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World Journal of Gastroenterology 2020年第15期26卷 1683-1690页

作者： paul brennan Kathleen Clare Jacob George John F Dillon Department of Molecular and Clinical Medicine University of DundeeNinewells Hospital and Medical SchoolDundee DD19SYUnited Kingdom Department of Neurology Queen Elizabeth HospitalGlasgow G514TFUnited Kingdom

There has long been a recognised association between non-alcoholic fatty liver disease(NAFLD)and the composite aspects of the metabolic *** of this association highlighted the supposed co-existence of elevated uric acid levels in those with *** is interest in exploitation of this as a putative diagnostic and prognostic biomarker in *** the increased economic and health burden associated with the NAFLD epidemic,improved methods of population-based,minimally-invasive methods and biomarkers are clearly highly sought and *** this opinion review we review the proposed role of uric acid in the pathogenesis of NAFLD and its potential utilisation in the diagnosis and monitoring of the disease process.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Uric acid Urate Non-invasive fibrosis markers Fatty liver index

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加拿大应用技术学院的特征研究及启示

中国职业技术教育 2019年第18期35卷 76-82页

作者：邓泽民 paul brennan 教育部职业技术教育中心研究所北京100029 加拿大学院大学协会加拿大

加拿大应用技术学院经过多年探索,逐步形成了以应用学位引领,突出应用研究,培养应用人才的"三应用"为基本特征的应用技术大学教育。我国建设应用技术大学,可以借鉴加拿大应用技术学院在应用学位、应用研究及应用人才培养等方面的办学经... 详细信息

加拿大应用技术学院经过多年探索,逐步形成了以应用学位引领,突出应用研究,培养应用人才的"三应用"为基本特征的应用技术大学教育。我国建设应用技术大学,可以借鉴加拿大应用技术学院在应用学位、应用研究及应用人才培养等方面的办学经验,实施应用学位教育计划,授予转型高校应用学位授予权;加大应用学位教育教学改革力度,加强应用研究,将应用研究作为应用学位授予权的重要评价指标;实施通过服务产业发展促进学生成长的教育理念和评价制度,逐步建立起有利于应用技术大学发展的制度和运行机制。

关键词：应用学位应用研究应用人才地方本科转型应用技术大学

Blood metal concentrations and cardiac structure and function in total joint arthroplasty patients

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World Journal of Orthopedics 2024年第8期15卷 773-782页

作者： Peter C brennan Stephanie M Peterson Thomas J O'Byrne Mariana L Laporta Cody C Wyles paul J Jannetto Garvan C Kane Maria Vassilaki Hilal Maradit Kremers Department of Orthopedic Surgery Mayo ClinicRochesterMN 55905United States Department of Quantitative Health Sciences Mayo ClinicRochesterMN 55905United States Department of Anesthesiology and Perioperative Medicine Mayo ClinicRochesterMN 55905United States Department of Laboratory Medicine and Pathology Mayo ClinicRochesterMN 55905United States Department of Cardiovascular Diseases Mayo ClinicRochesterMN 55905United States

BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)*** To determine the association of commonly used implant metals with echocardiographic measures in TJA *** The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium *** underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal *** and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac *** titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some *** studies are warranted to better understand the systemic effects of metals in TJA patients.

关键词： Total joint arthroplasty Metal-on-metal Cardiotoxicity Heart failure Echocardiography Cobalt

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold paul brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis of MAFLD

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 939-946页

作者： Kathleen Clare John F.Dillon paul N.brennan Royal Alexandra Hospital PaisleyNHS Greater Glasgow and ClydePA29PNUK University of Dundee Ninewells Hospital and Medical SchoolDundeeDD19SYUK University of Edinburgh Edinburgh BioQuarter5 Little France DriveEH164UUUK

