bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of organic nitrates on arterial diameter among healthy Japanese participants with different mitochondrial aldehyde dehydrogenase 2 genotypes: randomised crossover trial
Authors: Sakata Satoko , Yoshihara Tatsuya , Arima Hisatomi , Shiraishi Fumie , Oniki Hideyuki , Takahashi-Yanaga Fumi , Matsumura Kiyoshi , Sasaguri Toshiyuki 
Published: July 2011

ObjectivesTo determine whether polymorphisms at codon 487 (*1, GAA=Glu; *2, AAA=Lys) of mitochondrial aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerine (glyceryl trinitrate (GTN))-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is a more effective antianginal agent in each ALDH2 genotype.DesignA randomised, open-label, crossover trial with 117 healthy Japanese (20–39 years) whose genotypes were determined (*1/*1, n=47; *1/*2, n=48; *2/*2, n=22) was performed at Kyushu University Hospital, Fukuoka, Japan. Participants were randomly assigned to treatment: sublingual spray of GTN (0.3 mg) or ISDN (1.25 mg). After ≥1 week, measurements were repeated using the other drug. The main outcome measures were the maximal rate of increase in the brachial artery diameter determined by ultrasonography, the time required to attain maximal dilation (Tmax) and the time required to attain 90% maximal dilation (T0.9).ResultsThe maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, GTN Tmaxwas significantly longer for *2/*2 (299.7 s, 269.0–330.4) than *1/*1 (254.7 s, 238.6–273.4; p=0.0190). GTN T0.9was significantly longer in the *1/*2 (206.1 s, 191.7–219.3) and *2/*2 (231.4 s, 211.8–251.0) genotypes than *1/*1 (174.9 s, 161.5–188.3; p=0.0068, p<0.0001, respectively). In contrast, the time-course of ISDN-induced vasodilation did not differ among genotypes. GTN Tmaxand T0.9among *1 allele carriers (*1/*1 and *1/*2) were significantly shorter than those of ISDN, whereas the time course of GTN and ISDN vasodilation did not differ among participants carrying *2/*2.ConclusionsThe amplitude of GTN-induced vasodilation was not influenced by the ALDH2 genotype, but the response was significantly delayed in *2 allele carriers, especially *2/*2. GTN dilated the artery more quickly than ISDN in *1/*1 and *1/*2, but not in *2/*2.Trial registration numberUMIN000001492 (UMIN-CTR database).
Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding
Authors: Taha Ali S , McCloskey Caroline , Craigen Theresa , Angerson Wilson J , Shah Amir A , Morran Christopher G 
Published: July 2011

ObjectiveBlood transfusion remains an integral step in the management of acute non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being increasingly questioned in less severe cases. The authors aimed to measure 30-day and 2-year mortalities after blood transfusion for NV-UGIB.MethodsCox proportional hazards models were used to estimate the association of blood transfusion with mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute UGIB, admission status and medication intake prior to bleeding.Main outcome measuresDeath from any cause at 30 days and 2 years after NV-UGIB.Results1340 patients presented with NV-UGIB< (808 men (60.3%), median age 67 years) of whom 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 26.0% at 2 years in all patients. Comparing subjects with a haemoglobin concentration greater than 10.0 g/dl who were transfused with those who were not, 30-day mortalities (95% CIs) were 11.5% (6.7 to 18.0) versus 3.6% (2.3 to 5.3), respectively, p<0.001, and 2-year mortalities (95% CIs) were 40% (32 to 49) versus 20% (17 to 23), p<0.001. After adjusting for age, Charlson score, Rockall score and haemoglobin, the HRs (95% CIs) for death after transfusion were 1.88 (1.00 to 3.55) (p=0.051) at 30 days and 1.71 (1.28 to 2.28), (p<0.001) at 2 years.ConclusionIn patients with moderately severe NV-UGIB, mortality is higher following blood transfusion. Whether this reflects selection bias, an effect of comorbidity or an effect of transfusion requires urgent prospective study.
Conscientious objection in medical students: a questionnaire survey
Authors: Strickland Sophie LM 
Published: July 2011

