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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系统综述与网状Meta分析的PRISMA扩展声明显示文摘PRISMA声明旨在提高系统综述和META分析报告的完整性,该声明已经广泛用于指导系统综述和META分析的报告和发表。原始的PRISMA声明是针对两种干预措施比较的传统的系统综述与META分析而制定的,然而,随着多种干预措施比较的系统综述的发展,实施和报告这一类系统综述面临较大挑战。此时,针对网状META分析的PRISMA扩展声明应运而生,旨在提高网状META分析系统综述的报告质量。PRISMA扩展声明是由专家们通过DELPHI调查、面对面讨论和共识大会而最终确立的。PRISMA扩展声明是在原始PRISMA声明的报告清单的基础上经过修改,最终确定了32个条目,每个条目均与网状META分析报告的内容直接相关。本文对网状META分析的PRISMA扩展声明进行了阐述,对报告清单各条目进行了举例说明,并详细说明了在原始PRISMA声明的基础上新增和修改各条目的理由。此外,PRISMA扩展声明强调了在网状META分析的实际操作中需要重点关注的信息。本文的目标读者包括网状META分析的作者与读者,以及期刊杂志的编辑与同行评审。李志霞 杨俊 叶欣 周凌波 杨智荣 孙凤 詹思延 Brian Hutton Georgia Salanti Deborah M.Caldwell Anna Chaimani Christopher H.Schmid Chris Cameron John P.A.Ioannidis Sharon Straus Kristian Thorlund Jeroen P.Jansen Cynthia Mulrow Ferrán Catalá-López Peter C.Gozsche Kay Dickersin Isabelle Boutron Douglas G.Altman David Moher 2016中国循证心血管医学杂志2016,8,6:11
3Platelet-rich plasma for muscle injuries: A systematic review of the basic science literature显示文摘BACKGROUND Platelet-rich plasma(PRP) is an increasingly used biologic adjunct for muscle injuries, as it is thought to expedite healing. Despite its widespread use, little is known regarding the mechanisms by which PRP produces its efficacious effects in some patients.AIM To clarify the effects of PRP on muscular pathologies at the cellular and tissue levels by evaluating the basic science literature.METHODS A systematic review of PubMed/MEDLINE and EMBASE databases was performed using the Preferred Reporting Items for Systematic Reviews and MetaAnalyses(PRISMA) guidelines and checklist. Level III in vivo and in vitro studies examining PRP effects on muscles, myocytes and/or myoblasts were eligible for inclusion. Extracted data included PRP preparation methods and study results.RESULTS Twenty-three studies were included(15 in vivo, 6 in vitro, 2 in vitro/in vivo). Only one reported a complete PRP cytology(platelets, and red and white blood cell counts). Five in vitro studies reported increased cellular proliferation, four reported increased gene expression, and three reported increased cellular differentiation. Five in vivo studies reported increased gene expression, three reported superior muscle regeneration, and seven reported improved histological quality of muscular tissue.CONCLUSION The basic science literature on the use of PRP in muscle pathology demonstrates that PRP treatment confers several potentially beneficial effects on healing in comparison to controls. Future research is needed to determine optimal cytology,dosing, timing, and delivery methods of PRP for muscle pathologies.Kyle N Kunze Charles P Hannon Jared D Fialkoff Rachel M Frank Brian J Cole 2019World Journal of Orthopedics2019,10,7:6
4Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732).Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco 2012World Journal of Gastroenterology2012,18,26:6
5Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis显示文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone.Biomineralization is regulated by the ratio of inorganic phosphate(Pi) to mineral inhibitor pyrophosphate(PPi), where local Piand PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase(TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1(NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum.Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPienvironment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPihave little effect on cellular cementum formation, though matrix mineralization is affected.Laura E Zweifler Mudita K Patel Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster 2015International Journal of Oral Science2015,7,1:5
