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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | Nature:研究鉴定出蛋白Nlrp9b抵抗轮状病毒感染机制显示文摘轮状病毒(rotavirus)是婴儿和儿童罹患肠胃炎和腹泻的一种最为常见的原因,每年导致全世界大约21.5万人死亡。它是高度传染性的和潜在致命性的。这种病毒特异性地感染宿主小肠中的肠上皮细胞,并且已进化出抵抗干扰素和NF-KB信号的策略来躲避免疫系统,这就提出一个问题:其他的宿主因子是否参与肠道粘膜中的抗病毒反应。不过,针对体内(特别是通过NLR炎性体)检测和限制肠道病毒的机制,人们知之甚少。 | Shu Zhu, Zheng Wei, Noah W. Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R. de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Liang Shan, Richard A. Flavell Siyuan Ding, Ningguo Feng, Harry B. Greenberg Siyuan Ding, Harry B. Greenberg Penghua Wang, Yujiao Zhao Wen Pan, Jun Lu Jun Zhao, Yuval Kluger Kellie A. Jurado, Clara Abraham, Erol Fikrig Erol Fikrig, Richard A. Flavell | 2017 | 现代生物医学进展2017，17，27： | 10 |
| 3 | Comparative transcriptome analyses shed light on carotenoid production and plastid development in melon fruit显示文摘Carotenoids,such asβ-carotene,accumulate in chromoplasts of various fleshy fruits,awarding them with colors,aromas,and nutrients.The Orange(CmOr)gene controlsβ-carotene accumulation in melon fruit by posttranslationally enhancing carotenogenesis and repressingβ-carotene turnover in chromoplasts.Carotenoid isomerase(CRTISO)isomerizes yellow prolycopene into red lycopene,a prerequisite for further metabolism intoβ-carotene.We comparatively analyzed the developing fruit transcriptomes of orange-colored melon and its two isogenic EMS-induced mutants,low-β(Cmor)and yofi(Cmcrtiso).The Cmor mutation in low-βcaused a major transcriptomic change in the mature fruit.In contrast,the Cmcrtiso mutation in yofi significantly changed the transcriptome only in early fruit developmental stages.These findings indicate that melon fruit transcriptome is primarily altered by changes in carotenoid metabolic flux and plastid conversion,but minimally by carotenoid composition in the ripe fruit.Clustering of the differentially expressed genes into functional groups revealed an association between fruit carotenoid metabolic flux with the maintenance of the photosynthetic apparatus in fruit chloroplasts.Moreover,large numbers of thylakoid localized photosynthetic genes were differentially expressed in low-β.CmOR family proteins were found to physically interact with light-harvesting chlorophyll a–b binding proteins,suggesting a new role of CmOR for chloroplast maintenance in melon fruit.This study brings more insights into the cellular and metabolic processes associated with fruit carotenoid accumulation in melon fruit and reveals a new maintenance mechanism of the photosynthetic apparatus for plastid development. | Noam Chayut Hui Yuan Yuval Saar Yi Zheng Tianhu Sun Xuesong Zhou Anna Hermanns Elad Oren Adi Faigenboim Maixia Hui Zhangjun Fei Michael Mazourek Joseph Burger Yaakov Tadmor Li Li | 2021 | Horticulture Research2021，8，1： | 3 |
| 4 | Hydrophilic surface modification of PDMS for droplet microfluidics using a simple,quick,and robust method via PVA deposition显示文摘Polydimethylsiloxane(PDMS)is a dominant material in the fabrication of microfluidic devices to generate water-in-oil droplets,particularly lipid-stabilized droplets,because of its highly hydrophobic nature.However,its key property of hydrophobicity has hindered its use in the microfluidic generation of oil-in-water droplets,which requires channels to have hydrophilic surface properties.In this article,we developed,optimized,and characterized a method to produce PDMS with a hydrophilic surface via the deposition of polyvinyl alcohol following plasma treatment and demonstrated its suitability for droplet generation.The proposed method is simple,quick,effective,and low cost and is versatile with respect to surfactants,with droplets being successfully generated using both anionic surfactants and more biologically relevant phospholipids.This method also allows the device to be selectively patterned with both hydrophilic and hydrophobic regions,leading to the generation of double emulsions and inverted double emulsions. | Tatiana Trantidou Yuval Elani Edward Parsons Oscar Ces | 2017 | Microsystems & Nanoengineering2017，3，1： | 3 |
| 5 | Toward a General Margin of Appreciation Doctrine in International Law?显示文摘 | Yuval Shany | 2005 | European Journal of International Law2005，，： | 2 |
| 6 | Specifc inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss显示文摘Elevated osteoclast(OC)activity is a major contributor to inflammatory bone loss(IBL)during chronic inflammatory diseases.However,the specific OC precursors(OCPs)responding to inflammatory cues and the underlying mechanisms leading to IBL are poorly understood.We identified two distinct OCP subsets:Ly6C^(hi)CD11b^(hi) inflammatory OCPs(iOCPs)induced during chronic inflammation,and homeostatic Ly6C^(hi)CD11b^(lo)OCPs(hOCPs)which remained unchanged.Functional and proteomic characterization revealed that while iOCPs were rare and displayed low osteoclastogenic potential under normal conditions,they expanded during chronic inflammation and generated OCs with enhanced activity.In contrast,hOCPs were abundant and manifested high osteoclastogenic potential under normal conditions but generated OCs with low activity and were unresponsive to the inflammatory environment.Osteoclasts derived from iOCPs expressed higher levels of