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World Journal of Hepatology 2019年第1期11卷 65-73页

作者： Brianna J Shinn aaron martin Robert M Coben Mitchell I Conn Jorge Prieto Howard Kroop Anthony J DiMarino Hie-Won Hann Division of Gastroenterology and Hepatology Department of Medicine Thomas Jefferson University Hospital

Hepatitis B virus(HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma(HCC). During the last two decades, with the use of currently available anti-HBV therapies(lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBVassociated HCC(HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA(cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure(loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

关键词： Hepatitis B Hepatocellular carcinoma Antiviral therapy Persistent Risk for hepatocellular carcinoma Tumor ablation

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基于表面等离子共振的自动化系统

生命科学仪器 2010年第3期8卷 10-12页

作者： Jeffery HAVARD Nathan GILLOCK aaron martin John QUINN Chief Scientist of Bioinstrumentation Icx Nomadics800 Research Pkwy.Ste.100Oklahoma CityOK 73104U.S.A.

在过去的15年中,从药物发现到基础生命科学研究,生物分子相互作用的无标、实时分析越来越成为一种横跨各学科的重要技术。而这个领域中不断壮大的仪器供应队伍也使得这项强大的技术被各种科研团体所熟知和应用。目前发展的一种普遍趋势... 详细信息

在过去的15年中,从药物发现到基础生命科学研究,生物分子相互作用的无标、实时分析越来越成为一种横跨各学科的重要技术。而这个领域中不断壮大的仪器供应队伍也使得这项强大的技术被各种科研团体所熟知和应用。目前发展的一种普遍趋势是在系统中整合并行样品处理技术及更多的探测通道以增加实验通量。这既增加了设备的复杂性,又明显地提高了仪器成本。然而,自动化操作可以有效地保证样品处理的重现性,如再结合双参比相互作用数据集,那么几乎所有的运行流程都能得到一种极大的改善。Sens íQ Pioneer系统,一种高效的基于表面等离子共振技术(SPR)的生物探测系统,完整地涵盖了上述各种要素。

关键词：表面等离子共振技术自动化系统生物分子相互作用样品处理技术 Pioneer 自动化操作科学研究药物发现

跨界PM_(2.5)污染健康影响及其不平等性的历史演化

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Science Bulletin 2022年第4期67卷 437-444,M0004页

作者：陈璐璐林金泰 Randall martin 杜鸣溪翁宏健孔浩倪睿婧孟军张宇航张丽娟 aaron van Donkelaar Laboratory for Climate and Ocean-Atmospheric Studies Department of Atmospheric and Oceanic SciencesSchool of PhysicsPeking UniversityBeijing 100871China Department of Energy Environmental and Chemical EngineeringMckelvey School of EngineeringWashington University in St.LouisSt.LouisMO 63130USA Department of Physics and Atmospheric Science Dalhousie UniversityHalifaxNS B3H 4R2Canada Smithsonian Astrophysical Observatory Harvard-Smithsonian Center for AstrophysicsCambridgeMA 02138USA School of Public Policy and Administration Xi’an Jiaotong UniversityXi’an 710049China Department of Atmospheric and Oceanic Sciences University of CaliforniaLos AngelesCA 90095USA Shanghai Central Meteorological Observatory Shanghai 200030China

大气传输导致的PM;跨界输送会引起重大的跨境健康影响.在过去几十年间,各区域人为源污染物排放发生了巨大且不同的变化,但是,由此产生的全球跨界健康影响及其中隐含的健康不平等性问题仍不清楚.本研究发现,在1950~2014年间,全球人为源PM... 详细信息

大气传输导致的PM;跨界输送会引起重大的跨境健康影响.在过去几十年间,各区域人为源污染物排放发生了巨大且不同的变化,但是,由此产生的全球跨界健康影响及其中隐含的健康不平等性问题仍不清楚.本研究发现,在1950~2014年间,全球人为源PM_(2.5)累计导致了1.86(95%CI:1.16~2.56)亿例过早死亡,其中约14%是跨界PM;所致.在四个不同富裕程度的地区中,从对跨界PM;过早死亡的人均贡献的角度来说,越富裕的地区所造成的累计跨界健康影响越严重,而最贫穷的地区承受着最严重的跨界健康负担.这意味着,大气输送所造成的跨界健康影响不平等性问题十分严峻.并且,跨界健康效应及其不平等性随时间的变化也十分显著.降低PM;跨界污染需要全球紧密合作,而合作的基础应当将历史责任以及健康不平等性问题考虑在内.

