An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin.

The aim of this study was to develop a dynamic model-based approach to separately quantify the exogenous and endogenous contributions to total plasma insulin concentration and to apply it to assess the effects of inhaled-insulin administration on endogenous insulin secretion during a meal test. A three-step dynamic in-silico modeling approach was developed to estimate the two insulin contributions of total plasma insulin in a group of 21 healthy subjects who underwent two equivalent standardized meal tests on separate days, one of which preceded by inhalation of a Technosphere® Insulin dose (22U or 20U). In the 30-120 min test interval, the calculated endogenous insulin component showed a divergence in the time course between the test with and without inhaled insulin. Moreover, the supra-basal area-under-the-curve of endogenous insulin in the test with inhaled insulin was significantly lower than that in the test without (2.1 ± 1.7 × 104 pmol·min/L vs 4.2 ± 1.8 × 104 pmol·min/L, p < 0.01). The percentage of exogenous insulin reaching the plasma, relative to the inhaled dose, was 42 ± 21%. The proposed in-silico approach separates exogenous and endogenous insulin contributions to total plasma insulin, provides individual bioavailability estimates, and can be used to assess the effect of inhaled insulin on endogenous insulin secretion during a meal.

Cardiorespiratory DB: Collection of cardiorespiratory data acquired during normal breathing, deep breathing and breath holding.

The database is constituted by 50 datasets containing cardiorespiratory signals acquired from 50 healthy volunteer subjects (one dataset for each subject; 23 males and 27 females; age: 23±5 years) while performing normal breathing, deep breathing, and breath holding, and two spreadsheet files, namely the "SubjectsInfo.xlsx" and "DBInfo.xlsx" containing the metadata of subjects (including demographic data) and of acquired signals, respectively. Cardiorespiratory signals consisted in simultaneously recorded 12-lead electrocardiograms acquired by the clinical M12 Global InstrumentationⓇ digital Holter ECG recorder, and single-lead electrocardiograms and respiration signals acquired by the wearable chest strap BioHarness 3.0 by Zephyr. The database may be useful to: (1) validate the use of wearable sensors in the acquisition of cardiorespiratory data during different respiration kinds, including apnea; (2) investigate the physiological association between cardiovascular and respiratory systems; (3) validate algorithms able to indirectly extract the respiration signal from the electrocardiogram; (4) study the fatigue level induced by a series of controlled respiration patterns; and (5) investigate the effect of COVID-19 infection on the cardiorespiratory system.

Acquisition Devices for Fetal Phonocardiography: A Scoping Review.

Timely and reliable fetal monitoring is crucial to prevent adverse events during pregnancy and delivery. Fetal phonocardiography, i.e., the recording of fetal heart sounds, is emerging as a novel possibility to monitor fetal health status. Indeed, due to its passive nature and its noninvasiveness, the technique is suitable for long-term monitoring and for telemonitoring applications. Despite the high share of literature focusing on signal processing, no previous work has reviewed the technological hardware solutions devoted to the recording of fetal heart sounds. Thus, the aim of this scoping review is to collect information regarding the acquisition devices for fetal phonocardiography (FPCG), focusing on technical specifications and clinical use. Overall, PRISMA-guidelines-based analysis selected 57 studies that described 26 research prototypes and eight commercial devices for FPCG acquisition. Results of our review study reveal that no commercial devices were designed for fetal-specific purposes, that the latest advances involve the use of multiple microphones and sensors, and that no quantitative validation was usually performed. By highlighting the past and future trends and the most relevant innovations from both a technical and clinical perspective, this review will represent a useful reference for the evaluation of different acquisition devices and for the development of new FPCG-based systems for fetal monitoring.

Glucagon kinetics assessed by mathematical modelling during oral glucose administration in people spanning from normal glucose tolerance to type 2 diabetes.

