bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk
Authors: Pattison Jillian M. , Posternak Valeriya , Cole Michael D. 
Published: August 2016

Abstract
It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single-nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell-cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear because it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high-linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development.
Implications: A polymorphic KLF5 binding site near the CCNE1 gene explains genetic risk identified through GWAS. Mol Cancer Res; 14(11); 1078–86. ©2016 AACR.
Survival After Rate-Responsive Programming in Patients With Cardiac Resynchronization Therapy-Defibrillator Implants Is Associated With a Novel Parameter
Authors: Olshansky Brian , Richards Mark , Sharma Arjun , Wold Nicholas , Jones Paul , Perschbacher David , Wilkoff Bruce L. 
Published: August 2016

Background—
Rate-responsive pacing (DDDR) versus nonrate-responsive pacing (DDD) has shown no survival benefit for patients undergoing cardiac resynchronization therapy defibrillator (CRT-D) implants. The heart rate score (HRSc), an indicator of heart rate variation, may predict survival. We hypothesized that high-risk HRSc CRT-D patients will have improved survival with DDDR versus DDD alone.

Methods and Results—

All CRT-D patients in LATITUDE remote monitoring (2006–2011), programmed DDD, had HRSc calculated at first data upload after implant (median 1.4 months). Patients subsequently reprogrammed to DDDR 7.6 median months later were compared with a propensity-matched DDD group and followed for 21.4 median months by remote monitoring. Data were adjusted for age, sex, lower rate limit, percent atrial pacing, percent biventricular pacing, and implant year. The social security death index was used to identify deaths. Remote monitoring provided programming and histogram data. DDDR programming in CRT-D patients was associated with improved survival (adjusted hazard ratio =0.77;
P
<0.001). However, only those with baseline HRSc ≥70% (2308/6164) had improved HRSc with DDDR (from 88±9% to 78±15%;
P
<0.001) and improved survival (hazard ratio =0.74;
P
<0.001). Patients with a high baseline HRSc and significant improvement over time were more likely to survive (hazard ratio =0.63;
P
=0.006). For patients with HRSc <70%, DDDR reprogramming increased the HRSc from 46±11% to 50±15% (
P
<0.001); survival did not change. The HRSc did not change with DDD pacing over time.

Conclusions—
In CRT-D patients with HRSc ≥70%, DDDR reprogramming improved the HRSc and was associated with survival. Patients with lower HRSc had no change in survival with DDDR programming.
Directional Influences of Ventricular Activation on Myocardial Scar Characterization
Authors: Tung Roderick , Josephson Mark E. , Bradfield Jason S. , Shivkumar Kalyanam 
Published: August 2016

Background—
The effects of varying the wavefront of activation on ventricular scar characterization has not been systematically assessed.

Methods and Results—

Patients referred for ablation of scar-related ventricular tachycardia underwent voltage maps during a minimum of 2 wavefronts of activation. The bipolar and unipolar low-voltage areas were compared, and direct electrogram analysis was performed in regions where discrepancies were seen. Concordance between wavefronts was measured by calculating percentage of overlap between maps. Sixty endocardial voltage maps (360±147 points) were performed in 29 patients during 2 distinct wavefronts, with 3 wavefronts in 7 patients. With median bipolar and unipolar low-voltage areas of 37 and 116 cm
2
, respectively, 22% and 14% variability in median scar area was observed with a different activation wavefront. Concordance between wavefronts was lower in patients with mixed scar compared to those with dense scar (52% [interquartile range, 29%–70%] versus 84% [interquartile range, 71%–87%]), with septal scars exhibiting the lowest concordance [(27% (interquartile range, 21%–56%)]. Among 16 critical sites for ventricular tachycardia, 3 (18%) were in a discordant region of scar, with one of the wavefronts showing voltage >1.5 mV.

