In Diabetes Mellitus, the pancreas remains incapable of insulin administration that leads to hyperglycaemia, an escalated glycaemic concentration, which may stimulate many complications. To circumvent this situation, a closed-loop control strategy is much needed for the exogenous insulin infusion in diabetic patients. This closed-loop structure is often termed as an artificial pancreas that is generally established by the employment of different feedback control strategies. In this work, the authors have proposed an arbitrary-order sliding mode control approach for development of the said mechanism. The term, arbitrary, is exercised in the sense of its applicability to any n-order controllable canonical system. The proposed control algorithm affirms the finite-time effective stabilisation of the glucose–insulin regulatory system, at the desired level, with the alleviation of sharp fluctuations. The novelty of this work lies in the sliding manifold that incorporates indirect non-linear terms. In addition, the necessary discontinuous terms are filtered-out once before its employment to the plant, i.e. diabetic patient. The robustness, in the presence of external disturbances, i.e. meal intake is confirmed via rigorous mathematical stability analysis. In addition, the effectiveness of the proposed control strategy is ascertained by comparing the results with the standard literature.

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein–protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.

Computational analysis of microarray data is crucial for understanding the gene behaviours and deriving meaningful results. Clustering and biclustering of gene expression microarray data in the unsupervised domain are extremely important as their outcomes directly dominate healthcare research in many aspects. However, these approaches fail when the time factor is added as the third dimension to the microarray datasets. This three-dimensional data set can be analysed using triclustering that discovers similar gene sets that pursue identical behaviour under a subset of conditions at a specific time point. A novel triclustering algorithm (TriRNSC) is proposed in this manuscript to discover meaningful triclusters in gene expression profiles. TriRNSC is based on restricted neighbourhood search clustering (RNSC), a popular graph-based clustering approach considering the genes, the experimental conditions and the time points at an instance. The performance of the proposed algorithm is evaluated in terms of volume and some performance measures. Gene Ontology and KEGG pathway analysis are used to validate the TriRNSC results biologically. The efficiency of TriRNSC indicates its capability and reliability and also demonstrates its usability over other state-of-art schemes. The proposed framework initiates the application of the RNSC algorithm in the triclustering of gene expression profiles.

A simple model for the B₁₂-riboswitch regulatory network in Escherichia coli is first described and the same analysis is applied when changing the strain to Salmonella enterica. Model validation is undertaken by linking the dynamics of the riboswitch model to bacterial growth and comparing the results obtained with in vivo experimental measurements. Measurements of bacterial growth are relatively straightforward to obtain experimentally, but experimental measurements relating to the operation of the riboswitch are more difficult. Using the validated model, sliding mode observer design methods are used to estimate BtuB given measurements of the concentration of vitamin B₁₂. The sliding mode approach is selected because of its inherent robustness properties as well as for the ease of implementation. Validation of the estimates of BtuB produced by the observer is undertaken by comparing the BtuB and vitamin B₁₂ concentrations estimated from the observer with green fluorescent protein production and the concentration of vitamin B₁₂ obtained experimentally. These experimental results also provide further validation of the underpinning mathematical model. The results establish that using a sliding mode observer as a soft sensor is a useful approach to explore the operation of a vitamin B₁₂ riboswitch given measurements of the concentration of vitamin B₁₂.

