bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Biomarkers of Residual Disease after Surgical Debulking of High-Grade Serous Ovarian Cancer
Authors: Tucker Susan L. , Gharpure Kshipra , Herbrich Shelley M. , Unruh Anna K. , Nick Alpa M. , Crane Erin K. , Coleman Robert L. , Guenthoer Jamie , Dalton Heather J. , Wu Sherry Y. , Rupaimoole Rajesha , Lopez-Berestein Gabriel , Ozpolat Bulent , Ivan Cristina , Hu Wei , Baggerly Keith A. , Sood Anil K. 
Published: April 2014

AbstractPurpose: Residual disease following primary cytoreduction is associated with adverse overall survival in patients with epithelial ovarian cancer. Accurate identification of patients at high risk of residual disease has been elusive, lacking external validity and prompting many to undergo unnecessary surgical exploration. Our goal was to identify and validate molecular markers associated with high rates of residual disease.Methods: We interrogated two publicly available datasets from chemonaïve primary high-grade serous ovarian tumors for genes overexpressed in patients with residual disease and significant at a 10% false discovery rate (FDR) in both datasets. We selected genes with wide dynamic range for validation in an independent cohort using quantitative RT-PCR to assay gene expression, followed by blinded prediction of a patient subset at high risk for residual disease. Predictive success was evaluated using a one-sided Fisher exact test.Results: Forty-seven probe sets met the 10% FDR criterion in both datasets. These included FABP4 and ADH1B, which tracked tightly, showed dynamic ranges &gt;16-fold and had high expression levels associated with increased incidence of residual disease. In the validation cohort (n = 139), FABP4 and ADH1B were again highly correlated. Using the top quartile of FABP4 PCR values as a prespecified threshold, we found 30 of 35 cases of residual disease in the predicted high-risk group (positive predictive value = 86%) and 54 of 104 among the remaining patients (P = 0.0002; OR, 5.5).Conclusion: High FABP4 and ADH1B expression is associated with significantly higher risk of residual disease in high-grade serous ovarian cancer. Patients with high tumoral levels of these genes may be candidates for neoadjuvant chemotherapy. Clin Cancer Res; 20(12); 3280–8. ©2014 AACR.
A Pragmatic Definition of Therapeutic Synergy Suitable for Clinically Relevant In Vitro Multicompound Analyses
Authors: Kashif Muhammad , Andersson Claes , Åberg Magnus , Nygren Peter , Sjöblom Tobias , Hammerling Ulf , Larsson Rolf , Gustafsson Mats G. 
Published: April 2014

Abstract
For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. Mol Cancer Ther; 13(7); 1964–76. ©2014 AACR.
Association Between Down Syndrome and In-Hospital Death Among Children Undergoing Surgery for Congenital Heart Disease
Authors: Evans Jacqueline M. , Dharmar Madan , Meierhenry Erin , Marcin James P. , Raff Gary W. 
Published: April 2014

Background—
The prevalence of Down syndrome (DS)–affected births has increased during the past 30 years; moreover, children with DS have a higher incidence of congenital heart disease compared with their peers. Whether children with DS have better or worse outcomes after repair of congenital heart disease is unclear. We sought to identify differences in in-hospital mortality after cardiac surgery in pediatric patients with and without DS using a large national database.

Methods and Results—

Children aged <18 years who underwent surgical intervention for congenital heart disease were identified using the Kids’ Inpatient Database (2000, 2003, 2006, and 2009). Patients were stratified using the Risk Adjustment for Congenital Heart Surgery algorithm. A total of 4231 (8.2%) of the 51 309 patients studied had a diagnosis of DS. In-hospital death for patients with DS was significantly lower than that for patients without DS overall (1.9% versus 4.3%;
P
<0.05) as well as within risk categories 2 (1.0% versus 1.8%;
P
<0.05) and 3 (2.3% versus 5.1%;
P
<0.05). Multivariable logistic regression showed a lower odds of death among children with DS (odds ratio=0.60; 95% confidence interval, 0.47–0.76;
P
<0.05) after adjusting for Risk Adjustment for Congenital Heart Surgery risk category, premature birth, major noncardiac structural anomaly, and age.

