Psychological distress in early-stage breast cancer survivors is common and can worsen treatment adherence, disease progression, and survival. We present a two-stage hybrid framework for personalized, one-step-ahead prediction of mental-health deterioration, designed to support digital-health interventions. In Stage 1, a within-patient fixed-effects regression on longitudinal mental health status scores (Waves 0–2) captures each patient’s baseline mental-health trajectory and sensitivity to adverse life events. In Stage 2, these personalized estimates are combined with with the rest factors in machine-learning classifiers (SVM, Random Forest, Gradient Boosting) to predict the mental health status in the last unobserved Wave. Across four European cohorts (N = 1,330), the framework achieved 90 % accuracy and F _1 > 94 % in cross-validation, with similar out-of-sample performance. Subgroup and country-level analyses confirmed robustness, while highlighting vulnerable groups where prediction is more challenging. By linking deterioration risk to actionable drivers such as social support and financial strain, the framework provides interpretable, clinically relevant insights to enable timely, personalized psychosocial interventions in pervasive healthcare settings.

Using longitudinal data from Portugal, Italy, Finland, and Israel, this article attempts to explore the causal relationship between mental health and the Big Five personality traits of breast cancer patients with the appearance of adverse life events. The main conclusion is that patients with high scores in the Big Five personality traits index enjoy better mental health status than patients with low scores in that index. In addition, there is a significant negative correlation between mental health deterioration and personality traits as an index and as individual traits. The negative impact on the mental health of cumulative adverse life events is significant and cannot be moderated by personality traits. Single negative life events have a positive correlation with mental health status deterioration, though not all of them are significant and only work-related problems can moderated significantly by high scores in the personality trait index. Moreover, the most important control variable are the state of exercise, which if it changes from active to not active causes a significant drop in the mental health score and cancer stage. Lastly, this causal relationship is validated by the prediction accuracy of AI/ML models.

Identifying individual patient characteristics that contribute to long-term mental health deterioration following diagnosis of breast cancer (BC) is critical in clinical practice. The present study employed a supervised machine learning pipeline to address this issue in a subset of data from a prospective, multinational cohort of women diagnosed with stage I–III BC with a curative treatment intention. Patients were classified as displaying stable HADS scores (Stable Group; n = 328) or reporting a significant increase in symptomatology between BC diagnosis and 12 months later (Deteriorated Group; n = 50). Sociodemographic, life-style, psychosocial, and medical variables collected on the first visit to their oncologist and three months later served as potential predictors of patient risk stratification. The flexible and comprehensive machine learning (ML) pipeline used entailed feature selection, model training, validation and testing. Model-agnostic analyses aided interpretation of model results at the variable- and patient-level. The two groups were discriminated with a high degree of accuracy (Area Under the Curve = 0.864) and a fair balance of sensitivity (0.85) and specificity (0.87). Both psychological (negative affect, certain coping with cancer reactions, lack of sense of control/positive expectations, and difficulties in regulating negative emotions) and biological variables (baseline percentage of neutrophils, thrombocyte count) emerged as important predictors of mental health deterioration in the long run. Personalized break-down profiles revealed the relative impact of specific variables toward successful model predictions for each patient. Identifying key risk factors for mental health deterioration is an essential first step toward prevention. Supervised ML models may guide clinical recommendations toward successful illness adaptation.

