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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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An improved master-slave interventional surgery robotic system with force feedback

An improved master-slave interventional surgery robotic syst...

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IEEE International Conference on Mechatronics and Automation

作者： Shuxiang Guo Guangxuan Li Baofeng Gao Yuan Wang Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China Faculty of Engineering Kagawa University Takamatsu Kagawa Japan

ISBN: (纸本)9781509023974

The interventional surgery is a minimally invasive treatment, which uses the modern high technology. It takes the special catheter, guide wire and other precision instruments to import in the body to do the pathological diagnosis and local treatment under guide of medical imaging equipment. Interventional surgery has excellent characteristics like no operation, small trauma, rapid recovery, etc. It is one of the developing trend of the future medicine. Now, the interventional treatment has some shortage such as the radiation exposure on surgeons, and it is difficult to measure the front collision force on the guide wire. In this paper, we did some improvements on the master controller on the basis of Phantom, and analyzed the dynamic performance from the surgery robot system.

关键词： Surgery Wires Catheters Force Force feedback Control systems Phantoms

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Study on motion following with feedback force disturbance in interventional surgical robot system

Study on motion following with feedback force disturbance in...

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IEEE International Conference on Mechatronics and Automation

作者： Yuan Wang Shuxiang Guo Baofeng Gao Weili Peng Guangxuan Li Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China Faculty of Engineering Kagawa University Takamatsu Kagawa Japan

ISBN: (纸本)9781509023974

Neurological intervention surgery (NIS) is surgery branch vascular interventional surgery, one kind of the minimally invasive. And it has become the mainstream of the treatment in the cerebrovascular disease. Robotic surgery system with the functions of haptic feedback and the doctor-patient separation has enormous significance for the development of NIS. However, in previous studies, the haptic feedback greatly affected the motion detection accuracy. This paper presents a novel interventional surgical robot systems. The aim is improving the accuracy of motion control while providing haptic feedback. This researches take the design thought of master-slave system which realized the function of doctor-patient separation. The slave side includes a novel guide wire resistance measurement structure and guide wire manipulator. The master side can provide haptic feedback for doctors and collect guide wire control commands from doctors. In this paper, design of the developed interventional surgical robot system was presented. And design experiments to assess the follow of axial movement, rotation. The feasibility of the developed system is proved.

关键词： Wires Surgery Haptic interfaces Force Manipulators Catheters

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Design and evaluation of a novel guidewire navigation robot

Design and evaluation of a novel guidewire navigation robot

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IEEE International Conference on Mechatronics and Automation

作者： Xianqiang Bao Shuxiang Guo Nan Xiao Yuan Wang Mingyang Qin Yan Zhao Changqi Xu Weili Peng Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China Faculty of Engineering Kagawa University Takamatsu Kagawa Japan

ISBN: (纸本)9781509023974

Robotically controlled steerable guidewire navigation systems has been paid much attention to, because it can allow the surgeons to be released from radiation and heavy radiation protection garments, reduce radiation exposure, increase precision and stability of motion, and add operator comfort. The aim of the study was to improve the precision of axial motion, rotational motion and force measurement, as well as installation convenience. A novel guidewire navigation robot, composed of a master side and a slave side was developed, which can reach the high precision, measure the force/torque of guidewire, and realize the force/torque feedback to the surgeon. To evaluate feasibility of the novel guidewire navigation robot, a system evaluation was developed. The experimental results show that: axial error was no more than 0.5mm, the rotational error was no more than 1 degree, and force error was no more than 0.031N. The novel guidewire navigation robot, potentially increasing guidewire motion precision and accuracy, is feasible for minimally invasive surgery.

关键词： Surgery Grippers Robots Navigation Electromagnetics Brakes Force

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Study on slave side of interventional surgery robotic system focused on the feed-back force detection

Study on slave side of interventional surgery robotic system...