Conclusions—
In this large national study, children with DS who underwent repair of congenital heart disease were more likely to survive to discharge than children without DS. Future work is needed to better understand the factors underlying these differences.
Accelerated Degeneration of a Bovine Pericardial Bioprosthetic Aortic Valve in Children and Young Adults
Authors: Saleeb Susan F. , Newburger Jane W. , Geva Tal , Baird Christopher W. , Gauvreau Kimberlee , Padera Robert F. , del Nido Pedro J. , Borisuk Michele J. , Sanders Stephen P. , Mayer John E. 
Published: April 2014

Background—
Experience with aortic valve replacement (AVR) with current-generation pericardial bioprostheses in young patients is limited. The death of a child with accelerated bioprosthetic aortic stenosis prompted enhanced surveillance of all such patients at our institution.

Methods and Results—

We reviewed records of 27 patients who had undergone AVR (median follow-up, 13.7 months) with a bovine pericardial bioprosthesis at ≤30 years of age. In the Mitroflow LXA valve group (n=15), freedom from valve failure was 100% at 1 year, 53% (95% confidence interval, 12–82) at 2 years, and 18% (95% confidence interval, 1–53) at 3 years. No Magna/Magna Ease valves (n=12) failed by 3 years. Among valve failure patients, median age at AVR was 12 years (range, 10–21 years). Life-threatening prosthetic aortic stenosis was detected at a median of 6 months after prior echocardiograms showing mild or less gradients. Patients with Mitroflow LXA compared with Magna/Magna Ease valves were smaller (median body surface area, 1.42 versus 1.93 m
2
;
P
=0.002) and younger (median age, 13.0 versus 20.9 years;
P
=0.02) at AVR. Pathology demonstrated diffuse intrinsic leaflet calcification, not associated with inflammation or infection, and virtually immobile leaflets in closed position.

Conclusions—
Young patients undergoing AVR with Mitroflow LXA pericardial valves are at high risk for rapid progression from mild or less to severe aortic stenosis over months, highlighting their need for heightened echocardiographic surveillance and suggesting that this aortic bioprosthesis should not be implanted in the young. Current data are insufficient to assess the safety of AVR with other pericardial bioprostheses in children and the youngest adults.
Outcomes of Out‐of‐Hospital Cardiac Arrest by Public Location in the Public‐Access Defibrillation Era
Authors: Murakami Yukiko , Iwami Taku , Kitamura Tetsuhisa , Nishiyama Chika , Nishiuchi Tatsuya , Hayashi Yasuyuki , Kawamura Takashi ,   the Utstein Osaka Project
Published: April 2014

Background

The strategy to place public‐access automated external defibrillators (
AED
s) has not yet been established in real settings.

Methods and Results

This, prospective, population‐based observational study in Osaka, Japan, included consecutive out‐of‐hospital cardiac arrest (
OHCA
) patients with resuscitation attempts during 7 years, from January 2005 through December 2011. The trends in the proportion of public‐access
AED
use and 1‐month survival with neurologically favorable outcome were evaluated by location. Factors associated with neurologically favorable outcome (defined as cerebral performance category 1 or 2) after ventricular fibrillation were also assessed using multiple logistic regression analysis. A total of 9453 bystander‐witnessed
OHCA
s of cardiac origin were documented and 894 (9.5%) of them occurred at public places. The proportion of public‐access
AED
use significantly increased from 0.0% (0/20) in 2005 to 41.2% (7/17) in 2011 at railway stations and from 0.0% (0/7) to 56.5% (13/23) at sports facilities. Mean time from collapse to shock was 5.0 minutes among those who received shocks with public‐access
AED
s. The proportion of neurologically favorable outcome was 28.0% (33/118) at railway stations, 51.6% (48/93) at sports facilities, 23.3% (20/86) in public buildings, and 41.9% (13/31) in schools. In multivariate analysis, early defibrillation, irrespective of bystander or emergency medical service (EMS) personnel, was significantly associated with neurologically favorable outcome (adjusted odds ratio for 1‐minute increment, 0.89; 95% confidence interval, 0.87 to 0.92).

