By generating massive gene transcriptome data and analyzing transcriptomic variations at the cell level, single-cell RNA-sequencing (scRNA-seq) technology has provided new way to explore cellular heterogeneity and functionality. Clustering scRNA-seq data could discover the hidden diversity and complexity of cell populations, which can aid to the identification of the disease mechanisms and biomarkers. In this paper, a novel method (DSINMF) is presented for clustering single cell RNA sequencing data by using deep matrix factorization. Our proposed method comprises four steps: first, the feature selection is utilized to remove irrelevant features. Then, the dropout imputation is used to handle missing value problem. Further, the dimension reduction is employed to preserve data characteristics and reduce noise effects. Finally, the deep matrix factorization with bi-stochastic graph regularization is used to obtain cluster results from scRNA-seq data. We compare DSINMF with other state-of-the-art algorithms on nine datasets and the results show our method outperformances than other methods. The code can be downloaded from https://github.com/lanbiolab/DSINMF.

Brain disorders are associated with impairments in cognitive and social functioning, placing a substantial burden on families, healthcare systems, and communities. However, accurate diagnosis remains challenging due to complex higher order interactions among brain regions. Existing graph-based methods are largely limited to pairwise connectivity. In addition, these methods often fail to fully exploit well-established neuroscientific prior knowledge, resulting in limited biological interpretability and suboptimal diagnostic performance. Therefore, we propose a prior knowledge-guided adaptive hypergraph learning (PK-AHGL) framework that represents individual-level functional connectivity networks as hypergraphs to capture higher order multiregion interactions while incorporating neuroscientific prior knowledge for brain disorder diagnosis. PK-AHGL consists of three key modules: 1) an adaptive hypergraph convolution module. Unlike traditional hypergraph neural networks that use static hyperedge weights, this module adaptively learns the weights of different hyperedges; 2) a sparse affinity Laplacian module. Key brain regions are extracted from disorder related functional brain networks and used as prior knowledge. Based on these regions, we compute a hyperedge similarity matrix that encourages similar hyperedges to have similar weights; and 3) a proportional margin ranking module. This module further utilizes prior knowledge by guiding hyperedges containing a higher proportion of key brain regions to obtain larger weights. Experiments on autism brain imaging data exchange (ABIDE), Strategic Research Program for the Promotion of Brain Science (SRPBS)-schizophrenia (SCZ), SRPBS-major depressive disorder (MDD), and Alzheimer’s disease neuroimaging initiative (ADNI) show that PK-AHGL achieves accuracies of 75.78%, 82.66%, 74.89%, and 77.22%, respectively, outperforming multiple state-of-the-art methods. These results suggest that PK-AHGL provides an effective auxiliary tool for brain disorder diagnosis and may support community-oriented mental health services.

Survival risk prediction is crucial for personalized treatment of gliomas. Medical image foundational models can explore complex medical features, which are critical for prognosis in gliomas. We propose SAM-Risk, which uses a customized SAM-Med3D with multi-view representation fusion and clinical knowledge-based age-grade stratified loss for glioma survival risk prediction. First, to utilize potential interactions between multiple views at an early stage, we design a 3D representation generation module that transforms 1D handcrafted radiomics and clinical features into 3D representations, which are fused with multimodal MRIs through a multi-view representation fusion module. The fused representation is fed into the customized SAM-Med3D, fine-tuned using LoRA and a disparity function to extract survival risk-related features. We design a feature refinement module to explore the inter-channel relationships among the outputs of the fine-tuned SAM-Med3D. Additionally, we propose an age-grade stratified loss based on glioma prognosis standards to make the predicted risk more consistent with clinical prior knowledge. Validated on two publicly available UCSF-PDGM and BraTS2020 datasets, SAM-Risk achieves a C-index of 75.08% and 73.67%, respectively, outperforming several survival risk prediction methods.

Lung diseases represent a significant global health challenge, with Chest X-Ray (CXR) being a key diagnostic tool due to its accessibility and affordability. Nonetheless, the detection of pulmonary lesions is often hindered by overlapping bone structures in CXR images, leading to potential misdiagnoses. To address this issue, we develop an end-to-end framework called BS-LDM, designed to effectively suppress bone in high-resolution CXR images. This framework is based on conditional latent diffusion models and incorporates a multi-level hybrid loss-constrained vector-quantized generative adversarial network which is crafted for perceptual compression, ensuring the preservation of details. To further enhance the framework's performance, we utilize offset noise in the forward process, and a temporal adaptive thresholding strategy in the reverse process. These additions help minimize discrepancies in generating low-frequency information of soft tissue images. Additionally, we have compiled a high-quality bone suppression dataset named SZCH-X-Rays. This dataset includes 818 pairs of high-resolution CXR and soft tissue images collected from our partner hospital. Moreover, we processed 241 data pairs from the JSRT dataset into negative images, which are more commonly used in clinical practice. Our comprehensive experiments and downstream evaluations reveal that BS-LDM excels in bone suppression, underscoring its clinical value.

Incoherent k-space undersampling and deep learning-based reconstruction methods have shown great success in accelerating MRI. However, the performance of most previous methods will degrade dramatically under high acceleration factors, e.g., $8\times $ or higher. Recently, denoising diffusion models (DM) have demonstrated promising results in solving this issue; however, one major drawback of the DM methods is the long inference time due to a dramatic number of iterative reverse posterior sampling steps. In this work, a Single Step Diffusion Model-based reconstruction framework, namely SSDM-MRI, is proposed for restoring MRI images from highly undersampled k-space. The proposed method achieves one-step reconstruction by first training a conditional DM and then iteratively distilling this model four times using an iterative selective distillation algorithm, which works synergistically with a shortcut reverse sampling strategy for model inference. Comprehensive experiments were carried out on both publicly available fastMRI brain and knee images, as well as an in-house multi-echo GRE (QSM) subject. Overall, the results showed that SSDM-MRI outperformed other methods in terms of numerical metrics (e.g., PSNR and SSIM), error maps, image fine details, and latent susceptibility information hidden in MRI phase images. In addition, the reconstruction time for a ${320}\times {320}$ brain slice of SSDM-MRI is only 0.45 second, which is only comparable to that of a simple U-net, making it a highly effective solution for MRI reconstruction tasks.

The diverse applications of internet of things (IoT) have significantly increased the demand for efficient and reliable wireless networks, making power consumption a critical concern. Reconfigurable intelligent surface (RIS) have been proposed as a solution to mitigate power consumption in wireless communication systems by dynamically adjusting the signal propagation direction between transmitters and receivers. Due to the operational status of IoT devices and the complex association relationships between RISs and devices, a dynamic and highly variable communication environment is typically resulted, which renders power consumption optimization more challenging, as compared to conventional methods that do not incorporate RISs. This paper addresses the optimization of power consumption and IoT device coverage rate in an indoor communication scenario to improve system performance. We design an Adaptive Hybrid Optimization Strategy based on the association between RISs and devices to maximize the device coverage rate. Additionally, we optimize the phase shifts of multiple RISs to minimize system power consumption using the relaxation transformative method while satisfying the coverage rate constraint. Extensive simulation results demonstrate that, in an indoor environment with several obstacles, the proposed algorithm achieves a higher device-centric coverage rate compared to a solution without RIS and exhibits lower power consumption compared to strategies that rely more on base stations.

Accurately predicting isocitrate dehydrogenase (IDH) mutations is crucial for glioma diagnosis, but the limited availability of multimodal MRI restricts the generalization of existing methods. Fine-tuning foundation models is a common solution, yet their lack of domain-specific knowledge often impairs optimal performance. Clinical studies show that both the imagemodal T2-FLAIR mismatch sign knowledge and text-modal demographic information are useful for IDH genotyping. Thus, we propose a novel network that integrates multimodal clinical knowledge to guide the fine-tuning of the multimodal foundation model M3D for glioma IDH genotyping on multimodal MRI. To fully utilize multimodal knowledge, we first extract multigranularity T2-FLAIR mismatch features from different layers via a Mixture-of-Experts (MoE) pool-based mismatch adapter (incorporating an MoE-based pooling mechanism and a spatialchannel mismatch attention module). Meanwhile, demographic information is converted into text prompts and encoded by the M3D text encoder to generate demographic-based text embeddings. In the encoder, T2-FLAIR mismatch features are integrated at the end of each ViT Block to introduce imagingspecific knowledge, while text features are further processed via a cross-modal text-image attention fusion adapter to enhance representation learning in the joint feature space. We evaluated the approach on an internal dataset (from 3 public datasets, 871 patients) and an independent external dataset (501 patients). It achieved 93.25 % accuracy on the internal dataset and 86.03 % on the external dataset, with only$\mathbf{2. 6 7 M}$trainable parameters, outperforming 7 existing state-of-the-art IDH genotyping methods.

