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Percutaneous coronary intervention has been a standard treatment strategy for patients with coronary artery disease with continuous ebullient progress in technology and techniques. The application of artificial intelligence and deep learning in particular is currently boosting the development of interventional solutions, improving the efficiency and objectivity of diagnosis and treatment. The ever-growing amount of data and computing power together with cutting-edge algorithms pave the way for the integration of deep learning into clinical practice, which has revolutionized the interventional workflow in imaging processing, interpretation, and navigation. This review discusses the development of deep learning algorithms and their corresponding evaluation metrics together with their clinical applications. Advanced deep learning algorithms create new opportunities for precise diagnosis and tailored treatment with a high degree of automation, reduced radiation, and enhanced risk stratification. Generalization, interpretability, and regulatory issues are remaining challenges that need to be addressed through joint efforts from multidisciplinary community., Competing Interests: This study was supported by the Natural Science Foundation of China (82020108015 and 81871460). Dr Tu reported research grants and consultancy from Pulse Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Vaccination offers health, economic, and social benefits. However, three major issues-vaccine quality, demand forecasting, and trust among stakeholders-persist in the vaccine supply chain (VSC), leading to inefficiencies. The COVID-19 pandemic has exacerbated weaknesses in the VSC, while presenting opportunities to apply digital technologies to manage it. For the first time, this study establishes an intelligent VSC management system that provides decision support for VSC management during the COVID-19 pandemic. The system combines blockchain, internet of things (IoT), and machine learning that effectively address the three issues in the VSC. The transparency of blockchain ensures trust among stakeholders. The real-time monitoring of vaccine status by the IoT ensures vaccine quality. Machine learning predicts vaccine demand and conducts sentiment analysis on vaccine reviews to help companies improve vaccine quality. The present study also reveals the implications for the management of supply chains, businesses, and government., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Inc. All rights reserved.)

Head and neck radiotherapy induces important toxicity, and its efficacy and tolerance vary widely across patients. Advancements in radiotherapy delivery techniques, along with the increased quality and frequency of image guidance, offer a unique opportunity to individualize radiotherapy based on imaging biomarkers, with the aim of improving radiation efficacy while reducing its toxicity. Various artificial intelligence models integrating clinical data and radiomics have shown encouraging results for toxicity and cancer control outcomes prediction in head and neck cancer radiotherapy. Clinical implementation of these models could lead to individualized risk-based therapeutic decision making, but the reliability of the current studies is limited. Understanding, validating and expanding these models to larger multi-institutional data sets and testing them in the context of clinical trials is needed to ensure safe clinical implementation. This review summarizes the current state of the art of machine learning models for prediction of head and neck cancer radiotherapy outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Regardless of their nature of stochasticity and uncertain nature, wind and solar resources are the most abundant energy resources used in the development of microgrid systems. In microgrid systems and distribution networks, the uncertain nature of both solar and wind resources results in power quality and system stability issues. The randomization behavior of solar and wind energy resources is controlled through the precise development of a power prediction model. Fuzzy-based solar PV and wind prediction models may more efficiently manage this randomness and uncertain character. However, this method has several drawbacks, it has limited performance when the volumes of wind and solar resources historical data are huge in size and it has also many membership functions of the fuzzy input and output variables as well as multiple fuzzy rules available. The hybrid Fuzzy-PSO intelligent prediction approach improves the fuzzy system's limitations and hence increases the prediction model's performance. The Fuzzy-PSO hybrid forecast model is developed using MATLAB programming of the particle swarm optimization (PSO) algorithm with the help of the global optimization toolbox. In this paper, an error correction factor (ECF) is considered a new fuzzy input variable. It depends on the validation and forecasted data values of both wind and solar prediction models to improve the accuracy of the prediction model. The impact of ECF is observed in fuzzy, Fuzzy-PSO, and Fuzzy-GA wind and solar PV power forecasting models. The hybrid Fuzzy-PSO prediction model of wind and solar power generation has a high degree of accuracy compared to the Fuzzy and Fuzzy-GA forecasting models. The rest of this paper is organized as: Section II is about the analysis of solar and wind resources row data. The Fuzzy-PSO prediction model problem formulation is covered in Section III. Section IV, is about the results and discussion of the study. Section V contains the conclusion. The references and abbreviations are presented at the end of the paper., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Artificial Intelligence (AI) is a mathematical process of computer mediating designing of algorithms to support human intelligence. AI in hepatology has shown tremendous promise to plan appropriate management and hence improve treatment outcomes. The field of AI is in a very early phase with limited clinical use. AI tools such as machine learning, deep learning, and 'big data ' are in a continuous phase of evolution, presently being applied for clinical and basic research. In this review, we have summarized various AI applications in hepatology, the pitfalls and AI's future implications. Different AI models and algorithms are under study using clinical, laboratory, endoscopic and imaging parameters to diagnose and manage liver diseases and mass lesions. AI has helped to reduce human errors and improve treatment protocols. Further research and validation are required for future use of AI in hepatology., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

