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.

Convolutional neural network with group theory and random selection particle swarm optimizer for enhancing cancer image classification.

As an epitome of deep learning, convolutional neural network (CNN) has shown its advantages in solving many real-world problems. Successful CNN applications on medical prognosis and diagnosis have been achieved in recent years. Their common goal is to recognize the insights from the subtle details from medical images by building a suitable CNN model with maximum accuracy and minimum error. The CNN performance is extremely sensitive to the parameter tuning for any given network structure. To approach this concern, a novel self-tuning CNN model is proposed with a significant characteristic of having a metaheuristic-based optimizer. The most optimal set of parameters is often found via our proposed method, namely group theory and random selection-based particle swarm optimization (GTRS-PSO). The insights of symmetric essentials of model structure and parameter correlation are extracted, followed by the hierarchical partitioning of parameter space, and four operators on those partitions are designed for moving neighborhoods and formulating the swarm topology accordingly. The parameters are updated by a random selection strategy at each interval of partitions during the search process. Preliminary experiments over two radiology image datasets: breast cancer and lung cancer, are conducted for a comprehensive comparison of GTRS-PSO versus other optimization algorithms. The results show that CNN with GTRS-PSO optimizer can achieve the best performance for cancer image classifications, especially when there are symmetric components inside the data properties and model structures.

White learning methodology: A case study of cancer-related disease factors analysis in real-time PACS environment.

BACKGROUND AND OBJECTIVE: Bayesian network is a probabilistic model of which the prediction accuracy may not be one of the highest in the machine learning family. Deep learning (DL) on the other hand possess of higher predictive power than many other models. How reliable the result is, how it is deduced, how interpretable the prediction by DL mean to users, remain obscure. DL functions like a black box. As a result, many medical practitioners are reductant to use deep learning as the only tool for critical machine learning application, such as aiding tool for cancer diagnosis. METHODS: In this paper, a framework of white learning is being proposed which takes advantages of both black box learning and white box learning. Usually, black box learning will give a high standard of accuracy and white box learning will provide an explainable direct acyclic graph. According to our design, there are 3 stages of White Learning, loosely coupled WL, semi coupled WL and tightly coupled WL based on degree of fusion of the white box learning and black box learning. In our design, a case of loosely coupled WL is tested on breast cancer dataset. This approach uses deep learning and an incremental version of Naïve Bayes network. White learning is largely defied as a systemic fusion of machine learning models which result in an explainable Bayes network which could find out the hidden relations between features and class and deep learning which would give a higher accuracy of prediction than other algorithms. We designed a series of experiments for this loosely coupled WL model. RESULTS: The simulation results show that using WL compared to standard black-box deep learning, the levels of accuracy and kappa statistics could be enhanced up to 50%. The performance of WL seems more stable too in extreme conditions such as noise and high dimensional data. The relations by Bayesian network of WL are more concise and stronger in affinity too. CONCLUSION: The experiments results deliver positive signals that WL is possible to output both high classification accuracy and explainable relations graph between features and class.

Artificial intelligence in cancer diagnosis and prognosis: Opportunities and challenges.

Cancer is an aggressive disease with a low median survival rate. Ironically, the treatment process is long and very costly due to its high recurrence and mortality rates. Accurate early diagnosis and prognosis prediction of cancer are essential to enhance the patient's survival rate. Developments in statistics and computer engineering over the years have encouraged many scientists to apply computational methods such as multivariate statistical analysis to analyze the prognosis of the disease, and the accuracy of such analyses is significantly higher than that of empirical predictions. Furthermore, as artificial intelligence (AI), especially machine learning and deep learning, has found popular applications in clinical cancer research in recent years, cancer prediction performance has reached new heights. This article reviews the literature on the application of AI to cancer diagnosis and prognosis, and summarizes its advantages. We explore how AI assists cancer diagnosis and prognosis, specifically with regard to its unprecedented accuracy, which is even higher than that of general statistical applications in oncology. We also demonstrate ways in which these methods are advancing the field. Finally, opportunities and challenges in the clinical implementation of AI are discussed. Hence, this article provides a new perspective on how AI technology can help improve cancer diagnosis and prognosis, and continue improving human health in the future.

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.

Mining Prognosis Index of Brain Metastases Using Artificial Intelligence.

This study is to identify the optimum prognosis index for brain metastases by machine learning. Seven hundred cancer patients with brain metastases were enrolled and divided into 446 training and 254 testing cohorts. Seven features and seven prediction methods were selected to evaluate the performance of cancer prognosis for each patient. We used mutual information and rough set with particle swarm optimization (MIRSPSO) methods to predict patient's prognosis with the highest accuracy at area under the curve (AUC) = 0.978 ± 0.06. The improvement by MIRSPSO in terms of AUC was at 1.72%, 1.29%, and 1.83% higher than that of the traditional statistical method, sequential feature selection (SFS), mutual information with particle swarm optimization(MIPSO), and mutual information with sequential feature selection (MISFS), respectively. Furthermore, the clinical performance of the best prognosis was superior to conventional statistic method in accuracy, sensitivity, and specificity. In conclusion, identifying optimal machine-learning methods for the prediction of overall survival in brain metastases is essential for clinical applications. The accuracy rate by machine-learning is far higher than that of conventional statistic methods.

Gaussian mixture model for texture characterization with application to brain DTI images.

A Gaussian mixture model (GMM)-based classification technique is employed for a quantitative global assessment of brain tissue changes by using pixel intensities and contrast generated by b-values in diffusion tensor imaging (DTI). A hemisphere approach is also proposed. A GMM identifies the variability in the main brain tissues at a macroscopic scale rather than searching for tumours or affected areas. The asymmetries of the mixture distributions between the hemispheres could be used as a sensitive, faster tool for early diagnosis. The k-means algorithm optimizes the parameters of the mixture distributions and ensures that the global maxima of the likelihood functions are determined. This method has been illustrated using 18 sub-classes of DTI data grouped into six levels of diffusion weighting (b = 0; 250; 500; 750; 1000 and 1250 s/mm2) and three main brain tissues. These tissues belong to three subjects, i.e., healthy, multiple haemorrhage areas in the left temporal lobe and ischaemic stroke. The mixing probabilities or weights at the class level are estimated based on the sub-class-level mixing probability estimation. Furthermore, weighted Euclidean distance and multiple correlation analysis are applied to analyse the dissimilarity of mixing probabilities between hemispheres and subjects. The silhouette data evaluate the objective quality of the clustering. By using a GMM in the present study, we establish an important variability in the mixing probability associated with white matter and grey matter between the left and right hemispheres.