The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis. Importantly, evACE2 isolated from human plasma or cells neutralizes SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2 (rhACE2), evACE2 shows a 135-fold higher potency in blocking the binding of the viral spike protein RBD, and a 60- to 80-fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. Consistently, evACE2 protects the hACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. Furthermore, evACE2 inhibits the infection of SARS-CoV-2 variants (α, β, and δ) with equal or higher potency than for the wildtype strain, supporting a broad-spectrum antiviral mechanism of evACE2 for therapeutic development to block the infection of existing and future coronaviruses that use the ACE2 receptor.

Clinical text classification is an fundamental problem in medical natural language processing. Existing studies have cocnventionally focused on rules or knowledge sources-based feature engineering, but only a limited number of studies have exploited effective representation learning capability of deep learning methods. In this study, we propose a new approach which combines rule-based features and knowledge-guided deep learning models for effective disease classification. Critical Steps of our method include recognizing trigger phrases, predicting classes with very few examples using trigger phrases and training a convolutional neural network (CNN) with word embeddings and Unified Medical Language System (UMLS) entity embeddings. We evaluated our method on the 2008 Integrating Informatics with Biology and the Bedside (i2b2) obesity challenge. The results demonstrate that our method outperforms the state-of-the-art methods. We showed that CNN model is powerful for learning effective hidden features, and CUIs embeddings are helpful for building clinical text representations. This shows integrating domain knowledge into CNN models is promising.

Image representation is a fundamental task in computer vision. However, most of the existing approaches for image representation ignore the relations between images and consider each input image independently. Intuitively, relations between images can help to understand the images and maintain model consistency over related images, leading to better explainability. In this paper, we consider modeling the image-level relations to generate more informative image representations, and propose ImageGCN, an end-to-end graph convolutional network framework for inductive multi-relational image modeling. We apply ImageGCN to chest X-ray images where rich relational information is available for disease identification. Unlike previous image representation models, ImageGCN learns the representation of an image using both its original pixel features and its relationship with other images. Besides learning informative representations for images, ImageGCN can also be used for object detection in a weakly supervised manner. The experimental results on 3 open-source x-ray datasets, ChestX-ray14, CheXpert and MIMIC-CXR demonstrate that ImageGCN can outperform respective baselines in both disease identification and localization tasks and can achieve comparable and often better results than the state-of-the-art methods.

Background: Genetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic mutations as independent features for classification and are limited by study power. We aim to develop a novel method to effectively explore the landscape of genetic variants, including germline variants, and small insertions and deletions for cancer type prediction. Results: We proposed DeepCues, a deep learning model that utilizes convolutional neural networks to unbiasedly derive features from raw cancer DNA sequencing data for disease classification and relevant gene discovery. Using raw whole-exome sequencing as features, germline variants and somatic mutations, including insertions and deletions, were interactively amalgamated for feature generation and cancer prediction. We applied DeepCues to a dataset from TCGA to classify seven different types of major cancers and obtained an overall accuracy of 77.6%. We compared DeepCues to conventional methods and demonstrated a significant overall improvement (p < 0.001). Strikingly, using DeepCues, the top 20 breast cancer relevant genes we have identified, had a 40% overlap with the top 20 known breast cancer driver genes. Conclusion: Our results support DeepCues as a novel method to improve the representational resolution of DNA sequencings and its power in deriving features from raw sequences for cancer type prediction, as well as discovering new cancer relevant genes.

This paper presents a portable phenotyping system that is capable of integrating both rule-based and statistical machine learning based approaches. Our system utilizes UMLS to extract clinically relevant features from the unstructured text and then facilitates portability across different institutions and data systems by incorporating OHDSI’s OMOP Common Data Model (CDM) to standardize necessary data elements. Our system can also store the key components of rule-based systems (e.g., regular expression matches) in the format of OMOP CDM, thus enabling the reuse, adaptation and extension of many existing rule-based clinical NLP systems. We experimented with our system on the corpus from i2b2’s Obesity Challenge as a pilot study. Our system facilitates portable phenotyping of obesity and its 15 comorbidities based on the unstructured patient discharge summaries, while achieving a performance that often ranked among the top 10 of the challenge participants. Our system of standardization enables a consistent application of numerous rule-based and machine learning based classification techniques downstream across disparate datasets which may originate across different institutions and data systems.