Logic regression analysis of gene polymorphisms and HDL levels in a nationally representative sample of Iranian adolescents: The CASPIAN-III study

Background: To investigate the associations of genetic polymorphism with high-density lipoprotein-cholesterol (HDL-C) levels in Iranian adolescents. Methods: This multicentre study was conducted on 10 - 18 year-old students from 27 provinces in Iran. Logic regression approach was used to determine the main effects and interactions of polymorphisms related to HDL-C levels. Results: The rs708272 polymorphism was significantly related to HDL-C levels. Moreover, rs708272 increased HDL-C levels and had a protective effect on HDL-C. The interaction of rs2230808 and rs5880 polymorphisms as well as the interaction of rs320 and rs708272 polymorphisms were associated with lower HDL-C levels. Furthermore, the interaction of rs320 and rs1801177 polymorphisms was associated with lower HDL-C levels. Conclusions:We found that not only single SNPs, but also interactions of several SNPs affect HDL-C levels. Given the high prevalence of low HDL-C in Middle Eastern populations, further genetic studies are required for detailed analysis.Peer ReviewedPostprint (published version

Prediction of dyslipidemia using gene mutations, family history of diseases and anthropometric indicators in children and adolescents: The CASPIAN-III study

Dyslipidemia, the disorder of lipoprotein metabolism resulting in high lipid profile, is an important modifiable risk factor for coronary heart diseases. It is associated with more than four million worldwide deaths per year. Half of the children with dyslipidemia have hyperlipidemia during adulthood, and its prediction and screening are thus critical. We designed a new dyslipidemia diagnosis system. The sample size of 725 subjects (age 14.66¿±¿2.61 years; 48% male; dyslipidemia prevalence of 42%) was selected by multistage random cluster sampling in Iran. Single nucleotide polymorphisms (rs1801177, rs708272, rs320, rs328, rs2066718, rs2230808, rs5880, rs5128, rs2893157, rs662799, and Apolipoprotein-E2/E3/E4), and anthropometric, life-style attributes, and family history of diseases were analyzed. A framework for classifying mixed-type data in imbalanced datasets was proposed. It included internal feature mapping and selection, re-sampling, optimized group method of data handling using convex and stochastic optimizations, a new cost function for imbalanced data and an internal validation. Its performance was assessed using hold-out and 4-foldcross-validation. Four other classifiers namely as supported vector machines, decision tree, and multilayer perceptron neural network and multiple logistic regression were also used. The average sensitivity, specificity, precision and accuracy of the proposed system were 93%, 94%, 94% and 92%, respectively in cross validation. It significantly outperformed the other classifiers and also showed excellent agreement and high correlation with the gold standard. A non-invasive economical version of the algorithm was also implemented suitable for low- and middle-income countries. It is thus a promising new tool for the prediction of dyslipidemiaPeer ReviewedPostprint (published version

Rigorous performance assessment of the algorithms for resolving motor unit action potential superpositions

It is necessary to decompose the intra-muscular EMG signal to extract motor unit action potential (MUAP) waveforms and firing times. Some algorithms were proposed in the literature to resolve superimposed MUAPs, including Peel-Off (PO), branch and bound (BB), genetic algorithm (GA), and particle swarm optimization (PSO). This study aimed to compare these algorithms in terms of overall accuracy and running time. Two sets of two-to-five MUAP templates (set1: a wide range of energies, and set2: a high degree of similarity) were used. Such templates were time-shifted, and white Gaussian noise was added. A total of 1000 superpositions were simulated for each template and were resolved using PO (also, POI: interpolated PO), BB, GA, and PSO algorithms. The generalized estimating equation was used to identify which method significantly outperformed, while the overall rank product was used for overall ranking. The rankings were PSO, BB, GA, PO, and POI in the first, and BB, PSO, GA, PO, POI in the second set. The overall ranking was BB, PSO, GA, PO, and POI in the entire dataset. Although the BB algorithm is generally fast, there are cases where the BB algorithm is too slow and it is thus not suitable for real-time applications.This work was supported by the Spanish Ministry of Economy and Competitiveness - Spain (DPI2017-83989-R).Peer ReviewedPostprint (author's final draft

Fuzzy jump wavelet neural network based on rule induction for dynamic nonlinear system identification with real data applications

