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1. Ensuring electronic medical record simulation through better training, modeling, and evaluation

   https://doi.org/10.1093/jamia/ocz161  

   Zhang, Ziqi ; Yan, Chao ; Mesa, Diego A. ; Sun, Jimeng ; Malin, Bradley A. ( October 2019 , Journal of the American Medical Informatics Association)

   Electronic medical records (EMRs) can support medical research and discovery, but privacy risks limit the sharing of such data on a wide scale. Various approaches have been developed to mitigate risk, including record simulation via generative adversarial networks (GANs). While showing promise in certain application domains, GANs lack a principled approach for EMR data that induces subpar simulation. In this article, we improve EMR simulation through a novel pipeline that (1) enhances the learning model, (2) incorporates evaluation criteria for data utility that informs learning, and (3) refines the training process.

   We propose a new electronic health record generator using a GAN with a Wasserstein divergence and layer normalization techniques. We designed 2 utility measures to characterize similarity in the structural properties of real and simulated EMRs in the original and latent space, respectively. We applied a filtering strategy to enhance GAN training for low-prevalence clinical concepts. We evaluated the new and existing GANs with utility and privacy measures (membership and disclosure attacks) using billing codes from over 1 million EMRs at Vanderbilt University Medical Center.

   The proposed model outperformed the state-of-the-art approaches with significant improvement in retaining the nature of real records, including prediction performance and structural properties, without sacrificing privacy. Additionally, the filtering strategy achieved higher utility when the EMR training dataset was small.

   These findings illustrate that EMR simulation through GANs can be substantially improved through more appropriate training, modeling, and evaluation criteria.

    

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2. Robust explanation supervision for false positive reduction in pulmonary nodule detection

   https://doi.org/10.1002/mp.16937  

   Zhao, Qilong ; Chang, Chih‐Wei ; Yang, Xiaofeng ; Zhao, Liang ( January 2024 , Medical Physics)

   Lung cancer is the deadliest and second most common cancer in the United States due to the lack of symptoms for early diagnosis. Pulmonary nodules are small abnormal regions that can be potentially correlated to the occurrence of lung cancer. Early detection of these nodules is critical because it can significantly improve the patient's survival rates. Thoracic thin‐sliced computed tomography (CT) scanning has emerged as a widely used method for diagnosing and prognosis lung abnormalities.

   The standard clinical workflow of detecting pulmonary nodules relies on radiologists to analyze CT images to assess the risk factors of cancerous nodules. However, this approach can be error‐prone due to the various nodule formation causes, such as pollutants and infections. Deep learning (DL) algorithms have recently demonstrated remarkable success in medical image classification and segmentation. As an ever more important assistant to radiologists in nodule detection, it is imperative ensure the DL algorithm and radiologist to better understand the decisions from each other. This study aims to develop a framework integrating explainable AI methods to achieve accurate pulmonary nodule detection.

   A robust and explainable detection (RXD) framework is proposed, focusing on reducing false positives in pulmonary nodule detection. Its implementation is based on an explanation supervision method, which uses nodule contours of radiologists as supervision signals to force the model to learn nodule morphologies, enabling improved learning ability on small dataset, and enable small dataset learning ability. In addition, two imputation methods are applied to the nodule region annotations to reduce the noise within human annotations and allow the model to have robust attributions that meet human expectations. The 480, 265, and 265 CT image sets from the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC‐IDRI) dataset are used for training, validation, and testing.

   Using only 10, 30, 50, and 100 training samples sequentially, our method constantly improves the classification performance and explanation quality of baseline in terms of Area Under the Curve (AUC) and Intersection over Union (IoU). In particular, our framework with a learnable imputation kernel improves IoU from baseline by 24.0% to 80.0%. A pre‐defined Gaussian imputation kernel achieves an even greater improvement, from 38.4% to 118.8% from baseline. Compared to the baseline trained on 100 samples, our method shows less drop in AUC when trained on fewer samples. A comprehensive comparison of interpretability shows that our method aligns better with expert opinions.

   A pulmonary nodule detection framework was demonstrated using public thoracic CT image datasets. The framework integrates the robust explanation supervision (RES) technique to ensure the performance of nodule classification and morphology. The method can reduce the workload of radiologists and enable them to focus on the diagnosis and prognosis of the potential cancerous pulmonary nodules at the early stage to improve the outcomes for lung cancer patients.

