A Two-Step Feature Selection Radiomic Approach to Predict Molecular Outcomes in Breast Cancer.

Breast Cancer (BC) is the most common cancer among women worldwide and is characterized by intra- and inter-tumor heterogeneity that strongly contributes towards its poor prognosis. The Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67 antigen are the most examined markers depicting BC heterogeneity and have been shown to have a strong impact on BC prognosis. Radiomics can noninvasively predict BC heterogeneity through the quantitative evaluation of medical images, such as Magnetic Resonance Imaging (MRI), which has become increasingly important in the detection and characterization of BC. However, the lack of comprehensive BC datasets in terms of molecular outcomes and MRI modalities, and the absence of a general methodology to build and compare feature selection approaches and predictive models, limit the routine use of radiomics in the BC clinical practice. In this work, a new radiomic approach based on a two-step feature selection process was proposed to build predictors for ER, PR, HER2, and Ki67 markers. An in-house dataset was used, containing 92 multiparametric MRIs of patients with histologically proven BC and all four relevant biomarkers available. Thousands of radiomic features were extracted from post-contrast and subtracted Dynamic Contrast-Enanched (DCE) MRI images, Apparent Diffusion Coefficient (ADC) maps, and T2-weighted (T2) images. The two-step feature selection approach was used to identify significant radiomic features properly and then to build the final prediction models. They showed remarkable results in terms of F1-score for all the biomarkers: 84%, 63%, 90%, and 72% for ER, HER2, Ki67, and PR, respectively. When possible, the models were validated on the TCGA/TCIA Breast Cancer dataset, returning promising results (F1-score = 88% for the ER+/ER- classification task). The developed approach efficiently characterized BC heterogeneity according to the examined molecular biomarkers.

Labor Analgesia: A Systematic Review and Meta-Analysis of Non-Pharmacological Complementary and Alternative Approaches to Pain during First Stage of Labor.

the aim of the study was to conduct a meta-analysis to evaluate the efficacy of non-invasive and non-pharmacological techniques on labor first-stage pain intensity. Literature databases were searched from inception to May 2021, and research was expanded through the screening of previous systematic reviews. Inclusion criteria were: (1) population: women in first stage of labor; (2) intervention: non-pharmacological, non-invasive, or minimally invasive intrapartum analgesic techniques alternative and/or complementary to pharmacological analgesia; (3) comparison: routine intrapartum care or placebos; (4) outcomes: subjective pain intensity; and (5) study design: randomized controlled trial. Risk of bias of included studies was investigated, data analysis was performed using R version 3.5.1. Effect size was calculated as difference between the control and experimental groups at posttreatment in terms of mean pain score. A total of 63 studies were included, for a total of 6146 patients (3468 in the experimental groups and 2678 in the control groups). Techniques included were massage (n = 11), birth balls (n = 5) mind-body interventions (n = 8), heat application (n = 12), music therapy (n = 9), dance therapy (n = 2), acupressure (n = 16), and transcutaneous electrical nerve stimulation (TENS) (n = 8). The present review found significant evidence in support of the use of complementary and alternative medicine for labor analgesia, and different methods showed different impact. However, more high-quality trials are needed.

A Two-Step Approach for Classification in Alzheimer's Disease.

The classification of images is of high importance in medicine. In this sense, Deep learning methodologies show excellent performance with regard to accuracy. The drawback of these methodologies is the fact that they are black boxes, so no explanation is given to users on the reasons underlying their choices. In the medical domain, this lack of transparency and information, typical of black box models, brings practitioners to raise concerns, and the result is a resistance to the use of deep learning tools. In order to overcome this problem, a different Machine Learning approach to image classification is used here that is based on interpretability concepts thanks to the use of an evolutionary algorithm. It relies on the application of two steps in succession. The first receives a set of images in the inut and performs image filtering on them so that a numerical data set is generated. The second is a classifier, the kernel of which is an evolutionary algorithm. This latter, at the same time, classifies and automatically extracts explicit knowledge as a set of IF-THEN rules. This method is investigated with respect to a data set of MRI brain imagery referring to Alzheimer's disease. Namely, a two-class data set (non-demented and moderate demented) and a three-class data set (non-demented, mild demented, and moderate demented) are extracted. The methodology shows good results in terms of accuracy (100% for the best run over the two-class problem and 91.49% for the best run over the three-class one), F_score (1.0000 and 0.9149, respectively), and Matthews Correlation Coefficient (1.0000 and 0.8763, respectively). To ascertain the quality of these results, they are contrasted against those from a wide set of well-known classifiers. The outcome of this comparison is that, in both problems, the methodology achieves the best results in terms of accuracy and F_score, whereas, for the Matthews Correlation Coefficient, it has the best result over the two-class problem and the second over the three-class one.

