Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

NABat ML: Utilizing deep learning to enable crowdsourced development of automated, scalable solutions for documenting North American bat populations

Bats play crucial ecological roles and provide valuable ecosystem services, yet many populations face serious threats from various ecological disturbances. The North American Bat Monitoring Program (NABat) aims to use its technology infrastructure to assess status and trends of bat populations, while developing innovative and community-driven conservation solutions. Here, we present NABat ML, an automated machine-learning algorithm that improves the scalability and scientific transparency of NABat acoustic monitoring. This model combines signal processing techniques and convolutional neural networks (CNNs) to detect and classify recorded bat echolocation calls. We developed our CNN model with internet-based computing resources (‘cloud environment’), and trained it on \u3e600,000 spectrogram images. We also incorporated species range maps to improve the robustness and accuracy of the model for future ‘unseen’ data. We evaluated model performance using a comprehensive, independent, holdout dataset. NABat ML successfully distinguished 31 classes (30 species and a noise class) with overall weighted-average accuracy and precision rates of 92%, and ≥90% classification accuracy for 19 of the bat species. Using a single cloud-environment computing instance, the entire model training process took \u3c16 h. Synthesis and applications. Our convolutional neural network (CNN)-based model, NABat ML, classifies 30 North American bat species using their recorded echolocation calls with an overall accuracy of 92%. In addition to providing highly accurate species-level classification, NABat ML and its outputs are compatible with Bayesian and other statistical techniques for measuring uncertainty in classification. Our model is open-source and reproducible, enabling future implementations as software on end-user devices and cloud-based web applications. These qualities make NABat ML highly suitable for applications ranging from grassroots community science initiatives to big-data methods developed and implemented by researchers and professional practitioners. We believe the transparency and accessibility of NABat ML will encourage broad-scale participation in bat monitoring, and enable development of innovative solutions needed to conserve North American bat species