The pathogenesis of metabolic-associated fatty liver disease(MAFLD)is complex and thought to be dependent on multiple parallel hits on a background of genetic *** evidence suggests that MAFLD progression is a dynamic two-way process relating to repetitive bouts of metabolic stress and inflammation interspersed with endogenous anti-inflammatory reparative *** MAFLD,excessive hepatic lipid accumulation causes the production of lipotoxins that induce mitochondrial dysfunction,endoplasmic reticular stress,and over production of reactive oxygen species(ROS).Models of MAFLD show marked disruption of mitochondrial function and reduced oxidative capacitance with impact on cellular processes including mitophagy,oxidative phosphorylation,and mitochondrial *** excess,ROS modify insulin and innate immune signaling and alter the expression and activity of essential enzymes involved in lipid *** can also cause direct damage to intracellular structures causing hepatocyte injury and *** select cases,the use of anti-oxidants and ROS scavengers have been shown to diminish the proapoptopic effects of fatty *** this link,endogenous anti-oxidant pathways have been a target of interest,with Nrf2 activation showing a reduction in oxidative stress and inflammation in models of *** hormone receptorβ(THRβ)agonists and nuclear peroxisome proliferationactivated receptor(PPAR)family have also gained interest in reducing hepatic lipotoxicity and restoring hepatic function in models of ***,the true interplay between the clinical and molecular components of MAFLD progression remain only partly *** recently,multiomics-based strategies are being adopted for hypothesis-free analysis of the molecular changes in *** profiling maps the unique genotype-phenotype associations in MAFLD and with various single-cell tran scriptome-based projects underway,there is hope of novel physiological insigh

关键词： Fatty liver disease Metabolic-associated fatty liver disease Nonalcoholic steatohepatitis Reactive oxidation species Oxidative stress

Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

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Assessment of Lung Cancer Risk on the Basis of a Biomarker P...

Prospective,multicentre study of screening,investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青年科学家论坛

作者： sun,nan Florence,Guida Bantis,LeonidasE. Muller,DavidC. Li,Peng Taguchi,Ayumu Dhillon,Dilsher Kundnani,DeepaliL. Patel,NikulJ. Yan,Qingxiang Byrnes,Graham Moons,KarelG.M. Tj?nneland,Anne Panico,Salvatore Claudia ,Agnoli Vineis,Paolo Palli,Domenico Bueno-de-Mesquita,Bas Peeters,PetraH. Agudo,Antonio Huerta,JoseM. Dorronsoro,Miren Barranco,MiguelRodriguez Ardanaz,Eva Travis,RuthC. Byrne,KarlSmith Boeing,Heiner Steffen,Annika Kaaks,Rudolf Hüsing,Anika Trichopoulou,Antonia Lagiou,Pagona LaVecchia,Carlo Severi,Gianluca Boutron-Ruault,Marie-Christine Sandanger,TorkjelM. Weiderpass,Elisabete N?st,ThereseH. Tsilidis,Kostas Riboli,Elio Grankvist,Kjell Johansson,Mikael Goodman,GaryE. Feng,Ziding brennan,paul Johansson,Mattias Hanash,Samir M. The University of Texas MD Anderson Cancer Center Genetic Epidemiology Group International Agency for Research on Cancer Department of Biostatistics The University of Texas MD Anderson Cancer Center Department of Epidemiology and Biostatistics Imperial College London School of Public Health Laboratory of Population Health Max Planck Institute for Demographic Research Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Environment and Radiation Section International Agency for Research on Cancer Department of Epidemiology Julius Center for Health Sciences and Primary CareUniversity Medical Center Unit of Diet Genesand EnvironmentDanish Cancer Society Research Center Department of Clinical Medicine and Surgery Federico Ⅱ University Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Molecular and Genetic Epidemiology Unit Human Genetics Foundation Cancer Risk Factors and Life-Style Epidemiology Unit Cancer Research and Prevention Institute-Istituto per lo Studio ela Prevenzione Oncologica Department for Determinants of Chronic Diseases National Institute for Public Health and the Environment Unit of Nutirition and Cancer Cancer Epidemiology Research ProgramCatalan Institute of OncologyBellvitge Institute for Biomedical Research (IDIBELL)L’Hospitalet de Llobregat Department of Epidemiology Murcia Regional Health Council Biomedical Research Institute of Murcia(IMIB-Arrixaca) Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP) Public Health Direction and Biodonostia Research Institute-CIBERESP Escuela Andaluza de Salud Pública Instituto de Investigación Biosanitaria Hospitales Universitarios de Granada/Universidad de Granada Epidemiology Preventionand Promotion Health ServiceNavarra Public Health Institute Instituto de Investigación Sanitaria de Navarra (IdiSNA) Navarra Institute for Health Research Cancer Epidemiology Unit Nuffield Department of Population HealthUniversity of Oxford Department of Epidemi

IMPORTANCE:There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of ***:To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria.