Application of Reinforcement Learning and Deep Learning in Multiple-Input and Multiple-Output (MIMO) Systems.

The current wireless communication infrastructure has to face exponential development in mobile traffic size, which demands high data rate, reliability, and low latency. MIMO systems and their variants (i.e., Multi-User MIMO and Massive MIMO) are the most promising 5G wireless communication systems technology due to their high system throughput and data rate. However, the most significant challenges in MIMO communication are substantial problems in exploiting the multiple-antenna and computational complexity. The recent success of RL and DL introduces novel and powerful tools that mitigate issues in MIMO communication systems. This article focuses on RL and DL techniques for MIMO systems by presenting a comprehensive review on the integration between the two areas. We first briefly provide the necessary background to RL, DL, and MIMO. Second, potential RL and DL applications for different MIMO issues, such as detection, classification, and compression; channel estimation; positioning, sensing, and localization; CSI acquisition and feedback, security, and robustness; mmWave communication and resource allocation, are presented.

Virtual reality and music therapy as distraction interventions to alleviate anxiety and improve mood states in breast cancer patients during chemotherapy.

Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy-related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue.

Crosslingual named entity recognition for clinical de-identification applied to a COVID-19 Italian data set.

The COrona VIrus Disease 19 (COVID-19) pandemic required the work of all global experts to tackle it. Despite the abundance of new studies, privacy laws prevent their dissemination for medical investigations: through clinical de-identification, the Protected Health Information (PHI) contained therein can be anonymized so that medical records can be shared and published. The automation of clinical de-identification through deep learning techniques has proven to be less effective for languages other than English due to the scarcity of data sets. Hence a new Italian de-identification data set has been created from the COVID-19 clinical records made available by the Italian Society of Radiology (SIRM). Therefore, two multi-lingual deep learning systems have been developed for this low-resource language scenario: the objective is to investigate their ability to transfer knowledge between different languages while maintaining the necessary features to correctly perform the Named Entity Recognition task for de-identification. The systems were trained using four different strategies, using both the English Informatics for Integrating Biology & the Bedside (i2b2) 2014 and the new Italian SIRM COVID-19 data sets, then evaluated on the latter. These approaches have demonstrated the effectiveness of cross-lingual transfer learning to de-identify medical records written in a low resource language such as Italian, using one with high resources such as English.

A Wellness Mobile Application for Smart Health: Pilot Study Design and Results.

Wellness is one of the main factors crucial in the avoidance of illness or disease. Experience has shown that healthy lifestyle programs are an important strategy to prevent the major shared risk factors for many diseases including cardiovascular diseases, strokes, diabetes, obesity, and hypertension. Within the ambit of the Smart Health 2.0 project, a Wellness App has been developed which has the aim of providing people with something similar to a personal trainer. This Wellness App is able to gather information about the subject, to classify her/him by evaluating some of her/his specific characteristics (physical parameters and lifestyle) and to make personal recommendations to enhance her/his well-being. The application can also give feedback on the effectiveness of the specified characteristics by monitoring their evolution over time, and can provide a positive incentive to stimulate the subject to achieve her/his wellness goals. In this paper, we present a pilot study conducted in Calabria, a region of Italy, aimed at an evaluation of the validity, usability, and navigability of the app, and of people's level of satisfaction with it. The preliminary results show an average score of 77.16 for usability and of 76.87 for navigability, with an improvement of the Wellness Index with a significance average of 95% and of the Mediterranean Adequacy Index with a significance average of as high as 99%.

