Single-cell and spatial transcriptome analyses revealed cell heterogeneity and immune environment alternations in metastatic axillary lymph nodes in breast cancer.

BACKGROUND: Tumor heterogeneity plays essential roles in developing cancer therapies, including therapies for breast cancer (BC). In addition, it is also very important to understand the relationships between tumor microenvironments and the systematic immune environment. METHODS: Here, we performed single-cell, VDJ sequencing and spatial transcriptome analyses on tumor and adjacent normal tissue as well as axillar lymph nodes (LNs) and peripheral blood mononuclear cells (PBMCs) from 8 BC patients. RESULTS: We found that myeloid cells exhibited environment-dependent plasticity, where a group of macrophages with both M1 and M2 signatures possessed high tumor specificity spatially and was associated with worse patient survival. Cytotoxic T cells in tumor sites evolved in a separate path from those in the circulatory system. T cell receptor (TCR) repertoires in metastatic LNs showed significant higher consistency with TCRs in tumor than those in nonmetastatic LNs and PBMCs, suggesting the existence of common neo-antigens across metastatic LNs and primary tumor cites. In addition, the immune environment in metastatic LNs had transformed into a tumor-like status, where pro-inflammatory macrophages and exhausted T cells were upregulated, accompanied by a decrease in B cells and neutrophils. Finally, cell interactions showed that cancer-associated fibroblasts (CAFs) contributed most to shaping the immune-suppressive microenvironment, while CD8+ cells were the most signal-responsive cells. CONCLUSIONS: This study revealed the cell structures of both micro- and macroenvironments, revealed how different cells diverged in related contexts as well as their prognostic capacities, and displayed a landscape of cell interactions with spatial information.

Modelling dynamics of coronavirus disease 2019 spread for pandemic forecasting based on Simulink.

In this paper, we demonstrate the application of MATLAB to develop a pandemic prediction system based on Simulink. The susceptible-exposed-asymptomatic but infectious-symptomatic and infectious (severe infected population + mild infected population)-recovered-deceased (SEAI(I1+I2)RD) physical model for unsupervised learning and two types of supervised learning, namely, fuzzy proportional-integral-derivative (PID) and wavelet neural-network PID learning, are used to build a predictive-control system model that enables self-learning artificial intelligence (AI)-based control. After parameter setting, the data entering the model are predicted, and the value of the data set at a future moment is calculated. PID controllers are added to ensure that the system does not diverge at the beginning of iterative learning. To adapt to complex system conditions and afford excellent control, a wavelet neural-network PID control strategy is developed that can be adjusted and corrected in real time, according to the output error.

Discriminable Multi-Label Attribute Selection for Pre-Course Student Performance Prediction.

The university curriculum is a systematic and organic study complex with some immediate associated steps; the initial learning of each semester's course is crucial, and significantly impacts the learning process of subsequent courses and further studies. However, the low teacher-student ratio makes it difficult for teachers to consistently follow up on the detail-oriented learning situation of individual students. The extant learning early warning system is committed to automatically detecting whether students have potential difficulties-or even the risk of failing, or non-pass reports-before starting the course. Previous related research has the following three problems: first of all, it mainly focused on e-learning platforms and relied on online activity data, which was not suitable for traditional teaching scenarios; secondly, most current methods can only proffer predictions when the course is in progress, or even approaching the end; thirdly, few studies have focused on the feature redundancy in these learning data. Aiming at the traditional classroom teaching scenario, this paper transforms the pre-class student performance prediction problem into a multi-label learning model, and uses the attribute reduction method to scientifically streamline the characteristic information of the courses taken and explore the important relationship between the characteristics of the previously learned courses and the attributes of the courses to be taken, in order to detect high-risk students in each course before the course begins. Extensive experiments were conducted on 10 real-world datasets, and the results proved that the proposed approach achieves better performance than most other advanced methods in multi-label classification evaluation metrics.