N6-methyladenine (6mA) plays a critical role in various epigenetic processing including DNA replication, DNA repair, silencing, transcription, and diseases such as cancer. To understand such epigenetic mechanisms, 6 mA has been detected by high-throughput technologies on a genome-wide scale at single-base resolution, together with conventional methods such as immunoprecipitation, mass spectrometry and capillary electrophoresis, but these experimental approaches are time-consuming and laborious. To complement these problems, we have developed a CNN-based 6 mA site predictor, named CNN6mA, which proposed two new architectures: a position-specific 1-D convolutional layer and a cross-interactive network. In the position-specific 1-D convolutional layer, position-specific filters with different window sizes were applied to an inquiry sequence instead of sharing the same filters over all positions in order to extract the position-specific features at different levels. The cross-interactive network explored the relationships between all the nucleotide patterns within the inquiry sequence. Consequently, CNN6mA outperformed the existing state-of-the-art models in many species and created the contribution score vector that intelligibly interpret the prediction mechanism. The source codes and web application in CNN6mA are freely accessible at https://github.com/kuratahiroyuki/CNN6mA.git and http://kurata35.bio.kyutech.ac.jp/CNN6mA/, respectively., Competing Interests: All authors declare that they have no conflicts of interest., (© 2022 The Author(s).)

Background & Aims: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers., Methods: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA., Results: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples., Conclusions: Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA)., Impact and Implications: HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes., Competing Interests: At the time this study was conducted, AA, PO, JB, NvB, CM, SC, MVA, VS, TT, ST, AG, SF, LD, BF, and SB were employees and stockholders of Gilead Sciences, Inc. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

The process of designing biomolecules, in particular proteins, is witnessing a rapid change in available tooling and approaches, moving from design through physicochemical force fields, to producing plausible, complex sequences fast via end-to-end differentiable statistical models. To achieve conditional and controllable protein design, researchers at the interface of artificial intelligence and biology leverage advances in natural language processing (NLP) and computer vision techniques, coupled with advances in computing hardware to learn patterns from growing biological databases, curated annotations thereof, or both. Once learned, these patterns can be used to provide novel insights into mechanistic biology and the design of biomolecules. However, navigating and understanding the practical applications for the many recent protein design tools is complex. To facilitate this, we 1) document recent advances in deep learning (DL) assisted protein design from the last three years, 2) present a practical pipeline that allows to go from de novo -generated sequences to their predicted properties and web-powered visualization within minutes, and 3) leverage it to suggest a generated protein sequence which might be used to engineer a biosynthetic gene cluster to produce a molecular glue-like compound. Lastly, we discuss challenges and highlight opportunities for the protein design field., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CD was employed by VantAI and NVIDIA at different periods during the time of writing. MA, AG, LN are employees of VantAI. NVIDIA and VantAI had no influence on the contents of this manuscript., (© 2022 The Authors.)

Objective: To develop automated algorithms for the detection of posterior vitreous detachment (PVD) using OCT imaging., Design: Evaluation of a diagnostic test or technology., Subjects: Overall, 42 385 consecutive OCT images (865 volumetric OCT scans) obtained with Heidelberg Spectralis from 865 eyes from 464 patients at an academic retina clinic between October 2020 and December 2021 were retrospectively reviewed., Methods: We developed a customized computer vision algorithm based on image filtering and edge detection to detect the posterior vitreous cortex for the determination of PVD status. A second deep learning (DL) image classification model based on convolutional neural networks and ResNet-50 architecture was also trained to identify PVD status from OCT images. The training dataset consisted of 674 OCT volume scans (33 026 OCT images), while the validation testing set consisted of 73 OCT volume scans (3577 OCT images). Overall, 118 OCT volume scans (5782 OCT images) were used as a separate external testing dataset., Main Outcome Measures: Accuracy, sensitivity, specificity, F1-scores, and area under the receiver operator characteristic curves (AUROCs) were measured to assess the performance of the automated algorithms., Results: Both the customized computer vision algorithm and DL model results were largely in agreement with the PVD status labeled by trained graders. The DL approach achieved an accuracy of 90.7% and an F1-score of 0.932 with a sensitivity of 100% and a specificity of 74.5% for PVD detection from an OCT volume scan. The AUROC was 89% at the image level and 96% at the volume level for the DL model. The customized computer vision algorithm attained an accuracy of 89.5% and an F1-score of 0.912 with a sensitivity of 91.9% and a specificity of 86.1% on the same task., Conclusions: Both the computer vision algorithm and the DL model applied on OCT imaging enabled reliable detection of PVD status, demonstrating the potential for OCT-based automated PVD status classification to assist with vitreoretinal surgical planning., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2022 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Purpose: To compare the diagnostic accuracy and explainability of a Vision Transformer deep learning technique, Data-efficient image Transformer (DeiT), and ResNet-50, trained on fundus photographs from the Ocular Hypertension Treatment Study (OHTS) to detect primary open-angle glaucoma (POAG) and identify the salient areas of the photographs most important for each model's decision-making process., Design: Evaluation of a diagnostic technology., Subjects Participants and Controls: Overall 66 715 photographs from 1636 OHTS participants and an additional 5 external datasets of 16 137 photographs of healthy and glaucoma eyes., Methods: Data-efficient image Transformer models were trained to detect 5 ground-truth OHTS POAG classifications: OHTS end point committee POAG determinations because of disc changes (model 1), visual field (VF) changes (model 2), or either disc or VF changes (model 3) and Reading Center determinations based on disc (model 4) and VFs (model 5). The best-performing DeiT models were compared with ResNet-50 models on OHTS and 5 external datasets., Main Outcome Measures: Diagnostic performance was compared using areas under the receiver operating characteristic curve (AUROC) and sensitivities at fixed specificities. The explainability of the DeiT and ResNet-50 models was compared by evaluating the attention maps derived directly from DeiT to 3 gradient-weighted class activation map strategies., Results: Compared with our best-performing ResNet-50 models, the DeiT models demonstrated similar performance on the OHTS test sets for all 5 ground-truth POAG labels; AUROC ranged from 0.82 (model 5) to 0.91 (model 1). Data-efficient image Transformer AUROC was consistently higher than ResNet-50 on the 5 external datasets. For example, AUROC for the main OHTS end point (model 3) was between 0.08 and 0.20 higher in the DeiT than ResNet-50 models. The saliency maps from the DeiT highlight localized areas of the neuroretinal rim, suggesting important rim features for classification. The same maps in the ResNet-50 models show a more diffuse, generalized distribution around the optic disc., Conclusions: Vision Transformers have the potential to improve generalizability and explainability in deep learning models, detecting eye disease and possibly other medical conditions that rely on imaging for clinical diagnosis and management., (© 2022 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Alongside the currently used nasal swab testing, the COVID-19 pandemic situation would gain noticeable advantages from low-cost tests that are available at any-time, anywhere, at a large-scale, and with real time answers. A novel approach for COVID-19 assessment is adopted here, discriminating negative subjects versus positive or recovered subjects. The scope is to identify potential discriminating features, highlight mid and short-term effects of COVID on the voice and compare two custom algorithms. A pool of 310 subjects took part in the study; recordings were collected in a low-noise, controlled setting employing three different vocal tasks. Binary classifications followed, using two different custom algorithms. The first was based on the coupling of boosting and bagging, with an AdaBoost classifier using Random Forest learners. A feature selection process was employed for the training, identifying a subset of features acting as clinically relevant biomarkers. The other approach was centered on two custom CNN architectures applied to mel-Spectrograms, with a custom knowledge-based data augmentation. Performances, evaluated on an independent test set, were comparable: Adaboost and CNN differentiated COVID-19 positive from negative with accuracies of 100% and 95% respectively, and recovered from negative individuals with accuracies of 86.1% and 75% respectively. This study highlights the possibility to identify COVID-19 positive subjects, foreseeing a tool for on-site screening, while also considering recovered subjects and the effects of COVID-19 on the voice. The two proposed novel architectures allow for the identification of biomarkers and demonstrate the ongoing relevance of traditional ML versus deep learning in speech analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors Giovanni Costantini, Giovanni Saggio, and Antonio Pisani are advisory members of VoiceWise S.r.l., spin-off company of University of Rome Tor Vergata (Rome, Italy) developing voice analysis solutions for diagnostic purposes; Valerio Cesarini cooperates with VoiceWise and is employed by CloudWise S.r.l., a company developing cloud data storage and software solutions., (© 2022 Elsevier B.V. All rights reserved.)

