Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19.

Background: Corona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients. Methods: The four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockTools. Results: Firstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2. Conclusion: In the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.

A Face Detection and Standardized Mask-Wearing Recognition Algorithm.

In the era of coronavirus disease (COVID-19), wearing a mask could effectively protect people from the risk of infection and largely reduce transmission in public places. To prevent the spread of the virus, instruments are needed in public places to monitor whether people are wearing masks, which has higher requirements for the accuracy and speed of detection algorithms. To meet the demand for high accuracy and real-time monitoring, we propose a single-stage approach based on YOLOv4 to identify the face and whether to regulate the wearing of masks. In this approach, we propose a new feature pyramidal network based on the attention mechanism to reduce the loss of object information that can be caused by sampling and pooling in convolutional neural networks. The network is able to deeply mine the feature map for spatial and communication factors, and the multi-scale feature fusion makes the feature map equipped with location and semantic information. Based on the complete intersection over union (CIoU), a penalty function based on the norm is proposed to improve positioning accuracy, which is more accurate at the detection of small objects; the new bounding box regression function is called Norm CIoU (NCIoU). This function is applicable to various object-detection bounding box regression tasks. A combination of the two functions to calculate the confidence loss is used to mitigate the problem of the algorithm bias towards determinating no objects in the image. Moreover, we provide a dataset for recognizing faces and masks (RFM) that includes 12,133 realistic images. The dataset contains three categories: face, standardized mask and non-standardized mask. Experiments conducted on the dataset demonstrate that the proposed approach achieves mAP@.5:.95 69.70% and AP75 73.80%, outperforming the compared methods.

POLCOVID: a multicenter multiclass chest X-ray database (Poland, 2020-2021).

The outbreak of the SARS-CoV-2 pandemic has put healthcare systems worldwide to their limits, resulting in increased waiting time for diagnosis and required medical assistance. With chest radiographs (CXR) being one of the most common COVID-19 diagnosis methods, many artificial intelligence tools for image-based COVID-19 detection have been developed, often trained on a small number of images from COVID-19-positive patients. Thus, the need for high-quality and well-annotated CXR image databases increased. This paper introduces POLCOVID dataset, containing chest X-ray (CXR) images of patients with COVID-19 or other-type pneumonia, and healthy individuals gathered from 15 Polish hospitals. The original radiographs are accompanied by the preprocessed images limited to the lung area and the corresponding lung masks obtained with the segmentation model. Moreover, the manually created lung masks are provided for a part of POLCOVID dataset and the other four publicly available CXR image collections. POLCOVID dataset can help in pneumonia or COVID-19 diagnosis, while the set of matched images and lung masks may serve for the development of lung segmentation solutions.

Using Machine Learning Algorithms to Determine the Post-COVID State of a Person by Their Rhythmogram.

This study introduces a novel method for detecting the post-COVID state using ECG data. By leveraging a convolutional neural network, we identify "cardiospikes" present in the ECG data of individuals who have experienced a COVID-19 infection. With a test sample, we achieve an 87 percent accuracy in detecting these cardiospikes. Importantly, our research demonstrates that these observed cardiospikes are not artifacts of hardware-software signal distortions, but rather possess an inherent nature, indicating their potential as markers for COVID-specific modes of heart rhythm regulation. Additionally, we conduct blood parameter measurements on recovered COVID-19 patients and construct corresponding profiles. These findings contribute to the field of remote screening using mobile devices and heart rate telemetry for diagnosing and monitoring COVID-19.

Paper and screen media in current health education practices aimed at older adults: a scoping review protocol.

