bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventricular Conduction and Long-Term Heart Failure Outcomes and Mortality in African Americans
Authors: Mentz Robert J. , Greiner Melissa A. , DeVore Adam D. , Dunlay Shannon M. , Choudhary Gaurav , Ahmad Tariq , Khazanie Prateeti , Randolph Tiffany C. , Griswold Michael E. , Eapen Zubin J. , O’Brien Emily C. , Thomas Kevin L. , Curtis Lesley H. , Hernandez Adrian F. 
Published: December 2014

Background—
QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans.

Methods and Results—

We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56;
P
=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation.

Conclusions—
QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.
Effect of Physical Activity on Age-Related Changes in Cardiac Function and Performance in Women
Authors: Jakovljevic Djordje G. , Papakonstantinou Lida , Blamire Andrew M. , MacGowan Guy A. , Taylor Roy , Hollingsworth Kieren G. , Trenell Michael I. 
Published: December 2014

Background—
Higher levels of physical activity are associated with reduced cardiovascular mortality but its effect on age-related changes in cardiac structure and function is unknown. The present study defines the effect of daily physical activity on age-related changes in cardiac structure, function, metabolism, and performance in healthy women.

Methods and Results—

Sixty-three healthy women were grouped according to age (young, 20–30 years, n=21; middle, 40–50 years, n=22; and older, 65–81 years, n=20) and daily physical activity level (low active <7500 and high active >12 500 steps/d). Participants underwent cardiac MRI including tissue tagging and
31
P spectroscopy and exercise testing with noninvasive central hemodynamic measurements. Aging was associated with increased concentric remodeling (
P
<0.01) and left ventricular torsion (
P
<0.01), and a decline in diastolic function (
P
<0.01), cardiac phosphocreatine:ATP ratio (
P
<0.01), peak exercise cardiac power output (
P
<0.01), and O
2
consumption (
P
<0.01). Older high-active women demonstrated a phosphocreatine:ATP ratio and relative peak O
2
consumption similar to young low-active women, and 23% and 26% higher than older low-active women (phosphocreatine:ATP ratio, 1.9±0.2 versus 1.4±0.1;
P
<0.05 and O
2
consumption, 24.1±3.8 versus 17.8±2.0 mL/[kg·min];
P
<0.01). In older women, physical activity had no effect on eccentricity ratio (0.9±0.2 versus 0.8±0.1 g/mL;
P
=0.19), E/A ratio (1.3±0.5 versus 1.4±0.5;
P
=0.66), torsion (7.6±1.7 versus 8.0°±2.1°;
P
=0.20), and peak cardiac power output (3.4±0.7 versus 3.4±0.8 W;
P
=0.91).

Conclusions—
A higher level of daily physical activity preserves cardiac metabolism and exercise capacity with aging but has limited effect on age-related changes in concentric remodeling, diastolic function, and cardiac performance.
Role for Telomerase in Pulmonary Hypertension
Authors: Mouraret Nathalie , Houssaïni Amal , Abid Shariq , Quarck Rozenn , Marcos Elisabeth , Parpaleix Aurelien , Gary-Bobo Guillaume , Dubois-Randé Jean-Luc , Derumeaux Geneviève , Boczkowski Jorge , Delcroix Marion , Blasco Maria A. , Lipskaia Larissa , Amsellem Valérie , Adnot Serge 
Published: December 2014

Background—
Cells exhibiting dysregulated growth may express telomerase reverse transcriptase (TERT), the dual function of which consists of maintaining telomere length, in association with the RNA template molecule TERC, and controlling cell growth. Here, we investigated lung TERT in human and experimental pulmonary hypertension (PH) and its role in controlling pulmonary artery smooth muscle cell (PA-SMC) proliferation.

Methods and Results—

Marked TERT expression or activity was found in lungs from patients with idiopathic PH and from mice with PH induced by hypoxia or serotonin-transporter overexpression (SM22-5HTT
+
mice), chiefly within PA-SMCs. In cultured mouse PA-SMCs, TERT was expressed on growth stimulation by serum. The TERT inhibitor imetelstat and the TERT activator TA65 abrogated and stimulated PA-SMC growth, respectively. PA-SMCs from PH mice showed a heightened proliferative phenotype associated with increased TERT expression, which was suppressed by imetelstat treatment. TERC
−/−
mice at generation 2 and TERT
−/−
mice at generations 2, 3, and 4 developed less severe PH than did wild-type mice exposed to chronic hypoxia, with less distal pulmonary artery muscularization and fewer Ki67-stained proliferating PA-SMCs. Telomere length differed between TERC
−/−
and TERT
−/−
mice, whereas PH severity was similar in the 2 strains and across generations. Chronic imetelstat treatment reduced hypoxia-induced PH in wild-type mice or partially reversed established PH in SM22-5HTT
+
mice while simultaneously decreasing TERT expression. Opposite effects occurred in mice treated with TA65.