Background/Objectives: Glucagon is important in the maintenance of glucose homeostasis, with also effects on lipids. In this study, we aimed to apply a recently developed model of glucagon kinetics to determine the sensitivity of glucagon variations (especially, glucagon inhibition) to insulin levels ("alpha-cell insulin sensitivity"), during oral glucose administration. Subjects/Methods: We studied 50 participants (spanning from normal glucose tolerance to type 2 diabetes) undergoing frequently sampled 5-hr oral glucose tolerance test (OGTT). The alpha-cell insulin sensitivity and the glucagon kinetics were assessed by a mathematical model that we developed previously. Results: The alpha-cell insulin sensitivity parameter (named SGLUCA; "GLUCA": "glucagon") was remarkably variable among participants (CV=221%). SGLUCA was found inversely correlated with the mean glycemic values, as well as with 2-hr glycemia of the OGTT. When stratifying participants into two groups (normal glucose tolerance, NGT, N=28, and impaired glucose regulation/type 2 diabetes, IGR_T2D, N=22), we found that SGLUCA was lower in the latter (1.50 ± 0.50·10-2 vs. 0.26 ± 0.14·10-2 ng·L-1 GLUCA/pmol·L-1 INS, in NGT and IGR_T2D, respectively, p=0.009; "INS": "insulin"). Conclusions: The alpha-cell insulin sensitivity is highly variable among subjects, and it is different in groups at different glucose tolerance. This may be relevant for defining personalized treatment schemes, in terms of dietary prescriptions but also for treatments with glucagon-related agents.

Glucometabolism in Kidney Transplant Recipients with and without Posttransplant Diabetes: Focus on Beta-Cell Function.

Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min-1∙m-2∙mM-1 in PTDM versus 143.73 ± 112.91 pmol∙min-1∙m-2∙mM-1 in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.

Glucagon-like peptide-1 and interleukin-6 interaction in response to physical exercise: An in-silico model in the framework of immunometabolism.

BACKGROUND AND OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is classically identified as an incretin hormone, secreted in response to nutrient ingestion and able to enhance glucose-stimulated insulin secretion. However, other stimuli, such as physical exercise, may enhance GLP-1 plasma levels, and this exercise-induced GLP-1 secretion is mediated by interleukin-6 (IL-6), a cytokine secreted by contracting skeletal muscle. The aim of the study is to propose a mathematical model of IL-6-induced GLP-1 secretion and kinetics in response to physical exercise of moderate intensity. METHODS: The model includes the GLP-1 subsystem (with two pools: gut and plasma) and the IL-6 subsystem (again with two pools: skeletal muscle and plasma); it provides a parameter of possible clinical relevance representing the sensitivity of GLP-1 to IL-6 (k0). The model was validated on mean IL-6 and GLP-1 data derived from the scientific literature and on a total of 100 virtual subjects. RESULTS: Model validation provided mean residuals between 0.0051 and 0.5493 pg⋅mL-1 for IL-6 (in view of concentration values ranging from 0.8405 to 3.9718 pg⋅mL-1) and between 0.0133 and 4.1540 pmol⋅L-1 for GLP-1 (in view of concentration values ranging from 0.9387 to 17.9714 pmol⋅L-1); a positive significant linear correlation (r = 0.85, p<0.001) was found between k0 and the ratio between areas under GLP-1 and IL-6 curve, over the virtual subjects. CONCLUSIONS: The model accurately captures IL-6-induced GLP-1 kinetics in response to physical exercise.

Glucometabolic Alterations in Pregnant Women with Overweight or Obesity but without Gestational Diabetes Mellitus: An Observational Study.