Blood Pressure Drop Prediction by using HRV Measurements in Orthostatic Hypotension.

Orthostatic Hypotension is defined as a reduction of systolic and diastolic blood pressure within 3 minutes of standing, and may cause dizziness and loss of balance. Orthostatic Hypotension has been considered an important risk factor for falls since 1960. This paper presents a model to predict the systolic blood pressure drop due to orthostatic hypotension, relying on heart rate variability measurements extracted from 5 minute ECGs recorded before standing. This model was developed and validated with the leave-one-out cross-validation technique involving 10 healthy subjects, and finally tested with an additional 5 healthy subjects, whose data were not used during the training and cross-validation process. The results show that the model predicts correctly the systolic blood pressure drop in 80 % of all experiments, with an error rate below the measurement error of a sphygmomanometer digital device.

Monitoring Obstructive Sleep Apnea by means of a real-time mobile system based on the automatic extraction of sets of rules through Differential Evolution.

Real-time Obstructive Sleep Apnea (OSA) episode detection and monitoring are important for society in terms of an improvement in the health of the general population and of a reduction in mortality and healthcare costs. Currently, to diagnose OSA patients undergo PolySomnoGraphy (PSG), a complicated and invasive test to be performed in a specialized center involving many sensors and wires. Accordingly, each patient is required to stay in the same position throughout the duration of one night, thus restricting their movements. This paper proposes an easy, cheap, and portable approach for the monitoring of patients with OSA, which collects single-channel ElectroCardioGram (ECG) data only. It is easy to perform from the patient's point of view because only one wearable sensor is required, so the patient is not restricted to keeping the same position all night long, and the detection and monitoring can be carried out in any place through the use of a mobile device. Our approach is based on the automatic extraction, from a database containing information about the monitored patient, of explicit knowledge in the form of a set of IF…THEN rules containing typical parameters derived from Heart Rate Variability (HRV) analysis. The extraction is carried out off-line by means of a Differential Evolution algorithm. This set of rules can then be exploited in the real-time mobile monitoring system developed at our Laboratory: the ECG data is gathered by a wearable sensor and sent to a mobile device, where it is processed in real time. Subsequently, HRV-related parameters are computed from this data, and, if their values activate some of the rules describing the occurrence of OSA, an alarm is automatically produced. This approach has been tested on a well-known literature database of OSA patients. The numerical results show its effectiveness in terms of accuracy, sensitivity, and specificity, and the achieved sets of rules evidence the user-friendliness of the approach. Furthermore, the method is compared against other well known classifiers, and its discrimination ability is shown to be higher.

Promoting fairness in activity recognition algorithms for patient's monitoring and evaluation systems in healthcare.

Researchers face the challenge of defining subject selection criteria when training algorithms for human activity recognition tasks. The ongoing uncertainty revolves around which characteristics should be considered to ensure algorithmic robustness across diverse populations. This study aims to address this challenge by conducting an analysis of heterogeneity in the training data to assess the impact of physical characteristics and soft-biometric attributes on activity recognition performance. The performance of various state-of-the-art deep neural network architectures (tCNN, hybrid-LSTM, Transformer model) processing time-series data using the IntelliRehab (IRDS) dataset was evaluated. By intentionally introducing bias into the training data based on human characteristics, the objective is to identify the characteristics that influence algorithms in motion analysis. Experimental findings reveal that the CNN-LSTM model achieved the highest accuracy, reaching 88%. Moreover, models trained on heterogeneous distributions of disability attributes exhibited notably higher accuracy, reaching 51%, compared to those not considering such factors, which scored an average of 33%. These evaluations underscore the significant influence of subjects' characteristics on activity recognition performance, providing valuable insights into the algorithm's robustness across diverse populations. This study represents a significant step forward in promoting fairness and trustworthiness in artificial intelligence by quantifying representation bias in multi-channel time-series activity recognition data within the healthcare domain.

Ethical and regulatory challenges of AI technologies in healthcare: A narrative review.