Conclusions—
Telomerase exerts telomere-independent effects on PA-SMC growth in PH and may constitute a treatment target for PH.
Oxidative Stress Activates Endothelial Innate Immunity via Sterol Regulatory Element Binding Protein 2 (SREBP2) Transactivation of MicroRNA-92a
Authors: Chen Zhen , Wen Liang , Martin Marcy , Hsu Chien-Yi , Fang Longhou , Lin Feng-Mao , Lin Ting-Yang , Geary McKenna J. , Geary Greg G. , Zhao Yongli , Johnson David A. , Chen Jaw-Wen , Lin Shing-Jong , Chien Shu , Huang Hsien-Da , Miller Yury I. , Huang Po-Hsun , Shyy John Y-J. 
Published: December 2014

Background—
Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase–derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element–binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.

Methods and Results—
Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II–infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell–specific SREBP2 transgenic mice, locked nucleic acid–modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II–induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell–dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β.

Conclusions—
Our findings suggest that SREBP2–miR-92a–inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.
Genetic Architecture of White Matter Hyperintensities Differs in Hypertensive and Nonhypertensive Ischemic Stroke
Authors: Adib-Samii Poneh , Devan William , Traylor Matthew , Lanfranconi Silvia , Zhang Cathy R. , Cloonan Lisa , Falcone Guido J. , Radmanesh Farid , Fitzpatrick Kaitlin , Kanakis Allison , Rothwell Peter M. , Sudlow Cathie , Boncoraglio Giorgio B. , Meschia James F. , Levi Chris , Dichgans Martin , Bevan Steve , Rosand Jonathan , Rost Natalia S. , Markus Hugh S. 
Published: December 2014

Background and Purpose—

Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [
H
SNP
]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals.

Methods—

WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate
H
SNP
for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses.

Results—

A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (
H
SNP
=0.23;
P
=0.0026).
H
SNP
estimates were higher among hypertensive individuals (
H
SNP
=0.45;
P
=7.99×10
−5
); this increase was greater than expected by chance (
P
=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (
H
SNP
=0.13;
P
=0.13).

Conclusions—
A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction.
Variations in Acute Hospital Stroke Care and Factors Influencing Adherence to Quality Indicators in 6 European Audits
Authors: Wiedmann Silke , Hillmann Steffi , Abilleira Sònia , Dennis Martin , Hermanek Peter , Niewada Maciej , Norrving Bo , Asplund Kjell , Rudd Anthony G. , Wolfe Charles D.A. , Heuschmann Peter U. 
Published: December 2014

Background and Purpose—
We compared compliance with standards of acute stroke care between 6 European audits and identified factors associated with delivery of appropriate care.

Methods—
Data were derived from stroke audits in Germany, Poland, Scotland, Catalonia, Sweden, and England/Wales/Northern-Ireland participating within the European Implementation Score (EIS) collaboration. Associations between demographic and clinical characteristics with adherence to predefined quality indicators were investigated by hierarchical logistic regression analyses.

Results—
In 2007/2008 data from 329 122 patients with stroke were documented. Substantial variations in adherence to quality indicators were found; older age was associated with a lower probability of receiving thrombolytic therapy, anticoagulant therapy, or stroke unit treatment and a higher probability of being tested for dysphagia. Women were less likely to receive anticoagulant or antiplatelet therapy or stroke unit treatment. No major weekend effect was found.

Conclusions—
Detected variations in performance of acute stroke services were found. Differences in adherence to quality indicators might indicate population subgroups with specific needs for improving care delivery.
Hypertension Treatment Intensification Among Stroke Survivors With Uncontrolled Blood Pressure
Authors: Roumie Christianne L. , Zillich Alan J. , Bravata Dawn M. , Jaynes Heather A. , Myers Laura J. , Yoder Joseph , Cheng Eric M. 
Published: December 2014

Background and Purpose—
We examined blood pressure 1 year after stroke discharge and its association with treatment intensification.

Methods—
We examined the systolic blood pressure (SBP) stratified by discharge SBP (≤140, 141–160, or >160 mm Hg) among a national cohort of Veterans discharged after acute ischemic stroke. Hypertension treatment opportunities were defined as outpatient SBP >160 mm Hg or repeated SBPs >140 mm Hg. Treatment intensification was defined as the proportion of treatment opportunities with antihypertensive changes (range, 0%–100%, where 100% indicates that each elevated SBP always resulted in medication change).