Deformable image registration is fundamental in medical image analysis. Existing pyramid-based deep learning methods suffer from coarse deformation decomposition, poor inter-level transitions, and error accumulation. To address these, we propose GMReg, an unsupervised pyramid network for medical image registration based on Mamba correlation. GMReg introduces intra-level multi-scale decomposition: each pyramid level splits deformation fields into subfields with different receptive fields via grouping, using Group Mamba correlation layers for feature matching/fusion, and convolutional prediction for sub-fields. A channel attention-based context fusion module enhances inter-group interaction, while a multi-scale edge enhancement module guides subfield fusion to improve boundary sensitivity. Experiments on two public brain MRI datasets (LPBA40, Mind-Boggle) show GMReg significantly outperforms state-of-the-art methods in registration accuracy. Additionally, results on the FIRE dataset demonstrate that GMReg also holds potential for the fundus image registration task.

Millimeter-wave radar, with its ease of deployment and around-the-clock operation, has become widely adopted for monitoring daily human activities in mobile health. Human activity recognition (HAR) models trained on collected radar data enable persistent detection of critical incidents such as falls, which is critical for reducing in-home care costs and improving healthcare resource utilization efficiency. However, radar signals are easily disrupted by environmental variations, causing models trained in one setting to generalize poorly when applied to new environment. To address this challenge, we propose a radar-based cross-environment unsupervised domain adaptation (UDA) method, which significantly enhances generalization performance in unlabeled target domains (new environment) by leveraging fully labeled source domain data (historical environment). Our approach comprises two key components: a feature fusion module and a knowledge distillation module. First, the feature fusion module employs an attention mechanism to perform weighted linear interpolation between source domain and target domain features and uses an alignment loss to learn a shared feature rep-resentation robust to environmental changes. Next, temperature-scaled knowledge distillation generates soft pseudo labels for unlabeled target domain samples, improving the model's dis-criminatory power without ground-truth annotations. Evaluated on twelve cross-environment HAR tasks, the proposed method achieves an average recognition accuracy of 94.19%, offering an efficient and reliable solution for radar-based mobile health monitoring.

Large language models (LLMs) are increasingly being adopted to develop general-purpose AI agents. However, it remains challenging for these LLM-based AI agents to efficiently learn from feedback and iteratively optimize their strategies. To address this challenge, tremendous efforts have been dedicated to designing diverse feedback mechanisms for LLM-based AI agents. To provide a comprehensive overview of this rapidly evolving field, this paper presents a systematic review of these studies, offering a holistic perspective on the feedback mechanisms in LLM-based AI agents. We begin by discussing the construction of LLM-based AI agents, introducing a generalized framework that encapsulates much of the existing work. Next, we delve into the exploration of feedback mechanisms, categorizing them into four distinct types: internal feedback, external feedback, multi-agent feedback, and human feedback. Additionally, we provide an overview of evaluation protocols and benchmarks specifically tailored for LLM-based AI agents. Finally, we highlight the significant challenges and identify potential directions for future studies. The relevant papers are summarized and will be consistently updated at https://github.com/kevinson7515/Agents-Feedback-Mechanisms.

The use of estimators instead of stochastic gradients for updates has been shown to improve algorithm convergence rates of, but their impact on generalization remains under-explored. In this paper, we investigate how estimators influence generalization. Our focus is on two widely studied problems: stochastic optimization (SO) and stochastic compositional optimization (SCO), both under convex and non-convex settings. For SO problems, we first analyze the generalization error of the STORM algorithm as a foundational step. We then extend our analysis to SCO problems by introducing an algorithmic framework that encompasses several popular algorithmic approaches. Through this framework, we conduct a generalization analysis, uncovering new insights into the impact of estimators on generalization. Subsequently, we provide a detailed analysis of three specific algorithms within this framework: SCGD, SCSC, and COVER, to explore the effects of different estimator strategies. Furthermore, in the context of SCO, we propose a novel definition of stability and a new decomposition of excess risk in the non-convex setting. Our analysis indicates two key findings: (1) In SCO problems, eliminating the estimator for the gradient of the inner function does not impact generalization performance while significantly reducing computational and storage overhead. (2) Faster convergence rates are consistently associated with better generalization performance.

Graph learning-based multi-modal integration and classification is one of the most challenging tasks for disease prediction. To effectively offset the negative impact among modalities in the process of multi-modal integration and heterogeneous information extractions from graphs, we propose a novel method called Multi-modal Multi-Kernel Graph Learning (MMKGL). To solve the problem of negative impact among modalities, we propose a multi-modal graph embedding module to construct a multi-modal graph. Different from conventional methods that manually construct static graphs for all modalities, each modality generates a separate graph by adaptive learning, where a function graph and a supervision graph are introduced for optimization during the multi-graph fusion embedding process. We then propose a multi-kernel graph learning module to extract heterogeneous information from the multi-modal graph. The information in the multi-modal graph at different levels is aggregated by convolutional kernels with different receptive field sizes, followed by generating a cross-kernel discovery tensor for disease prediction. Our method is evaluated on the benchmark Autism Brain Imaging Data Exchange (ABIDE) dataset and outperforms the state-of-the-art methods. In addition, discriminative brain regions associated with autism are identified by our model, providing guidance for the study of autism pathology.

Pathological diagnosis assists in saving human lives, but such models are annotation hungry and pathological images are notably expensive to annotate. Contrastive learning could be a promising solution that relies only on the unlabeled training data to generate informative representations. However, the majority of current methods in contrastive learning have the following two issues: (1) positive samples produced through random augmentation are less challenging, and (2) false negative pairs problem caused by negative sampling bias. To alleviate the above issues, we propose a novel contrastive learning method called Cluster-Aware Adversarial Contrastive Learning (CA2CL). Specifically, a mixed data augmentation technique is provided to learn more transferable representations by generating more discriminative sample pairs. Furthermore, to mitigate the effects of inherent false negative pairs, we adopt a cluster-aware loss to identify similarities between instances and incorporate them into the process of contrastive learning. Finally, we generate challenging contrastive data pairs by adversarial learning, and adversarially learn robust representations in the representation space without the labeled training data, which aims to maximize the similarity between the augmented sample and the related adversarial sample. Our proposed CA2CL is evaluated on two public datasets: NCT-CRC-HE and PCam for the fine-tuning and linear evaluation tasks and on two other public datasets: GlaS and CARG for the detection and segmentation tasks, respectively. Extensive experimental results demonstrate the superior performance improvement of our method over several Self-supervised learning (SSL) methods and ImageNet pretraining particularly in scenarios with limited data availability for all four tasks.

Functional Magnetic Resonance Imaging (fMRI) is used for extracting blood oxygen signals from brain regions to map brain functional connectivity for brain disease prediction. Despite its effectiveness, fMRI has not been widely used: on the one hand, collecting and labeling the data is time-consuming and costly, which limits the amount of valid data collected at a single healthcare site; on the other hand, integrating data from multiple sites is challenging due to data privacy restrictions. To address these issues, we propose a novel, integrated Federated learning and Split learning Spatio-temporal Graph framework (F G). Specifically, we introduce federated learning and split learning techniques to split a spatio-temporal model into a client temporal model and a server spatial model. In the client temporal model, we propose a time-aware mechanism to focus on changes in brain functional states and use an InceptionTime model to extract information about changes in the brain states of each subject. In the server spatial model, we propose a united graph convolutional network to integrate multiple graph convolutional networks. Integrating federated learning and split learning, F G can utilize multi-site fMRI data without violating data privacy protection and reduce the risk of overfitting as it is capable of learning from limited training data sets. Moreover, it boosts the extraction of spatio-temporal features of fMRI using spatio-temporal graph networks. Experiments on ABIDE and ADHD200 datasets demonstrate that our proposed method outperforms state-of-the-art methods. In addition, we explore biomarkers associated with brain disease prediction using community discovery algorithms using intermediate results of F G. The source code is available at https://github.com/yutian0315/FS2G.

