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TILLING and ecotilling the Plant Kingdom

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分子植物育种 2007年第2期5卷 238-239页

作者： B. Till J. Cooper C. Codomo A. Holm M. Darlow e. Greene L. Comai S. Henikoff fred Hutchinson Cancer Research Center 1100 Fairview Ave N Seattle WA 98109-1024 USA Section of Plant Biology and Genome Center UC Davis Davis California 95616 USA

The modern crop scientist has a large amount of available nucleotide sequence information to identify genes of potential agronomic importance. Using reverse genetic approaches, specifi c genes can be disrupted, and hy-

关键词：基因突变植物耕种

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早期乳腺癌最佳辅助化疗方案与人类表皮生长因子受体2阳性乳腺癌辅助靶向治疗选择：依据 ASCO 对 CCO临床实践指南的改编

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中国全科医学 2016年第18期19卷 2113-2114页

作者： Neelima Denduluri Mark R Somerfield Andrea eisen Jamie N Holloway Arti Hurria Tari A King Gary H Lyman Ann H Partridge Melinda L Telli Maureen e Trudeau Antonio C Wolff 本刊编辑部 US Oncology Network Virginia Cancer Specialists American Society of Clinical Oncology Sunnybrook Health Sciences Centre and Cancer Care Ontario City of Hope Dana-Farber/Brigham and Women' s Cancer Center fred Hutchinson Cancer Research Center Dana-Farber Cancer Institute Stanford University The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

目的研究加拿大安大略癌症治疗中心(CCO)关于早期乳腺癌最佳辅助化疗方案,包括人类表皮生长因子受体2(HeR2)阳性乳腺癌辅助靶向治疗方案,并对其进行改编。方法按照美国临床肿瘤协会(ASCO)对其他组织临床实践指南改编的策略和程序,对CCO... 详细信息

目的研究加拿大安大略癌症治疗中心(CCO)关于早期乳腺癌最佳辅助化疗方案,包括人类表皮生长因子受体2(HeR2)阳性乳腺癌辅助靶向治疗方案,并对其进行改编。方法按照美国临床肿瘤协会(ASCO)对其他组织临床实践指南改编的策略和程序,对CCO临床实践指南的严谨性与内容适用性进行回顾。结果基于对CCO临床实践指南内容的回顾,ASCO小组认为,CCO临床实践指南在整体上清晰全面,以最确切的科学证据为基础,为患者提供可接受的治疗选项。推荐关于辅助化疗方案的决定,应考虑到基线复发风险、毒性、利益可能性和宿主因素(如合并症)。对于高风险HeR2阴性的身体状况良好的人群,蒽环类和紫杉烷治疗方案是标准治疗方案。4个周期的多西他赛和环磷酰胺治疗方案是可接受的非蒽环类治疗方案。对于高风险HeR2阳性患者,推荐蒽环类与紫杉烷序贯疗法联合曲妥单抗或多西他赛、卡铂、曲妥单抗进行6个周期的治疗。对于低风险、非淋巴结转移、HeR2阳性人群,推荐每周一次的紫杉醇和曲妥单抗连续进行12个周期的替代治疗。曲妥单抗应持续使用1年。不应采用铂复合盐对三阴性人群进行常规的辅助管理,除非出现有效的生存数据加以支持。

关键词：乳腺肿瘤抗肿瘤联合化疗方案受体,表皮生长因子指南

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Ventilation practices in burn patients—an international prospective observational cohort study

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Burns & Trauma 2021年第1期9卷 47-57页