Results—
Among 3153 patients with ischemic stroke, 38% had ≥1 elevated outpatient SBP eligible for treatment intensification in the 1 year after stroke. Thirty percent of patients had a discharge SBP ≤140 mm Hg, and an average 1.93 treatment opportunities and treatment intensification occurred in 58% of eligible visits. Forty-seven percent of patients discharged with SBP 141 to160 mm Hg had an average of 2.1 opportunities for intensification and treatment intensification occurred in 60% of visits. Sixty-three percent of the patients discharged with an SBP >160 mm Hg had an average of 2.4 intensification opportunities, and treatment intensification occurred in 65% of visits.

Conclusions—
Patients with discharge SBP >160 mm Hg had numerous opportunities to improve hypertension control. Secondary stroke prevention efforts should focus on initiation and review of antihypertensives before acute stroke discharge; management of antihypertensives and titration; and patient medication adherence counseling.
Characterizing Congo Basin Rainfall and Climate Using Tropical Rainfall Measuring Mission (TRMM) Satellite Data and Limited Rain Gauge Ground Observations
Authors: Munzimi Yolande A. , Hansen Matthew C. , Adusei Bernard , Senay Gabriel B. 
Published: December 2014

AbstractQuantitative understanding of Congo River basin hydrological behavior is poor because of the basin’s limited hydrometeorological observation network. In cases such as the Congo basin where ground data are scarce, satellite-based estimates of rainfall, such as those from the joint NASA/JAXA Tropical Rainfall Measuring Mission (TRMM), can be used to quantify rainfall patterns. This study tests and reports the use of limited rainfall gauge data within the Democratic Republic of Congo (DRC) to recalibrate a TRMM science product (TRMM 3B42, version 6) in characterizing precipitation and climate in the Congo basin. Rainfall estimates from TRMM 3B42, version 6, are compared and adjusted using ground precipitation data from 12 DRC meteorological stations from 1998 to 2007. Adjustment is achieved on a monthly scale by using a regression-tree algorithm. The output is a new, basin-specific estimate of monthly and annual rainfall and climate types across the Congo basin. This new product and the latest version-7 TRMM 3B43 science product are validated by using an independent long-term dataset of historical isohyets. Standard errors of the estimate, root-mean-square errors, and regression coefficients r were slightly and uniformly better with the recalibration from this study when compared with the 3B43 product (mean monthly standard errors of 31 and 40 mm of precipitation and mean r2 of 0.85 and 0.82, respectively), but the 3B43 product was slightly better in terms of bias estimation (1.02 and 1.00). Despite reasonable doubts that have been expressed in studies of other tropical regions, within the Congo basin the TRMM science product (3B43) performed in a manner that is comparable to the performance of the recalibrated product that is described in this study.
Simulation of Flash-Flood-Producing Storm Events in Saudi Arabia Using the Weather Research and Forecasting Model*
Authors: Deng Liping , McCabe Matthew F. , Stenchikov Georgiy , Evans Jason P. , Kucera Paul A. 
Published: December 2014

Abstract
The challenges of monitoring and forecasting flash-flood-producing storm events in data-sparse and arid regions are explored using the Weather Research and Forecasting (WRF) Model (version 3.5) in conjunction with a range of available satellite, in situ, and reanalysis data. Here, we focus on characterizing the initial synoptic features and examining the impact of model parameterization and resolution on the reproduction of a number of flood-producing rainfall events that occurred over the western Saudi Arabian city of Jeddah. Analysis from the European Centre for Medium-Range Weather Forecasts (ECMWF) interim reanalysis (ERA-Interim) data suggests that mesoscale convective systems associated with strong moisture convergence ahead of a trough were the major initial features for the occurrence of these intense rain events. The WRF Model was able to simulate the heavy rainfall, with driving convective processes well characterized by a high-resolution cloud-resolving model. The use of higher (1 km vs 5 km) resolution along the Jeddah coastline favors the simulation of local convective systems and adds value to the simulation of heavy rainfall, especially for deep-convection-related extreme values. At the 5-km resolution, corresponding to an intermediate study domain, simulation without a cumulus scheme led to the formation of deeper convective systems and enhanced rainfall around Jeddah, illustrating the need for careful model scheme selection in this transition resolution. In analysis of multiple nested WRF simulations (25, 5, and 1 km), localized volume and intensity of heavy rainfall together with the duration of rainstorms within the Jeddah catchment area were captured reasonably well, although there was evidence of some displacements of rainstorm events.
Recent Randomized Controlled Trials in Otolaryngology
Authors: Banglawala Sarfaraz M. , Lawrence Lauren A. , Franko‐Tobin Emily , Soler Zachary M. , Schlosser Rodney J. , Ioannidis John 
Published: December 2014

