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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | 华北平原不同粮作模式下作物水分利用显示文摘利用田间定位试验的研究方法,对在华北地区通过种植模式调整实现农业节水的潜力进行了研究。通过系统比较3种不同种植模式单季和周年作物水分利用效率以及水量平衡方程,获得如下结论:1)冬小麦-夏玉米一年两熟常规模式(对照)具有显著产量优势,但水分利用率较低,对地下水消耗较大,不利于本地区农业的可持续发展;2)与对照相比,春玉米一熟模式可以实现最小灌溉或者零灌溉,充分利用自然降雨的同时,还有助于地下水的恢复,但周年产量降低较多(降低41%),考虑到粮食安全的需求,该模式不适宜在当前推广;3)与对照相比,两年三熟模式3年总灌溉量降低48%,产量降低11%,节水效果明显,水分利用效率显著提高,该模式进一步完善后可适当推广。本研究结果为在华北平原地区兼顾粮食安全基础上拓展节水农业提供了新的思路,对发展可持续性农业做了有益探索。 | 郭步庆 陶洪斌 王璞 Heike KNRZER Wilhelm CLAUPEIN | 2013 | 中国农业大学学报2013，18，1： | 27 |
| 3 | A high-quality genome assembly of quinoa provides insights into the molecular basis of salt bladder-based salinity tolerance and the exceptional nutritional value显示文摘 | Changsong Zou Aojun Chen Lihong Xiao Heike M Muller Peter Ache Georg Haberer Meiling Zhang Wei Jia Ping Deng Ru Huang Daniel Lang Feng Li Dongliang Zhan Xiangyun Wu Hui Zhang Jennifer Bohm Renyi Liu Sergey Shabala Rainer Hedrich Jian-Kang Zhu Heng Zhang | 2017 | Cell Research2017，27，11： | 22 |
| 4 | 欧洲刺槐种源群体遗传结构和多样性显示文摘对来自欧洲和美国的 18个刺槐种源子代进行了等位酶分析。可进行遗传分析的 7个酶系统 (Amy,Fe,L ap,Idh,Mdh,6 Pgd,Skd)中有 14个基因位点 ,其中 12个位点具有多态性。每个多态位点平均等位基因数 (A/L )变化在 1.5 6~ 3.6 7之间 ,平均基因型数 (G/L)变化在 1.6 1~ 7.11之间 ,平均等位基因有效数目 (Ae)变化在 1.0 2~ 2 .5 0之间 ,预期杂合度 (H e)变化在0 .0 2~ 0 .5 6之间。不同种源群体之间也存在较大的遗传差异 ,在 8个德国种源中 ,各群体的 A、Ae、和 H e等相对较小 ,但不同群体间差异较大。各位点等位基因频率在不同种源群体间变化也较大 ,表明德国各种源群体内遗传变异相对较小 ,但群体间差异较大。来自匈牙利和斯洛伐克的 8个种源群则相反 ,各群体的 A、Ae、和 H e等相对较大 ,而不同种源群体间差异则较小 ,各位点等位基因频率在种源群体间变化相对一致 ,表明这两个国家的种源群体内变异较大 ,但不同种源群体间差异较小。欧洲的刺槐种源并未形成明显的地理变异模式 ,而且欧洲的种源和来自原产地的美国种源相比 ,没有发现明显的差异。经过 Hardy-Weinberg平衡检测证明 ,88.4 1%位点符合 H- W遗传平衡 ,表明各群体基因频率和基因型频率保持较高的稳定性 ,且种源内的变异大于种源间变异 ,94 . | 杨敏生 Heike Hertel Volker Schneck | 2004 | 生态学报2004，24，12： | 19 |
| 5 | 欧洲中部刺槐种源群体等位酶变异研究显示文摘从欧洲中部及美国收集了 18个刺槐种源种子 ,以 2年生苗木为材料 ,采用水平切片淀粉凝胶电泳和聚丙烯酰胺凝胶电泳对 11个酶系统进行了检测 ,共发现 2 0个酶位点 ,其中 14个为多态位点 ,多态性位点百分数为70 %。在参加计算的 7个酶系统的 12个多态性位点中 ,平均每个位点的等位基因数 (A)和平均每位点等位基因有效数 (Ae)为 2 733和 1.794 ,平均每个位点的实际杂合度 (Ho)和预期杂合度 (He)为 0 36 8和 0 4 0 0 ,固定指数 (F)为 0 0 80 ,绝大多数位点固定指数为正值。各基因位点遗传参数与 12个位点平均值进行相关分析表明 ,Fe b和Lap a的大部分群体遗传参数 (A、Ae、Ho、He等 )与平均值存在紧密的相关关系 ,其他位点各项遗传参数和总平均值相关不明显 ,这些位点的重要性可能比相关性较好的位点更大。德国 8个种源群体间遗传距离变化在 0 0 9~0 2 6之间 ,来自匈牙利的 6个种源之间遗传距离很小 ,绝大部分均在 0 11以下 ;德国的 8个种源与匈牙利和斯洛伐克的 8个种源之间的遗传距离变化在 0 0 9~ 0 2 4之间 ;来自美国的 2个种源 ,与欧洲的种源间的遗传距离在0 0 9~ 0 2 3之间 ,这一距离没有超出欧洲种源之间的差异。匈牙利和斯洛伐克的 8个种源群体的各项遗传参数均高于德国种源 ,表明这? | 杨敏生 Heike Hertel Volker Schneck | 2004 | Acta Genetica Sinica2004，31，12： | 16 |
