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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 | On-the-fly active learning of interpretable Bayesian force fields for atomistic rare events显示文摘Machine learned force fields typically require manual construction of training sets consisting of thousands of first principles calculations,which can result in low training efficiency and unpredictable errors when applied to structures not represented in the training set of the model.This severely limits the practical application of these models in systems with dynamics governed by important rare events,such as chemical reactions and diffusion.We present an adaptive Bayesian inference method for automating the training of interpretable,low-dimensional,and multi-element interatomic force fields using structures drawn on the fly from molecular dynamics simulations.Within an active learning framework,the internal uncertainty of a Gaussian process regression model is used to decide whether to accept the model prediction or to perform a first principles calculation to augment the training set of the model.The method is applied to a range of single-and multi-element systems and shown to achieve a favorable balance of accuracy and computational efficiency,while requiring a minimal amount of ab initio training data.We provide a fully opensource implementation of our method,as well as a procedure to map trained models to computationally efficient tabulated force fields. | Jonathan Vandermause Steven B.Torrisi Simon Batzner Yu Xie Lixin Sun Alexie M.Kolpak Boris Kozinsky | 2020 | npj Computational Materials2020，，1： | 17 |
| 3 | Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery显示文摘AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery. | Amilcare Parisi Daniel Reim Felice Borghi Ninh T Nguyen Feng Qi Andrea Coratti Fabio Cianchi Maurizio Cesari Francesca Bazzocchi Orhan Alimoglu Johan Gagnière Graziano Pernazza Simone D'Imporzano Yan-Bing Zhou Juan-Santiago Azagra Olivier Facy Steven T Brower Zhi-Wei Jiang Lu Zang Arda Isik Alessandro Gemini Stefano Trastulli Alexander Novotny Alessandra Marano Tong Liu Mario Annecchiarico Benedetta Badii Giacomo Arcuri Andrea Avanzolini Metin Leblebici Denis Pezet Shou-Gen Cao Martine Goergen Shu Zhang Giorgio Palazzini Vito D'Andrea Jacopo Desiderio | 2017 | World Journal of Gastroenterology2017，23，13： | 17 |
| 4 | Immune checkpoint inhibitor-related hepatotoxicity:A review显示文摘The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research. | Devika Remash David S Prince Catriona McKenzie Simone I Strasser Steven Kao Ken Liu | 2021 | World Journal of Gastroenterology2021，27，32： | 9 |
| 5 | A new strategy for estimating risks of transfusion‐transmitted viral infections based on rates of detection of recently infected donors显示文摘 | Michael P.Busch Simone A.Glynn Susan L.Stramer D. MichaelStrong SallyCaglioti David J.Wright BrandeePappalardo Steven H.Kleinman | 2005 | Transfusion2005，，2： | 4 |
| 6 | Heart Disease and Stroke Statistics—2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee显示文摘 | Donald Lloyd-Jones Robert Adams Mercedes Carnethon Giovanni De Simone T Bruce Ferguson Katherine Flegal Earl Ford Karen Furie Alan Go Kurt Greenlund Nancy Haase Susan Hailpern Michael Ho Virginia Howard Brett Kissela Steven Kittner Daniel Lackland Lynda L | 2009 | Circulation2009，，3： | 4 |
| 7 | Precision Phenotyping Reveals Novel Loci for Quantitative Resistance to Septoria Tritici Blotch显示文摘Accurate,high-throughput phenotyping for quantitative traits is a limiting factor for progress in plant breeding.We developed an automated image analysis to measure quantitative resistance to septoria tritici blotch(STB),a globally important wheat disease,enabling identification of small chromosome intervals containing plausible candidate genes for STB resistance.335 winter wheat cultivars were included in a replicated field experiment that experienced natural epidemic development by a highly diverse but fungicide-resistant pathogen population.More than 5.4 million automatically generated phenotypes were associated with 13,648 SNP markers to perform the GWAS.We identified 26 chromosome intervals explaining 1.9-10.6%of the variance associated with four independent resistance traits.Sixteen of the intervals overlapped with known STB resistance intervals,suggesting that our phenotyping approach can identify simultaneously(i.e.,in a single experiment)many previously defined STB resistance intervals.Seventeen of the intervals were less than 5 Mbp in size and encoded only 173 genes,including many genes associated with disease resistance.Five intervals contained four or fewer genes,providing high priority targets for functional validation.Ten chromosome intervals were not previously associated with STB resistance,perhaps representing resistance to pathogen strains that had not been tested in earlier experiments.The SNP markers associated with these chromosome intervals can be used to recombine different forms of quantitative STB resistance that are likely to be more durable than pyramids of major resistance genes.Our experiment illustrates how high-throughput automated phenotyping can accelerate breeding for quantitative disease resistance. | Steven Yates Alexey Mikaberidze Simon GKrattinger Michael Abrouk Andreas Hund Kang Yu Bruno Studer Simone Fouche Lukas Meile Danilo Pereira Petteri Karisto Bruce A.McDonald | 2019 | Plant Phenomics2019，1，1： | 2 |