This paper delves into the realm of stochastic optimization for compositional minimax optimization—a pivotal challenge across various machine learning domains, including deep AUC and reinforcement learning policy evaluation. Despite its significance, the problem of compositional minimax optimization is still under-explored. Adding to the complexity, current methods of compositional minimax optimization are plagued by sub-optimal complexities or heavy reliance on sizable batch sizes. To respond to these constraints, this paper introduces a novel method, called Nested STOchastic Recursive Momentum (NSTORM), which can achieve the optimal sample complexity and obtain the nearly accuracy solution, matching the existing minimax methods. We also demonstrate that NSTORM can achieve the same sample complexity under the Polyak-Lojasiewicz (PL)-condition—an insightful extension of its capabilities. Yet, NSTORM encounters an issue with its requirement for low learning rates, potentially constraining its real-world applicability in machine learning. To overcome this hurdle, we present ADAptive NSTORM (ADA-NSTORM) with adaptive learning rates. We demonstrate that ADA-NSTORM can achieve the same sample complexity but the experimental results show its more effectiveness. All the proposed complexities indicate that our proposed methods can match lower bounds to existing minimax optimizations, without requiring a large batch size in each iteration. Extensive experiments support the efficiency of our proposed methods.

In recent years, the increasing number of individuals diagnosed with depression and the growing awareness of its impact on modern society have highlighted the significance of accurate depression diagnosis. Microarray data has played a crucial role in uncovering the genetic mechanisms underlying depression. However, existing methods for depression prediction using microarray data often rely on the selection of differentially expressed genes. This approach disregards important information from other genes and is susceptible to batch effects, thereby limiting generalizability and model stability. To address these limitations, we propose DP-BERT, a depression prediction model based on Bidirectional Encoder Representations from Transformers (BERT). DP-BERT follows a pre-training and fine-tuning paradigm, leveraging a large amount of unlabeled microarray data from diverse sequencing platforms for pretraining to extract comprehensive genetic-level representations of psychiatric disorders. Subsequently, supervised fine-tuning is performed for depression prediction. Experimental results demonstrate that the pre-trained model achieves superior performance in depression prediction. The source code can be obtained from https://github.com/CSUBioGroup/DP-BERT.

Sleep posture identification is crucial for accurately assessing sleep quality and diagnosing related diseases. In the realm of non-intrusive sleep monitoring, non-contact technologies are becoming increasingly mainstream. Millimeter-wave radar is frequently utilized in sleep posture identification due to its high resolution, strong penetration, and excellent sensitivity. However, traditional radar-based methods for sleep posture identification often struggle with reliability when dealing with diverse individuals and complex sleep environments. To address these challenges, we propose UniSleepPos, which designs a novel dual-view fusion mechanism to integrate depression and elevation angle signals obtained from radar, thus accurately capturing the posture information of the monitored subject in three-dimensional space. Furthermore, we combine sleep posture identification with individual characteristics, utilizing existing individual labels as prior knowledge to assist in sleep posture identification. The integration of prior knowledge provides a valuable information source for the model, helping to enhance its understanding of the data and improve its performance. We collected sleep posture data from eight volunteers using millimeter-wave radar devices under various environmental conditions. Leave-one-subject-out experiments were conducted to validate the effectiveness of UniSleepPos. The results indicated that UniSleepPos significantly outperforms existing methods, demonstrating its potential for practical applications.

Abnormal retinal vascular morphology is commonly associated with cardiac, cerebrovascular, and systemic diseases. Hence, automated artery/vein(A/V) classification is crucial for the diagnosis of ophthalmic and systemic diseases. However, existing methods still face limitations in A/V classification and are prone to errors especially in microvessels and in noisy backgrounds. To alleviate these problems, this paper proposes an Evidence Probability Network (EP-Net) to achieve accurate A/V classification. Concretely, the multi-scale feature module in the EP-Net learns various vessel features, and the evidence probability module measures uncertainty and evidence for each pixel to overcome misclassification because of over-/under-confidence. Experiments on two public fundus image datasets demonstrate the superiority of the proposed EP-Net over state-of-the-art A/V classification methods.

Human activity recognition based on millimeter-wave radar is dedicated to monitor people’s daily activities and detect specific dangerous actions. Although existing methods achieve some improvement, they rarely consider the challenges of domain difference, such as ages and environments. To address this challenge, we propose a source-free domain adaptation method for millimeter wave radar based human activity recognition, which achieves knowledge transfer from the source domain to the target domain. Firstly, we propose balanced clustering to obtain cluster centers of source domain as the prior-knowledge through the pre-trained model. Then, in order to perform domain adaptation, the model is fine-tuned by the integration of domain adaptation and self-supervision of the target domain. Experiment results on several transfer tasks show that our proposed method is effective in human activity recognition and outperforms some other advanced transfer learning methods.

Effective diagnosis of Mild Cognitive Impairment (MCI), a preclinical stage of cognitive decline, is significant for delaying disease progression.While most current spontaneous speechbased diagnostic methods focus on English speech, the Interspeech 2024 TAUKADIAL Challenge proposed an innovative research direction to develop a language-agnostic approach to diagnose MCI.This paper proposes an MCI diagnosis method by analyzing and combining linguistic and acoustic features using the bilingual Chinese-English speech dataset provided by the challenge.We employed a pre-trained multilingual model and expressivity encoder to extract language-agnostic speech features.To overcome the challenges of data scarcity and language diversity, we implemented data augmentation and alignment to enhance the model's generalization.Our approach achieved 77.5% accuracy, demonstrating its effectiveness and potential on cross-lingual data.

Clustering cells based on single-cell multi-modal sequencing technologies provides an unprecedented opportunity to create high-resolution cell atlas, reveal cellular critical states and study health and diseases. However, effectively integrating different sequencing data for cell clustering remains a challenging task. Motivated by the successful application of Louvain in scRNA-seq data, we propose a single-cell multi-modal Louvain clustering framework, called scMLC, to tackle this problem. scMLC builds multiplex single- and cross-modal cell-to-cell networks to capture modal-specific and consistent information between modalities and then adopts a robust multiplex community detection method to obtain the reliable cell clusters. In comparison with 15 state-of-the-art clustering methods on seven real datasets simultaneously measuring gene expression and chromatin accessibility, scMLC achieves better accuracy and stability in most datasets. Synthetic results also indicate that the cell-network-based integration strategy of multi-omics data is superior to other strategies in terms of generalization. Moreover, scMLC is flexible and can be extended to single-cell sequencing data with more than two modalities.

Single cell sequencing technology has provided unprecedented opportunities for comprehensively deciphering cell heterogeneity. Nevertheless, the high dimensionality and intricate nature of cell heterogeneity have presented substantial challenges to computational methods. Numerous novel clustering methods have been proposed to address this issue. However, none of these methods achieve the consistently better performance under different biological scenarios. In this study, we developed CAKE, a novel and scalable self-supervised clustering method, which consists of a contrastive learning model with a mixture neighborhood augmentation for cell representation learning, and a self-Knowledge Distiller model for the refinement of clustering results. These designs provide more condensed and cluster-friendly cell representations and improve the clustering performance in term of accuracy and robustness. Furthermore, in addition to accurately identifying the major type cells, CAKE could also find more biologically meaningful cell subgroups and rare cell types. The comprehensive experiments on real single-cell RNA sequencing datasets demonstrated the superiority of CAKE in visualization and clustering over other comparison methods, and indicated its extensive application in the field of cell heterogeneity analysis. Contact: Ruiqing Zheng. ([email protected]).

Handwriting images are commonly used to diagnose Parkinson's disease due to their intuitive nature and easy accessibility. However, existing methods have not explored the potential of the fusion of different handwriting image sources for diagnosis. To address this issue, this study proposes a hybrid fusion approach that makes use of the visual information derived from different handwriting images and handwriting templates, significantly enhancing the performance in diagnosing Parkinson's disease. The proposed method involves several key steps. Initially, different preprocessed handwriting images undergo pixel-level fusion using Laplacian transformation. Subsequently, the fused and original images are fed into a pre-trained CNN separately to extract visual features. Finally, feature-level fusion is performed by concatenating the feature vectors extracted from the flatten layer, and the fused feature vectors are input into SVM to obtain classification results. Our experimental results validate that the proposed method achieves excellent performance by only utilizing visual features from images, with 95.45% accuracy on the NewHandPD. Furthermore, the results obtained on our dataset verify the strong generalizability of the proposed approach.