ObjectiveTo assess recent trends in the prevalence and quality of reporting of randomized controlled trials (RCTs) in 4 otolaryngology journals.Study DesignMethodology and reporting analysis.SettingRandomized controlled trials in 4 otolaryngology journals.Subjects and MethodsAll RCTs published from 2011 to 2013 in 4 major otolaryngology journals were examined for characteristics of study design, quality of design and reporting, and funding.ResultsOf 5279 articles published in 4 leading otolaryngology journals from 2011 to 2013, 189 (3.3%) were RCTs. The majority of RCTs were clinical studies (86%), with the largest proportion consisting of sinonasal topics (31%). Most interventions were medical (46%), followed by surgical (38%) and mixed (16%). In terms of quality, randomization method was reported in 54% of RCTs, blinding in 33%, and adverse events in 65%. Intention‐to‐treat analysis was used in 32%; P values were reported in 87% and confidence intervals in 10%. Research funding was most often absent or not reported (55%), followed by not‐for‐profit (25%).ConclusionsBased on review of 4 otolaryngology journals, RCTs are still a small proportion of all published studies in the field of otolaryngology. There seem to be trends toward improvement in quality of design and reporting of RCTs, although many quality features remain suboptimal. Practitioners both designing and interpreting RCTs should critically evaluate RCTs for quality.
TORP Ossiculoplasty Outcomes with and without a Stapes Footplate Prosthesis
Authors: Cox Matthew D. , Russell James S. , Dornhoffer John L. 
Published: December 2014

ObjectiveThe titanium stapes footplate prosthesis (FPP) was designed to ensure a stable connection of a total ossicular replacement prosthesis (TORP) to the stapes footplate and maximize acoustic coupling by centering the footplate on the oval window. Our goal was to assess the impact of the FPP on TORP ossiculoplasty outcomes.Study DesignCase series with chart review.SettingTertiary care center.SubjectsAdult patients undergoing TORP ossiculoplasty with (n = 53) or without (n = 108) a stapes FPP.MethodsRate of prosthesis displacement and audiologic outcomes were tabulated for statistical analysis.ResultsA lower rate of prosthesis displacement and statistically better audiologic outcomes were seen in FPP patients. The pure‐tone average air‐bone gap (PTA‐ABG) was closed to <20 dB in 69.8% (37/53) of patients in the study arm and 44.4% (48/108) of patients in the control arm (P =. 003). The PTA‐ABG was decreased by a mean ± SD of 19.3 ± 11.7 dB and 12.6 ± 11.0 dB in the study and control groups, respectively (P =. 0012).ConclusionsUse of the titanium stapes FPP during TORP ossiculoplasty provides a statistically significant advantage in short‐term PTA‐ABG closure and a higher rate of successful rehabilitation of conductive hearing loss. Further studies are necessary to assess any long‐term advantages a FPP may offer.
Assessment of Mitochondrial Membrane Potential in HEI‐OC1 and LLC‐PK1 Cells Treated with Gentamicin and Mitoquinone
Authors: Ng Maria Raye Anne V. , Antonelli Patrick J. , Joseph Jerin , Dirain Carolyn Ojano 
Published: December 2014

ObjectiveTo determine the effects of concurrent treatment with gentamicin and the mitochondria‐targeted antioxidant mitoquinone (MitoQ; which may prevent gentamicin ototoxicity) on change in the mitochondrial membrane potential (Δψm), a precursor of apoptosis.Study DesignProspective and controlled.SettingAcademic research laboratory.Subjects and MethodsLLC‐PK1 (Lilly Laboratories Culture–Pig Kidney Type 1) and HEI‐OC1 (House Ear Institute Organ of Corti 1) cells—renal and auditory cell lines, respectively—were used in this study. Δψm was assessed by flow cytometry through the MitoProbe JC‐1 Kit for Flow Cytometry in untreated LLC‐PK1 and HEI‐OC1 cells and cells exposed to low‐ (100µM) or high‐ (2000µM) dose gentamicin for 24 hours, with and without 0.5µM each of MitoQ or idebenone (IDB; an untargeted ubiquinone).ResultsΔψm was not different in untreated LLC‐PK1 cells and cells coincubated with low‐dose gentamicin and MitoQ or IDB (P >. 05). In HEI‐OC1 cells, coincubation with low‐dose gentamicin and MitoQ decreased Δψm (P =. 002). Coincubation of LLC‐PK1 cells with high‐dose gentamicin and DMSO, MitoQ, or IDB depolarized Δψm (P <. 0001), with MitoQ depolarizing the Δψm to a greater extent than that of IDB (P =. 03). In contrast, HEI‐OC1 cells demonstrated a hyperpolarized Δψm when coincubated with high‐dose gentamicin and DMSO, MitoQ, or IDB (P <. 001).ConclusionThe combination of gentamicin and MitoQ holds the potential to disrupt Δψm. This suggests a heightened need to monitor for toxicity in patients receiving both agents.