RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

The Restoration House COVID-19 Vaccination Clinic: Challenging Systemic Racism and Ableism through Community Solidarity and Action

This paper reviews the advocacy efforts, community organizing, establishment, operation, and lessons learned from a project in Hamilton, Ontario to build the first-ever COVID-19 clinic for Black and other racialized people, people with disabilities, and those experiencing barriers to access COVID-19 vaccinations. Community advocates, academics, and health leaders who are from and serve Black and other racialized and marginalized groups in Hamilton responded to the overwhelming impacts of COVID-19 on marginalized Black and other racialized groups in Hamilton through relational solidarities that allowed for community members to lead the advocacy, design, and operation of a clinic to serve those most in need with the knowledge and expertise most capable of such an intervention. Amidst resistance of municipal and provincial officials to act for healthy equity, racist backlash, and problematic organizational and institutional responses to the needs of Black and other racialized community leaders, Restoration House clinic advocates and community leaders responded to the demand by maintaining focus on community through collective solidarities. The Restoration House example offers several contributions to how we think about community and public health advocacy, organizing, and operational interventions through crises and beyond. Cet article passe en revue la campagne de revendication, les efforts d’organisation communautaire, la mise en place, le fonctionnement et les leçons tirées d’un projet mené à Hamilton, en Ontario, et visant à établir la toute première clinique COVID-19 pour les personnes Noires et racialisées, les personnes handicapées et celles qui rencontrent des obstacles à l’accès aux vaccinations COVID-19. Les défenseurs de la communauté, les universitaires et les dirigeants du secteur de la santé issus et au service des personnes Noires, racialisées ou marginalisées de Hamilton voulaient trouver une réponse adéquate aux effets disproportionnés de la COVID-19 sur les personnes Noires, racialisées ou marginalisées de Hamilton en utilisant les solidarités relationnelles qui ont permis aux membres de la communauté de diriger la revendication, la conception et les activités d’une clinique pour servir les personnes qui en ont le plus besoin avec les connaissances et l’expertise les plus à même de mener une telle intervention. Dans un contexte d’hésitation des autorités municipales et provinciales à agir résolument pour l’équité en santé, de réactions racistes et de réponses organisationnelles et institutionnelles défaillantes aux besoins des leaders de la communauté Noire et d’autres communautés racialisées, les défenseurs de la clinique Restoration House et les dirigeants communautaires ont répondu à la demande en maintenant l’accent sur la communauté par le biais de solidarités collectives. L’exemple de la Restoration House apporte plusieurs contributions à notre réflexion sur la défense des intérêts de la communauté et de la santé publique, l’organisation et les interventions opérationnelles en cas de crise et au-delà

Clinically validated markers of the extracellular matrix remodelling are altered by potential anti-fibrotic compounds in a human lung fibrosis ex vivo model

Background: Pulmonary fibrosis (PF) is characterized by excessive extracellular matrix (ECM) remodeling. Clinically validated ECM neoepitopes markers, related to progressive PF, may be useful for the evaluation of potential anti-fibrotic effects. Aim: The aim was to evaluate ECM remodelling (ECMR) in a human ex vivo precision-cut lung slice (PCLS) model. Methods: Human PF tissue was collected from two donors during lung transplantation. Within 24hours, the lungs were processed into PCLSs. The slices were cultured 2 pr/well and in triplicates for 48hours in serum free medium with 1nM-10μM nintedanib or 100pM-1µM mTOR/PI3K inhibitor omipalisib (GSK2126458). Responsiveness was tested using Lipopolysaccaride (LPS) and cytotoxicity using lactate dehydrogenase (LDH). Markers of collagen type I, III and VI formation (P1NP, PRO-C3, PRO-C6) and type III collagen degradation (C3M) were assessed in the supernatants. The subpleural and central lung regions were used and evaluated by hematoxylin and eosin staining. Results: The tissue from both donors was responsive to LPS and no toxicity was seen with the selected compound doses using LDH. P1NP, PRO-C3, and C3M were significantly reduced by 1nM-1µM omipalisib (p<0.05-0.001) including the IC50 value around 40-50nM. Non-significant reductions of PRO-C6 were seen. Data varied depending on region and donor. Similar trends were observed for nintedanib, however no significant changes were seen in this model. Conclusion: We found that an mTOR/PI3K inhibitor decreased markers of ECMR in a human PF ex vivo model, potential as a tool for evaluating anti-fibrotic compounds in a 3D PF structure

Predicting Temperature-Dependent Aqueous Henry’s Law Constants Using Group Contribution Methods

A first-order temperature-dependent group contribution method was developed to predict Henry’s law constants of hydrocarbons, alcohols, ketones, and formates in which none of the functional groups are attached directly to a benzene ring. Efforts to expand this method to include ester and ether groups were unsuccessful. Second-order groups were developed at a reference condition of 298.15 K and 100 kPa. A second-order temperature-dependent group contribution method was then developed for hydrocarbons, ketones, esters, ethers, and alcohols. These methods were compared to existing literature prediction methods

Whodunnit? Inferring what happened from multimodal evidence

Humans are remarkably adept at inferring the causes of events in their environment; doing so often requires incorporating information from multiple sensory modalities. For instance, if a car slows down in front of us, inferences about why they did so are rapidly revised if we also hear sirens in the distance. Here, we investigate the ability to reconstruct others' actions and events from the past by integrating multimodal information. Participants were asked to infer which of two agents performed an action in a household setting given either visual evidence, auditory evidence, or both. We develop a computational model that makes inferences by generating multimodal simulations, and also evaluate our task on a large language model (GPT-4) and a large multimodal model (GPT-4V). We find that humans are relatively accurate overall and perform best when given multimodal evidence. GPT-4 and GPT-4V performance comes close overall, but is very weakly correlated with participants across individual trials. Meanwhile, the simulation model captures the pattern of human responses well. Multimodal event reconstruction represents a challenge for current AI systems, and frameworks that draw on the cognitive processes underlying people's ability to reconstruct events offer a promising avenue forward