Graph learning methods have achieved noteworthy performance in disease diagnosis due to their ability to represent unstructured information such as inter-subject relationships. While it has been shown that imaging, genetic and clinical data are crucial for degenerative disease diagnosis, existing methods rarely consider how best to use their relationships. How best to utilize information from imaging, genetic and clinical data remains a challenging problem. This study proposes a novel graph-based fusion (GBF) approach to meet this challenge. To extract effective imaging-genetic features, we propose an imaging-genetic fusion module which uses an attention mechanism to obtain modality-specific and joint representations within and between imaging and genetic data. Then, considering the effectiveness of clinical information for diagnosing degenerative diseases, we propose a multi-graph fusion module to further fuse imaging-genetic and clinical features, which adopts a learnable graph construction strategy and a graph ensemble method. Experimental results on two benchmarks for degenerative disease diagnosis (Alzheimers Disease Neuroimaging Initiative and Parkinson's Progression Markers Initiative) demonstrate its effectiveness compared to state-of-the-art graph-based methods. Our findings should help guide further development of graph-based models for dealing with imaging, genetic and clinical data.

The diagnosis of mild cognitive impairment (MCI), which is an early stage of Alzheimer’s disease (AD), has great clinical significance. Medical imaging and gene sequencing technologies have provided sufficient multimodality data for MCI diagnostic studies. However, how to effectively extract the rich representations from multimodality data remains a challenging task. To address this challenging task, we propose a new multimodality multiview graph representations and knowledge embedding (MMGK) framework to diagnose MCI. First, to obtain rich information from multimodality data, we extract multiview feature representations from magnetic resonance imaging (MRI) and genetic data. Afterward, considering the correlations between subjects, all subjects are constructed into a graph based on the different single-view feature representations, respectively. To further enrich the correlations between subjects, demographic data are utilized through knowledge embedding. Finally, to perform MCI diagnosis on multiview graphs, graph convolutional networks (GCNs) are utilized. In addition, to further improve the performance of MCI diagnosis, a two-step ensemble learning method is proposed. The proposed framework is evaluated on 188 subjects from the AD Neuroimaging Initiative (ADNI). Experimental results show that our proposed framework achieves good performance with accuracy reaching 0.888, and outperforms some state-of-the-art (SOTA) methods. In addition, the proposed framework is applied to Parkinson’s disease (PD) diagnosis and achieves 0.856 accuracy. Overall, our proposed method has potential for clinical application in MCI diagnosis and other diseases via integrating MRI, genetic data, and demographic data. Our code is available at:https://github.com/miacsu/MMGK.

Lesion segmentation is a fundamental step for the diagnosis of acute ischemic stroke (AIS). Non-contrast CT (NCCT) is still a mainstream imaging modality for AIS lesion measurement. However, AIS lesion segmentation on NCCT is challenging due to low contrast, noise and artifacts. To achieve accurate AIS lesion segmentation on NCCT, this study proposes a hybrid convolutional neural network (CNN) and Transformer network with circular feature interaction and bilateral difference learning. It consists of parallel CNN and Transformer encoders, a circular feature interaction module, and a shared CNN decoder with a bilateral difference learning module. A new Transformer block is particularly designed to solve the weak inductive bias problem of the traditional Transformer. To effectively combine features from CNN and Transformer encoders, we first design a multi-level feature aggregation module to combine multi-scale features in each encoder and then propose a novel feature interaction module containing circular CNN-to-Transformer and Transformer-to-CNN interaction blocks. Besides, a bilateral difference learning module is proposed at the bottom level of the decoder to learn the different information between the ischemic and contralateral sides of the brain. The proposed method is evaluated on three AIS datasets: the public AISD, a private dataset and an external dataset. Experimental results show that the proposed method achieves Dices of 61.39% and 46.74% on the AISD and the private dataset, respectively, outperforming 17 state-of-the-art segmentation methods. Besides, volumetric analysis on segmented lesions and external validation results imply that the proposed method is potential to provide support information for AIS diagnosis.

Medical image denoising, as a part of medical image processing, is significant for the assessment and diagnosis of diseases. To improve the medical image denoising performance of existing deep learning methods, we propose a lightweight plug-and-play module (LP2M) with low complexity, which can be plugged before current image denoising methods. Specifically, the proposed LP2M contains three stacked Convolutional Neural Network (CNN) based blocks: a image receptor block, an adaptive receptive field selection block and a high-low frequency processing block. The image receptor block can perceive color or grayscale images and perform preliminary processing. The adaptive receptive field selection block includes two parallel paths with different receptive fields (i.e., convolution kernel sizes) and the adaptive weighting operation, which can process multi-scale information in the image. The high-low frequency processing block consists of a low frequency pathway using convolutional layers with large kernel sizes, and a high frequency pathway using covolutional layers with small kernel sizes, which can process the low and high frequency components in images. Extensive validation experiments are performed on five state-of-the-art denoising methods on multiple medical image datasets for three different medical image denoising tasks (X-ray image denoising, magnetic resonance image denoising and dermoscopic image denoising). Experimental results show that our proposed LP2M can effectively improve the results of these five state-of-the-art methods for three denoising tasks with only increasing 0.996K parameters and 63.112M FLOPs, and it can provide potential direction for improving image denoising.

Currently, most medical institutions face the challenge of training a unified model using fragmented and isolated data to address disease prediction problems. Although federated learning has become the recognized paradigm for privacy-preserving model training, how to integrate federated learning with fMRI temporal characteristics to enhance predictive performance remains an open question for functional disease prediction. To address this challenging task, we propose a novel Federated Graph Spatio-Temporal (FedGST) framework for brain functional disease prediction. Specifically, anchor sampling is used to process variable-length time series data on local clients. Then dynamic functional connectivity graphs are generated via sliding windows and Pearson correlation coefficients. Next, we propose an InceptionTime model to extract temporal information from the dynamic functional connectivity graphs on the local clients. Finally, the hidden activation variables are sent to a global server. We propose a UniteGCN model on the global server to receive and process the hidden activation variables from clients. Then, the global server returns gradient information to clients for backpropagation and model parameter updating. Client models aggregate model parameters on the local server and distribute them to clients for the next round of training. We demonstrate that FedGST outperforms other federated learning methods and baselines on ABIDE-1 and ADHD200 datasets.

Self-supervised learning provides a possible solution to extract effective visual representations from unlabeled pathological images. However, most of the existing methods either do not effectively utilize domain-specific information or are designed and optimized for image classification, resulting in these pre-trained models that may not be optimal for pathological image segmentation. In this paper, we propose DKSL: Domain-specific Knowledge guided Self-supervised Learning, which uses image reconstruction tasks to aid contrastive learning and exploits single-dye stained pathological images after stain separation as domain-specific knowledge to guide the model. Our method provides a novel way to exploit the domain-specific knowledge of pathological images. In contrastive learning, we add single-dye stained images as an expansion of the original positive samples to the contrastive learning process to preserve more global semantic information. In image reconstruction, the model is forced to focus on local image details relevant to downstream tasks by reconstructing single-dye stained images from the representation extracted by the encoder of contrastive learning. Finally, the encoder and decoder from the pre-training stage are fine-tuned by the downstream segmentation task. Fine-tuning experimental results demonstrate that DKSL outperforms state-of-the-art methods with Dices of 90.50% and 79.68% on two publicly available datasets, GlaS and MoNuSeg, respectively.

Isocitrate dehydrogenase (IDH) is a key molecular feature for gliomas, and the prediction of IDH is also an important task for computer-aided diagnosis using magnetic resonance imaging (MRI). To address this changllenge, we introduce a multi-modal MRI-based characteristics inspired network for IDH Genotyping (M3CI-Net), which pay more attention to the different characteristics information of different MRI modalities T1, T2, T1ce, Flair. In M3CI-Net, a pre-fusion module with multi-channel attention mechanism is used to fuse T1ce and Flair modalities and capture as much as possible luminance and contrast information, and the edge information is obtained from T2 modality by using edge detection module. Finally, the feature information between modalities are fused and input into a CNN-Transformer based encoder structure to extract shared spatial and global information from multi-modal MRI, and the information of multiple scales frome encoder are input into the linear layer for IDH genotype classification after pooling, meanwhile, the CNN based decoder with skip-connection for glioma segmentation works for assisting IDH genotyping. Then, we proposed images’ pre-fusion loss, segmentation loss, IDH genotyping loss, and use uncertainty weight training method to balance the weights of these loss. we evaluate our proposed method on Brats2020, and achieve an acceracy of 0.88, an AUC of 0.94, a specificity of 0.92, a sensitivity of 0.84 in IDH genotyping, which is superior to the state-of-the-art methods.