INTRODUCTION: With technological advancement and the COVID-19 pandemic, paper-based media are giving way to screen-based media to promote healthy ageing. However, there is no review available covering paper and screen media use by older people, so the objective of this review is to map the current use of paper-based and/or screen-based media for health education aimed at older people. METHODS AND ANALYSIS: The literature will be searched in Scopus, Web of Science, Medline, Embase, Cinahl, The ACM Guide to Computing Literature and Psyinfo databases. Studies in English, Portuguese, Italian or Spanish published from 2012 to the date of the search will be examined. In addition, an additional strategy will be carried out, which will be a Google Scholar search, in which the first 300 studies according to Google's relevance algorithm will be verified. The terms used in the search strategy will be focused on older adults, health education, paper-based and screen-based media, preferences, intervention and other related terms. This review will include studies where the average age of the participants was 60 years or older and were users of health education strategies through paper-based or screen-based media. Two reviewers will carry out the selection of studies in five steps: identification of studies and removal of duplicates, pilot test, selection by reading titles and abstracts, full-text inclusion and search for additional sources. A third reviewer will resolve disagreements. To record information from the included studies, a data extraction form will be used. The quantitative data will be presented in a descriptive way and the qualitative data through Bardin's content analysis. ETHICS AND DISSEMINATION: Ethical approval is not applicable to the scoping review. The results will be disseminated through presentations at significant scientific events and published in journals in the area. PROTOCOL REGISTRATION NUMBER: Open science framework (DOI: DOI 10.17605/OSF.IO/GKEAH).

Triage and Diagnostic Accuracy of Online Symptom Checkers: Systematic Review.

BACKGROUND: In the context of a deepening global shortage of health workers and, in particular, the COVID-19 pandemic, there is growing international interest in, and use of, online symptom checkers (OSCs). However, the evidence surrounding the triage and diagnostic accuracy of these tools remains inconclusive. OBJECTIVE: This systematic review aimed to summarize the existing peer-reviewed literature evaluating the triage accuracy (directing users to appropriate services based on their presenting symptoms) and diagnostic accuracy of OSCs aimed at lay users for general health concerns. METHODS: Searches were conducted in MEDLINE, Embase, CINAHL, Health Management Information Consortium (HMIC), and Web of Science, as well as the citations of the studies selected for full-text screening. We included peer-reviewed studies published in English between January 1, 2010, and February 16, 2022, with a controlled and quantitative assessment of either or both triage and diagnostic accuracy of OSCs directed at lay users. We excluded tools supporting health care professionals, as well as disease- or specialty-specific OSCs. Screening and data extraction were carried out independently by 2 reviewers for each study. We performed a descriptive narrative synthesis. RESULTS: A total of 21,296 studies were identified, of which 14 (0.07%) were included. The included studies used clinical vignettes, medical records, or direct input by patients. Of the 14 studies, 6 (43%) reported on triage and diagnostic accuracy, 7 (50%) focused on triage accuracy, and 1 (7%) focused on diagnostic accuracy. These outcomes were assessed based on the diagnostic and triage recommendations attached to the vignette in the case of vignette studies or on those provided by nurses or general practitioners, including through face-to-face and telephone consultations. Both diagnostic accuracy and triage accuracy varied greatly among OSCs. Overall diagnostic accuracy was deemed to be low and was almost always lower than that of the comparator. Similarly, most of the studies (9/13, 69 %) showed suboptimal triage accuracy overall, with a few exceptions (4/13, 31%). The main variables affecting the levels of diagnostic and triage accuracy were the severity and urgency of the condition, the use of artificial intelligence algorithms, and demographic questions. However, the impact of each variable differed across tools and studies, making it difficult to draw any solid conclusions. All included studies had at least one area with unclear risk of bias according to the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. CONCLUSIONS: Although OSCs have potential to provide accessible and accurate health advice and triage recommendations to users, more research is needed to validate their triage and diagnostic accuracy before widescale adoption in community and health care settings. Future studies should aim to use a common methodology and agreed standard for evaluation to facilitate objective benchmarking and validation. TRIAL REGISTRATION: PROSPERO CRD42020215210; https://tinyurl.com/3949zw83.

Cell-attribute aware community detection improves differential abundance testing from single-cell RNA-Seq data.

