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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021,24,9: | 34 |
| 2 | Multiparametric analysis of colorectal cancer immune responses显示文摘Colorectal cancer(CRC) is a heterogeneous disease, with a diverse and plastic immune cell infiltrate. These immune cells play an important role in regulating tumour growth-progression or elimination. Some populations of cells have a strong correlation with disease-free survival, making them useful prognostic markers. In particular, the infiltrate of CD3^+ and CD8^+ T cells into CRC tumours has been validated worldwide as a valuable indicator of patient prognosis. However, the heterogeneity of the immune response, both between patients with tumours of different molecular subtypes, and within the tumour itself, necessitates the use of multiparametric analysis in the investigation of tumour-specific immune responses. This review will outline the multiparametric analysis techniques that have been developed and applied to studying the role of immune cells in the tumour, with a focus on colorectal cancer. Because much of the data in this disease relates to T cell subsets and heterogeneity, we have used T cell populations as examples throughout. Flow and mass cytometry give a detailed representation of the cells within the tumour in a single-cell suspension on a per-cell basis. Imaging technologies, such as imaging mass cytometry, are used to investigate increasing numbers of markers whilst retaining the spatial and structural information of the tumour section and the infiltrating immune cells. Together, the analyses of multiple immune parameters can provide valuable information to guide clinical decision-making in CRC. | Julia KH Leman Sarah K Sandford Janet L Rhodes Roslyn A Kemp | 2018 | World Journal of Gastroenterology2018,24,27: | 12 |
| 3 | Cardiometabolic health among gastric bypass surgery patients with polycystic ovarian syndrome显示文摘AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice.Separate repeated measures linear mixed models were fit using the MIXED procedureto assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic,non-Hispanic black(NHB) and white(NHW)].RESULTS:The majority of the sample was Hispanic(66%,25% NHB,9% NHW).Mean body mass index significantly improved 1 year post-surgery for all ethnic groups(45.5 to 35.5 kg/m2 for Hispanics,46.8 to 37.7 kg/m2 for NHB and 45.7 to 36.7 kg/m2 for NHW,P < 0.001).Among Hispanic women mean total cholesterol(198.1 to 160.2 mg/dL),low-density lipoproteins(LDL) cholesterol(120.9 to 91.0 mg/dL),triglycerides(148.6 to 104.8 mg/dL),hemoglobin A1c(6.2% to 5.6%),alanine aminotransferase(28.1 to 23.0 U/L) and aspartate aminotransferase(23.5 to 21.6 U/L) decreased significantly(P < 0.001).Among NHB,mean total cholesterol(184.5 to 154.7 mg/dL),LDL cholesterol(111.7 to 88.9 mg/dL) and triglycerides(99.7 to 70.0 mg/dL) decreased significantly(P < 0.05).Among NHW,mean total cholesterol(200.9 to 172.8 mg/dL) and LDL cholesterol(124.2 to 96.6 mg/dL),decreased significantly(P < 0.05).Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome.CONCLUSION:Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women. | Carley A Gomez-Meade Adriana Carrillo Gabriela Lopez-Mitnik Sarah E Messiah Kristopher L Arheart Nestor de la Cruz-Muoz | 2013 | World Journal of Diabetes2013,4,3: | 6 |
| 4 | 针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。 | Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) | 2020 | 英国医学杂志中文版2020,23,9: | 5 |
| 5 | Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/Ipr mouse model of systemic lupus erythematosus显示文摘热吃惊蛋白质 90 的提高的表示(HSP90 ) 在全身的豺狼座 erythematosus (SLE ) 的肾和浆液被发现了病人和 MRL/Mp-Fas lpr /Fas lpr (MRL/lpr ) 自体免疫的老鼠。如果 HSP90 的抑制将在 MRL/lpr 老鼠减少疾病,我们调查了。在在 vivo 的 vitro,有在 IL-6 的有免疫力刺激的显示出的减少的表示以前的 HSP90 禁止者 Geldanamycin 的 mesangial 房间的预告的处理, IL-12 和号码,我们发现当与 C57BL/6 相比鼠标和 MRL/lpr 鼠标与 HSP90 禁止者 17-DMAG 对待时, HSP90 表示在 MRL/lpr 肾被提高。与 17-DMAG 对待的 MRL/lpr 老鼠显示出减少的 proteinuria 并且减少了浆液 anti-dsDNA 抗体生产。Glomerulonephritis 和 glomerular IgG 和 C3 没被 17-DMAG 的管理显著地在 MRL/lpr 影响。17-DMAG 增加了 CD8 + T 房间,减少的双 negative T 房间,减少 CD4/CD8 比率和减少的小囊的 B 房间。这些研究建议 HSP90 可以在调整 T 房间区别和激活起一个作用并且 HSP90 抑制可以在豺狼座减少发炎。 | Samuel K Shimp III Cristen B Chafin Nicole L Regna Sarah E Hammond Molly A Read David L Caudell Marissa Nichole Rylander Christopher M Reilly | 2012 | Cellular & Molecular Immunology2012,9,3: | 3 |
| 6 | 1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor显示文摘AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress. | Sarah A Hosgood Phillip J Yates Michael L Nicholson | 2014 | World Journal of Transplantation2014,4,4: | 2 |