Accurately predicting survival of esophageal cancer is essential for clinical precision treatment. However, the existing region of interest (ROI) based methods not only require prior medical knowledge to complete the delineation of tumor, but may also lead to excessive sensitivity of the model towards ROI. To address these challenges, we design a fully automated CT-guided learning that combines a CNN-Transformer size aware U-Net and a ranked survival prediction network together to automatically predict the survival of patients with esophageal cancer. Specifically, we first incorporate the Transformer with shifted windowing multi-head self-attention mechanism into the base of the encoder in the U-Net to capture the long-range dependency in the 3D CT images. Then, to alleviate the imbalance between the ROI and the background in CT images, we design a size-aware coefficient for the segmentation loss. Finally, we design a ranked pair sorting loss to learn more fully the ranked information hidden in esophageal cancer patients. To validate the effectiveness of our method, we conduct extensive experiments on a dataset containing 759 esophageal cancer samples. The experimental results demonstrate that our proposed method can still achieve the best performance in survival prediction without ROI ground truth.

Discovering visual evidence is of great importance in making glaucoma diagnosis trustworthy, with interpretable processes and reliable results. Existing works usually learn image representation for glaucoma diagnosis, where the cup-to-disc ratios (CDRs) are employed as the quantitative evidence to interpret the diagnosis model. However, they rely on global visual features which are insufficient for the trustworthy interpretation of medical image for disease diagnosis. To enable interpretable and reliable glaucoma diagnosis, this paper proposes confidence-guided weakly-supervised learning (CG-WSL) by exploiting the intrinsic visual-semantic interactions in fundus images. The CG-WSL discovers the evidential local regions to support the reliable glaucoma diagnosis with fine-grained anatomical representations, only given the image-level annotations. The evidential local regions not only provide the localization information about the lesions and anatomies for visual interpretation, but also enhance the feature presentation with fine-grained anatomy-level features to discriminate the abnormal cases. Specifically, it consists of two parts: confidence-guided evidence discovery (CGED) for multi-scale fine-grained visual evidence discovery, and feature weighted fusion (FWF) for coarse-to-fine grained representation learning. Experimental results on two datasets demonstrate the effectiveness of proposed method on glaucoma diagnosis with accuracy of 0.981 (LAG) and 0.956 (RIM-ONE r2). Visualization results indicate the visual evidence for glaucoma diagnosis, which makes the diagnosis process interpretable and results reliable.

Existing computer-aided diagnosis models only focus on the statistical accuracy for glaucoma diagnosis, but ignore its reliability for the predictions. Reliability refers to the degree how the model’s prediction can be trusted when be used to assess glaucoma. Predictions with higher reliability can help the clinician make a confident decision, while the prediction with lower reliability will confuse the decision-making. Researches indicate that reliability is high related to the uncertainty both from model and data. In this paper, a method, multi-sample evidential deep learning (MS-EBDL), is proposed to enable the glaucoma assessment model with high reliability. The proposed MS-EBDL gives the disease prediction with quantitative confidence to indicate its reliability by capturing sufficient epistemic. Therefore, the proposed MS-EBDL consists of two parts: evidential deep learning for fundamental epistemic uncertainty and multi-sample dropout for additional epistemic uncertainty. Experimental results on two glaucoma datasets shown that the proposed MS-EBDL outperforms the benchmark with 97.75%(LAG) and 92.20%(RIM-ONE-R2) of accuracy, and provides reliable prediction confidence, which helps clinician make the right decision.

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed.

Medical image segmentation is indispensable for diagnosis and prognosis of many diseases. To improve the segmentation performance, this study proposes a new 2D body and edge aware network with multi-scale short-term concatenation for medical image segmentation. Multi-scale short-term concatenation modules which concatenate successive convolution layers with different receptive fields, are proposed for capturing multi-scale representations with fewer parameters. Body generation modules with feature adjustment based on weight map computing via enlarging the receptive fields, and edge generation modules with multi-scale convolutions using Sobel kernels for edge detection, are proposed to separately learn body and edge features from convolutional features in decoders, making the proposed network be body and edge aware. Based on the body and edge modules, we design parallel body and edge decoders whose outputs are fused to achieve the final segmentation. Besides, deep supervision from the body and edge decoders is applied to ensure the effectiveness of the generated body and edge features and further improve the final segmentation. The proposed method is trained and evaluated on six public medical image segmentation datasets to show its effectiveness and generality. Experimental results show that the proposed method achieves better average Dice similarity coefficient and 95% Hausdorff distance than several benchmarks on all used datasets. Ablation studies validate the effectiveness of the proposed multi-scale representation learning modules, body and edge generation modules and deep supervision.

Ki67 is a promising molecular biomarker for the diagnosis of lung adenocarcinoma. However, previous methods to determine Ki67 status often require tumor tissue sampling, which is invasive for patients. This study proposes a multi-view signature fusion network (MVSF), combining deep learning encoded (DLE) signatures, handcrafted radiomics (HCR) signatures, and clinical information to noninvasively predict Ki67 status. Multi-view signatures are combined through a tensor fusion network to obtain potentially high-dimensional signatures. Finally, a cooperative game theory-based approach is applied to quantitatively interpret the contribution of signatures to decision-making. The proposed MVSF is evaluated on a retrospectively collected dataset of 661 patients. Experimental results show that the MVSF achieves encouraging performance, with an area under the receiver operating characteristic curve of 0.80 and an accuracy of 0.78, outperforming several state-of-the-art Ki67 status prediction methods, which implies that our proposed method could provide potential support for Ki67 status prediction.

Parkinson’s disease (PD) is a common neurodegenerative disorder that impairs the patient’s quality of life. Medical imaging technology has provided a variety of neuroimages for PD diagnosis studies. However, how to effectively integrate the rich representations from multi-modality data is still a challenging task. To address this challenging task, we propose a multiplane embedding and spatial-temporal Transformer (MEST) framework for PD diagnosis. Firstly, we project structural magnetic resonance imaging (sMRI) into 2D images from coronal, sagittal and axial directions, respectively. Then, the multi-plane dynamic images are learned by pre-trained VGG11 and attention mechanism for representation learning. Afterwards, time series information of functional magnetic resonance imaging (fMRI) is used to construct dynamic functional connection images. To capture information changes in brain, spatial-temporal connectivity Transformer (SCTransformer) is utilized to address spatial-temporal redundancy and dependencies. To integrate multimodality data, ensemble learning is designed based on majority voting strategy to perform PD diagnosis. We evaluate the proposed method on 279 subjects from an in-house and Parkinsons Progression Markers Initiative (PPMI) dataset. Experimental results show that the MEST achieves promising performance with accuracies of 0.856 and 0.885, and outperforms some state-of-the-art methods.

Resting-state functional magnetic resonance imaging (rs-fMRI) images have been widely used for diagnosis of schizophrenia. With rs-fMRI, most existing schizophrenia diagnostic methods have revealed schizophrenia’s functional abnormalities from the following three scales, i.e., regional neural activity alterations, functional connectivity abnormalities and brain network dysfunctions. However, many schizophrenia diagnosis methods do not consider the fusion of features from the three scales. In this study, we propose a schizophrenia diagnostic method based on multi-scale feature representation and ensemble learning. Firstly, features including the three scales (region, connectivity and network) are extracted from rs-fMRI images using the brainnetome atlas. For each scale, feature selection, i.e., least absolute shrinkage and selection operator, is applied to identify effective sub-features related to schizophrenia classification by a grid search. Then the selected sub-features of each scale are input to support vector machine with linear kernel to classify schizophrenia patients and healthy controls respectively. To further improve the schizophrenia diagnostic performance, an ensemble learning framework named E-RCN is proposed to average the probabilities obtained by the classifiers of each scale in decision level. By leave-one-out cross-validation on the center for biomedical research excellence dataset (COBRE), our proposed method achieves encouraging diagnosis performance, outperforming several state-of-the-art methods. In addition, ranked by the occurence frequency of each brain region within the leave-one-out cross-validation experiments, some brain regions related to schizophrenia, i.e., thalamus and middle temporal gyrus, and important elaborate subregions, i.e., Tha_L_8_8, MTG_L_4_4 and MTG_R_4_4, are found.