ObjectiveTo explore attitudes towards conscientious objections among medical students in the UK.MethodsMedical students at St George's University of London, Cardiff University, King's College London and Leeds University were emailed a link to an anonymous online questionnaire, hosted by an online survey company. The questionnaire contained nine questions. A total of 733 medical students responded.ResultsNearly half of the students in this survey stated that they believed in the right of doctors to conscientiously object toanyprocedure. Demand for the right to conscientiously object is greater in Muslim medical students when compared with other groups of religious medical students.DiscussionAbortion continues to be a contentious issue among medical students and this may contribute to the looming crisis in abortion services over the coming years. This project sheds some light on how future doctors view some of their ethical rights and obligations. Using empirical evidence, it reveals that conscientious objection is an issue in the UK medical student body today. These data could help anticipate problems that may arise when these medical students qualify and practise medicine in the community.ConclusionClearer guidance is needed for medical students about the issue of conscientious objection at medical school.
Computed tomographic angiography versus digital subtraction angiography for the postoperative detection of residual aneurysms: a single-institution series and meta-analysis
Authors: Thaker Nikhil Gautam , Turner Jay D , Cobb William S , Hussain Ibrahim , Janjua Nazli , He Wenzhuan , Gandhi Chirag D , Prestigiacomo Charles Joseph 
Published: July 2011

BackgroundComputed tomographic angiography (CTA) has recently emerged as a non-invasive alternative to digital subtraction angiography (DSA) for the detection of residual cerebral aneurysms (RA).ObjectiveTo compare the diagnostic accuracy of CTA with the current ‘gold standard’, DSA, in the postoperative detection of RA.MethodsPatient data from this single institution were prospectively gathered, and imaging results retrospectively blinded and analyzed. Between 2001 and 2005 eligible patients received microsurgical repair of cerebral aneurysms and were evaluated postoperatively by DSA and CTA. These single-institutional data were compiled with qualified studies published from 1997 to 2009, and a meta-analysis was performed.ResultsThis institutional series reports sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of 100%. Eleven studies met the inclusion criteria for the meta-analysis. A total of 427 patients with 513 aneurysms were included, with 61 RA detected by DSA and 40 detected by CTA. Unweighted analysis resulted in pooled sensitivity of 73.8%, specificity of 96.3%, PPV of 91.0% and NPV of 86.1%. Stratified analysis of studies using 16-slice CTA versus 2D DSA reported pooled sensitivity of 92.6%, specificity of 99.3%, PPV of 95.8%, and NPV of 97.8%.ConclusionsThis meta-analysis supports CTA as an acceptable modality for postoperative detection of RA, although DSA remains the gold standard. By implementing multidetector CTA technology in experienced centers, the sensitivity and specificity of CTA may approach that of traditional DSA for detecting RA. As a cost-effective, non-invasive modality, CTA is a promising alternative to DSA for initial and long-term evaluation of RA.
Stent assisted coiling of the ruptured wide necked intracranial aneurysm
Authors: Lodi Y M , Latorre J G , El-Zammar Z , Swarnkar A , Deshaies E , Fessler R D 
Published: July 2011

BackgroundStent assisted coiling of unruptured wide necked intracranial aneurysms require antiplatelets to prevent stent thrombosis. The effect of the loading dose of antiplatelets prior to the stent coiling procedure in an unsecured wide necked ruptured intracranial aneurysm is not known.ObjectiveTo report any potential complication associated with the use of both aspirin and clopidogrel in stent assisted coiling of ruptured wide necked intracranial aneurysms.MethodsConsecutive patients who underwent stent assisted coiling for ruptured wide necked intracranial aneurysm were enrolled from 2005 to 2009. Patients' demographics, including Hunt and Hess grade, Fisher scale, and location and size of aneurysms, were collected. Complications such as rupture of aneurysm, thromboembolic events, ventriculostomy associated or systemic hemorrhages were recorded. Additionally, a 90 day outcome measurement was obtained using the Glasgow Outcome Scale.Results22 patients with a mean age of 50±13 years underwent stent assisted coiling. A loading dose of clopidogrel 300 mg and aspirin 325 mg orally were given prior to stent placement. There was no intraoperative rupture of aneurysm, ventriculostomy associated hemorrhage or systemic hemorrhagic event. There were two episodes of stent thrombosis; one was an asymptomatic event which developed during the stent assisted coiling procedure and resolved spontaneously; the other was symptomatic which required intra-arterial administration of glycoprotein IIbIIIa receptor antagonist. There was no mortality and good outcome was observed in 82% of patients.ConclusionIn our series of carefully selected patients, therapeutic dual antiplatelet loading prior to stent assisted coiling of ruptured wide necked intracranial aneurysm was not associated with increased bleeding complications. However, thromboembolic events remain the main challenge. Further study is required to confirm the safety of antiplatelet loading in stent assisted ruptured intracranial aneurysm coiling.
Prioritizing Candidate Disease miRNAs by Topological Features in the miRNA Target–Dysregulated Network: Case Study of Prostate Cancer
Authors: Xu Juan , Li Chuan-Xing , Lv Jun-Ying , Li Yong-Sheng , Xiao Yun , Shao Ting-Ting , Huo Xiao , Li Xiang , Zou Yan , Han Qing-Lian , Li Xia , Wang Li-Hua , Ren Huan 
Published: July 2011