Background: Loosening is the leading cause of total knee arthroplasty (TKA) revision. This is a heavy burden toward the healthcare system owing to the difficulty in diagnosis and complications occurring from the delay management. Based on automatic analytical model building, machine learning, may potentially help to automatically recognize the risk of loosening based on radiographs alone. The aim of this study was to build an image-based machine-learning model for detecting TKA loosening., Methods: Image-based machine-learning model was developed based on ImageNet, Xception model and a TKA patient X-ray image dataset. Based on a dataset with TKA patient clinical parameters, another system was then created for developing the clinical-information-based machine learning model with random forest classifier. In addition, the Xception Model was pre-trained on the ImageNet database with python and TensorFlow deep learning library for the prediction of loosening. Class activation maps were also used to interpret the prediction decision made by model. Two senior orthopaedic specialists were invited to assess loosening from X-ray images for 3 attempts in setting up comparison benchmark., Result: In the image-based machine learning loosening model, the precision rate and recall rate were 0.92 and 0.96, respectively. While for the accuracy rate, 96.3% for visualization classification was observed. However, the addition of clinical-information-based model, with precision rate of 0.71 and recall rate of 0.20, did not further showed improvement on the accuracy. Moreover, as class activation maps showed corresponding signals over bone-implant interface that is loosened radiographically, this confirms that the current model utilized a similar image recognition pattern as that of inspection by clinical specialists., Conclusion: The image-based machine learning model developed demonstrated high accuracy and predictability of knee arthroplasty loosening. And the class activation heatmap matched well with the radiographic features used clinically to detect loosening, which highlighting its potential role in assisting clinicians in their daily practice. However, addition of clinical-information-based machine-learning model did not offer further improvement in detection. As far as we know, this is the first report of pure image-based machine learning model with high detection accuracy. Importantly, this is also the first model to show relevant class activation heatmap corresponding to loosening location., Translational Potential: The finding in this study indicated image-based machine learning model can detect knee arthroplasty loosening with high accuracy and predictability, which the class activation heatmap can potentially assist surgeons to identify the sites of loosening., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2022 The Chinese University of Hong Kong.)