Aim Fuzzy wavelet neural network (FWNN) has proven to be a promising strategy in the identification of nonlinear systems. The network considers both global and local properties, deals with imprecision present in sensory data, leading to desired precisions. In this paper, we proposed a new FWNN model nominated “Fuzzy Jump Wavelet Neural Network” (FJWNN) for identifying dynamic nonlinear-linear systems, especially in practical applications. Methods The proposed FJWNN is a fuzzy neural network model of the Takagi-Sugeno-Kang type whose consequent part of fuzzy rules is a linear combination of input regressors and dominant wavelet neurons as a sub-jump wavelet neural network. Each fuzzy rule can locally model both linear and nonlinear properties of a system. The linear relationship between the inputs and the output is learned by neurons with linear activation functions, whereas the nonlinear relationship is locally modeled by wavelet neurons. Orthogonal least square (OLS) method and genetic algorithm (GA) are respectively used to purify the wavelets for each sub-JWNN. In this paper, fuzzy rule induction improves the structure of the proposed model leading to less fuzzy rules, inputs of each fuzzy rule and model parameters. The real-world gas furnace and the real electromyographic (EMG) signal modeling problem are employed in our study. In the same vein, piecewise single variable function approximation, nonlinear dynamic system modeling, and Mackey–Glass time series prediction, ratify this method superiority. The proposed FJWNN model is compared with the state-of-the-art models based on some performance indices such as RMSE, RRSE, Rel ERR%, and VAF%. Results The proposed FJWNN model yielded the following results: RRSE (mean±std) of 10e-5±6e-5 for piecewise single-variable function approximation, RMSE (mean±std) of 2.6–4±2.6e-4 for the first nonlinear dynamic system modelling, RRSE (mean±std) of 1.59e-3±0.42e-3 for Mackey–Glass time series prediction, RMSE of 0.3421 for gas furnace modelling and VAF% (mean±std) of 98.24±0.71 for the EMG modelling of all trial signals, indicating a significant enhancement over previous methods. Conclusions The FJWNN demonstrated promising accuracy and generalization while moderating network complexity. This improvement is due to applying main useful wavelets in combination with linear regressors and using fuzzy rule induction. Compared to the state-of-the-art models, the proposed FJWNN yielded better performance and, therefore, can be considered a novel tool for nonlinear system identificationPeer ReviewedPostprint (published version

Fetal ECG Extraction from Maternal ECG using Attention-based CycleGAN

Non-invasive fetal electrocardiogram (FECG) is used to monitor the electrical pulse of the fetal heart. Decomposing the FECG signal from maternal ECG (MECG) is a blind source separation problem, which is hard due to the low amplitude of FECG, the overlap of R waves, and the potential exposure to noise from different sources. Traditional decomposition techniques, such as adaptive filters, require tuning, alignment, or pre-configuration, such as modeling the noise or desired signal. to map MECG to FECG efficiently. The high correlation between maternal and fetal ECG parts decreases the performance of convolution layers. Therefore, the masking region of interest using the attention mechanism is performed for improving signal generators' precision. The sine activation function is also used since it could retain more details when converting two signal domains. Three available datasets from the Physionet, including A&D FECG, NI-FECG, and NI-FECG challenge, and one synthetic dataset using FECGSYN toolbox, are used to evaluate the performance. The proposed method could map abdominal MECG to scalp FECG with an average 98% R-Square [CI 95%: 97%, 99%] as the goodness of fit on A&D FECG dataset. Moreover, it achieved 99.7 % F1-score [CI 95%: 97.8-99.9], 99.6% F1-score [CI 95%: 98.2%, 99.9%] and 99.3% F1-score [CI 95%: 95.3%, 99.9%] for fetal QRS detection on, A&D FECG, NI-FECG and NI-FECG challenge datasets, respectively. These results are comparable to the state-of-the-art; thus, the proposed algorithm has the potential of being used for high-performance signal-to-signal conversion

Kernel density estimation of electromyographic signals and ensemble learning for highly accurate classification of a large set of hand/wrist motions

The performance of myoelectric control highly depends on the features extracted from surface electromyographic (sEMG) signals. We propose three new sEMG features based on the kernel density estimation. The trimmed mean of density (TMD), the entropy of density, and the trimmed mean absolute value of derivative density were computed for each sEMG channel. These features were tested for the classification of single tasks as well as of two tasks concurrently performed. For single tasks, correlation-based feature selection was used, and the features were then classified using linear discriminant analysis (LDA), non-linear support vector machines, and multi-layer perceptron. The eXtreme gradient boosting (XGBoost) classifier was used for the classification of two movements simultaneously performed. The second and third versions of the Ninapro dataset (conventional control) and Ameri’s movement dataset (simultaneous control) were used to test the proposed features. For the Ninapro dataset, the overall accuracy of LDA using the TMD feature was 98.99 ± 1.36% and 92.25 ± 9.48% for able-bodied and amputee subjects, respectively. Using ensemble learning of the three classifiers, the average macro and micro-F-score, macro recall, and precision on the validation sets were 98.23 ± 2.02, 98.32 ± 1.93, 98.32 ± 1.93, and 98.88 ± 1.31%, respectively, for the intact subjects. The movement misclassification percentage was 1.75 ± 1.73 and 3.44 ± 2.23 for the intact subjects and amputees. The proposed features were significantly correlated with the movement classes [Generalized Linear Model (GLM); P-value < 0.05]. An accurate online implementation of the proposed algorithm was also presented. For the simultaneous control, the overall accuracy was 99.71 ± 0.08 and 97.85 ± 0.10 for the XGBoost and LDA classifiers, respectively. The proposed features are thus promising for conventional and simultaneous myoelectric control.Peer ReviewedPostprint (published version