Conclusions

This large, population‐based
OHCA
registry demonstrated that earlier shock, irrespective the shock provider (bystander or
EMS
personnel), contributed to improving outcome, and a public‐access defibrillation program was successfully implemented so that shocks with public‐access
AED
s were delivered to over 40% of bystander‐witnessed
OHCA
s and time to shock was shortened in some kinds of public places.
Association of Physical Activity in Childhood and Early Adulthood With Carotid Artery Elasticity 21 Years Later: The Cardiovascular Risk in Young Finns Study
Authors: Pälve Kristiina S. , Pahkala Katja , Magnussen Costan G. , Koivistoinen Teemu , Juonala Markus , Kähönen Mika , Lehtimäki Terho , Rönnemaa Tapani , Viikari Jorma S. A. , Raitakari Olli T. 
Published: April 2014

Background
Decreased arterial elasticity is a risk factor for several cardiovascular outcomes. Longitudinal data on the effect of physical activity in youth on adult arterial elasticity are limited. The aim of this study was to determine the long‐term effects of physical activity in children and young adults on carotid artery elasticity after 21 years of follow‐up.

Methods and Results

Participants were 1417 children (aged 9 to 15 years) and 999 young adults (aged 18 to 24 years) from the prospective Cardiovascular Risk in Young Finns Study. Participants had questionnaire measures of leisure‐time physical activity available from 1986 and ultrasound‐derived indices of carotid artery elasticity measured in 2007. Carotid artery elasticity indices were distensibility (%/10 mm Hg), Young's elastic modulus (kPa), and stiffness index (unitless). Physical activity at age 18 to 24 years was directly associated with distensibility (β=0.068,
P
=0.014) and inversely with Young's elastic modulus (β=−0.057,
P
=0.0037) and indirectly with stiffness index (β=−0.050,
P
=0.0028) 21 years later in males and females. The associations remained after adjustment for age, sex, body mass index, smoking, systolic blood pressure, serum lipids and insulin, and 21‐year change in physical activity. At age 9 to 15 years, the favorable association, remaining after adjustment, was found in males (distensibility [β=0.097,
P
=0.010], Young's elastic modulus [β=−0.060,
P
=0.028], and stiffness index [β=−0.062,
P
=0.007]) but not in females (
P
=0.70,
P
=0.85, and
P
=0.91, respectively).

Conclusions
Leisure‐time physical activity in boys and young adults is associated with carotid artery elasticity later in life, suggesting that higher levels of physical activity in youth may benefit future cardiovascular health.
Risk Factors and Outcome of Fontan‐Associated Plastic Bronchitis: A Case‐Control Study
Authors: Schumacher Kurt R. , Singh Tajinder P. , Kuebler Joseph , Aprile Kayla , O'Brien Molly , Blume Elizabeth D. 
Published: April 2014

Background

The onset of plastic bronchitis (
PB
) can be debilitating in survivors of Fontan surgery. The rarity of this complication makes designing studies to understand risk factors for
PB
challenging. This 2‐center case‐control study aimed to describe patient outcomes and to assess the association of antecedent patient factors with
PB
development.

Methods and Results

Using center registries,
PB
patients (n=25) were matched 1:2 to non‐
PB
Fontans (n=43) by date of Fontan surgery and center. The groups were compared for baseline characteristics. Association of patient characteristics with
PB
was assessed using logistic regression and of potential risk factors with onset of
PB
using time‐to‐event analyses. The median time from Fontan to
PB
diagnosis was 2.5 years. Overall, 12/25
PB
patients died or underwent heart transplant; the median transplant‐free survival was 8.3 years after diagnosis. Factors associated with developing
PB
included post‐surgical chylothorax (44%
PB
versus 10% control; odds ratio [
OR
] 7.3;
P
=0.003), chest tube (
CT
) duration at stage 2 (
P
=0.04) and Fontan (
P
=0.004), and postoperative ascites (36%
PB
versus 12% control;
OR
4.2;
P
=0.003).
CT
drainage >13 days at Fontan was associated with earlier
PB
onset (
P
=0.04). Early‐onset
PB
was associated with an increased risk of death (
OR
5.0;
P
=0.002).

