Motivation: In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using it (NH). Results: The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Significant Wilcoxon test results confirm that incorporating historical information improves consistently predictive accuracy for treatment outcomes. The better performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in mutations, offering insights into HIV infection complexities. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. Supplementary information: Supplementary material is available.
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Bayesian parameter inference is useful to improve Li-ion battery diagnostics and can help formulate battery aging models. However, it is computationally intensive and cannot be easily repeated for multiple cycles, multiple operating conditions, or multiple replicate cells. To reduce the computational cost of Bayesian calibration, numerical solvers for physics-based models can be replaced with faster surrogates. A physics-informed neural network (PINN) is developed as a surrogate for the pseudo-2D (P2D) battery model calibration. For the P2D surrogate, additional training regularization was needed as compared to the PINN single-particle model (SPM) developed in Part I. Both the PINN SPM and P2D surrogate models are exercised for parameter inference and compared to data obtained from a direct numerical solution of the governing equations. A parameter inference study highlights the ability to use these PINNs to calibrate scaling parameters for the cathode Li diffusion and the anode exchange current density. By realizing computational speed-ups of 2250x for the P2D model, as compared to using standard integrating methods, the PINN surrogates enable rapid state-of-health diagnostics. In the low-data availability scenario, the testing error was estimated to 2mV for the SPM surrogate and 10mV for the P2D surrogate which could be mitigated with additional data.
Despite the breakthroughs in biomarker discovery facilitated by differential gene analysis, challenges remain, particularly at the single-cell level. Traditional methodologies heavily rely on user-supplied cell annotations, focusing on individually expressed data, often neglecting the critical interactions between biological conditions, such as healthy versus diseased states. In response, here we introduce scBeacon, an innovative framework built upon a deep contrastive siamese network. scBeacon pioneers an unsupervised approach, adeptly identifying matched cell populations across varied conditions, enabling a refined differential gene analysis. By utilizing a VQ-VAE framework, a contrastive siamese network, and a greedy iterative strategy, scBeacon effectively pinpoints differential genes that hold potential as key biomarkers. Comprehensive evaluations on a diverse array of datasets validate scBeacon's superiority over existing single-cell differential gene analysis tools. Its precision and adaptability underscore its significant role in enhancing diagnostic accuracy in biomarker discovery. With the emphasis on the importance of biomarkers in diagnosis, scBeacon is positioned to be a pivotal asset in the evolution of personalized medicine and targeted treatments.
Breast cancer continues to be a significant cause of mortality among women globally. Timely identification and precise diagnosis of breast abnormalities are critical for enhancing patient prognosis. In this study, we focus on improving the early detection and accurate diagnosis of breast abnormalities, which is crucial for improving patient outcomes and reducing the mortality rate of breast cancer. To address the limitations of traditional screening methods, a novel unsupervised feature correlation network was developed to predict maps indicating breast abnormal variations using longitudinal 2D mammograms. The proposed model utilizes the reconstruction process of current year and prior year mammograms to extract tissue from different areas and analyze the differences between them to identify abnormal variations that may indicate the presence of cancer. The model is equipped with a feature correlation module, an attention suppression gate, and a breast abnormality detection module that work together to improve the accuracy of the prediction. The proposed model not only provides breast abnormal variation maps, but also distinguishes between normal and cancer mammograms, making it more advanced compared to the state-of the-art baseline models. The results of the study show that the proposed model outperforms the baseline models in terms of Accuracy, Sensitivity, Specificity, Dice score, and cancer detection rate.
Pocock and Simon's minimization method is a popular approach for covariate-adaptive randomization in clinical trials. Valid statistical inference with data collected under the minimization method requires the knowledge of the limiting covariance matrix of within-stratum imbalances, whose existence is only recently established. In this work, we propose a bootstrap-based estimator for this limit and establish its consistency, in particular, by Le Cam's third lemma. As an application, we consider in simulation studies adjustments to existing robust tests for treatment effects with survival data by the proposed estimator. It shows that the adjusted tests achieve a size close to the nominal level, and unlike other designs, the robust tests without adjustment may have an asymptotic size inflation issue under the minimization method.
We extend to multi-dimensions the work of [1], where new fully explicit kinetic methods were built for the approximation of linear and non-linear convection-diffusion problems. The fundamental principles from the earlier work are retained: (1) rather than aiming for the desired equations in the strict limit of a vanishing relaxation parameter, as is commonly done in the diffusion limit of kinetic methods, diffusion terms are sought as a first-order correction of this limit in a Chapman-Enskog expansion, (2) introducing a coupling between the conserved variables within the relaxation process by a specifically designed collision matrix makes it possible to systematically match a desired diffusion. Extending this strategy to multi-dimensions cannot, however, be achieved through simple directional splitting, as diffusion is likely to couple space directions with each other, such as with shear viscosity in the Navier-Stokes equations. In this work, we show how rewriting the collision matrix in terms of moments can address this issue, regardless of the number of kinetic waves, while ensuring conservation systematically. This rewriting allows for introducing a new class of kinetic models called \emph{regularized} models, simplifying the numerical methods and establishing connections with Jin-Xin models. Subsequently, new explicit arbitrary high-order kinetic schemes are formulated and validated on standard two-dimensional cases from the literature. Excellent results are obtained in the simulation of a shock-boundary layer interaction, validating their ability to approximate the Navier-Stokes equations with kinetic speeds obeying nothing but a subcharacteristic condition along with a hyperbolic constraint on the time step.