A new SEAIRD pandemic prediction model with clinical and epidemiological data analysis on COVID-19 outbreak.

Measuring the spread of disease during a pandemic is critically important for accurately and promptly applying various lockdown strategies, so to prevent the collapse of the medical system. The latest pandemic of COVID-19 that hits the world death tolls and economy loss very hard, is more complex and contagious than its precedent diseases. The complexity comes mostly from the emergence of asymptomatic patients and relapse of the recovered patients which were not commonly seen during SARS outbreaks. These new characteristics pertaining to COVID-19 were only discovered lately, adding a level of uncertainty to the traditional SEIR models. The contribution of this paper is that for the COVID-19 epidemic, which is infectious in both the incubation period and the onset period, we use neural networks to learn from the actual data of the epidemic to obtain optimal parameters, thereby establishing a nonlinear, self-adaptive dynamic coefficient infectious disease prediction model. On the basis of prediction, we considered control measures and simulated the effects of different control measures and different strengths of the control measures. The epidemic control is predicted as a continuous change process, and the epidemic development and control are integrated to simulate and forecast. Decision-making departments make optimal choices. The improved model is applied to simulate the COVID-19 epidemic in the United States, and by comparing the prediction results with the traditional SEIR model, SEAIRD model and adaptive SEAIRD model, it is found that the adaptive SEAIRD model's prediction results of the U.S. COVID-19 epidemic data are in good agreement with the actual epidemic curve. For example, from the prediction effect of these 3 different models on accumulative confirmed cases, in terms of goodness of fit, adaptive SEAIRD model (0.99997) ≈ SEAIRD model (0.98548) > Classical SEIR model (0.66837); in terms of error value: adaptive SEAIRD model (198.6563) < < SEAIRD model(4739.8577) < < Classical SEIR model (22,652.796); The objective of this contribution is mainly on extending the current spread prediction model. It incorporates extra compartments accounting for the new features of COVID-19, and fine-tunes the new model with neural network, in a bid of achieving a higher level of prediction accuracy. Based on the SEIR model of disease transmission, an adaptive model called SEAIRD with internal source and isolation intervention is proposed. It simulates the effects of the changing behaviour of the SARS-CoV-2 in U.S. Neural network is applied to achieve a better fit in SEAIRD. Unlike the SEIR model, the adaptive SEAIRD model embraces multi-group dynamics which lead to different evolutionary trends during the epidemic. Through the risk assessment indicators of the adaptive SEAIRD model, it is convenient to measure the severity of the epidemic situation for consideration of different preventive measures. Future scenarios are projected from the trends of various indicators by running the adaptive SEAIRD model.

Mining Massive E-Health Data Streams for IoMT Enabled Healthcare Systems.

With the increasing popularity of the Internet-of-Medical-Things (IoMT) and smart devices, huge volumes of data streams have been generated. This study aims to address the concept drift, which is a major challenge in the processing of voluminous data streams. Concept drift refers to overtime change in data distribution. It may occur in the medical domain, for example the medical sensors measuring for general healthcare or rehabilitation, which may switch their roles for ICU emergency operations when required. Detecting concept drifts becomes trickier when the class distributions in data are skewed, which is often true for medical sensors e-health data. Reactive Drift Detection Method (RDDM) is an efficient method for detecting long concepts. However, RDDM has a high error rate, and it does not handle class imbalance. We propose an Enhanced Reactive Drift Detection Method (ERDDM), which systematically generates strategies to handle concept drift with class imbalance in data streams. We conducted experiments to compare ERDDM with three contemporary techniques in terms of prediction error, drift detection delay, latency, and ability to handle data imbalance. The experimentation was done in Massive Online Analysis (MOA) on 48 synthetic datasets customized to possess the capabilities of data streams. ERDDM can handle abrupt and gradual drifts and performs better than all benchmarks in almost all experiments.