| 6 | Land Use Change and Causes in the Xiangxi Catchment, Three Gorges Area Derived from Multispectral Data显示文摘The construction of the Three Gorges Dam on the Yangtze River has extensive impact on the ecosystems and the population of the Three Gorges Area (TGA). Inundation and resettlement have induced far-reaching land use and land cover change (LUCC). The areas that are affected by measures of resettlement are in a tense situation between the implementation of various governmental tasks addressing sustainable land use and water retention and the fulfilment of the population’s economic needs, which primarily depend on agricultural production. Destabilization of slopes and soil erosion are immediate hazards induced by the impoundment. Farming is a very important source of income and has to persist on the one hand to assure the income of the rural population. On the other hand, the environment has to be protected from runoff, soil erosion and instabilities connected to relief, geology and hydraulic influences. In this study, supervised classifications are performed using Landsat-TM (1987 and 2007) and ASTER (2007) images. LUCC is assessed by post-classification change analysis. On the catchment scale, arable land has decreased significantly, while garden land (citrus orchards) and woodland have increased. LUCC mainly affects the area surrounding the reservoir ('backwater') of the Xiangxi ( 香溪 ) River, driven by local resettlement, newly built infrastructure, relocation of land cultivation, and conversion of arable land to garden land. In the hinterland, LUCC occurs in form of abandonment of land cultivation as a consequence of the Grain-forGreen programme. | Christoph Seeber Heike Hartmann 项伟 Lorenz King | 2010 | Journal of Earth Science2010，21，6： | 12 |
| 7 | The Isogene 1-Deoxy-D-Xylulose 5-Phosphate Synthase 2 Controls Isoprenoid Profiles, Precursor Pathway Allocation, and Density of Tomato Trichomes显示文摘植物 isoprenoids 从先锋被形成由 mevalonate (MVA ) 综合了在 cytosol 或由 methyl-D-erythritol 4 磷酸盐(MEP ) 的小径在质体的小径。尽管先锋的一些交换发生, cytosolic sesquiterpenes 被假定主要源于 MVA,当 plastidial monoterpenes 从 MEP 先锋优先地被生产时。另外的复杂性在 MEP 小径的第一步产生,它被二分叉的 1-deoxy-D-xylulose 5 磷酸盐 synthase isoforms 典型地催化(DXS1, DXS2 ) 。在西红柿(茄属 lycopersicum ) , SlDXS1 基因无所不在地在而 SlDXS2 抄本充满仅仅很少纸巾,成熟的水果期间与高水平被表示,包括年轻叶子,花瓣,和孤立的毛状体。SlDXS2 表示的特定的下面规定被 RNA 干扰在转基因的植物执行调查反馈机制。SlDXS2 下面规定在在二 sesquiterpenes 的 monoterpene -phellandrene 和毛状体的增加导致了减少。而且,进剩余 monoterpenes 并且进 sesquiterpenes 的导出 MVA 的先锋的加入是由 13C 的比较决定了到 12C 天赋同位素比率被提高。SlDXS1 的一条补偿起来规定没被观察。也展出的下面调整的线增加了毛状体密度并且由喂叶的 Spodoptera littoralis 毛虫显示出更少的损坏。结果在 isoprenoid 先锋分配在 modulating isoprenoid 新陈代谢和显著粘性揭示 DXS2 的新奇、非冗余的角色。 | Heike Paetzold Stefan Garms Stefan Bartram Jenny Wieczorek Eva-Maria Uros-Gracia Manuel Rodriguez-Concepcion Wilhelm Boland Dieter Strack Bettina Hause Michael H. Walter | 2010 | Molecular Plant2010，3，5： | 11 |
| 8 | 德国公共剧院的效率:随机前沿分析法显示文摘近年来,文化服务机构等非营利性部门的经济表现一直是一个备受关注的问题。一方面是因为文化机构对公共资金的依赖度较高,另一方面是因为对公共预算的需求量越来越大。为了能够以最小成本来有效分配资源,负责对公共预算进行分配的政府部门就必须借助于可靠的表现指标。针对这一问题,本文对德国公共剧院1991/1992年和2005/2006年各季度的效率进行了分析。本研究采用了随机前沿分析法,检验了成本最小化行为在这一领域是否存在。此外,本文还采用了若干个面板数据模型来分析非观测到的异质性对效率估计的影响,不同模型对非观测到的异质性的解释力有所差别。研究结果表明,成本最小化行为在这一领域并不存在。因此,对于德国公共剧院来说,基于成本函数分析的效率分析法似乎并不适用。此外,研究还发现,不同剧院之间存在较大的非观测到的异质性,因而在各模型的效率分析中出现了显著差异。这说明,如果不将非观测到的异质性考虑在内,效率值就会有所偏颇。总之,此项研究发现,在公共文化领域要实现资源的合理应用,仍有很多工作要做。 | Anne-Kathrin Last Heike Wetzel 马绯璠 | 2010 | 文化艺术研究2010，3，4： | 6 |