INTRODUCTION: Maternal overweight is a risk factor for gestational diabetes mellitus (GDM). However, emerging evidence suggests that an increased maternal body mass index (BMI) promotes the development of perinatal complications even in women who do not develop GDM. This study aims to assess physiological glucometabolic changes associated with increased BMI. METHODS: Twenty-one women with overweight and 21 normal weight controls received a metabolic assessment at 13 weeks of gestation, including a 60-min frequently sampled intravenous glucose tolerance test. A further investigation was performed between 24 and 28 weeks in women who remained normal glucose tolerant. RESULTS: At baseline, mothers with overweight showed impaired insulin action, whereby the calculated insulin sensitivity index (CSI) was lower as compared to normal weight controls (3.5 vs. 6.7 10-4 min-1 [microU/mL]-1, p = 0.025). After excluding women who developed GDM, mothers with overweight showed higher average glucose during the oral glucose tolerance test (OGTT) at the third trimester. Moreover, early pregnancy insulin resistance and secretion were associated with increased placental weight in normal glucose-tolerant women. CONCLUSION: Mothers with overweight or obesity show an unfavorable metabolic environment already at the early stage of pregnancy, possibly associated with perinatal complications in women who remain normal glucose tolerant.

Model-based Estimators of QT Series Time Delay in Following Heart-Rate Changes.

Sudden cardiac death is the leading cause of death among cardiovascular diseases. Markers for patient risk stratification focusing on QT-interval dynamics in response to heart-rate (HR) changes can be characterized in terms of parametric QT to RR dependence and QT/RR hysteresis. The QT/RR hysteresis can be quantified by the time delay the QT interval takes to accommodate for the HR changes. The exercise stress test has been proposed as a proper test, with large HR dynamics, to evaluate the QT/RR hysteresis. The present study aims at evaluating several time-delay estimators based on noise statistic (Gaussian or Laplacian) and HR changes profile at stress test (gradual transition change). The estimator's performance was assessed on a simulated QT transition contaminated by noise and in a clinical study including patients affected by coronary arteries disease (CAD). As expected, the Laplacian and Gaussian estimators yield the best results when noise follows the respective distribution. Further, the Laplacian estimator showed greater discriminative power in classifying different levels of cardiac risk in CAD patients, suggesting that real data fit better the Laplacian distribution than the Gaussian one. The Laplacian estimator appears to be the choice for time-delay estimation of QT/RR hysteresis lag in response to HR changes in stress test.Clinical Relevance-The proposed time-delay estimator of QT/RR hysteresis lag improves its significance as biomarkers for coronary artery diseases risk stratification.

On-cloud decision-support system for non-small cell lung cancer histology characterization from thorax computed tomography scans.

Non-Small Cell Lung Cancer (NSCLC) accounts for about 85% of all lung cancers. Developing non-invasive techniques for NSCLC histology characterization may not only help clinicians to make targeted therapeutic treatments but also prevent subjects from undergoing lung biopsy, which is challenging and could lead to clinical implications. The motivation behind the study presented here is to develop an advanced on-cloud decision-support system, named LUCY, for non-small cell LUng Cancer histologY characterization directly from thorax Computed Tomography (CT) scans. This aim was pursued by selecting thorax CT scans of 182 LUng ADenocarcinoma (LUAD) and 186 LUng Squamous Cell carcinoma (LUSC) subjects from four openly accessible data collections (NSCLC-Radiomics, NSCLC-Radiogenomics, NSCLC-Radiomics-Genomics and TCGA-LUAD), in addition to the implementation and comparison of two end-to-end neural networks (the core layer of whom is a convolutional long short-term memory layer), the performance evaluation on test dataset (NSCLC-Radiomics-Genomics) from a subject-level perspective in relation to NSCLC histological subtype location and grade, and the dynamic visual interpretation of the achieved results by producing and analyzing one heatmap video for each scan. LUCY reached test Area Under the receiver operating characteristic Curve (AUC) values above 77% in all NSCLC histological subtype location and grade groups, and a best AUC value of 97% on the entire dataset reserved for testing, proving high generalizability to heterogeneous data and robustness. Thus, LUCY is a clinically-useful decision-support system able to timely, non-invasively and reliably provide visually-understandable predictions on LUAD and LUSC subjects in relation to clinically-relevant information.