Fabry disease is a congenital lysosomal storage disease, and most of these cases develop organ damage in middle age. There are some promising therapeutic options for this disorder, which can stabilize the progression of the disease. However, a long delay in diagnosis prevents early intervention, resulting in treatment failure. Because Fabry disease is a rare disease, it is not well recognized and disease specific screening tests are rarely performed. Hence, a novel approach to for detecting patients with a widely practiced clinical test is crucial for the early detection of the disease. Recently, decision support systems based on artificial intelligence (AI) have been developed in many clinical fields. However, the construction of these models requires datasets from a large number of samples; this aspect is one of the main obstacles in AI-based approaches for rare diseases. In this study, with a novel image amplification method to construct the dataset for AI-model training, we built the deep neural-network model to detect Fabry cases from their urine samples. Sensitivity, specificity, and the AUC of the models on validation dataset were 0.902 (95% CI, 0.900-0.903), 0.977 (0.950-0.980), and 0.968 (0.964-0.972), respectively. This model could also extract disease-specific findings that are interpretable with human recognition. These results indicate that we can apply novel AI models for rare diseases based on this image amplification method we developed. We expect this approach could contribute to the diagnosis of Fabry disease., Synopsis: This is the first reported AI-based decision support system to detect undiagnosed Fabry cases, and our new image amplification method will contribute to the AI models for other rare disorders., Competing Interests: All authors have no conflict of interest to declare., (© 2022 The Authors. Published by Elsevier Inc.)

Objective: To characterize the utility of an existing electrocardiogram (ECG)-artificial intelligence (AI) algorithm of left ventricular dysfunction (LVD) in immune-mediated necrotizing myopathy (IMNM)., Patients and Methods: A retrospective cohort observational study was conducted within our tertiary-care neuromuscular clinic for patients with IMNM meeting European Neuromuscular Centre diagnostic criteria (January 1, 2000, to December 31, 2020). A validated AI algorithm using 12-lead standard ECGs to detect LVD was applied. The output was presented as a percent probability of LVD. Electrocardiograms before and while on immunotherapy were reviewed. The LVD-predicted probability scores were compared with echocardiograms, immunotherapy treatment response, and mortality., Results: The ECG-AI algorithm had acceptable accuracy in LVD prediction in 74% (68 of 89) of patients with IMNM with available echocardiograms (discrimination threshold, 0.74; 95% CI, 0.6-0.87). This translates into a sensitivity of 80.0% and specificity of 62.8% to detect LVD. Best cutoff probability prediction was 7 times more likely to have LVD (odds ratio, 6.75; 95% CI, 2.11-21.51; P =.001). Early detection occurred in 18% (16 of 89) of patients who initially had normal echocardiograms and were without cardiorespiratory symptoms, of which 6 subsequently advanced to LVD cardiorespiratory failure. The LVD probability scores improved for patients on immunotherapy (median slope, -3.96; R  = -0.12; P =.002). Mortality risk was 7 times greater with abnormal LVD probability scores (hazard ratio, 7.33; 95% CI, 1.63-32.88; P =.009)., Conclusion: In IMNM, an AI-ECG algorithm assists detection of LVD, enhancing the decision to advance to echocardiogram testing, while also informing on mortality risk, which is important in the decision of immunotherapy escalation and monitoring., (© 2022 The Authors.)

Purpose: Two novel deep learning methods using a convolutional neural network (CNN) and a recurrent neural network (RNN) have recently been developed to forecast future visual fields (VFs). Although the original evaluations of these models focused on overall accuracy, it was not assessed whether they can accurately identify patients with progressive glaucomatous vision loss to aid clinicians in preventing further decline. We evaluated these 2 prediction models for potential biases in overestimating or underestimating VF changes over time., Design: Retrospective observational cohort study., Participants: All available and reliable Swedish Interactive Thresholding Algorithm Standard 24-2 VFs from Massachusetts Eye and Ear Glaucoma Service collected between 1999 and 2020 were extracted. Because of the methods' respective needs, the CNN data set included 54 373 samples from 7472 patients, and the RNN data set included 24 430 samples from 1809 patients., Methods: The CNN and RNN methods were reimplemented. A fivefold cross-validation procedure was performed on each model, and pointwise mean absolute error (PMAE) was used to measure prediction accuracy. Test data were stratified into categories based on the severity of VF progression to investigate the models' performances on predicting worsening cases. The models were additionally compared with a no-change model that uses the baseline VF (for the CNN) and the last-observed VF (for the RNN) for its prediction., Main Outcome Measures: PMAE in predictions., Results: The overall PMAE 95% confidence intervals were 2.21 to 2.24 decibels (dB) for the CNN and 2.56 to 2.61 dB for the RNN, which were close to the original studies' reported values. However, both models exhibited large errors in identifying patients with worsening VFs and often failed to outperform the no-change model. Pointwise mean absolute error values were higher in patients with greater changes in mean sensitivity (for the CNN) and mean total deviation (for the RNN) between baseline and follow-up VFs., Conclusions: Although our evaluation confirms the low overall PMAEs reported in the original studies, our findings also reveal that both models severely underpredict worsening of VF loss. Because the accurate detection and projection of glaucomatous VF decline is crucial in ophthalmic clinical practice, we recommend that this consideration is explicitly taken into account when developing and evaluating future deep learning models., (© 2022 by the American Academy of Ophthalmology.)

Artificial intelligence (AI) has recently made great advances in image classification and malignancy prediction in the field of dermatology. However, understanding the applicability of AI in clinical dermatology practice remains challenging owing to the variability of models, image data, database characteristics, and variable outcome metrics. This systematic review aims to provide a comprehensive overview of dermatology literature using convolutional neural networks. Furthermore, the review summarizes the current landscape of image datasets, transfer learning approaches, challenges, and limitations within current AI literature and current regulatory pathways for approval of models as clinical decision support tools., (© 2022 The Authors.)

