It is becoming increasingly emphasis on the importance of LLM participating in clinical diagnosis decision-making. However, the low specialization refers to that current medical LLMs can not provide specific medical advice, which are more like a medical Q\&A. And there is no suitable clinical guidance tree data set that can be used directly with LLM. To address this issue, we first propose LLM-executavle clinical guidance tree(CGT), which can be directly used by large language models, and construct medical diagnostic decision-making dataset (MedDM), from flowcharts in clinical practice guidelines. We propose an approach to screen flowcharts from medical literature, followed by their identification and conversion into standardized diagnostic decision trees. Constructed a knowledge base with 1202 decision trees, which came from 5000 medical literature and covered 12 hospital departments, including internal medicine, surgery, psychiatry, and over 500 diseases.Moreover, we propose a method for reasoning on LLM-executable CGT and a Patient-LLM multi-turn dialogue framework.
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Colorectal cancer (CRC) is among the top three malignant tumor types in terms of morbidity and mortality. Histopathological images are the gold standard for diagnosing colon cancer. Cellular nuclei instance segmentation and classification, and nuclear component regression tasks can aid in the analysis of the tumor microenvironment in colon tissue. Traditional methods are still unable to handle both types of tasks end-to-end at the same time, and have poor prediction accuracy and high application costs. This paper proposes a new UNet model for handling nuclei based on the UNet framework, called MGTUNet, which uses Mish, Group normalization and transposed convolution layer to improve the segmentation model, and a ranger optimizer to adjust the SmoothL1Loss values. Secondly, it uses different channels to segment and classify different types of nucleus, ultimately completing the nuclei instance segmentation and classification task, and the nuclei component regression task simultaneously. Finally, we did extensive comparison experiments using eight segmentation models. By comparing the three evaluation metrics and the parameter sizes of the models, MGTUNet obtained 0.6254 on PQ, 0.6359 on mPQ, and 0.8695 on R2. Thus, the experiments demonstrated that MGTUNet is now a state-of-the-art method for quantifying histopathological images of colon cancer.
Sparsity is a highly desired feature in deep neural networks (DNNs) since it ensures numerical efficiency, improves the interpretability of models (due to the smaller number of relevant features), and robustness. In machine learning approaches based on linear models, it is well known that there exists a connecting path between the sparsest solution in terms of the $\ell^1$ norm,i.e., zero weights and the non-regularized solution, which is called the regularization path. Very recently, there was a first attempt to extend the concept of regularization paths to DNNs by means of treating the empirical loss and sparsity ($\ell^1$ norm) as two conflicting criteria and solving the resulting multiobjective optimization problem. However, due to the non-smoothness of the $\ell^1$ norm and the high number of parameters, this approach is not very efficient from a computational perspective. To overcome this limitation, we present an algorithm that allows for the approximation of the entire Pareto front for the above-mentioned objectives in a very efficient manner. We present numerical examples using both deterministic and stochastic gradients. We furthermore demonstrate that knowledge of the regularization path allows for a well-generalizing network parametrization.
Peptides offer great biomedical potential and serve as promising drug candidates. Currently, the majority of approved peptide drugs are directly derived from well-explored natural human peptides. It is quite necessary to utilize advanced deep learning techniques to identify novel peptide drugs in the vast, unexplored biochemical space. Despite various in silico methods having been developed to accelerate peptide early drug discovery, existing models face challenges of overfitting and lacking generalizability due to the limited size, imbalanced distribution and inconsistent quality of experimental data. In this study, we propose PepGB, a deep learning framework to facilitate peptide early drug discovery by predicting peptide-protein interactions (PepPIs). Employing graph neural networks, PepGB incorporates a fine-grained perturbation module and a dual-view objective with contrastive learning-based peptide pre-trained representation to predict PepPIs. Through rigorous evaluations, we demonstrated that PepGB greatly outperforms baselines and can accurately identify PepPIs for novel targets and peptide hits, thereby contributing to the target identification and hit discovery processes. Next, we derive an extended version, diPepGB, to tackle the bottleneck of modeling highly imbalanced data prevalent in lead generation and optimization processes. Utilizing directed edges to represent relative binding strength between two peptide nodes, diPepGB achieves superior performance in real-world assays. In summary, our proposed frameworks can serve as potent tools to facilitate peptide early drug discovery.
Epilepsy is a clinical neurological disorder characterized by recurrent and spontaneous seizures consisting of abnormal high-frequency electrical activity in the brain. In this condition, the transmembrane potential dynamics are characterized by rapid and sharp wavefronts traveling along the heterogeneous and anisotropic conduction pathways of the brain. This work employs the monodomain model, coupled with specific neuronal ionic models characterizing ion concentration dynamics, to mathematically describe brain tissue electrophysiology in grey and white matter at the organ scale. This multiscale model is discretized in space with the high-order discontinuous Galerkin method on polygonal and polyhedral grids (PolyDG) and advanced in time with a Crank-Nicolson scheme. This ensures, on the one hand, efficient and accurate simulations of the high-frequency electrical activity that is responsible for epileptic seizure and, on the other hand, keeps reasonably low the computational costs by a suitable combination of high-order approximations and agglomerated polytopal meshes. We numerically investigate synthetic test cases on a two-dimensional heterogeneous squared domain discretized with a polygonal grid, and on a two-dimensional brainstem in a sagittal plane with an agglomerated polygonal grid that takes full advantage of the flexibility of the PolyDG approximation of the semidiscrete formulation. Finally, we provide a theoretical analysis of stability and an a-priori convergence analysis for a simplified mathematical problem.
