Epigenetic Instability Induced by DNA Base Lesion via DNA Base Excision Repair

DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, we initially discovered that an oxidized nucleotide, 5’,2-cyclo-2-deoxyadenosine in DNA duplex can either cause misinsertion by DNA polymerase β (pol β) during pol β-mediated BER or inhibit lesion bypass of pol β resulting in DNA strand breaks. We then explored how a T/G mismatch resulting from active DNA demethylation can affect genome integrity during BER and found that pol β can extend the mismatched T to cause mutation. We found that AP endonuclease 1 (APE1) can use its 3\u27-5\u27 exonuclease to remove the mismatched T before pol β can extend the nucleotide preventing a C to T mutation. The results demonstrate that the 3\u27-5\u27 exonuclease activity of APE1 can serve as a proofreader for pol β to prevent mutation. We further explored the effects of exposure of environmental toxicants, bromate and chromate on the DNA methylation pattern on the promoter region of BRCA1 gene with bisulfite DNA sequencing. We found that bromate and chromate induced demethylation of 5-methylcytosines (5mC) at the CpG sites as well as created additional methylation at several unmethylated CpG sites at BRCA1 gene in human embryonic kidney (HEK) 293 cells. We further demonstrated that the demethylation was mediated by pol β nucleotide misinsertion and an interaction between pol β and DNA methyltransferase 1 (DNMT1) suggesting a cross-talk between BER and DNA methyltransferases. We suggest that DNA base damage and BER govern the interactions among the environment, the genome and epigenome, modulating the stability of the genome and epigenome and disease development

Clinical Assistant Diagnosis for Electronic Medical Record Based on Convolutional Neural Network

Automatically extracting useful information from electronic medical records along with conducting disease diagnoses is a promising task for both clinical decision support(CDS) and neural language processing(NLP). Most of the existing systems are based on artificially constructed knowledge bases, and then auxiliary diagnosis is done by rule matching. In this study, we present a clinical intelligent decision approach based on Convolutional Neural Networks(CNN), which can automatically extract high-level semantic information of electronic medical records and then perform automatic diagnosis without artificial construction of rules or knowledge bases. We use collected 18,590 copies of the real-world clinical electronic medical records to train and test the proposed model. Experimental results show that the proposed model can achieve 98.67\% accuracy and 96.02\% recall, which strongly supports that using convolutional neural network to automatically learn high-level semantic features of electronic medical records and then conduct assist diagnosis is feasible and effective.Comment: 9 pages, 4 figures, Accepted by Scientific Report

Robotic Ultrasound Imaging: State-of-the-Art and Future Perspectives

Ultrasound (US) is one of the most widely used modalities for clinical intervention and diagnosis due to the merits of providing non-invasive, radiation-free, and real-time images. However, free-hand US examinations are highly operator-dependent. Robotic US System (RUSS) aims at overcoming this shortcoming by offering reproducibility, while also aiming at improving dexterity, and intelligent anatomy and disease-aware imaging. In addition to enhancing diagnostic outcomes, RUSS also holds the potential to provide medical interventions for populations suffering from the shortage of experienced sonographers. In this paper, we categorize RUSS as teleoperated or autonomous. Regarding teleoperated RUSS, we summarize their technical developments, and clinical evaluations, respectively. This survey then focuses on the review of recent work on autonomous robotic US imaging. We demonstrate that machine learning and artificial intelligence present the key techniques, which enable intelligent patient and process-specific, motion and deformation-aware robotic image acquisition. We also show that the research on artificial intelligence for autonomous RUSS has directed the research community toward understanding and modeling expert sonographers' semantic reasoning and action. Here, we call this process, the recovery of the "language of sonography". This side result of research on autonomous robotic US acquisitions could be considered as valuable and essential as the progress made in the robotic US examination itself. This article will provide both engineers and clinicians with a comprehensive understanding of RUSS by surveying underlying techniques.Comment: Accepted by Medical Image Analysi

