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Glioblastoma stem cells(GSCs)epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs

Genes & Diseases 2015年第2期2卷 152-163页

作者： Ahmad R.Safa Mohammad Reza Saadatzadeh aaron A.cohen-Gadol Karen E.Pollok Khadijeh Bijangi-Vishehsaraei Indiana University Simon Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA Department of Pharmacology and Toxicology Indiana University School of MedicineIndianapolisIN 46202USA Department of Neurosurgery IU School of Medicine and Goodman Campbell Brain and SpineIndiana University School of MedicineIndianapolisIN 46202USA Herman B.Wells Center for Pediatric Research Indiana University School of MedicineIndianapolisIN 46202USA Otolaryngology-Head and Neck Surgery Indiana University School of MedicineIndianapolisIN 46202USA

Cancer stem cells(CSCs)or cancer initiating cells(CICs)maintain self-renewal and multilineage differentiation properties of various tumors,as well as the cellular heterogeneity consisting of several subpopulations within *** display the malignant phenotype,self-renewal ability,altered genomic stability,specific epigenetic signature,and most of the time can be phenotyped by cell surface markers(e.g.,CD133,CD24,and CD44).Numerous studies support the concept that non-stem cancer cells(non-CSCs)are sensitive to cancer therapy while CSCs are relatively resistant to *** glioblastoma stem cells(GSCs),there is clonal heterogeneity at the genetic level with distinct tumorigenic potential,and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to *** level of complexity in glioblastoma multiforme(GBM)tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs,and the potential for non-GSCs to revert(dedifferentiate)to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell ***,exposure of the differentiated GBM cells to therapeutic doses of temozolomide(TMZ)or ionizing radiation(IR)increases the GSC pool both in vitro and in *** review describes various subtypes of GBM,discusses the evolution of CSC models and epigenetic plasticity,as well as interconversion between GSCs and differentiated non-GSCs,and offers strategies to potentially eliminate GSCs.

关键词： Cancer stem cells Epigenetic GBM plasticity Glioblastoma Stemness Dedifferentiation GBM stem cells

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Emerging targets for glioblastoma stem cell therapy

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The Journal of Biomedical Research 2016年第1期30卷 19-31页

作者： Ahmad R.Safa Mohammad Reza Saadatzadeh aaron A.cohen-Gadol Karen E.Pollok Khadijeh Bijangi-Vishehsaraei Indiana University Simon Cancer Center IU School of Medicine and Goodman Campbell Brain and Spine Department of Pharmacology and Toxicology IU School of Medicine and Goodman Campbell Brain and Spine Department of Neurosurgery IU School of Medicine and Goodman Campbell Brain and Spine Herman B.Wells Center for Pediatric Research Indiana University School of MedicineIndianapolisIN 46202USA.

Glioblastoma multiforme（GBM）,designated as World Health Organization（WHO）grade IV astrocytoma,is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations,including GBM stem cells（GSCs）which are believed to contribute to tumor recurrence following initial response to *** evidence demonstrates that GBM tumors are initiated from *** development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate sternness,proliferation and migration of GSCs,immunotherapy,and non-coding microRNAs may provide better means of treating *** and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting *** signaling pathways including mTOR,AKT,maternal embryonic leucine zipper kinase（MELK）,NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133,CD44,Oct4,Sox2,Nanog,and ALDHlA1 maintain GSC ***,the data published in the Cancer Genome Atlas（TCGA）specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM *** such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation ***,recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs,but the differentiated GBM cells and the entire bulk of tumor cells.

关键词： glioblastoma multiforme stem cells dedifferentiation CD133 CD44 ALDHlAl SOX2

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Improved air quality and reduced burden of preterm birth in China:2013–2017

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Science Bulletin 2022年第9期67卷 879-882,M0003页