| 9 | Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline显示文摘 | Michael F. Holick Neil C. Binkley Heike A. Bischoff-Ferrari Catherine M. Gordon David A. Hanley Robert P. Heaney M. Hassan Murad Connie M. Weaver | 2011 | The Journal of Clinical Endocrinology & Metabolism2011，，7： | 5 |
| 10 | Parameters affecting different acoustic radiation force impulse applications in the diagnosis of fibrotic liver changes显示文摘AIM: To analyze the virtual touch tissue quantification(VTTQ) and virtual touch imaging quantification(VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements.METHODS: One hundred and eighty-six(104 women/82 men) of 323 subjects met the inclusion criteria(age > 18 years, no history of chronic or gastrointestinal disease, body-mass index(BMI) < 30 kg/m2, a fasting period of at least three hours, no history of hepatotoxic pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and normal findings upon ultrasound examination of the abdomen). Measurements were taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner acquired six measurements per position, thereby giving 24 measurements in total.RESULTS: The 95% confidence intervals of mean were1.23-1.29 m/s for VTTQ and 1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and 25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only superficial measurements in the right hepatic lobe with the VTIQ method exhibited an effect of age on shear wave velocity. Measurements acquired using the 6C1 probe with the VTTQ method showed no dependence on BMI. By comparison, BMI influenced measurements taken with the VTIQ method using the 9L4 probe in the superficial and deep areas of the right hepatic lobe, as well as in the left hepatic lobe(P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the right hepatic lobe(P = 0.0001, P = 0.0269). Significant differences were found between measurements with the 6C1(VTTQ) and 9L4 probes(VTIQ)(P = 0.0067), between superficial and deep measurements(P < 0.0001), and between the right and left lobes of the liver(P < 0.0001). CONCLUSION: Measurements in the right lobe and deep regions are preferable. Gender differences must be considered. BMI must be considered when assessing VTIQ technology. | Sabrina Galgenmueller Heike Jaeger Wolfgang Kratzer Stefan A Schmidt Suemeyra Oeztuerk Mark M Haenle Richard A Mason Tilmann Graeter | 2015 | World Journal of Gastroenterology2015，21，27： | 5 |
| 11 | 华北平原不同种植模式的水氮利用显示文摘2007~2009年在河北省中国农业大学吴桥实验站进行两年的田间定位试验,试验设3个种植模式,分别为冬小麦-夏玉米一年两熟常规模式、春玉米一熟优化管理模式和冬小麦-夏玉米-春玉米两年三熟优化管理模式,探讨在华北地区通过调整种植模式的途径实现农业节水减氮的潜力。结果表明,冬小麦-夏玉米一年两熟常规模式(对照)具有显著产量优势,但水分利用率和氮肥利用率均较低,水氮浪费较为严重,不利于华北平原地区农业的可持续发展;与对照相比,春玉米一熟模式水氮消耗量最小,水氮利用率均显著提高,具有良好的环境效应,但其产量降低较多,不适宜在生产中单独推广;两年三熟模式两年总灌溉用水量降低了63%,氮肥用量降低了75%,产量降低了21%,节水减氮效果明显,水氮利用效率显著提高,该模式进一步完善后可适当推广。 | 郭步庆 陶洪斌 盛耀辉 王璞 Heike Knorzer Wilhelm Claupein | 2013 | 玉米科学2013，21，6： | 4 |
