Classification of glucose records from patients at diabetes risk using a combined permutation entropy algorithm

[EN] Background and objectives : The adoption in clinical practice of electronic portable blood or interstitial glucose monitors has enabled the collection, storage, and sharing of massive amounts of glucose level readings. This availability of data opened the door to the application of a multitude of mathematical methods to extract clinical information not discernible with conventional visual inspection. The objective of this study is to assess the capability of Permutation Entropy (PE) to find differences between glucose records of healthy and potentially diabetic subjects. Methods : PE is a mathematical method based on the relative frequency analysis of ordinal patterns in time series that has gained a lot of attention in the last years due to its simplicity, robustness, and per- formance. We study in this paper the applicability of this method to glucose records of subjects at risk of diabetes in order to assess the predictability value of this metric in this context. Results : PE, along with some of its derivatives, was able to find significant differences between diabetic and non¿diabetic patients from records acquired up to 3 years before the diagnosis. The quantitative results for PE were 3.5878 ±0.3916 for the nondiabetic class, and 3.1564 ±0.4166 for the diabetic class. With a classification accuracy higher than 70%, and by means of a Cox regression model, PE demonstrated that it is a very promising candidate as a risk stratification tool for continuous glucose monitoring. Conclusion : PE can be considered as a prospective tool for the early diagnosis of the glucoregulatory system.Cuesta Frau, D.; Miró Martínez, P.; Oltra Crespo, S.; Jordán Núñez, J.; Vargas-Rojo, B.; Vigil-Medina, L. (2018). Classification of glucose records from patients at diabetes risk using a combined permutation entropy algorithm. Computer Methods and Programs in Biomedicine. 165:197-204. https://doi.org/10.1016/j.cmpb.2018.08.018S19720416

Permutation Entropy and Bubble Entropy: Possible interactions and synergies between order and sorting relations

[EN] Despite its widely demonstrated usefulness, there is still room for improvement in the basic Permutation Entropy (PE) algorithm, as several subsequent studies have proposed in the recent years. For example, some improved PE variants try to address possible PE weaknesses, such as its only focus on ordinal information, and not on amplitude, or the possible detrimental impact of equal values in subsequences due to motif ambiguity. Other evolved PE methods try to reduce the influence of input parameters. A good representative of this last point is the Bubble Entropy (BE) method. BE is based on sorting relations instead of ordinal patterns, and its promising capabilities have not been extensively assessed yet. The objective of the present study was to comparatively assess the classification performance of this new method, and study and exploit the possible synergies between PE and BE. The claimed superior performance of BE over PE was first evaluated by conducting a series of time series classification tests over a varied and diverse experimental set. The results of this assessment apparently suggested that there is a complementary relationship between PE and BE, instead of a superior/inferior relationship. A second set of experiments using PE and BE simultaneously as the input features of a clustering algorithm, demonstrated that with a proper algorithm configuration, classification accuracy and robustness can benefit from both measures.Cuesta Frau, D.; Vargas-Rojo, B. (2020). Permutation Entropy and Bubble Entropy: Possible interactions and synergies between order and sorting relations. Mathematical Biosciences and Engineering. 17(2):1637-1658. https://doi.org/10.3934/mbe.2020086S163716581721. C. Bandt and B. Pompe, Permutation entropy: A natural complexity measure for time series, Phys. Rev. Lett., 88 (2002), 174102.2. M. Zanin, L. Zunino, O. A. Rosso and D. 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Influence of Duodenal-Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods

[EN] Diabetes is a disease of great and rising prevalence, with the obesity epidemic being a significant contributing risk factor. Duodenal¿jejunal bypass liner (DJBL) is a reversible implant that mimics the effects of more aggressive surgical procedures, such as gastric bypass, to induce weight loss. We hypothesized that DJBL also influences the glucose dynamics in type II diabetes, based on the induced changes already demonstrated in other physiological characteristics and parameters. In order to assess the validity of this assumption, we conducted a quantitative analysis based on several nonlinear algorithms (Lempel¿Ziv Complexity, Sample Entropy, Permutation Entropy, and modified Permutation Entropy), well suited to the characterization of biomedical time series. We applied them to glucose records drawn from two extreme cases available of DJBL implantation: before and after 10 months. The results confirmed the hypothesis and an accuracy of 86.4% was achieved with modified Permutation Entropy. Other metrics also yielded significant classification accuracy results, all above 70%, provided a suitable parameter configuration was chosen. With the Leave¿One¿Out method, the results were very similar, between 72% and 82% classification accuracy. There was also a decrease in entropy of glycaemia records during the time interval studied. These findings provide a solid foundation to assess how glucose metabolism may be influenced by DJBL implantation and opens a new line of research in this field.The Czech clinical partners were supported by DRO IKEM 000023001 and RVO VFN 64165. The Czech technical partners were supported by Research Centre for Informatics grant numbers CZ.02.1.01/0.0/16 - 019/0000765 and SGS16/231/OHK3/3T/13-Support of interactive approaches to biomedical data acquisition and processing. No funding was received to support this research work by the Spanish and British partnersCuesta Frau, D.; Novák, D.; Burda, V.; Abasolo, D.; Adjei, T.; Varela, M.; Vargas, B.... (2019). Influence of Duodenal-Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods. Complexity. 2019. https://doi.org/10.1155/2019/6070518S2019Kassirer, J. P., & Angell, M. (1998). Losing Weight — An Ill-Fated New Year’s Resolution. New England Journal of Medicine, 338(1), 52-54. doi:10.1056/nejm199801013380109Van Gaal, L., & Dirinck, E. (2016). Pharmacological Approaches in the Treatment and Maintenance of Weight Loss. Diabetes Care, 39(Supplement 2), S260-S267. doi:10.2337/dcs15-3016De Jonge, C., Rensen, S. S., Verdam, F. J., Vincent, R. P., Bloom, S. R., Buurman, W. A., … Greve, J. W. M. (2015). Impact of Duodenal-Jejunal Exclusion on Satiety Hormones. Obesity Surgery, 26(3), 672-678. doi:10.1007/s11695-015-1889-yMuñoz, R., Dominguez, A., Muñoz, F., Muñoz, C., Slako, M., Turiel, D., … Escalona, A. (2013). Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients. Surgical Endoscopy, 28(4), 1056-1062. doi:10.1007/s00464-013-3283-yOgata, H., Tokuyama, K., Nagasaka, S., Ando, A., Kusaka, I., Sato, N., … Yamamoto, Y. (2007). Long-range Correlated Glucose Fluctuations in Diabetes. Methods of Information in Medicine, 46(02), 222-226. doi:10.1055/s-0038-1625411Rodríguez de Castro, C., Vigil, L., Vargas, B., García Delgado, E., García Carretero, R., Ruiz-Galiana, J., & Varela, M. (2016). Glucose time series complexity as a predictor of type 2 diabetes. Diabetes/Metabolism Research and Reviews, 33(2), e2831. doi:10.1002/dmrr.2831DeFronzo, R. A. (2004). Pathogenesis of type 2 diabetes mellitus. Medical Clinics of North America, 88(4), 787-835. doi:10.1016/j.mcna.2004.04.013Zhang, X.