resorptive and metabolic proteins than those generated from hOCPs,highlighting that different osteoclast populations are formed by distinct precursors.We further identified the TNF-αand S100A8/A9 proteins as key regulators that control the iOCP response during chronic inflammation.Furthermore,we demonstrated that the response of iOCPs but not that of hOCPs was abrogated in tnf-α^(-/-)mice,in correlation with attenuated IBL.Our findings suggest a central role for iOCPs in IBL induction.iOCPs can serve as potential biomarkers for IBL detection and possibly as new therapeutic targets to combat IBL in a wide range of inflammatory conditions. | Yaron Meirow Milena Jovanovic Yuval Zur Juliana Habib Daniele Filippo Colombo Nira Twaik Hadas Ashkenazi-Preiser Kerem Ben-Meir Ivan Mikula Jr. Or Reuven Guy Kariv Leonor Daniel Saja Baraghithy Yehuda Klein Jeroen Krijgsveld Noam Levaot Michal Baniyash | 2022 | Bone Research2022，10，3： | 2 |
| 7 | Spontaneous supratentorial intracerebral hemorrhage显示文摘 | Chen Hallevy Gal Ifergane Ella Kordysh Yuval Herishanu | 2002 | Journal of Neurology2002，，12： | 2 |
| 8 | Reactive optical matter: light-induced motility in electrodynamically asymmetric nanoscale scatterers显示文摘From Newton’s third law,which is known as the principle of actio et reactio1,we expect the forces between interacting particles to be equal and opposite for closed systems.Otherwise,“nonreciprocal”forces can arise.2 This has been shown theoretically in the interaction between dissimilar optically trapped particles that are mediated by an external field.3 As a result,despite the incident external field not having a transverse component of momentum,the particle pair experiences a force in a direction that is transverse to the light propagation direction.3,4 In this letter,we directly measure the net nonreciprocal forces in electrodynamically interacting asymmetric nanoparticle dimers and nanoparticle structures that are illuminated by plane waves and confined to pseudo one-dimensional geometries.We show via electrodynamic theory and simulations that interparticle interactions cause asymmetric scattering from heterodimers.Therefore,the putative nonreciprocal forces are actually a consequence of momentum conservation.Our study demonstrates that asymmetric scatterers exhibit directed motion due to the breakdown of mirror symmetry in their electrodynamic interactions with external fields. | Yuval Yifat Delphine Coursault Curtis W.Peterson John Parker Ying Bao Stephen K.Gray Stuart A.Rice Norbert F.Scherer | 2018 | Light(Science & Applications)2018，7，1： | 2 |
| 9 | Anti-VEGF and beyond: shaping a new generation of anti-angiogenic therapies for cancer显示文摘 | Francesco Bertolini Paola Marighetti Ines Martin-Padura Patrizia Mancuso Dana D. Hu-Lowe Yuval Shaked Alberto D’Onofrio | 2011 | Drug Discovery Today2011，，23： | 1 |
| 10 | Active Networks for Efficient Distributed Network Management 显示文摘 | Yuval Shavitt | 2000 | IEEE Communications Magazine2000，38，3： | 1 |
| 11 | Trailer to door assignment in a synchronous cross-dock operation显示文摘 | Yuval Cohen Baruch Keren | 2009 | Logistics systems and management2009，5，5： | 1 |
| 12 | Standardization and modularization driven by inimizing overall process effort显示文摘 | Yuval S Yoram R | 2006 | Computer-Aided Desin2006，38，5： | 1 |
| 13 | Disrup- tion of Napl4, a plastid - localized non-intrin- sic ABC protein in krabidopsis thaliana results in the over-accumulation of transition metals and in aberrant chloroplast structures 显示文摘 | Shimoni S E Hassidim M Yuval N N | 2010 | Plant Cell&Environment2010，33，6： | 1 |
| 14 | Tail estimates for one-dimensional random walk in random environment显示文摘 | Amir Dembo Yuval Peres Ofer Zeitouni | 1996 | Communications in Mathematical Physics1996，，3： | 1 |
| 15 | Enhanced-resolution using modified configuration of Fresnel incoherent holographic recorder with synthetic aperture显示文摘 | Yuval Kashter Joseph Rosen | 2014 | Opt Express2014，20，20： | 1 |
| 16 | Gut bacterial communities in the Mediterranean fruit fly ( Ceratitis capitata) and their impact on host longevity显示文摘 | Behar A Yuval B Jurkevitch E | 2008 | Journal of Insect Physiology2008，54，9： | 1 |
| 17 | Spontaneous supratentorial intracerebral hemorrhage显示文摘 | Chen Hallevy Gal Ifergane Ella Kordysh Yuval Herishanu | 2002 | Journal of Neurology2002，，12： | 1 |
| 18 | Inhibition of CXCR4/CXCL12 signaling:a translational perspective for Alzheimer’s disease treatment显示文摘The mechanism of AD remains uncovered:The current mainstream doctrine in Alzheimer’s disease(AD)is the amyloid cascade hypothesis.According to this hypothesis,amyloid-β(Aβ)deposition is the main reason for neurofibrillary tangles formation and synaptic dysfunction. | Yuval Gavriel Inna Rabinovich-Nikitin Beka Solomon | 2022 | Neural Regeneration Research2022，17，1： | 1 |
| 19 | The true in- cidence of gastric GIST-a study based on morbidly obese patients undergoing sleeve gastrectomy显示文摘 | Yuval JB Khalaileh A Abu-Gazala M | 2014 | Obesity sur- gery2014，24，12： | 1 |
| 20 | Optimal allocation of work in assembly lines for lots with homogenous learning 显示文摘 | Yuval Cohen Gad Vitner Subhash C Satin | 2006 | European Journal of Operational Research2006，168，6： | 1 |
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