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| 1 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 2 | Factor analysis identifies subgroups of constipation显示文摘AIM:To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction.METHODS:One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item,wide-ranging selfreport questionnaire.One hundred of these patients had colonic transit measured scintigraphically.Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology.Cluster analysis was used to determine whether indi-vidual patients naturally group into distinct subtypes.RESULTS:Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors.Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit,irritable bowel syndrome positive criteria and regular stool frequency.The majority of patients with these characteristics also reported regular laxative use.CONCLUSION:Factor analysis identified four constipation subgroups,based on severity and laxative unresponsiveness,in a constipated population.However,clear stratification into clinically identifiable groups remains imprecise. | Philip G Dinning Mike Jones Linda Hunt Sergio E Fuentealba Jamshid Kalanter Denis W King David Z Lubowski Nicholas J Talley Ian J Cook | 2011 | World Journal of Gastroenterology2011，17，11： | 3 |
| 3 | Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study显示文摘BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine. | Nicholas V Mendez Yehuda Raveh Joshua J Livingstone Gaetano Ciancio Giselle Guerra George W Burke III Vadim B Shatz Fouad G Souki Linda J Chen Mahmoud Morsi Jose M Figueiro Tony M Ibrahim Werviston L DeFaria Ramona Nicolau-Raducu | 2021 | World Journal of Transplantation2021，11，4： | 2 |
| 4 | Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study显示文摘 | Zheng Ye Stephen J Sharp Stephen Burgess Robert A Scott Fumiaki Imamura Claudia Langenberg Nicholas J Wareham Nita G Forouhi | 2015 | The Lancet Diabetes & Endocrinology2015，，1： | 1 |
| 5 | Diameter-selective encapsulation of metallocenes in single walled carbon nanotubes 显示文摘 | Li L J Khlobystov A N Wiltshire J G Briggs G A D Nicholas R J | 2005 | Nature Materials2005，4，： | 1 |
| 6 | Diameter-selective encapsulation of metallocenes in single walled carbon nanotubes 显示文摘 | Li L J Khlobystov A N Wiltshire J G Briggs G A D Nicholas R J | 2005 | Nature Materials2005，4，： | 1 |
| 7 | Upregulation of connexin43 gap junctions between neointimal smooth muscle cells显示文摘 | Gabriele Plenz Yu-Shien Ko Hung-I Yeh Heike Eschert Jürgen R. Sindermann Anja Dorszewski Oliver Hofnagel Horst Robenek Günther Breithardt Nicholas J. Severs | 2004 | European Journal of Cell Biology2004，，10： | 1 |
| 8 | Crystallization damage by sodium sulfate 显示文摘 | Nicholas T Flatt R J Scherer G W | 2003 | J Cult Herit2003，4，10： | 1 |
| 9 | A Compilation of New and Published Major and Trace Element Data for NIST SRM 61- and NIST S 612 Glass Reference Materials 显示文摘 | Nicholas J G P William T P John A W | 1997 | Geostandards and Geoanalytical Research1997，，1： | 1 |
| 10 | A compilation of new and published major and trace element data for NIST SRM 610 and NIST SRM 612 glass reference materials显示文摘 | Nicholas J G Pearce William T Perkins John A Westgate | 1997 | Journal of Geostandards and Geoanalysis1997，，6： | 1 |
| 11 | Effect of ABA,fusicoccin,and thiourea on germination and K+ and glucose uptake in chickpea seeds of different temperatures显示文摘 | ALDOSARO J MANTILLA A NICHOLAS G | | 0，，02： | 1 |
| 12 | An SCN9A chan- nelopathy causes congenital inability to experience pain显示文摘 | Cox J J Reimann F Nicholas AK Thornton G Roberts E SpringelL K | 2006 | Nature2006，444，7121： | 1 |
| 13 | Patterns and causes of species richness:a general simulation model for macroecology显示文摘 | Nicholas J G Marti J A | 2009 | Ecology Letters2009，12，9： | 1 |
| 14 | The diagnostic accuracy of radiographs in Lisfranc injury and the potential value of a eranio- caudal projectlon显示文摘 | Rankine J J Nicholas CM Wells G | 2012 | A JR Am J Roentgenol2012，198，4： | 1 |
| 15 | Uniformization and hypergraph partitioning for the distributed computation of response time densities in very large Markov models显示文摘 | Peter G Harrison William J Knottenbelt | 2004 | Journal of Parallel and Distributed Computing2004，64，： | 1 |
| 16 | Roles for cyclopentenyl cations in the synthesis of hydrocarbons from methanol on zeolite catalyst HZSM-5显示文摘 | Haw J F Nicholas J B Song W G | 2000 | J Am Chem Soc2000，122，： | 1 |
| 17 | A comparison of the stable and student distributions as statistical models for stock prices 显示文摘 | Blattberg R C Nicholas J G | 1974 | Journal of Business1974，47，2： | 1 |
| 18 | Crystallization dam- age by sodium sulfate 显示文摘 | NICHOLAS T FLATT R J SCHERER G W | 2003 | Journai of Cultural Heritage2003，4，2： | 1 |
| 19 | Lagrange constraints for transient finite element surface contact 显示文摘 | Carpenter Nicholas J Taylor Robert L Katona Michael G | 1991 | International Journal for Numerical Methods in Engineering1991，32，1： | 1 |
| 20 | Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure显示文摘AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity.Previous reports have suggested that the compound thalidomide attenuates portal hypertension(PHT).However, the mechanism for this action is not fully elucidated.One hypothesis is that thalidomide destabilizes tumor necrosis factor α(TNFα) mR NA and therefore diminishes TNFα induction of nitric oxide synthase(NOS) and the production of nitric oxide(NO).To examine this hypothesis, we utilized the murine partial portal vein ligation(PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice.METHODS: Wild type, inducible nitric oxide synthase(i NOS)-/- and endothelial nitric oxide synthase(e NOS)-/-mice received either PVL or sham surgery and were given either thalidomide or vehicle.Serum nitrate(total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis.Serum TNFα level was quantified by enzyme-linked immunosorbent assay.TNFα m RNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction.PHT was determined by recording splenic pulp pressure(SPP) and abdominal aortic flow after 0-7 d.Response to thalidomide was determined by measurement of SPP and mean arterial pressure(MAP).RESULTS: SPP, abdominal aortic flow(Qao) and plasma NOx were increased in wild type and i NOS-/-PVL mice when compared to sham operated control mice.In contrast, SPP, Qao and plasma NOx were not increased in e NOS-/- PVL mice when compared to sham controls.Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used.Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, e NOS-/-or i NOS-/- mice.Thalidomide acutely increased plasma NOx in wild type and e NOS-/- mice but not i NOS-/-mice.Moreover, thalidomide temporarily(0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e NOS-/- and i NOS-/- PVL mice, after which time levels returned to the respective baseline.CONCLUSION: Thalidomide does not reduce portalpressure in the murine PVL model by modulation of NO biosynthesis.Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism. | Nicholas G Theodorakis Yining N Wang Vyacheslav A Korshunov Mary A Maluccio Nicholas J Skill | 2015 | World Journal of Gastroenterology2015，21，14： | 1 |
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