Conclusions—
Significant differences in bipolar and unipolar low-voltage characterization of scar were observed with different ventricular activation wavefronts, particularly in septal locations and in patients without dense scar. In patients with a paucity of dense, low-voltage regions identified during substrate mapping, an alternate activation wavefront may increase the sensitivity to detect arrhythmogenic substrate and critical sites for ventricular tachycardia.
Validation and Comparison of Seven Mortality Prediction Models for Hospitalized Patients With Acute Decompensated Heart Failure
Authors: Lagu Tara , Pekow Penelope S. , Shieh Meng-Shiou , Stefan Mihaela , Pack Quinn R. , Kashef Mohammad Amin , Atreya Auras R. , Valania Gregory , Slawsky Mara T. , Lindenauer Peter K. 
Published: August 2016

Background—
Heart failure (HF) inpatient mortality prediction models can help clinicians make treatment decisions and researchers conduct observational studies; however, published models have not been validated in external populations.

Methods and Results—
We compared the performance of 7 models that predict inpatient mortality in patients hospitalized with acute decompensated heart failure: 4 HF-specific mortality prediction models developed from 3 clinical databases (ADHERE [Acute Decompensated Heart Failure National Registry], EFFECT study [Enhanced Feedback for Effective Cardiac Treatment], and GWTG-HF registry [Get With the Guidelines-Heart Failure]); 2 administrative HF mortality prediction models (Premier, Premier+); and a model that uses clinical data but is not specific for HF (Laboratory-Based Acute Physiology Score [LAPS2]). Using a multihospital, electronic health record–derived data set (HealthFacts [Cerner Corp], 2010–2012), we identified patients ≥18 years admitted with HF. Of 13 163 eligible patients, median age was 74 years; half were women; and 27% were black. In-hospital mortality was 4.3%. Model-predicted mortality ranges varied: Premier+ (0.8%–23.1%), LAPS2 (0.7%–19.0%), ADHERE (1.2%–17.4%), EFFECT (1.0%–12.8%), GWTG-Eapen (1.2%–13.8%), and GWTG-Peterson (1.1%–12.8%). The LAPS2 and Premier models outperformed the clinical models (C statistics: LAPS2 0.80 [95% confidence interval 0.78–0.82], Premier models 0.81 [95% confidence interval 0.79–0.83] and 0.76 [95% confidence interval 0.74–0.78], and clinical models 0.68 to 0.70).

Conclusions—
Four clinically derived, inpatient, HF mortality models exhibited similar performance, with C statistics near 0.70. Three other models, 1 developed in electronic health record data and 2 developed in administrative data, also were predictive, with C statistics from 0.76 to 0.80. Because every model performed acceptably, the decision to use a given model should depend on practical concerns and intended use.
Implications of Using Different Definitions on Outcomes in Worsening Heart Failure
Authors: Kelly Jacob P. , Cooper Lauren B. , Gallup Dianne , Anstrom Kevin J. , Chen Horng H. , Redfield Margaret M. , O’Connor Christopher M. , Mentz Robert J. , Hernanadez Adrian F. , Felker G. Michael 
Published: August 2016

Background—
In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions.

Methods and Results—

We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days. We also assessed for a differential relationship between the timing of WHF development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE, 6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated with an increase in the composite end point (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11–2.42;
P
=0.01). However, the association between WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95% CI, 1.45–4.91;
P
<0.01 and HR, 1.28; 95% CI, 0.79–2.08;
P
=0.31, respectively). Development of WHF between baseline to 24 hours compared with 24 to 48 hours or 48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI, 0.21–1.17;
P
=0.11 and HR, 0.45; 95% CI, 0.20–1.04;
P
=0.06, respectively).

Conclusions—
A WHF definition that excluded the intensification of diuretics resulted in a lower event rate but a stronger association with outcomes. These data support the need for continued efforts to standardize WHF definitions in clinical trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00577135 (DOSE) and NCT01132846 (ROSE).
Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells
Authors: Graw Jan A. , Mayeur Claire , Rosales Ivy , Liu Yumin , Sabbisetti Venkata S. , Riley Frank E. , Rechester Osher , Malhotra Rajeev , Warren H. Shaw , Colvin Robert B. , Bonventre Joseph V. , Bloch Donald B. , Zapol Warren M. 
Published: August 2016

Background:
Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35–40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.

Methods:
To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin.

Results:
Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.