Variations of cell-type proportions within tissues could be informative of biological aging and disease risk. Single-cell RNA-sequencing offers the opportunity to detect such differential abundance patterns, yet this task can be statistically challenging due to the noise in single-cell data, inter-sample variability and because such patterns are often of small effect size. Here we present a differential abundance testing paradigm called ELVAR that uses cell attribute aware clustering when inferring differentially enriched communities within the single-cell manifold. Using simulated and real single-cell and single-nucleus RNA-Seq datasets, we benchmark ELVAR against an analogous algorithm that uses Louvain for clustering, as well as local neighborhood-based methods, demonstrating that ELVAR improves the sensitivity to detect cell-type composition shifts in relation to aging, precancerous states and Covid-19 phenotypes. In effect, leveraging cell attribute information when inferring cell communities can denoise single-cell data, avoid the need for batch correction and help retrieve more robust cell states for subsequent differential abundance testing. ELVAR is available as an open-source R-package.

NHGNN-DTA: a node-adaptive hybrid graph neural network for interpretable drug-target binding affinity prediction.

MOTIVATION: Large-scale prediction of drug-target affinity (DTA) plays an important role in drug discovery. In recent years, machine learning algorithms have made great progress in DTA prediction by utilizing sequence or structural information of both drugs and proteins. However, sequence-based algorithms ignore the structural information of molecules and proteins, while graph-based algorithms are insufficient in feature extraction and information interaction. RESULTS: In this article, we propose NHGNN-DTA, a node-adaptive hybrid neural network for interpretable DTA prediction. It can adaptively acquire feature representations of drugs and proteins and allow information to interact at the graph level, effectively combining the advantages of both sequence-based and graph-based approaches. Experimental results have shown that NHGNN-DTA achieved new state-of-the-art performance. It achieved the mean squared error (MSE) of 0.196 on the Davis dataset (below 0.2 for the first time) and 0.124 on the KIBA dataset (3% improvement). Meanwhile, in the case of cold start scenario, NHGNN-DTA proved to be more robust and more effective with unseen inputs than baseline methods. Furthermore, the multi-head self-attention mechanism endows the model with interpretability, providing new exploratory insights for drug discovery. The case study on Omicron variants of SARS-CoV-2 illustrates the efficient utilization of drug repurposing in COVID-19. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/hehh77/NHGNN-DTA.

SEMtree: tree-based structure learning methods with structural equation models.

MOTIVATION: With the exponential growth of expression and protein-protein interaction (PPI) data, the identification of functional modules in PPI networks that show striking changes in molecular activity or phenotypic signatures becomes of particular interest to reveal process-specific information that is correlated with cellular or disease states. This requires both the identification of network nodes with reliability scores and the availability of an efficient technique to locate the network regions with the highest scores. In the literature, a number of heuristic methods have been suggested. We propose SEMtree(), a set of tree-based structure discovery algorithms, combining graph and statistically interpretable parameters together with a user-friendly R package based on structural equation models framework. RESULTS: Condition-specific changes from differential expression and gene-gene co-expression are recovered with statistical testing of node, directed edge, and directed path difference between groups. In the end, from a list of seed (i.e. disease) genes or gene P-values, the perturbed modules with undirected edges are generated with five state-of-the-art active subnetwork detection methods. The latter are supplied to causal additive trees based on Chu-Liu-Edmonds' algorithm (Chow and Liu, Approximating discrete probability distributions with dependence trees. IEEE Trans Inform Theory 1968;14:462-7) in SEMtree() to be converted in directed trees. This conversion allows to compare the methods in terms of directed active subnetworks. We applied SEMtree() to both Coronavirus disease (COVID-19) RNA-seq dataset (GEO accession: GSE172114) and simulated datasets with various differential expression patterns. Compared to existing methods, SEMtree() is able to capture biologically relevant subnetworks with simple visualization of directed paths, good perturbation extraction, and classifier performance. AVAILABILITY AND IMPLEMENTATION: SEMtree() function is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph.