Increasing evidences have proved that circRNA plays a significant role in the development of many diseases. In addition, many researches have shown that circRNA can be considered as the potential biomarker for clinical diagnosis and treatment of disease. Some computational methods have been proposed to predict circRNA-disease associations. However, the performance of these methods is limited as the sparsity of low-order interaction information. In this paper, we propose a new computational method (KGANCDA) to predict circRNA-disease associations based on knowledge graph attention network. The circRNA-disease knowledge graphs are constructed by collecting multiple relationship data among circRNA, disease, miRNA and lncRNA. Then, the knowledge graph attention network is designed to obtain embeddings of each entity by distinguishing the importance of information from neighbors. Besides the low-order neighbor information, it can also capture high-order neighbor information from multisource associations, which alleviates the problem of data sparsity. Finally, the multilayer perceptron is applied to predict the affinity score of circRNA-disease associations based on the embeddings of circRNA and disease. The experiment results show that KGANCDA outperforms than other state-of-the-art methods in 5-fold cross validation. Furthermore, the case study demonstrates that KGANCDA is an effective tool to predict potential circRNA-disease associations.

MOTIVATION: Recently, with the development of high-throughput experimental technology, reconstruction of gene regulatory network (GRN) has ushered in new opportunities and challenges. Some previous methods mainly extract gene expression information based on RNA-seq data, but the associated information is very limited. With the establishment of gene expression image database, it is possible to infer GRN from image data with rich spatial information. RESULTS: First, we propose a new convolutional neural network (called SDINet), which can extract gene expression information from images and identify the interaction between genes. SDINet can obtain the detailed information and high-level semantic information from the images well. And it can achieve satisfying performance on image data (Acc: 0.7196, F1: 0.7374). Second, we apply the idea of our SDINet to build an RNA-model, which also achieves good results on RNA-seq data (Acc: 0.8962, F1: 0.8950). Finally, we combine image data and RNA-seq data, and design a new fusion network to explore the potential relationship between them. Experiments show that our proposed network fusing two modalities can obtain satisfying performance (Acc: 0.9116, F1: 0.9118) than any single data. AVAILABILITY AND IMPLEMENTATION: Data and code are available from https://github.com/guofei-tju/Combine-Gene-Expression-images-and-RNA-seq-data-For-infering-GRN.

The accurate prediction of glioma grade before surgery is essential for treatment planning and prognosis. Since the gold standard (i.e., biopsy)for grading gliomas is both highly invasive and expensive, and there is a need for a noninvasive and accurate method. In this study, we proposed a novel radiomics-based pipeline by incorporating the intratumoral and peritumoral features extracted from preoperative mpMRI scans to accurately and noninvasively predict glioma grade. To address the unclear peritumoral boundary, we designed an algorithm to capture the peritumoral region with a specified radius. The mpMRI scans of 285 patients derived from a multi-institutional study were adopted. A total of 2153 radiomic features were calculated separately from intratumoral volumes (ITVs)and peritumoral volumes (PTVs)on mpMRI scans, and then refined using LASSO and mRMR feature ranking methods. The top-ranking radiomic features were entered into the classifiers to build radiomic signatures for predicting glioma grade. The prediction performance was evaluated with five-fold cross-validation on a patient-level split. The radiomic signatures utilizing the features of ITV and PTV both show a high accuracy in predicting glioma grade, with AUCs reaching 0.968. By incorporating the features of ITV and PTV, the AUC of IPTV radiomic signature can be increased to 0.975, which outperforms the state-of-the-art methods. Additionally, our proposed method was further demonstrated to have strong generalization performance in an external validation dataset with 65 patients. The source code of our implementation is made publicly available at https://github.com/chengjianhong/glioma_grading.git.

Accurate and rapid diagnosis of coronavirus disease 2019 (COVID-19) from chest CT scans is of great importance and urgency during the worldwide outbreak. However, radiologists have to distinguish COVID-19 pneumonia from other pneumonia in a large number of CT scans, which is tedious and inefficient. Thus, it is urgently and clinically needed to develop an efficient and accurate diagnostic tool to help radiologists to fulfill the difficult task. In this study, we proposed a deep supervised autoencoder (DSAE) framework to automatically identify COVID-19 using multi-view features extracted from CT images. To fully explore features characterizing CT images from different frequency domains, DSAE was proposed to learn the latent representation by multi-task learning. The proposal was designed to both encode valuable information from different frequency features and construct a compact class structure for separability. To achieve this, we designed a multi-task loss function, which consists of a supervised loss and a reconstruction loss. Our proposed method was evaluated on a newly collected dataset of 787 subjects including COVID-19 pneumonia patients, other pneumonia patients, and normal subjects without abnormal CT findings. Extensive experimental results demonstrated that our proposed method achieved encouraging diagnostic performance and may have potential clinical application for the diagnosis of COVID-19.

Accumulating evidences have shown that circRNA plays an important role in human diseases. It can be used as potential biomarker for diagnose and treatment of disease. Although some computational methods have been proposed to predict circRNA-disease associations, the performance still need to be improved. In this paper, we propose a new computational model based on Improved Graph convolutional network and Negative Sampling to predict CircRNA-Disease Associations. In our method, it constructs the heterogeneous network based on known circRNA-disease associations. Then, an improved graph convolutional network is designed to obtain the feature vectors of circRNA and disease. Further, the multi-layer perceptron is employed to predict circRNA-disease associations based on the feature vectors of circRNA and disease. In addition, the negative sampling method is employed to reduce the effect of the noise samples, which selects negative samples based on circRNA's expression profile similarity and Gaussian Interaction Profile kernel similarity. The 5-fold cross validation is utilized to evaluate the performance of the method. The results show that IGNSCDA outperforms than other state-of-the-art methods in the prediction performance. Moreover, the case study shows that IGNSCDA is an effective tool for predicting potential circRNA-disease associations.

It has been proved that long noncoding RNA (lncRNA) plays critical roles in many human diseases. Therefore, inferring associations between lncRNAs and diseases can contribute to disease diagnosis, prognosis and treatment. To overcome the limitation of traditional experimental methods such as expensive and time-consuming, several computational methods have been proposed to predict lncRNA-disease associations by fusing different biological data. However, the prediction performance of lncRNA-disease associations identification needs to be improved. In this study, we propose a computational model (named LDICDL) to identify lncRNA-disease associations based on collaborative deep learning. It uses an automatic encoder to denoise multiple lncRNA feature information and multiple disease feature information, respectively. Then, the matrix decomposition algorithm is employed to predict the potential lncRNA-disease associations. In addition, to overcome the limitation of matrix decomposition, the hybrid model is developed to predict associations between new lncRNA (or disease) and diseases (or lncRNA). The ten-fold cross validation and de novo test are applied to evaluate the performance of method. The experimental results show LDICDL outperforms than other state-of-the-art methods in prediction performance.

Effective fusion of multimodal magnetic resonance imaging (MRI) is of great significance to boost the accuracy of glioma grading thanks to the complementary information provided by different imaging modalities. However, how to extract the common and distinctive information from MRI to achieve complementarity is still an open problem in information fusion research. In this study, we propose a deep neural network model termed as multimodal disentangled variational autoencoder (MMD-VAE) for glioma grading based on radiomics features extracted from preoperative multimodal MRI images. Specifically, the radiomics features are quantized and extracted from the region of interest for each modality. Then, the latent representations of variational autoencoder for these features are disentangled into common and distinctive representations to obtain the shared and complementary data among modalities. Afterwards, cross-modality reconstruction loss and common-distinctive loss are designed to ensure the effectiveness of the disentangled representations. Finally, the disentangled common and distinctive representations are fused to predict the glioma grades, and SHapley Additive exPlanations (SHAP) is adopted to quantitatively interpret and analyze the contribution of the important features to grading. Experimental results on two benchmark datasets demonstrate that the proposed MMD-VAE model achieves encouraging predictive performance (AUC:0.9939) on a public dataset, and good generalization performance (AUC:0.9611) on a cross-institutional private dataset. These quantitative results and interpretations may help radiologists understand gliomas better and make better treatment decisions for improving clinical outcomes.