    

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3. Deep neural networks for wearable sensor-based activity recognition in Parkinson’s disease: investigating generalizability and model complexity

   https://doi.org/10.1186/s12938-024-01214-2  

   Davidashvilly, Shelly ; Cardei, Maria ; Hssayeni, Murtadha ; Chi, Christopher ; Ghoraani, Behnaz ( February 2024 , BioMedical Engineering OnLine)

   The research gap addressed in this study is the applicability of deep neural network (NN) models on wearable sensor data to recognize different activities performed by patients with Parkinson’s Disease (PwPD) and the generalizability of these models to PwPD using labeled healthy data.

   The experiments were carried out utilizing three datasets containing wearable motion sensor readings on common activities of daily living. The collected readings were from two accelerometer sensors. PAMAP2 and MHEALTH are publicly available datasets collected from 10 and 9 healthy, young subjects, respectively. A private dataset of a similar nature collected from 14 PwPD patients was utilized as well. Deep NN models were implemented with varying levels of complexity to investigate the impact of data augmentation, manual axis reorientation, model complexity, and domain adaptation on activity recognition performance.

   A moderately complex model trained on the augmented PAMAP2 dataset and adapted to the Parkinson domain using domain adaptation achieved the best activity recognition performance with an accuracy of 73.02%, which was significantly higher than the accuracy of 63% reported in previous studies. The model’s F1 score of 49.79% significantly improved compared to the best cross-testing of 33.66% F1 score with only data augmentation and 2.88% F1 score without data augmentation or domain adaptation.

   These findings suggest that deep NN models originating on healthy data have the potential to recognize activities performed by PwPD accurately and that data augmentation and domain adaptation can improve the generalizability of models in the healthy-to-PwPD transfer scenario. The simple/moderately complex architectures tested in this study could generalize better to the PwPD domain when trained on a healthy dataset compared to the most complex architectures used. The findings of this study could contribute to the development of accurate wearable-based activity monitoring solutions for PwPD, improving clinical decision-making and patient outcomes based on patient activity levels.

    

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4. Sensitivity analyses in longitudinal clinical trials via distributional imputation

   https://doi.org/10.1177/09622802221135251  

   Liu, Siyi ; Yang, Shu ; Zhang, Yilong ; Liu, Guanghan ( November 2022 , Statistical Methods in Medical Research)

   Missing data is inevitable in longitudinal clinical trials. Conventionally, the missing at random assumption is assumed to handle missingness, which however is unverifiable empirically. Thus, sensitivity analyses are critically important to assess the robustness of the study conclusions against untestable assumptions. Toward this end, regulatory agencies and the pharmaceutical industry use sensitivity models such as return-to-baseline, control-based, and washout imputation, following the ICH E9(R1) guidance. Multiple imputation is popular in sensitivity analyses; however, it may be inefficient and result in an unsatisfying interval estimation by Rubin’s combining rule. We propose distributional imputation in sensitivity analysis, which imputes each missing value by samples from its target imputation model given the observed data. Drawn on the idea of Monte Carlo integration, the distributional imputation estimator solves the mean estimating equations of the imputed dataset. It is fully efficient with theoretical guarantees. Moreover, we propose weighted bootstrap to obtain a consistent variance estimator, taking into account the variabilities due to model parameter estimation and target parameter estimation. The superiority of the distributional imputation framework is validated in the simulation study and an antidepressant longitudinal clinical trial.

    

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5. Ensemble Generative Adversarial Imputation Network with Selective Multi-Generator (ESM-GAIN) for Missing Data Imputation

   https://doi.org/10.1109/CASE49997.2022.9926629  

   Li, Yuxuan ; Dogan, Ayse ; Liu, Chenang ( August 2022 , 2022 IEEE 18th International Conference on Automation Science and Engineering (CASE))

   As a pervasive issue, missing data may influence the data modeling performance and lead to more difficulties of completing the desired tasks. Many approaches have been developed for missing data imputation. Recently, by taking advantage of the emerging generative adversarial network (GAN), an effective missing data imputation approach termed generative adversarial imputation nets (GAIN) was developed. However, its modeling architecture may still lead to significant imputation bias. In addition, with the GAN structure, the training process of GAIN may be unstable and the imputation variation may be high. Hence, to address these two limitations, the ensemble GAIN with selective multi-generator (ESM-GAIN) is proposed to improve the imputation accuracy and robustness. The contributions of the proposed ESM-GAIN consist of two aspects: (1) a selective multi-generation framework is proposed to identify high-quality imputations; (2) an ensemble learning framework is incorporated for GAIN imputation to improve the imputation robustness. The effectiveness of the proposed ESM-GAIN is validated by both numerical simulation and two real-world breast cancer datasets. 

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