Ratio Indexes Based on Spectral Electroencephalographic Brainwaves for Assessment of Mental Involvement: A Systematic Review.

BACKGROUND: This review systematically examined the scientific literature about electroencephalogram-derived ratio indexes used to assess human mental involvement, in order to deduce what they are, how they are defined and used, and what their best fields of application are. (2) Methods: The review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. (3) Results: From the search query, 82 documents resulted. The majority (82%) were classified as related to mental strain, while 12% were classified as related to sensory and emotion aspects, and 6% to movement. The electroencephalographic electrode montage used was low-density in 13%, high-density in 6% and very-low-density in 81% of documents. The most used electrode positions for computation of involvement indexes were in the frontal and prefrontal cortex. Overall, 37 different formulations of involvement indexes were found. None of them could be directly related to a specific field of application. (4) Conclusions: Standardization in the definition of these indexes is missing, both in the considered frequency bands and in the exploited electrodes. Future research may focus on the development of indexes with a unique definition to monitor and characterize mental involvement.

A computational model of the effects of macronutrients absorption and physical exercise on hormonal regulation and metabolic homeostasis.

Regular physical exercise and appropriate nutrition affect metabolic and hormonal responses and may reduce the risk of developing chronic non-communicable diseases such as high blood pressure, ischemic stroke, coronary heart disease, some types of cancer, and type 2 diabetes mellitus. Computational models describing the metabolic and hormonal changes due to the synergistic action of exercise and meal intake are, to date, scarce and mostly focussed on glucose absorption, ignoring the contribution of the other macronutrients. We here describe a model of nutrient intake, stomach emptying, and absorption of macronutrients in the gastrointestinal tract during and after the ingestion of a mixed meal, including the contribution of proteins and fats. We integrated this effort to our previous work in which we modeled the effects of a bout of physical exercise on metabolic homeostasis. We validated the computational model with reliable data from the literature. The simulations are overall physiologically consistent and helpful in describing the metabolic changes due to everyday life stimuli such as multiple mixed meals and variable periods of physical exercise over prolonged periods of time. This computational model may be used to design virtual cohorts of subjects differing in sex, age, height, weight, and fitness status, for specialized in silico challenge studies aimed at designing exercise and nutrition schemes to support health.

Advanced repeated structuring and learning procedure to detect acute myocardial ischemia in serial 12-lead ECGs.

Objectives. Acute myocardial ischemia in the setting of acute coronary syndrome (ACS) may lead to myocardial infarction. Therefore, timely decisions, already in the pre-hospital phase, are crucial to preserving cardiac function as much as possible. Serial electrocardiography, a comparison of the acute electrocardiogram with a previously recorded (reference) ECG of the same patient, aids in identifying ischemia-induced electrocardiographic changes by correcting for interindividual ECG variability. Recently, the combination of deep learning and serial electrocardiography provided promising results in detecting emerging cardiac diseases; thus, the aim of our current study is the application of our novel Advanced Repeated Structuring and Learning Procedure (AdvRS&LP), specifically designed for acute myocardial ischemia detection in the pre-hospital phase by using serial ECG features.Approach. Data belong to the SUBTRACT study, which includes 1425 ECG pairs, 194 (14%) ACS patients, and 1035 (73%) controls. Each ECG pair was characterized by 28 serial features that, with sex and age, constituted the inputs of the AdvRS&LP, an automatic constructive procedure for creating supervised neural networks (NN). We created 100 NNs to compensate for statistical fluctuations due to random data divisions of a limited dataset. We compared the performance of the obtained NNs to a logistic regression (LR) procedure and the Glasgow program (Uni-G) in terms of area-under-the-curve (AUC) of the receiver-operating-characteristic curve, sensitivity (SE), and specificity (SP).Main Results. NNs (median AUC = 83%, median SE = 77%, and median SP = 89%) presented a statistically (Pvalue lower than 0.05) higher testing performance than those presented by LR (median AUC = 80%, median SE = 67%, and median SP = 81%) and by the Uni-G algorithm (median SE = 72% and median SP = 82%).Significance. In conclusion, the positive results underscore the value of serial ECG comparison in ischemia detection, and NNs created by AdvRS&LP seem to be reliable tools in terms of generalization and clinical applicability.

