bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone Deacetylase Inhibitor Entinostat Inhibits Tumor-Initiating Cells in Triple-Negative Breast Cancer Cells
Authors: Schech Amanda , Kazi Armina , Yu Stephen , Shah Preeti , Sabnis Gauri 
Published: June 2015

Abstract
Mortality following breast cancer diagnosis is mainly due to the development of distant metastasis. To escape from the primary site, tumor cells undergo the epithelial-to-mesenchymal transition (EMT), which helps them acquire a more motile and invasive phenotype. In our previous study, we showed that class I selective HDAC inhibitor entinostat reverses the EMT phenotype through reversal of epigenetic repression of E-cadherin. Recent evidence suggests that a subset of cells within a breast tumor may drive the metastatic outgrowth following escape from the primary site. These cells, termed tumor-initiating cells (TIC), represent a great threat to overall prognosis. They are critical in terms of drug resistance and tumor initiation at metastatic sites. Acquisition of EMT traits has also been shown to impart TIC phenotype to the cells, making EMT a “dual-threat” for prognosis. In the current study, we show that entinostat treatment can reduce the percentage of TIC cells from triple-negative breast cancer (TNBC) cells. Entinostat treatment was able to reduce the CD44high/CD24low cell population, ALDH-1 activity, as well as protein and mRNA expression of known TIC markers such as Bmi-1, Nanog, and Oct-4. Next, we inoculated MDA-MB-231 cells transfected with firefly luciferase (231/Luc) in mammary fat pad of NSG mice. The mice were then treated with entinostat (2.5 mg/kg/d), and tumor development and formation of metastasis were assessed by bioluminescence imaging. Treatment with entinostat significantly reduced tumor formation at the primary site as well as lung metastasis. As such, entinostat may help prevent development of distant metastasis. Mol Cancer Ther; 14(8); 1848–57. ©2015 AACR.
Long-Term Outcomes With Cardiac Resynchronization Therapy in Patients With Mild Heart Failure With Moderate Renal Dysfunction
Authors: Daimee Usama A. , Moss Arthur J. , Biton Yitschak , Solomon Scott D. , Klein Helmut U. , McNitt Scott , Polonsky Bronislava , Zareba Wojciech , Goldenberg Ilan , Kutyifa Valentina 
Published: June 2015

Background—
We aimed to determine the impact of renal function on long-term outcomes with cardiac resynchronization therapy with defibrillator among patients with mild heart failure (HF).

Methods and Results—

We stratified 1820 Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy patients by QRS morphology into those with and without left bundle-branch block. Subgroups within each QRS morphology category were created based on glomerular filtration rate (GFR): GFR <60 and ≥60 mL/min per 1.73 m
2
. Primary end point was death; secondary end points were HF/death and HF events alone during long-term follow-up. Among 1274 left bundle-branch block patients, 413 (32%) presented with GFR <60 (mean, 48.1±8.3) mL/min per 1.73 m
2
. Relative to the 861 (68%) patients with GFR ≥60 (mean, 79.6±16.0) mL/min per 1.73 m
2
, low-GFR patients experienced higher risk of death (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.53–2.86;
P
<0.01) and HF/death (HR, 1.46; 95% CI, 1.17–1.82;
P
<0.01). In both GFR groups, cardiac resynchronization therapy with defibrillator was associated with reduction in death (GFR <60: HR, 0.66; 95% CI, 0.44–1.00;
P
=0.05 and GFR ≥60: HR, 0.68; 95% CI, 0.44–1.05;
P
=0.08) and HF/death (GFR <60: HR, 0.49; 95% CI, 0.36–0.67;
P
<0.01 and GFR ≥60: HR, 0.50; 95% CI, 0.38–0.66;
P
<0.01). In the low-GFR group, there was greater absolute reduction in risk of death (GFR <60: 14% and GFR ≥60: 6%) and HF/death (GFR <60: 25 and GFR ≥60: 15%). Among non–left bundle-branch block patients, low GFR predicted outcomes; however, no benefit from cardiac resynchronization therapy with defibrillator was observed.