Over the past decade, there has been a notable surge in AI-driven research, specifically geared toward enhancing crucial clinical processes and outcomes. The potential of AI-powered decision support systems to streamline clinical workflows, assist in diagnostics, and enable personalized treatment is increasingly evident. Nevertheless, the introduction of these cutting-edge solutions poses substantial challenges in clinical and care environments, necessitating a thorough exploration of ethical, legal, and regulatory considerations. A robust governance framework is imperative to foster the acceptance and successful implementation of AI in healthcare. This article delves deep into the critical ethical and regulatory concerns entangled with the deployment of AI systems in clinical practice. It not only provides a comprehensive overview of the role of AI technologies but also offers an insightful perspective on the ethical and regulatory challenges, making a pioneering contribution to the field. This research aims to address the current challenges in digital healthcare by presenting valuable recommendations for all stakeholders eager to advance the development and implementation of innovative AI systems.

Synchronization of a Virtual Reality Scenario to Uterine Contractions for Labor Pain Management: Development Study and Randomized Controlled Trial.

Background: Labor is described as one of the most painful events women can experience through their lives, and labor pain shows unique features and rhythmic fluctuations. Purpose: The present study aims to evaluate virtual reality (VR) analgesic interventions for active labor with biofeedback-based VR technologies synchronized to uterine activity. Materials and Methods: We developed a VR system modeled on uterine contractions by connecting it to cardiotocographic equipment. We conducted a randomized controlled trial on a sample of 74 cases and 80 controls during active labor. Results: Results of the study showed a significant reduction of pain scores compared with both preintervention scores and to control group scores; a significant reduction of anxiety levels both compared with preintervention assessment and to control group and significant reduction in fear of labor experience compared with controls. Conclusion: VR may be considered as an effective nonpharmacological analgesic technique for the treatment of pain and anxiety and fear of childbirth experience during labor. The developed system could improve personalization of care, modulating the multisensory stimulation tailored to labor progression. Further studies are needed to compare the synchronized VR system to uterine activity and unsynchronized VR interventions.

An extensible six-step methodology to automatically generate fuzzy DSSs for diagnostic applications.

BACKGROUND: The diagnosis of many diseases can be often formulated as a decision problem; uncertainty affects these problems so that many computerized Diagnostic Decision Support Systems (in the following, DDSSs) have been developed to aid the physician in interpreting clinical data and thus to improve the quality of the whole process. Fuzzy logic, a well established attempt at the formalization and mechanization of human capabilities in reasoning and deciding with noisy information, can be profitably used. Recently, we informally proposed a general methodology to automatically build DDSSs on the top of fuzzy knowledge extracted from data. METHODS: We carefully refine and formalize our methodology that includes six stages, where the first three stages work with crisp rules, whereas the last three ones are employed on fuzzy models. Its strength relies on its generality and modularity since it supports the integration of alternative techniques in each of its stages. RESULTS: The methodology is designed and implemented in the form of a modular and portable software architecture according to a component-based approach. The architecture is deeply described and a summary inspection of the main components in terms of UML diagrams is outlined as well. A first implementation of the architecture has been then realized in Java following the object-oriented paradigm and used to instantiate a DDSS example aimed at accurately diagnosing breast masses as a proof of concept. CONCLUSIONS: The results prove the feasibility of the whole methodology implemented in terms of the architecture proposed.

Generating a novel synthetic dataset for rehabilitation exercises using pose-guided conditioned diffusion models: A quantitative and qualitative evaluation.

Machine learning has emerged as a promising approach to enhance rehabilitation therapy monitoring and evaluation, providing personalized insights. However, the scarcity of data remains a significant challenge in developing robust machine learning models for rehabilitation. This paper introduces a novel synthetic dataset for rehabilitation exercises, leveraging pose-guided person image generation using conditioned diffusion models. By processing a pre-labeled dataset of class movements for 6 rehabilitation exercises, the described method generates realistic human movement images of elderly subjects engaging in home-based exercises. A total of 22,352 images were generated to accurately capture the spatial consistency of human joint relationships for predefined exercise movements. This novel dataset significantly amplified variability in the physical and demographic attributes of the main subject and the background environment. Quantitative metrics used for image assessment revealed highly favorable results. The generated images successfully maintained intra-class and inter-class consistency in motion data, producing outstanding outcomes with distance correlation values exceeding the 0.90. This innovative approach empowers researchers to enhance the value of existing limited datasets by generating high-fidelity synthetic images that precisely augment the anthropometric and biomechanical attributes of individuals engaged in rehabilitation exercises.