Purpose: A deep learning model was developed to detect nonexudative macular neovascularization (neMNV) using OCT B-scans., Design: Retrospective review of a prospective, observational study., Participants: Normal control eyes and patients with age-related macular degeneration (AMD) with and without neMNV., Methods: Swept-source OCT angiography (SS-OCTA) imaging (PLEX Elite 9000, Carl Zeiss Meditec, Inc) was performed using the 6 × 6-mm scan pattern. Individual B-scans were annotated to distinguish between drusen and the double-layer sign (DLS) associated with the neMNV. The machine learning model was tested on a dataset graded by humans, and model performance was compared with the human graders., Main Outcome Measures: Intersection over Union (IoU) score was measured to evaluate segmentation network performance. Area under the receiver operating characteristic curve values, sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were measured to assess the performance of the final classification performance. Chance-corrected agreement between the algorithm and the human grader determinations was measured with Cohen's kappa., Results: A total of 251 eyes from 210 patients, including 182 eyes with DLS and 115 eyes with drusen, were used for model training. Of 125 500 B-scans, 6879 B-scans were manually annotated. A vision transformer segmentation model was built to extract DLS and drusen from B-scans. The extracted prediction masks from all B-scans in a volume were projected to an en face image, and an eye-level projection map was obtained for each eye. A binary classification algorithm was established to identify eyes with neMNV from the projection map. The algorithm achieved 82%, 90%, 79%, and 91% sensitivity, specificity, PPV, and NPV, respectively, on a separate test set of 100 eyes that were evaluated by human graders in a previous study. The area under the curve value was calculated as 0.91 (95% confidence interval, 0.85-0.98). The results of the algorithm showed excellent agreement with the senior human grader (kappa = 0.83, P < 0.001) and moderate agreement with the junior grader consensus (kappa = 0.54, P < 0.001)., Conclusions: Our network (code is available at https://github.com/uw-biomedical-ml/double&#95;layer&#95;vit) was able to detect the presence of neMNV from structural B-scans alone by applying a purely transformer-based model., (© 2022 by the American Academy of Ophthalmology.)

Post-translational modifications (PTMs) are closely linked to numerous diseases, playing a significant role in regulating protein structures, activities, and functions. Therefore, the identification of PTMs is crucial for understanding the mechanisms of cell biology and diseases therapy. Compared to traditional machine learning methods, the deep learning approaches for PTM prediction provide accurate and rapid screening, guiding the downstream wet experiments to leverage the screened information for focused studies. In this paper, we reviewed the recent works in deep learning to identify phosphorylation, acetylation, ubiquitination, and other PTM types. In addition, we summarized PTM databases and discussed future directions with critical insights., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Poor efficacy of some anthelmintics and rising concerns about the widespread drug resistance have highlighted the need for new drug discovery. The parasitic nematode Haemonchus contortus is an important model organism widely used for studies of drug resistance and drug screening with the current gold standard being the motility assay. We applied a deep learning approach Mask R-CNN for analysing motility videos containing varying rates of motile worms and compared it to other commonly used algorithms with different levels of complexity, namely the Wiggle Index and the Wide Field-of-View Nematode Tracking Platform. Mask R-CNN consistently outperformed the other algorithms in terms of the detection of worms as well as the precision of motility forecasts, having a mean absolute percentage error of 7.6% and a mean absolute error of 5.6% for the detection and motility forecasts, respectively. Using Mask R-CNN for motility assays confirmed the common problem with algorithms that use non-maximum suppression in detecting overlapping objects, which negatively impacts the overall precision. The use of intersect over union as a measure of the classification of motile / non-motile instances had an overall accuracy of 89%, indicating that it is a viable alternative to previously used methods based on movement characteristics, such as body bends. In comparison to the existing methods evaluated here, Mask R-CNN performed better and we anticipate that this method will broaden the number of possible approaches to video analysis of worm motility., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Chest X-ray (CXR) imaging is a low-cost, easy-to-use imaging alternative that can be used to diagnose/screen pulmonary abnormalities due to infectious diseaseX: Covid-19, Pneumonia and Tuberculosis (TB). Not limited to binary decisions (with respect to healthy cases) that are reported in the state-of-the-art literature, we also consider non-healthy CXR screening using a lightweight deep neural network (DNN) with a reduced number of epochs and parameters. On three diverse publicly accessible and fully categorized datasets, for non-healthy versus healthy CXR screening, the proposed DNN produced the following accuracies: 99.87% on Covid-19 versus healthy, 99.55% on Pneumonia versus healthy, and 99.76% on TB versus healthy datasets. On the other hand, when considering non-healthy CXR screening, we received the following accuracies: 98.89% on Covid-19 versus Pneumonia, 98.99% on Covid-19 versus TB, and 100% on Pneumonia versus TB. To further precisely analyze how well the proposed DNN worked, we considered well-known DNNs such as ResNet50, ResNet152V2, MobileNetV2, and InceptionV3. Our results are comparable with the current state-of-the-art, and as the proposed CNN is light, it could potentially be used for mass screening in resource-constraint regions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Inc. All rights reserved.)