Segmentation of Anatomical Structures of the Left Heart from Echocardiographic Images Using Deep Learning.

Knowledge about the anatomical structures of the left heart, specifically the atrium (LA) and ventricle (i.e., endocardium-Vendo-and epicardium-LVepi) is essential for the evaluation of cardiac functionality. Manual segmentation of cardiac structures from echocardiography is the baseline reference, but results are user-dependent and time-consuming. With the aim of supporting clinical practice, this paper presents a new deep-learning (DL)-based tool for segmenting anatomical structures of the left heart from echocardiographic images. Specifically, it was designed as a combination of two convolutional neural networks, the YOLOv7 algorithm and a U-Net, and it aims to automatically segment an echocardiographic image into LVendo, LVepi and LA. The DL-based tool was trained and tested on the Cardiac Acquisitions for Multi-Structure Ultrasound Segmentation (CAMUS) dataset of the University Hospital of St. Etienne, which consists of echocardiographic images from 450 patients. For each patient, apical two- and four-chamber views at end-systole and end-diastole were acquired and annotated by clinicians. Globally, our DL-based tool was able to segment LVendo, LVepi and LA, providing Dice similarity coefficients equal to 92.63%, 85.59%, and 87.57%, respectively. In conclusion, the presented DL-based tool proved to be reliable in automatically segmenting the anatomical structures of the left heart and supporting the cardiological clinical practice.

Physiological and Biomechanical Monitoring in American Football Players: A Scoping Review.

American football is the sport with the highest rates of concussion injuries. Biomedical engineering applications may support athletes in monitoring their injuries, evaluating the effectiveness of their equipment, and leading industrial research in this sport. This literature review aims to report on the applications of biomedical engineering research in American football, highlighting the main trends and gaps. The review followed the PRISMA guidelines and gathered a total of 1629 records from PubMed (n = 368), Web of Science (n = 665), and Scopus (n = 596). The records were analyzed, tabulated, and clustered in topics. In total, 112 studies were selected and divided by topic in the biomechanics of concussion (n = 55), biomechanics of footwear (n = 6), biomechanics of sport-related movements (n = 6), the aerodynamics of football and catch (n = 3), injury prediction (n = 8), heat monitoring of physiological parameters (n = 8), and monitoring of the training load (n = 25). The safety of players has fueled most of the research that has led to innovations in helmet and footwear design, as well as improvements in the understanding and prevention of injuries and heat monitoring. The other important motivator for research is the improvement of performance, which has led to the monitoring of training loads and catches, and studies on the aerodynamics of football. The main gaps found in the literature were regarding the monitoring of internal loads and the innovation of shoulder pads.

Wearable and Portable Devices for Acquisition of Cardiac Signals while Practicing Sport: A Scoping Review.

Wearable and portable devices capable of acquiring cardiac signals are at the frontier of the sport industry. They are becoming increasingly popular for monitoring physiological parameters while practicing sport, given the advances in miniaturized technologies, powerful data, and signal processing applications. Data and signals acquired by these devices are increasingly used to monitor athletes' performances and thus to define risk indices for sport-related cardiac diseases, such as sudden cardiac death. This scoping review investigated commercial wearable and portable devices employed for cardiac signal monitoring during sport activity. A systematic search of the literature was conducted on PubMed, Scopus, and Web of Science. After study selection, a total of 35 studies were included in the review. The studies were categorized based on the application of wearable or portable devices in (1) validation studies, (2) clinical studies, and (3) development studies. The analysis revealed that standardized protocols for validating these technologies are necessary. Indeed, results obtained from the validation studies turned out to be heterogeneous and scarcely comparable, since the metrological characteristics reported were different. Moreover, the validation of several devices was carried out during different sport activities. Finally, results from clinical studies highlighted that wearable devices are crucial to improve athletes' performance and to prevent adverse cardiovascular events.

