Peripheral arterial disease (PAD) is associated with a high risk of cardiovascular events and death and is postulated to be a critical socioeconomic cost in the future. Extracellular vesicles (EVs) have emerged as potential candidates for new biomarker discovery related to their protein and nucleic acid cargo. In search of new prognostic and therapeutic targets in PAD, we determined the prothrombotic activity, the cellular origin and the transcriptomic profile of circulating EVs. This prospective study included control and PAD patients. Coagulation time (Procoag-PPL kit), EVs cellular origin and phosphatidylserine exposure were determined by flow cytometry in plateletfree plasma (n = 45 PAD). Transcriptomic profiles of medium/large EVs were generated using the MARS-Seq RNA-Seq protocol (n = 12/group). The serum concentration of the differentially expressed gene S100A9, in serum calprotectin (S100A8/A9), was validated by ELISA in control (n = 100) and PAD patients (n = 317). S100A9 was also determined in EVs and tissues of human atherosclerotic plaques (n = 3). Circulating EVs of PAD patients were mainly of platelet origin, predominantly Annexin V positive and were associated with the procoagulant activity of plateletfree plasma. Transcriptomic analysis of EVs identified 15 differentially expressed genes. Among them, serum calprotectin was elevated in PAD patients (p < 0.05) and associated with increased amputation risk before and after covariate adjustment (mean follow-up 3.6 years, p < 0.01). The combination of calprotectin with hs-CRP in the multivariate analysis further improved risk stratification (p < 0.01). Furthermore, S100A9 was also expressed in femoral plaque derived EVs and tissues. In summary, we found that PAD patients release EVs, mainly of platelet origin, highly positive for AnnexinV and rich in transcripts related to platelet biology and immune responses. Amputation risk prediction improved with calprotectin and was significantly higher when combined with hs-CRP. Our results suggest that EVs can be a promising component of liquid biopsy to identify the molecular signature of PAD patients.
In 2019, the EPMA celebrated its 10th anniversary at the 5th World Congress in Pilsen, Czech Republic. The history of the International Professional Network dedicated to Predictive, Preventive and Personalised Medicine (PPPM / 3PM) is rich in achievements. Facing the coronavirus COVID-19 pandemic it is getting evident globally that the predictive approach, targeted prevention and personalisation of medical services is the optimal paradigm in healthcare demonstrating the high potential to save lives and to benefit the society as a whole. The EPMA World Congress Supplement 2020 highlights advances in 3P medicine.
Recent progress in Single-Cell Genomics has produced different library protocols and techniques for molecular profiling. We formulate a unifying, data-driven, integrative, and predictive methodology for different libraries, samples, and paired-unpaired data modalities. Our design of scAEGAN includes an autoencoder (AE) network integrated with adversarial learning by a cycleGAN (cGAN) network. The AE learns a low-dimensional embedding of each condition, whereas the cGAN learns a non-linear mapping between the AE representations. We evaluate scAEGAN using simulated data and real scRNA-seq datasets, different library preparations (Fluidigm C1, CelSeq, CelSeq2, SmartSeq), and several data modalities as paired scRNA-seq and scATAC-seq. The scAEGAN outperforms Seurat3 in library integration, is more robust against data sparsity, and beats Seurat 4 in integrating paired data from the same cell. Furthermore, in predicting one data modality from another, scAEGAN outperforms Babel. We conclude that scAEGAN surpasses current state-of-the-art methods and unifies integration and prediction challenges.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.