Conclusions—
In patients with mild HF, moderate renal dysfunction is associated with higher risk of death and HF during long-term follow-up. Patients with left bundle-branch block, regardless of baseline renal function, derive long-term benefit from cardiac resynchronization therapy with defibrillator, with greater absolute risk reduction in death and HF among those with moderate renal dysfunction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.
Characterization of Right Ventricular Remodeling in Pulmonary Hypertension Associated With Patient Outcomes by 3-Dimensional Wall Motion Tracking Echocardiography
Authors: Ryo Keiko , Goda Akiko , Onishi Tetsuari , Delgado-Montero Antonia , Tayal Bhupendar , Champion Hunter C. , Simon Marc A. , Mathier Michael A. , Gladwin Mark T. , Gorcsan John 
Published: June 2015

Background—
Adverse right ventricular (RV) remodeling has significant prognostic and therapeutic implications to patients with pulmonary hypertension (PH). However, differentiating RV adaption from adverse remodeling associated with poor outcomes is difficult. We hypothesized that novel 3-dimensional (3D) wall motion tracking echocardiography can differentiate morphological features of RV adaption from adverse remodeling heralding an unfavorable short-term prognosis in patients with PH.

Methods and Results—

We studied 112 subjects: 92 patients with PH and 20 normal controls with 3D wall motion tracking for RV end-systolic volume index (ESVi), RV ejection fraction (EF), and RV global area strain. Patients with PH also had invasive hemodynamic measurements. Pressure–volume relations classified patients with PH into 3 groups, such as RV adapted, RV adapted–remodeled, and RV adverse–remodeled. The predefined combined end point was PH-related hospitalization, death, or lung surgery (lung transplantation or pulmonary endarterectomy) during 6 months. The 92 patients with PH had significantly larger RV volumes, lower RVEF and global area strain than normal controls as expected. Patients with PH classified as RV adapted (ESVi,
≤
72 mL/m
2
) had a more favorable clinical outcome than those classified as RV adapted–remodeled (ESVi, 73–113 mL/m
2
) or RV adverse–remodeled (ESVi,
≥
114 mL/m
2
): hazard ratio, 0.15; 95% confidence intervals, 0.07 to 0.39;
P
<0.0001. RV adverse–remodeled patients (ESVi,
≥
114 mL/m
2
) had worse short-term outcome than the RV adapted–remodeled patients: hazard ratio, 2.2; 95% confidence interval, 0.91 to 5.39;
P
=0.04.

Conclusions—
Quantitative 3D echocardiography in patients with PH demonstrated morphological subsets of RV adaption and remodeling associated with clinical outcomes.
Early Medication Nonadherence After Acute Myocardial Infarction
Authors: Mathews Robin , Peterson Eric D. , Honeycutt Emily , Chin Chee Tang , Effron Mark B. , Zettler Marjorie , Fonarow Gregg C. , Henry Timothy D. , Wang Tracy Y. 
Published: June 2015

Background—
Nonadherence to prescribed evidence-based medications after acute myocardial infarction (MI) can contribute to worse outcomes and higher costs. We sought to better understand the modifiable factors contributing to early nonadherence of evidence-based medications after acute MI.

Methods and Results—
We assessed 7425 acute MI patients treated with percutaneous coronary intervention at 216 US hospitals participating in TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) between April 2010 and May 2012. Using the validated Morisky instrument to assess cardiovascular medication adherence at 6 weeks post MI, we stratified patients into self-reported high (score, 8), moderate (score, 6–7), and low (score, <6) adherence groups. Moderate and low adherence was reported in 25% and 4% of patients, respectively. One third of low adherence patients described missing doses of antiplatelet therapy at least twice a week after percutaneous coronary intervention. Signs of depression and patient-reported financial hardship because of medication expenses were independently associated with a higher likelihood of medication nonadherence. Patients were more likely to be adherent at 6 weeks if they had follow-up appointments made before discharge and had a provider explain potential side effects of their medications. Lower medication adherence may be associated with a higher risk of 3-month death/readmission (adjusted hazard ratio, 1.35; 95% confidence interval, 0.98–1.87) although this did not reach statistical significance.

