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  1. Learning representations for individual instances when only bag-level labels are available is a fundamental challenge in multiple instance learning (MIL). Recent works have shown promising results using contrastive self-supervised learning (CSSL), which learns to push apart representations corresponding to two different randomly-selected instances. Unfortunately, in real-world applications such as medical image classification, there is often class imbalance, so randomly-selected instances mostly belong to the same majority class, which precludes CSSL from learning inter-class differences. To address this issue, we propose a novel framework, Iterative Self-paced Supervised Contrastive Learning for MIL Representations (ItS2CLR), which improves the learned representation by exploiting instance-level pseudo labels derived from the bag-level labels. The framework employs a novel self-paced sampling strategy to ensure the accuracy of pseudo labels. We evaluate ItS2CLR on three medical datasets, showing that it improves the quality of instance-level pseudo labels and representations, and outperforms existing MIL methods in terms of both bag and instance level accuracy. Code is available at this https URL 
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  2. Learning representations for individual instances when only bag-level labels are available is a fundamental challenge in multiple instance learning (MIL). Recent works have shown promising results using contrastive self-supervised learning (CSSL), which learns to push apart representations corresponding to two different randomly-selected instances. Unfortunately, in real-world applications such as medical image classification, there is often class imbalance, so randomly-selected instances mostly belong to the same majority class, which precludes CSSL from learning inter-class differences. To address this issue, we propose a novel framework, Iterative Self-paced Supervised Contrastive Learning for MIL Representations (ItS2CLR), which improves the learned representation by exploiting instance-level pseudo labels derived from the bag-level labels. The framework employs a novel self-paced sampling strategy to ensure the accuracy of pseudo labels. We evaluate ItS2CLR on three medical datasets, showing that it improves the quality of instance-level pseudo labels and representations, and outperforms existing MIL methods in terms of both bag and instance level accuracy. Code is available at https://github.com/Kangningthu/ItS2CLR 
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  3. Abstract

    Early diagnosis of Alzheimer’s disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer’s disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer’s dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer’s disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease.

