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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 | Effects of therapeutic horseback riding on post-traumatic stress disorder in military veterans显示文摘Background:Large numbers of post-deployment U.S.veterans are diagnosed with post-traumatic stress disorder(PTSD)and/or traumatic brain injury(TBI),leading to an urgent need for effective interventions to reduce symptoms and increase veterans’coping.PTSD includes anxiety,flashbacks,and emotional numbing.The symptoms increase health care costs for stress-related illnesses and can make veterans’civilian life difficult.Methods:We used a randomized wait-list controlled design with repeated measures of U.S.military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding(THR)program for decreasing PTSD symptoms and increasing coping self-efficacy,emotion regulation,social and emotional loneliness.Fiftyseven participants were recruited and 29 enrolled in the randomized trial.They were randomly assigned to either the horse riding group(n=15)or a wait-list control group(n=14).The wait-list control group experienced a 6-week waiting period,while the horse riding group began THR.The wait-list control group began riding after 6 weeks of participating in the control group.Demographic and health history information was obtained from all the participants.PTSD symptoms were measured using the standardized PTSD Checklist-Military Version(PCL-M).The PCL-M as well as other instruments including,The Coping Self Efficacy Scale(CSES),The Difficulties in Emotion Regulation Scale(DERS)and The Social and Emotional Loneliness Scale for Adults-short version(SELSA)were used to access different aspects of individual well-being and the PTSD symptoms.Results:Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR(P≤0.01)as well as a statistically and clinically significant decrease after 6 weeks of THR(P≤0.01).Logistic regression showed that participants had a 66.7%likelihood of having lower PTSD scores at 3 weeks and 87.5%likelihood at 6 weeks.Under the generalized linear model(GLM),our ANOVA findings for the coping self-efficacy,emotion regulation,and social and emotional loneliness did not reach statistical significance.The results for coping self-efficacy and emotion regulation trended in the predicted direction.Results for emotional loneliness were opposite the predicted direction.Logistic regression provided validation that outcome effects were caused by riding longer.Conclusion:The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans. | Rebecca A.Johnson David L.Albright James R.Marzolf Jessica L.Bibbo Hayley D.Yaglom Sandra M.Crowder Gretchen K.Carlisle Amy Willard Cynthia L.Russell Karen Grindler Steven Osterlind Marita Wassman Nathan Harms | 2018 | Military Medical Research2018，5，1： | 3 |
| 3 | Transcriptional suppression of mir‐29b‐1/mir‐29a promoter by c‐Myc, hedgehog, and NF‐kappaB显示文摘 | Justin L.Mott SatoshiKurita Sophie C.Cazanave Steven F.Bronk Nathan W.Werneburg Martin E.Fernandez‐Zapico | 2010 | J. Cell. Biochem2010，，5： | 3 |
| 4 | Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. | Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni | 2016 | World Journal of Hepatology2016，8，23： | 2 |
| 5 | Appendectomy and Clostridium difficile colitis:Relationships revealed by clinical observations and immunology显示文摘Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics. | Nathan L Sanders R Randal Bollinger Ryan Lee Steven Thomas William Parker | 2013 | World Journal of Gastroenterology2013，19，34： | 2 |
| 6 | Dynamic Patterns of Gene Expression Additivity and Regulatory Variation throughout Maize Development显示文摘Gene expression variation is a key component underlying phenotypic variation and heterosis. Transcriptome profiling was performed on 23 different tissues or developmental stages of two maize inbreds, B73 and Mo17, as well as their hybrid. The obtained large-scale datasets provided opportunities to monitor the developmental dynamics of differential expression, additivity for gene expression, and regulatory variation. The transcriptome can be divided into .30 000 genes that are expressed in at least one tissue of one in bred and an additional ~10 000 “silent” genes that are not expressed in any tissue of any genotype, 90% of which are non-syntenic relative to other grasses. Many (.74%) of the expressed genes exhibit differential expression in at least one tissue. However, the majority of genes with differential expression do not exhibit consistent differential expression in different tissues. These genes often exhibit tissue-specific differential expression with equivalent expression in other tissues, and in many cases they switch the directionality of differential expression in different tissues. This suggests widespread variation for tissue-specific regulation of gene expression between the two maize inbreds B73 and Mo17. Nearly 5000 genes