We present a pipeline for unbiased and robust multimodal registration of neuroimaging modalities with minimal pre-processing. While typical multimodal studies need to use multiple independent processing pipelines, with diverse options and hyperparameters, we propose a single and structured framework to jointly process different image modalities. The use of state-of-the-art learning-based techniques enables fast inferences, which makes the presented method suitable for large-scale and/or multi-cohort datasets with a diverse number of modalities per session. The pipeline currently works with structural MRI, resting state fMRI and amyloid PET images. We show the predictive power of the derived biomarkers using in a case-control study and study the cross-modal relationship between different image modalities. The code can be found in https: //github.com/acasamitjana/JUMP.
Artificial intelligence (AI) models are increasingly used in the medical domain. However, as medical data is highly sensitive, special precautions to ensure its protection are required. The gold standard for privacy preservation is the introduction of differential privacy (DP) to model training. Prior work indicates that DP has negative implications on model accuracy and fairness, which are unacceptable in medicine and represent a main barrier to the widespread use of privacy-preserving techniques. In this work, we evaluated the effect of privacy-preserving training of AI models regarding accuracy and fairness compared to non-private training. For this, we used two datasets: (1) A large dataset (N=193,311) of high quality clinical chest radiographs, and (2) a dataset (N=1,625) of 3D abdominal computed tomography (CT) images, with the task of classifying the presence of pancreatic ductal adenocarcinoma (PDAC). Both were retrospectively collected and manually labeled by experienced radiologists. We then compared non-private deep convolutional neural networks (CNNs) and privacy-preserving (DP) models with respect to privacy-utility trade-offs measured as area under the receiver-operator-characteristic curve (AUROC), and privacy-fairness trade-offs, measured as Pearson's r or Statistical Parity Difference. We found that, while the privacy-preserving trainings yielded lower accuracy, they did largely not amplify discrimination against age, sex or co-morbidity. Our study shows that -- under the challenging realistic circumstances of a real-life clinical dataset -- the privacy-preserving training of diagnostic deep learning models is possible with excellent diagnostic accuracy and fairness.
The classification of carotid artery ultrasound images is a crucial means for diagnosing carotid plaques, holding significant clinical relevance for predicting the risk of stroke. Recent research suggests that utilizing plaque segmentation as an auxiliary task for classification can enhance performance by leveraging the correlation between segmentation and classification tasks. However, this approach relies on obtaining a substantial amount of challenging-to-acquire segmentation annotations. This paper proposes a novel weakly supervised auxiliary task learning network model (WAL-Net) to explore the interdependence between carotid plaque classification and segmentation tasks. The plaque classification task is primary task, while the plaque segmentation task serves as an auxiliary task, providing valuable information to enhance the performance of the primary task. Weakly supervised learning is adopted in the auxiliary task to completely break away from the dependence on segmentation annotations. Experiments and evaluations are conducted on a dataset comprising 1270 carotid plaque ultrasound images from Wuhan University Zhongnan Hospital. Results indicate that the proposed method achieved an approximately 1.3% improvement in carotid plaque classification accuracy compared to the baseline network. Specifically, the accuracy of mixed-echoic plaques classification increased by approximately 3.3%, demonstrating the effectiveness of our approach.
Languages have long been described according to their perceived rhythmic attributes. The associated typologies are of interest in psycholinguistics as they partly predict newborns' abilities to discriminate between languages and provide insights into how adult listeners process non-native languages. Despite the relative success of rhythm metrics in supporting the existence of linguistic rhythmic classes, quantitative studies have yet to capture the full complexity of temporal regularities associated with speech rhythm. We argue that deep learning offers a powerful pattern-recognition approach to advance the characterization of the acoustic bases of speech rhythm. To explore this hypothesis, we trained a medium-sized recurrent neural network on a language identification task over a large database of speech recordings in 21 languages. The network had access to the amplitude envelopes and a variable identifying the voiced segments, assuming that this signal would poorly convey phonetic information but preserve prosodic features. The network was able to identify the language of 10-second recordings in 40% of the cases, and the language was in the top-3 guesses in two-thirds of the cases. Visualization methods show that representations built from the network activations are consistent with speech rhythm typologies, although the resulting maps are more complex than two separated clusters between stress and syllable-timed languages. We further analyzed the model by identifying correlations between network activations and known speech rhythm metrics. The findings illustrate the potential of deep learning tools to advance our understanding of speech rhythm through the identification and exploration of linguistically relevant acoustic feature spaces.
This work is thought as an operative guide to discrete exterior calculus (DEC), but at the same time with a rigorous exposition. We present a version of (DEC) on cubic cell, defining it for discrete manifolds. An example of how it works, it is done on the discrete torus, where usual Gauss and Stokes theorems are recovered.
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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