作者： Yixuan Jiang Yuan He Shenpeng Wu Renjie Chen Ying Yang Jihong Xu Ya Zhang Qiaomei Wang Haiping Shen Yiping Zhang Donghai Yan Zuoqi Peng Xudong Dong Hongping Zhang Lifang Jiang Huichu Li Yixiang Zhu Cong Liu Weidong Wang Xia Meng Tao Pei Ci Song aaron cohen Xu Ma Jing Cai Haidong Kan School of Public Health Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology AssessmentFudan UniversityShanghai 200032China National Research Institute for Health and Family Planning Beijing 100081China National Human Genetic Resources Center Beijing 101199China Peking Union Medical College Beijing 100730China Chinese Academy of Medical Sciences Beijing 100730China Department of Maternal and Child Health National Health Commission of the People’s Republic of ChinaBeijing 100044China The Obstetrical Department of the First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and TechnologyKunming 650500China Wenzhou People’s Hospital Wenzhou Maternal and Child Health Care HospitalThe Third Clinical Institute Affiliated to Wenzhou Medical UniversityWenzhou 305006China National Health Commission Key Laboratory of Birth Defects Prevention Henan Key Laboratory of Population Defects PreventionHenan Institute of Reproduction Health Science and TechnologyZhengzhou 450002China Department of Environmental Health Harvard T.H.Chan School of Public HealthBoston 02115USA State Key Laboratory of Resources and Environmental Information System Institute of Geographical Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China College of Resources and Environment University of Chinese Academy of SciencesBeijing 101408China Health Effects Institute Boston 02110USA Institute for Health Metrics and Evaluation University of WashingtonSeattle 98195USA Children’s Hospital of Fudan University National Center for Children’s HealthShanghai 201102China

Preterm birth(PTB)is a leading cause of perinatal mortality and morbidity worldwide[1].Since maternal and fetal health protection has been included in the United Nations Sustainable Development Goals,identification of modifiable risk factors for PTB is particularly *** Global Burden of Disease(GBD)Study 2019 recognized fine particulate matter(PM2.5)pollution as a risk factor for decreased gestational age and low birth weight.

关键词： pollution 空气质量改善疾病负担

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评估大气细颗粒物暴露引起的全球疾病负担的一个综合风险函数

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环境与职业医学 2014年第11期31卷 898-903页

作者： Richard T.Burnett C.Arden Pope III Majid Ezzati Casey Olives Stephen S.Lim Sumi Mehta Hwashin H.Shin Gitanjali Singh Bryan Hubbell Michael Brauer H.Ross Anderson Kirk R.Smith John R.Balmes Nigel G.Bruce Haidong Kan Francine Laden Annette Prüss-Ustün Michelle C.Turner Susan M.Gapstur W.Ryan Diver aaron cohen 何蓉张伊人金泰廙 Health Canada OttawaOntarioCanada Brigham Young University MRC-PHE Centre for Environment and Health School of Public HealthImperial College London School of Public Health University of Washington Institute for Health Metrics and Evaluation Global Alliance for Clean Cookstoves Harvard School of Public Health Harvard University U.S. Environmental Protection Agency Research Triangle Park School of Population and Public Health University of British ColombiaVancouverBritish ColumbiaCanada MRC-PHE Centre for Environment and Health King’s College London University of California BerkeleyBerkeleyCaliforniaUSA School of Medicine University of CaliforniaSan FranciscoSan FranciscoCaliforniaUSA School of Medicine University of CaliforniaBerkeleyBerkeleyCaliforniaUSA Department of Public Health and Policy University of Liverpool School of Public Health Fudan University Exposure Epidemiologyand Risk ProgramDepartment of Environmental HealthHarvard School of Public Health World Health Organization Institute of Population Health University of OttawaOttawaOntarioCanada American Cancer Society AtlantaGeorgiaUSA Health Effects Institute BostonMassachusettsUSA

[背景]评估由于环境空气中细颗粒物（PM2.5）长期暴露引起的疾病负担,需要了解相对风险度（RR）函数的图形和幅度。然而,在世界上很多观察到高PM2.5环境浓度的地方,都缺乏足够的直接证据确定死亡RR函数的图形。[目的]建立可用于全球PM2.... 详细信息

[背景]评估由于环境空气中细颗粒物（PM2.5）长期暴露引起的疾病负担,需要了解相对风险度（RR）函数的图形和幅度。然而,在世界上很多观察到高PM2.5环境浓度的地方,都缺乏足够的直接证据确定死亡RR函数的图形。[目的]建立可用于全球PM2.5暴露范围内成人死因的RR函数：缺血性心脏病（IHD）、脑血管疾病（脑卒中）、慢性阻塞性肺病（COPD）和肺癌（LC）。建立急性下呼吸道感染（ALRI）发病的RR函数,用于估算〈5岁的儿童中死亡率和健康生活损失年数。[方法]通过整合现有的来自于环境空气污染（AAP）、二手烟草烟雾、家用固体烹饪用燃料和主动吸烟（AS）等研究的RR信息,拟合综合暴露-反应（IER）模型。采用颗粒物质的吸入剂量,通过转化AS暴露来估计全年PM2.5的暴露当量。在估算全球环境PM2.5浓度的基础上,得出各国的人群归因分数（PAFs）。[结果]与以往负担评估中使用的其他7种模型相比,IER模型是一种优越的RR预测方法。在不同国家中,归因于AAP暴露的PAF百分数各不相同,分别为：IHD,2~41;脑卒中,1~43;COPD,〈1~21;LC,〈1~25;ALRI,〈1~38。[结论]我们建立了一种以细颗粒物为基础的RR模型,它通过整合来自不同类型的燃烧所产生颗粒物排放的RR信息,涵盖全球范围的暴露。当获得新的RR信息时,可以对这个模型进行更新。