Use of data mining approaches to explore the association between type 2 diabetes mellitus with SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Corona virus causes respiratory tract infections in mammals. The latest type of Severe Acute Respiratory Syndrome Corona-viruses 2 (SARS-CoV-2), Corona virus spread in humans in December 2019 in Wuhan, China. The purpose of this study was to investigate the relationship between type 2 diabetes mellitus (T2DM), and their biochemical and hematological factors with the level of infection with COVID-19 to improve the treatment and management of the disease. MATERIAL AND METHOD: This study was conducted on a population of 13,170 including 5780 subjects with SARS-COV-2 and 7390 subjects without SARS-COV-2, in the age range of 35-65 years. Also, the associations between biochemical factors, hematological factors, physical activity level (PAL), age, sex, and smoking status were investigated with the COVID-19 infection. RESULT: Data mining techniques such as logistic regression (LR) and decision tree (DT) algorithms were used to analyze the data. The results using the LR model showed that in biochemical factors (Model I) creatine phosphokinase (CPK) (OR: 1.006 CI 95% (1.006,1.007)), blood urea nitrogen (BUN) (OR: 1.039 CI 95% (1.033, 1.047)) and in hematological factors (Model II) mean platelet volume (MVP) (OR: 1.546 CI 95% (1.470, 1.628)) were significant factors associated with COVID-19 infection. Using the DT model, CPK, BUN, and MPV were the most important variables. Also, after adjustment for confounding factors, subjects with T2DM had higher risk for COVID-19 infection. CONCLUSION: There was a significant association between CPK, BUN, MPV and T2DM with COVID-19 infection and T2DM appears to be important in the development of COVID-19 infection.

Competition for popularity and interventions on a Chinese microblogging site.

Microblogging sites are important vehicles for the users to obtain information and shape public opinion thus they are arenas of continuous competition for popularity. Most popular topics are usually indicated on ranking lists. In this study, we investigate the public attention dynamics through the Hot Search List (HSL) of the Chinese microblog Sina Weibo, where trending hashtags are ranked based on a multi-dimensional search volume index. We characterize the rank dynamics by the time spent by hashtags on the list, the time of the day they appear there, the rank diversity, and by the ranking trajectories. We show how the circadian rhythm affects the popularity of hashtags, and observe categories of their rank trajectories by a machine learning clustering algorithm. By analyzing patterns of ranking dynamics using various measures, we identify anomalies that are likely to result from the platform provider's intervention into the ranking, including the anchoring of hashtags to certain ranks on the HSL. We propose a simple model of ranking that explains the mechanism of this anchoring effect. We found an over-representation of hashtags related to international politics at 3 out of 4 anchoring ranks on the HSL, indicating possible manipulations of public opinion.

Prediction of COVID-19 Mortality in the Intensive Care Unit Using Machine Learning.

Since its emergence, the COVID-19 pandemic still poses a major global health threat. In this setting, a number of useful machine learning applications have been explored to assist clinical decision-making, predict the severity of disease and admission to the intensive care unit, and also to estimate future demand for hospital beds, equipment, and staff. The present study examined demographic data, hematological and biochemical markers routinely measured in Covid-19 patients admitted to the intensive care unit (ICU) of a public tertiary hospital, in relation to the ICU outcome, during the second and third Covid-19 waves, from October 2020 until February 2022. In this dataset, we applied eight well-known classifiers of the caret package for machine learning of the R programming language, to evaluate their performance in forecasting ICU mortality. The best performance regarding area under the receiver operating characteristic curve (AUC-ROC) was observed with Random Forest (0.82), while k-nearest neighbors (k-NN) were the lowest performing machine learning algorithm (AUC-ROC: 0.59). However, in terms of sensitivity, XGB outperformed the other classifiers (max Sens: 0.7). The six most important predictors of mortality in the Random Forest model were serum urea, age, hemoglobin, C-reactive protein, platelets, and lymphocyte count.

