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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 | The rheology of two-dimensional foams显示文摘 | Simon C Denis W James A G | 2004 | Rheol Acta2004，43，5： | 1 |
| 3 | Fluid dynamics of cricket ball swing 显示文摘 | SCOBIE JAMES A PICKERING SIMON G ALMOND DARRYL P LOCK GARY D | 2013 | Proceedings of the Institution of Mechanical Engineers Part P: Journal of Sports Engineering and Technology2013，227，3： | 1 |
| 4 | The rheology of Twodimensional foams显示文摘 | Simon C Denis W James A G | 2004 | Rheol Acta2004，43，5： | 1 |
| 5 | Petroleum Resins; Separatlon,Character,and Role in Petroleum显示文摘 | Simon I A James G S | 2001 | Pet Sci Technol2001，19，1： | 1 |
| 6 | Changes in surface elec- tromyography signals and kinetics associated with progres- sion of fatigue at two speeds during wheelchair propulsion 显示文摘 | Qi L P James W L Simon G | 2012 | JRRD2012，49，1： | 1 |
| 7 | Direct evidence for the interaction of the mechanisms of thermally initiated and atom transfer radical polymerization 显示文摘 | James Parker Richard G Jones Simon J Holder | 2000 | Macromolecules2000，33，： | 1 |
| 8 | Analysis of the Casson and Carreau-Yasuda non-Newtonian blood mo- dels in steady and oscillatory flows using the lattice Boltzmann method显示文摘 | JOSHUA B JAMES M B SIMON G | 2007 | Physics of Fluids2007，19，9： | 1 |
| 9 | Proppant flowback control in high temperature wells显示文摘 | SIMON G JAMES MICHAEI L SAMUELSON GIENN W REED | | SPE0，，： | 1 |
| 10 | Learning Matter:Materials Design with Machine Learning andAtomistic Simulations显示文摘CONSPECTUS:Designing new materials is vital for addressing pressing societal challenges in health,energy,and sustainability.The combination of physicochemical laws and empirical trial and error has long guided material design,but this approach is limited by the cost of experiments and the difficulty of deriving complex guiding principles.The space of hypothetical materials to be considered is incredibly large,and only a small fraction of possible compounds can ever be tested experimentally.The computational techniques of atomistic simulation and machine learning(ML)offer an avenue to rapidly invent new materials and navigate this enormous space.Together,they can be used to infer complex design principles and identify high-quality candidates more rapidly than trial-and-error experimentation.In this Account,we review our group’s recent contributions to simulation and ML for materials design.We begin by discussing the numerical representation of materials for use in ML.Representations can be produced through deterministic algorithms,learnable encodings,or physics-based methods and lead to vector,graph,and matrix outputs.We describe how these different approaches offer distinct material-and application-specific advantages.We provide demonstrations from our own work on small-molecule drugs,macromolecules,dyes,electrolytes,and zeolites.In several cases,we show how the appropriate representation led to guiding principles that facilitated experimental materials design.Next,we highlight the development of ML methods for enhancing atomistic simulation.These advances help to improve simulation accuracy and expand the time and length scales that can be explored.They include differentiable atomistic simulations in which ensemble-averaged quantities are differentiated with respect to system parameters,and novel autoregressive methods for enhanced sampling of challenging physical distributions.Other developments include learnable coarse-grained models,which can accelerate molecular dynamics while minimizing the loss of all-atom information,and ML interatomic potentials,which can be trained on maximally informative quantum chemistry data through active learning and adversarial uncertainty attacks.Next,we show how these combined computational advances have enabled high-throughput virtual screening.This has led to the discovery of low-cost organic structure-directing agents for zeolite synthesis,polymer electrolytes,and efficient photoswitches for targeted medicine.We conclude by discussing the limitations of ML and simulation.These include the large data requirements and limited chemical transferability of the former and the speed−accuracy trade-offs of the latter.We predict that advancements in quantum chemistry will further accelerate simulations,while the incorporation of physical principles will improve the reliability of ML. | Simon Axelrod Daniel Schwalbe-Koda Somesh Mohapatra James Damewood Kevin P.Greenman Rafael Gómez-Bombarelli | 2022 | Accounts of Materials Research2022，3，3： | 0 |
| 11 | Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID- 19 pandemic显示文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction. | Thanh N Nguyen Diogo C Haussen Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka Ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk Omer F Eker Laura Mechtouff Michel Piotin Fabricio Oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David Ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby John Emma Griffin John Thornton Jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla Ozcan Ozdemir Ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-Oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki Ohara Daisuke Watanabe Dong Hun Shin Pedro SC Magalhaes Raghid Kikano Santiago Ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann Roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud Octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong Robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez Jordi Blasco Alejandro Rodriguez Vasquez Luisa Fonseca M Luis Silva Teddy Y Wu Simon John Alex Brehm Marios Psychogios William J Mack Matthew Tenser Tatemi Todaka Miki Fujimura Roberta Novakovic Jun Deguchi Yuri Sugiura Hiroshi Tokimura Rakesh Khatri Michael Kelly Lissa Peeling Yuichi Murayama Hugh Stephen Winters Johnny Wong Mohamed Teleb Jeremy Payne Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sugimura Masaaki Uno Yohei Takenobu Yuji Matsumaru Satoshi Yamada Ryuhei Kono Takuya Kanamaru Masafumi Morimoto Junichi Iida Vasu Saini Dileep Yavagal Saif Bushnaq Wenguo Huang Italo Linfante Jawad Kirmani David S Liebeskind Viktor Szeder Ruchir Shah Thomas G Devlin Lee Birnbaum Jun Luo Anchalee Churojana Hesham E Masoud Carlos Ynigo Lopez Brendan Steinfort Alice Ma Ameer E Hassan Amal Al Hashmi Mollie McDermott Maxim Mokin Alex Chebl Odysseas Kargiotis Georgios Tsivgoulis Jane G Morris Clifford J Eskey Jesse Thon Leticia Rebello Dorothea Altschul Oriana Cornett Varsha Singh Jeyaraj Pandian Anirudh Kulkarni Pablo M Lavados Veronica V Olavarria Kenichi Todo Yuki Yamamoto Gisele Sampaio Silva Serdar Geyik Jasmine Johann Sumeet Multani Artem Kaliaev Kazutaka Sonoda Hiroyuki Hashimoto Adel Alhazzani David Y Chung Stephan A Mayer Johanna T Fifi Michael D Hill Hao Zhang Zhengzhou Yuan Xianjin Shang Alicia C Castonguay Rishi Gupta Tudor G Jovin Jean Raymond Osama O Zaidat Raul G Nogueira SVIN COVID-19 Registry,the Middle East North Africa Stroke and Interventional Neurotherapies Organization(MENA-SINO),Japanese Society of Vascular and Interventional Neurology Society(JVIN) | 2021 | Stroke & Vascular Neurology2021，6，4： | 0 |
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