are expressed in only one parent in at least one tissue (single parent expression) and 97% of these genes are expressed at mid-parent levels or higher in the hybrid, providing extensive opportunities for hybrid complementation in heterosis. In general, additive expression patterns are much more common than non-additive patterns, and this trend is more pronounced for genes with strong differential expression or single pare nt expressi on. There is relatively little evidence for non-additive expression patterns that are maintained in multiple tissues. The analysis of allele-specific expression allowed classification of cis. and trans-regulatory variation. Genes with c/s-regulatory variation often exhibit additive expression and tend to have more consistent regulatory variation throughout development. In contrast, genes with trans-reguiatory variation are enriched for non-additive patterns and often show tissue-specific differential expression. Taken together, this study provides a deeper understatiding of regulatory variation and the degree of additive gene expression throughout maize development. The dynamic nature of differential expression, additivity, and regulatory variation imply abundant variability for tissue-specific regulatory mechanisms and suggest that connections between transcriptome and phenome will require expression data from multiple tissues. | Peng Zhou Candice N.Hirsch Steven P.Briggs Nathan M.Springer | 2019 | Molecular Plant2019，12，3： | 2 |
| 7 | Neufeld, Sacroiliac joint pain : a comprehensive review of epidemiology,diagnosis & treatment 显示文摘 | STEVEN P C YIAN C NATHAN J | 2013 | Expert Rev Neurother2013，13，1： | 1 |
| 8 | Dye-doped inorganic/organic composite films as fluorescence sensors for methanol vapor 显示文摘 | Nathan Stevens Akins D L | 2007 | Sensors and Actuators B2007，，123： | 1 |
| 9 | Significance of arterial hypotension after resuscitation from cardiac arrest显示文摘 | Stephen Trzeciak Alan E. Jones J Hope Kilgannon Barry Milcarek Krystal Hunter Nathan I. Shapiro Steven M. Hollenberg R Phillip Dellinger Joseph E. Parrillo | 2009 | Critical Care Medicine2009，，11： | 1 |
| 10 | Crystallographic Identification and Functional Characterization of Phospholipids as Ligands for the Orphan Nuclear Receptor Steroidogenic Factor-1显示文摘 | Yong Li Mihwa Choi Greg Cavey Jennifer Daugherty Kelly Suino Amanda Kovach Nathan C. Bingham Steven A. Kliewer H.Eric Xu | 2005 | Molecular Cell2005，，4： | 1 |
| 11 | Categorization and impact of pulmonary hypertension in patients with advanced COPD显示文摘 | Michael J. Cuttica Ravi Kalhan Oksana A. Shlobin Shahzad Ahmad Mark Gladwin Roberto F. Machado Scott D. Barnett Steven D. Nathan | 2010 | Respiratory Medicine2010，，12： | 1 |
| 12 | The Pacific Decadal Oscillation显示文摘 | Nathan J. Mantua Steven R. Hare | 2002 | Journal of Oceanography2002，，1： | 1 |
| 13 | A smartphone - based painmanagement app for adolescents with cancer: establishing systemrequirements and a pain care algorithm based on literature review,interviews, and consensus 显示文摘 | Jibb LA Stevens BJ Nathan PC | 2014 | JMIR Res Protoc2014，3，1： | 1 |
| 14 | Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression显示文摘 | Naina Shah Dipok Dhar Fatma El Zahraa Mohammed Abeba Habtesion Nathan A. Davies Maria Jover-Cobos Jane Macnaughtan Vikram Sharma Steven W.M. Olde Damink Rajeshwar P. Mookerjee Rajiv Jalan | 2012 | Journal of Hepatology2012，，5： | 1 |
| 15 | cFLIPL prevents TRAIL-induced apoptosis of hepatocellular carcinoma cells by inhibiting the lysosomal pathway of apoptosis显示文摘 | MARIA EUGENIA GUICCIARDI STEVEN F BRONK NATHAN W WERNEBURG | | 0，，05： | 1 |
| 16 | Epigenetic and Genetic Influences on DNA Methylation Variation in Maize Populations[W]显示文摘 | Steven R. Eichten Roman Briskine Jawon Song Qing Li Ruth Swanson-Wagner Peter J. Hermanson Amanda J. Waters Evan Starr Patrick T. West Peter Tiffin Chad L. Myers Matthew W. Vaughn Nathan M. Springer | 2013 | The Plant Cell2013，，8： | 1 |
| 17 | A Pacific interdecadal climate oscillation with impacts on salmon production显示文摘 | NATHAN J M STEVEN R H YUAN Zhang | 1997 | Bulletin of the American Meteorological Society1997，78，： | 1 |
| 18 | Mapping of the Ogura fertility restorer gene Rfo and development of Rfo allele-specific markers in canola (Brassica napus L.)显示文摘 | Xueyi Hu Mandy Sullivan-Gilbert Tom Kubik Jason Danielson Nathan Hnatiuk Wesley Marchione Thomas Greene Steven A. Thompson | 2008 | Molecular Breeding2008，，4： | 1 |
| 19 | Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure显示文摘 | Rajiv Jalan Steven W. M. Olde Damink Nicolaas E. P. Deutz Nathan A. Davies Oliver J. Garden Krishna K. Madhavan Peter C. Hayes Alistair Lee | 2003 | Transplantation2003，，12： | 1 |
| 20 | Updated physician,s guide to the off-label uses of oral isotretinoin 显示文摘 | Steven B Nathan P Michael P | 2014 | J Clin Aesthet Dermatol2014，7，4： | 1 |
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