BACKGROUND:Health professionals are often faced with the need to identify women at risk of manifesting poor psychological resilience following the diagnosis and treatment of breast cancer. Machine learning algorithms are increasingly used to support clinical decision support (CDS) tools in helping health professionals identify women who are at risk of adverse well-being outcomes and plan customized psychological interventions for women at risk. Clinical flexibility, cross-validated performance accuracy, and model explainability permitting person-specific identification of risk factors are highly desirable features of such tools. OBJECTIVE:This study aimed to develop and cross-validate machine learning models designed to identify breast cancer survivors at risk of poor overall mental health and global quality of life and identify potential targets of personalized psychological interventions according to an extensive set of clinical recommendations. METHODS:A set of 12 alternative models was developed to improve the clinical flexibility of the CDS tool. All models were validated using longitudinal data from a prospective, multicenter clinical pilot at 5 major oncology centers in 4 countries (Italy, Finland, Israel, and Portugal; the Predicting Effective Adaptation to Breast Cancer to Help Women to BOUNCE Back [BOUNCE] project). A total of 706 patients with highly treatable breast cancer were enrolled shortly after diagnosis and before the onset of oncological treatments and were followed up for 18 months. An extensive set of demographic, lifestyle, clinical, psychological, and biological variables measured within 3 months after enrollment served as predictors. Rigorous feature selection isolated key psychological resilience outcomes that could be incorporated into future clinical practice. RESULTS:Balanced random forest classifiers were successful at predicting well-being outcomes, with accuracies ranging between 78% and 82% (for 12-month end points after diagnosis) and between 74% and 83% (for 18-month end points after diagnosis). Explainability and interpretability analyses built on the best-performing models were used to identify potentially modifiable psychological and lifestyle characteristics that, if addressed systematically in the context of personalized psychological interventions, would be most likely to promote resilience for a given patient. CONCLUSIONS:Our results highlight the clinical utility of the BOUNCE modeling approach by focusing on resilience predictors that can be readily available to practicing clinicians at major oncology centers. The BOUNCE CDS tool paves the way for personalized risk assessment methods to identify patients at high risk of adverse well-being outcomes and direct valuable resources toward those most in need of specialized psychological interventions.

A preliminary analysis was conducted on data acquired from RNA sequencing and SomaScan platforms, for the classification of patients with Inflammation of Unknown Origin. To this end, a multimodal data integration approach was designed, by combining the two platforms, in order to assess the potentiality of learning estimators, using the differentially expressed features from the independent profiling experiments of both platforms. The classification framing was the differentiation of Inflammation of Unknown Origin patients against a multitude of Systemic Autoinflammatory disease patients. Separate false discovery rate analyses were performed on each dataset to extract statistically significant features between the two designated sample groups. Genomic analysis managed higher overall classification metrics compared to proteomic analysis, averaging an ~19% increase overall metrics and classifiers, with a ~0.07% increase in standard error. The multimodal data integration approach achieved similar results to the individual platforms’ analyses. More specifically, it managed the same classification accuracy, sensitivity, and specificity scores as the best individual analysis, with the simple Logistic Regression estimator.Clinical Relevance— This study highlights the advantage of exploiting RNA sequencing data to identify potential Inflammation of Unknown Origin disease specific biomarkers, even against other Systemic Autoinflammatory diseases. These findings are further emphasized given the non-apparent clinical discrepancy between Inflammation of Unknown Origin and other Systemic Autoinflammatory diseases.

This study aimed to describe distinct trajectories of anxiety/depression symptoms and overall health status/quality of life over a period of 18 months following a breast cancer diagnosis, and identify the medical, socio‐demographic, lifestyle, and psychological factors that predict these trajectories.

The diagnosis of breast cancer has a significant impact on a patient’s quality of life. Several demographic and clinical factors have been reported to affect the quality of life of breast cancer patients. However, few studies have a sufficient sample size for multifactorial assays to be tested. In the present work, we explore a rich set of clinical, psychological, socio-demographic, and lifestyle data from a large multicenter study of breast cancer patients (n = 765), with the aim to predict their global quality of life (QoL) 18 months after the diagnosis and to identify possible QoL-related prognostic factors. For QoL prediction, a set of Machine Learning methods were explored, namely Random Forest (RF), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN). Depending on the model used, prediction accuracy varied between 0.305 and 0.864. Across models, a largely common set of psychological characteristics (optimism, perceived ability to deal with trauma, resilience as a trait, ability to understand the disease), as well as subjective perceptions of personal functionality (physical, social, cognitive function), were identified as key prognostic factors of long-term quality of life after a breast cancer diagnosis.Clinical Relevance—Early detection of protective and obstructive factors associated with patient well-being can help health professionals to tailor preventive psychological programs aimed at enhancing the ability of breast cancer patients to adapt effectively to the disease.