Conclusions

PB
is a life‐threatening disorder. A longer duration of
CT
drainage after surgery, chylothorax, and development of ascites are all associated with developing
PB
. Understanding the pathophysiology of peri‐operative complications in individual patients and using targeted interventions may delay the onset of the
PB
phenotype.
Geomagnetic Storms Can Trigger Stroke
Authors: Feigin Valery L. , Parmar Priya G. , Barker-Collo Suzanne , Bennett Derrick A. , Anderson Craig S. , Thrift Amanda G. , Stegmayr Birgitta , Rothwell Peter M. , Giroud Maurice , Bejot Yannick , Carvil Phillip , Krishnamurthi Rita , Kasabov Nikola 
Published: April 2014

Background and Purpose—
Although the research linking cardiovascular disorders to geomagnetic activity is accumulating, robust evidence for the impact of geomagnetic activity on stroke occurrence is limited and controversial.

Methods—
We used a time-stratified case-crossover study design to analyze individual participant and daily geomagnetic activity (as measured by Ap Index) data from several large population-based stroke incidence studies (with information on 11 453 patients with stroke collected during 16 031 764 person-years of observation) in New Zealand, Australia, United Kingdom, France, and Sweden conducted between 1981 and 2004. Hazard ratios and corresponding 95% confidence intervals (CIs) were calculated.

Results—

Overall, geomagnetic storms (Ap Index 60+) were associated with 19% increase in the risk of stroke occurrence (95% CI, 11%–27%). The triggering effect of geomagnetic storms was most evident across the combined group of all strokes in those aged <65 years, increasing stroke risk by >50%: moderate geomagnetic storms (60–99 Ap Index) were associated with a 27% (95% CI, 8%–48%) increased risk of stroke occurrence, strong geomagnetic storms (100–149 Ap Index) with a 52% (95% CI, 19%–92%) increased risk, and severe/extreme geomagnetic storms (Ap Index 150+) with a 52% (95% CI, 19%–94%) increased risk (test for trend,
P
<2×10
−16
).

Conclusions—
Geomagnetic storms are associated with increased risk of stroke and should be considered along with other established risk factors. Our findings provide a framework to advance stroke prevention through future investigation of the contribution of geomagnetic factors to the risk of stroke occurrence and pathogenesis.
N-Terminal Pro–B-type Natriuretic Peptide and Stroke Risk
Authors: Cushman Mary , Judd Suzanne E. , Howard Virginia J. , Kissela Brett , Gutiérrez Orlando M. , Jenny Nancy S. , Ahmed Ali , Thacker Evan L. , Zakai Neil A. 
Published: April 2014

Background and Purpose—
Improved identification of those at risk of stroke might improve prevention. We evaluated the association of the cardiac function biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP) with stroke risk in the 30 239 black and white participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Methods—
During 5.4 years of follow-up after enrollment in 2003 to 2007, NT-proBNP was measured in baseline blood samples of 546 subjects with incident ischemic stroke and 956 without stroke.

Results—

NT-proBNP was higher with older age and in those with heart disease, kidney disease, atrial fibrillation, and lower low-density lipoprotein-cholesterol. Adjusting for age, race, sex, income, education, and traditional stroke risk factors, there was an increased risk of stroke across quartiles of NT-proBNP; participants with NT-proBNP in the top versus the bottom quartile had a hazard ratio of 2.9 (95% confidence interval, 1.9–4.5). There was no impact of added adjustment for kidney function and heart failure. Among pathogenetic stroke subtypes, the association was largest for cardioembolic stroke, with a hazard ratio of 9.1 (95% confidence interval, 2.9–29.2). Associations did not differ by age, sex, or race, or after excluding those with baseline heart failure or atrial fibrillation. Predicted stroke risk was more accurate in 27% of participants if NT-proBNP was considered after traditional stroke risk factors (
P
<0.001).

Conclusions—
NT-proBNP was a major independent risk marker for stroke. Considering this and other data for stroke, coronary disease, and atrial fibrillation, the clinical use of NT-proBNP measurement in primary prevention settings should be considered.
Serial Montreal Cognitive Assessments Demonstrate Reversible Cognitive Impairment in Patients With Acute Transient Ischemic Attack and Minor Stroke
Authors: Sivakumar Leka , Kate Mahesh , Jeerakathil Thomas , Camicioli Richard , Buck Brian , Butcher Ken 
Published: April 2014

Background and Purpose—
Cognitive changes after ischemic stroke are often overlooked, particularly acutely and in patients with mild or transient deficits. We assessed patients with transient ischemic attack (TIA)/minor stroke with serial cognitive screening tests. We tested the hypothesis that mild acute deficits are transient and improve after TIA/minor stroke.

