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"Maini, Monika"
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Common conditions of use elements. Atomic concepts for consistent and effective information governance
2024
Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse ‘use conditions’. We report a core lexicon of terms that are atomic, non-directional ‘concepts of use’, called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.
Journal Article
SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies
by
Gopal, Robin
,
Zambon, Maria
,
Jeffery-Smith, Anna
in
Aged
,
Antibodies
,
Antibodies, Neutralizing - immunology
2022
Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2-specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer-binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein- (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2-specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.
Journal Article
Economics of Artificial Intelligence in Healthcare: Diagnosis vs. Treatment
by
Singh, Inder M.
,
Liblik, Kiera
,
Saba, Luca
in
Analysis
,
Artificial intelligence
,
Decision making
2022
Motivation: The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.
Journal Article
Cardiovascular Risk Stratification in Diabetic Retinopathy via Atherosclerotic Pathway in COVID-19/Non-COVID-19 Frameworks Using Artificial Intelligence Paradigm: A Narrative Review
by
Singh, Inder M.
,
Saba, Luca
,
Jujaray, Tanay
in
Algorithms
,
Artificial intelligence
,
Atherosclerosis
2022
Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for low-income countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, low-cost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework.
Journal Article
Vascular Implications of COVID-19: Role of Radiological Imaging, Artificial Intelligence, and Tissue Characterization: A Special Report
by
Singh, Inder M.
,
Liblik, Kiera
,
Saba, Luca
in
Artificial intelligence
,
Blood vessels
,
Cardiovascular disease
2022
The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.
Journal Article
Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review
by
Saba, Luca
,
Suri, Jasjit S
,
Al-Maini, Mustafa
in
Artificial intelligence
,
Biomarkers
,
Cardiovascular disease
2023
The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™–aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.
Journal Article
COVLIAS 1.0 vs. MedSeg: Artificial Intelligence-Based Comparative Study for Automated COVID-19 Computed Tomography Lung Segmentation in Italian and Croatian Cohorts
by
Columbu, Marta
,
Singh, Inder M.
,
Saba, Luca
in
Algorithms
,
Artificial intelligence
,
Automation
2021
(1) Background: COVID-19 computed tomography (CT) lung segmentation is critical for COVID lung severity diagnosis. Earlier proposed approaches during 2020–2021 were semiautomated or automated but not accurate, user-friendly, and industry-standard benchmarked. The proposed study compared the COVID Lung Image Analysis System, COVLIAS 1.0 (GBTI, Inc., and AtheroPointTM, Roseville, CA, USA, referred to as COVLIAS), against MedSeg, a web-based Artificial Intelligence (AI) segmentation tool, where COVLIAS uses hybrid deep learning (HDL) models for CT lung segmentation. (2) Materials and Methods: The proposed study used 5000 ITALIAN COVID-19 positive CT lung images collected from 72 patients (experimental data) that confirmed the reverse transcription-polymerase chain reaction (RT-PCR) test. Two hybrid AI models from the COVLIAS system, namely, VGG-SegNet (HDL 1) and ResNet-SegNet (HDL 2), were used to segment the CT lungs. As part of the results, we compared both COVLIAS and MedSeg against two manual delineations (MD 1 and MD 2) using (i) Bland–Altman plots, (ii) Correlation coefficient (CC) plots, (iii) Receiver operating characteristic curve, and (iv) Figure of Merit and (v) visual overlays. A cohort of 500 CROATIA COVID-19 positive CT lung images (validation data) was used. A previously trained COVLIAS model was directly applied to the validation data (as part of Unseen-AI) to segment the CT lungs and compare them against MedSeg. (3) Result: For the experimental data, the four CCs between COVLIAS (HDL 1) vs. MD 1, COVLIAS (HDL 1) vs. MD 2, COVLIAS (HDL 2) vs. MD 1, and COVLIAS (HDL 2) vs. MD 2 were 0.96, 0.96, 0.96, and 0.96, respectively. The mean value of the COVLIAS system for the above four readings was 0.96. CC between MedSeg vs. MD 1 and MedSeg vs. MD 2 was 0.98 and 0.98, respectively. Both had a mean value of 0.98. On the validation data, the CC between COVLIAS (HDL 1) vs. MedSeg and COVLIAS (HDL 2) vs. MedSeg was 0.98 and 0.99, respectively. For the experimental data, the difference between the mean values for COVLIAS and MedSeg showed a difference of <2.5%, meeting the standard of equivalence. The average running times for COVLIAS and MedSeg on a single lung CT slice were ~4 s and ~10 s, respectively. (4) Conclusions: The performances of COVLIAS and MedSeg were similar. However, COVLIAS showed improved computing time over MedSeg.
Journal Article
Deep Learning Paradigm for Cardiovascular Disease/Stroke Risk Stratification in Parkinson’s Disease Affected by COVID-19: A Narrative Review
2022
Background and Motivation: Parkinson’s disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method: The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results: We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19. Conclusion: The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.
Journal Article
Inter-Variability Study of COVLIAS 1.0: Hybrid Deep Learning Models for COVID-19 Lung Segmentation in Computed Tomography
2021
Background: For COVID-19 lung severity, segmentation of lungs on computed tomography (CT) is the first crucial step. Current deep learning (DL)-based Artificial Intelligence (AI) models have a bias in the training stage of segmentation because only one set of ground truth (GT) annotations are evaluated. We propose a robust and stable inter-variability analysis of CT lung segmentation in COVID-19 to avoid the effect of bias. Methodology: The proposed inter-variability study consists of two GT tracers for lung segmentation on chest CT. Three AI models, PSP Net, VGG-SegNet, and ResNet-SegNet, were trained using GT annotations. We hypothesized that if AI models are trained on the GT tracings from multiple experience levels, and if the AI performance on the test data between these AI models is within the 5% range, one can consider such an AI model robust and unbiased. The K5 protocol (training to testing: 80%:20%) was adapted. Ten kinds of metrics were used for performance evaluation. Results: The database consisted of 5000 CT chest images from 72 COVID-19-infected patients. By computing the coefficient of correlations (CC) between the output of the two AI models trained corresponding to the two GT tracers, computing their differences in their CC, and repeating the process for all three AI-models, we show the differences as 0%, 0.51%, and 2.04% (all < 5%), thereby validating the hypothesis. The performance was comparable; however, it had the following order: ResNet-SegNet > PSP Net > VGG-SegNet. Conclusions: The AI models were clinically robust and stable during the inter-variability analysis on the CT lung segmentation on COVID-19 patients.
Journal Article
SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies
2022
Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2-specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer-binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein- (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2-specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.
Journal Article