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阿尔茨海默病的血液生物标志物:一项基于中国多中心的横断面和纵向研究

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Science Bulletin 2023年第16期68卷 1800-1808,M0004页

作者：高峰戴林斌王琼刘畅邓克学程昭昭吕心怡吴燕张子伊陶青青袁晶李世平王越苏娅程忻倪俊吴志英张舒婷施炯申勇 China aging and Neurodegenerative Initiative(CANDI)consortium Department of Neurology Institute on Aging and Brain DisordersThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Neurodegenerative Disorder Research Center Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Department of Radiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Neurology West China HospitalSichuan UniversityChengdu 610041China Department of Neurology and Research Center of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of Neurology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100006China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurology National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China Anhui Province Key Laboratory of Biomedical aging Research University of Science and Technology of ChinaHefei 230001China 不详

阿尔茨海默病(AD)的生物标志物在血液中含量可能因种族、老年性疾病与各种环境风险因素等不同而存在差异,尚缺乏系统性的研究来评估AD生物标志物在中国老年及AD患者人群中的变化以及是否具有准确预测脑内淀粉样蛋白沉积的能力.本工作为... 详细信息

阿尔茨海默病(AD)的生物标志物在血液中含量可能因种族、老年性疾病与各种环境风险因素等不同而存在差异,尚缺乏系统性的研究来评估AD生物标志物在中国老年及AD患者人群中的变化以及是否具有准确预测脑内淀粉样蛋白沉积的能力.本工作为一项多中心纵向队列研究,共纳入来自全国各地6个不同临床中心的817个血液样本.研究测量了多个国际上通用的AD生物标志物,包括β-淀粉样蛋白40与42、磷酸化Tau(pTau)蛋白、总Tau蛋白、神经纤维丝轻链(NFL)和胶质纤维酸性蛋白(GFAP),并使用淀粉样斑块PET示踪剂和核磁结构影像对受试者进行综合评估.研究发现,APOE基因型与血浆pTau或血清GFAP组合的预测模型对脑内淀粉样斑块的沉积状态具有较好的区分能力.此外,研究还发现GFAP基线水平越高的患者其神经退行性变的速度越快.本研究结果基于多中心数据,论证了AD血液生物标志物在中国汉族人群中的实用性和应用前景,提示了血液pTau和GFAP是检测AD早期症状的有效指标,为我国AD的早期诊断和治疗提供了参考.

关键词：临床中心 Tau蛋白神经退行性变生物标志物老年性疾病基线水平血液样本示踪剂

Responsible research and innovation training programmes:implementation and evaluation of the HEIRRI project

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Forensic Sciences Research 2021年第3期6卷 320-330页

作者： Ružica Tokalić Ivan Buljan Niels Mejlgaard Mar Carrió Alexander Lang Gema Revuelta Ana Marušić HEIRRI consortium Department of research in Biomedicine and health University of split school of Medicinesplitcroatia Danish centre for studies in research and research Policy Department of Political scienceaarhus UniversityaarhusDenmark health sciences education research Group Department of experimental and health sciencesPompeu Fabra UniversityBarcelonaspain Techno-science&societal Transformation research Group institut für höhere studien-institute for advanced studies(i)Viennaaustria estudies centre on science communication and societyDepartment of experimental and health sciencesPompeu Fabra UniversityBarcelonaspain

Responsible research and innovation,or RRI,is a concept that aims to bring together society and science for a better *** are six key elements of RRI:public engagement,gender equality,science education,open access,ethics and *** Education Institutions and Responsible Research and Innovation(HEIRRI)project aimed to bring the concept of RRI into the educational *** state-of-the-art review of good practices,HEIRRI team developed 10 training programmes on RRI for different higher education institution educational levels,including a summer school and a massive open online course(MOOC).We conducted pilot of the trainings and evaluated participants’*** with HEIRRI training programmes on responsible research and innovation was high,both for participants and for the trainers,and trainings raised awareness of ***’feedback was used to identify areas that need improvement and provided for recommendations for final versions of the HEIRRI training *** order to equip researchers with skills to recognize and apply RRI values,RRI should be included in their *** training is suitable for a range of different disciplines,including forensic science,and is free to use and adjust for specific contexts(available from:https://***/heirri-training-programmes).