Objective: This study aims to use artificial intelligence to realize the automatic planning of laminectomy, and verify the method. Methods: We propose a two-stage approach for automatic laminectomy cutting plane planning. The first stage was the identification of key points. 7 key points were manually marked on each CT image. The Spatial Pyramid Upsampling Network (SPU-Net) algorithm developed by us was used to accurately locate the 7 key points. In the second stage, based on the identification of key points, a personalized coordinate system was generated for each vertebra. Finally, the transverse and longitudinal cutting planes of laminectomy were generated under the coordinate system. The overall effect of planning was evaluated. Results: In the first stage, the average localization error of the SPU-Net algorithm for the seven key points was 0.65mm. In the second stage, a total of 320 transverse cutting planes and 640 longitudinal cutting planes were planned by the algorithm. Among them, the number of horizontal plane planning effects of grade A, B, and C were 318(99.38%), 1(0.31%), and 1(0.31%), respectively. The longitudinal planning effects of grade A, B, and C were 622(97.18%), 1(0.16%), and 17(2.66%), respectively. Conclusions: In this study, we propose a method for automatic surgical path planning of laminectomy based on the localization of key points in CT images. The results showed that the method achieved satisfactory results. More studies are needed to confirm the reliability of this approach in the future.
Recent years have seen increasing efforts to forecast infectious disease burdens, with a primary goal being to help public health workers make informed policy decisions. However, there has only been limited discussion of how predominant forecast evaluation metrics might indicate the success of policies based in part on those forecasts. We explore one possible tether between forecasts and policy: the allocation of limited medical resources so as to minimize unmet need. We use probabilistic forecasts of disease burden in each of several regions to determine optimal resource allocations, and then we score forecasts according to how much unmet need their associated allocations would have allowed. We illustrate with forecasts of COVID-19 hospitalizations in the US, and we find that the forecast skill ranking given by this allocation scoring rule can vary substantially from the ranking given by the weighted interval score. We see this as evidence that the allocation scoring rule detects forecast value that is missed by traditional accuracy measures and that the general strategy of designing scoring rules that are directly linked to policy performance is a promising direction for epidemic forecast evaluation.
Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.
Graph representation learning for hypergraphs can be used to extract patterns among higher-order interactions that are critically important in many real world problems. Current approaches designed for hypergraphs, however, are unable to handle different types of hypergraphs and are typically not generic for various learning tasks. Indeed, models that can predict variable-sized heterogeneous hyperedges have not been available. Here we develop a new self-attention based graph neural network called Hyper-SAGNN applicable to homogeneous and heterogeneous hypergraphs with variable hyperedge sizes. We perform extensive evaluations on multiple datasets, including four benchmark network datasets and two single-cell Hi-C datasets in genomics. We demonstrate that Hyper-SAGNN significantly outperforms the state-of-the-art methods on traditional tasks while also achieving great performance on a new task called outsider identification. Hyper-SAGNN will be useful for graph representation learning to uncover complex higher-order interactions in different applications.
Radiologist is "doctor's doctor", biomedical image segmentation plays a central role in quantitative analysis, clinical diagnosis, and medical intervention. In the light of the fully convolutional networks (FCN) and U-Net, deep convolutional networks (DNNs) have made significant contributions in biomedical image segmentation applications. In this paper, based on U-Net, we propose MDUnet, a multi-scale densely connected U-net for biomedical image segmentation. we propose three different multi-scale dense connections for U shaped architectures encoder, decoder and across them. The highlights of our architecture is directly fuses the neighboring different scale feature maps from both higher layers and lower layers to strengthen feature propagation in current layer. Which can largely improves the information flow encoder, decoder and across them. Multi-scale dense connections, which means containing shorter connections between layers close to the input and output, also makes much deeper U-net possible. We adopt the optimal model based on the experiment and propose a novel Multi-scale Dense U-Net (MDU-Net) architecture with quantization. Which reduce overfitting in MDU-Net for better accuracy. We evaluate our purpose model on the MICCAI 2015 Gland Segmentation dataset (GlaS). The three multi-scale dense connections improve U-net performance by up to 1.8% on test A and 3.5% on test B in the MICCAI Gland dataset. Meanwhile the MDU-net with quantization achieves the superiority over U-Net performance by up to 3% on test A and 4.1% on test B.
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