Best practices for portfolio optimization by quantum computing, experimented on real quantum devices.

In finance, portfolio optimization aims at finding optimal investments maximizing a trade-off between return and risks, given some constraints. Classical formulations of this quadratic optimization problem have exact or heuristic solutions, but the complexity scales up as the market dimension increases. Recently, researchers are evaluating the possibility of facing the complexity scaling issue by employing quantum computing. In this paper, the problem is solved using the Variational Quantum Eigensolver (VQE), which in principle is very efficient. The main outcome of this work consists of the definition of the best hyperparameters to set, in order to perform Portfolio Optimization by VQE on real quantum computers. In particular, a quite general formulation of the constrained quadratic problem is considered, which is translated into Quadratic Unconstrained Binary Optimization by the binary encoding of variables and by including constraints in the objective function. This is converted into a set of quantum operators (Ising Hamiltonian), whose minimum eigenvalue is found by VQE and corresponds to the optimal solution. In this work, different hyperparameters of the procedure are analyzed, including different ansatzes and optimization methods by means of experiments on both simulators and real quantum computers. Experiments show that there is a strong dependence of solutions quality on the sufficiently sized quantum computer and correct hyperparameters, and with the best choices, the quantum algorithm run on real quantum devices reaches solutions very close to the exact one, with a strong convergence rate towards the classical solution, even without error-mitigation techniques. Moreover, results obtained on different real quantum devices, for a small-sized example, show the relation between the quality of the solution and the dimension of the quantum processor. Evidences allow concluding which are the best ways to solve real Portfolio Optimization problems by VQE on quantum devices, and confirm the possibility to solve them with higher efficiency, with respect to existing methods, as soon as the size of quantum hardware will be sufficiently high.

The role of sense of presence in expressing cognitive abilities in a virtual reality task: an initial validation study.

There is a raised interest in literature to use Virtual Reality (VR) technology as an assessment tool for cognitive domains. One of the essential advantages of transforming tests in an immersive virtual environment is the possibility of automatically calculating the test's score, a time-consuming process under natural conditions. Although the characteristics of VR can deliver different degrees of immersion in a virtual environment, the sense of presence could jeopardize the evolution of these practices. The sense of presence results from a complex interaction between human, contextual factors, and the VR environment. The present study has two aims: firstly, it contributes to the validation of a virtual version of the naturalistic action test (i.e., virtual reality action test); second, it aims to evaluate the role of sense of presence as a critical booster of the expression of cognitive abilities during virtual reality tasks. The study relies on healthy adults tested in virtual and real conditions in a cross-over research design. The study's results support the validity of the virtual reality action test. Furthermore, two structural equation models are tested to comprehend the role of sense of presence as a moderator in the relationship between cognitive abilities and virtual task performance.

Classification of Covid-19 chest X-ray images by means of an interpretable evolutionary rule-based approach.

In medical practice, all decisions, as for example the diagnosis based on the classification of images, must be made reliably and effectively. The possibility of having automatic tools helping doctors in performing these important decisions is highly welcome. Artificial Intelligence techniques, and in particular Deep Learning methods, have proven very effective on these tasks, with excellent performance in terms of classification accuracy. The problem with such methods is that they represent black boxes, so they do not provide users with an explanation of the reasons for their decisions. Confidence from medical experts in clinical decisions can increase if they receive from Artificial Intelligence tools interpretable output under the form of, e.g., explanations in natural language or visualized information. This way, the system outcome can be critically assessed by them, and they can evaluate the trustworthiness of the results. In this paper, we propose a new general-purpose method that relies on interpretability ideas. The approach is based on two successive steps, the former being a filtering scheme typically used in Content-Based Image Retrieval, whereas the latter is an evolutionary algorithm able to classify and, at the same time, automatically extract explicit knowledge under the form of a set of IF-THEN rules. This approach is tested on a set of chest X-ray images aiming at assessing the presence of COVID-19.