This paper proposes a time-series stochastic socioeconomic model for analyzing the impact of the pandemic on the regulated distribution electricity market. The proposed methodology combines the optimized tariff model (socioeconomic market model) and the random walk concept (risk assessment technique) to ensure robustness/accuracy. The model enables both a past and future analysis of the impact of the pandemic, which is essential to prepare regulatory agencies beforehand and allow enough time for the development of efficient public policies. By applying it to six Brazilian concession areas, results demonstrate that consumers have been/will be heavily affected in general, mainly due to the high electricity tariffs that took place with the pandemic, overcoming the natural trend of the market. In contrast, the model demonstrates that the pandemic did not/will not significantly harm power distribution companies in general, mainly due to the loan granted by the regulator agency, named COVID-account. Socioeconomic welfare losses averaging 500 (MR$/month) are estimated for the equivalent concession area, i.e., the sum of the six analyzed concession areas. Furthermore, this paper proposes a stochastic optimization problem to mitigate the impact of the pandemic on the electricity market over time, considering the interests of consumers, power distribution companies, and the government. Results demonstrate that it is successful as the tariffs provided by the algorithm compensate for the reduction in demand while increasing the socioeconomic welfare of the market., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

The coronavirus pandemic has affected people all over the world and posed a great challenge to international health systems. To aid early detection of coronavirus disease-2019 (COVID-19), this study proposes a real-time detection system based on the Internet of Things framework. The system collects real-time data from users to determine potential coronavirus cases, analyses treatment responses for people who have been treated, and accurately collects and analyses the datasets. Artificial intelligence-based algorithms are an alternative decision-making solution to extract valuable information from clinical data. This study develops a deep learning optimisation system that can work with imbalanced datasets to improve the classification of patients. A synthetic minority oversampling technique is applied to solve the problem of imbalance, and a recursive feature elimination algorithm is used to determine the most effective features. After data balance and extraction of features, the data are split into training and testing sets for validating all models. The experimental predictive results indicate good stability and compatibility of the models with the data, providing maximum accuracy of 98% and precision of 97%. Finally, the developed models are demonstrated to handle data bias and achieve high classification accuracy for patients with COVID-19. The findings of this study may be useful for healthcare organisations to properly prioritise assets., Competing Interests: The authors whose names are listed immediately below certify that they have no Affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, Employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or Materials discussed in this manuscript., (© 2022 Elsevier Ltd. All rights reserved.)

Purpose: To develop and validate an automated deep learning (DL)-based artificial intelligence (AI) platform for diagnosing and grading cataracts using slit-lamp and retroillumination lens photographs based on the Lens Opacities Classification System (LOCS) III., Design: Cross-sectional study in which a convolutional neural network was trained and tested using photographs of slit-lamp and retroillumination lens photographs., Participants: One thousand three hundred thirty-five slit-lamp images and 637 retroillumination lens images from 596 patients., Methods: Slit-lamp and retroillumination lens photographs were graded by 2 trained graders using LOCS III. Image datasets were labeled and divided into training, validation, and test datasets. We trained and validated AI platforms with 4 key strategies in the AI domain: (1) region detection network for redundant information inside data, (2) data augmentation and transfer learning for the small dataset size problem, (3) generalized cross-entropy loss for dataset bias, and (4) class balanced loss for class imbalance problems. The performance of the AI platform was reinforced with an ensemble of 3 AI algorithms: ResNet18, WideResNet50-2, and ResNext50., Main Outcome Measures: Diagnostic and LOCS III-based grading prediction performance of AI platforms., Results: The AI platform showed robust diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.9992 [95% confidence interval (CI), 0.9986-0.9998] and 0.9994 [95% CI, 0.9989-0.9998]; accuracy, 98.82% [95% CI, 97.7%-99.9%] and 98.51% [95% CI, 97.4%-99.6%]) and LOCS III-based grading prediction performance (AUC, 0.9567 [95% CI, 0.9501-0.9633] and 0.9650 [95% CI, 0.9509-0.9792]; accuracy, 91.22% [95% CI, 89.4%-93.0%] and 90.26% [95% CI, 88.6%-91.9%]) for nuclear opalescence (NO) and nuclear color (NC) using slit-lamp photographs, respectively. For cortical opacity (CO) and posterior subcapsular opacity (PSC), the system achieved high diagnostic performance (AUC, 0.9680 [95% CI, 0.9579-0.9781] and 0.9465 [95% CI, 0.9348-0.9582]; accuracy, 96.21% [95% CI, 94.4%-98.0%] and 92.17% [95% CI, 88.6%-95.8%]) and good LOCS III-based grading prediction performance (AUC, 0.9044 [95% CI, 0.8958-0.9129] and 0.9174 [95% CI, 0.9055-0.9295]; accuracy, 91.33% [95% CI, 89.7%-93.0%] and 87.89% [95% CI, 85.6%-90.2%]) using retroillumination images., Conclusions: Our DL-based AI platform successfully yielded accurate and precise detection and grading of NO and NC in 7-level classification and CO and PSC in 6-level classification, overcoming the limitations of medical databases such as few training data or biased label distribution., (© 2022 by the American Academy of Ophthalmology.)

Objectives: 1) To develop a deep learning (DL) pipeline allowing quantification of COVID-19 pulmonary lesions on low-dose computed tomography (LDCT). 2) To assess the prognostic value of DL-driven lesion quantification., Methods: This monocentric retrospective study included training and test datasets taken from 144 and 30 patients, respectively. The reference was the manual segmentation of 3 labels: normal lung, ground-glass opacity(GGO) and consolidation(Cons). Model performance was evaluated with technical metrics, disease volume and extent. Intra- and interobserver agreement were recorded. The prognostic value of DL-driven disease extent was assessed in 1621 distinct patients using C-statistics. The end point was a combined outcome defined as death, hospitalization>10 days, intensive care unit hospitalization or oxygen therapy., Results: The Dice coefficients for lesion (GGO+Cons) segmentations were 0.75±0.08, exceeding the values for human interobserver (0.70±0.08; 0.70±0.10) and intraobserver measures (0.72±0.09). DL-driven lesion quantification had a stronger correlation with the reference than inter- or intraobserver measures. After stepwise selection and adjustment for clinical characteristics, quantification significantly increased the prognostic accuracy of the model (0.82 vs. 0.90; p <0.0001)., Conclusions: A DL-driven model can provide reproducible and accurate segmentation of COVID-19 lesions on LDCT. Automatic lesion quantification has independent prognostic value for the identification of high-risk patients., Competing Interests: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (© 2022 The Authors.)

