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      Development and external validation of a mixed-effects deep learning model to diagnose COVID-19 from CT imaging

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          Abstract

          Background

          The automatic analysis of medical images has the potential improve diagnostic accuracy while reducing the strain on clinicians. Current methods analyzing 3D-like imaging data, such as computerized tomography imaging, often treat each image slice as individual slices. This may not be able to appropriately model the relationship between slices.

          Methods

          Our proposed method utilizes a mixed-effects model within the deep learning framework to model the relationship between slices. We externally validated this method on a data set taken from a different country and compared our results against other proposed methods. We evaluated the discrimination, calibration, and clinical usefulness of our model using a range of measures. Finally, we carried out a sensitivity analysis to demonstrate our methods robustness to noise and missing data.

          Results

          In the external geographic validation set our model showed excellent performance with an AUROC of 0.930 (95%CI: 0.914, 0.947), with a sensitivity and specificity, PPV, and NPV of 0.778 (0.720, 0.828), 0.882 (0.853, 0.908), 0.744 (0.686, 0.797), and 0.900 (0.872, 0.924) at the 0.5 probability cut-off point. Our model also maintained good calibration in the external validation dataset, while other methods showed poor calibration.

          Conclusion

          Deep learning can reduce stress on healthcare systems by automatically screening CT imaging for COVID-19. Our method showed improved generalizability in external validation compared to previous published methods. However, deep learning models must be robustly assessed using various performance measures and externally validated in each setting. In addition, best practice guidelines for developing and reporting predictive models are vital for the safe adoption of such models.

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          Most cited references50

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          Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

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            pROC: an open-source package for R and S+ to analyze and compare ROC curves

            Background Receiver operating characteristic (ROC) curves are useful tools to evaluate classifiers in biomedical and bioinformatics applications. However, conclusions are often reached through inconsistent use or insufficient statistical analysis. To support researchers in their ROC curves analysis we developed pROC, a package for R and S+ that contains a set of tools displaying, analyzing, smoothing and comparing ROC curves in a user-friendly, object-oriented and flexible interface. Results With data previously imported into the R or S+ environment, the pROC package builds ROC curves and includes functions for computing confidence intervals, statistical tests for comparing total or partial area under the curve or the operating points of different classifiers, and methods for smoothing ROC curves. Intermediary and final results are visualised in user-friendly interfaces. A case study based on published clinical and biomarker data shows how to perform a typical ROC analysis with pROC. Conclusions pROC is a package for R and S+ specifically dedicated to ROC analysis. It proposes multiple statistical tests to compare ROC curves, and in particular partial areas under the curve, allowing proper ROC interpretation. pROC is available in two versions: in the R programming language or with a graphical user interface in the S+ statistical software. It is accessible at http://expasy.org/tools/pROC/ under the GNU General Public License. It is also distributed through the CRAN and CSAN public repositories, facilitating its installation.
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              Adam: A Method for Stochastic Optimization

              We introduce Adam, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. The method is straightforward to implement, is computationally efficient, has little memory requirements, is invariant to diagonal rescaling of the gradients, and is well suited for problems that are large in terms of data and/or parameters. The method is also appropriate for non-stationary objectives and problems with very noisy and/or sparse gradients. The hyper-parameters have intuitive interpretations and typically require little tuning. Some connections to related algorithms, on which Adam was inspired, are discussed. We also analyze the theoretical convergence properties of the algorithm and provide a regret bound on the convergence rate that is comparable to the best known results under the online convex optimization framework. Empirical results demonstrate that Adam works well in practice and compares favorably to other stochastic optimization methods. Finally, we discuss AdaMax, a variant of Adam based on the infinity norm. Published as a conference paper at the 3rd International Conference for Learning Representations, San Diego, 2015
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                23 August 2023
                2023
                23 August 2023
                : 10
                : 1113030
                Affiliations
                [1] 1Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, United Kingdom
                [2] 2Department of Respiratory Medicine, Liverpool Heart and Chest Hospital NHS Foundation Trust , Liverpool, United Kingdom
                [3] 3Department of Radiology, Liverpool Heart and Chest Hospital NHS Foundation Trust , Liverpool, United Kingdom
                [4] 4Advanced Research Computing, University of Liverpool , Liverpool, United Kingdom
                [5] 5Alces Flight Limited , Bicester, United Kingdom
                [6] 6Amazon Web Services , London, United Kingdom
                [7] 7Department of Radiology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Hubei University of Chinese Medicine , Wuhan, China
                [8] 8Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences , Ningbo, China
                Author notes

                Edited by: Jinming Duan, University of Birmingham, United Kingdom

                Reviewed by: Yuexiang Li, Tencent Jarvis Lab, China; Fei He, Coventry University, United Kingdom

                *Correspondence: Yalin Zheng, Yalin.Zheng@ 123456liverpool.ac.uk
                Article
                10.3389/fmed.2023.1113030
                10481527
                37680621
                8537e386-81e7-4572-8bad-5071339493c9
                Copyright © 2023 Bridge, Meng, Zhu, Fitzmaurice, McCann, Addison, Wang, Merritt, Franks, Mackey, Messenger, Sun, Zhao and Zheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 November 2022
                : 08 August 2023
                Page count
                Figures: 12, Tables: 5, Equations: 10, References: 53, Pages: 16, Words: 9979
                Categories
                Medicine
                Original Research
                Custom metadata
                Nuclear Medicine

                ct,covid-19,deep learning,diagnosis,imaging
                ct, covid-19, deep learning, diagnosis, imaging

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