p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Designing the Architecture of a Convolutional Neural Network Automatically for Diabetic Retinopathy Diagnosis

Diabetic retinopathy (DR) is a leading cause of blindness in middle-aged diabetic patients. Regular screening for DR using fundus imaging aids in detecting complications and delays the progression of the disease. Because manual screening takes time and is subjective, deep learning has been used to help graders. Pre-trained or brute force CNN models are used in existing DR grading CNN-based approaches that are not suited to fundus image complexity. To solve this problem, we present a method for automatically customizing CNN models based on fundus image lesions. It uses k-medoid clustering, principal component analysis (PCA), and inter-class and intra-class variations to determine the CNN model’s depth and width. The designed models are lightweight, adapted to the internal structures of fundus images, and encode the discriminative patterns of DR lesions. The technique is validated on a local dataset from King Saud University Medical City, Saudi Arabia, and two challenging Kaggle datasets: EyePACS and APTOS2019. The auto-designed models outperform well-known pre-trained CNN models such as ResNet152, DenseNet121, and ResNeSt50, as well as Google’s AutoML and Auto-Keras models based on neural architecture search (NAS). The proposed method outperforms current CNN-based DR screening methods. The proposed method can be used in various clinical settings to screen for DR and refer patients to ophthalmologists for further evaluation and treatment

Designing the Architecture of a Convolutional Neural Network Automatically for Diabetic Retinopathy Diagnosis

Diabetic retinopathy (DR) is a leading cause of blindness in middle-aged diabetic patients. Regular screening for DR using fundus imaging aids in detecting complications and delays the progression of the disease. Because manual screening takes time and is subjective, deep learning has been used to help graders. Pre-trained or brute force CNN models are used in existing DR grading CNN-based approaches that are not suited to fundus image complexity. To solve this problem, we present a method for automatically customizing CNN models based on fundus image lesions. It uses k-medoid clustering, principal component analysis (PCA), and inter-class and intra-class variations to determine the CNN model’s depth and width. The designed models are lightweight, adapted to the internal structures of fundus images, and encode the discriminative patterns of DR lesions. The technique is validated on a local dataset from King Saud University Medical City, Saudi Arabia, and two challenging Kaggle datasets: EyePACS and APTOS2019. The auto-designed models outperform well-known pre-trained CNN models such as ResNet152, DenseNet121, and ResNeSt50, as well as Google’s AutoML and Auto-Keras models based on neural architecture search (NAS). The proposed method outperforms current CNN-based DR screening methods. The proposed method can be used in various clinical settings to screen for DR and refer patients to ophthalmologists for further evaluation and treatment

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press