关键词： Research integrity research ethics responsible research and innovation responsibility societal inclusion higher education institutions RRI teaching

Animal models of hepatitis E infection: Advances and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 171-180页

作者： Ze Xiang Xiang-Lin He Chuan-Wu Zhu Jia-Jia Yang Lan Huang Chun Jiang Jian Wu Chinese consortium for the Study of Hepatitis E(CCSHE) Zhejiang University School of Medicine Hangzhou 310030China Department of Infectious Diseases The Fifth People’s Hospital of SuzhouSuzhou 215007China Department of Infection Management The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China Department of Clinical Laboratory The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China 不详

Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis *** most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and *** infection may become chronic in immunosuppressed *** addition,HEV infection can also cause several extrahepatic *** exists in a wide range of hosts in nature and can be transmitted across ***,animals susceptible to HEV can be used as *** establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis *** review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other *** each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV *** advantages and disadvantages of these animal models were also *** review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

关键词： Hepatitis E virus Animal models Pathogenesis Prevention Treatment

Discovering and timing a high altitude extreme ecotype of Arabidopsis thaliana from Tibet

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Discovering and timing a high altitude extreme ecotype of Ar...

A map of human genome variation from population-scale sequencing

2016年全国植物生物学大会

作者： The Tibetan Arabidopsis thaliana Research consortium The Tibetan Arabidopsis thaliana Research consortium

Arabidopsis thaliana illuminates the plant world for *** on *** have unraveled the mystery of plant genetics,physiology,and adaptive *** more than ten years of exploration,we discovered a wild *** population and named it Tibet-0 representing 4200 m above sea level in Qinghai-Tibet Plateau(QTP).Phylogenetic analysis and coalescent methods based on genome-wide resequencing both showed that Tibet-0 is the most primitive *** ecotypes.

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A map of human genome variation from population-scale sequen...

Identification of Genetic Variants Underlying Anxiety and Multiple Sclerosis in Heterogeneous Stock Rats

培育生物产业，发展绿色经济——第五届中国生物产业大会·2011基因科学与产业发展论坛

作者： The 1000 Genomes Project consortium The 1000 Genomes Project consortium

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and *** we present results of the pilot phase of the project,designed to develop and compare different strategies for genome-wide sequencing with high-throughput *** undertook three projects:low-coverage whole-genome sequencing of 179 individuals from four populations;high-coverage sequencing of two mother-father-child trios;and exon-targeted sequencing of 697 individuals from seven *** describe the location,allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms,1 million short insertions and deletions,and 20,000 structural variants,most of which were previously *** show that,because we have catalogued the vast majority of common variation,over 95%of the currently accessible variants found in any individual are present in this data *** average,each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited *** demonstrate how these results can be used to inform association and functional *** the two trios,we directly estimate the rate of de novo germline base substitution mutations to be approximately 10 per base pair per *** explore the data with regard to signatures of natural selection,and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked *** methods and public data will support the next phase of human genetic research.

关键词： A map of human genome variation from population-scale sequencing

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World Journal of Neuroscience 2014年第3期4卷 216-224页

作者： Amelie Baud Jonathan Flint Alberto Fernandez-Teruel The Rat Genome Sequencing Mapping consortium EMBL-EBI Wellcome Trust Genome Campus Hinxton UK Medical Psychology Unit Department of Psychiatry & Forensic Medicine Institute of Neurosciences Universitat Autònoma de Barcelona Barcelona Spain. The Rat Genome Sequencing Mapping consortium Wellcome Trust Centre for Human Genetics Oxford UK

Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.