Methods—
Patients with acute TIA/minor ischemic stroke, without a history of cognitive impairment, presenting with a National Institute of Health Stroke Scale score ≤3 were assessed <72 hours of onset. Patients were administered the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) at days 1, 7, 30, and 90. Cognitive impairment was defined as MoCA <26 and MMSE ≤26.

Results—

One hundred patients with a median (interquartile range) National Institute of Health Stroke Scale score of 1 (2) and median age of 68 (20) years were included. Baseline median MoCA score (26 [4]) was lower than the MMSE (29 [2];
P
<0.0001). Cognitive impairment was detected in 54 of 100 patients (54%) with MoCA and 16 of 100 (16%;
P
=0.001) with MMSE. MoCA scores improved at day 7 (27 [5]), day 30 (28 [2]), and day 90 (28 [2];
P
<0.0001). Resolution of cognitive deficits was because of resolution of recall deficits.

Conclusions—
Acute temporary cognitive impairment after TIA/minor stroke is common. The MoCA is sensitive to these changes, but the MMSE is not. Routine cognitive assessment after TIA/minor stroke may be warranted and relevant to return to activities even when other neurological deficits are not evident.
Three new species of Evolvulus (Convolvulaceae) from Bahia, Brazil
Authors: DA SILVA CINTIA VIEIRA , SIMÃO-BIANCHINI ROSANGELA 
Published: April 2014

The semi-arid region of Bahia is rich in species of Convolvulaceae, particularly in the genera Evolvulus, Ipomoea, and Jacquemontia. Field work in this region and taxonomic revision of Evolvulus section Phyllostachyi revealed the occurrence of three new species: Evolvulus altissimus, the tallest species of the genus, is a subshrub up to two metres tall; Evolvulus delicatus is a flexible branched species with small, stiff, and narrow pointed leaves; Evolvulus harleyi is a herb with glabrous or nearly glabrous leaves and a globose inflorescence. These three species are described and illustrated. Their similarities with allied taxa are discussed. A região do semi-árido da Bahia é rica em espécies de Convolvulaceae, particularmente os gêneros Evolvulus, Ipomoea e Jacquemontia. Diversos trabalhos de campo nesta região para a revisão taxonômica de Evolvulus seção Phyllostachyi revelaram a ocorrência de três novas espécies: Evolvulus altissimus, a mais alta dentre todas as espécies do gênero, é um subarbusto de até dois metros de altura; Evolvulus delicatus é uma espécie de ramos flexíveis com folhas pequenas, estreitas, duras e pontiagudas; Evolvulus harleyi é uma erva com folhas glabras ou quase glabras e inflorescência globosa. Estas três espécies são descritas e ilustradas. As relações com espécies próximas são discutidas.
The Effect of Greenhouse Gas–Induced Changes in SST on the Annual Cycle of Zonal Mean Tropical Precipitation
Authors: Dwyer John G. , Biasutti Michela , Sobel Adam H. 
Published: April 2014

Abstract
Models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) project changes to the seasonality of both tropical sea surface temperature (SST) and precipitation when forced by an increase in greenhouse gases. Nearly all models project an amplification and a phase delay of the annual cycle for both quantities, indicating a greater annual range and extrema reached later in the year. The authors investigate the nature of the seasonal precipitation changes in AGCM experiments forced by SST perturbations, which represent idealizations of the changes in annual mean, amplitude, and phase as simulated by CMIP5 models. A uniform SST warming is sufficient to force both amplification and a delay of the annual cycle of precipitation. The amplification is due to an increase in the annual mean vertical water vapor gradient, while the delay is affected by changes in the seasonality of the circulation. A budget analysis of this simulation reveals a large degree of similarity with the CMIP5 results. In the second experiment, only the seasonal characteristics of SST are changed. In response to an amplified annual cycle of SST, the annual cycle of precipitation is amplified, while for a delayed SST, the annual cycle of precipitation is delayed. Assuming that SST changes can entirely explain the seasonal precipitation changes, the AGCM simulations herein suggest that the annual mean warming explains most of the amplitude increase and much of the phase delay in the CMIP5 models. However, imperfect agreement between the changes in the SST-forced AGCM simulations and the CMIP5 coupled simulations suggests that coupled effects may play a significant role.