Algor-ethics: charting the ethical path for AI in critical care.

The integration of Clinical Decision Support Systems (CDSS) based on artificial intelligence (AI) in healthcare is groundbreaking evolution with enormous potential, but its development and ethical implementation, presents unique challenges, particularly in critical care, where physicians often deal with life-threating conditions requiring rapid actions and patients unable to participate in the decisional process. Moreover, development of AI-based CDSS is complex and should address different sources of bias, including data acquisition, health disparities, domain shifts during clinical use, and cognitive biases in decision-making. In this scenario algor-ethics is mandatory and emphasizes the integration of 'Human-in-the-Loop' and 'Algorithmic Stewardship' principles, and the benefits of advanced data engineering. The establishment of Clinical AI Departments (CAID) is necessary to lead AI innovation in healthcare, ensuring ethical integrity and human-centered development in this rapidly evolving field.

Learning Ordinal-Hierarchical Constraints for Deep Learning Classifiers.

Real-world classification problems may disclose different hierarchical levels where the categories are displayed in an ordinal structure. However, no specific deep learning (DL) models simultaneously learn hierarchical and ordinal constraints while improving generalization performance. To fill this gap, we propose the introduction of two novel ordinal-hierarchical DL methodologies, namely, the hierarchical cumulative link model (HCLM) and hierarchical-ordinal binary decomposition (HOBD), which are able to model the ordinal structure within different hierarchical levels of the labels. In particular, we decompose the hierarchical-ordinal problem into local and global graph paths that may encode an ordinal constraint for each hierarchical level. Thus, we frame this problem as simultaneously minimizing global and local losses. Furthermore, the ordinal constraints are set by two approaches ordinal binary decomposition (OBD) and cumulative link model (CLM) within each global and local function. The effectiveness of the proposed approach is measured on four real-use case datasets concerning industrial, biomedical, computer vision, and financial domains. The extracted results demonstrate a statistically significant improvement to state-of-the-art nominal, ordinal, and hierarchical approaches.

A novel missing data imputation approach based on clinical conditional Generative Adversarial Networks applied to EHR datasets.

The missing data mechanism is a relevant problem in Machine Learning (ML) and biomedical informatics communities. Real-world Electronic Health Record (EHR) datasets comprise several missing values, thus revealing a high level of spatiotemporal sparsity in the predictors' matrix. Several approaches in the state-of-the-art tried to deal with this problem by proposing different data imputation strategies that (i) are often unrelated to the ML model, (ii) are not conceived for EHR data where laboratory exams are not prescribed uniformly over time and percentage of missing values is high (iii) exploit only univariate and linear information on the observed features. Our paper proposes a data imputation strategy based on a clinical conditional Generative Adversarial Network (ccGAN) capable of imputing missing values by exploiting non-linear and multivariate information across patients. Unlike other GAN data imputation-based approaches, our method deals explicitly with the high level of missingness of routine EHR data by conditioning the imputing strategy to the observable values and those fully-annotated. We demonstrated the statistical significance of the ccGAN to other state-of-the-art approaches in terms of imputation (around 19.79% of gain to the best competitor) and predictive performance (up to 1.60% of gain to the best competitor) on a real multi-diabetic centers dataset. We also demonstrated its robustness across different missingness rates (up to 1.61% of gain to the best competitor in the highest missingness rates condition) on an additional benchmark EHR dataset.

Visuo-motor interference is modulated by task interactivity: A kinematic study.

Extensive evidence shows that action observation can influence action execution, a phenomenon often referred to as visuo-motor interference. Little is known about whether this effect can be modulated by the type of interaction agents are involved in, as different studies show conflicting results. In the present study, we aimed at shedding light on this question by recording and analyzing the kinematic unfolding of reach-to-grasp movements performed in interactive and noninteractive settings. Using a machine learning approach, we investigated whether the extent of visuo-motor interference would be enhanced or reduced in two different joint action settings compared with a noninteractive one. Our results reveal that the detrimental effect of visuo-motor interference is reduced when the action performed by the partner is relevant to achieve a common goal, regardless of whether this goal requires to produce a concrete sensory outcome in the environment (joint outcome condition) or only a joint movement configuration (joint movement condition). These findings support the idea that during joint actions we form dyadic motor plans, in which both our own and our partner's actions are represented in predictive terms and in light of the common goal to be achieved. The formation of a dyadic motor plan might allow agents to shift from the automatic simulation of an observed action to the active prediction of the consequences of a partner's action. Overall, our results demonstrate the unavoidable impact of others' action on our motor behavior in social contexts, and how strongly this effect can be modulated by task interactivity.

