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Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner Mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi katalin Bartyik Krisztina Míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss Miklós Garami István Peták Oncompass Medicine Hungary Kft Retek Str.34Budapest 1024Hungary Division of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary Department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(rithm for therapeutic decision ***,a molecular tumor board(MTB)evaluated the results to provide therapy *** Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the evidence *** approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

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A SARS-CoV-2-specific CAR-T-cell model identifies felodipine,fasudil,imatinib,and caspofungin as potential treatments for lethal COVID-19

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Cellular & Molecular Immunology 2023年第4期20卷 351-364页

作者： in Xia Lun-zhi Yuan Ya-hong Hu Jun-yi Liu Guo-sheng Hu Ruo-yao Qi Tian-ying Zhang Hua-long Xiong Zao-zao Zheng Hong-wei Lin Jia-mo Zhang Chao Yu Ming Zhou Jian ma Tong Cheng ri-rong Chen Yi Guan Ning-shao Xia Wen Liu State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019(COVID-19)severity and ***,drugs that are effective against inflammation to treat lethal COVID-19 are still urgently ***,we constructed a SARS-CoV-2 spike protein-specific CAR,and human T cells infected with this CAR(SARS-CoV-2-S CAR-T)and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients,causing cytokine storm and displaying a distinct memory,exhausted,and regulatory T-cell ***1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in *** on this"two-cell"(CAR-T and THP1 cells)model,we screened an FDA-approved drug library and found that felodipine,fasudil,imatinib,and caspofungin were effective in suppressing the release of cytokines,which was likely due to their ability to suppress the NF-kB pathway in ***,fasudi,imatinib,and caspofungin were further demonstrated,although to different extents,to attenuate lethal inflammation,ameliorate severe pneumonia,and prevent mortality in a SARS-CoV-2-infected Syrian hamster model,which were also linked to their suppressive role in *** summary,we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput *** drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe,inexpensive,and easily accessible for immediateuseinmostcountries.

关键词： COVID-19 SARS-CoV-2 CAR-T anti-inflammation NF-kB pathway

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CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai Yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva bila.ishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert maarten Boonekamp marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen Huirun Chen Jinhui Chen Ji-Yuan Chen kai Chen mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu kaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced Science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and Technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

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一种大模场沟槽辅助型扇形瓣状光纤的研究

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中国激光 2018年第12期45卷 197-204页

作者：刘诗男宁提纲马绍朔郑晶晶许建温晓东北京交通大学全光网络与现代通信网教育部重点实验室北京100044 曲阜师范大学物理工程学院山东曲阜273165

设计了一种抗弯曲大模场面积单模光纤方案——沟槽辅助型瓣状光纤。纤芯中间加入了低折射率辅助沟槽,纤芯四周围绕高折射率扇形瓣。利用COMSOL软件计算模式损耗、模场面积等性能。研究表明:在弯曲半径为15cm的情况下,光纤模场面积可达70... 详细信息

设计了一种抗弯曲大模场面积单模光纤方案——沟槽辅助型瓣状光纤。纤芯中间加入了低折射率辅助沟槽,纤芯四周围绕高折射率扇形瓣。利用COMSOL软件计算模式损耗、模场面积等性能。研究表明:在弯曲半径为15cm的情况下,光纤模场面积可达700μm2,高阶模和基模损耗比大于100,能够实现有效单模操作。此外,当弯曲方向在[-180°,180°]范围内变化时,光纤性能保持稳定。这种光纤在紧凑型高功率光纤激光器和放大器领域显示出巨大的潜力。

关键词：光纤光学弯曲不敏感大模场面积少模光纤

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禹门口南黄河东岸沙丘初步研究

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中国沙漠 1999年第2期19卷 184-186页

作者：马志正胡晓猛李有利山西师范大学地理系北京大学城市与环境学系

在禹门口南山西省河津、万荣县境内黄河阶地上发育了一些固定、半固定沙丘，注入黄河的汾河将这些沙丘分成了南北两部分。北部的沙丘多在海拔４００ｍ左右，高出现代黄河约３５ｍ，位于黄河的第二级阶地上，由两条南北向的沙垄和两垄之... 详细信息

在禹门口南山西省河津、万荣县境内黄河阶地上发育了一些固定、半固定沙丘，注入黄河的汾河将这些沙丘分成了南北两部分。北部的沙丘多在海拔４００ｍ左右，高出现代黄河约３５ｍ，位于黄河的第二级阶地上，由两条南北向的沙垄和两垄之间分布的抛物线形沙丘构成特殊的景观。这些抛物线形沙丘一般高度约７～８ｍ，背风面突出，迎风坡坡度一般为１５°～２０°，背风坡坡度一般大于４０°。风沙堆积下伏的河流堆积物的１４Ｃ年龄为２６．４０±０．８ｋａＢＰ，表明沙丘形成于距今２６ｋａ以来。南部沙丘海拔高度近５００ｍ，高出现代黄河水面１５０ｍ，覆盖于黄河第三级阶地之上。一个天然剖面揭示，第三阶地的底部为黄色中粗砂与灰绿色粉砂粘土互层，中部为灰黄色黄土，顶部为黄色风沙层。在黄土地层中可以识别出Ｓ１古土壤和位于风沙堆积下面的可能为Ｌ１ＳＳ１的弱成土层。由此推断风沙堆积于距今３万ａ以来。黄河阶地上的沙丘是在特殊的地区和特定的时期；强大的风力、丰富的沙源和气候变干条件下形成的。虽然东岸沙丘已是固定、半固定沙丘，但沙化仍然是该地区的一个问题。由于３～４ａ前开始在丘前洼地栽种苹果树，破坏了下风向沙丘迎风面的植被，造成了原来已固定沙丘的活化，在沙丘顶部生成了新?

关键词：沙丘局部环境气候变化人类活动黄河

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