| 7 | Obesity and cardiometabolic disease risk factors among US adolescents with disabilities显示文摘AIM: To generate prevalence estimates of weight status and cardiometabolic disease risk factors among adolescents with and without disabilities.METHODS: Analysis of the 1999-2010 National Health and Nutrition Examination Survey data was conducted among 12-18 years old with(n = 256) and without disabilities(n = 5020). Mean values of waist circumference, fasting glucose, high-density-lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure and metabolic syndrome(Met S, ≥ 3 risk factors present) were examined by the following standardized body mass index(BMI) categories for those with and without disabilities; overweight(BMI ≥ 85th- < 95 th percentile for age and sex), obesity(BMI ≥ 95 th percentile) and severe obesity(BMI ≥35 kg/m2). Linear regression models were fit with each cardiometabolic disease risk factor independently as continuous outcomes to show relationships with disability status. RESULTS: Adolescents with disabilities were significantlymore likely to be overweight(49.3%), obese(27.6%) and severely obese(12%) vs their peers without disabilities(33.1%, 17.5% and 3.6%, respectively, P ≤ 0.01 for all). A higher proportion of overweight, obese and severely obese children with disabilities had abnormal SBP, fasting lipids and glucose as well as Met S(18.9% of overweight, 32.3% of obese, 55% of severely obese) vs their peers without disabilities(9.7%, 16.8%, 36.3%, respectively). US adolescents with disabilities are over three times as likely to have Met S(OR = 3.45, 95%CI: 1.08-10.99, P = 0.03) vs their peers with no disabilities.CONCLUSION: Results show that adolescents with disabilities are disproportionately affected by obesity and poor cardiometabolic health vs their peers with no disabilities. Health care professionals should monitor the cardiometabolic health of adolescents with disabilities. | Sarah E Messiah Denise C Vidot Gabriel Somarriba Kanathy Haney Semra Aytur Ruby A Natale Jeffrey P Brosco Kristopher L Arheart | 2015 | World Journal of Diabetes2015,6,1: | 2 |
| 8 | Effect of storage temperature on the in vitro reproduction of Radopholus similis显示文摘 | Fallas G A Sarah J L | | 0,,02: | 1 |
| 9 | Activity of selected antimicrobial agents against strains of Staphylococcus aureus isolated from bovine intramammary infections that produce β-Lactamase显示文摘 | Jeffery L Sarah A | 1997 | J Dairy Sci1997,80,: | 1 |
| 10 | Over-expression of sphingosinekinase-1 enhances a progenitor phenotype in humanendothelial cells显示文摘 | Barrett Jeffrey M Parham Kate A Pippal Jyotsna B CockshellMichaelia P Moretti Paul A B Brice Sarah L Pitson StuartM Bonder Claudine S | 2011 | Microcirculation2011,187,: | 1 |
| 11 | Microfabricated drug delivery systems:From particles to pores显示文摘 | Desai Tejal A | 2003 | Advanced Drug Delivery Reviews2003,55,3: | 1 |
| 12 | 显示文摘 | Tao Sarah L Desai Tejal A | 2003 | Advanced Drug Delivery Reviews2003,55,3: | 1 |
| 13 | Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2显示文摘 | Sos Brandon C Harris Charles Nordstrom Sarah M Tran Jennifer L Balázs Mercedesz Caplazi Patrick Febbraio Maria Applegate Milana A B Wagner Kay-Uwe Weiss Ethan J | 2011 | Journal of Clinical Investigation2011,,4: | 1 |
| 14 | Neurobiology of Sehizophrenia显示文摘 | Christopher A Ross R L M Sarah A J | 2006 | Neuron2006,52,: | 1 |
| 15 | Effectiveness of inter- ventions targeting physical activity, nutrition and healthy weight for u- niversity and college students:A systematic review and meta-analysis 显示文摘 | RONALD C SARAH A REBECCA L | 2015 | Int J Bebav Nut Phy Act2015,12,1: | 1 |
| 16 | Motor outcome after subcortical stroke correlates with the degree of cortical reorganization显示文摘 | Gary W Thickbroom Michelle L Byrnes Sarah A Archer Frank L Mastaglia | 2004 | Clinical Neurophysiology2004,,: | 1 |
| 17 | Comparative X-ray and27AlNMR spectroscopic studies of the speciation of aluminum in aqueous systems:Al(Ⅲ)Complexes of N(CH2CO2H)2(CH2CH2OH)显示文摘 | Sarah L H Peter A J Ian D J | 1995 | Journal of Inorgranic Biochemistry1995,59,4: | 1 |
| 18 | Disparities in Breast Cancer Survival Among Asian Women by Ethnicity and Immigrant Status: A Population-Based Study显示文摘 | Gomez Scarlett Lin Clarke Christina A Shema Sarah J Chang Ellen T Keegan Theresa H M Glaser Sally L | 2010 | American Journal of Public Health2010,,5: | 1 |
| 19 | Activity of selected antimicrobial agents against strains of Staphylococcus aureus isolated from bovine intramammary infections that produce β-lactamase显示文摘 | Jeffery L Sarah A | 1997 | J Dairy Sci1997,80,: | 1 |
| 20 | Effect of Storage Temperature on the in Vitro Reproduction of Radopholus similis 显示文摘 | FALLAS G A SARAH J L | 1994 | Ne- matropiea1994,24,2: | 1 |