Optimization of urban emergency support material distribution under major public health emergencies based on improved sparrow search algorithm.

The outbreak of major public health emergencies such as the coronavirus epidemic has put forward new requirements for urban emergency management procedures. Accuracy and effective distribution model of emergency support materials, as an effective tool to inhibit the deterioration of the public health sector, have gradually become a research hotspot. The distribution of urban emergency support devices, under the secondary supply chain structure of "material transfer center-demand point," which may involve confusing demands, is studied to determine the actual situation of fuzzy requests under the impact of an epidemic outbreak. An optimization model of urban emergency support material distribution, based on Credibility theory, is first constructed. Then an improved sparrow search algorithm, ISSA, was designed by introducing Sobol sequence, Cauchy variation and bird swarm algorithm into the structure of the classical SSA. In addition, numerical validation and standard test set validation were carried out and the experimental results showed that the introduced improved strategy effectively improved the global search capability of the algorithm. Furthermore, simulation experiments are conducted, based on Shanghai, and the comparison with existing cutting-edge algorithms shows that the designed algorithm has stronger superiority and robustness. And the simulation results show that the designed algorithm can reduce vehicle cost by 4.83%, time cost by 13.80%, etc. compared to other algorithms. Finally, the impact of preference value on the distribution of emergency support materials is analyzed to help decision-makers to develop reasonable and effective distribution strategies according to the impact of major public health emergencies. The results of the study provide a practical reference for the solution of urban emergency support materials distribution problems.

Extracting Temporal Relationships in EHR: Application to COVID-19 Patients.

Association rules are one of the most used data mining techniques. The first proposals have considered relations over time in different ways, resulting in the so-called Temporal Association Rules (TAR). Although there are some proposals to extract association rules in OLAP systems, to the best of our knowledge, there is no method proposed to extract temporal association rules over multidimensional models in these kinds of systems. In this paper we study the adaptation of TAR to multidimensional structures, identifying the dimension that establishes the number of transactions and how to find time relative correlations between the other dimensions. A new method called COGtARE is presented as an extension of a previous approach proposed to reduce the complexity of the resulting set of association rules. The method is tested in application to COVID-19 patients data.

An external validation of the QCOVID3 risk prediction algorithm for risk of hospitalisation and death from COVID-19: An observational, prospective cohort study of 1.66m vaccinated adults in Wales, UK.

INTRODUCTION: At the start of the COVID-19 pandemic there was an urgent need to identify individuals at highest risk of severe outcomes, such as hospitalisation and death following infection. The QCOVID risk prediction algorithms emerged as key tools in facilitating this which were further developed during the second wave of the COVID-19 pandemic to identify groups of people at highest risk of severe COVID-19 related outcomes following one or two doses of vaccine. OBJECTIVES: To externally validate the QCOVID3 algorithm based on primary and secondary care records for Wales, UK. METHODS: We conducted an observational, prospective cohort based on electronic health care records for 1.66m vaccinated adults living in Wales on 8th December 2020, with follow-up until 15th June 2021. Follow-up started from day 14 post vaccination to allow the full effect of the vaccine. RESULTS: The scores produced by the QCOVID3 risk algorithm showed high levels of discrimination for both COVID-19 related deaths and hospital admissions and good calibration (Harrell C statistic: ≥ 0.828). CONCLUSION: This validation of the updated QCOVID3 risk algorithms in the adult vaccinated Welsh population has shown that the algorithms are valid for use in the Welsh population, and applicable on a population independent of the original study, which has not been previously reported. This study provides further evidence that the QCOVID algorithms can help inform public health risk management on the ongoing surveillance and intervention to manage COVID-19 related risks.

IMC-MDA: Prediction of miRNA-disease association based on induction matrix completion.