-S., Roy, R. J., & Jensen, E. W. (2001). EEG complexity as a measure of depth of anesthesia for patients. IEEE Transactions on Biomedical Engineering, 48(12), 1424-1433. doi:10.1109/10.966601Bandt, C., & Pompe, B. (2002). Permutation Entropy: A Natural Complexity Measure for Time Series. Physical Review Letters, 88(17). doi:10.1103/physrevlett.88.174102Bian, C., Qin, C., Ma, Q. D. Y., & Shen, Q. (2012). Modified permutation-entropy analysis of heartbeat dynamics. Physical Review E, 85(2). doi:10.1103/physreve.85.021906Zhao, L., Wei, S., Zhang, C., Zhang, Y., Jiang, X., Liu, F., & Liu, C. (2015). Determination of Sample Entropy and Fuzzy Measure Entropy Parameters for Distinguishing Congestive Heart Failure from Normal Sinus Rhythm Subjects. Entropy, 17(12), 6270-6288. doi:10.3390/e17096270Weinstein, R. L., Schwartz, S. L., Brazg, R. L., Bugler, J. R., Peyser, T. A., & McGarraugh, G. V. (2007). Accuracy of the 5-Day FreeStyle Navigator Continuous Glucose Monitoring System: Comparison with frequent laboratory reference measurements. Diabetes Care, 30(5), 1125-1130. doi:10.2337/dc06-1602Weber, C., & Schnell, O. (2009). The Assessment of Glycemic Variability and Its Impact on Diabetes-Related Complications: An Overview. Diabetes Technology & Therapeutics, 11(10), 623-633. doi:10.1089/dia.2009.0043Cuesta-Frau, D., Miró-Martínez, P., Oltra-Crespo, S., Jordán-Núñez, J., Vargas, B., González, P., & Varela-Entrecanales, M. (2018). Model Selection for Body Temperature Signal Classification Using Both Amplitude and Ordinality-Based Entropy Measures. Entropy, 20(11), 853. doi:10.3390/e20110853Cuesta–Frau, D., Miró–Martínez, P., Oltra–Crespo, S., Jordán–Núñez, J., Vargas, B., & Vigil, L. (2018). Classification of glucose records from patients at diabetes risk using a combined permutation entropy algorithm. Computer Methods and Programs in Biomedicine, 165, 197-204. doi:10.1016/j.cmpb.2018.08.018Cuesta–Frau, D., Varela–Entrecanales, M., Molina–Picó, A., & Vargas, B. (2018). Patterns with Equal Values in Permutation Entropy: Do They Really Matter for Biosignal Classification? Complexity, 2018, 1-15. doi:10.1155/2018/1324696Mayer, C. C., Bachler, M., Hörtenhuber, M., Stocker, C., Holzinger, A., & Wassertheurer, S. (2014). Selection of entropy-measure parameters for knowledge discovery in heart rate variability data. BMC Bioinformatics, 15(S6). doi:10.1186/1471-2105-15-s6-s2Sheng Lu, Xinnian Chen, Kanters, J. K., Solomon, I. C., & Chon, K. H. (2008). Automatic Selection of the Threshold Value $r$ for Approximate Entropy. IEEE Transactions on Biomedical Engineering, 55(8), 1966-1972. doi:10.1109/tbme.2008.919870Crenier, L., Lytrivi, M., Van Dalem, A., Keymeulen, B., & Corvilain, B. (2016). Glucose Complexity Estimates Insulin Resistance in Either Nondiabetic Individuals or in Type 1 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 101(4), 1490-1497. doi:10.1210/jc.2015-4035Cuesta, D., Varela, M., Miró, P., Galdós, P., Abásolo, D., Hornero, R., & Aboy, M. (2007). Predicting survival in critical patients by use of body temperature regularity measurement based on approximate entropy. Medical & Biological Engineering & Computing, 45(7), 671-678. doi:10.1007/s11517-007-0200-3Chen, W., Zhuang, J., Yu, W., & Wang, Z. (2009). Measuring complexity using FuzzyEn, ApEn, and SampEn. Medical Engineering & Physics, 31(1), 61-68. doi:10.1016/j.medengphy.2008.04.005Xiao-Feng, L., & Yue, W. (2009). Fine-grained permutation entropy as a measure of natural complexity for time series. Chinese Physics B, 18(7), 2690-2695. doi:10.1088/1674-1056/18/7/011Fadlallah, B., Chen, B., Keil, A., & Príncipe, J. (2013). 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Biology-guided algorithms:Improved cardiovascular risk prediction and biomarker discovery

