVE1-MHC-IIhiCCR2+ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets. Ischemic injury reduced TIMD4+ and TIMD4- resident macrophage abundance, whereas CCR2+ monocyte-derived macrophages adopted multiple cell fates within infarcted tissue, including those nearly indistinguishable from resident macrophages. Recruited macrophages did not express TIMD4, highlighting the ability of TIMD4 to track a subset of resident macrophages in the absence of fate mapping. Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, revealing a nonredundant, cardioprotective role of resident cardiac macrophages.

Engaging Patients in Care (EPIC): A Framework for Heart Function and Heart Transplant-Specific Patient Engagement.

Engaging Patients in Care (EPIC) is a local patient engagement initiative at the University Health Network for patients and families who have received care for heart failure, heart transplant, or mechanical circulatory support (left ventricular assist device). Patients and caregivers can engage at 4 different levels, including sharing, consulting, deliberating, and collaborating, depending on their knowledge, experience, and available time. The Engaging Patients In Care framework has 4 priority areas: Care Delivery and Policy, Patient Advocacy, Peer Support, and Research. We have identified key engagement barriers with a discussion of possible solutions. We hope this framework can be adapted as an evidentiary baseline for other heart failure and transplant institutions across Canada.

E ngaging P atients i n C are (EPIC) est une initiative locale de participation des patients du University Health Network pour les patients et les familles qui ont reçu des soins en lien avec l'insuffisance cardiaque, la transplantation du cœur ou l'assistance circulatoire mécanique (dispositif d'assistance ventriculaire gauche). Les patients et les soignants peuvent participer à 4 niveaux différents, à savoir le partage, la consultation, la délibération et la collaboration, selon leurs connaissances, leur expérience et leur disponibilité. Le cadre EPIC comporte 4 volets prioritaires : la prestation de soins et les politiques, la défense des droits des patients, le soutien aux pairs et la recherche. Nous avons déterminé les principaux obstacles à la participation par un échange sur les solutions possibles. Nous espérons que ce cadre peut servir de référence en matière de preuves à d'autres établissements offrant des soins aux patients atteints d'insuffisance cardiaque et la transplantation du Canada.

A CD103+ Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.

Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103+ and CD11b+, which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogated antigen-specific CD8+ T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. These effects were mediated by CD103+ cDCs, which are dependent on the transcription factor BATF3 for their development. Collectively, our findings identified resident cardiac cDC subsets, defined their origins, and revealed an essential role for CD103+ cDCs in antigen-specific T cell responses during subclinical viral myocarditis.

DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells.

Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript reveal that DIGIT is required for definitive endoderm differentiation. In addition, we identify the mouse ortholog of DIGIT and show that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator of definitive endoderm.