Composite Monte Carlo decision making under high uncertainty of novel coronavirus epidemic using hybridized deep learning and fuzzy rule induction.

In the advent of the novel coronavirus epidemic since December 2019, governments and authorities have been struggling to make critical decisions under high uncertainty at their best efforts. In computer science, this represents a typical problem of machine learning over incomplete or limited data in early epidemic Composite Monte-Carlo (CMC) simulation is a forecasting method which extrapolates available data which are broken down from multiple correlated/casual micro-data sources into many possible future outcomes by drawing random samples from some probability distributions. For instance, the overall trend and propagation of the infested cases in China are influenced by the temporal-spatial data of the nearby cities around the Wuhan city (where the virus is originated from), in terms of the population density, travel mobility, medical resources such as hospital beds and the timeliness of quarantine control in each city etc. Hence a CMC is reliable only up to the closeness of the underlying statistical distribution of a CMC, that is supposed to represent the behaviour of the future events, and the correctness of the composite data relationships. In this paper, a case study of using CMC that is enhanced by deep learning network and fuzzy rule induction for gaining better stochastic insights about the epidemic development is experimented. Instead of applying simplistic and uniform assumptions for a MC which is a common practice, a deep learning-based CMC is used in conjunction of fuzzy rule induction techniques. As a result, decision makers are benefited from a better fitted MC outputs complemented by min-max rules that foretell about the extreme ranges of future possibilities with respect to the epidemic.

Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models.

Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug-in-milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug-in-milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight-normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight-normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high-risk period of exposure at 2-4 weeks of age was identified and can inform future drug-in-milk risk assessments.

Development of interventions for an intelligent and individualized mobile health care system to promote healthy diet and physical activity: using an intervention mapping framework.

BACKGROUND: The mortality of coronary heart disease can be largely reduced by modifying unhealthy lifestyles. However, the long-term effectiveness of interventions for modifying unhealthy diet and physical inactivity of patients with coronary heart disease remain unsatisfactory worldwide. This study aims to systematically design a set of theory-based and evidence-based, individualized, and intelligent interventions for promoting the adoption and maintenance of a healthy diet and physical activity level in patients with coronary heart disease. METHODS: The interventions will be delivered by a mobile health care system called Individualized, Intelligent and Integrated Cardiovascular Application for Risk Elimination. Three steps of the intervention mapping framework were used to systematically develop the interventions. Step 1: needs assessment, which was carried out by a literature review, in-depth interviews and focus group discussions. Step 2: development of objective matrix for diet and physical activity changes, based on the intersection of objectives and determinants from the Contemplation-Action-Maintenance behavior change model. Step 3: formulation of evidence-based methods and strategies, and practical applications, through a systematic review of existing literature, research team discussions, and consultation with multidisciplinary expert panels. RESULTS: Three needs relevant to content of the intervention, one need relevant to presentation modes of the intervention, and four needs relevant to functional features of the application were identified. The objective matrix includes three performance objectives, and 24 proximal performance objectives. The evidence-based and theory-based interventions include 31 strategies, 61 evidence-based methods, and 393 practical applications. CONCLUSIONS: This article describes the development of theory-based and evidence-based interventions of the mobile health care system for promoting the adoption and maintenance of a healthy diet and physical activity level in a structured format. The results will provide a theoretical and methodological basis to explore the application of intervention mapping in developing effective behavioral mobile health interventions for patients with coronary heart disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16010242. Registered 24 December 2016. http://www.chictr.org.cn/index.aspx.

A Novel Sensor Data Pre-Processing Methodology for the Internet of Things Using Anomaly Detection and Transfer-By-Subspace-Similarity Transformation.