Medical research has seen a stark increase in the amount of available data. The sheer volume and complexity of measured variables challenge the use of traditional statistical methods and are beyond the ability of any human to comprehend. Solving this problem demands powerful models capable of capturing the variable interactions and how those are non-linearly related to the condition under study. In this thesis, we first use Machine Learning (ML) methods to achieve better cardiovascular risk prediction/disease biomarker identification and then describe novel bio-inspired algorithms to solve some of the challenges. On the clinical side, we demonstrate how combining targeted plasma proteomics with ML models outperforms traditional clinical risk factors in predicting first-time acute myocardial infarction as well as recurrent atherosclerotic cardiovascular disease. We then shed some light on the pathophysiological pathways involved in heart failure development using a multi-domain ML model. To improve prediction, we develop a novel graph kernel that incorporates protein-protein interaction information, and suggest a manifold mixing algorithm to increase inter-domain information flow in multi-domain models. Finally, we address global model interpretability to uncover the most important variables governing the prediction. Permutation importance is an intuitive and scalable method commonly used in practice, but it is biased in the presence of covariates. We propose a novel framework to disentangle the shared information between covariates, making permutation importance competitive against methodologies where all marginal contributions of a feature are considered, such as SHAP

Using the Information Provided by Forbidden Ordinal Patterns in Permutation Entropy to Reinforce Time Series Discrimination Capabilities

[EN] Despite its widely tested and proven usefulness, there is still room for improvement in the basic permutation entropy (PE) algorithm, as several subsequent studies have demonstrated in recent years. Some of these new methods try to address the well-known PE weaknesses, such as its focus only on ordinal and not on amplitude information, and the possible detrimental impact of equal values found in subsequences. Other new methods address less specific weaknesses, such as the PE results¿ dependence on input parameter values, a common problem found in many entropy calculation methods. The lack of discriminating power among classes in some cases is also a generic problem when entropy measures are used for data series classification. This last problem is the one specifically addressed in the present study. Toward that purpose, the classification performance of the standard PE method was first assessed by conducting several time series classification tests over a varied and diverse set of data. Then, this performance was reassessed using a new Shannon Entropy normalisation scheme proposed in this paper: divide the relative frequencies in PE by the number of different ordinal patterns actually found in the time series, instead of by the theoretically expected number. According to the classification accuracy obtained, this last approach exhibited a higher class discriminating power. It was capable of finding significant differences in six out of seven experimental datasets¿whereas the standard PE method only did in four¿and it also had better classification accuracy. It can be concluded that using the additional information provided by the number of forbidden/found patterns, it is possible to achieve a higher discriminating power than using the classical PE normalisation method. The resulting algorithm is also very similar to that of PE and very easy to implement.Cuesta Frau, D. (2020). Using the Information Provided by Forbidden Ordinal Patterns in Permutation Entropy to Reinforce Time Series Discrimination Capabilities. Entropy. 22(5):1-17. https://doi.org/10.3390/e22050494S117225Bandt, C., & Pompe, B. (2002). Permutation Entropy: A Natural Complexity Measure for Time Series. Physical Review Letters, 88(17). doi:10.1103/physrevlett.88.174102Zanin, M., Zunino, L., Rosso, O. A., & Papo, D. (2012). Permutation Entropy and Its Main Biomedical and Econophysics Applications: A Review. Entropy, 14(8), 1553-1577. doi:10.3390/e14081553Li, J., Yan, J., Liu, X., & Ouyang, G. (2014). Using Permutation Entropy to Measure the Changes in EEG Signals During Absence Seizures. Entropy, 16(6), 3049-3061. doi:10.3390/e16063049Ravelo-García, A., Navarro-Mesa, J., Casanova-Blancas, U., Martin-Gonzalez, S., Quintana-Morales, P., Guerra-Moreno, I., … Hernández-Pérez, E. (2015). Application of the Permutation Entropy over the Heart Rate Variability for the Improvement of Electrocardiogram-based Sleep Breathing Pause Detection. Entropy, 17(3), 914-927. doi:10.3390/e17030914Cuesta-Frau, D., Miró-Martínez, P., Oltra-Crespo, S., Jordán-Núñez, J., Vargas, B., González, P., & Varela-Entrecanales, M. (2018). Model Selection for Body Temperature Signal Classification Using Both Amplitude and Ordinality-Based Entropy Measures. Entropy, 20(11), 853. doi:10.3390/e20110853Cuesta–Frau, D., Miró–Martínez, P., Oltra–Crespo, S., Jordán–Núñez, J., Vargas, B., & Vigil, L. (2018). Classification of glucose records from patients at diabetes risk using a combined permutation entropy algorithm. Computer Methods and Programs in Biomedicine, 165, 197-204. doi:10.1016/j.cmpb.2018.08.018Gao, Y., Villecco, F., Li, M., & Song, W. (2017). Multi-Scale Permutation Entropy Based on Improved LMD and HMM for Rolling Bearing Diagnosis. 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Weighted-permutation entropy: A complexity measure for time series incorporating amplitude information. Physical Review E, 87(2). doi:10.1103/physreve.87.022911Xiao-Feng, L., & Yue, W. (2009). Fine-grained permutation entropy as a measure of natural complexity for time series. Chinese Physics B, 18(7), 2690-2695. doi:10.1088/1674-1056/18/7/011Azami, H., & Escudero, J. (2016). Amplitude-aware permutation entropy: Illustration in spike detection and signal segmentation. Computer Methods and Programs in Biomedicine, 128, 40-51. doi:10.1016/j.cmpb.2016.02.008Cuesta–Frau, D. (2019). Permutation entropy: Influence of amplitude information on time series classification performance. Mathematical Biosciences and Engineering, 16(6), 6842-6857. doi:10.3934/mbe.2019342Bian, C., Qin, C., Ma, Q. D. Y., & Shen, Q. (2012). Modified permutation-entropy analysis of heartbeat dynamics. 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Predicting risk of preterm birth in singleton pregnancies using machine learning algorithms