关键词： Health inequality Transboundary pollution Anthropogenic PM_(2.5)Historical mortality Affluence Atmospheric transport

帕博利珠单抗单药治疗PD-L1阳性伴脑转移的非小细胞肺癌患者的疗效：KEYNOTE-001、010、024和042研究的汇总分析

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中国肺癌杂志 2022年第9期25卷 701-712页

作者： aaron S. MANSFIELD Roy S. HERBST Gilberto de CASTRO Jr. Rina HUI Nir PELED Dong-Wan KIM Silvia NOVELLO Miyako SATOUCHI Yi-Long WU Edward B.GARON martin RECK Andrew G.ROBINSON Ayman SAMKaRI Bilal PIPERDI Victoria EBIANA Jianxin LIN Tony S.K.MOK 黎扬斯 Division of Medical Oncology Mayo Clinic Yale Comprehensive Cancer Center Yale University School of Medicine Instituto do Cancer do Estado de S?o Paulo Westmead Hospital and the University of Sydney Soroka Cancer Center Ben Gurion University Seoul National University Hospital Seoul National University College of Medicine Azienda Ospedaliero-Universitaria San Luigi Gonzaga University of Turin Hyogo Cancer Center Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences David Geffen School of Medicine at the University of California Los Angeles Lung Clinic Grosshansdorf Airway Research Center North German Center of Lung Research Cancer Centre of Southeastern Ontario at Kingston General Hospital Merck & Co. Inc. State Key Laboratory of Translational Oncology Chinese University of Hong Kong 广东省人民医院广东省人民医院肿瘤医院广东省肺癌研究所

背景与目的我们回顾性评估了程序性死亡配体1（programmed death ligand 1, PD-L1）阳性非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的预后，以比较基线（即入组时）脑转移与帕博利珠单抗及化疗的疗效关系。方法我们汇总... 详细信息

背景与目的我们回顾性评估了程序性死亡配体1（programmed death ligand 1, PD-L1）阳性非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的预后，以比较基线（即入组时）脑转移与帕博利珠单抗及化疗的疗效关系。方法我们汇总分析了KEYNOTE-001（NCT01295827）、KEYNOTE-010（NCT01905657）、KEYNOTE-024（NCT02142738）和KEYNOTE-042（NCT02220894）研究中既往接受过治疗或未接受过的PD-L1阳性[肿瘤细胞阳性比例评分（tumor proportion score, TPS）≥1%]的晚期或转移性NSCLC患者的数据。患者接受帕博利珠单抗（2 mg/kg,10 mg/kg，或每3周200 mg或每2周10 mg/kg）治疗；而化疗是除KEYNOTE-001外所有研究的对照组。所有研究都纳入了既往接受过治疗的稳定脑转移的患者。结果共计纳入3,170例患者，基线时，293例（9.2%）患者伴有脑转移，而2,877例（90.8%）是无脑转移患者；数据截止时，中位（范围）随访时间为12.9（0.1-43.7）个月。与化疗相比，帕博利珠单抗可改善基线伴有脑转移及无脑转移患者的总生存期：PD-L1 TPS≥50%[分别为0.67（95%CI:0.44-1.02）和0.66（95%CI:0.58-0.76）]和PD-L1 TPS≥1%[分别为0.83（95%CI:0.62-1.10）和0.78（95%CI:0.71-0.85）]。无论是否有脑转移，与化疗相比，接受帕博利珠单抗治疗患者的无进展生存期更长，客观缓解率更高，缓解持续时间更长。在脑转移患者中，帕博利珠单抗与化疗的治疗相关不良事件发生率分别为66.3%和84.4%，在无脑转移患者中分别为67.2%和88.3%。结论对于既往未接受治疗或接受过治疗的PD-L1阳性晚期/转移性NSCLC患者，无论基线时是否存在治疗后稳定的脑转移，帕博利珠单抗单药治疗显示出明显的疗效改善，且与化疗相比，不良事件更少。

关键词：帕博利珠单抗脑转移化疗非小细胞肺癌 PD-L1

Variation in Total Soil Organic Carbon Stocks in Relation to Some Land Use Systems in the Bamenda Highlands, Cameroon