Conclusions—
Even early after MI, a substantial proportion of patients report suboptimal adherence to prescribed medications. Tailored patient education and pre discharge planning may represent actionable opportunities to optimize patient adherence and clinical outcomes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01088503.
Age and Sex Differences in Long‐Term Outcomes Following Implantable Cardioverter‐Defibrillator Placement in Contemporary Clinical Practice: Findings From the Cardiovascular Research Network
Authors: Masoudi Frederick A. , Go Alan S. , Magid David J. , Cassidy‐Bushrow Andrea E. , Gurwitz Jerry H. , Liu Taylor I. , Reynolds Kristi , Smith David H. , Reifler Liza M. , Glenn Karen A. , Fiocchi Frances , Goldberg Robert , Gupta Nigel , Peterson Pamela N. , Schuger Claudio , Vidaillet Humberto , Hammill Stephen C. , Greenlee Robert T. 
Published: June 2015

Background
Patient sex and age may influence rates of death after receiving an implantable cardioverter‐defibrillator for primary prevention. Differences in outcomes other than mortality and whether these differences vary by heart failure symptoms, etiology, and left ventricular ejection fraction are not well characterized.

Methods and Results

We studied 2954 patients with left ventricular ejection fraction ≤0.35 undergoing first‐time implantable cardioverter‐defibrillator for primary prevention within the Cardiovascular Research Network; 769 patients (26%) were women, and 2827 (62%) were aged >65 years. In a median follow‐up of 2.4 years, outcome rates per 1000 patient‐years were 109 for death, 438 for hospitalization, and 111 for heart failure hospitalizations. Procedure‐related complications occurred in 8.36%. In multivariable models, women had significantly lower risks of death (hazard ratio 0.67, 95%
CI
0.56 to 0.80) and heart failure hospitalization (hazard ratio 0.82, 95% CI 0.68 to 0.98) and higher risks for complications (hazard ratio 1.38, 95% CI 1.01 to 1.90) than men; patients aged >65 years had higher risks of death (hazard ratio 1.55, 95% CI 1.30 to 1.86) and heart failure hospitalization (hazard ratio 1.25, 95% CI 1.05 to 1.49) than younger patients. Age and sex differences were generally consistent in strata according to symptoms, etiology, and severity of left ventricular systolic dysfunction, except the higher risk of complications in women, which differed by New York Heart Association classification (
P
=0.03 for sex–New York Heart Association interaction), and the risk of heart failure hospitalization in older patients, which differed by etiology of heart failure (
P
=0.05 for age–etiology interaction).

Conclusions
The burden of adverse outcomes after receipt of an implantable cardioverter‐defibrillator for primary prevention is substantial and varies according to patient age and sex. These differences in outcome generally do not vary according to baseline heart failure characteristics.
Marked Regional Variation in Acute Stroke Treatment Among Medicare Beneficiaries
Authors: Skolarus Lesli E. , Meurer William J. , Shanmugasundaram Krithika , Adelman Eric E. , Scott Phillip A. , Burke James F. 
Published: June 2015

Background and Purpose—
Little is known about how regions vary in their use of thrombolysis (intravenous tissue-type plasminogen activator and intra-arterial treatment) for acute stroke. We sought to determine regional variation in thrombolysis treatment and investigate the extent to which regional variation is accounted for by patient demographics, regional factors, and elements of stroke systems of care.

Methods—
Retrospective cross-sectional study of all fee-for-service Medicare patients with ischemic stroke admitted via the Emergency Department from 2007 to 2010 who were assigned to 1 of 3436 hospital service areas. Multilevel logistic regression was used to estimate regional thrombolysis rates, determine the variation in thrombolysis treatment attributable to the region and estimate thrombolysis treatment rates and disability prevented under varied improvement scenarios.

Results—
There were 844 241 ischemic stroke admissions of which 3.7% received intravenous tissue-type plasminogen activator and 0.5% received intra-arterial stroke treatment without or without intravenous tissue-type plasminogen activator over the 4-year period. The unadjusted proportion of patients with ischemic stroke who received thrombolysis varied from 9.3% in the highest treatment quintile compared with 0% in the lowest treatment quintile. Measured demographic and stroke system factors were weakly associated with treatment rates. Region accounted for 7% to 8% of the variation in receipt of thrombolysis treatment. If all regions performed at the level of 75th percentile region, ≈7000 additional patients with ischemic stroke would be treated with thrombolysis.