To comprehend the etiology and pathogenesis of many illnesses, it is essential to identify disease-associated microRNAs (miRNAs). However, there are a number of challenges with current computational approaches, such as the lack of "negative samples", that is, confirmed irrelevant miRNA-disease pairs, and the poor performance in terms of predicting miRNAs related with "isolated diseases", i.e. illnesses with no known associated miRNAs, which presents the need for novel computational methods. In this study, for the purpose of predicting the connection between disease and miRNA, an inductive matrix completion model was designed, referred to as IMC-MDA. In the model of IMC-MDA, for each miRNA-disease pair, the predicted marks are calculated by combining the known miRNA-disease connection with the integrated disease similarities and miRNA similarities. Based on LOOCV, IMC-MDA had an AUC of 0.8034, which shows better performance than previous methods. Furthermore, experiments have validated the prediction of disease-related miRNAs for three major human diseases: colon cancer, kidney cancer, and lung cancer.

Level Set Image Feature Detection and Application in COVID-19 Image Feature Knowledge Detection.

Artificial intelligence (AI) scholars and mediciners have reported AI systems that accurately detect medical imaging and COVID-19 in chest images. However, the robustness of these models remains unclear for the segmentation of images with nonuniform density distribution or the multiphase target. The most representative one is the Chan-Vese (CV) image segmentation model. In this paper, we demonstrate that the recent level set (LV) model has excellent performance on the detection of target characteristics from medical imaging relying on the filtering variational method based on the global medical pathology facture. We observe that the capability of the filtering variational method to obtain image feature quality is better than other LV models. This research reveals a far-reaching problem in medical-imaging AI knowledge detection. In addition, from the analysis of experimental results, the algorithm proposed in this paper has a good effect on detecting the lung region feature information of COVID-19 images and also proves that the algorithm has good adaptability in processing different images. These findings demonstrate that the proposed LV method should be seen as an effective clinically adjunctive method using machine-learning healthcare models.

Artificial Intelligence in Emergency Medicine: Viewpoint of Current Applications and Foreseeable Opportunities and Challenges.

Emergency medicine and its services have reached a breaking point during the COVID-19 pandemic. This pandemic has highlighted the failures of a system that needs to be reconsidered, and novel approaches need to be considered. Artificial intelligence (AI) has matured to the point where it is poised to fundamentally transform health care, and applications within the emergency field are particularly promising. In this viewpoint, we first attempt to depict the landscape of AI-based applications currently in use in the daily emergency field. We review the existing AI systems; their algorithms; and their derivation, validation, and impact studies. We also propose future directions and perspectives. Second, we examine the ethics and risk specificities of the use of AI in the emergency field.

Unsupervised machine learning framework for discriminating major variants of concern during COVID-19.

Due to the high mutation rate of the virus, the COVID-19 pandemic evolved rapidly. Certain variants of the virus, such as Delta and Omicron emerged with altered viral properties leading to severe transmission and death rates. These variants burdened the medical systems worldwide with a major impact to travel, productivity, and the world economy. Unsupervised machine learning methods have the ability to compress, characterize, and visualize unlabelled data. This paper presents a framework that utilizes unsupervised machine learning methods to discriminate and visualize the associations between major COVID-19 variants based on their genome sequences. These methods comprise a combination of selected dimensionality reduction and clustering techniques. The framework processes the RNA sequences by performing a k-mer analysis on the data and further visualises and compares the results using selected dimensionality reduction methods that include principal component analysis (PCA), t-distributed stochastic neighbour embedding (t-SNE), and uniform manifold approximation projection (UMAP). Our framework also employs agglomerative hierarchical clustering to visualize the mutational differences among major variants of concern and country-wise mutational differences for selected variants (Delta and Omicron) using dendrograms. We also provide country-wise mutational differences for selected variants via dendrograms. We find that the proposed framework can effectively distinguish between the major variants and has the potential to identify emerging variants in the future.