Dynamic biological systems can be modelled to an equivalent modular structure using Booleannetworks (BNs) due to their simple construction and relative ease of integration. The chemotaxisnetwork of the bacterium Escherichia coli (E. coli) is one of themost investigated biological systems. In this study, the authors developed a multi-bit Booleanapproach to model the drifting behaviour of the E. coli chemotaxis system. Theirapproach, which is slightly different than the conventional BNs, is designed to provide finerresolution to mimic high-level functional behaviour. Using this approach, they simulated thetransient and steady-state responses of the chemoreceptor sensory module. Furthermore, theyestimated the drift velocity under conditions of the exponential nutrient gradient. Theirpredictions on chemotactic drifting are in good agreement with the experimental measurements undersimilar input conditions. Taken together, by simulating chemotactic drifting, they propose thatmulti-bit Boolean methodology can be used for modelling complex biological networks. Application ofthe method towards designing bio-inspired systems such as nano-bots is discussed.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure and sudden death. The hallmark pathological findings are progressive myocyte loss and fibro fatty replacement, with a predilection for the right ventricle. This study focuses on the adipose tissue formation in cardiomyocyte by considering the signal transduction pathways including Wnt/ -catenin and Wnt/Ca²⁺ regulation system. These pathways are modelled and analysed using stochastic petri nets (SPN) in order to increase our comprehension of ARVC and in turn its treatment regimen. The Wnt/ -catenin model predicts that the dysregulation or absence of Wnt signalling, inhibition of dishevelled and elevation of glycogen synthase kinase 3 along with casein kinase I are key cytotoxic events resulting in apoptosis. Moreover, the Wnt/Ca²⁺ SPN model demonstrates that the Bcl2 gene inhibited by c-Jun N-terminal kinase protein in the event of endoplasmic reticulum stress due to action potential and increased amount of intracellular Ca²⁺ which recovers the Ca²⁺ homeostasis by phospholipase C, this event positively regulates the Bcl2 to suppress the mitochondrial apoptosis which causes ARVC.

The authors demonstrated an optimal stochastic control algorithm to obtain desirable cancer treatment based on the Gompertz model. Two external forces as two time-dependent functions are presented to manipulate the growth and death rates in the drift term of the Gompertz model. These input signals represent the effect of external treatment agents to decrease tumour growth rate and increase tumour death rate, respectively. Entropy and variance of cancerous cells are simultaneously controlled based on the Gompertz model. They have introduced a constrained optimisation problem whose cost function is the variance of a cancerous cells population. The defined entropy is based on the probability density function of affected cells was used as a constraint for the cost function. Analysing growth and death rates of cancerous cells, it is found that the logarithmic control signal reduces the growth rate, while the hyperbolic tangent–like control function increases the death rate of tumour growth. The two optimal control signals were calculated by converting the constrained optimisation problem into an unconstrained optimisation problem and by using the real–coded genetic algorithm. Mathematical justifications are implemented to elucidate the existence and uniqueness of the solution for the optimal control problem.

Prediction of cardiovascular disease (CVD) is a critical challenge in the area of clinical data analysis. In this study, an efficient heart disease prediction is developed based on optimal feature selection. Initially, the data pre-processing process is performed using data cleaning, data transformation, missing values imputation, and data normalisation. Then the decision function-based chaotic salp swarm (DFCSS) algorithm is used to select the optimal features in the feature selection process. Then the chosen attributes are given to the improved Elman neural network (IENN) for data classification. Here, the sailfish optimisation (SFO) algorithm is used to compute the optimal weight value of IENN. The combination of DFCSS–IENN-based SFO (IESFO) algorithm effectively predicts heart disease. The proposed (DFCSS–IESFO) approach is implemented in the Python environment using two different datasets such as the University of California Irvine (UCI) Cleveland heart disease dataset and CVD dataset. The simulation results proved that the proposed scheme achieved a high-classification accuracy of 98.7% for the CVD dataset and 98% for the UCI dataset compared to other classifiers, such as support vector machine, K-nearest neighbour, Elman neural network, Gaussian Naive Bayes, logistic regression, random forest, and decision tree.

This study was to identify important circRNA–miRNA–mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset GSE97332 and miRNA dataset GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug–gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa-miR-25-3p, hsa-miR-3692-5p, hsa-miR-4270, hsa-miR-331-3p, and hsa-miR-125a-3p. Among the network, hsa-miR-25-3p targeted the most genes, hsa-miR-3692-5p and hsa-miR-4270 were targeted by more circRNAs than other miRNAs, hsa-circ-0034326 and hsa-circ-0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug–gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa-circ-0034326 and hsa-circ-0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR-25-3p, miR-3692-5p, and miR-4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.