关键词：细颗粒物环境空气污染风险函数全球疾病负担相对风险慢性阻塞性肺病全球环境缺血性心脏病颗粒物质烟草烟雾

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评估大气细颗粒物暴露所致全球疾病负担的一个综合风险函数

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环境与职业医学 2014年第7期31卷 554-554页

作者： Richard T.Burnett C.Arden Pope Ⅲ Majid Ezzati Casey Olives Stephen S.Lim Sumi Mehta Hwashin H.Shin Gitanjali Singh Bryan Hubbell Michael Brauer H.Ross erson Kirk R.Smith John R.Balmes Nigel G.Bruce Haidong Kan Francine Laden Annette Prüss-Ustün Michelle C.Turner Susan M.Gapstur W.Ryan Diver aaron cohen

[背景]评估归因于环境空气中细颗粒物（PM2.5）长期暴露所致的疾病负担，需要具备相对风险（RR）函数形状和幅度两方面的知识。然而，在世界上很多观察到高PM2.5环境浓度的地方，都缺乏足够的直接证据确定死亡率RR函数的形状。

关键词：大气细颗粒物疾病负担相对风险函数评估 PM2 5 长期暴露环境空气

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Retrospective evaluation of frozen section use for thyroid nodules with a prior fine needle aspiration diagnosis of Bethesda Ⅱ-Ⅵ: The Weill Cornell Medical College experience

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2015年第1期1卷 -页

作者： Marc A.cohen Krupa R.Patel Jonathan Gromis David I.Kutler William I.Kuhel Brian J.Stater aaron Schulman Department of Otolaryngology-Head and Neck Surgery New York Presbyterian Hospital/Weill Cornell Medical Center New York NY 10065 USA Weill Cornell Medical College New York NY 10065 USA Department of Endocrinology New York Presbyterian Hospital/Weill Cornell Medical CenterNew York NY 10065 USA

Objective: To evaluate the Weill Cornell Medical CoLlege (WCMC)/New York Presbyterian Hospital (NYPH) experience with intraoperative frozen (IOF) section in the management of thyroid nodules with a fine needle aspiration (FNA) diagnosis of Bethesda Ⅱ-Ⅵ and to analyze the cost and pathology benefit it ***: The surgical and cytopathology files at WCMC/NYPH were searched within the time period of January 2008 to May 2013.A total of 435 thyroid specimens were identified for which both an FNA and subsequent IOF section was *** FNA was correlated with the locations of the resected nodule and the nodule frozen for intraoperative *** results of the FNA were compared to the IOF section diagnosis and final diagnosis (FD).Results: Among 435 cases, the FNA diagnosis was Bethesda Ⅱ:149 cases, Bethesda Ⅲ:170 cases, Bethesda Ⅳ: 91 cases, Bethesda Ⅴ: 19 cases, and Bethesda Ⅵ: 6 *** were a total of 83 carcinomas identified on FD, which included 69 papillary thyroid carcinomas (PTCs), 12 follicular carcinomas, and 2 poorly differentiated *** preoperative FNA diagnosis for these carcinomas was as follows: Bethesda Ⅱ, 11/149 (7.4％), Bethesda Ⅲ, 24/170 (14％), Bethesda Ⅳ, 26/91 (29％), Bethesda Ⅴ, 16/19 (84％), and Bethesda Ⅵ, 6/6 (100％).IOF section contributed to the diagnosis of malignancy in 16/429 (4％) cases: 1/149 (0.7％) Bethesda Ⅱ, 5/170 (3％) Bethesda Ⅲ, 2/91 (1.1％) Bethesda Ⅳ, and 8/19 (42％) Bethesda Ⅴ.The diagnosis of malignancy was confirmed in the 6 Bethesda Ⅵl cases by IOF *** were no false positives on IOF *** had a sensitivity and specificity of 26％ and 100％, ***: The role of IOF section is limited in the evaluation of thyroid *** section is most useful for nodules with an FNA diagnosis of Bethesda V *** diagnosis of follicular variant of PTC remains difficult on frozen section.

