bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naproxen Induces Cell-Cycle Arrest and Apoptosis in Human Urinary Bladder Cancer Cell Lines and Chemically Induced Cancers by Targeting PI3K
Authors: Kim Mi-Sung , Kim Jong-Eun , Lim Do Young , Huang Zunnan , Chen Hanyong , Langfald Alyssa , Lubet Ronald A. , Grubbs Clinton J. , Dong Zigang , Bode Ann M. 
Published: December 2013

Abstract
Naproxen [(S)-6-methoxy-α-methyl-2-naphthaleneacetic acid] is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, antipyretic, and anti-inflammatory activities. Naproxen, as well as other nonsteroidal anti-inflammatory drug, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphoinositide 3-kinase (PI3K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UM-UC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through cyclin-dependent kinase 4, cyclin D1, and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase-3, caspase-7, and PARP in both cell types. Naproxen-induced cell death was mainly because of apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Cancer Prev Res; 7(2); 236–45. ©2013 AACR.
Impact of Vitamin D Supplementation on Inflammatory Markers in African Americans: Results of a Four-Arm, Randomized, Placebo-Controlled Trial
Authors: Chandler Paulette D. , Scott Jamil B. , Drake Bettina F. , Ng Kimmie , Manson JoAnn E. , Rifai Nader , Chan Andrew T. , Bennett Gary G. , Hollis Bruce W. , Giovannucci Edward L. , Emmons Karen M. , Fuchs Charles S. 
Published: December 2013

Abstract
African Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [25(OH)D]. The effect of vitamin D3 (cholecalciferol) supplementation on inflammatory markers is uncertain. We conducted a randomized, double-blind, placebo-controlled trial of supplemental oral vitamin D (placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 orally for 3 months) in 328 African Americans (median age, 51 years) of public housing communities in Boston, MA, who were enrolled over three consecutive winter periods (2007–2010). Change from 0 to 3 months of plasma levels of 25(OH)D, high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-10, and soluble TNF-α receptor type 2 (sTNF-R2) in 292 (89%) participants were measured. Overall, no statistically significant changes in CRP, IL-6, IL-10, and sTNF-R2 were observed after the vitamin D supplementation period. Baseline CRP was significantly inversely associated with the baseline 25(OH)D level (P &lt; 0.001) in unadjusted and adjusted models. An interaction between baseline 25(OH)D and vitamin D supplementation was observed for outcome change in log CRP (month 3–month 0; P for interaction = 0.04). Within an unselected population of African Americans, short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers. This study confirms the strong independent association of CRP with 25(OH)D status even after adjusting for body mass index. Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African Americans. Cancer Prev Res; 7(2); 218–25. ©2013 AACR.
Patient outcomes using the European label for dabigatran
Authors: Clemens Andreas , Noack Herbert , Ferreira Jorge , Connolly Stuart J. , Yusuf Salim , Lip Gregory Y. H. 
Published: December 2013

SummaryIn the RE-LY trial dabigatran 150 mg twice daily (D150) showed significantly fewer strokes, and 110 mg (D110) significantly fewer major bleeding events (MBE) compared to well-controlled warfarin in patients with atrial fibrillation (AF). The European (EU) label currently recommends the use of D150 in AF patients who are aged < 80 years without an increased risk for bleeding (e.g. HAS-BLED score <3) and not on concomitant verapamil. In other patients, D110 is recommended. In this post-hoc analysis of the RE-LY dataset, we simulated how dabigatran (n=6,004) would compare to well-controlled warfarin (n=6,022) used according to the EU label. “EU label simulated dabigatran treatment” was associated with significant reductions in stroke and systemic embolism (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60–0.91), haemorrhagic stroke (HR 0.22; 95%CI 0.11–0.44), death (HR 0.86; 95%CI 0.75–0.98), and vascular death (HR 0.80; 95%CI 0.68–0.95) compared to warfarin. Dabigatran was also associated with less major bleeding (HR 0.85; 95%CI 0.73–0.98), life-threatening bleeding (HR 0.72; 95%CI 0.58–0.91), intracranial haemorrhage (HR 0.28; 95%CI 0.17–0.45), and “any bleeds” (HR 0.86; 95%CI 0.81–0.92), but not gastrointestinal major bleeding (HR 1.23; 95%CI 0.96–1.59). The net clinical benefit was significantly better for dabigatran compared to warfarin. In conclusion, this post-hoc simulation of dabigatran usage based on RE-LY trial dataset indicates that “EU label simulated dabigatran treatment” may be associated with superior efficacy and safety compared to warfarin, and are in support of the EU label and the 2012 European Society of Cardiology AF guideline recommendations. Thus, adherence to European label/guideline use results in a clinically relevant benefit for dabigatran over warfarin, for both efficacy and safety.Note: The editorial process for this paper was fully handled by Prof Christian Weber, Editor in Chief.
Association of Body Mass Index and Mortality After Acute Ischemic Stroke
Authors: Skolarus Lesli E. , Sanchez Brisa N. , Levine Deborah A. , Baek Jonggyu , Kerber Kevin A. , Morgenstern Lewis B. , Smith Melinda A. , Lisabeth Lynda D. 
Published: December 2013

Background—
The prevalence of severe obesity is rising in the United States. Although mild to moderately elevated body mass index (BMI) is associated with reduced mortality after acute ischemic stroke, less is known about severe obesity.

Methods and Results—

Patients with acute ischemic stroke (n=1791) ≥45 years were identified from the biethnic population–based Brain Attack Surveillance in Corpus Christi (BASIC) study from June 1, 2005, to December 31, 2010. Median follow-up was 660 days. BMI was abstracted from the medical record. Survival was estimated by BMI category (underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and severe obesity) using Kaplan-Meier methods. Hazard ratios for the relationship between BMI modeled continuously and mortality were estimated from Cox regression models after adjustment for patient factors. The median BMI was 27.1 kg/m
2
(interquartile range, 23.7–31.2 kg/m
2
), and 56% were Mexican American. A total of 625 patients (35%) died during the study period. Persons with higher baseline BMI had longer survival in unadjusted analysis (
P
<0.01). After adjustment for demographics, stroke severity, and stroke and mortality risk factors, the relationship between BMI and mortality was U shaped. The lowest mortality risk was observed among patients with an approximate BMI of 35 kg/m
2
, whereas those with lower or higher BMI had higher mortality risk.

Conclusions—
Severe obesity is associated with increased poststroke mortality in middle-aged and older adults. Stroke patients with class 2 obesity had the lowest mortality risk. More research is needed to determine weight management goals among stroke survivors.
Association of Body Mass Index and Long-Term Outcomes in Older Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: O’Brien Emily C. , Fosbol Emil L. , Peng S. Andrew , Alexander Karen P. , Roe Matthew T. , Peterson Eric D. 
Published: December 2013

Background—
Prior studies have found that obese patients have paradoxically lower in-hospital mortality after non–ST-segment–elevation myocardial infarction than their normal-weight counterparts, yet whether these associations persist long term is unknown.

Methods and Results—
We linked detailed clinical data for patients with non–ST-segment–elevation myocardial infarction aged ≥65 years in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Registry to Medicare claims data to obtain longitudinal outcomes. Using height and weight measured on admission, patients were categorized into 6 body mass index (BMI [kilograms per meter squared]) groups. Multivariable Cox proportional hazards models were used to estimate the association between BMI and (1) all-cause mortality, (2) all-cause readmission, (3) cardiovascular readmission, and (4) noncardiovascular readmission for 3 years after hospital discharge. Among older patients with non–ST-segment–elevation myocardial infarction (n=34 465), 36.3% were overweight and 27.7% were obese. Obese patients were younger and more likely to have hypertension, diabetes mellitus, and dyslipidemia than normal or underweight patients. Relative to normal-weight patients, long-term mortality was lower for patients classified as overweight (BMI, 25.0–29.9), obese class I (BMI, 30.0–34.9), and obese class II (BMI, 35.0–39.9), but not obese class III (BMI ≥40.0). In contrast, 3-year all-cause and cardiovascular readmission were similar across BMI categories. Relative to normal-weight patients, noncardiovascular readmissions were similar for obese class I but higher for obese class II and obese class III.

Conclusions—
All-cause long-term mortality was generally lower for overweight and obese older patients after non–ST-segment–elevation myocardial infarction relative to those with normal weight. Longitudinal readmissions were similar or higher with increasing BMI.
Racial/Ethnic and Gender Gaps in the Use of and Adherence to Evidence-Based Preventive Therapies Among Elderly Medicare Part D Beneficiaries After Acute Myocardial Infarction
Authors: Lauffenburger Julie C. , Robinson Jennifer G. , Oramasionwu Christine , Fang Gang 
Published: December 2013

Background—
It is unclear whether gender and racial/ethnic gaps in the use of and patient adherence to β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins after acute myocardial infarction have persisted after establishment of the Medicare Part D prescription program.

Methods and Results—

This retrospective cohort study used 2007 to 2009 Medicare service claims among Medicare beneficiaries ≥65 years of age who were alive 30 days after an index acute myocardial infarction hospitalization in 2008. Multivariable logistic regression models examined racial/ethnic (white, black, Hispanic, Asian, and other) and gender differences in the use of these therapies in the 30 days after discharge and patient adherence at 12 months after discharge, adjusting for patient baseline sociodemographic and clinical characteristics. Of 85 017 individuals, 55%, 76%, and 61% used angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins, respectively, within 30 days after discharge. No marked differences in use were found by race/ethnicity, but women were less likely to use angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers compared with men. However, at 12 months after discharge, compared with white men, black and Hispanic women had the lowest likelihood (≈30%–36% lower;
P
<0.05) of being adherent, followed by white, Asian, and other women and black and Hispanic men (≈9%–27% lower;
P
<0.05). No significant difference was shown between Asian/other men and white men.

Conclusions—
Although minorities were initially no less likely to use the therapies after acute myocardial infarction discharge compared with white patients, black and Hispanic patients had significantly lower adherence over 12 months. Strategies to address gender and racial/ethnic gaps in the elderly are needed.
Diagnosing Intracranial Aneurysms With MR Angiography
Authors: Sailer Anna M.H. , Wagemans Bart A.J.M. , Nelemans Patricia J. , de Graaf Rick , van Zwam Willem H. 
Published: December 2013

Background and Purpose—
The aim of this study was to evaluate the sensitivity and specificity of MR angiography (MRA) in the diagnosis of ruptured and unruptured intracranial aneurysms.

Methods—
A systematic search was performed on 4 electronic databases on relevant articles that were published from January 1998 to October 2013. Inclusion criteria were met by 12 studies that compared MRA with digital subtraction angiography as reference standard. Two independent reviewers evaluated the methodological quality of the studies. Data from eligible studies were extracted and used to construct 2×2 contingency tables on a per-aneurysm level. Pooled estimates of sensitivity and specificity were calculated for all studies and subgroups of studies. Heterogeneity was tested, and risk for publication bias was assessed.

Results—

Included studies were of high methodological quality. Studies with larger sample size tended to have higher diagnostic performance. Most studies used time-of-flight MRA technique. Among the 960 patients assessed, 772 aneurysms were present. Heterogeneity with reference to sensitivity and specificity was moderate to high. Pooled sensitivity of MRA was 95% (95% confidence interval, 89%–98%), and pooled specificity was 89% (95% confidence interval, 80%–95%). False-negative and false-positive aneurysms detected on MRA were mainly located at the skull base and middle cerebral artery. Freehand 3-dimensional reconstructions performed by the radiologist significantly increased diagnostic performance. Studies performed on 3 Tesla showed a trend toward higher performance (
P
=0.054).

Conclusions—
Studies on diagnostic performance of MRA show high sensitivity with large variation in specificity in the detection of intracranial aneurysms.
The Transition to a Subtropical Jet Regime and Its Maintenance
Authors: Lachmy Orli , Harnik Nili 
Published: December 2013

Abstract
An abrupt transition from a merged jet regime to a subtropical jet regime is analyzed using a two-layer modified quasigeostrophic (QG) spherical model. Unlike the common version of QG models, this model includes advection of the zonal mean momentum by the ageostrophic mean meridional circulation, allowing for a relatively realistic momentum balance in the tropics and subtropics. The merged jet is a single jet inside the Ferrel cell created by a merging of the subtropical and eddy-driven jets, and the subtropical jet is a mainly thermally driven jet at the Hadley cell edge. The maintenance of each type of jet depends on the dominant baroclinic modes. In the merged jet regime, the spectrum is dominated by intermediate-scale (wavenumbers 4–6) fast waves at the midlatitudes that grow close to the jet maximum. In the subtropical jet regime, the spectrum is dominated by long (wavenumbers 1–3) slow westward-propagating waves at high latitudes and somewhat weaker intermediate-scale slow waves at the midlatitudes. In the subtropical jet regime, waves equilibrate at weaker amplitudes than in the merged jet regime. A mechanism is found that explains why baroclinic instability is weaker in the subtropical jet regime, although the vertical shear of the mean flow is stronger, which has to do with the lower-level potential vorticity (PV) structure. The relevance of these results to the real atmosphere seams to hold in local zonal sections but not for the zonal mean.
The Linkage between the Warm and the Cold Conveyor Belts in an Idealized Extratropical Cyclone*
Authors: Schemm Sebastian , Wernli Heini 
Published: December 2013

Abstract
This study continues the investigation of airstreams in idealized moist baroclinic waves and addresses the formation of the cold conveyor belt (CCB), its linkage to the warm conveyor belt (WCB), and their impact on the development of a midlatitude cyclone. The CCB is identified as a coherent bundle of trajectories, characterized by weak ascent and a strong increase of potential vorticity (PV) along the flow, in contrast to the WCB, defined as the trajectories with maximum ascent. The authors illuminate the role of the two conveyor belts in the formation of two strong PV anomalies that form in the upper (WCB, negative PV anomaly) and lower troposphere (CCB, positive PV anomaly), respectively, and thereby establish a link between these airstreams and relevant aspects of the dynamics of extratropical cyclones. The CCB moves close to the surface along the colder side of the bent-back front and experiences a PV increase as it passes below a region of maximum latent heat release at midtropospheric levels. Accordingly, it arrives with high PV values at the tail of the bent-back front where the most intense low-level winds occur. The WCB, which rises above the bent-back front, causes the formation of the midtropospheric heating rate maximum and thereby not only influences the upper-level downstream development, but also drives the increase of PV along the CCB and, in consequence, indirectly drives the formation of the low-level jet at the tail of the bent-back front.
Modified Hyoid Suspension Technique in the Treatment of Multilevel Related Obstructive Sleep Apnea
Authors: Piccin Ottavio , Scaramuzzino Giuseppe , Martone Chiara , Marra Francesca , Gobbi Riccardo , Sorrenti Giovanni 
Published: December 2013

ObjectiveUsing the Hörmann technique of hyoid suspension in sleep apnea surgery, a steel wire is placed through the thyroid cartilage and slung around the hyoid bone. However, we experienced thyroid cartilage fracture by steel wire traction. A modification is presented to avoid thyroid cartilage fracture.Study DesignCase series with chart review.SettingUniversity hospital.Subjects and MethodsTwenty‐seven patients affected by obstructive sleep apnea syndrome underwent Hörmann hyoid suspension. In 2 patients, the steel wire caused a fracture of the thyroid cartilage. The technique was therefore modified in 25 subsequent patients. The wire is threaded through an adaptation titanium miniplate placed on the surface of the thyroid cartilage.ResultsThe apnea‐hypopnea index decreased from 43.1 to 10.9/h. Nineteen patients (76%) met the criteria for a successful outcome. No complications related to this modification were noted.ConclusionsThe Hörmann hyoid suspension is a procedure that advances the hyoid bone to expand the airway, and its effectiveness has been proven previously. The modified hyoid suspension presented here promises similar results without the risk of serious complications such as thyroid cartilage fracture.
Accuracy of computed tomography findings in acute pericarditis
Authors: Hammer Mark M , Raptis Constantine A , Javidan-Nejad Cylen , Bhalla Sanjeev 
Published: December 2013

Background: Acute pericarditis is a close clinical mimic of pulmonary embolism (PE) in the emergency department, and thus many of these patients are evaluated with chest computed tomography (CT). Purpose: To study whether CT findings can be diagnostic of acute pericarditis. Material and Methods: Using the electronic medical record, we retrospectively identified 46 cases of acute pericarditis and 46 control patients with pericardial effusions due to volume overload, all of whom underwent CT examination. Cases were reviewed by two blinded academic thoracic radiologists. Results: The majority, 67%, of the pericarditis cases were evaluated with PE-protocol CTs. Pericardial thickening/enhancement was the most accurate single parameter for pericarditis, with sensitivity of 54–59% and specificity of 91–96%. Conclusion: CT findings, while not sensitive for pericarditis, are diagnostic, with few false-positives. Radiologists should be attentive to pericardial thickening or enhancement on CT studies done for chest pain, as they may be able to suggest pericarditis as an alternative diagnosis for the chest pain.
Mechanism of temozolomide-induced antitumour effects on glioma cells
Authors: Shen Wei , Hu Jun-An , Zheng Jie-Sheng 
Published: December 2013

Objective To investigate the mechanisms of action of the tumoricidal effects of temozolomide against the human glioma cell line U251 in vitro, and to provide preclinical proof-of-concept studies of the effects of temozolomide-containing regimens. Methods U251 cells were exposed to 100 µmol/l temozolomide. Morphological alterations were monitored by light microscopy. Cell viability was measured using the 3 -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and the rate of apoptosis were determined using flow cytometry and the number of acidic vesicular organelles stained with acridine orange were analysed by fluorescence microscopy. The scratch recovery test was used to measure cell migration. Results U251 cells that were treated with temozolomide displayed morphological alterations indicative of a rounder shape and impaired cellular adhesion to the cell culture plate compared with control U251 cells. Temozolomide reduced cell viability as measured by the MTT assay, caused cell cycle arrest in the gap 2/mitosis phase, inhibited cell migration and promoted autophagy in U251 cells. Conclusion Temozolomide induced autophagic, but not apoptotic processes, in U251 cells and thus reduced their viability and migration.
Upper extremity morbidity after radial forearm flap harvest: a prospective study
Authors: Fang Qi-Gen , Shi Shuang , Zhang Xu , Li Zhen-Ning , Liu Fa-Yu , Sun Chang-Fu 
Published: December 2013

Objective To determine the effect of radial forearm free (RFF) flap harvest on patient-reported postoperative upper extremity disability. Methods Patients undergoing RFF flap reconstruction following resection of head and neck cancer were recruited and matched with similar patients undergoing non-RFF reconstruction. All subjects completed the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire preoperatively and at least 1 year postoperatively. Results Postoperative DASH scores were significantly higher (more severe disability) in patients undergoing RFF flap reconstruction (6.93 ± 5.54; n = 52) compared with those undergoing non-RFF flap surgeries (2.95 ± 4.42; n = 52). Preoperative DASH score, flap size, patient age and tumour stage were significantly correlated with postoperative DASH score. Conclusion Excluding the effect of neck dissection, RFF flap reconstruction has a significant deleterious effect on upper extremity function.