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IEEE International Conference on Mechatronics and Automation

作者： Zhao Yan Shuxiang Guo Liwei Shi Yuan Wang Guangxuan Li Weili Peng Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China Faculty of Engineering Kagawa University Takamatsu Kagawa Japan

ISBN: (纸本)9781509023974

Minimally invasive interventional surgery shows its advantages compared to traditional operation. The master-slave robotic system technology can further significantly improve the accuracy, efficiency and safety of this complicated and high risk operation. However, one of the critical issues in the robotic system, guide wire force feed-back, needs more research. The mechanical structure of the salve robot is designed basing on modularizing design principle. Ball spline pair, guide pair and herringbone gear pair are adopted in the structure concept. The experimental equipment is developed and the verifying experiments are conducted. The guide wire detected feedback force matches well with the detected resistance force. It indicates that the designed slave part and design method is rational from the point of feedback force detection.

关键词： Clamps Robots Wires Force Surgery Catheters Fasteners

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A novel application of positioning method with force feedback for interventional surgery robot

A novel application of positioning method with force feedbac...

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IEEE International Conference on Mechatronics and Automation

作者： Shuxiang Guo Changqi Xu Nan Xiao Yuan Wang Weili Peng Faculty of Engineering Kagawa University Takamatsu Kagawa Japan Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China

ISBN: (纸本)9781509023974

The interventional surgery is a type of minimally invasive operation which can reduce hospitalization time and greatly decrease patient morbidity compared to traditional methods. In our previous study, a master-slave interventional operation system has been developed. The master side was a Phantom device and the PID control was used through upper machine. To further improve the precision and synchronization performance, two laser range finders were applied to measure the position of the master side in this paper. And positioning compensation on the basis of force feedback was added to the position close-loop. Compared to the previous result, the new method had advantages on precision and accuracy.

关键词： Wires Surgery Catheters Manipulators Force feedback Brushless DC motors

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MRI Image Segmentation by Fully Convolutional Networks

MRI Image Segmentation by Fully Convolutional Networks

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IEEE International Conference on Mechatronics and Automation

作者： Yabiao Wang Zeyu Sun Chang Liu Wenbo Peng Juhua Zhang Key Laboratory of Convergence Medical Engineering System and Healthcare Technology the Ministry of Industry and Information Technology School of Life Science Beijing Institute of Technology Beijing China

ISBN: (纸本)9781509023974

With the development of various imaging technologies, medical imaging has been playing more important roles on providing scientific proof for doctors to make decisions on clinical diagnosis. At the same time, it is very important to excavate valuable information hidden in those images and take over some auxiliary medical works from doctors by the computer. Therefore, a large number of image segmentation methods, including some classic algorithms have been proposed and some of them perform well. In this paper, we built a deep convolutional neural network to segment the MRI brain images. Results show that the network has a good performance on segmentation of the gray and white matter of brains, it also had a good generalization ability.

关键词： MRI brain imaging image segmentation deep convolutional network fully convolutional network

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An improved VR training system for vascular interventional surgery

An improved VR training system for vascular interventional s...

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2016 IEEE International Conference on Robotics and Biomimetics, ROBIO 2016

作者： Guo, Shuxiang Cai, Xiaojuan Gao, Baofeng Yuhua, Jiang Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Ministry of Industry and Information Technology School of Life Science Beijing Institute of Technology No.5 Zhongguancun South Street Haidian District100081 China Department of Interventional Neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan Hospital China Faculty of Engineering Kagawa University 2217-20 Hayashi-cho Takamatsu Japan

ISBN: (纸本)9781509043644

Minimally invasive surgery is a specialized surgical technique that permits vascular interventions through very small incisions. It minimizes the patient's trauma and permits a faster recovery compared to traditional surgery. Although traditional invasive surgery training system can complete general training work, real-time performance and accuracy of most training system failed to meet the requirements of training work. Therefore, in this study, three parts, including 3D modeling, collision detection algorithm and application architecture were improved in the existing training system. Firstly, an improved Marching cubes algorithm was adopted to simplify the mathematical modeling of vessels by merging the related points of the mesh model. Secondly, a hybrid collision detection algorithm was proposed and implemented. Lastly, the CPU-GPU parallel computing architecture was adopted. Particularly, the design of the improved VR-based system and the experimental results were presented and analyzed. Moreover, experimental results showed that the proposed system was beneficial to improve the skill of surgeons in manipulating the catheter and guide wire. Thus, the simulators could be used for trial surgery training. © 2016 IEEE.