作者： Gerie J.Glas Janneke Horn Markus W.Hollmann Benedikt Preckel Kirsten Colpaert Manu Malbrain Ary Serpa Neto Karim Asehnoune Marcello Gamma de Abreu Ignacio Martin-Loeches Paolo Pelosi Folke Sjoerg Jan M.Binnekade Berry Cleffken Nicole P.Juffermans Paul Knape Bert G.Loef David P.Mackie Perenlei enkhbaatar Nadia Depetris Anders Perner eva Herrero Lucia Cachafeiro Marc Jeschke Jeffrey Lipman Matthieu Legrand Johannes Horter Athina Lavrentieva Alex Kazemi Anne Berit Guttormsen frederik Huss Mark Kol Helen Wong Therese Starr Luc De Crop Wilson de Oliveira Filho Joa Manoel Silva Junior Cintia M.C.Grion Marjorie Burnett frederik Mondrup Francois Ravat Mathieu Fontaine Renan Le Floch Mathieu Jeanne Morgane Bacus Maite Chaussard Marcus Lehnhardt Bassem Daniel Mikhail Jochen Gille Aidan Sharkey Nicole Trommel Auke C.Reidinga Nadine Vieleers Anna Tilsley Henning Onarheim Maria Teresa Bouza Alexander Agrifoglio Filip fredén Tina Palmieri Lynda e.Painting Marcus J.Schultz LAMiNAR investigators Academic Medical Center University of AmsterdamAmsterdamAZ 1105The Netherlands Department of Anaesthesia and Intensive Therapy Medical University of Lublin Aleje Racklawickie 1–20-059 Lublin–Poland AZ JAN PALFIJN GeNT Watersportlaan 5–9000 Gent–Belgium ABC Medical School SaPauloBangúSP 5001Brazil Service d’Anesthésie Réanimation Chirurgicale Nantes 44093France University Hospital Carl Gustav Carus Dresden 01307Germany St James University Hospital Dublin D08 NHY1Ireland University of Genoa GenoaGE 16128Italy Linkoing University Hospital Linkoing 58185Sweden Maasstad Hospital RotterdamDZ 3079The Netherlands Red Cross Hospital BeverwijkLE 1942The Netherlands Martini Hospital GroningenNT 9728The Netherlands University of Texas Medical Branch GalvestonTX 77555USA Turin CTO Burn Center TurinTO 10126Italy Rigshospitalet Copenhagen 2100Denmark La Paz University Hospital Madrid 28046Spain Ross Tilley Burn Centre Sunnybrook Health Sciences CentreToronto M4N 3M5Canada Royal Brisbane and Women’s Hospital Queensland UniversityHerstonQLD 4029Australia Australian and New Zealand Intensive Care Research Centre.Monash University MelbourneVIC 3004Australia GH St-Louis-Lariboisière APHPParis 75010France BG Klinik Ludwigshafen Ludwigshafen 67071Germany Papanikoalou Hospital Thessaloniki 54621Greece Middlemore Hospital OtahuhuAuckland 2025New Zealand Haukeland University Hospital Bergen 5021Norway Uppsala University Hospital Uppsala 75185Sweden Concord Repatriation General Hospital NSW University of SydneyConcord 2139Australia Ziekenhuis Netwerk Antwerpen-Stuivenberg Antwerpen 2060Belgium Universidade de Sao Paulo Sao Paulo 01246-903Brazil Universidade estadual de Londrina Londrina 86057-970Brazil Sunnybrook Health Sciences Centre Toronto M4N 3M5Canada CHU Lyon St Luc Lyon 69007France CHU Nantes Service dánesthesie reanimation chirugicale Nantes 44093France Hopital Roger Salengro CHRU LilleLille 59037France Saint-Louis Hospital Paris 75010France BG University Hospital Bergmannsheil Bo

Background:It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from *** study aimed to determine ventilation practices in burn intensive care units(ICUs)and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28(VFD-28).Methods:This is an international prospective observational cohort study including adult burn patients requiring mechanical *** tidal volume(V_(T))was defined as V_(T)≤8 mL/kg predicted body weight(PBW).Levels of positive end-expiratory pressure(PeeP)and maximum airway pressures were *** association between V_(T) and VFD-28 was analyzed using a competing risk *** settings were presented for all patients,focusing on the first day of *** also compared ventilation settings between patients with and without inhalation ***:A total of 160 patients from 28 ICUs in 16 countries were *** V_(T) was used in 74%of patients,median V_(T) size was 7.3[interquartile range(IQR)6.2–8.3]mL/kg PBW and did not differ between patients with and without inhalation trauma(p=0.58).Median VFD-28 was 17(IQR 0–26),without a difference between ventilation with low or high V_(T)(p=0.98).All patients were ventilated with PeeP levels≥5 cmH_(2)O;80%of patients had maximum airway pressuresernational cohort study we found that lung-protective ventilation is used in the majority of burn patients,irrespective of the presence of inhalation *** of low V_(T) was not associated with a reduction in *** registration:*** *** of registration:9 December 2014.