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Journal of Geoscience and Environment Protection 2021年第9期9卷 150-165页

作者： Christian Tegha Kum aaron Suh Tening martin Ngwabie Cornelius Tsamo Department of Agricultural and Environmental Engineering College of Technology The University of Bamenda Bamenda Cameroon Department of Agronomic and Applied Molecular Sciences Faculty of Agriculture and Veterinary Medicine University of Buea Buea Cameroon

Climate change and food security are among the pressing challenges facing humanity in the 21st century. Soil organic carbon (SOC) stocks, total nitrogen (TN), texture, and bulk density (BD) are important soil properties, which control climate change. Three land use systems (smallholder farmlands, grazing lands, and forest lands) that coexist in the Bamenda Highlands (BH) influence ecosystem services and induce soil degradation with the loss of SOC. The objective of this study was to evaluate the variation of SOC and some soil physicochemical properties as affected by the three land use systems (LUS). A total of 21 composite soil samples collected from 7 microclimatic zones of BH following “S” shape plots to the depth of 0 - 30 cm, were analysed for moisture content (MC), SOC, TN, BD, available phosphorus (Av.P), pH and texture. The results revealed that grazing land had the lowest mean sand content (40.79 ± 4.07). Mean MC, TN and SOC (%) content were significantly higher (p in forest land than those in the grazing land and smallholder farmlands. Conversely, BD and Av.P were significantly higher

Long-term effects of PM_(2.5) components on incident dementia in the northeastern United States

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The Innovation 2022年第2期3卷 95-102页

作者： Jing Li Yifan Wang Kyle Steenland Pengfei Liu aaron van Donkelaar Randall V.martin Howard H.Chang W.Michael Caudle Joel Schwartz Petros Koutrakis Liuhua Shi Department of Environmental Health Harvard T.H.Chan School of Public HealthBostonMA 02115USA Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30322USA School of Earth and Atmospheric Sciences Georgia Institute of TechnologyAtlantaGA 30332USA Department of Energy Environmental&Chemical EngineeringWashington University at St.LouisMO 63130USA Department of Biostatistics and Bioinformatics Rollins School of Public HealthEmory UniversityAtlantaGA 30322USA

Growing evidence has linked long-term fine particulate matter(PM_(2.5))exposure to neurological *** is known about the individual effects of PM_(2.5) components.A population-based cohort study investigated the association between long-term(1-year average)exposure to PM_(2.5) components and dementia incidence among the elderly population(age,R65 years)in the United States.

关键词： northeastern incident exposure

Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis

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Journal of Pancreatology 2020年第2期3卷 86-92页

作者： Bachul Piotr J. Grybowski Damian J. Anteby Roi Basto Lindsay Perea Laurencia Golab Karolina Wang Ling-Jia Tibudan martin Gutierrez Angelica P. Komorniczak Michal Nagpal Sajan Lucander aaron Fung John Matthews Jeffrey B. Witkowski Piotr Department of Surgery University of ChicagoChicagoILUSA Faculty of Medicine Tel Aviv UniversityTel AvivIsrael Department of Nephrology Transplantology and Internal MedicineMedical University of GdańskGdańskPoland Department of Medicine University of ChicagoChicagoILUSA

Total pancreatectomy with islet autotransplantation(TPIAT)is an effective treatment option for non-diabetic patients with intractable chronic *** outcome and potential benefits for pre-diabetic and diabetic patients are less well ***-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control:diabetes mellitus(DM)(n=5,15%),pre-DM(n=11,32%)and non-DM(n=18,54%).Pre-operative fasting c-peptide was detectable and similar in all 3 *** yield in the DM group was comparable to pre-DM and non-DM groups(median islet equivalents[IEQ]was 191,800,111,800,and 232,000 IEQ,respectively).Patients received islet mass of over the target level of 2000 IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group:45%(5/11)and 60%(3/5)for a combined 50%(8/16)rate,respectively,compared to 83%(15/18)for the non-DM *** 1 year,fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in *** transplantation failed(negative c-peptide)only in 1 ***,all patients experienced pancreatic pain with daily opioid dependence in 60%to 70%.Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic *** patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT,with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted *** surprisingly,endocrine outcomes for diabetic and prediabetics patients are substantially worse than in those with normal pre-operative glucose control.

关键词： Autotransplantation Islets Outcomes Pancreatectomy Pre-diabetes

In situ frequency gating and beam splitting of vacuum- and extreme-ultraviolet pulses

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Light(Science & Applications) 2016年第1期5卷 396-402页

作者： Rajendran Rajeev Johannes Hellwagner Anne Schumacher Inga Jordan martin Huppert Andres Tehlar Bhargava Ram Niraghatam Denitsa Baykusheva Nan Lin aaron von Conta Hans Jakob Wörner Laboratory of Physical Chemistry Department of Chemistry and Applied BiosciencesVladimir-Prelog-Weg 2ETH ZurichZurich 8093Switzerland

Monochromatization of high-harmonic sources has opened fascinating perspectives regarding time-resolved photoemission from all phases of *** studies have invariably involved the use of spectral filters or spectrally dispersive optical components that are inherently lossy and technically *** we present a new technique for the spectral selection of near-threshold harmonics and their spatial separation from the driving beams without any optical *** discover the existence of a narrow phase-matching gate resulting from the combination of the non-collinear generation geometry in an extended medium,atomic resonances and *** technique offers a filter contrast of up to 104 for the selected harmonics against the adjacent ones and offers multiple temporally synchronized beamlets in a single unified *** demonstrate the selective generation of 133,80 or 56 nm femtosecond pulses from a 400-nm driver,which is specific to the target *** results open new pathways towards phase-sensitive multi-pulse spectroscopy in the vacuum-and extreme-ultraviolet,and frequencyselective output coupling from enhancement cavities.

关键词： beam splitting below-threshold harmonics coherent extreme-ultraviolet pulses frequency gating non-collinear generation

卫星观测在全球细颗粒物浓度长期暴露评估中的应用

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环境与职业医学 2015年第8期32卷 801-805,F0004页

作者： aaron van Donkelaar Randall V.martin Michael Brauer Brian L.Boys 王晓宇张伊人金泰廙 Department of Physics and Atmospheric Science Dalhousie University Halifax NovaScofia Canada Harvard-Smithsortian Center for Astrophysics Cambridge Massachusetts USA School of Environmental Health University of British Columbia. Vancouver. British Columbia Canada

[背景]十余年的卫星观测提供了全球细颗粒物（PM2.5）人群暴露趋势和大小的信息。[目的]利用多个卫星的测量值推断的PM：5浓度，建立和改进大气PM2.5质量和趋势的全球暴露评估。[方法]结合3个卫星反演的PM25源数据，得出1998-2012年10km... 详细信息

[背景]十余年的卫星观测提供了全球细颗粒物（PM2.5）人群暴露趋势和大小的信息。[目的]利用多个卫星的测量值推断的PM：5浓度，建立和改进大气PM2.5质量和趋势的全球暴露评估。[方法]结合3个卫星反演的PM25源数据，得出1998-2012年10km×10km尺度上全球PM2．5估计值。对每一个源数据，通过GEOS—Chem化学物运输模型把气溶胶光学厚度总柱反演与近地面PM2.5联系起来，以表示当地的气溶胶光学性能和垂直廓线。从文献中收集210个全球基于地面的PM2.5观测值，用北美和欧洲之外其他地区的测量值来评估基于卫星的估计值。[结果]1998--2012年，全球人口加权的大气PM25浓度每年增加0．55gg／m3（95％CI：0．43～0．67）（2．1％／年；95％CI：1．6％-2．6％）。尽管在一些发达地区PM2.5减少，但在一些发展中地区PM2．s的增加推动了这一全球性的变化。在东亚，PMzs水平高于世界卫生组织（WHO）第一个中期目标35μg／m3的人口比例从1998--2000年的51％上升到2010---2012年的70％。相比之下，北美高于WHO空气质量指南10μg/m3的人口比例，从1998--2000年的62％下降到2010---2012年的19％。北美及欧洲以外地区的卫星反演估计值和地面测量值之间存在关联（r=0．81；n=210；斜率=0．68）。卫星反演的估计值偏低，提示真实的全球浓度可能更高。[结论]卫星观测值提供了大气PM2.5浓度的全球性长期变化的新认识。从这项研究中获得的PM2.5的卫星反演估计值和地面观测值可供公众使用。

关键词：细颗粒物卫星浓度评估长期暴露观测 PM2.5 应用