| 12 | Current techniques for AB0-incompatible living donor liver transplantation显示文摘For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible(AB0i) grafts. Improvements in AB0 i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0 i living donor liver transplantation(LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0 i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0 i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0 i LDLT is a feasible option today and almost free of severe complications. | Silke Rummler Astrid Bauschke Erik B?rthel Heike Jütte Katrin Maier Patrice Ziehm Christina Malessa Utz Settmacher | 2016 | World Journal of Transplantation2016，6，3： | 4 |
| 13 | Clinical feasibility of liver elastography by acoustic radiation force impulse imaging (ARFI)显示文摘 | Kinan Rifai Janet Cornberg Ingmar Mederacke Matthias J. Bahr Heiner Wedemeyer Philipp Malinski Heike Bantel Bita Boozari Andrej Potthoff Michael P. Manns Michael Gebel | 2011 | Digestive and Liver Disease2011，，6： | 4 |
| 14 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘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 unknown.By 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 variants.We 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 sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional 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 related.Our 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. | 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 | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 15 | Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis显示文摘Polyreactive 天生类型的 B 房间说明在圆周表示自我反应的许多 B 房间。这些 B 房间的不适当的规定可以是位于自体免疫的疾病下面的一个重要因素。这里,我们在导致骨胶原的关节炎(中央情报局) 的开发探索了自我反应的天生的 B 房间的影响,风湿性关节炎的一个鼠标模型。我们显示出那个脾的边缘的地区(MZ ) ,然而并非 B-1 B 房间在 naı 展出自发的 IgM 反应到自体同源的骨胶原 II; ¨ ve 老鼠。在有在完全的 Freund’ 的 heterologous 骨胶原 II 的免疫之上;骨胶原反应的 MZ B 房间很快扩展了的 s 助手,当 B-1 B 房间显示出谦虚反骨胶原回答时。MZ B 房间被像使用费的受体(TLR ) 容易激活 4 并且在 vitro,导致的增长和 cytokine 分泌物的 9-ligands,暗示 B 房间受体和 TLR 的那个双约会可以把有免疫力的反应提升到自我抗原。而且,告知骨胶原的 MZ B 房间显示出在 vivo 在 IgG 反骨胶原抗体的 vitro 和正式就职由血缘的 T 房间增长思考了的重要介绍抗原的能力。在 1 和 2 表明了的补充受体是缺乏的 MZ B 房间增加了增长和 cytokine 生产,当时 Fcγ房间的受体 IIb 缺乏导致增加的 cytokine 生产和抗原表示。在结论,我们的数据在中央情报局作为自体免疫的反应的开始者加亮自我反应的 MZ B 房间,在补充和 Fc 受体在在房间控制自我反应是相关的的地方。 | Anna-Karin E Palm Heike C Friedrich Anja Mezger Maya Salomonsson Linda K Myers Sandra Kleinau | 2015 | Cellular & Molecular Immunology2015，12，4： | 3 |
| 16 | Lack of microRNA‐101 causes E‐cadherin functional deregulation through EZH2 up‐regulation in intestinal gastric cancer显示文摘 | Joana Carvalho Nicole C van Grieken Patricia M Pereira Sónia Sousa Marianne Tijssen Tineke E Buffart Bego?a Diosdado Heike Grabsch Manuel AS Santos Gerrit Meijer Raquel Seruca Beatriz Carvalho Carla Oliveira | 2012 | J Pathol2012，，1： | 3 |