关键词： Genetic Mapping Imputation Causal Variants Anxiety Multiple Sclerosis Complex Traits

Mako:A Graph-based Pattern Growth Approach to Detect Complex Structural Variants

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Genomics, Proteomics & Bioinformatics 2022年第1期20卷 205-218页

作者： Jiadong Lin Xiaofei Yang Walter Kosters Tun Xu Yanyan Jia Songbo Wang Qihui Zhu Mallory Ryan Li Guo Chengsheng Zhang The Human Genome Structural Variation consortium Charles Lee Scott E.Devine Evan E.Eichler Kai Ye School of Automation Science and Engineering Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China MOE Key Lab for Intelligent Networks&Networks Security Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China Genome Institute the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Leiden Institute of Advanced Computer Science Faculty of ScienceLeiden UniversityLeiden 2311EZNetherland School of Computer Science and Technology Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China The Jackson Laboratory for Genomic Medicine FarmingtonCT 06032USA Precision Medicine Center the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Institute for Genome Sciences University of Maryland School of MedicineBaltimoreMD 21201USA Department of Genome Sciences University of Washington School of MedicineSeattleWA 98119USA Howard Hughes Medical Institute University of WashingtonSeattleWA 98195USA The School of Life Science and Technology Xi’an Jiaotong UniversityXi’an 710049China 不详

Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural ***,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match *** a result,there has been limited progress for CSV discovery compared with simple structural ***,we systematically analyzed the multi-breakpoint connection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read ***,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined *** evaluations on both simulated and real datasets revealed that Mako outperformed other ***,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,***,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed *** analysis of these CSVs also revealed the impact of sequence homology on the formation of *** is publicly available at https://***/xjtu-omics/Mako.

关键词： Next-generation sequencing Complex structural variant Pattern growth Graph mining Formation mechanism

Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer's disease

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Translational Neurodegeneration 2020年第3期9卷 458-472页

作者： Jin Xu Giulia Bankov Min Kim Asger Wretlind Jodie Lord Rebecca Green Angela Hodges Abdul Hye Dag Aarsland Latha Velayudhan Richard J.B.Dobson Petroula Proitsi Cristina Legido-Quigley on behalf of the AddNeuroMed consortium Institute of Pharmaceutical Science King's College LondonLondonUK. Institute of Psychiatry Psychology&NeuroscienceKing's College LondonLondonUK. Steno Diabetes Center Copenhagen GentofteDenmark Center for Age Related Medicine Stavanger University HospitalStavangerNorway 不详

Background:There is an urgent need to understand the pathways and processes underlying Alzheimer's disease(AD)for early diagnosis and development of effective *** study was aimed to investigate Alzheimer's dementia using an unsupervised lipid,protein and gene multi-omics integrative ***:A lipidomics dataset comprising 185 AD patients,40 mild cognitive impairment(MCI)individuals and 185 controls,and two proteomics datasets(295 AD,159 MCI and 197 controls)were used for weighted gene CO-expression network analyses(WGCNA).Correlations of modules created within each modality with clinical AD diagnosis,brain atrophy measures and disease progression,as well as their correlations with each other,were *** ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD *** species were annotated in the lipid modules associated with AD *** associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also ***:Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis,brain atrophy measures and disease *** lipid modules comprising phospholipids,triglycerides,sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid *** five protein modules involved in positive regulation of cytokine production,neutrophil-mediated immunity,and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism(the APOE ε4 genotype).Conclusions:Modules of tightly regulated lipids and proteins,drivers in lipid homeostasis and innate immunity,are strongly associated with AD phenotypes.

关键词： Alzheimer's disease Dementia Brain atrophy sMRI Rate of cognitive decline Lipidomics Proteomics AD risk loci WGCNA

2011第二届亚洲青少年钢琴艺术节暨纪念李斯特诞辰200周年国际青少年钢琴公开赛

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小演奏家 2011年第5期 66-67页

作者： (International Arts Education consortium Limited) 国际艺术教育联盟

艺术简介此次活动是在＂2010第一届亚洲青少年钢琴艺术节暨纪念肖邦诞辰200周年＂活动的基础上发起的,旨在通过开展普及性钢琴艺术活动,以加强同行业之间的交流,以期共同繁荣、发展与提高普遍的钢琴教育及管理水平。

关键词：钢琴教育青少年艺术节诞辰纪念亚洲公开赛李斯特