The accurate prediction of isocitrate dehydrogenase (IDH) mutation and glioma segmentation are important tasks for computer-aided diagnosis using preoperative multimodal magnetic resonance imaging (MRI). The two tasks are ongoing challenges due to the significant inter-tumor and intra-tumor heterogeneity. The existing methods to address them are mostly based on single-task approaches without considering the correlation between the two tasks. In addition, the acquisition of IDH genetic labels is expensive and costly, resulting in a limited number of IDH mutation data for modeling. To comprehensively address these problems, we propose a fully automated multimodal MRI-based multi-task learning framework for simultaneous glioma segmentation and IDH genotyping. Specifically, the task correlation and heterogeneity are tackled with a hybrid CNN-Transformer encoder that consists of a convolutional neural network and a transformer to extract the shared spatial and global information learned from a decoder for glioma segmentation and a multi-scale classifier for IDH genotyping. Then, a multi-task learning loss is designed to balance the two tasks by combining the segmentation and classification loss functions with uncertain weights. Finally, an uncertainty-aware pseudo-label selection is proposed to generate IDH pseudo-labels from larger unlabeled data for improving the accuracy of IDH genotyping by using semi-supervised learning. We evaluate our method on a multi-institutional public dataset. Experimental results show that our proposed multi-task network achieves promising performance and outperforms the single-task learning counterparts and other existing state-of-the-art methods. With the introduction of unlabeled data, the semi-supervised multi-task learning framework further improves the performance of glioma segmentation and IDH genotyping. The source codes of our framework are publicly available at https://github.com/miacsu/MTTU-Net.git.

Medical image segmentation is a fundamental step for diagnosis and prognosis. This study proposes a new body and edge aware network for automated 2D medical image segmentation (called BEA-SegNet). The proposed BEA-SegNet consists of a shared encoder, a body and edge decouple (BEdecouple) module, two parallel decoders for body and edge segmentation. In the encoder and decoders, short-term multi-scale concatenation (STMSC) modules are utilized to implement multi-scale representation. We design a BEdecouple module to decouple the convolutional features into the body and edge features, making the proposed method be body and edge aware. The body and edge decoders utilize Bedecouple modules in each level to learn more effective features for the body and edge segmentation respectively, and their outputs are fused to generate the final segmentation. Besides, the body and edge supervision are applied to improve the final segmentation. The proposed BEA-SegNet is trained and evaluated on the International Skin Imaging Collaboration challenge 2018 dataset (ISIC2018). Experimental results show that the proposed BEA-SegNet achieves an average Dice similarity coefficient of 90.3% and an average Hausdorff distance of 15.9 for the skin lesion segmentation task and outperforms five benchmarks for skin lesion segmentation.

Automatic detection of Alzheimer’s disease (AD) is conducive to intervention in the disease progression. MMSE score prediction can reveal the development of AD. In recent years, some studies have designed multi-task methods for AD detection and MMSE score prediction to take advantage of the correlation between them. However, how to use the correlation between the two task features is still a problem. To address this challenge, we propose a multi-task feature interactive leanrning network (MTFIL-Net) to perform AD detection and MMSE score prediction. First, we interact the features acquired by CNNs corresponding to the two tasks to take advantage of the feature correlation between the two tasks. The interaction module extracts the shared features of the two tasks and concatenate them with the features of the two task. Then, we design a joint loss based on cross entropy and smooth L1 function. We use the distribution of MMSE scores to dynamically adjust the relationship between the two tasks. We validate our method with subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We use the ADNI1 dataset for training and testing, and used the ADNI2 dataset as an external validation set. Our proposed MTFIL-Net reached an ACC of 0.86 for AD detection and a correlation coefficient of 0.67 for MMSE score prediction on the ADNI1 dataset, and reached an ACC of 0.85 for AD detection and a correlation coefficient of 0.66 for MMSE score prediction on the ADNI2 dataset. Experiment results show that MTFIL-Net effectively utilizes the correlation between AD and MMSE score.

Automatic identification of adventitious respiratory sound has still been a challenging problem in recent years. To address this challenge, we propose an adventitious respiratory sound classification network (ARSC-Net), which combines residual block with channel-spatial attention for accurate classification. Specifically, we extract two types of features from adventitious respiratory sound, including Mel-Frequency Cepstral Coefficients (MFCCs) and Mel-spectrogram. The two types of features are entered into the parallel encoders paths with residual attention for extracting feature representation, and then fused into a channel-spatial attention module to adaptively focus on the important features between channel and spatial part for the classification task. Moreover, the channel-spatial attention can enhance the feature representation, in which the channel attention explores the inter-channel relationship of the spectrums, and then the inter-spatial correlation mapping is generated by the spatial attention introduced serially. We evaluate our proposed method on ICBHI 2017 database. Experimental results show that our proposed method achieves encouraging predictive performance with an accuracy of 80.0% for identifying abnormal sounds from normal sounds, and with an accuracy of 92.4% for distinguishing crackles from wheezes. In addition, our method also achieves a score of 56.76% for the four-class sound classification of adventitious sounds and outperforms several state-of-the-art methods.

Epidermal growth factor receptor (EGFR) genotyping is essential to treatment guidelines for the use of tyrosine kinase inhibitors in lung adenocarcinoma. However, accurate and noninvasive methods to detect the EGFR gene are ongoing challenges. In this study, we propose a hybrid framework, namely HC-DLR, to noninvasively predict EGFR mutation status by fusing multi-source features including low-level handcrafted radiomics (HCR) features, high-level deep learning-based radiomics (DLR) features, and demographics features. The HCR features first are selected from massive handcrafted features extracted from CT images. The DLR features are also extracted from CT images using the pre-trained 3D DenseNet. Then, multi-source feature representations are refined and fused to build an HC-DLR model for improving the predictive performance of EGFR mutations. The proposed method is evaluated on a newly collected dataset with 670 patients. Experimental results show that the HC-DLR model achieves an encouraging predictive performance with an AUC of 0.76, an accuracy of 72.47%, and an F1-score of 71.35%, which may have potential clinical value for predicting EGFR mutations in lung adenocarcinoma.

The dysregulation and mutation of long non-coding RNAs (lncRNAs) have been proved to result in a variety of human diseases. Identifying potential disease-related lncRNAs may benefit disease diagnosis, treatment and prognosis. A number of methods have been proposed to predict the potential lncRNA-disease relationships. However, most of them may give rise to incorrect results due to relying on single similarity measure. This article proposes a novel framework (ILDMSF) by fusing the lncRNA similarities and disease similarities, which are measured by lncRNA-related gene and known lncRNA-disease interaction and disease semantic interaction, and known lncRNA-disease interaction, respectively. Further, the support vector machine is employed to identify the potential lncRNA-disease associations based on the integrated similarity. The leave-one-out cross validation is performed to compare ILDMSF with other state of the art methods. The experimental results demonstrate our method is prospective in exploring potential correlations between lncRNA and disease.

The cause of Alzheimer's disease (AD) is insufficient to understand so far, and its diagnosis is challenging in clinical practice. Recently, the convolutional neural network (CNN) model has shown impressive performance in medical image analysis. Combining CNN with magnetic resonance imaging (MRI) image has excellent potential for AD diagnosis. However, it is still a challenging task. To address the challenge, we propose a joint learning method based on multi-scale representation (JL-MSR). The multi-scale representation is proposed to obtain more feature maps by the multi-scale atrous convolutions. Furthermore, in order to use the intrinsic relationship between diagnostic results and clinical scores, we propose a joint learning strategy using the diagnosis result as the primary label and the Mini-Mental State Examination (MMSE) score as the secondary label to joint training. The proposed method is evaluated on a dataset of 417 subjects (including 188 AD and 229 health controls (HC)) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The experimental results show that our proposed method achieves an accuracy of 88.1% and an area under the receiver operating characteristic (ROC) curve (AUC) value of 0.942 for AD diagnosis, respectively. Compared with a state-of-the-art method in AD diagnosis, our proposed method performs better, and has potential in clinical diagnosis.