Conclusions:
In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension.
Will Global Warming Make Hurricane Forecasting More Difficult?
Authors: Emanuel Kerry 
Published: August 2016

Abstract
Hurricane track forecasts have improved steadily over the past few decades, yet forecasting hurricane intensity remains challenging. Of special concern are the rare instances of tropical cyclones that intensify rapidly just before landfall, catching forecasters and populations off guard, thereby risking large casualties. Here, we review two historical examples of such events and use scaling arguments and models to show that rapid intensification just before landfall is likely to become increasingly frequent and severe as the globe warms.
The Robustness of Midlatitude Weather Pattern Changes due to Arctic Sea Ice Loss
Authors: Chen Hans W. , Zhang Fuqing , Alley Richard B. 
Published: August 2016

Abstract
The significance and robustness of the link between Arctic sea ice loss and changes in midlatitude weather patterns is investigated through a series of model simulations from the Community Atmosphere Model, version 5.3, with systematically perturbed sea ice cover in the Arctic. Using a large ensemble of 10 sea ice scenarios and 550 simulations, it is found that prescribed Arctic sea ice anomalies produce statistically significant changes for certain metrics of the midlatitude circulation but not for others. Furthermore, the significant midlatitude circulation changes do not scale linearly with the sea ice anomalies and are not present in all scenarios, indicating that the remote atmospheric response to reduced Arctic sea ice can be statistically significant under certain conditions but is generally nonrobust. Shifts in the Northern Hemisphere polar jet stream and changes in the meridional extent of upper-level large-scale waves due to the sea ice perturbations are generally small and not clearly distinguished from intrinsic variability. Reduced Arctic sea ice may favor a circulation pattern that resembles the negative phase of the Arctic Oscillation and may increase the risk of cold outbreaks in eastern Asia by almost 50%, but this response is found in only half of the scenarios with negative sea ice anomalies. In eastern North America the frequency of extreme cold events decreases almost linearly with decreasing sea ice cover. This study’s finding of frequent significant anomalies without a robust linear response suggests interactions between variability and persistence in the coupled system, which may contribute to the lack of convergence among studies of Arctic influences on midlatitude circulation.
Wind and Wave Climate in the Arctic Ocean as Observed by Altimeters
Authors: Liu Qingxiang , Babanin Alexander V. , Zieger Stefan , Young Ian R. , Guan Changlong 
Published: August 2016

Abstract
Twenty years (1996–2015) of satellite observations were used to study the climatology and trends of oceanic winds and waves in the Arctic Ocean in the summer season (August–September). The Atlantic-side seas, exposed to the open ocean, host more energetic waves than those on the Pacific side. Trend analysis shows a clear spatial (regional) and temporal (interannual) variability in wave height and wind speed. Waves in the Chukchi Sea, Beaufort Sea (near the northern Alaska), and Laptev Sea have been increasing at a rate of 0.1–0.3 m decade−1, found to be statistically significant at the 90% level. The trend of waves in the Greenland and Barents Seas, on the contrary, is weak and not statistically significant. In the Barents and Kara Seas, winds and waves initially increased between 1996 and 2006 and later decreased. Large-scale atmospheric circulations such as the Arctic Oscillation and Arctic dipole anomaly have a clear impact on the variation of winds and waves in the Atlantic sector. Comparison between altimeter observations and ERA-Interim shows that the reanalysis winds are on average 1.6 m s−1 lower in the Arctic Ocean, which translates to a low bias of significant wave height (−0.27 m) in the reanalysis wave data.
Do early internalizing and externalizing problems predict later irritability in adolescents with attention-deficit/hyperactivity disorder?
Authors: Mulraney Melissa , Zendarski Nardia , Mensah Fiona , Hiscock Harriet , Sciberras Emma 
Published: August 2016