Uncovering the potential of innovation ecosystems in the healthcare sector after the COVID-19 crisis.

Industry 4.0 technologies are expected to enhance healthcare quality at the minimum cost feasible by using innovative solutions based on a fruitful exchange of knowledge and resources among institutions, firms and academia. These collaborative mechanisms are likely to occur in an innovation ecosystem where different stakeholders and resources interact to provide ground-breaking solutions to the market. The paper proposes a framework for studying the creation and development of innovation ecosystems in the healthcare sector by using a set of interrelated dimensions including, technology, value, and capabilities within a Triple-Helix model guided by focal actors. The model is applied to an exemplary Italian innovation ecosystem providing cloud and artificial intelligence-based solutions to general practitioners (GPs) under the focal role of the Italian association of GPs. Primary and secondary data are examined starting from the innovation ecosystem's origins and continuing until the COVID-19 crisis. The findings show that the pandemic represented the turning point that altered the ecosystem's dimensions in order to find immediate solutions for monitoring health conditions and organizing the booking of swabs and vaccines. The data triangulation points out the technical, organizational, and administrative barriers hindering the widespread adoption of these solutions at the national and regional levels, revealing several implications for health policy.

Decoding social decisions from movement kinematics.

Decisions, including social decisions, are ultimately expressed through actions. However, very little is known about the kinematics of social decisions, and whether movements might reveal important aspects of social decision-making. We addressed this question by developing a motor version of a widely used behavioral economic game - the Ultimatum Game - and using a multivariate kinematic decoding approach to map parameters of social decisions to the single-trial kinematics of individual responders. Using this approach, we demonstrated that movement contains predictive information about both the fairness of a proposed offer and the choice to either accept or reject that offer. This information is expressed in personalized kinematic patterns that are consistent within a given responder, but that varies from one responder to another. These results provide insights into the relationship between decision-making and sensorimotor control, as they suggest that hand kinematics can reveal hidden parameters of complex, social interactive, choice.

Prediction of complications of type 2 Diabetes: A Machine learning approach.

AIM: To construct predictive models of diabetes complications (DCs) by big data machine learning, based on electronic medical records. METHODS: Six groups of DCs were considered: eye complications, cardiovascular, cerebrovascular, and peripheral vascular disease, nephropathy, diabetic neuropathy. A supervised, tree-based learning approach (XGBoost) was used to predict the onset of each complication within 5 years (task 1). Furthermore, a separate prediction for early (within 2 years) and late (3-5 years) onset of complication (task 2) was performed. A dataset of 147.664 patients seen during 15 years by 23 centers was used. External validation was performed in five additional centers. Models were evaluated by considering accuracy, sensitivity, specificity, and area under the ROC curve (AUC). RESULTS: For all DCs considered, the predictive models in task 1 showed an accuracy > 70 %, and AUC largely exceeded 0.80, reaching 0.97 for nephropathy. For task 2, all predictive models showed an accuracy > 70 % and an AUC > 0.85. Sensitivity in predicting the early occurrence of the complication ranged between 83.2 % (peripheral vascular disease) and 88.5 % (nephropathy). CONCLUSIONS: Machine learning approach offers the opportunity to identify patients at greater risk of complications. This can help overcoming clinical inertia and improving the quality of diabetes care.

A Unified Hierarchical XGBoost model for classifying priorities for COVID-19 vaccination campaign.

The current ML approaches do not fully focus to answer a still unresolved and topical challenge, namely the prediction of priorities of COVID-19 vaccine administration. Thus, our task includes some additional methodological challenges mainly related to avoiding unwanted bias while handling categorical and ordinal data with a highly imbalanced nature. Hence, the main contribution of this study is to propose a machine learning algorithm, namely Hierarchical Priority Classification eXtreme Gradient Boosting for priority classification for COVID-19 vaccine administration using the Italian Federation of General Practitioners dataset that contains Electronic Health Record data of 17k patients. We measured the effectiveness of the proposed methodology for classifying all the priority classes while demonstrating a significant improvement with respect to the state of the art. The proposed ML approach, which is integrated into a clinical decision support system, is currently supporting General Pracitioners in assigning COVID-19 vaccine administration priorities to their assistants.

A Semi-Supervised Multi-Task Learning Approach for Predicting Short-Term Kidney Disease Evolution.