The Internet of Things (IoT) and sensors are becoming increasingly popular, especially in monitoring large and ambient environments. Applications that embrace IoT and sensors often require mining the data feeds that are collected at frequent intervals for intelligence. Despite the fact that such sensor data are massive, most of the data contents are identical and repetitive; for example, human traffic in a park at night. Most of the traditional classification algorithms were originally formulated decades ago, and they were not designed to handle such sensor data effectively. Hence, the performance of the learned model is often poor because of the small granularity in classification and the sporadic patterns in the data. To improve the quality of data mining from the IoT data, a new pre-processing methodology based on subspace similarity detection is proposed. Our method can be well integrated with traditional data mining algorithms and anomaly detection methods. The pre-processing method is flexible for handling similar kinds of sensor data that are sporadic in nature that exist in many ambient sensing applications. The proposed methodology is evaluated by extensive experiment with a collection of classical data mining models. An improvement over the precision rate is shown by using the proposed method.

Medical cyber-physical systems: A survey.

Medical cyber-physical systems (MCPS) are healthcare critical integration of a network of medical devices. These systems are progressively used in hospitals to achieve a continuous high-quality healthcare. The MCPS design faces numerous challenges, including inoperability, security/privacy, and high assurance in the system software. In the current work, the infrastructure of the cyber-physical systems (CPS) are reviewed and discussed. This article enriched the researches of the networked Medical Device (MD) systems to increase the efficiency and safety of the healthcare. It also can assist the specialists of medical device to overcome crucial issues related to medical devices, and the challenges facing the design of the medical device's network. The concept of the social networking and its security along with the concept of the wireless sensor networks (WSNs) are addressed. Afterward, the CPS systems and platforms have been established, where more focus was directed toward CPS-based healthcare. The big data framework of CPSs is also included.

A Survey of Data Mining and Deep Learning in Bioinformatics.

The fields of medicine science and health informatics have made great progress recently and have led to in-depth analytics that is demanded by generation, collection and accumulation of massive data. Meanwhile, we are entering a new period where novel technologies are starting to analyze and explore knowledge from tremendous amount of data, bringing limitless potential for information growth. One fact that cannot be ignored is that the techniques of machine learning and deep learning applications play a more significant role in the success of bioinformatics exploration from biological data point of view, and a linkage is emphasized and established to bridge these two data analytics techniques and bioinformatics in both industry and academia. This survey concentrates on the review of recent researches using data mining and deep learning approaches for analyzing the specific domain knowledge of bioinformatics. The authors give a brief but pithy summarization of numerous data mining algorithms used for preprocessing, classification and clustering as well as various optimized neural network architectures in deep learning methods, and their advantages and disadvantages in the practical applications are also discussed and compared in terms of their industrial usage. It is believed that in this review paper, valuable insights are provided for those who are dedicated to start using data analytics methods in bioinformatics.

Gaussian Guided Self-Adaptive Wolf Search Algorithm Based on Information Entropy Theory.

Nowadays, swarm intelligence algorithms are becoming increasingly popular for solving many optimization problems. The Wolf Search Algorithm (WSA) is a contemporary semi-swarm intelligence algorithm designed to solve complex optimization problems and demonstrated its capability especially for large-scale problems. However, it still inherits a common weakness for other swarm intelligence algorithms: that its performance is heavily dependent on the chosen values of the control parameters. In 2016, we published the Self-Adaptive Wolf Search Algorithm (SAWSA), which offers a simple solution to the adaption problem. As a very simple schema, the original SAWSA adaption is based on random guesses, which is unstable and naive. In this paper, based on the SAWSA, we investigate the WSA search behaviour more deeply. A new parameter-guided updater, the Gaussian-guided parameter control mechanism based on information entropy theory, is proposed as an enhancement of the SAWSA. The heuristic updating function is improved. Simulation experiments for the new method denoted as the Gaussian-Guided Self-Adaptive Wolf Search Algorithm (GSAWSA) validate the increased performance of the improved version of WSA in comparison to its standard version and other prevalent swarm algorithms.

Training Classifiers with Shadow Features for Sensor-Based Human Activity Recognition.