DefCor-Net: Physics-Aware Ultrasound Deformation Correction

The recovery of morphologically accurate anatomical images from deformed ones is challenging in ultrasound (US) image acquisition, but crucial to accurate and consistent diagnosis, particularly in the emerging field of computer-assisted diagnosis. This article presents a novel anatomy-aware deformation correction approach based on a coarse-to-fine, multi-scale deep neural network (DefCor-Net). To achieve pixel-wise performance, DefCor-Net incorporates biomedical knowledge by estimating pixel-wise stiffness online using a U-shaped feature extractor. The deformation field is then computed using polynomial regression by integrating the measured force applied by the US probe. Based on real-time estimation of pixel-by-pixel tissue properties, the learning-based approach enables the potential for anatomy-aware deformation correction. To demonstrate the effectiveness of the proposed DefCor-Net, images recorded at multiple locations on forearms and upper arms of six volunteers are used to train and validate DefCor-Net. The results demonstrate that DefCor-Net can significantly improve the accuracy of deformation correction to recover the original geometry (Dice Coefficient: from $14.3\pm20.9$ to $82.6\pm12.1$ when the force is $6N$).Comment: Accepted by MedIA. code is availabl

Thoracic Cartilage Ultrasound-CT Registration using Dense Skeleton Graph

Autonomous ultrasound (US) imaging has gained increased interest recently, and it has been seen as a potential solution to overcome the limitations of free-hand US examinations, such as inter-operator variations. However, it is still challenging to accurately map planned paths from a generic atlas to individual patients, particularly for thoracic applications with high acoustic-impedance bone structures under the skin. To address this challenge, a graph-based non-rigid registration is proposed to enable transferring planned paths from the atlas to the current setup by explicitly considering subcutaneous bone surface features instead of the skin surface. To this end, the sternum and cartilage branches are segmented using a template matching to assist coarse alignment of US and CT point clouds. Afterward, a directed graph is generated based on the CT template. Then, the self-organizing map using geographical distance is successively performed twice to extract the optimal graph representations for CT and US point clouds, individually. To evaluate the proposed approach, five cartilage point clouds from distinct patients are employed. The results demonstrate that the proposed graph-based registration can effectively map trajectories from CT to the current setup for displaying US views through limited intercostal space. The non-rigid registration results in terms of Hausdorff distance (Mean$\pm$SD) is 9.48$\pm$0.27 mm and the path transferring error in terms of Euclidean distance is 2.21$\pm$1.11 mm.Comment: Accepted by IROS2

Motion Magnification in Robotic Sonography: Enabling Pulsation-Aware Artery Segmentation

Ultrasound (US) imaging is widely used for diagnosing and monitoring arterial diseases, mainly due to the advantages of being non-invasive, radiation-free, and real-time. In order to provide additional information to assist clinicians in diagnosis, the tubular structures are often segmented from US images. To improve the artery segmentation accuracy and stability during scans, this work presents a novel pulsation-assisted segmentation neural network (PAS-NN) by explicitly taking advantage of the cardiac-induced motions. Motion magnification techniques are employed to amplify the subtle motion within the frequency band of interest to extract the pulsation signals from sequential US images. The extracted real-time pulsation information can help to locate the arteries on cross-section US images; therefore, we explicitly integrated the pulsation into the proposed PAS-NN as attention guidance. Notably, a robotic arm is necessary to provide stable movement during US imaging since magnifying the target motions from the US images captured along a scan path is not manually feasible due to the hand tremor. To validate the proposed robotic US system for imaging arteries, experiments are carried out on volunteers' carotid and radial arteries. The results demonstrated that the PAS-NN could achieve comparable results as state-of-the-art on carotid and can effectively improve the segmentation performance for small vessels (radial artery).Comment: Accepted Paper IROS 202

MI-SegNet: Mutual Information-Based US Segmentation for Unseen Domain Generalization

Generalization capabilities of learning-based medical image segmentation across domains are currently limited by the performance degradation caused by the domain shift, particularly for ultrasound (US) imaging. The quality of US images heavily relies on carefully tuned acoustic parameters, which vary across sonographers, machines, and settings. To improve the generalizability on US images across domains, we propose MI-SegNet, a novel mutual information (MI) based framework to explicitly disentangle the anatomical and domain feature representations; therefore, robust domain-independent segmentation can be expected. Two encoders are employed to extract the relevant features for the disentanglement. The segmentation only uses the anatomical feature map for its prediction. In order to force the encoders to learn meaningful feature representations a cross-reconstruction method is used during training. Transformations, specific to either domain or anatomy are applied to guide the encoders in their respective feature extraction task. Additionally, any MI present in both feature maps is punished to further promote separate feature spaces. We validate the generalizability of the proposed domain-independent segmentation approach on several datasets with varying parameters and machines. Furthermore, we demonstrate the effectiveness of the proposed MI-SegNet serving as a pre-trained model by comparing it with state-of-the-art networks.Comment: Accepted by MICCAI 202