Kidney Disease (KD) may hide complex causes and is associated with a tremendous socio-economic impact. Timely identification and management from the first level of medical care represent the most effective strategy to address the growing global burden sustainably. Clinical practice guidelines suggest utilizing estimated Glomerular Filtration Rate (eGFR) for routine evaluation within a screening purpose. Accordingly, the analysis of Electronic Health Records (EHRs) using Machine Learning techniques offers great opportunities to monitor and predict the eGFR trend over time. This paper aims to propose a novel Semi-Supervised Multi-Task Learning (SS-MTL) approach for predicting short-term KD evolution on multiple General Practitioners' EHR data. We demonstrated that the SS-MTL approach can (i) capture the eGFR temporal evolution by imposing a temporal relatedness between consecutive time windows and (ii) exploit useful information from unlabeled patients when labeled patients are less numerous with a gain of up to 4.1% in terms of Recall. This situation reflects the real-case scenario, where available labeled samples are limited, but those unlabeled much more abundant. The SS-MTL approach, also given the high level of interpretability, might be the ideal candidate in general practice to get integrated within a decision support system for KD screening purposes.

Identifying the signature of prospective motor control in children with autism.

Failure to develop prospective motor control has been proposed to be a core phenotypic marker of autism spectrum disorders (ASD). However, whether genuine differences in prospective motor control permit discriminating between ASD and non-ASD profiles over and above individual differences in motor output remains unclear. Here, we combined high precision measures of hand movement kinematics and rigorous machine learning analyses to determine the true power of prospective movement data to differentiate children with autism and typically developing children. Our results show that while movement is unique to each individual, variations in the kinematic patterning of sequential grasping movements genuinely differentiate children with autism from typically developing children. These findings provide quantitative evidence for a prospective motor control impairment in autism and indicate the potential to draw inferences about autism on the basis of movement kinematics.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic. This article provides a blend of discussions on the contribution of these digital technologies, propose several complementary and multidisciplinary techniques to combat COVID-19, offer opportunities for more holistic studies, and accelerate knowledge acquisition and scientific discoveries in pandemic research. First, four areas, where IoT can contribute are discussed, namely: 1) tracking and tracing; 2) remote patient monitoring (RPM) by wearable IoT (WIoT); 3) personal digital twins (PDTs); and 4) real-life use case: ICT/IoT solution in South Korea. Second, the role and novel applications of AI are explained, namely: 1) diagnosis and prognosis; 2) risk prediction; 3) vaccine and drug development; 4) research data set; 5) early warnings and alerts; 6) social control and fake news detection; and 7) communication and chatbot. Third, the main uses of robotics and drone technology are analyzed, including: 1) crowd surveillance; 2) public announcements; 3) screening and diagnosis; and 4) essential supply delivery. Finally, we discuss how distributed ledger technologies (DLTs), of which blockchain is a common example, can be combined with other technologies for tackling COVID-19.

Machine learning using the extreme gradient boosting (XGBoost) algorithm predicts 5-day delta of SOFA score at ICU admission in COVID-19 patients.

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients' Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs. 0.69, P < 0.01 [paired t-test with 95% confidence interval]). Conclusions: The XGBoost model predicted the change in SOFA score in critically ill COVID-19 patients admitted to the ICU and can guide clinical decision support systems (CDSSs) aimed at optimizing available resources.

Functional evaluation of triceps surae during heel rise test: from EMG frequency analysis to machine learning approach.

Soleus muscle flap as coverage tissue is a possible surgical solution adopted to cover the wounds due to open fractures. Despite this procedure presents many clinical advantages, relatively poor information is available about the loss of functionality of triceps surae of the treated leg. In this study, a group of patients who underwent a soleus muscle flap surgical procedure has been analyzed through the heel rise test (HRT), in order to explore the triceps surae residual functionalities. A frequency band analysis was performed in order to assess whether the residual heads of triceps surae exhibit different characteristics with respect to both the non-treated lower limb and an age-matched control group. Then, an in-depth analysis based on a machine learning approach was proposed for discriminating between groups by generalizing across new unseen subjects. Experimental results showed the reliability of the proposed analyses for discriminating between-group at a specific time epoch and the high interpretability of the proposed machine learning algorithm allowed the temporal localization of the most discriminative frequency bands. Findings of this study highlighted that significant differences can be recognized in the myoelectric spectral characteristics between the treated and contralateral leg in patients who underwent soleus flap surgery. These experimental results may support the clinical decision-making for assessing triceps surae performance and for supporting the choice of treatment in plastic and reconstructive surgery. Graphical Abstract The Graphical abstract presents the scope of the proposed analysis of myoelectric signals of soleus and gastrocnemius muscles of patiens groups during Hell Rise Test, highlighting the applied methods and the obtained results.