In this paper, a novel training/testing process for building/using a classification model based on human activity recognition (HAR) is proposed. Traditionally, HAR has been accomplished by a classifier that learns the activities of a person by training with skeletal data obtained from a motion sensor, such as Microsoft Kinect. These skeletal data are the spatial coordinates (x, y, z) of different parts of the human body. The numeric information forms time series, temporal records of movement sequences that can be used for training a classifier. In addition to the spatial features that describe current positions in the skeletal data, new features called 'shadow features' are used to improve the supervised learning efficacy of the classifier. Shadow features are inferred from the dynamics of body movements, and thereby modelling the underlying momentum of the performed activities. They provide extra dimensions of information for characterising activities in the classification process, and thereby significantly improve the classification accuracy. Two cases of HAR are tested using a classification model trained with shadow features: one is by using wearable sensor and the other is by a Kinect-based remote sensor. Our experiments can demonstrate the advantages of the new method, which will have an impact on human activity detection research.

A novel hybrid self-adaptive bat algorithm.

Nature-inspired algorithms attract many researchers worldwide for solving the hardest optimization problems. One of the newest members of this extensive family is the bat algorithm. To date, many variants of this algorithm have emerged for solving continuous as well as combinatorial problems. One of the more promising variants, a self-adaptive bat algorithm, has recently been proposed that enables a self-adaptation of its control parameters. In this paper, we have hybridized this algorithm using different DE strategies and applied these as a local search heuristics for improving the current best solution directing the swarm of a solution towards the better regions within a search space. The results of exhaustive experiments were promising and have encouraged us to invest more efforts into developing in this direction.

Towards enhancement of performance of K-means clustering using nature-inspired optimization algorithms.

Traditional K-means clustering algorithms have the drawback of getting stuck at local optima that depend on the random values of initial centroids. Optimization algorithms have their advantages in guiding iterative computation to search for global optima while avoiding local optima. The algorithms help speed up the clustering process by converging into a global optimum early with multiple search agents in action. Inspired by nature, some contemporary optimization algorithms which include Ant, Bat, Cuckoo, Firefly, and Wolf search algorithms mimic the swarming behavior allowing them to cooperatively steer towards an optimal objective within a reasonable time. It is known that these so-called nature-inspired optimization algorithms have their own characteristics as well as pros and cons in different applications. When these algorithms are combined with K-means clustering mechanism for the sake of enhancing its clustering quality by avoiding local optima and finding global optima, the new hybrids are anticipated to produce unprecedented performance. In this paper, we report the results of our evaluation experiments on the integration of nature-inspired optimization methods into K-means algorithms. In addition to the standard evaluation metrics in evaluating clustering quality, the extended K-means algorithms that are empowered by nature-inspired optimization methods are applied on image segmentation as a case study of application scenario.

A biometric authentication model using hand gesture images.

A novel hand biometric authentication method based on measurements of the user's stationary hand gesture of hand sign language is proposed. The measurement of hand gestures could be sequentially acquired by a low-cost video camera. There could possibly be another level of contextual information, associated with these hand signs to be used in biometric authentication. As an analogue, instead of typing a password 'iloveu' in text which is relatively vulnerable over a communication network, a signer can encode a biometric password using a sequence of hand signs, 'i' , 'l' , 'o' , 'v' , 'e' , and 'u'. Subsequently the features from the hand gesture images are extracted which are integrally fuzzy in nature, to be recognized by a classification model for telling if this signer is who he claimed himself to be, by examining over his hand shape and the postures in doing those signs. It is believed that everybody has certain slight but unique behavioral characteristics in sign language, so are the different hand shape compositions. Simple and efficient image processing algorithms are used in hand sign recognition, including intensity profiling, color histogram and dimensionality analysis, coupled with several popular machine learning algorithms. Computer simulation is conducted for investigating the efficacy of this novel biometric authentication model which shows up to 93.75% recognition accuracy.