Purpose: Developing robust artificial intelligence (AI) models for medical image analysis requires large quantities of diverse, well-chosen data that can prove challenging to collect because of privacy concerns, disease rarity, or diagnostic label quality. Collecting image-based datasets for retinopathy of prematurity (ROP), a potentially blinding disease, suffers from these challenges. Progressively growing generative adversarial networks (PGANs) may help, because they can synthesize highly realistic images that may increase both the size and diversity of medical datasets., Design: Diagnostic validation study of convolutional neural networks (CNNs) for plus disease detection, a component of severe ROP, using synthetic data., Participants: Five thousand eight hundred forty-two retinal fundus images (RFIs) collected from 963 preterm infants., Methods: Retinal vessel maps (RVMs) were segmented from RFIs. PGANs were trained to synthesize RVMs with normal, pre-plus, or plus disease vasculature. Convolutional neural networks were trained, using real or synthetic RVMs, to detect plus disease from 2 real RVM test datasets., Main Outcome Measures: Features of real and synthetic RVMs were evaluated using uniform manifold approximation and projection (UMAP). Similarities were evaluated at the dataset and feature level using Fréchet inception distance and Euclidean distance, respectively. CNN performance was assessed via area under the receiver operating characteristic curve (AUC); AUCs were compared via bootstrapping and Delong's test for correlated receiver operating characteristic curves. Confusion matrices were compared using McNemar's chi-square test and Cohen's κ value., Results: The CNN trained on synthetic RVMs showed a significantly higher AUC (0.971; P = 0.006 and P  = 0.004) and classified plus disease more similarly to a set of 8 international experts (κ = 0.922) than the CNN trained on real RVMs (AUC = 0.934; κ = 0.701). Real and synthetic RVMs overlapped, by plus disease diagnosis, on the UMAP manifold, showing that synthetic images spanned the disease severity spectrum. Fréchet inception distance and Euclidean distances suggested that real and synthetic RVMs were more dissimilar to one another than real RVMs were to one another, further suggesting that synthetic RVMs were distinct from the training data with respect to privacy considerations., Conclusions: Synthetic datasets may be useful for training robust medical AI models. Furthermore, PGANs may be able to synthesize realistic data for use without protected health information concerns., (© 2022 by the American Academy of Ophthalmology.)

Clinical routine in hepatology involves the diagnosis and treatment of a wide spectrum of metabolic, infectious, autoimmune and neoplastic diseases. Clinicians integrate qualitative and quantitative information from multiple data sources to make a diagnosis, prognosticate the disease course, and recommend a treatment. In the last 5 years, advances in artificial intelligence (AI), particularly in deep learning, have made it possible to extract clinically relevant information from complex and diverse clinical datasets. In particular, histopathology and radiology image data contain diagnostic, prognostic and predictive information which AI can extract. Ultimately, such AI systems could be implemented in clinical routine as decision support tools. However, in the context of hepatology, this requires further large-scale clinical validation and regulatory approval. Herein, we summarise the state of the art in AI in hepatology with a particular focus on histopathology and radiology data. We present a roadmap for the further development of novel biomarkers in hepatology and outline critical obstacles which need to be overcome., Competing Interests: JNK declares consulting services for Owkin (France) and Panakeia (UK) and has received honoraria for scientific talks and participation in advisory boards by MSD, Eisai and Bayer. JC is a consultant for Guerbet, Bayer and Philips. VP is involved in a collaborative study with Owkin, France. DN and TPS declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Purpose: Develop computer vision models for image-based differentiation of bacterial and fungal corneal ulcers and compare their performance against human experts., Design: Cross-sectional comparison of diagnostic performance., Participants: Patients with acute, culture-proven bacterial or fungal keratitis from 4 centers in South India., Methods: Five convolutional neural networks (CNNs) were trained using images from handheld cameras collected from patients with culture-proven corneal ulcers in South India recruited as part of clinical trials conducted between 2006 and 2015. Their performance was evaluated on 2 hold-out test sets (1 single center and 1 multicenter) from South India. Twelve local expert cornea specialists performed remote interpretation of the images in the multicenter test set to enable direct comparison against CNN performance., Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) individually and for each group collectively (i.e., CNN ensemble and human ensemble)., Results: The best-performing CNN architecture was MobileNet, which attained an AUC of 0.86 on the single-center test set (other CNNs range, 0.68-0.84) and 0.83 on the multicenter test set (other CNNs range, 0.75-0.83). Expert human AUCs on the multicenter test set ranged from 0.42 to 0.79. The CNN ensemble achieved a statistically significantly higher AUC (0.84) than the human ensemble (0.76; P < 0.01). CNNs showed relatively higher accuracy for fungal (81%) versus bacterial (75%) ulcers, whereas humans showed relatively higher accuracy for bacterial (88%) versus fungal (56%) ulcers. An ensemble of the best-performing CNN and best-performing human achieved the highest AUC of 0.87, although this was not statistically significantly higher than the best CNN (0.83; P  = 0.17) or best human (0.79; P  = 0.09)., Conclusions: Computer vision models achieved superhuman performance in identifying the underlying infectious cause of corneal ulcers compared with cornea specialists. The best-performing model, MobileNet, attained an AUC of 0.83 to 0.86 without any additional clinical or historical information. These findings suggest the potential for future implementation of these models to enable earlier directed antimicrobial therapy in the management of infectious keratitis, which may improve visual outcomes. Additional studies are ongoing to incorporate clinical history and expert opinion into predictive models., (© 2022 by the American Academy of Ophthalmology.)

