Pathogenetic profiling of COVID-19 and SARS-like viruses.

The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA-DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein-chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein-chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic

Therapeutic potential of oleic acid nanovesicles prepared from petroleum ether extract of Sargassum binderi in streptozotocin–induced diabetic wound in Wistar rats

Purpose: To study the effectiveness of phyto-oleic acid nanovesicles (PONVs) developed from Sargassum binderi (an alga) in healing diabetic wound in a rat model, and to establish the associated changes in cytokine network.Methods: Phyto-extract was obtained from the whole plant of Sargassum binderi by Soxhlet extraction using petroleum ether as solvent. The crude extract was subjected to phytochemical analysis and used in the formulation of POVNs. The PONVs were formulated by entrapping petroleum ether extract of Sargassum binderi using the film hydration technique. Wound healing property was determined by measuring both pro-inflammatory and anti-inflammatory cytokines using enzyme-linked immunosorbent assay (ELISA).Results: Tannins and steroids were the major components of the petroleum ether extract of Sargassum binderi. Serum cytokine levels were increased after inducing diabetes and creating the wound. The serum levels of IL-2, TNF-α and IL-1β were 37.3 ± 3.3, 76.3 ± 5.2 and 3307.6 ± 350 pg/ml, respectively. Treatment with PONVs modulated the serum cytokine levels through significant decreases in serum IL-2, TNF-α, IL-1β levels, and significant elevation of serum IL-4.Conclusion: These results indicate that PONVs have promising potentials for application as topical treatment for diabetic wounds.Keywords: Brown algae, Sargassum binderi, Oleic acid nanovesicles, Diabetic wound, Cytokine

Network-based genetic profiling reveals cellular pathway differences between follicular thyroid carcinoma and follicular thyroid adenoma

Molecular mechanisms underlying the pathogenesis and progression of malignant thyroid cancers, such as follicular thyroid carcinomas (FTCs), and how these differ from benign thyroid lesions, are poorly understood. In this study, we employed network-based integrative analyses of FTC and benign follicular thyroid adenoma (FTA) lesion transcriptomes to identify key genes and pathways that differ between them. We first analysed a microarray gene expression dataset (Gene Expression Omnibus GSE82208, n = 52) obtained from FTC and FTA tissues to identify differentially expressed genes (DEGs). Pathway analyses of these DEGs were then performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources to identify potentially important pathways, and protein-protein interactions (PPIs) were examined to identify pathway hub genes. Our data analysis identified 598 DEGs, 133 genes with higher and 465 genes with lower expression in FTCs. We identified four significant pathways (one carbon pool by folate, p53 signalling, progesterone-mediated oocyte maturation signalling, and cell cycle pathways) connected to DEGs with high FTC expression; eight pathways were connected to DEGs with lower relative FTC expression. Ten GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression DEGs. PPI analysis then identified 12 potential hub genes based on degree and betweenness centrality; namely, TOP2A, JUN, EGFR, CDK1, FOS, CDKN3, EZH2, TYMS, PBK, CDH1, UBE2C, and CCNB2. Moreover, transcription factors (TFs) were identified that may underlie gene expression differences observed between FTC and FTA, including FOXC1, GATA2, YY1, FOXL1, E2F1, NFIC, SRF, TFAP2A, HINFP, and CREB1. We also identified microRNA (miRNAs) that may also affect transcript levels of DEGs; these included hsa-mir-335-5p, -26b-5p, -124-3p, -16-5p, -192-5p, -1-3p, -17-5p, -92a-3p, -215-5p, and -20a-5p. Thus, our study identified DEGs, molecular pathways, TFs, and miRNAs that reflect molecular mechanisms that differ between FTC and benign FTA. Given the general similarities of these lesions and common tissue origin, some of these differences may reflect malignant progression potential, and include useful candidate biomarkers for FTC and identifying factors important for FTC pathogenesis

An icteric newborn with bad obstetric history

This article has no abstract. The first 100 words appear below:A 34 week preterm baby was admitted with the complaints of respiratory distress soon after birth. The mother had bad obstetric history. She is having the fifth gravida with the first two alive and healthy who were born by the normal vaginal delivery at home. The third child was born with severe jaundice and was treated by exchange transfusion. Subsequently the baby developed bilirubin encephalopathy. Then the baby developed cerebral palsy and ultimately died due to aspiration pneumonia at the age of 2.5 years. Her first three pregnancies were not on any antenatal check-up by the health care provider due to poor socio-economic background and illiteracy