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Stroke & Vascular Neurology 2023年第3期8卷 207-216,I0028-I0059页

作者： James J M Loan Steven Tominey Kirun Baweja Julie Woodfield Thomas J G Chambers Mark Haley Simran S Kundu H Y Josephine Tang Anthony N Wiggins Michael T C Poon paul M brennan Translational Neurosurgery The University of Edinburgh Centre for Clinical Brain SciencesEdinburghUK Neurosurgery NHS LothianEdinburghUK Neurosurgery Institute of Neurological SciencesGlasgowUK Department of Medicine School of MedicineDentisty and NuringUniversity of GlasgowGlasgowUK Internal Medicine Queen's UniversityKingstonOntarioCanada Centre for Discovery Brain Sciences University of EdinburghEdinburghUK Edinburgh Centre for Diabetes and Endocrinology NHS LothianEdinburghUK Radiology University Hospitals Plymouth NHS TrustPlymouthUK Department of Medicine Cork University HospitalUniversity College CorkCorkIreland

Background Hyponatraemia often occurs after subarachnoid haemorrhage(SAH).However,its clinical significance and optimal management are *** audited the screening,investigation and management of hyponatraemia after *** We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or *** reviewed medical records daily from admission to discharge,21 days or death and extracted all measurements of serum sodium to identify hyponatraemia(10 *** of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission *** assessed hyponatraemia-free survival using multivariable Cox *** 175/407(43%)patients admitted to 24 neurosurgical units developed hyponatraemia.5976 serum sodium measurements were *** osmolality,urine osmolality and urine sodium were measured in 30/166(18%)hyponatraemic patients with complete *** most frequently target daily fluid intake was>3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes.26%(n/N=42/164)patients with hyponatraemia received sodium supplementation.133(35%)patients were dead or dependent within the study period and 240(68%)patients had hospital admission for over 10 *** the multivariable analyses,hyponatraemia was associated with less dependency(adjusted OR(aOR)=0.35(95%CI 0.17 to 0.69))but longer admissions(aOR=3.2(1.8 to 5.7)).World Federation of Neurosurgical Societies grade I-III,modified Fisher 2-4 and posterior circulation aneurysms were associated with greater hazards of *** In this comprehensive multicentre prospective-adjusted analysis of patients with SAH,hyponatraemia was investigated inconsistently and,for most patients,was not associated with changes in management or clinical outcome.T

关键词： admitted urine centre

Synchrophasing Vibration Control of Machines Supported by Discrete Isolators

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Journal of Marine Science and Application 2019年第2期18卷 195-204页

作者： Di Huang Tiejun Yang Zhigang Liu Michael J.brennan Xinhui Li College of Power and Energy Engineering Harbin Engineering UniversityHarbin 150001China Departamento de Engenharia Mecanica UNESPSt.Paul 03001-000Brazil

This paper describes an analytical investigation into synchrophasing,a vibration control strategy on a machinery installation in which two rotational machines are attached to a beam-like raft by discrete resilient *** and moments introduced by sources are considered,which effectively represent a practical engineering *** the relative phase angle between the machines has been theoretically demonstrated to greatly reduce the cost function,which is defined as the sum of velocity squares of attaching points on the raft at each frequency of *** effect of the position of the machine is also *** show that altering the position of the secondary source may cause a slight change to the mode shape of the composite system and therefore change the optimum phase between the two *** the analysis is based on a one-dimensional Euler– Bernoulli beam and each machine is considered as a rigid-body,a key principle can be derived from the ***,the factors that can influence the synchrophasing control performance would become coupled and highly *** condition has to be considered in practice.

关键词： Discrete supported machines Vibration isolation Raft Synchrophasing control.Different forms of excitations