Many physiological processes and pathological phenomena in the liver tissue are spatially heterogeneous. At a local scale, biomarkers can be quantified along the axis of the blood flow, from portal fields (PFs) to central veins (CVs), i.e., in zonated form. This requires detecting PFs and CVs. However, manually annotating these structures in multiple whole-slide images is a tedious task. We describe and evaluate a fully automated method, based on a convolutional neural network, for simultaneously detecting PFs and CVs in a single stained section. Trained on scans of hematoxylin and eosin-stained liver tissue, the detector performed well with an F1 score of 0.81 compared to annotation by a human expert. It does, however, not generalize well to previously unseen scans of steatotic liver tissue with an F1 score of 0.59. Automated PF and CV detection eliminates the bottleneck of manual annotation for subsequent automated analyses, as illustrated by two proof-of-concept applications: We computed lobulus sizes based on the detected PF and CV positions, where results agreed with published lobulus sizes. Moreover, we demonstrate the feasibility of zonated quantification of biomarkers detected in different stainings based on lobuli and zones obtained from the detected PF and CV positions. A negative control (hematoxylin and eosin) showed the expected homogeneity, a positive control (glutamine synthetase) was quantified to be strictly pericentral, and a plausible zonation for a heterogeneous F4/80 staining was obtained. Automated detection of PFs and CVs is one building block for automatically quantifying physiologically relevant heterogeneity of liver tissue biomarkers. Perspectively, a more robust and automated assessment of zonation from whole-slide images will be valuable for parameterizing spatially resolved models of liver metabolism and to provide diagnostic information., (© 2022 The Authors.)

Viral infections represent a major health concern worldwide. The alarming rate at which SARS-CoV-2 spreads, for example, led to a worldwide pandemic. Viruses incorporate genetic material into the host genome to hijack host cell functions such as the cell cycle and apoptosis. In these viral processes, protein-protein interactions (PPIs) play critical roles. Therefore, the identification of PPIs between humans and viruses is crucial for understanding the infection mechanism and host immune responses to viral infections and for discovering effective drugs. Experimental methods including mass spectrometry-based proteomics and yeast two-hybrid assays are widely used to identify human-virus PPIs, but these experimental methods are time-consuming, expensive, and laborious. To overcome this problem, we developed a novel computational predictor, named cross-attention PHV, by implementing two key technologies of the cross-attention mechanism and a one-dimensional convolutional neural network (1D-CNN). The cross-attention mechanisms were very effective in enhancing prediction and generalization abilities. Application of 1D-CNN to the word2vec-generated feature matrices reduced computational costs, thus extending the allowable length of protein sequences to 9000 amino acid residues. Cross-attention PHV outperformed existing state-of-the-art models using a benchmark dataset and accurately predicted PPIs for unknown viruses. Cross-attention PHV also predicted human-SARS-CoV-2 PPIs with area under the curve values >0.95. The Cross-attention PHV web server and source codes are freely available at https://kurata35.bio.kyutech.ac.jp/Cross-attention&#95;PHV/ and https://github.com/kuratahiroyuki/Cross-Attention&#95;PHV, respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objectives: When diagnosing Coronavirus disease 2019(COVID-19), radiologists cannot make an accurate judgments because the image characteristics of COVID-19 and other pneumonia are similar. As machine learning advances, artificial intelligence(AI) models show promise in diagnosing COVID-19 and other pneumonias. We performed a systematic review and meta-analysis to assess the diagnostic accuracy and methodological quality of the models., Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase, preprints from medRxiv and bioRxiv to locate studies published before December 2021, with no language restrictions. And a quality assessment (QUADAS-2), Radiomics Quality Score (RQS) tools and CLAIM checklist were used to assess the quality of each study. We used random-effects models to calculate pooled sensitivity and specificity, I 2 values to assess heterogeneity, and Deeks' test to assess publication bias., Results: We screened 32 studies from the 2001 retrieved articles for inclusion in the meta-analysis. We included 6737 participants in the test or validation group. The meta-analysis revealed that AI models based on chest imaging distinguishes COVID-19 from other pneumonias: pooled area under the curve (AUC) 0.96 (95 % CI, 0.94-0.98), sensitivity 0.92 (95 % CI, 0.88-0.94), pooled specificity 0.91 (95 % CI, 0.87-0.93). The average RQS score of 13 studies using radiomics was 7.8, accounting for 22 % of the total score. The 19 studies using deep learning methods had an average CLAIM score of 20, slightly less than half (48.24 %) the ideal score of 42.00., Conclusions: The AI model for chest imaging could well diagnose COVID-19 and other pneumonias. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the quality of research methodology and further improve the generalizability of the developed predictive models., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)