| 8 | The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy显示文摘Leprosy is a chronic infectious disease caused by Mycobacterium leprae.According to official reports from 121 countries across five WHO regions,there were 213899 newly diagnosed cases in 2014.Although leprosy affects the skin and peripheral nerves,it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals.These forms comprise the extremes of tuberculoid leprosy(TT),with a M.leprae-specific Th1,but also a Th17,response that limits M.leprae multiplication,through to lepromatous leprosy(LL),with M.leprae-specific Th2 and T regulatory responses that do not control M.leprae replication but rather allow bacterial dissemination.The interpolar borderline clinical forms present with similar,but less extreme,immune biases.Acute inflammatory episodes,known as leprosy reactions,are complications that may occur before,during or after treatment,and cause further neurological damages that can cause irreversible chronic disabilities.This review discusses the innate and adaptive immune responses,and their interactions,that are known to affect pathogenesis and influence the clinical outcome of leprosy. | Adriana Barbosa de Lima Fonseca Marise do Vale Simon Rodrigo Anselmo Cazzaniga Tatiana Rodrigues de Moura Roque Pacheco de Almeida Malcolm S.Duthie Steven G.Reed Amelia Ribeiro de Jesus | 2017 | Infectious Diseases of Poverty2017，6，1： | 2 |
| 9 | Investigation of the Parameters Affecting the Cetane Number of Biodiesel显示文摘 | Kapila Wadumesthrige Jeremiah C. Smith John R. Wilson Steven O. Salley K. Y. Simon Ng | 2008 | Journal of the American Oil Chemists’ Society2008，，11： | 2 |
| 10 | Predicting Systemic Disease in Patients With Esophageal Cancer After Esophagectomy: A Multinational Study on the Significance of the Number of Involved Lymph Nodes显示文摘 | Christian G. Peyre Jeffrey A. Hagen Steven R. DeMeester Jan J. B. Van Lanschot Arnulf H?lscher Simon Law Alberto Ruol Ermanno Ancona S Michael Griffin Nasser K. Altorki Thomas W. Rice John Wong Toni Lerut Tom R. DeMeester | 2008 | Annals of Surgery2008，，6： | 1 |
| 11 | Phylogeny of Proteobacteria and Bacteroidetes from oxic habitats of a tidal flat ecosystem 显示文摘 | Stevens H Stubner M Simon M | 2005 | FEMS Mierobiol Eeol2005，54，3： | 1 |
| 12 | The Relationship Between Perceived Practice Quality and Quality Improvement Activities and Physician Practice Dissatisfaction, Professional Isolation, and Work-Life Stress显示文摘 | Mariah A. Quinn Allison Wilcox E John Orav David W. Bates Steven R. Simon | 2009 | Medical Care2009，，8： | 1 |
| 13 | Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets 显示文摘 | James B Steven T Janet D Simon J Dunmore | 2002 | FEBS Letters2002，513，： | 1 |
| 14 | Museums: A supply-Side perspective显示文摘 | Steven Tufts Simon Milne | 1999 | Annals of Tourism Research1999，26，3： | 1 |
| 15 | Caspase‐3 Mediated Neuronal Death After Traumatic Brain Injury in Rats显示文摘 | Robert S. B.Clark Patrick M.Kochanek Simon C.Watkins MinzhiChen C. EdwardDixon Neal A.Seidberg JohnMelick J. EricLoeffert Paula D.Nathaniel Kun LinJin Steven H.Graham | 2001 | Journal of Neurochemistry2001，，2： | 1 |
| 16 | A foundation for interoperability in next-generation product development systems显示文摘 | Simon Szykman Steven J Fenves Walid Keirouz | 2001 | Computer-Aided Design2001，33，7： | 1 |
| 17 | Potential mechanisms regulating pulmonary pathology in inflammatory bowel disease显示文摘 | Mateer Sean W. Maltby Steven Marks Ellen Foster Paul S. Horvat Jay C. Hansbro Philip M. Keely Simon | 2015 | Journal of Leukocyte Biology2015，，5： | 1 |
| 18 | A foundation for interoperability in next - generation product development systems显示文摘 | Simon Szykman Steven J Fenves Walid Keirouz | 2001 | Computer - Aided Design2001，33，7： | 1 |
| 19 | Solid-phase synthesis of lidocaine and rocainamide analogues using backbone amide linker(BAL)anchoring显示文摘 | Simon KS Mandy JP Steven AK | 2003 | J Comb Chem2003，5，6： | 1 |
| 20 | A prospective clinicopathological and endoscopic evaluation of flat and depressed colorectal lesions in the United Kingdom显示文摘 | David P Hurlstone Simon S Cross Ian Adam Andrew J Shorthouse Steven Brown David S Sanders Alan J Lobo | 2003 | The American Journal of Gastroenterology2003，，11： | 1 |
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