A conversational agent for querying Italian Patient Information Leaflets and improving health literacy.

In the last years, the rise of digital technologies has enormously augmented the possibility for people to access health information and consult online versions of Patient Information Leaflets (PILs), enabling them to improve their knowledge about medication and adherence to therapies. However, health information may often be difficult to consult and comprehend due to an excessively lengthy and undersized text, coupled with the presence of many incomprehensible medical terms. To face these issues, this paper proposes a conversational agent as a valuable solution to simplify health information retrieval and improve health literacy in Italian by codifying PILs and making them query-able in natural language. In particular, the system has been devised to: i) comprehend natural language questions on medicines of interest; ii) proactively ask the user or automatically infer from the dialog state all the missing information necessary to generate an answer; iii) extract the answer from a structured knowledge base built from PILs of registered drugs. An experimental study has been carried out to evaluate both the performance and usability of the proposed system. Results showed an adequate ability of the system to handle most of the dialogues started by participants correctly, good users satisfaction, and, thus, proved its feasibility and usefulness.

Virtual Reality Rehabilitation Systems for Cancer Survivors: A Narrative Review of the Literature.

Rehabilitation plays a crucial role in cancer care, as the functioning of cancer survivors is frequently compromised by impairments that can result from the disease itself but also from the long-term sequelae of the treatment. Nevertheless, the current literature shows that only a minority of patients receive physical and/or cognitive rehabilitation. This lack of rehabilitative care is a consequence of many factors, one of which includes the transportation issues linked to disability that limit the patient's access to rehabilitation facilities. The recent COVID-19 pandemic has further shown the benefits of improving telemedicine and home-based rehabilitative interventions to facilitate the delivery of rehabilitation programs when attendance at healthcare facilities is an obstacle. In recent years, researchers have been investigating the benefits of the application of virtual reality to rehabilitation. Virtual reality is shown to improve adherence and training intensity through gamification, allow the replication of real-life scenarios, and stimulate patients in a multimodal manner. In our present work, we offer an overview of the present literature on virtual reality-implemented cancer rehabilitation. The existence of wide margins for technological development allows us to expect further improvements, but more randomized controlled trials are needed to confirm the hypothesis that VRR may improve adherence rates and facilitate telerehabilitation.

BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images.

Breast cancer is the most commonly diagnosed cancer and registers the highest number of deaths for women. Advances in diagnostic activities combined with large-scale screening policies have significantly lowered the mortality rates for breast cancer patients. However, the manual inspection of tissue slides by pathologists is cumbersome, time-consuming and is subject to significant inter- and intra-observer variability. Recently, the advent of whole-slide scanning systems has empowered the rapid digitization of pathology slides and enabled the development of Artificial Intelligence (AI)-assisted digital workflows. However, AI techniques, especially Deep Learning, require a large amount of high-quality annotated data to learn from. Constructing such task-specific datasets poses several challenges, such as data-acquisition level constraints, time-consuming and expensive annotations and anonymization of patient information. In this paper, we introduce the BReAst Carcinoma Subtyping (BRACS) dataset, a large cohort of annotated Hematoxylin and Eosin (H&E)-stained images to advance AI development in the automatic characterization of breast lesions. BRACS contains 547 Whole-Slide Images (WSIs) and 4539 Regions Of Interest (ROIs) extracted from the WSIs. Each WSI and respective ROIs are annotated by the consensus of three board-certified pathologists into different lesion categories. Specifically, BRACS includes three lesion types, i.e., benign, malignant and atypical, which are further subtyped into seven categories. It is, to the best of our knowledge, the largest annotated dataset for breast cancer subtyping both at WSI and ROI levels. Furthermore, by including the understudied atypical lesions, BRACS offers a unique opportunity for leveraging AI to better understand their characteristics. We encourage AI practitioners to develop and evaluate novel algorithms on the BRACS dataset to further breast cancer diagnosis and patient care. Database URL: https://www.bracs.icar.cnr.it/.