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Circulating IL-17F, but not IL-17A, is elevated in severe COVID-19 and leads to an ERK1/2 and p38 MAPK-dependent increase in ICAM-1 cell surface expression and neutrophil adhesion on endothelial cells
Severe COVID-19 is associated with neutrophilic inflammation and immunothrombosis. Several members of the IL-17 cytokine family have been as… (see more)sociated with neutrophilic inflammation and activation of the endothelium. Therefore, we investigated whether these cytokines were associated with COVID-19.We investigated the association between COVID-19 and circulating plasma levels of IL-17 cytokine family members in participants to the Biobanque québécoise de la COVID-19 (BQC19), a prospective observational cohort and an independent cohort from Western University (London, Ontario). We measured the in vitro impact of IL-17F on intercellular adhesion molecule 1 (ICAM-1) cell surface expression and neutrophil adhesion on endothelial cells in culture. The contribution of two Mitogen Activated Protein Kinase (MAPK) pathways was determined using small molecule inhibitors PD184352 (a MKK1/MKK2 inhibitor) and BIRB0796 (a p38 MAPK inhibitor).We found increased IL-17D and IL-17F plasma levels when comparing SARS-CoV-2-positive vs negative hospitalized participants. Moreover, increased plasma levels of IL-17D, IL-17E and IL-17F were noted when comparing severe versus mild COVID-19. IL-17F, but not IL-17A, was significantly elevated in people with COVID-19 compared to healthy controls and with more severe disease. In vitro work on endothelial cells treated with IL-17F for 24h showed an increase cell surface expression of ICAM-1 accompanied by neutrophil adhesion. The introduction of two MAPK inhibitors significantly reduced the binding of neutrophils while also reducing ICAM-1 expression at the surface level of endothelial cells, but not its intracellular expression.Overall, these results have identified an association between two cytokines of the IL-17 family (IL-17D and IL-17F) with COVID-19 and disease severity. Considering that IL-17F stimulation promotes neutrophil adhesion to the endothelium in a MAPK-dependent manner, it is attractive to speculate that this pathway may contribute to pathogenic immunothrombosis in concert with other molecular effectors.
Automatic subphenotyping from electronic health records (EHRs)provides numerous opportunities to understand diseases with unique subgroups a… (see more)nd enhance personalized medicine for patients. However, existing machine learning algorithms either focus on specific diseases for better interpretability or produce coarse-grained phenotype topics without considering nuanced disease patterns. In this study, we propose a guided topic model, MixEHR-Nest, to infer sub-phenotype topics from thousands of disease using multi-modal EHR data. Specifically, MixEHR-Nest detects multiple subtopics from each phenotype topic, whose prior is guided by the expert-curated phenotype concepts such as Phenotype Codes (PheCodes) or Clinical Classification Software (CCS) codes. We evaluated MixEHR-Nest on two EHR datasets: (1) the MIMIC-III dataset consisting of over 38 thousand patients from intensive care unit (ICU) from Beth Israel Deaconess Medical Center (BIDMC) in Boston, USA; (2) the healthcare administrative database PopHR, comprising 1.3 million patients from Montreal, Canada. Experimental results demonstrate that MixEHR-Nest can identify subphenotypes with distinct patterns within each phenotype, which are predictive for disease progression and severity. Consequently, MixEHR-Nest distinguishes between type 1 and type 2 diabetes by inferring subphenotypes using CCS codes, which do not differentiate these two subtype concepts. Additionally, MixEHR-Nest not only improved the prediction accuracy of short-term mortality of ICU patients and initial insulin treatment in diabetic patients but also revealed the contributions of subphenotypes. For longitudinal analysis, MixEHR-Nest identified subphenotypes of distinct age prevalence under the same phenotypes, such as asthma, leukemia, epilepsy, and depression. The MixEHR-Nest software is available at GitHub: https://github.com/li-lab-mcgill/MixEHR-Nest.