关键词： Thyroid Nodule Frozen section Fine-needle aspiration Sensitivity Specificity

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圆环体住宅

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中国建筑装饰装修 2011年第12期 50-53页

作者： Preston Scott cohen Alexandra Barker Chris Hoxie aaron D'Innocenzo Judy Hodge

住宅内部设计了一条贯穿多个平面的曲线——墙面、墙壁、地板和天花板——形成一种波浪效果。其他各个平面的直线与曲线结构相交叉。客户希望在屋顶招待客人,同时可以画画。

关键词：住宅圆环体曲线结构内部设计天花板平面客人墙面

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中国大陆肺炎发病率与死亡率:1985-2008年中英文文献的系统分析

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公共卫生与预防医学 2011年第1期22卷 14-19页

作者：官旭华 Benjamin J Silk Wenkai Li aaron T. Fleishchauer 邢学森蒋晓清余宏杰 Sonja J. Olsen Adam L. cohen 湖北省疾病预防控制中心武汉430079 美国疾病预防控制中心呼吸道疾病部和细菌性疾病部美国疾病预防控制中心新发传染病和监测服务部中国疾病预防控制中心

目的肺炎是全球传染性疾病最主要的死因之一,但中国的肺炎疾病负担还知之甚少,因为很多数据资料都是以非英文文献的形式发表的。方法系统回顾了中国大陆关于肺炎发病率与死亡率的中文和英文文献,这些研究都是具有第一手数据的研究,1985-... 详细信息

目的肺炎是全球传染性疾病最主要的死因之一,但中国的肺炎疾病负担还知之甚少,因为很多数据资料都是以非英文文献的形式发表的。方法系统回顾了中国大陆关于肺炎发病率与死亡率的中文和英文文献,这些研究都是具有第一手数据的研究,1985-2008年有37篇论文符合纳入标准。结果各项研究的质量差异较大。5岁以下儿童肺炎发病率为(0.06～0.27)次/人年,肺炎死亡率为184/10万～1 223/10万人口。肺炎的发病率与死亡率随着时间稳定不变或者呈下降趋势,且农村高于城市。结论肺炎仍然是中国儿童的主要公共卫生问题之一。肺炎发病率与死亡率估计的变化差异大。继续降低发病率与死亡率需要可靠的监测数据和新的预防措施的实施,特别是在农村等高发地区。

关键词：肺炎发病率死亡率中国大陆

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*** impact of visual impairment on the Montreal Cognitive Assessment

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Annals of Eye Science 2019年第1期 208-208页

作者： Elliott Morrice Zoey Stark Caitlin Murphy Walter Wittich aaron Johnson Department of Psychology Concordia UniversityMontrealQCCanada CRIR/Centre de Réadaptation MAB-Mackay du CIUSSS du Centre Ouest del’Île de Montréal QCCanada Optometry University of MontrealQCCanada

Background:Cognitive assessments,such as the Montreal Cognitive Assessment(MoCA),use components that assume intact sensory abilities,however,adults show concomitant decreases in visual acuity with increasing *** on cognitive assessments are typically lower for individuals with visual impairments compared to individuals with normal/corrected to normal *** it is not clear if lowers scores on cognitive assessments are due to the assessments relying on visual stimuli,or if individuals with visual impairments are actually more likely to have cognitive *** we simulated visual impairments,i.e.,reduced visual acuity and contrast sensitivity,in young healthy adults to determine how this impacts their scores on a measure of cognitive ability,i.e.,the ***:Participants(n=19)completed one of the three version of the MoCA under three conditions(20/20,simulated 20/80,simulated 20/200).The MoCA was administered following the clinical *** participants that scored>26(i.e.,normal cognitive function)at 20/20 were included in the *** comparison,we included MoCA data from a sample of older adults with normal vision(n=19,Mage=74,Acuity M=0.04 logMAR,SD=0.16)or visual impairment(n=19,Mage=79,Acuity M=0.35 logMAR,SD=0.3).Results:Acuity of participants at 20/20(M=0.06 LogMAR,SD=0.1),simulated 20/80(M=0.63,SD=0.18)and simulated 20/200(M=0.88,SD=0.19)showed that the participants experienced simulated acuity loss with the *** the MoCA scores,we found a main effect of acuity(F=16.22,Pcohen’s d=1.33).However,no difference was observed between 20/80 and 20/200(t=−1.99,ptukey=0.125,d=0.572).The MoCA scores in older adults with normal vision(M=27.32,SD=2.41)and with visual impa

关键词： Visual impairment cognitive assessment simulated visual impairment Montreal Cognitive Assessment(MoCA)

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