Conclusions—
There is substantial regional variation in thrombolysis treatment. Future studies to determine features of high-performing thrombolysis treatment regions may identify opportunities to improve thrombolysis rates.
The Heated Condensation Framework. Part I: Description and Southern Great Plains Case Study
Authors: Tawfik Ahmed B. , Dirmeyer Paul A. , Santanello Joseph A. 
Published: June 2015

Abstract
This study extends the heated condensation framework (HCF) presented in Tawfik and Dirmeyer to include variables for describing the convective background state of the atmosphere used to quantify the contribution of the atmosphere to convective initiation within the context of land–atmosphere coupling. In particular, the ability for the full suite of HCF variables to 1) quantify the amount of latent and sensible heat energy necessary for convective initiation, 2) identify the transition from moistening advantage to boundary layer growth advantage, 3) identify locally originating convection, and 4) compare models and observations, directly highlighting biases in the convective state, is demonstrated. These capabilities are illustrated for a clear-sky and convectively active day over the Atmospheric Radiation Measurement Program Southern Great Plains central station using observations, the Rapid Update Cycle (RUC) operational model, and the North American Regional Reanalysis (NARR). The clear-sky day had a higher and unattainable convective threshold, making convective initiation unlikely. The convectively active day had a lower threshold that was attained by midafternoon, reflecting local convective triggering. Compared to observations, RUC tended to have the most difficulty representing the convective state and captured the threshold for the clear-sky case only because of compensating biases in the moisture and temperature profiles. Despite capturing the observed moisture profile very well, a stronger surface inversion in NARR returned overestimates in the convective threshold. The companion paper applies the HCF variables introduced here across the continental United States to examine the climatological behavior of convective initiation and local land–atmosphere coupling.
Raised circulating Neurokinin A predicts prognosis in metastatic small bowel neuroendocrine tumours. Lowering Neurokinin A indicates improved prognosis
Authors: Ardill Joy ES , McCance David R , Stronge Wendy V , Johnston Brian T 
Published: June 2015

Background Assessing prognosis is important in patients with neuroendocrine tumours of the small bowel as disease progression and survival is variable. We previously identified raised Neurokinin A as an independent indicator of poor prognosis and have shown that prognosis worsens when circulating Neurokinin A rises ≥50 ng/L. In the present study we have examined survival in relation to Neurokinin A concentrations. Methods Patients in whom Neurokinin A rose ≥50 ng/L between January 1989 and December 2010 were identified. All circulating Neurokinin A concentrations were recorded and survival was followed up to 31 December 2014 or to death. Results Median survival, from the date when Neurokinin A was first ≥50 ng/L was 11.1 (2.0–117.8) months if Neurokinin A remained ≥50 ng/L and 72.4 (4.8–152.6) months when Neurokinin A was reduced below 50 ng/L and controlled below that concentration for ≥3 months (P < 0.001). Survival was significantly better for patients attending the neuroendocrine tumour specialist clinic than for those not attending (P = 0.009). Comparing patients identified during 1989–2000, and those during 2001–2010, Neurokinin A was successfully reduced in the earlier period in 30.3% patients with median survival 23.2 (2.0–152.6) months and this improved in 58.1% with median survival of 43.3 (2.0–141.1) months in the later period (P = 0.019). Significance was greater between the earlier and later periods when only patients attending the neuroendocrine tumour clinic were compared (P = 0.016). Conclusions Circulating Neurokinin A ≥ 50 ng/L is a strong indicator of poor prognosis when Neurokinin A remains above this concentration. Lowering Neurokinin A below 50 ng/L indicates a significant improvement in prognosis (P < 0.001). This prognostic indicator reflects improved treatment and survival in more recent years.
Assessing formal accountability for public policies: the case of health policy in Spain
Authors: Pérez Durán Ixchel 
Published: June 2015