Objective: Irritable mood is common in children with attention-deficit/hyperactivity disorder. Research to date has primarily comprised cross-sectional studies; thus, little is known about the antecedents of irritability. Furthermore, existing cross-sectional studies generally focus on the association between irritability and comorbidities and do not examine broader aspects of functioning. Finally, previous research has neglected to include child-report of irritability. This study aimed to address these gaps using data from a longitudinal study of children with attention-deficit/hyperactivity disorder. Method: Children aged 5–13 years (mean = 10.2; standard deviation = 1.9) with attention-deficit/hyperactivity disorder were recruited from pediatric practices across Victoria, Australia. This study reports on those who had reached adolescence (12 years or older, mean = 13.8; standard deviation = 1.2) at the 3-year follow-up ( n = 140). Internalizing and externalizing problems were measured using the Strengths and Difficulties Questionnaire. At follow-up, parent-reported and adolescent self-reported irritability was assessed using the Affective Reactivity Index. Parent and adolescent outcomes measured at follow-up included attention-deficit/hyperactivity disorder symptom severity, sleep, behavior and parent mental health. Results: Children with externalizing problems at age 10 had higher parent-reported irritability (β = 0.31, 95% confidence interval = [0.17,–0.45], p = 0.001) in adolescence. Cross-sectional analyses found that irritability was associated with increased attention-deficit/hyperactivity disorder symptom severity and sleep problems; poorer emotional, behavioral and social functioning; and poorer parent mental health. Conclusion: Our findings highlight the importance of assessing for and managing early conduct problems in children with attention-deficit/hyperactivity disorder, as these predict ongoing irritability which, in turn, is associated with poorer functioning across a number of domains.
Nurse’s perceptions of organisational barriers to delivering compassionate care: A qualitative study
Authors: Valizadeh Leila , Zamanzadeh Vahid , Dewar Belinda , Rahmani Azad , Ghafourifard Mansour 
Published: August 2016

Background: Compassionate care is an international priority of healthcare professionals. There is little understanding about how workplace issues impact provision of compassionate care in nursing practice. Therefore, it is important to address the workplace issues and organizational factors which may hinder compassionate care delivery within nursing practice. Objective: The aim of this study was to explore workplace and organizational barriers to compassionate care from the nurses’ perspective. Research design: The study used a qualitative exploratory design, and data were analyzed by conventional content analysis. Participants and research context: A total of 15 nurses working in different fields of nursing were recruited from four hospitals at northwest of Iran. Participants were selected by purposive sampling. Semistructured interviews were conducted for data collection. Ethical consideration: Ethical approval of this study was gained from the Ethical Review Board of Tabriz University of Medical Sciences. Findings: The main theme which emerged from data analysis was “unsupportive organizational culture.” This theme had two main categories including “excessive workload alongside inadequate staffing” and “the lack of value on compassionate care.” Discussion: Organizational barriers to development of compassionate in clinical practice were identified in this study. A closer examination of these barriers is required to move compassionate practice from an individual responsibility to a collective responsibility that is owned and shared by organizations. Conclusion: For compassionate care to flourish, policy makers, managers, and healthcare providers must foster an organizational atmosphere conducive to compassionate care.
Clinical results of renal artery embolization to control postoperative hemorrhage after partial nephrectomy
Authors: Jeon Chang Ho , Seong Nak Jong , Yoon Chang Jin , Byun Seok-Soo , Lee Sang Eun 
Published: August 2016

Background With the wider application of nephron-sparing surgery, there has been an increase in the occurrence of postoperative hemorrhage. However, despite such an increase, there are only a limited number of reports regarding renal artery embolization (RAE) for the management of postoperative bleeding after nephron-sparing surgery, especially after robot-assisted laparoscopic partial nephrectomy (RALPN). Purpose To evaluate the safety and clinical efficacy of transcatheter RAE for postoperative hemorrhage after open partial nephrectomy (OPN) and RALPN. Material and Methods A total of 29 patients (17 men, 12 women; age range, 31–70 years) who were referred to our hospital for postoperative hemorrhage after partial nephrectomy, between December 2003 and December 2014, were selected. We retrospectively reviewed patients’ clinical data, angiographic findings, embolization details, and clinical outcomes. Results Embolization was performed in patients who underwent OPN (25/29) and RALPN (4/29). The angiographic findings were as follows: renal artery pseudoaneurysm (n = 18), contrast extravasation (n = 8), and arteriovenous fistula (n = 3). Fiber-coated microcoil and n-butyl-2-cyanoacrylate (NBCA) was administered to the targeted bleeding renal arteries in 12 and 11 patients, respectively. In six patients, fiber-coated microcoil and NBCA were used concurrently. Technical and clinical successes were achieved in all patients (100%). Bleeding cessation was achieved in all patients, and no further relevant surgeries or interventions were required for hemorrhage control. There were no episodes of hemorrhagic recurrence during the follow-up period (median, 20 days; range, 7–108 days). Conclusion Angiography and RAE identified the origin of bleeding and could successfully preserve the residual renal function.