     
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  4. Lung squamous cell carcinoma (LSCC) has a high recurrence and metastasis rate. Factors influencing recurrence and metastasis are currently unknown and there are no distinct histopathological or morphological features indicating the risks of recurrence and metastasis in LSCC. Our study focuses on the recurrence prediction of LSCC based on H&E-stained histopathological whole-slide images (WSI). Due to the small size of LSCC cohorts in terms of patients with available recurrence information, standard end-to-end learning with various convolutional neural networks for this task tends to overfit. Also, the predictions made by these models are hard to interpret. Histopathology WSIs are typically very large and are therefore processed as a set of smaller tiles. In this work, we propose a novel conditional self-supervised learning (SSL) method to learn representations of WSI at the tile level first, and leverage clustering algorithms to identify the tiles with similar histopathological representations. The resulting representations and clusters from self-supervision are used as features of a survival model for recurrence prediction at the patient level. Using two publicly available datasets from TCGA and CPTAC, we show that our LSCC recurrence prediction survival model outperforms both LSCC pathological stage-based approach and machine learning baselines such as multiple instance learning. The proposed method also enables us to explain the recurrence histopathological risk factors via the derived clusters. This can help pathologists derive new hypotheses regarding morphological features associated with LSCC recurrence. 
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  5. Abstract Background We previously developed and validated a predictive model to help clinicians identify hospitalized adults with coronavirus disease 2019 (COVID-19) who may be ready for discharge given their low risk of adverse events. Whether this algorithm can prompt more timely discharge for stable patients in practice is unknown. Objectives The aim of the study is to estimate the effect of displaying risk scores on length of stay (LOS). Methods We integrated model output into the electronic health record (EHR) at four hospitals in one health system by displaying a green/orange/red score indicating low/moderate/high-risk in a patient list column and a larger COVID-19 summary report visible for each patient. Display of the score was pseudo-randomized 1:1 into intervention and control arms using a patient identifier passed to the model execution code. Intervention effect was assessed by comparing LOS between intervention and control groups. Adverse safety outcomes of death, hospice, and re-presentation were tested separately and as a composite indicator. We tracked adoption and sustained use through daily counts of score displays. Results Enrolling 1,010 patients from May 15, 2020 to December 7, 2020, the trial found no detectable difference in LOS. The intervention had no impact on safety indicators of death, hospice or re-presentation after discharge. The scores were displayed consistently throughout the study period but the study lacks a causally linked process measure of provider actions based on the score. Secondary analysis revealed complex dynamics in LOS temporally, by primary symptom, and hospital location. Conclusion An AI-based COVID-19 risk score displayed passively to clinicians during routine care of hospitalized adults with COVID-19 was safe but had no detectable impact on LOS. Health technology challenges such as insufficient adoption, nonuniform use, and provider trust compounded with temporal factors of the COVID-19 pandemic may have contributed to the null result. Trial registration ClinicalTrials.gov identifier: NCT04570488. 
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  6. We show that bringing intermediate layers' representations of two augmented versions of an image closer together in self-supervised learning helps to improve the momentum contrastive (MoCo) method. To this end, in addition to the contrastive loss, we minimize the mean squared error between the intermediate layer representations or make their cross-correlation matrix closer to an identity matrix. Both loss objectives either outperform standard MoCo, or achieve similar performances on three diverse medical imaging datasets: NIH-Chest Xrays, Breast Cancer Histopathology, and Diabetic Retinopathy. The gains of the improved MoCo are especially large in a low-labeled data regime (e.g. 1% labeled data) with an average gain of 5% across three datasets. We analyze the models trained using our novel approach via feature similarity analysis and layer-wise probing. Our analysis reveals that models trained via our approach have higher feature reuse compared to a standard MoCo and learn informative features earlier in the network. Finally, by comparing the output probability distribution of models fine-tuned on small versus large labeled data, we conclude that our proposed method of pre-training leads to lower Kolmogorov-Smirnov distance, as compared to a standard MoCo. This provides additional evidence that our proposed method learns more informative features in the pre-training phase which could be leveraged in a low-labeled data regime. 
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  7. Abstract

    During the coronavirus disease 2019 (COVID-19) pandemic, rapid and accurate triage of patients at the emergency department is critical to inform decision-making. We propose a data-driven approach for automatic prediction of deterioration risk using a deep neural network that learns from chest X-ray images and a gradient boosting model that learns from routine clinical variables. Our AI prognosis system, trained using data from 3661 patients, achieves an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.745–0.830) when predicting deterioration within 96 hours. The deep neural network extracts informative areas of chest X-ray images to assist clinicians in interpreting the predictions and performs comparably to two radiologists in a reader study. In order to verify performance in a real clinical setting, we silently deployed a preliminary version of the deep neural network at New York University Langone Health during the first wave of the pandemic, which produced accurate predictions in real-time. In summary, our findings demonstrate the potential of the proposed system for assisting front-line physicians in the triage of COVID-19 patients.

     
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  8. Abstract The COVID-19 pandemic has challenged front-line clinical decision-making, leading to numerous published prognostic tools. However, few models have been prospectively validated and none report implementation in practice. Here, we use 3345 retrospective and 474 prospective hospitalizations to develop and validate a parsimonious model to identify patients with favorable outcomes within 96 h of a prediction, based on real-time lab values, vital signs, and oxygen support variables. In retrospective and prospective validation, the model achieves high average precision (88.6% 95% CI: [88.4–88.7] and 90.8% [90.8–90.8]) and discrimination (95.1% [95.1–95.2] and 86.8% [86.8–86.9]) respectively. We implemented and integrated the model into the EHR, achieving a positive predictive value of 93.3% with 41% sensitivity. Preliminary results suggest clinicians are adopting these scores into their clinical workflows. 
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