The optimal training of a vision transformer for brain encoding depends on three factors: model size, data size, and computational resources… (see more). This study investigates these three pillars, focusing on the effects of data scaling, model scaling, and high-performance computing on brain encoding results. Using VideoGPT to extract efficient spatiotemporal features from videos and training a Ridge model to predict brain activity based on these features, we conducted benchmark experiments with varying data sizes (10k, 100k, 1M, 6M) and different model configurations of GPT-2, including hidden layer dimensions, number of layers, and number of attention heads. We also evaluated the effects of training models with 32-bit vs 16-bit floating point representations. Our results demonstrate that increasing the hidden layer dimensions significantly improves brain encoding performance, as evidenced by higher Pearson correlation coefficients across all subjects. In contrast, the number of attention heads does not have a significant effect on the encoding results. Additionally, increasing the number of layers shows some improvement in brain encoding correlations, but the trend is not as consistent as that observed with hidden layer dimensions. The data scaling results show that larger training datasets lead to improved brain encoding performance, with the highest Pearson correlation coefficients observed for the largest dataset size (6M). These findings highlight that the effects of data scaling are more significant compared to model scaling in enhancing brain encoding performance. Furthermore, we explored the impact of floating-point precision by comparing 32-bit and 16-bit representations. Training with 16-bit precision yielded the same brain encoding accuracy as 32-bit, while reducing training time by 1.17 times, demonstrating its efficiency for high-performance computing tasks.
The optimal training of a vision transformer for brain encoding depends on three factors: model size, data size, and computational resources… (see more). This study investigates these three pillars, focusing on the effects of data scaling, model scaling, and high-performance computing on brain encoding results. Using VideoGPT to extract efficient spatiotemporal features from videos and training a Ridge model to predict brain activity based on these features, we conducted benchmark experiments with varying data sizes (10k, 100k, 1M, 6M) and different model configurations of GPT-2, including hidden layer dimensions, number of layers, and number of attention heads. We also evaluated the effects of training models with 32-bit vs 16-bit floating point representations. Our results demonstrate that increasing the hidden layer dimensions significantly improves brain encoding performance, as evidenced by higher Pearson correlation coefficients across all subjects. In contrast, the number of attention heads does not have a significant effect on the encoding results. Additionally, increasing the number of layers shows some improvement in brain encoding correlations, but the trend is not as consistent as that observed with hidden layer dimensions. The data scaling results show that larger training datasets lead to improved brain encoding performance, with the highest Pearson correlation coefficients observed for the largest dataset size (6M). These findings highlight that the effects of data scaling are more significant compared to model scaling in enhancing brain encoding performance. Furthermore, we explored the impact of floating-point precision by comparing 32-bit and 16-bit representations. Training with 16-bit precision yielded the same brain encoding accuracy as 32-bit, while reducing training time by 1.17 times, demonstrating its efficiency for high-performance computing tasks.
Real-time aerial image segmentation plays an important role in the environmental perception of Uncrewed Aerial Vehicles (UAVs). We introduce… (see more) BlabberSeg, an optimized Vision-Language Model built on CLIPSeg for on-board, real-time processing of aerial images by UAVs. BlabberSeg improves the efficiency of CLIPSeg by reusing prompt and model features, reducing computational overhead while achieving real-time open-vocabulary aerial segmentation. We validated BlabberSeg in a safe landing scenario using the Dynamic Open-Vocabulary Enhanced SafE-Landing with Intelligence (DOVESEI) framework, which uses visual servoing and open-vocabulary segmentation. BlabberSeg reduces computational costs significantly, with a speed increase of 927.41% (16.78 Hz) on a NVIDIA Jetson Orin AGX (64GB) compared with the original CLIPSeg (1.81Hz), achieving real-time aerial segmentation with negligible loss in accuracy (2.1% as the ratio of the correctly segmented area with respect to CLIPSeg). BlabberSeg's source code is open and available online.