A Decision Support System for Diabetes Chronic Care Models Based on General Practitioner Engagement and EHR Data Sharing.

Objective Decision support systems (DSS) have been developed and promoted for their potential to improve quality of health care. However, there is a lack of common clinical strategy and a poor management of clinical resources and erroneous implementation of preventive medicine. Methods To overcome this problem, this work proposed an integrated system that relies on the creation and sharing of a database extracted from GPs' Electronic Health Records (EHRs) within the Netmedica Italian (NMI) cloud infrastructure. Although the proposed system is a pilot application specifically tailored for improving the chronic Type 2 Diabetes (T2D) care it could be easily targeted to effectively manage different chronic-diseases. The proposed DSS is based on EHR structure used by GPs in their daily activities following the most updated guidelines in data protection and sharing. The DSS is equipped with a Machine Learning (ML) method for analyzing the shared EHRs and thus tackling the high variability of EHRs. A novel set of T2D care-quality indicators are used specifically to determine the economic incentives and the T2D features are presented as predictors of the proposed ML approach. Results The EHRs from 41237 T2D patients were analyzed. No additional data collection, with respect to the standard clinical practice, was required. The DSS exhibited competitive performance (up to an overall accuracy of 98%±2% and macro-recall of 96%±1%) for classifying chronic care quality across the different follow-up phases. The chronic care quality model brought to a significant increase (up to 12%) of the T2D patients without complications. For GPs who agreed to use the proposed system, there was an economic incentive. A further bonus was assigned when performance targets are achieved. Conclusions The quality care evaluation in a clinical use-case scenario demonstrated how the empowerment of the GPs through the use of the platform (integrating the proposed DSS), along with the economic incentives, may speed up the improvement of care.

Faster R-CNN approach for detection and quantification of DNA damage in comet assay images.

BACKGROUND AND OBJECTIVE: DNA damage analysis can provide valuable information in several areas ranging from the diagnosis/treatment of a disease to the monitoring of the effects of genetic and environmental influences. The evaluation of the damage is determined by comet scoring, which can be performed by a skilled operator with a manual procedure. However, this approach becomes very time-consuming and the operator dependency results in the subjectivity of the damage quantification and thus in a high inter/intra-operator variability. METHODS: In this paper, we aim to overcome this issue by introducing a Deep Learning methodology based on Faster R-CNN to completely automatize the overall approach while discovering unseen discriminative patterns in comets. RESULTS: The experimental results performed on two real use-case datasets reveal the higher performance (up to mean absolute precision of 0.74) of the proposed methodology against other state-of-the-art approaches. Additionally, the validation procedure performed by expert biologists highlights how the proposed approach is able to unveil true comets, often unseen from the human eye and standard computer vision methodology. CONCLUSIONS: This work contributes to the biomedical informatics field by the introduction of a novel approach based on established object detection Deep Learning technique for evaluating the DNA damage. The main contribution is the application of Faster R-CNN for the detection and quantification of DNA damage in comet assay images, by fully automatizing the detection/classification DNA damage task. The experimental results extracted in two real use-case datasets demonstrated (i) the higher robustness of the proposed methodology against other state-of-the-art Deep Learning competitors, (ii) the speeding up of the comet analysis procedure and (iii) the minimization of the intra/inter-operator variability.

Early temporal prediction of Type 2 Diabetes Risk Condition from a General Practitioner Electronic Health Record: A Multiple Instance Boosting Approach.

Early prediction of target patients at high risk of developing Type 2 diabetes (T2D) plays a significant role in preventing the onset of overt disease and its associated comorbidities. Although fundamental in early phases of T2D natural history, insulin resistance is not usually quantified by General Practitioners (GPs). Triglyceride-glucose (TyG) index has been proven useful in clinical studies for quantifying insulin resistance and for the early identification of individuals at T2D risk but still not applied by GPs for diagnostic purposes. The aim of this study is to propose a multiple instance learning boosting algorithm (MIL-Boost) for creating a predictive model capable of early prediction of worsening insulin resistance (low vs high T2D risk) in terms of TyG index. The MIL-Boost is applied to past electronic health record (EHR) patients' information stored by a single GP. The proposed MIL-Boost algorithm proved to be effective in dealing with this task, by performing better than the other state-of-the-art ML competitors (Recall from 0.70 and up to 0.83). The proposed MIL-based approach is able to extract hidden patterns from past EHR temporal data, even not directly exploiting triglycerides and glucose measurements. The major advantages of our method can be found in its ability to model the temporal evolution of longitudinal EHR data while dealing with small sample size and variability in the observations (e.g., a small variable number of prescriptions for non-hospitalized patients). The proposed algorithm may represent the main core of a clinical decision support system.