Software Packages and Tools for the Analysis of Continuous Glucose Monitoring Data.

The advancement of technology in the field of glycemic control has led to the widespread use of continuous glucose monitoring (CGM), which can be nowadays obtained from wearable devices equipped with a minimally invasive sensor, that is, transcutaneous needle type or implantable, and a transmitter that sends information to a receiver or smart device for data storage and display. This work aims to review the currently available software packages and tools for the analysis of CGM data. Based on the purposes of this work, 12 software packages have been identified from the literature, published until December 2021, namely: GlyCulator, EasyGV (Easy Glycemic Variability), CGM-GUIDE© (Continuous Glucose Monitoring Graphical User Interface for Diabetes Evaluation), GVAP (Glycemic Variability Analyzer Program), Tidepool, CGManalyzer, cgmanalysis, GLU, CGMStatsAnalyser, iglu, rGV, and cgmquantify. Comparison of available software packages and tools has been done in terms of main characteristics (i.e., publication year, presence of a graphical user interface, availability, open-source code, number of citations, programming language, supported devices, supported data format and organization of the data structure, documentation, presence of a toy example, video tutorial, data upload and download, measurement-units conversion), preprocessing procedures, data display options, and computed metrics; also, each of the computed metrics has been analyzed in terms of its adherence to the American Diabetes Association (ADA) 2017 international consensus on CGM data analysis and the ADA 2019 international consensus on time in range. Eventually, the agreement between metrics computed by different software and tools has been investigated. Based on such comparison, usability and complexity of data management, as well as the possibility to perform customized or patients-group analyses, have been discussed by highlighting limitations and strengths, also in relation to possible different user categories (i.e., patients, clinicians, researchers). The information provided could be useful to researchers interested in working in the diabetic research field as to clinicians and endocrinologists who need tools capable of handling CGM data effectively.

Identification of Respiration Types Through Respiratory Signal Derived From Clinical and Wearable Electrocardiograms.

GOAL: To evaluate suitability of respiratory signals derived from clinical 12-lead electrocardiograms (ECGs) and wearable 1-lead ECG to identify different respiration types. METHODS: ECGs were simultaneously acquired through the M12R ECG Holter by Global Instrumentation and the chest strap BioHarness 3.0 by Zephyr from 42 healthy subjects alternating normal breathing, breath holding, and deep breathing. Respiration signals were derived from the ECGs through the Segmented-Beat Modulation Method (SBMM)-based algorithm and the algorithms by Van Gent, Charlton, Soni and Sarkar, and characterized in terms of breathing rate and amplitude. Respiration classification was performed through a linear support vector machine and evaluated by F1 score. RESULTS: Best F1 scores were 86.59%(lead V2) and 80.57%, when considering 12-lead and 1-lead ECGs, respectively, and using SBMM-based algorithm. CONCLUSION: ECG-derived respiratory signals allow reliable identification of different respiration types even when acquired through wearable sensors, if associated to appropriate processing algorithms, such as the SBMM-based algorithm.

Chemical Compounds and Ambient Factors Affecting Pancreatic Alpha-Cells Mass and Function: What Evidence?