A meta-analysis study was conducted to compare high-throughput technologies in the classification of Adult-Onset Still's Disease patients, using differentially expressed genes from independent profiling experiments. We exploited two publicly available datasets from the Gene Expression Omnibus and performed a separate differential expression analysis on each dataset to extract statistically important genes. We then mapped the genes of the two datasets and subsequently we employed well-established machine learning algorithms to evaluate the denoted genes as candidate biomarkers. Using next-generation sequencing data, we managed to achieve the maximum (100%) classification accuracy, sensitivity and specificity with the Gradient Boosting and the Random Forest classifiers, compared to the 83% of the DNA microarray data. Clinical Relevance- When biomarkers derived from one study are applied to the data of another, in many cases the results may diverge significantly. Here we establish that in cross-profiling meta-analysis approaches based on differential expression analysis, next-generation sequencing data provide more accurate results than microarray experiments in the classification of Adult-Onset Still's Disease patients.

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.

Being diagnosed with breast cancer (BC) can be a traumatic experience for patients who may experience symptoms of depression. In order to facilitate the prevention of such symptoms, it is crucial to understand how and why depressive symptoms emerge and evolve for each individual, from diagnosis through treatment and recovery. In the present work, data from a multicentric study of 706 BC patients followed for 12 months are analyzed. First, a trajectory-based unsupervised clustering based on K-means is performed to capture the dynamic patterns of change in patients' depressive symptoms after BC diagnosis and to identify distinct trajectory clusters. Then a supervised learning approach was employed to build a classification model of depression progression and to identify potential predictors. Patients were clustered into 4 groups: stable low, stable high, improving, and worsening depressive symptoms. In a nested cross-validation pipeline, the performance of the Support Vector Machine model for discriminating between “good” and “poor” progression was 0.78±0.05 in terms of AUC. Several psychological variables emerged as highly predictive of the evolution of depressive symptoms with the most important ones being negative affectivity and anxious preoccupation. Clinical Relevance—The findings of the present study may help clinicians tailor individualized psychological interventions aiming at alleviating the burden of these symptoms in women with breast cancer and improving their overall well-being.

Mental health impairment after breast cancer diagnosis may persist for months or years. The present work leverages on novel machine learning techniques to identify distinct trajectories of mental health progression in an 18-month period following BC diagnosis and develop an explainable predictive model of mental health progression using a large list of clinical, sociodemographic and psychological variables. The modelling process was conducted in two phases. The first modeling step included an unsupervised clustering to define the number of trajectory clusters, by means of a longitudinal K-means algorithm. In the second modeling step an explainable ML framework was developed, on the basis of Extreme Gradient Boosting (XGBoost) model and SHAP values, in order to identify the most prominent variables that can discriminate between good and unfavorable mental health progression and to explain how they contribute to model's decisions. The trajectory analysis revealed 5 distinct trajectory groups with the majority of patients following stable good (56%) or improving (21%) trends, while for others mental health levels either deteriorated (12%) or remained at unsatisfactory levels (11%). The model's performance for classifying patient mental health into good and unfavorable progression achieved an AUC of $0.82\pm 0.04$ . The top ranking predictors driving the classification task were the higher number of sick leave days, aggressive cancer type (triple-negative) and higher levels of negative affect, anxious preoccupation, helplessness, arm and breast symptoms, as well as lower values of optimism, social and emotional support and lower age.

BACKGROUND:Although several studies have been launched towards the prediction of risk factors for mortality and admission in the intensive care unit (ICU) in COVID-19, none of them focuses on the development of explainable AI models to define an ICU scoring index using dynamically associated biological markers.METHODS:We propose a multimodal approach which combines explainable AI models with dynamic modeling methods to shed light into the clinical features of COVID-19. Dynamic Bayesian networks were used to seek associations among cytokines across four time intervals after hospitalization. Explainable gradient boosting trees were trained to predict the risk for ICU admission and mortality towards the development of an ICU scoring index.RESULTS:Our results highlight LDH, IL-6, IL-8, Cr, number of monocytes, lymphocyte count, TNF as risk predictors for ICU admission and survival along with LDH, age, CRP, Cr, WBC, lymphocyte count for mortality in the ICU, with prediction accuracy 0.79 and 0.81, respectively. These risk factors were combined with dynamically associated biological markers to develop an ICU scoring index with accuracy 0.9.CONCLUSIONS:to our knowledge, this is the first multimodal and explainable AI model which quantifies the risk of intensive care with accuracy up to 0.9 across multiple timepoints.

The coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is consistently causing profound wounds in the global healthcare system due to its increased transmissibility. Currently, there is an urgent unmet need to identify the underlying dynamic associations among COVID-19 patients and distinguish patient subgroups with common clinical profiles towards the development of robust classifiers for ICU admission and mortality. To address this need, we propose a four step pipeline which: (i) enhances the quality of multiple timeseries clinical data through an automated data curation workflow, (ii) deploys Dynamic Bayesian Networks (DBNs) for the detection of features with increased connectivity based on dynamic association analysis across multiple points, (iii) utilizes Self Organizing Maps (SOMs) and trajectory analysis for the early identification of COVID-19 patients with common clinical profiles, and (iv) trains robust multiple additive regression trees (MART) for ICU admission and mortality classification based on the extracted homogeneous clusters, to identify risk factors and biomarkers for disease progression. The contribution of the extracted clusters and the dynamically associated clinical data improved the classification performance for ICU admission to sensitivity 0.83 and specificity 0.83, and for mortality to sensitivity 0.74 and specificity 0.76. Additional information was included to enhance the performance of the classifiers yielding an increase by 4% in sensitivity and specificity for mortality. According to the risk factor analysis, the number of lymphocytes, SatO2, PO2/FiO2, and O2 supply type were highlighted as risk factors for ICU admission and the percentage of neutrophils and lymphocytes, PO2/FiO2, LDH, and ALP for mortality, among others. To our knowledge, this is the first study that combines dynamic modeling with clustering analysis to identify homogeneous groups of COVID-19 patients towards the development of robust classifiers for ICU admission and mortality.

Breast cancer diagnosis has been associated with poor mental health, with significant impairment of quality of life. In order to ensure support for successful adaptation to this illness, it is of paramount importance to identify the most prominent factors affecting well-being that allow for accurate prediction of mental health status across time. Here we exploit a rich set of clinical, psychological, socio-demographic and lifestyle data from a large multicentre study of patients recently diagnosed with breast cancer, in order to classify patients based on their mental health status and further identify potential predictors of such status. For this purpose, a supervised learning pipeline using cross-sectional data was implemented for the formulation of a classification scheme of mental health status 6 months after diagnosis. Model performance in terms of AUC ranged from 0.81± 0.04 to 0.90± 0.03. Several psychological variables, including initial levels of anxiety and depression, emerged as highly predictive of short-term mental health status of women diagnosed with breast cancer.

Artificial Intelligence (AI) has recently altered the landscape of cancer research and medical oncology using traditional Machine Learning (ML) algorithms and cutting-edge Deep Learning (DL) architectures. In this review article we focus on the ML aspect of AI applications in cancer research and present the most indicative studies with respect to the ML algorithms and data used. The PubMed and dblp databases were considered to obtain the most relevant research works of the last five years. Based on a comparison of the proposed studies and their research clinical outcomes concerning the medical ML application in cancer research, three main clinical scenarios were identified. We give an overview of the well-known DL and Reinforcement Learning (RL) methodologies, as well as their application in clinical practice, and we briefly discuss Systems Biology in cancer research. We also provide a thorough examination of the clinical scenarios with respect to disease diagnosis, patient classification and cancer prognosis and survival. The most relevant studies identified in the preceding year are presented along with their primary findings. Furthermore, we examine the effective implementation and the main points that need to be addressed in the direction of robustness, explainability and transparency of predictive models. Finally, we summarize the most recent advances in the field of AI/ML applications in cancer research and medical oncology, as well as some of the challenges and open issues that need to be addressed before data-driven models can be implemented in healthcare systems to assist physicians in their daily practice. (C) 2021 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Displaying resilience following a diagnosis of breast cancer is crucial for successful adaptation to illness, wellbeing, and health outcomes. Several theoretical and computational models have been proposed toward understanding the complex process of illness adaptation, involving a large variety of patient sociodemographic, lifestyle, medical, and psychological characteristics. To date, conventional multivariate statistical methods have been used extensively to model resilience. In the present work we describe a computational pipeline designed to identify the most prominent predictors of mental health outcomes following breast cancer diagnosis. A machine learning framework was developed and tested on the baseline data (recorded immediately post diagnosis) from an ongoing prospective, multinational study. This fully annotated dataset includes socio-demographic, lifestyle, medical and self-reported psychological characteristics of women recently diagnosed with breast cancer (N = 609). Nine different feature selection and cross-validated classification schemes were compared on their performance in classifying patients into low vs high depression symptom severity. Best-performing approaches involved a meta-estimator combined with a Support Vector Machines (SVMs) classification algorithm, exhibiting balanced accuracy of 0.825, and a fair balance between sensitivity (90%) and specificity (74%). These models consistently identified a set of psychological traits (optimism, perceived ability to cope with trauma, resilience as trait, ability to comprehend the illness), and subjective perceptions of personal functionality (physical, social, cognitive) as key factors accounting for concurrent depression symptoms. A comprehensive supervised learning pipeline is proposed for the identification of predictors of depression symptoms which could severely impede adaptation to illness.