| 17 | HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value – conclusions from 924 cases of two independent series显示文摘 | Heike Grabsch Shivan Sivakumar Sally Gray Helmut E. Gabbert Wolfram Müller | 2010 | Cellular Oncology (-)2010，，1： | 3 |
| 18 | Antibodies as Tailor-Made Chiral Selectors: an Interdisciplinary Approach to Enantiomer Separation and Detection显示文摘It has long been known that the configurational isomers of biologically active compounds, e.g., nutrients, pesticides, and drugs, may exhibit different activities in a chiral environment such as the human body. Although the majority of drugs presently in development are chiral, analytical and preparative methods for the quantitative determination and purification of stereoisomers still lag behind. One reason is that commonly used chiral selectors for the direct resolution of enantiomers are not tailor-made for a specific analyte. The identification of suitable selectors for a particular pair of enantiomers still requires considerable experimentation and is generally demanding with regard to material, time and labor. The rational design of chiral host molecules, therefore, represents a challenge in facilitating enantiomer analysis. In this article, we describe how a combination of techniques ranging from organic synthesis to molecular biology yields antibodies of predetermined specificity and stereoselectivity that can be used as tailor-made chiral selectors for the chromatographic separation of enantiomers and their sensitive detection in immunosensors. | HOFSTETTER Heike HOFSTETTER Oliver | 2005 | 色谱2005，23，5： | 3 |
| 19 | Contrast-enhanced coronary artery visualization by dual-source computed tomography—Initial experience显示文摘 | Stephan Achenbach Dieter Ropers Axel Kuettner Thomas Flohr Bernd Ohnesorge Herbert Bruder Heike Theessen Meri Karakaya Werner G. Daniel Werner Bautz Willi A. Kalender Katharina Anders | 2005 | European Journal of Radiology2005，，3： | 3 |
| 20 | Trends in treatment and overall survival among patients with proximal esophageal cancer显示文摘BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.5-5.1)in 1989-1994,and 5.1 mo(95%CI:4.3-5.9)in 2010-2014(logrank P=0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer,likely to be associated with an increased use of CRT.Patterns in metastatic disease did not change significantly over time. | Judith de Vos-Geelen Sandra ME Geurts Liselot BJ Valkenburg-van Iersel Evelien JM de Jong Vivianne CG Tjan-Heijnen Margreet van Putten Valery EPP Lemmens Heike I Grabsch Nadia Haj Mohammad Frank JP Hoebers Chantal V Hoge Paul M Jeene Hanneke WM van Laarhoven Tom Rozema Marije Slingerland Grard AP Nieuwenhuijzen | 2019 | World Journal of Gastroenterology2019，25，47： | 2 |
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