Deep CNN-LSTM With Self-Attention Model for Human Activity Recognition Using Wearable Sensor

Human Activity Recognition (HAR) systems are devised for continuously observing human behavior - primarily in the fields of environmental compatibility, sports injury detection, senior care, rehabilitation, entertainment, and the surveillance in intelligent home settings. Inertial sensors, e.g., accelerometers, linear acceleration, and gyroscopes are frequently employed for this purpose, which are now compacted into smart devices, e.g., smartphones. Since the use of smartphones is so widespread now-a-days, activity data acquisition for the HAR systems is a pressing need. In this article, we have conducted the smartphone sensor-based raw data collection, namely H-Activity , using an Android-OS-based application for accelerometer, gyroscope, and linear acceleration. Furthermore, a hybrid deep learning model is proposed, coupling convolutional neural network and long-short term memory network (CNN-LSTM), empowered by the self-attention algorithm to enhance the predictive capabilities of the system. In addition to our collected dataset ( H-Activity ), the model has been evaluated with some benchmark datasets, e.g., MHEALTH, and UCI-HAR to demonstrate the comparative performance of our model. When compared to other models, the proposed model has an accuracy of 99.93% using our collected H-Activity data, and 98.76% and 93.11% using data from MHEALTH and UCI-HAR databases respectively, indicating its efficacy in recognizing human activity recognition. We hope that our developed model could be applicable in the clinical settings and collected data could be useful for further research.publishedVersio

Machine Learning and Meta-Analysis Approach to Identify Patient Comorbidities and Symptoms that Increased Risk of Mortality in COVID-19

Background: Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus is a significant global challenge. Many individuals who become infected have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative about individual risk of severe illness and mortality. Accurately determining how comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. Methods: To assess the interaction of patient comorbidities with COVID-19 severity and mortality we performed a meta-analysis of the published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Results: Our meta-analysis identified chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictor of mortality, in terms of symptom-comorbidity combinations, it was observed that Pneumonia-Hypertension, Pneumonia-Diabetes and Acute Respiratory Distress Syndrome (ARDS)-Hypertension showed the most significant effects on COVID-19 mortality. Conclusions: These results highlight patient cohorts most at risk of COVID-19 related severe morbidity and mortality which have implications for prioritization of hospital resources

Diagnosis of hearing deficiency using EEG based AEP signals: CWT and improved-VGG16 pipeline

Hearing deficiency is the world’s most common sensation of impairment and impedes human communication and learning. Early and precise hearing diagnosis using electroencephalogram (EEG) is referred to as the optimum strategy to deal with this issue. Among a wide range of EEG control signals, the most relevant modality for hearing loss diagnosis is auditory evoked potential (AEP) which is produced in the brain’s cortex area through an auditory stimulus. This study aims to develop a robust intelligent auditory sensation system utilizing a pre-train deep learning framework by analyzing and evaluating the functional reliability of the hearing based on the AEP response. First, the raw AEP data is transformed into time-frequency images through the wavelet transformation. Then, lower-level functionality is eliminated using a pre-trained network. Here, an improved-VGG16 architecture has been designed based on removing some convolutional layers and adding new layers in the fully connected block. Subsequently, the higher levels of the neural network architecture are fine-tuned using the labelled time-frequency images. Finally, the proposed method’s performance has been validated by a reputed publicly available AEP dataset, recorded from sixteen subjects when they have heard specific auditory stimuli in the left or right ear. The proposed method outperforms the state-of-art studies by improving the classification accuracy to 96.87% (from 57.375%), which indicates that the proposed improved-VGG16 architecture can significantly deal with AEP response in early hearing loss diagnosis

Use of multidimensional item response theory methods for dementia prevalence prediction : an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

Background Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Methods Using cognitive testing data and data on functional limitations from Wave A (2001-2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. Results Our algorithm had a cross-validated predictive accuracy of 88% (86-90), and an area under the curve of 0.97 (0.97-0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3-4) in individuals 70-79, 11% (9-12) in individuals 80-89 years old, and 28% (22-35) in those 90 and older. Conclusions Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys