bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of Chemically Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy
Authors: Lubet Ronald A. , Scheiman James M. , Bode Ann , White Jonathan , Minasian Lori , Juliana M. Margaret , Boring Daniel L. , Steele Vernon E. , Grubbs Clinton J. 
Published: March 2015

Abstract
The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2–specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder–specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN–treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN–treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P &lt; 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. Cancer Prev Res; 8(4); 296–302. ©2015 AACR.
Association rate constants rationalise the pharmacodynamics of apixaban and rivaroxaban
Authors: Jourdi Georges , Siguret Virginie , Martin Anne Céline , Golmard Jean-Louis , Godier Anne , Samama Charles-Marc , Gaussem Pascale , Gouin-Thibault Isabelle , Bonniec Bernard Le 
Published: March 2015

SummaryRivaroxaban and apixaban are selective direct inhibitors of free and prothrombinase-bound factor Xa (FXa). Surprisingly prothrombin time (PT) is little sensitive to clinically relevant changes in drug concentration, especially with apixaban. To investigate this pharmacodynamic discrepancy we have compared the kinetics of FXa inhibition in strictly identical conditions (pH 7.48, 37 °C, 0.15 M). KI values of 0.74 ± 0.03 and 0.47 ± 0.02 nM and kon values of 7.3 ± 1.6 106 and 2.9 ± 0.6 107 M-1 s-1 were obtained for apixaban and rivaroxaban, respectively. To investigate if these constants rationalise the inhibitor pharmacodynamics, we used numerical integration to evaluate impact of FXa inhibition on thrombin generation assay (TGA) and PT. Simulation predicted that in TGA triggered with 20 pM tissue factor, 100 ng/ml apixaban or rivaroxaban increased 1.8– or 3.0-fold the lag time and 1.4– or 2.0-fold the time to peak, whilst decreasing 1.2– or 3.1-fold the maximum thrombin and 1.7– or 3.5-fold the endogenous thrombin potential. These numbers were consistent with those obtained through the corresponding TGA triggered in plasma spiked with apixaban or rivaroxaban. Simulated PT ratios were also consistent with the corresponding plasma PT: markedly less sensitive to apixaban than to rivaroxaban. Analogous differences in TGA and PT were obtained irrespective of the drug amount added. We concluded that kon values for FXa of apixaban and rivaroxaban rationalise the unexpected lower sensitivity of PT and TGA to the former.
Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy
Authors: Kuehl Uwe , Lassner Dirk , Gast Martina , Stroux Andrea , Rohde Maria , Siegismund Christine , Wang Xiaomin , Escher Felicitas , Gross Michael , Skurk Carsten , Tschoepe Carsten , Loebel Madlen , Scheibenbogen Carmen , Schultheiss Heinz-Peter , Poller Wolfgang 
Published: March 2015

Background—
Investigation of disease pathogenesis confined to protein-coding regions of the genome may be incomplete because many noncoding variants are associated with disease. We aimed to identify novel predictive markers for the course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements influencing the grossly different antiviral capacity of individual patients.

Methods and Results—
Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared with those with virus persistence on follow-up. miR profiling revealed highly significant differences in cardiac levels of 16 miRs, but not of protein-coding genes. Evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate receiver operating characteristic curve analysis, confirmed this pattern as highly predictive for disease course (area under the curve, 0.897±0.071; 95% confidence interval, 0.758–1.000). Eight miRs were strongly induced in CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. They are predicted to target multiple immune response genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b, 190, and 422a in the monocytic THP-1 cell line.

Conclusions—
An immediate clinical application of the data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage.
Reduced Fetal Cerebral Oxygen Consumption Is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease
Authors: Sun Liqun , Macgowan Christopher K. , Sled John G. , Yoo Shi-Joon , Manlhiot Cedric , Porayette Prashob , Grosse-Wortmann Lars , Jaeggi Edgar , McCrindle Brian W. , Kingdom John , Hickey Edward , Miller Steven , Seed Mike 
Published: March 2015

Background—
Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation.

Methods and Results—

We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (
P
<0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (
P
<0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (
P
=0.08) and 32% reduction cerebral V
o
2
in CHD fetuses (
P
<0.001), which were associated with a 13% reduction in fetal brain volume (
P
<0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral V
o
2
(
r
=0.37,
P
=0.004).

Conclusions—
This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.
Circulating Brain‐Derived Neurotrophic Factor Concentrations and the Risk of Cardiovascular Disease in the Community
Authors: Kaess Bernhard M. , Preis Sarah R. , Lieb Wolfgang , Beiser Alexa S. , Yang Qiong , Chen Tai C. , Hengstenberg Christian , Erdmann Jeanette , Schunkert Heribert , Seshadri Sudha , Vasan Ramachandran S. ,   CARDIoGRAM
Published: March 2015

Background

Brain‐derived neurotrophic factor (
BDNF
) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating
BDNF
levels are associated with risk of cardiovascular disease (
CVD
).

Methods and Results

We prospectively investigated the association of circulating
BDNF
levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (
FHS
). Using a common nonsynonomous single nucleotide polymorphism (
SNP
) in the

BDNF

gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome‐Wide Replication And Meta‐Analysis) consortium (>22 000 coronary artery disease [
CAD
] cases, >60 000 controls) to investigate whether
SNP
rs6265 was associated with
CAD
in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on
FHS
data. On follow‐up (median 8.9 years), 467 individuals (261 women) in
FHS
experienced a
CVD
event, and 835 (430 women) died. In multivariable‐adjusted Cox regression, serum
BDNF
was associated inversely with
CVD
risk (hazard ratio [
HR
] per 1‐
SD
increase 0.88, 95%
CI
0.80 to 0.97,
P
=0.01) and with mortality (
HR
0.87, 95%
CI
0.80 to 0.93,
P
=0.0002).
SNP
rs6265 was associated with
BDNF
concentrations (0.772 ng/mL increase per minor allele copy) in
FHS
. In CARDIoGRAM,
SNP
rs6265 was associated with
CAD
(odds ratio 0.957, 95%
CI
0.923 to 0.992), a magnitude consistent with the predicted effect (
HR
per minor allele copy 0.99, 95%
CI
0.98 to 1.0;
P
=0.06 for difference between predicted and observed effect).

Conclusion

Higher serum
BDNF
is associated with a decreased risk of
CVD
and mortality. Mendelian randomization suggests a causal protective role of
BDNF
in the pathogenesis of
CVD
.
Effect of Prehospital Induction of Mild Hypothermia on 3‐Month Neurological Status and 1‐Year Survival Among Adults With Cardiac Arrest: Long‐Term Follow‐up of a Randomized, Clinical Trial
Authors: Maynard Charles , Longstreth W. T. , Nichol Graham , Hallstrom Al , Kudenchuk Peter J. , Rea Thomas , Copass Michael K. , Carlbom David , Deem Steven , Olsufka Michele , Cobb Leonard A. , Kim Francis 
Published: March 2015

Background
Randomized trials of prehospital cooling after cardiac arrest have shown that neither prehospital cooling nor targeted temperature management differentially affected short‐term survival or neurological function. In this follow‐up study, we assess the association of prehospital hypothermia with neurological function at least 3 months after cardiac arrest and survival 1 year after cardiac arrest.

Methods and Results

There were 508 individuals who were discharged alive from hospitals in King County, Washington; 373 (73%) were interviewed by telephone 123±43 days after the initial event. Overall, 59% of the treatment group and 58% of the control group had Cerebral Performance Category (
CPC
) 1 or 2 (
P
=0.70), and 50% of the treatment group and 49% of the control group had slight disability or better by the Modified Rankin Scale (
MRS
; (
P
=0.35). One‐year survival was 87% in the treatment group and 84% in the control group (
P
=0.42). Of those with
CPC
1 at hospital discharge, 68% had
CPC
1 or 2 at follow‐up, and 59% had
MRS
of slight disability or better. Of 41 patients with
CPC
3 or 4 at discharge, only 12% had
CPC
2 at follow‐up, and just 5% had
MRS
of slight disability or better. One‐year survival was 92% for
CPC
1 at discharge, but only 40% for
CPC
4.

Conclusion
In addition to excellent survival, patients who had good neurological function at discharge continued to have good function at least 3 months after the event.

Clinical Trial Registration
URL: Clinicaltrials.gov. Unique identifier: NCT00391469
Chicago’s Heat Island and Climate Change: Bridging the Scales via Dynamical Downscaling
Authors: Conry Patrick , Sharma Ashish , Potosnak Mark J. , Leo Laura S. , Bensman Edward , Hellmann Jessica J. , Fernando Harindra J. S. 
Published: March 2015

AbstractThe interaction of global climate change and urban heat islands (UHI) is expected to have far-reaching impacts on the sustainability of the world’s rapidly growing urban population centers. Given that a wide range of spatiotemporal scales contributed by meteorological forcing and complex surface heterogeneity complicates UHI, a multimodel nested approach is used in this paper to study climate-change impacts on the Chicago, Illinois, UHI, covering a range of relevant scales. One-way dynamical downscaling is used with a model chain consisting of global climate (Community Atmosphere Model), regional climate (Weather Research and Forecasting Model), and microscale (“ENVI-met”) models. Nested mesoscale and microscale models are evaluated against the present-day observations (including a dedicated urban miniature field study), and the results favorably demonstrate the fidelity of the downscaling techniques that were used. A simple building-energy model is developed and used in conjunction with microscale-model output to calculate future energy demands for a building, and a substantial increase (as much as 26% during daytime) is noted for future (~2080) climate. Although winds and lake-breeze circulation for future climate are favorable for reducing energy usage by 7%, the benefits are outweighed by such factors as exacerbated UHI and air temperature. An adverse change in human-comfort indicators is also noted in the future climate, with 92% of the population experiencing thermal discomfort. The model chain that was used has general applicability for evaluating climate-change impacts on city centers and, hence, for urban-sustainability studies.
Endoscopic Resection of Sinonasal Tract Schwannoma
Authors: Forer Boaz , Lin Leong Jern , Sethi Dharmbir Singh , Landsberg Roee 
Published: March 2015

Background: Sinonasal schwannoma (SNS) is a rare sinonasal tract tumor whose presentation is similar to that of other benign nasal tumors. Very few case series appear in the literature. This study aims to describe the presentation, treatment, and outcome of 10 SNS cases from 3 referral centers. Methods: All SNS cases were analyzed retrospectively. Patient demographics, tumor data, surgical procedures, and outcome were recorded. Results: Five males and 5 females (mean age, 49.1 ± 21.4 years) were included in the study. The tumor was on the left side in 9 patients and on the right side in 1. It originated in the middle turbinate in 4 cases, the ethmoid and sphenoid sinuses in 2 cases, and the nasal septum and infratemporal fossa in 1 case each. Tumor resection was done endoscopically in all cases, and there was no need for an external procedure, and 5 patients did not require a sinusotomy. All 10 patients remained disease-free after a mean follow-up of 65.3 months (range, 2-120 months). Conclusion: Safe and effective endoscopic resection of SNS is feasible. If the tumor is contained within the nasal cavity, simple tumor excision without sinusotomy can be enough to resect the tumor. In more extensive disease, a wider endoscopic approach may be needed, but an external approach was not necessary in this series.
Lower-limb exoskeletons for individuals with chronic spinal cord injury: findings from a feasibility study
Authors: Benson Ian , Hart Kirsten , Tussler Dot , van Middendorp Joost J 
Published: March 2015

Objective: To assess the feasibility of conducting a well-powered trial evaluating the neurological and functional effects of using an exoskeleton in individuals with chronic spinal cord injury. Design: A longitudinal, prospective, self-controlled feasibility study. Setting: Specialist Spinal Cord Injuries Centre, UK; 8 months during 2013–2014. Subjects: Individuals with chronic motor complete or incomplete spinal cord injury. Interventions: Enrolled subjects were assigned to 20 exoskeleton (ReWalk™, Argo Medical Technologies Ltd, Yokneam Ilit, Israel) training sessions over a 10-week training period. Main measures: Feasibility measures, clinical and mobility outcome measures and measures appraising subjects’ disability and attitude towards assistive technology were assessed before, during and after the study. Descriptive statistics were applied. Results: Out of 60 candidates, ten (17%) were enrolled and five (8%) completed the training programme. Primary reasons for not enrolling were ineligibility ( n = 24, 40%) and limited interest to engage in a 10-week training programme ( n = 16, 27%). Five out of ten enrolled subjects experienced grade I/II skin aberrations. While walking speeds were higher and walking distances were longer in all exoskeleton users when compared with non-use, the exoskeleton did generally not meet subjects’ high expectations in terms of perceived benefits. Conclusions: The conduct of a controlled trial evaluating the benefits of using exoskeletons that require a lengthy user-commitment to training of individuals with chronic motor complete or incomplete spinal cord injury comes with considerable feasibility challenges. Vigilance is required for preventing and detecting medical complications in spinal cord injury exoskeleton users.
The value of serum mean platelet volume in testicular torsion
Authors: Cicek Tufan , Togan Turhan , Akbaba Kaan , Narci Huseyin , Aygun Cem 
Published: March 2015

Objective To compare the serum mean platelet volume (MPV) in patients with testicular torsion and healthy control subjects. Methods This retrospective study compared clinical and demographic data from patients who underwent surgery for testicular torsion and healthy controls. Testicular torsion was diagnosed with a physical examination and Doppler ultrasonography. Age, leukocyte count, platelet count and MPV were recorded for all participants. Results A total of 50 patients with testicular torsion and 51 healthy control subjects were enrolled. There was no significant difference in age and platelet count between the two groups. Patients with testicular torsion had a significantly higher leukocyte count and MPV, compared with controls. According to receiver operating characteristic curve analysis performed for the prediction of testicular torsion, the best cut-off point for MPV was 7.7 fl (sensitivity 62%, specificity 96%), and the best cut-off point for leukocyte count was 9.5 × 109/l (sensitivity 58%, specificity 80%). Conclusions The MPV may be useful as an ancillary test for the diagnosis of testicular torsion. Further studies are needed in order to confirm these preliminary results.
Leptin levels and lipoprotein profiles in patients with cholelithiasis
Authors: Saraç Serdar , Atamer Aytaç , Atamer Yildiz , Can Ahmet Selçuk , Bilici Aslan , Taçyildiz İbrahim , Koçyiğit Yüksel , Yenice Necati 
Published: March 2015

Objective To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis. Methods Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay. Results A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1. Conclusions Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis.
Lateral Trunk Lean in Pitchers Affects Both Ball Velocity and Upper Extremity Joint Moments
Authors: Solomito Matthew J. , Garibay Erin J. , Woods Jessica R. , Õunpuu Sylvia , Nissen Carl W. 
Published: March 2015

Background: The incidence of upper extremity injuries in baseball pitchers is increasing. Over the past decade there has been a great deal of research attempting to elucidate the cause of these injuries, focusing mainly on the mechanics of the pitching arm with no examination of other key segments, such as the trunk. This is surprising, as coaches will often comment on trunk position in an effort to improve pitching outcomes. Purpose: To determine the association between contralateral trunk lean and ball velocity and the moments about the elbow and glenohumeral joint. Study Design: Descriptive laboratory study. Methods: A total of 99 pitchers were recruited for this study and underwent a pitching analysis using 3-dimensional motion analysis techniques. A random intercept mixed-effects regression model was used to determine if statistically significant associations existed between contralateral trunk lean (away from the pitching arm side) and ball velocity, as well as the elbow varus moment and glenohumeral internal rotation moment. Results: The results demonstrated that the greatest contralateral trunk lean occurs around the time of the peak elbow varus moment. Statistically significant associations were found between contralateral trunk lean and increased ball velocity ( P = .003) indicating that for every 10° increase in contralateral lean, ball velocity increased 0.5 m/s. Results also indicated that for every 10° increase in contralateral lean, elbow varus moments increased by 3.7 N·m and glenohumeral internal rotation moments increased by 2.5 N·m ( P < .001 for both). Conclusion: Study findings indicate that the positioning of the trunk plays a substantial role in pitching performance and pitcher injury potential. This work helps to demonstrate the importance of proper trunk mechanics in pitching and highlights the need for future research to understand the contribution of the trunk to pitching mechanics. Clinical Relevance: Pitching coaches and trainers can use the results of this study to stress the importance of proper trunk mechanics in pitching. Specifically, improving core strength and trunk control in an effort to maintain a more upright posture through the pitching cycle can reduce upper extremity joint stresses.