Discovering the Type 2 Diabetes in Electronic Health Records Using the Sparse Balanced Support Vector Machine.

The diagnosis of type 2 diabetes (T2D) at an early stage has a key role for an adequate T2D integrated management system and patient's follow-up. Recent years have witnessed an increasing amount of available electronic health record (EHR) data and machine learning (ML) techniques have been considerably evolving. However, managing and modeling this amount of information may lead to several challenges, such as overfitting, model interpretability, and computational cost. Starting from these motivations, we introduced an ML method called sparse balanced support vector machine (SB-SVM) for discovering T2D in a novel collected EHR dataset (named Federazione Italiana Medici di Medicina Generale dataset). In particular, among all the EHR features related to exemptions, examination, and drug prescriptions, we have selected only those collected before T2D diagnosis from an uniform age group of subjects. We demonstrated the reliability of the introduced approach with respect to other ML and deep learning approaches widely employed in the state-of-the-art for solving this task. Results evidence that the SB-SVM overcomes the other state-of-the-art competitors providing the best compromise between predictive performance and computation time. Additionally, the induced sparsity allows to increase the model interpretability, while implicitly managing high-dimensional data and the usual unbalanced class distribution.

TyG-er: An ensemble Regression Forest approach for identification of clinical factors related to insulin resistance condition using Electronic Health Records.

BACKGROUND: Insulin resistance is an early-stage deterioration of Type 2 diabetes. Identification and quantification of insulin resistance requires specific blood tests; however, the triglyceride-glucose (TyG) index can provide a surrogate assessment from routine Electronic Health Record (EHR) data. Since insulin resistance is a multi-factorial condition, to improve its characterisation, this study aims to discover non-trivial clinical factors in EHR data to determine where the insulin-resistance condition is encoded. METHODS: We proposed a high-interpretable Machine Learning approach (i.e., ensemble Regression Forest combined with data imputation strategies), named TyG-er. We applied three different experimental procedures to test TyG-er reliability on the Italian Federation of General Practitioners dataset, named FIMMG_obs dataset, which is publicly available and reflects the clinical use-case (i.e., not all laboratory exams are prescribed on a regular basis over time). RESULTS: Results detected non-conventional clinical factors (i.e., uricemia, leukocytes, gamma-glutamyltransferase and protein profile) and provided novel insight into the best combination of clinical factors for detecting early glucose tolerance deterioration. The robustness of these extracted clinical factors was confirmed by the high agreement (from 0.664 to 0.911 of Lin's correlation coefficient (rc)) of the TyG-er approach among different experimental procedures. Moreover, the results of the three experimental procedures outlined the predictive power of the TyG-er approach (up to a mean absolute error of 5.68% and rc=0.666,p<.05). CONCLUSIONS: The TyG-er approach is able to carry information about the identification of the TyG index, strictly correlated with the insulin-resistance condition, while extracting the most relevant non-glycemic features from routine data.

The KIMORE Dataset: KInematic Assessment of MOvement and Clinical Scores for Remote Monitoring of Physical REhabilitation.

This paper proposes a free dataset, available at the following link,1named KIMORE, regarding different rehabilitation exercises collected by a RGB-D sensor. Three data inputs including RGB, depth videos, and skeleton joint positions were recorded during five physical exercises, specific for low back pain and accurately selected by physicians. For each exercise, the dataset also provides a set of features, specifically defined by the physicians, and relevant to describe its scope. These features, validated with respect to a stereophotogrammetric system, can be analyzed to compute a score for the subject's performance. The dataset also contains an evaluation of the same performance provided by the clinicians, through a clinical questionnaire. The impact of KIMORE has been analyzed by comparing the output obtained by an example of rule and template-based approaches and the clinical score. The dataset presented is intended to be used as a benchmark for human movement assessment in a rehabilitation scenario in order to test the effectiveness and the reliability of different computational approaches. Unlike other existing datasets, the KIMORE merges a large heterogeneous population of 78 subjects, divided into 2 groups with 44 healthy subjects and 34 with motor dysfunctions. It provides the most clinically-relevant features and the clinical score for each exercise.1https://univpm-my.sharepoint.com/:f:/g/personal/p008099_staff_univpm_it/EiwbKIzk6N9NoJQx4J8aubIBx0o7tIa1XwclWp1NmRkA-w?e=F3jtBk.