6Laparoscopic vs open partial colectomy in elderly patients:Insights from the American College of Surgeons- National Surgical Quality Improvement Program database显示文摘AIM: To compare the outcomes between the laparoscopic and open approaches for partial colectomy in elderly patients aged 65 years and over using the American College of Surgeons- National Surgical Quality Improvement Program(ACS NSQIP) database. METHODS: The ACS NSQIP database for the years 2005-2011 was queried for all patients 65 years and above who underwent partial colectomy. 1:1 propensity score matching using the nearest- neighbor method was performed to ensure both groups had similar preoperative comorbidities. Outcomes including postoperative complications, length of stay and mortality were compared between the laparoscopic and open groups. χ2 and Fisher's exact test were used for discrete variables and Student's t-test for continuous variables. P < 0.05 was considered significant and odds ratios with 95%CI were reported when applicable. RESULTS: The total number of patients in the ACS NSQIP database of the years 2005-2011 was 1777035. We identified 27604 elderly patients who underwent partial colectomy with complete data sets. 12009(43%) of the cases were done laparoscopically and15595(57%) were done with open. After propensity score matching, there were 11008 patients each in the laparoscopic(LC) and open colectomy(OC) cohorts. The laparoscopic approach had lower post-operative complications(LC 15.2%, OC 23.8%, P < 0.001), shorter length of stay(LC 6.61 d, OC 9.62 d, P < 0.001) and lower mortality(LC 1.6%, OC 2.9%, P < 0.001). CONCLUSION: Even after propensity score matching, elderly patients in the ACS NSQIP database having a laparoscopic partial colectomy had better outcomes than those having open colectomies. In the absence of specific contraindications, elderly patients requiring a partial colectomy should be offered the laparoscopic approach.Umashankkar Kannan Vemuru Sunil K Reddy Amar N Mukerji Vellore S Parithivel Ajay K Shah Brian F Gilchrist Daniel T Farkas 2015World Journal of Gastroenterology2015,21,45:3
7Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight 2010Cellular & Molecular Immunology2010,7,3:3
8Developing a global interconnected power system model显示文摘Decarbonizing the power sector is a necessary step towards a low-carbon future. Interconnecting power systems on different continents could be a method to contribute to such a future, by utilizing highly efficient renewable resources around the globe, while simultaneously providing additional benefits of power system integration. In this paper, we describe the process of constructing and simulating a global interconnected power system model with high technical and temporal resolution. Being the first of its kind on the global scale, this paper is designed to showcase the proof of concept as an intermediate step to a high resolution global model, by integrating an existing European power system model with the North-American continent. The work to date has been focused on testing the methodology and building up necessary knowledge to realistically simulate the functionality of a possible future global grid. Some initial results are analysed to support the viability of the model and the concept in general. Furthermore, key factors influencing the development and optimal performance of the global interconnected power system model are identified.Maarten Brinkerink Paul Deane Seán Collins Brian Ó Gallachóir 2018Global Energy Interconnection2018,1,3:2
9新型酶基毛毯保洁剂在防止淀粉堵塞毛毯中的应用显示文摘John T Sarraf Brian N Altherr 伍子奇(编译) 2008造纸化学品2008,20,4:2
10Critical evaluation of unscientific arguments disparaging affirmative infant male circumcision policy显示文摘We evaluate recent claims opposing infant male circumcision,a procedure now supported by the evidencebased policy of the American Academy of Pediatrics.We find those criticisms depend on speculative claims about the foreskin and obfuscation of the strong scientific evidence supporting pediatric policy development.An argument that circumcision should be delayed to allow a boy to make up his own mind as an adult fails to appreciate the psychological,scheduling and financial burdens later circumcision entails,so reducing the likelihood that it will occur.In contrast,early infant circumcision is convenient,safer,quicker,lower risk,healing is faster,cosmetic outcome is routinely good and the lifetime benefits accrue immediately.Benefits include reduction in urinary tract infections,inflammatory skin conditions,foreskin