关键词： Three dimensional computer graphics

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Macrostructural and microstructural sleep variables for distinguishing normal sleep from pathologic sleep

Macrostructural and microstructural sleep variables for dist...

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IEEE International Conference on Mechatronics and Automation

作者： Xiaoying Tang Zhi Xu Yanjun Li Shaojie Shan Key Laboratory of Convergence Medical Engineering System and Healthcare Technology the Ministry of Industry and Information Technology School of Life Science Beijing Institute of Technology Beijing 100081 China

ISBN: (纸本)9781509023974

The aim of the present study is to examine the function of indices of macrostructural sleep and microstructural sleep for the objective evaluation of sleep quality, to test and find out the indices which could distinguish normal sleep from four types of pathologic sleep, including insomnia, nocturnal frontal lobe epilepsy (NFLE), periodic leg movements and rapid eye movement (REM) behavior disorder. The role of sleep indices for the evaluation of sleep quality was analyzed, including 29 macrostructure indices and 23 microstructure indices. Totally five sleep groups were selected from the cyclic alternating pattern (CAP) sleep database, including controls (no pathology, N=16), insomniacs (N=9), nocturnal epileptics (N=40), periodic leg movements (N=10) and REM behavior disorder (N=22). The macrostructure indices were calculated according to the sleep stages annotation in the database, and the microstructure sleep indices were obtained by analyzing the CAP annotation. The discrimination ability of these macrostructure and microstructure indices was tested by analysis of variance for distinguishing the normal sleep from four types of pathologic sleep. For macrostructure sleep indices, four REM-related indices of controls were distinguished from that of pathologic groups significantly (P<0.05, controls vs. each pathologic group), including the time of REM sleep, the percent of REM sleep to all sleep period time, the ratio of REM sleep to non-rapid eye movement (NREM) sleep, and the maximal sustained REM sleep time. For microstructure sleep indices, three phase A3-related indices of controls were significantly distinguished from that of pathologic groups (P<0.05, controls vs. each pathologic group), including the number of phase A3 per hour during NREM sleep, the total number of phase A3, and the total duration of phase A3. In conclusion, REM sleep indices can distinguish normal sleep from four types of pathologic sleep, including insomnia, nocturnal epilepsy, periodic l

关键词： sleep quality macrostructural sleep microstructural sleep insomnia epilepsy periodic leg movements REM behavior disorder

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Leader-follower cooperative movement method for multiple amphibious spherical robots

Leader-follower cooperative movement method for multiple amp...

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IEEE International Conference on Mechatronics and Automation

作者： Liwei Shi Kun Tang Shuxiang Guo Xianqiang Bao Shaowu Pan Ping Guo Key Laboratory of Biomimetic Robots and Systems Beijing Institute of Technology Beijing China Faculty of Engineering Kagawa University Kagawa Japan Key Laboratory of Convergence Medical Engineering System and Healthcare Technology Beijing Institute of Technology Beijing China

ISBN: (纸本)9781509023974

Information exchanges and cooperative movements of multiple robots have become a hot topic in robotics. To increase the adaptability of robots in amphibious scenarios, an improved amphibious spherical robot was designed in this paper. However, the ability of single robot was limited. To further increase the sensing range and work efficiency of own amphibious spherical robots, a Leader-follower method, which could realize the coordinated movement and formation keeping for three or more robots, was adopted in this paper. The theoretical analysis show that the Leader-follower method could be easily applied in amphibious spherical robots for practical applications. And a simulation experiment platform named Player/Stage was used for verifying the effectiveness of this method. The construction of the experimental environment and the final simulation results were provided in this paper. Through the analysis of experimental results, the feasibility of the Leader-follower method was verified, and this method will be used to implement multiple amphibious spherical robots cooperative motion in future works.

关键词： Robot sensing systems Robot kinematics Legged locomotion Buildings Angular velocity Biology

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