Modelling Clustering of Wireless Sensor Networks with Synchronised Hyperedge Replacement

This paper proposes Synchronised Hyperedge Replacement (SHR) as a suitable modelling framework for Wireless Sensor Networks (WSNs). SHR facilitates explicit modelling of WSNs applications environmental conditions (that significantly affect applications performance) while providing a sufficiently high level of abstraction for the specification of the underling coordination mechanisms. Because it is an intractable problem to solve in distributed manner, and distribution is important, we propose a new Nutrient-flow-based Distributed Clustering (NDC) algorithm to be used as a working example. The key contribution of this work is to demonstrate that SHR is sufficiently expressive to describe WSNs algorithms and their behaviour at a suitable level of abstraction to allow onward analysis

Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

BACKGROUND: The coronavirus disease 2019 (COVID-19), a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide, was described to be frequently accompanied by extrapulmonary manifestations, including liver dysfunction. Liver dysfunction and elevated liver enzymes were observed in about 53% of COVID-19 patients. AIM: To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction. METHODS: The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed. Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways. The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis, fibrosis, non-alcoholic fatty liver disease (NAFLD), and hepatitis A/B/C. Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR. RESULTS: Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes, DNAJB1, IGF2, EGFR, and HDGF. Concordantly, the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling (liver cirrhosis, Fibrosis, NAFLD, and hepatitis A/B/C). Moreover, we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function, including cytochrome P450 family members, ACAD11, CIDEB, GNMT, and GPAM. Consequently, drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity. In correspondence with the RNA-seq data analysis, we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction. CONCLUSION: Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling, mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction

Current Status of Baricitinib as a Repurposed Therapy for COVID-19

The emergence of the COVID-19 pandemic has mandated the instant (re)search for potential drug candidates. In response to the unprecedented situation, it was recognized early that repurposing of available drugs in the market could timely save lives, by skipping the lengthy phases of preclinical and initial safety studies. BenevolentAI’s large knowledge graph repository of structured medical information suggested baricitinib, a Janus-associated kinase inhibitor, as a potential repurposed medicine with a dual mechanism; hindering SARS-CoV2 entry and combatting the cytokine storm; the leading cause of mortality in COVID-19. However, the recently-published Adaptive COVID-19 Treatment Trial-2 (ACTT-2) positioned baricitinib only in combination with remdesivir for treatment of a specific category of COVID-19 patients, whereas the drug is not recommended to be used alone except in clinical trials. The increased pace of data output in all life sciences fields has changed our understanding of data processing and manipulation. For the purpose of drug design, development, or repurposing, the integration of different disciplines of life sciences is highly recommended to achieve the ultimate benefit of using new technologies to mine BIG data, however, the final say remains to be concluded after the drug is used in clinical practice. This review demonstrates different bioinformatics, chemical, pharmacological, and clinical aspects of baricitinib to highlight the repurposing journey of the drug and evaluates its placement in the current guidelines for COVID-19 treatment

In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer

Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan–Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone

Visual Analytics Dashboard Promises to Improve Hypertension Guideline Implementation

BACKGROUND: Primary care management of hypertension under new guidelines incorporates assessment of cardiovascular disease risk and commonly requires review of electronic health record (EHR) data. Visual analytics can streamline the review of complex data and may lessen the burden clinicians face using the EHR. This study sought to assess the utility of a visual analytics dashboard in addition to EHR in managing hypertension in a primary care setting. METHODS: Primary care physicians within an urban, academic internal medicine clinic were tasked with performing two simulated patient encounters for HTN management: the first using standard EHR, and the second using EHR paired with a visual dashboard. The dashboard included graphical blood pressure trends with guideline-directed targets, calculated ASCVD risk score, and relevant medications. Guideline-appropriate antihypertensive prescribing, correct target blood pressure goal, and total encounter time were assessed. RESULTS: We evaluated 70 case simulations. Use of the dashboard with the EHR compared to use of the EHR alone was associated with greater adherence to prescribing guidelines (95% vs. 62%, p\u3c0.001) and more correct identification of BP target (95% vs. 57%, p\u3c0.01). Total encounter time fell an average of 121 seconds (95% CI 69 - 157 seconds, p\u3c0.001) in encounters that used the dashboard combined with the EHR. CONCLUSIONS: The integration of a hypertension-specific visual analytics dashboard with EHR demonstrates the potential to reduce time and improve hypertension guideline implementation. Further widespread testing in clinical practice is warranted