We aimed to develop, train, and validate machine learning models for predicting preterm birth (<37 weeks' gestation) in singleton pregnancies at different gestational intervals. Models were developed based on complete data from 22,603 singleton pregnancies from a prospective population-based cohort study that was conducted in 51 midwifery clinics and hospitals in Wenzhou City of China between 2014 and 2016. We applied Catboost, Random Forest, Stacked Model, Deep Neural Networks (DNN), and Support Vector Machine (SVM) algorithms, as well as logistic regression, to conduct feature selection and predictive modeling. Feature selection was implemented based on permutation-based feature importance lists derived from the machine learning models including all features, using a balanced training data set. To develop prediction models, the top 10%, 25%, and 50% most important predictive features were selected. Prediction models were developed with the training data set with 5-fold cross-validation for internal validation. Model performance was assessed using area under the receiver operating curve (AUC) values. The CatBoost-based prediction model after 26 weeks' gestation performed best with an AUC value of 0.70 (0.67, 0.73), accuracy of 0.81, sensitivity of 0.47, and specificity of 0.83. Number of antenatal care visits before 24 weeks' gestation, aspartate aminotransferase level at registration, symphysis fundal height, maternal weight, abdominal circumference, and blood pressure emerged as strong predictors after 26 completed weeks. The application of machine learning on pregnancy surveillance data is a promising approach to predict preterm birth and we identified several modifiable antenatal predictors

Non-communicable Diseases, Big Data and Artificial Intelligence

This reprint includes 15 articles in the field of non-communicable Diseases, big data, and artificial intelligence, overviewing the most recent advances in the field of AI and their application potential in 3P medicine

Assessment of Outliers and Detection of Artifactual Network Segments using Univariate and Multivariate Dispersion Entropy on Physiological Signals

Network physiology has emerged as a promising paradigm for the extraction of clinically relevant information from physiological signals by moving from univariate to multivariate analysis, allowing for the inspection of interdependencies between organ systems. However, for its successful implementation, the disruptive effects of artifactual outliers, which are a common occurrence in physiological recordings, have to be studied, quantified, and addressed. Within the scope of this study, we utilize Dispersion Entropy (DisEn) to initially quantify the capacity of outlier samples to disrupt the values of univariate and multivariate features extracted with DisEn from physiological network segments consisting of synchronised, electroencephalogram, nasal respiratory, blood pressure, and electrocardiogram signals. The DisEn algorithm is selected due to its efficient computation and good performance in the detection of changes in signals for both univariate and multivariate time-series. The extracted features are then utilised for the training and testing of a logistic regression classifier in univariate and multivariate configurations in an effort to partially automate the detection of artifactual network segments. Our results indicate that outlier samples cause significant disruption in the values of extracted features with multivariate features displaying a certain level of robustness based on the number of signals formulating the network segments from which they are extracted. Furthermore, the deployed classifiers achieve noteworthy performance, where the percentage of correct network segment classification surpasses 95% in a number of experimental setups, with the effectiveness of each configuration being affected by the signal in which outliers are located. Finally, due to the increase in the number of features extracted within the framework of network physiology and the observed impact of artifactual samples in the accuracy of their values, the implementation of algorithmic steps capable of effective feature selection is highlighted as an important area for future research