关键词： Mechanical ventilation Inhalation trauma Lung-protective Critical care

Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection

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World Journal of AIDS 2013年第1期3卷 36-40页

作者： Jonathan e. Schelfhout Danijela A. Stojanovic Amy Houtchens Heidi M. Crane edward R. Cachay elizabeth R. Brown Sonia M. Napravnik Mari M. Kitahata Michael S. Saag Peter W. Hunt Teresa L. Kauf Joseph A. C. Delaney Department of epidemiology University of Washington Seattle WA Department of Medicine University of Alabama at Birmingham Birmingham USA Department of Medicine University of California at San Diego San Diego USA Department of Medicine University of California at San Francisco San Francisco USA Department of Medicine University of North Carolina Chapel Hill USA Division of Allergy & Infectious Disease Department of Medicine University of Washington Seattle USA Food and Drug Administration Silver Spring USA Vaccine and Infectious Disease and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center Seattle USA

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL;p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL;p-value 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

关键词： HCV HIV AIDS Co-Infection Platelet Count Thrombocytopenia

CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

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Health 2013年第5期5卷 23-40页

作者： Roger A. Schultz Karen Tsuchiya Aubry Furrow Marilyn L. Slovak Lisa D. McDaniel Meaghan Wall eric Crawford Yi Ning Reza Saleki Min Fang Victoria Cawich Caitlin e. Johnson Sara L. Minier Nicholas J. Neill S. Annie Morton Steve Byerly Urvashi Surti Theresa C. Brown Blake C. Ballif Lisa G. Shaffer Department of Molecular and Human Genetics Baylor College of Medicine Houston USA empire Genomics Buffalo USA fred Hutchinson Cancer Research Center Seattle USA Genetics Associates Inc. Nashville USA Johns Hopkins University School of Medicine Baltimore USA Magee-Womens Hospital University of Pittsburgh Medical Center Pittsburgh USA Pathology Associates Medical Laboratories (PAML) Spokane USA Paw Print Genetics Genetic Veterinary Sciences Inc. Spokane USA Seattle Children’s Hospital Seattle USA Signature Genomic Laboratories PerkinElmer Inc. Spokane USA Signature Genomic Laboratories PerkinElmer Inc. Spokane USA Sonora Quest Laboratories Tempe USA Victorian Cancer Cytogenetics Service St. Vincent’s Hospital Melbourne Fitzroy Australia

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the majority of cases being of precursor B-cell phenoltype. Conventional cytogenetic analysis plays an important role in the diagnosis of B-cell ALL, identifying characteristic chromosomal abnormalities associated with a given prognosis therein facilitating optimized treatment. The more recent introduction of microarray technology to the analysis of B-cell ALL has afforded both higher resolution for the detection of known abnormalities and an ability to identify novel copy number abnormalities (CNAs) with potential clinical relevance. In the current study, microarray analysis was performed on 20 cytogenetically abnormal B-cell ALL cases (10 pediatric and 10 adult), while a novel microarray-based balanced-translocation detection methodology (translocation CGH or tCGH) was applied to that subset of cases with a known or suspected recurrent balanced translocation. Standard microarray analysis identified that CNAs was not detected by previous conventional cytogenetics in 75% (15/20) cases. tCGH identified 9/9 (100%) balanced translocations defining BCR/ABL1 (x4), eTV6/RUNX1 (x3), and MLL/AFF1 (x2) breakpoints with high resolution. The results illustrate the improved molecular detail afforded by these technologies and a comparison of translocation breakpoints, CNAs and patient age offers new insights into tumor biology with potential prognostic significance.

关键词： Acute Lymphoblastic Leukemia B-Cell ALL Microarray Balanced Translocation Translocation CGH Hematologic Malignancies

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

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