The aim of this study is to present a framework for analyzing and assessing accountability for public policies. First, I suggest two dimensions for analyzing accountability for policies (the informative/justifying dimension, and the evaluative/sanctioning dimension), applied to the implementation phase of the policy and, in particular, to three central elements that make up this phase (the actors responsible, the resources, and the policy results). Second, I suggest assessing accountability for a public policy starting from the degree of formalization and, specifically, from compliance with four characteristics of its regulatory framework: specific, binding, public and autonomous character. Third, I develop an empirical application of this proposal to the analysis of health policy in Spain, whose decentralized design, where regional governments are responsible for its implementation, allows us to analyze the differences in the levels of accountability for this policy across regions. Points for practitioners This study identifies and limits the components that can be incorporated into the analysis of accountability for public policies by providing an analytical framework that can be used to measure and compare levels of accountability for different kinds of policies (e.g. health, education, pensions) in different contexts (e.g. countries, regions, local governments). In order to test the validity of the proposal developed here, this article presents an empirical application to the analysis of health policy in Spain, whose decentralized design allows us to analyze the differences in accountability across regional governments.
Allergic Reactions in Hospitalized Patients With a Self-Reported Penicillin Allergy Who Receive a Cephalosporin or Meropenem
Authors: Crotty Danielle Joset , Chen Xian Jie Cindy , Scipione Marco R. , Dubrovskaya Yanina , Louie Eddie , Ladapo Joseph A. , Papadopoulos John 
Published: June 2015

Background: Cefepime and meropenem are used frequently in hospitalized patients for broad-spectrum empiric coverage, however, practitioners are often reluctant to prescribe these antibiotics for patients with a self-reported nonsevere, nontype I allergic reaction to penicillin. Methods: Retrospective review of electronic medical records of adults with a self-reported allergy to penicillin who received at least 1 dose of cefepime, ceftriaxone, cefoxitin, cephalexin, or meropenem to assess incidence and type of allergic reactions. Results: Of 175 patients included, 10 (6%) patients experienced an allergic reaction. The incidence for individual study drugs were cefepime 6% (6 of 96), meropenem 5% (3 of 56), cefoxitin 8% (1 of 13), ceftriaxone 0% (0 of 69), and cephalexin 0% (0 of 8). The majority of patients experienced a rash with or without pruritus and fever. Patients with a concomitant “sulfa” allergy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21, P = .02) or ≥3 other drug allergies (OR 6.4, 95% CI 1.3-32, P = .025) were more likely to have an allergic reaction. Conclusions: In one of the largest retrospective reviews of hospitalized patients who received full dose therapy with cefepime, ceftriaxone, and meropenem, the incidence of allergic reactions was low and reactions were mild. Cefepime, ceftriaxone, and meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy.
Association of the interleukin-6 polymorphisms with systemic lupus erythematosus: a meta-analysis
Authors: Cui Y X , Fu C W , Jiang F , Ye L X , Meng W 
Published: June 2015

Background Interleukin (IL)-6, an important proinflammatory cytokine, plays a potential pathological role in systemic lupus erythematosus (SLE). Studies on the relationship of IL-6 gene polymorphisms with SLE are inconclusive. The aim of this study was to estimate the relationship more precisely. Methods The databases of PubMed and Web of Science updated to 30 August 2014 were retrieved. Meta-analysis was conducted using allelic contrast, dominant, recessive and homozygote contrast models. Fifteen studies were included in this study and ethnicity-specific meta-analysis was performed on European, Iranian and Asian populations. Results Analysis for the IL-6-174 G/C polymorphism under all models except the homozygote contrast model indicated an association in the overall population (allelic contrast model: odds ratio (OR) 1.428, 95% confidence interval (CI) 1.124–1.812, dominant model: OR 1.382, 95% CI 1.037–1.842, recessive model: OR 1.610, 95% CI 1.158–2.240, homozygote contrast model: OR 1.759, 95% CI 0.989–3.127), as well as in European individuals under all four genetic models (allelic contrast model: OR 1.557, 95% CI 1.155–2.098, dominant model: OR 1.699, 95% CI 1.203–2.400, recessive model: OR 1.506, 95% CI 1.176–1.930, homozygote contrast model: OR 2.118, 95% CI 1.103–4.065). Analysis for the IL-6-572 G/C polymorphism indicated significant association in overall ethnicities under the recessive model (OR 1.491, 95% CI 1.104–2.014), but not under other models or in Asian individuals. In addition, significant association between the IL-6-174 G/C polymorphism and discoid skin lesions and antinuclear antibodies (ANAs) were found under the allelic contrast model and recessive model, respectively (discoid skin lesions: OR 2.271, 95% CI 1.053–4.895; ANAs: OR 2.244, 95% CI 1.141–4.416). Conclusion This meta-analysis provides evidence of the association between the IL-6 polymorphism and the risk of SLE, hinting that the IL-6-174 G/C and IL-6-572 G/C polymorphisms may play a role in SLE susceptibility.