An Unfortunate Case of Nonuremic Calciphylaxis

Learning Objective #1: Recognize and distinguish calciphylaxis from other forms of ulcerating vasculitides in nonuremic patients. CASE: A 74-year-old female smoker with a history of diabetes and peripheral artery disease (PAD) presents with painful persistent ulcers on her left arm and bilateral legs. She had a similar presentation one year ago and was diagnosed with thromboangiitis obliterans (Buerger\u27s disease) after a biopsy of the leg ulcer showed inflammatory intraluminal thrombus. At that time, the patient was treated with antibiotics and counseled on smoking cessation. She successfully quit smoking, however skin ulcers continued to progress, which is unusual in Buerger\u27s disease. She returned one year later with painful necrotic skin lesions involving the proximal legs, feet, and arms. Extensive rheumatological, hematological, endocrinological, vascular and genetic testing were all negative. A repeat punch biopsy was performed and revealed calcification and thrombosis of arterioles in the dermis and subcutaneous adipose tissue. Given extensive necrosis, she required bilateral transmetacarpal amputations. IMPACT/DISCUSSION: We present a rare case of extensive non-uremic calciphylaxis in a patient with normal renal function. Calciphylaxis is an ischemic skin disorder recognized in patients with end-stage renal disease (ESRD). Our patient\u27s history of heavy smoking, diabetes, and PAD gave suspicion to Buerger\u27s disease, diabetic foot ulcerations, or ischemic ulcerations. It is essential to make the proper diagnosis, as treatment varies. The ulcers in Buerger\u27s disease normally involve the distal legs and feet, whereas those in calciphylaxis involve the proximal extremities. Histologically, Buerger\u27s disease has an intraluminal thrombus with relative sparing of the vessel wall and internal elastic lamina. This contrasts with calciphylaxis, which has thrombotic occlusion with dermal arteriolar calcification and subintimal fibrosis. Although rare, a systematic review revealed 36 reported cases of nonuremic calciphylaxis. The exact incidence of the disease is unknown. The only available treatment for calciphylaxis is sodium thiosulfate, but this is ineffective in patients with normal kidney function because it gets cleared by the kidneys too quickly to have any effect. Conclusion: Calciphylaxis is a potentially lethal disorder that carries high morbidity and mortality if not recognized early. Although it is most commonly seen in patients with ESRD, clinical suspicion in non-uremic patients with the appropriate lesion distribution and histological findings is essential to early treatment. Further clinical research is needed to better understand non-renal etiologies and treatment

Map as a Service: A Framework for Visualising and Maximising Information Return from Multi-Modal Wireless Sensor Networks

This paper presents a distributed information extraction and visualisation service, called the mapping service, for maximising information return from large-scale wireless sensor networks. Such a service would greatly simplify the production of higher-level, information-rich, representations suitable for informing other network services and the delivery of field information visualisations. The mapping service utilises a blend of inductive and deductive models to map sense data accurately using externally available knowledge. It utilises the special characteristics of the application domain to render visualisations in a map format that are a precise reflection of the concrete reality. This service is suitable for visualising an arbitrary number of sense modalities. It is capable of visualising from multiple independent types of the sense data to overcome the limitations of generating visualisations from a single type of sense modality. Furthermore, the mapping service responds dynamically to changes in the environmental conditions, which may affect the visualisation performance by continuously updating the application domain model in a distributed manner. Finally, a distributed self-adaptation function is proposed with the goal of saving more power and generating more accurate data visualisation. We conduct comprehensive experimentation to evaluate the performance of our mapping service and show that it achieves low communication overhead, produces maps of high fidelity, and further minimises the mapping predictive error dynamically through integrating the application domain model in the mapping service

The FTO genetic variants are associated with dietary intake and body mass index amongst Emirati population.

BACKGROUND:The risk of obesity is determined by complex interactions between genetic and environmental factors. Little research to date has investigated the interaction between gene and food intake. The aim of the current study is to explore the potential effect of fat mass and obesity-associated protein gene (FTO) rs9939609 and rs9930506 single nucleotide polymorphism (SNP) on the pattern of food intake in the Emirati population. METHODS:Adult healthy Emirati subjects with Body mass index (BMI) of 16-40 kg/m2 were included in the study. Genotyping for FTO rs9939609(A>T) and rs9930506(A>G) was performed using DNA from saliva samples. Subjects were categorized according to the WHO classification by calculating the BMI to compare different classes. Dietary intake was assessed by a sixty-one-item FFQ that estimated food and beverage intakes over the past year. The daily energy, macronutrient, and micronutrient consumption were computed. RESULTS:We included 169 subjects in the final analysis (mean age 30.49± 9.1years, 57.4% females). The mean BMI of the study population was 26.19 kg/m2. Both SNPs were in Hardy Weinberg Equilibrium. The rs9939609 AA genotype was significantly associated with higher BMI (p = 0.004); the effect was significant in females (p = 0.028), but not in males (p = 0.184). Carbohydrate intake was significantly higher in AA subjects with a trend of lower fat intake compared to other genotypes. The odds ratio for the AA was 3.78 in the fourth quartile and 2.67 for the A/T in the second quartile of total carbohydrate intake, considering the first quartile as a reference (95% CI = 1.017-14.1 and 1.03-6.88, respectively). Fat intake was significantly lower in the FTO rs9930506 GG subjects. The presence of FTO rs9930506 GG genotype decreased the fat intake in subjects with FTO rs9939609 AA (p = 0.037). CONCLUSIONS:The results of this study highlight the interaction of the FTO risk alleles on the food intake in Emirati subjects. The FTO rs9939609 AA subjects had higher carbohydrate and lower fat intake. The latter was accentuated in presence of rs9930506 GG genotype