Differential privacy preserved federated learning for prognostic modeling in COVID-19 patients using large multi-institutional chest CT dataset.

BACKGROUND: Notwithstanding the encouraging results of previous studies reporting on the efficiency of deep learning (DL) in COVID-19 prognostication, clinical adoption of the developed methodology still needs to be improved. To overcome this limitation, we set out to predict the prognosis of a large multi-institutional cohort of patients with COVID-19 using a DL-based model. PURPOSE: This study aimed to evaluate the performance of deep privacy-preserving federated learning (DPFL) in predicting COVID-19 outcomes using chest CT images. METHODS: After applying inclusion and exclusion criteria, 3055 patients from 19 centers, including 1599 alive and 1456 deceased, were enrolled in this study. Data from all centers were split (randomly with stratification respective to each center and class) into a training/validation set (70%/10%) and a hold-out test set (20%). For the DL model, feature extraction was performed on 2D slices, and averaging was performed at the final layer to construct a 3D model for each scan. The DensNet model was used for feature extraction. The model was developed using centralized and FL approaches. For FL, we employed DPFL approaches. Membership inference attack was also evaluated in the FL strategy. For model evaluation, different metrics were reported in the hold-out test sets. In addition, models trained in two scenarios, centralized and FL, were compared using the DeLong test for statistical differences. RESULTS: The centralized model achieved an accuracy of 0.76, while the DPFL model had an accuracy of 0.75. Both the centralized and DPFL models achieved a specificity of 0.77. The centralized model achieved a sensitivity of 0.74, while the DPFL model had a sensitivity of 0.73. A mean AUC of 0.82 and 0.81 with 95% confidence intervals of (95% CI: 0.79-0.85) and (95% CI: 0.77-0.84) were achieved by the centralized model and the DPFL model, respectively. The DeLong test did not prove statistically significant differences between the two models (p-value = 0.98). The AUC values for the inference attacks fluctuate between 0.49 and 0.51, with an average of 0.50 ± 0.003 and 95% CI for the mean AUC of 0.500 to 0.501. CONCLUSION: The performance of the proposed model was comparable to centralized models while operating on large and heterogeneous multi-institutional datasets. In addition, the model was resistant to inference attacks, ensuring the privacy of shared data during the training process.

The role of milk-derived exosomes in the treatment of diseases.

Exosomes (EXOs) are natural nanoparticles of endosome origin that are secreted by a variety of cells in the body. Exosomes have been found in bio-fluids such as urine, saliva, amniotic fluid, and ascites, among others. Milk is the only commercially available biological liquid containing EXOs. Proof that exosomes are essential for cell-to-cell communication is increasingly being reported. Studies have shown that they migrate from the cell of origin to various bioactive substances, including membrane receptors, proteins, mRNAs, microRNAs, and organelles, or they can stimulate target cells directly through interactions with receptors. Because of the presence of specific proteins, lipids, and RNAs, exosomes act in physiological and pathological conditions in vivo. Other salient features of EXOs include their long half-life in the body, no tumorigenesis, low immune response, good biocompatibility, ability to target cells through their surface biomarkers, and capacity to carry macromolecules. EXOs have been introduced to the scientific community as important, efficient, and attractive nanoparticles. They can be extracted from different sources and have the same characteristics as their parents. EXOs present in milk can be separated by size exclusion chromatography, density gradient centrifugation, or (ultra) centrifugation; however, the complex composition of milk that includes casein micelles and milk fat globules makes it necessary to take additional issues into consideration when employing the mentioned techniques with milk. As a rich source of EXOs, milk has unique properties that, in addition to its role as a carrier, promotes its use in treating diseases such as digestive problems, skin ulcers, and cancer, Moreover, EXOs derived from camel milk are reported to reduce the risk of oxidative stress and cancer. Milk-derived exosomes (MDEs) from yak milk improves gastrointestinal tract (GIT) development under hypoxic conditions. Furthermore, yak-MDEs have been suggested to be the best treatment for intestinal epithelial cells (IEC-6 cell line). Because of their availability as well as the non-invasiveness and cost-effectiveness of their preparation, isolates from mammals milk can be excellent resources for studies related to EXOs. These features also make it possible to exploit MDEs in clinical trials. The current study aimed to investigate the therapeutic applications of EXOs isolated from various milk sources.

Differentiating Glioblastoma Multiforme from Brain Metastases Using Multidimensional Radiomics Features Derived from MRI and Multiple Machine Learning Models.

Due to different treatment strategies, it is extremely important to differentiate between glioblastoma multiforme (GBM) and brain metastases (MET). It often proves difficult to distinguish between GBM and MET using MRI due to their similar appearance on the imaging modalities. Surgical methods are still necessary for definitive diagnosis, despite the importance of magnetic resonance imaging in detecting, characterizing, and monitoring brain tumors. We introduced an accurate, convenient, and user-friendly method to differentiate between GBM and MET through routine MRI sequence and radiomics analyses. We collected 91 patients from one institution, including 50 with GBM and 41 with MET, which were proven pathologically. The tumors separately were segmented on all MRI images (T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (T1C), T2-weighted imaging (T2WI), and fluid-attenuated inversion recovery (FLAIR)) to form the volume of interest (VOI). Eight ML models and feature reduction strategies were evaluated using routine MRI sequences (T1W, T2W, T1-CE, and FLAIR) in two methods with (second model) and without wavelet transform (first model) radiomics. The optimal model was selected based on each model's accuracy, AUC-roc, and F1-score values. In this study, we have achieved the result of 0.98, 0.99, and 0.98 percent for accuracy, AUC-roc, and F1-score, respectively, which have yielded a better result than the first model. In most investigated models, there were significant improvements in the multidimensional wavelets model compared to the non-multidimensional wavelets model. Multidimensional discrete wavelet transform can analyze hidden features of the MRI from a different perspective and generate accurate features which are highly correlated with the model accuracy.

COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients.

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.