Abstract
Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target–dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis. Mol Cancer Ther; 10(10); 1857–66. ©2011 AACR.
An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B
Authors: Winter Georg E. , Rix Uwe , Lissat Andrej , Stukalov Alexey , Müllner Markus K. , Bennett Keiryn L. , Colinge Jacques , Nijman Sebastian M. , Kubicek Stefan , Kovar Heinrich , Kontny Udo , Superti-Furga Giulio 
Published: July 2011

AbstractEwing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option. Mol Cancer Ther; 10(10); 1846–56. ©2011 AACR.
Gulf Survey of Atrial Fibrillation Events (Gulf SAFE)
Authors: Zubaid Mohammad , Rashed Wafa A. , Alsheikh-Ali Alawi A. , AlMahmeed Wael , Shehab Abdullah , Sulaiman Kadhim , Al-Zakwani Ibrahim , AlQudaimi Ahmed , Asaad Nidal , Amin Haitham 
Published: July 2011

Background—
Atrial fibrillation (AF) is the most common serious cardiac arrhythmia, and its prevalence is expected to increase. There is lack of data about patient characteristics, practice patterns, and outcomes of AF in the Arab Middle East.

Methods and Results—
The Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) is a prospective, observational registry of patients with AF with a 12-month follow-up. The registry was emergency room based. Between October 2009 and June 2010, 2043 consecutive patients with AF were enrolled from 23 hospitals in 6 Middle Eastern Gulf countries. Data were collected on a standardized case report form and entered online. Data collected included patient demographics, medical history, type of AF, treatment, and outcome of emergency room visit. If patients were admitted, details of their treatment, investigations, and outcomes during hospital stay were collected. Completion of 12-month follow-up is expected by July 2011. The mean age was 57 years, and 52% were men. The most common concomitant condition was hypertension, present in 1072 (52%) patients. At enrollment, 28% of patients had a history of coronary artery disease, 30% had diabetes, and 16% had rheumatic valve disease. History of stroke and transient ischemic attacks were reported in 9% and 4% of patients, respectively. The most common type of AF, first attack AF, occurred in 37%, whereas 19% of patients had lone AF.

Conclusions—
Gulf SAFE will provide valuable insights into AF management and outcomes in the Gulf region of the Middle East.
Flow-Dependent Regulation of Krüppel-Like Factor 2 Is Mediated by MicroRNA-92a
Authors: Wu Wei , Xiao Han , Laguna-Fernandez Andrés , Villarreal Guadalupe , Wang Kuei-Chun , Geary Greg G. , Zhang Yuzhi , Wang Wei-Chi , Huang Hsien-Da , Zhou Jing , Li Yi-Shuan , Chien Shu , Garcia-Cardena Guillermo , Shyy John Y.-J. 
Published: July 2011

Background—
Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow–regulated KLF2.

Methods and Results—

Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA.
In silico
analysis predicted that miR-92a could bind to the 3′ untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow.

Conclusions—
Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.
Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism
Authors: Lin Xiaobo , Racette Susan B. , Lefevre Michael , Ma Lina , Spearie Catherine Anderson , Steger-May Karen , Ostlund Richard E. 
Published: July 2011

Background—
Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism.

Methods and Results—

Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both
P
<0.0001). Fecal cholesterol excretion was significantly greater (
P
<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (
P
<0.0001 relative to control).

Conclusion—
The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00863265.
Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents
Authors: Gutiérrez-Chico Juan Luis , Regar Evelyn , Nüesch Eveline , Okamura Takayuki , Wykrzykowska Joanna , di Mario Carlo , Windecker Stephan , van Es Gerrit-Anne , Gobbens Pierre , Jüni Peter , Serruys Patrick W. 
Published: July 2011

Background—
Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown.

Methods and Results—

Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I
2
=38.40) but not in the other comparisons.

Conclusions—
Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00389220, NCT00617084.