Artificial Intelligence (AI) has recently altered the landscape of cancer research and medical oncology using traditional Machine Learning (ML) algorithms and cutting-edge Deep Learning (DL) architectures. In this review article we focus on the ML aspect of AI applications in cancer research and present the most indicative studies with respect to the ML algorithms and data used. The PubMed and dblp databases were considered to obtain the most relevant research works of the last five years. Based on a comparison of the proposed studies and their research clinical outcomes concerning the medical ML application in cancer research, three main clinical scenarios were identified. We give an overview of the well-known DL and Reinforcement Learning (RL) methodologies, as well as their application in clinical practice, and we briefly discuss Systems Biology in cancer research. We also provide a thorough examination of the clinical scenarios with respect to disease diagnosis, patient classification and cancer prognosis and survival. The most relevant studies identified in the preceding year are presented along with their primary findings. Furthermore, we examine the effective implementation and the main points that need to be addressed in the direction of robustness, explainability and transparency of predictive models. Finally, we summarize the most recent advances in the field of AI/ML applications in cancer research and medical oncology, as well as some of the challenges and open issues that need to be addressed before data-driven models can be implemented in healthcare systems to assist physicians in their daily practice.

In this study, we propose a dynamic Bayesian network (DBN)-based approach to behavioral modelling of community dwelling older adults at risk for falls during the daily sessions of a hologram-enabled vestibular rehabilitation therapy programme. The component of human behavior being modelled is the level of frustration experienced by the user at each exercise, as it is assessed by the NASA Task Load Index. Herein, we present the topology of the DBN and test its inference performance on real-patient data.

In the current study, a model-based system for predicting resilience in silico, as part of personalizing precision medicine, to better understand the needs for improved therapeutic protocols of each patient is proposed. The computational environment, which is currently under implementation within the BOUNCE EU project (“Predicting Effective Adaptation to Breast Cancer to Help Women to BOUNCE Back”), will help clinicians and care-givers to predict the patient’s resilience trajectory throughout cancer continuum. The overall proposed system architecture contributes to clinical outcomes and patient well-being by taking into consideration biological, social, environmental, occupational and lifestyle factors for resilience prediction in women with breast cancer. Supervised, semisupervised and unsupervised learning algorithms are adopted with the inherent ability to represent the time-varying behaviour of the underlying system which allows for a better representation of spatiotemporal input-output dependencies. The in silico resilience prediction approach accommodates numerous diverse factors contributing to multi-scale models of cancer, in order to better specify clinically useful aspects of recovery, treatment and intervention.

Lymphoma development constitutes one of the most serious clinico-pathological manifestations of patients with Sjögren's Syndrome (SS). Over the last decades the risk for lymphomagenesis in SS patients has been studied aiming to identify novel biomarkers and risk factors predicting lymphoma development in this patient population. Objective: The current study aims to explore whether genetic susceptibility profiles of SS patients along with known clinical, serological and histological risk factors enhance the accuracy of predicting lymphoma development in this patient population. Methods: The potential predicting role of both genetic variants, clinical and laboratory risk factors were investigated through a Machine Learning-based (ML) framework which encapsulates ensemble classifiers. Results: Ensemble methods empower the classification accuracy with approaches which are sensitive to minor perturbations in the training phase. The evaluation of the proposed methodology based on a 10-fold stratified cross validation procedure yielded considerable results in terms of balanced accuracy (GB: 0.7780 ± 0.1514, RF Gini: 0.7626 ± 0.1787, RF Entropy: 0.7590 ± 0.1837). Conclusions: The initial clinical, serological, histological and genetic findings at an early diagnosis have been exploited in an attempt to establish predictive tools in clinical practice and further enhance our understanding towards lymphoma development in SS.