problems,and,when older,substantial protection against sexually transmitted infections and genital cancers in the male and his female sexual partners.Some authorities regard the failure to offer parents early infant circumcision as unethical,just as it would be unethical to fail to encourage the vaccination of children.In conclusion,the criticisms of evidence-based infant male circumcision policy are seriously flawed and should be dismissed as unhelpful to evidence-based development and implementation of pediatric policy intended to improve public health and individual wellbeing.Brian J Morris John N Krieger Jeffrey D Klausner 2016World Journal of Clinical Pediatrics2016,5,3:2
11Physical activity and nutrition attitudes in obese Hispanic children with non-alcoholic steatohepatitis显示文摘AIM:To assess nutrition,physical activity and health-ful knowledge in obese children with biopsy-proven nonalcoholic steatohepatitis(NASH or NA)compared to children without liver disease.METHODS:Children with biopsy-proven NASH comprised the NASH group.Age,sex and ethnicity matched control groups consisted of obese(OB)and lean(CO) children with no liver disease.Subjects were adminis-tered the School Physical Activity and Nutrition Survey and one blood draw was obtained.RESULTS:Fifty-seven patients were enrolled with a mean age of 12.1±2.1 years,and all were Hispanic.Even though the OB and NA had a similar increased body mass index(%),35%of the NA group always read nutrition labels compared to none in the OB(P<0.05),and more NA children felt their diet is'less healthy'.NA consumed the least amount of fruits with only 25%having≥1 fruit/d vs 45%in OB and 64.7% in CO(P<0.05 NA vs CO).Only 15%of NA subjects performed light exercise vs 35%and 59%of OB and CO groups,respectively(P=0.02).The mean physical activity score was lowest in the NA group(P<0.05).Amongst the subjects with NASH,we found that 100% of patients with grade 2 or 3 fibrosis had a sedentary score>2 compared to only 63.6%of those with grade 1 or no fibrosis(P<0.05).CONCLUSION:Children with NASH had increased sedentary behavior,decreased activity,and fruit intake.Larger studies may determine the benefit of changing these behaviors as treatment for NASH.Lana N Hattar Theresa A Wilson Leanel A Tabotabo E O'Brian Smith Stephanie H Abrams 2011World Journal of Gastroenterology2011,17,39:2
12Nanorover for Mars 显示文摘BRIAN W ANNETTE N RICK W A 1997Space Technology1997,17,3:1
13Uncoupling of cardiae cells by fatty acids structure activity relations hips显示文摘Burt J M Massey K D Brian N 1991Am J Physiol1991,20,3:1
14Validation of a sensitive LC-MS assay for quantification of glyburide and its metabolite 4-Wanshydroxy glyburide in plasma and urine: an OPRU Network study original research article显示文摘SURESH B N BRIAN J K MARY F H 2007Journal of Chromatography B2007,860,1:1
15Prehospital diagnosis and treatment of acute myocardial infarction:a north-south perspective显示文摘Brian GW Kereiakes J Edward N 1991Am Heart J1991,121,:1
16Paracrine activation of hepatic stellate cells in platelet‐derived growth factor C transgenic mice: Evidence for stromal induction of hepatocellular carcinoma显示文摘Jocelyn H. Wright Melissa M. Johnson Masami Shimizu‐Albergine Renay L. Bauer Brian J. Hayes James Surapisitchat Kelly L. Hudkins Kimberly J. Riehle Simon C. Johnson Matthew M. Yeh Theodor K. Bammler Richard P. Beyer Debra G. Gilbertson Charles E. Alpers N 2014Int. J. Cancer2014,,4:1
17DNA immunization of dairy cows with the clumping factor A of Staph- ylococcus aureus显示文摘ADEL N M NOUR EL-DIN LULZIM SHKRETA BRIAN G TALBOT 2006Vaccine2006,24,:1
18Serum troponin T measurement in patients with chronic renal impairment predicts survival and vascular disease: a 2 year prospective study显示文摘GRAHAME N BRIAN K 2003Nephrol Dial Transplant2003,18,8:1
19Maca: An Andean crop with multi-pharmacological functions显示文摘Wang Y L Wang Y C Brian M N 2007Food Research International2007,40,7:1
20Sodium and sodium-ion energy storagebatterics显示文摘BRIAN L E LINDA F N 2012Current Opinion in Solid State and Materials Science2012,16,:1
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