The exposure to different substances present in the environment can affect the ability of the human body to maintain glucose homeostasis. Some review studies summarized the current evidence about the relationships between environment and insulin resistance or beta-cell dysfunction. Instead, no reviews focused on the relationships between the environment and the alpha cell, although in recent years clear indications have emerged for the pivotal role of the alpha cell in glucose regulation. Thus, the aim of this review was to analyze the studies about the effects of chemical, biological, and physical environmental factors on the alpha cell. Notably, we found studies focusing on the effects of different categories of compounds, including air pollutants, compounds of known toxicity present in common objects, pharmacological agents, and compounds possibly present in food, plus studies on the effects of physical factors (mainly heat exposure). However, the overall number of relevant studies was limited, especially when compared to studies related to the environment and insulin sensitivity or beta-cell function. In our opinion, this was likely due to the underestimation of the alpha-cell role in glucose homeostasis, but since such a role has recently emerged with increasing strength, we expect several new studies about the environment and alpha-cell in the near future.

Brain-on-Cloud for automatic diagnosis of Alzheimer's disease from 3D structural magnetic resonance whole-brain scans.

BACKGROUND AND OBJECTIVE: Alzheimer's disease accounts for approximately 70% of all dementia cases. Cortical and hippocampal atrophy caused by Alzheimer's disease can be appreciated easily from a T1-weighted structural magnetic resonance scan. Since a timely therapeutic intervention during the initial stages of the syndrome has a positive impact on both disease progression and quality of life of affected subjects, Alzheimer's disease diagnosis is crucial. Thus, this study relies on the development of a robust yet lightweight 3D framework, Brain-on-Cloud, dedicated to efficient learning of Alzheimer's disease-related features from 3D structural magnetic resonance whole-brain scans by improving our recent convolutional long short-term memory-based framework with the integration of a set of data handling techniques in addition to the tuning of the model hyper-parameters and the evaluation of its diagnostic performance on independent test data. METHODS: For this objective, four serial experiments were conducted on a scalable GPU cloud service. They were compared and the hyper-parameters of the best experiment were tuned until reaching the best-performing configuration. In parallel, two branches were designed. In the first branch of Brain-on-Cloud, training, validation and testing were performed on OASIS-3. In the second branch, unenhanced data from ADNI-2 were employed as independent test set, and the diagnostic performance of Brain-on-Cloud was evaluated to prove its robustness and generalization capability. The prediction scores were computed for each subject and stratified according to age, sex and mini mental state examination. RESULTS: In its best guise, Brain-on-Cloud is able to discriminate Alzheimer's disease with an accuracy of 92% and 76%, sensitivity of 94% and 82%, and area under the curve of 96% and 92% on OASIS-3 and independent ADNI-2 test data, respectively. CONCLUSIONS: Brain-on-Cloud shows to be a reliable, lightweight and easily-reproducible framework for automatic diagnosis of Alzheimer's disease from 3D structural magnetic resonance whole-brain scans, performing well without segmenting the brain into its portions. Preserving the brain anatomy, its application and diagnostic ability can be extended to other cognitive disorders. Due to its cloud nature, computational lightness and fast execution, it can also be applied in real-time diagnostic scenarios providing prompt clinical decision support.

Artificial Intelligence Methodologies Applied to Technologies for Screening, Diagnosis and Care of the Diabetic Foot: A Narrative Review.

Diabetic foot syndrome is a multifactorial pathology with at least three main etiological factors, i.e., peripheral neuropathy, peripheral arterial disease, and infection. In addition to complexity, another distinctive trait of diabetic foot syndrome is its insidiousness, due to a frequent lack of early symptoms. In recent years, it has become clear that the prevalence of diabetic foot syndrome is increasing, and it is among the diabetes complications with a stronger impact on patient's quality of life. Considering the complex nature of this syndrome, artificial intelligence (AI) methodologies appear adequate to address aspects such as timely screening for the identification of the risk for foot ulcers (or, even worse, for amputation), based on appropriate sensor technologies. In this review, we summarize the main findings of the pertinent studies in the field, paying attention to both the AI-based methodological aspects and the main physiological/clinical study outcomes. The analyzed studies show that AI application to data derived by different technologies provides promising results, but in our opinion future studies may benefit from inclusion of quantitative measures based on simple sensors, which are still scarcely exploited.