A novel spatial feature for the identification of motor tasks using high-density electromyography

Estimation of neuromuscular intention using electromyography (EMG) and pattern recognition is still an open problem. One of the reasons is that the pattern-recognition approach is greatly influenced by temporal changes in electromyograms caused by the variations in the conductivity of the skin and/or electrodes, or physiological changes such as muscle fatigue. This paper proposes novel features for task identification extracted from the high-density electromyographic signal (HD-EMG) by applying the mean shift channel selection algorithm evaluated using a simple and fast classifier-linear discriminant analysis. HD-EMG was recorded from eight subjects during four upper-limb isometric motor tasks (flexion/extension, supination/pronation of the forearm) at three different levels of effort. Task and effort level identification showed very high classification rates in all cases. This new feature performed remarkably well particularly in the identification at very low effort levels. This could be a step towards the natural control in everyday applications where a subject could use low levels of effort to achieve motor tasks. Furthermore, it ensures reliable identification even in the presence of myoelectric fatigue and showed robustness to temporal changes in EMG, which could make it suitable in long-term applications

A novel spatial feature for the identification of motor tasks using high-density electromyography

Estimation of neuromuscular intention using electromyography (EMG) and pattern recognition is still an open problem. One of the reasons is that the pattern-recognition approach is greatly influenced by temporal changes in electromyograms caused by the variations in the conductivity of the skin and/or electrodes, or physiological changes such as muscle fatigue. This paper proposes novel features for task identification extracted from the high-density electromyographic signal (HD-EMG) by applying the mean shift channel selection algorithm evaluated using a simple and fast classifier-linear discriminant analysis. HD-EMG was recorded from eight subjects during four upper-limb isometric motor tasks (flexion/extension, supination/pronation of the forearm) at three different levels of effort. Task and effort level identification showed very high classification rates in all cases. This new feature performed remarkably well particularly in the identification at very low effort levels. This could be a step towards the natural control in everyday applications where a subject could use low levels of effort to achieve motor tasks. Furthermore, it ensures reliable identification even in the presence of myoelectric fatigue and showed robustness to temporal changes in EMG, which could make it suitable in long-term applications.Peer ReviewedPostprint (published version

Detection of multiple innervation zones from multi-channel surface EMG recordings with low signal-to-noise ratio using graph-cut segmentation

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies.The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the Seventh Framework Programme of the European Union (FP7/2007-2013) under REA grant agreement no. 600388 (TECNIOspring programme), from the Agency for Business Competitiveness of the Government of Catalonia, ACCIÓ, and from Spanish Ministry of Economy and Competitiveness- Spain (project DPI2014-59049-R).Peer ReviewedPostprint (published version

Target trial emulation using hospital-based observational data: demonstration and application in COVID-19

Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survival information beyond hospital discharge is available: a condition common to coronavirus disease 2019 (COVID-19) research data. This exemplary study includes a cohort of 618 hospitalized patients with COVID-19. We describe methodological opportunities and challenges that cannot be overcome applying traditional statistical methods. We demonstrate the practical implementation of this trial emulation approach via clone–censor–weight techniques. We undertake a competing risk analysis, reporting the cause-specific cumulative hazards and cumulative incidence probabilities. Our analysis demonstrates that a target trial emulation framework can be extended to account for competing risks in COVID-19 hospital studies. In our analysis, we avoid immortal time bias, time-fixed confounding bias, and competing risks bias simultaneously. Choosing the length of the grace period is justified from a clinical perspective and has an important advantage in ensuring reliable results. This extended trial emulation with the competing risk analysis enables an unbiased estimation of treatment effects, along with the ability to interpret the effectiveness of treatment on all clinically important outcomes.This research was funded by the German Research Foundation (original: Deutsche Forschungsgemeinschaft), grant number WO 1746/5-1.Peer ReviewedPostprint (published version