BACKGROUND: The identification of early mild cognitive impairment (EMCI), which is an early stage of Alzheimer's disease (AD) and is associated with brain structural and functional changes, is still a challenging task. Recent studies show great promises for improving the performance of EMCI identification by combining multiple structural and functional features, such as grey matter volume and shortest path length. However, extracting which features and how to combine multiple features to improve the performance of EMCI identification have always been a challenging problem. To address this problem, in this study we propose a new EMCI identification framework using multi-modal data and graph convolutional networks (GCNs). Firstly, we extract grey matter volume and shortest path length of each brain region based on automated anatomical labeling (AAL) atlas as feature representation from T1w MRI and rs-fMRI data of each subject, respectively. Then, in order to obtain features that are more helpful in identifying EMCI, a common multi-task feature selection method is applied. Afterwards, we construct a non-fully labelled subject graph using imaging and non-imaging phenotypic measures of each subject. Finally, a GCN model is adopted to perform the EMCI identification task. RESULTS: Our proposed EMCI identification method is evaluated on 210 subjects, including 105 subjects with EMCI and 105 normal controls (NCs), with both T1w MRI and rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results show that our proposed framework achieves an accuracy of 84.1% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.856 for EMCI/NC classification. In addition, by comparison, the accuracy and AUC values of our proposed framework are better than those of some existing methods in EMCI identification. CONCLUSION: Our proposed EMCI identification framework is effective and promising for automatic diagnosis of EMCI in clinical practice.

Accurate segmentation of glioma from 3D medical images is vital to numerous clinical endpoints. While manual segmentation is subjective and time-consuming, fully automated extraction is quite imperative and challenging due to the intrinsic heterogeneity of tumor structures. In this study, we propose a multi-level glioma segmentation framework, 3D Residual-Attention-Atrous U-Net (RAAU-Net), using 3D U-Net combined attention mechanism with atrous convolution. The 3D RAAU-Net can extract contextual information by combining low- and high-resolution feature maps. The attention mechanism is embedded in each skip connection layer of 3D RAAU-Net to enhance feature representations. Meanwhile, the atrous convolution is adopted in the whole network architecture to incorporate large and rich semantic information. Furthermore, we design a new training scheme to reduce false positives and enhance generalization. Eventually, our proposed segmentation method is evaluated on the validation dataset from the Multimodal Brain Tumor Image Segmentation Challenge (BraTS) 2018 and achieve a competitive result with average Dice score of 88% for the whole tumor, 79% for the tumor core and 73% for the enhancing tumor, respectively. Quantitative results and visual analysis have proven that these improvements in 3D RAAU-Net are effective and achieve a better segmentation accuracy compared with the baseline.

MicroRNAs (miRNAs) are a type of non-coding RNAs with about ∼22nt nucleotides. Increasing evidences have shown that miRNAs play critical roles in many human diseases. The identification of human disease-related miRNAs is helpful to explore the underlying pathogenesis of diseases. More and more experimental validated associations between miRNAs and diseases have been reported in the recent studies, which provide useful information for new miRNA-disease association discovery. In this study, we propose a computational framework, KBMF-MDI, to predict the associations between miRNAs and diseases based on their similarities. The sequence and function information of miRNAs are used to measure similarity among miRNAs while the semantic and function information of disease are used to measure similarity among diseases, respectively. In addition, the kernelized Bayesian matrix factorization method is employed to infer potential miRNA-disease associations by integrating these data sources. We applied this method to 6,084 known miRNA-disease associations and utilized 5-fold cross validation to evaluate the performance. The experimental results demonstrate that our method can effectively predict unknown miRNA-disease associations.

Regions of interest (ROIs) based classification has been widely investigated for analysis of brain magnetic resonance imaging (MRI) images to assist the diagnosis of Alzheimer's disease (AD) including its early warning and developing stages, e.g., mild cognitive impairment (MCI) including MCI converted to AD (MCIc) and MCI not converted to AD (MCInc). Since an ROI representation of brain structures is obtained either by pre-definition or by adaptive parcellation, the corresponding ROI in different brains can be measured. However, due to noise and small sample size of MRI images, representations generated from single or multiple ROIs may not be sufficient to reveal the underlying anatomical differences between the groups of disease-affected patients and health controls (HC). In this paper, we employ a whole brain hierarchical network (WBHN) to represent each subject. The whole brain of each subject is divided into 90, 54, 14, and 1 regions based on Automated Anatomical Labeling (AAL) atlas. The connectivity between each pair of regions is computed in terms of Pearson's correlation coefficient and used as classification feature. Then, to reduce the dimensionality of features, we select the features with higher scores. Finally, we use multiple kernel boosting (MKBoost) algorithm to perform the classification. Our proposed method is evaluated on MRI images of 710 subjects (200 AD, 120 MCIc, 160 MCInc, and 230 HC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our proposed method achieves an accuracy of 94.65 percent and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.954 for AD/HC classification, an accuracy of 89.63 percent and an AUC of 0.907 for AD/MCI classification, an accuracy of 85.79 percent and an AUC of 0.826 for MCI/HC classification, and an accuracy of 72.08 percent and an AUC of 0.716 for MCIc/MCInc classification, respectively. Our results demonstrate that our proposed method is efficient and promising for clinical applications for the diagnosis of AD via MRI images.

Several anatomical magnetic resonance imaging (MRI) markers for Alzheimer's disease (AD) have been identified. Cortical gray matter volume, cortical thickness, and subcortical volume have been used successfully to assist the diagnosis of Alzheimer's disease including its early warning and developing stages, e.g., mild cognitive impairment (MCI) including MCI converted to AD (MCIc) and MCI not converted to AD (MCInc). Currently, these anatomical MRI measures have mainly been used separately. Thus, the full potential of anatomical MRI scans for AD diagnosis might not yet have been used optimally. Meanwhile, most studies currently only focused on morphological features of regions of interest (ROIs) or interregional features without considering the combination of them. To further improve the diagnosis of AD, we propose a novel approach of extracting ROI features and interregional features based on multiple measures from MRI images to distinguish AD, MCI (including MCIc and MCInc), and health control (HC). First, we construct six individual networks based on six different anatomical measures (i.e., CGMV, CT, CSA, CC, CFI, and SV) and Automated Anatomical Labeling (AAL) atlas for each subject. Then, for each individual network, we extract all node (ROI) features and edge (interregional) features, and denoted as node feature set and edge feature set, respectively. Therefore, we can obtain six node feature sets and six edge feature sets from six different anatomical measures. Next, each feature within a feature set is ranked by -score in descending order, and the top ranked features of each feature set are applied to MKBoost algorithm to obtain the best classification accuracy. After obtaining the best classification accuracy, we can get the optimal feature subset and the corresponding classifier for each node or edge feature set. Afterwards, to investigate the classification performance with only node features, we proposed a weighted multiple kernel learning (wMKL) framework to combine these six optimal node feature subsets, and obtain a combined classifier to perform AD classification. Similarly, we can obtain the classification performance with only edge features. Finally, we combine both six optimal node feature subsets and six optimal edge feature subsets to further improve the classification performance. Experimental results show that the proposed method outperforms some state-of-the-art methods in AD classification, and demonstrate that different measures contain complementary information.

Motivation: Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in many human diseases. Therefore, predicting novel lncRNA-disease associations would contribute to dissect the complex mechanisms of disease pathogenesis. Some computational methods have been developed to infer lncRNA-disease associations. However, most of these methods infer lncRNA-disease associations only based on single data resource. Results: In this paper, we propose a new computational method to predict lncRNA-disease associations by integrating multiple biological data resources. Then, we implement this method as a web server for lncRNA-disease association prediction (LDAP). The input of the LDAP server is the lncRNA sequence. The LDAP predicts potential lncRNA-disease associations by using a bagging SVM classifier based on lncRNA similarity and disease similarity. Availability and Implementation: The web server is available at http://bioinformatics.csu.edu.cn/ldap Contact: [email protected]. Supplimentary Information: Supplementary data are available at Bioinformatics online.

MicroRNAs (miRNAs) are a set of small non-coding RNAs that play critical roles in many human diseases. Identifying potential miRNA-disease association is helpful to explore the underlying molecular mechanisms of disease. Currently, it is expensive and time-consuming to detect miRNA-disease associations with experimental methods. On the other hand, many known associations between miRNAs and diseases provide useful information for new miRNA-disease interaction discovery. In this study, we propose a computational framework to infer the relationship between miRNA and disease by integrating multiple data resources. We use sequence and function information of miRNA and semantic and function information of disease to measure similarity of miRNA and disease, respectively. In addition, kernelized Bayesian matrix factorization method is employed to infer potential miRNA-disease association by integrating these data resources. The experimental results demonstrate that our method can effectively predict unknown miRNA-disease association.