A review on multimodal machine learning in medical diagnostics.

Nowadays, the increasing number of medical diagnostic data and clinical data provide more complementary references for doctors to make diagnosis to patients. For example, with medical data, such as electrocardiography (ECG), machine learning algorithms can be used to identify and diagnose heart disease to reduce the workload of doctors. However, ECG data is always exposed to various kinds of noise and interference in reality, and medical diagnostics only based on one-dimensional ECG data is not trustable enough. By extracting new features from other types of medical data, we can implement enhanced recognition methods, called multimodal learning. Multimodal learning helps models to process data from a range of different sources, eliminate the requirement for training each single learning modality, and improve the robustness of models with the diversity of data. Growing number of articles in recent years have been devoted to investigating how to extract data from different sources and build accurate multimodal machine learning models, or deep learning models for medical diagnostics. This paper reviews and summarizes several recent papers that dealing with multimodal machine learning in disease detection, and identify topics for future research.

Using hierarchical time series clustering algorithm and wavelet classifier for biometric voice classification.

Voice biometrics has a long history in biosecurity applications such as verification and identification based on characteristics of the human voice. The other application called voice classification which has its important role in grouping unlabelled voice samples, however, has not been widely studied in research. Lately voice classification is found useful in phone monitoring, classifying speakers' gender, ethnicity and emotion states, and so forth. In this paper, a collection of computational algorithms are proposed to support voice classification; the algorithms are a combination of hierarchical clustering, dynamic time wrap transform, discrete wavelet transform, and decision tree. The proposed algorithms are relatively more transparent and interpretable than the existing ones, though many techniques such as Artificial Neural Networks, Support Vector Machine, and Hidden Markov Model (which inherently function like a black box) have been applied for voice verification and voice identification. Two datasets, one that is generated synthetically and the other one empirically collected from past voice recognition experiment, are used to verify and demonstrate the effectiveness of our proposed voice classification algorithm.

Using medical history embedded in biometrics medical card for user identity authentication: data representation by AVT hierarchical data tree.

User authentication has been widely used by biometric applications that work on unique bodily features, such as fingerprints, retina scan, and palm vessels recognition. This paper proposes a novel concept of biometric authentication by exploiting a user's medical history. Although medical history may not be absolutely unique to every individual person, the chances of having two persons who share an exactly identical trail of medical and prognosis history are slim. Therefore, in addition to common biometric identification methods, medical history can be used as ingredients for generating Q&A challenges upon user authentication. This concept is motivated by a recent advancement on smart-card technology that future identity cards are able to carry patents' medical history like a mobile database. Privacy, however, may be a concern when medical history is used for authentication. Therefore in this paper, a new method is proposed for abstracting the medical data by using attribute value taxonomies, into a hierarchical data tree (h-Data). Questions can be abstracted to various level of resolution (hence sensitivity of private data) for use in the authentication process. The method is described and a case study is given in this paper.

Using medical history embedded in biometrics medical card for user identity authentication: privacy preserving authentication model by features matching.

Many forms of biometrics have been proposed and studied for biometrics authentication. Recently researchers are looking into longitudinal pattern matching that based on more than just a singular biometrics; data from user's activities are used to characterise the identity of a user. In this paper we advocate a novel type of authentication by using a user's medical history which can be electronically stored in a biometric security card. This is a sequel paper from our previous work about defining abstract format of medical data to be queried and tested upon authentication. The challenge to overcome is preserving the user's privacy by choosing only the useful features from the medical data for use in authentication. The features should contain less sensitive elements and they are implicitly related to the target illness. Therefore exchanging questions and answers about a few carefully chosen features in an open channel would not easily or directly expose the illness, but yet it can verify by inference whether the user has a record of it stored in his smart card. The design of a privacy preserving model by backward inference is introduced in this paper. Some live medical data are used in experiments for validation and demonstration.