bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of dietary habits and metabolic risk factors on cardiovascular and diabetes mortality in countries of the Middle East and North Africa in 2010: a comparative risk assessment analysis
Authors: Afshin Ashkan , Micha Renata , Khatibzadeh Shahab , Fahimi Saman , Shi Peilin , Powles John , Singh Gitanjali , Yakoob Mohammad Yawar , Abdollahi Morteza , Al-Hooti Suad , Farzadfar Farshad , Houshiar-rad Anahita , Hwalla Nahla , Koksal Eda , Musaiger Abdulrahman , Pekcan Gulden , Sibai Abla Mehio , Zaghloul Sahar , Danaei Goodarz , Ezzati Majid , Mozaffarian Dariush 
Published: May 2015

Objective/designWe conducted a comparative risk assessment analysis to estimate the cardiometabolic disease (CMD) mortality attributable to 11 dietary and 4 metabolic risk factors in 20 countries of the Middle East by age, sex and time. The national exposure distributions were obtained from a systematic search of multiple databases. Missing exposure data were estimated using a multilevel Bayesian hierarchical model. The aetiological effect of each risk factor on disease-specific mortality was obtained from clinical trials and observational studies. The number of disease-specific deaths was obtained from the 2010 Global Burden of Disease mortality database. Mortality due to each risk factor was determined using the population attributable fraction and total number of disease-specific deaths.Setting/populationAdult population in the Middle East by age, sex, country and time.ResultsSuboptimal diet was the leading risk factor for CMD mortality in 11 countries accounting for 48% (in Morocco) to 72% (in the United Arab Emirates) of CMD deaths. Non-optimal systolic blood pressure was the leading risk factor for CMD deaths in eight countries causing 45% (in Bahrain) to 68% (in Libya) of CMD deaths. Non-optimal body mass index and fasting plasma glucose were the third and fourth leading risk factors for CMD mortality in most countries. Among individual dietary factors, low intake of fruits accounted for 8% (in Jordan) to 21% (in Palestine) of CMD deaths and low intake of whole grains was responsible for 7% (in Palestine) to 22% (in the United Arab Emirates) of CMD deaths. Between 1990 and 2010, the CMD mortality attributable to most risk factors had decreased except for body mass index and trans-fatty acids.ConclusionsOur findings highlight key similarities and differences in the impact of the dietary and metabolic risk factors on CMD mortality in the countries of the Middle East and inform priorities for policy measures to prevent CMD.
Plasma C-Reactive Protein and Risk of Breast Cancer in Two Prospective Studies and a Meta-analysis
Authors: Wang Jun , Lee I-Min , Tworoger Shelley S. , Buring Julie E. , Ridker Paul M. , Rosner Bernard , Hankinson Susan E. 
Published: May 2015

Abstract
Background: C-reactive protein (CRP) has been evaluated as a risk factor for breast cancer in epidemiologic studies. However, results from prospective studies are inconsistent.
Methods: We evaluated the association using prediagnostic blood samples in a case–control study nested within the Nurses' Health Study (NHS) and the full cohort of the Women's Health Study (WHS). A total of 943 cases in the NHS and 1,919 cases in the WHS contributed to the analysis. Conditional logistic regression and Cox proportional hazards model were used in the NHS and WHS, respectively. We pooled our results with prior prospective studies using random effect meta-analysis.
Results: In the NHS, higher CRP levels were associated with a suggestively increased risk of breast cancer [quintile 5 vs. 1: relative risk (RR), 1.27; 95% confidence interval (CI), 0.93–1.73; Ptrend = 0.02]; results did not vary significantly by tumor invasiveness or hormone receptor status. However, no association was observed in the WHS for overall risk (quintile 5 vs. 1: RR, 0.89; 95% CI, 0.76–1.06; Ptrend = 0.38) or by tumor invasiveness or hormone receptor status. The meta-analysis (including 5,371 cases from 11 studies) showed a modestly increased risk among women in the highest versus lowest categories of CRP (RR, 1.26; 95% CI, 1.07–1.49).
Conclusions: Existing data from prospective studies suggest that CRP, a nonspecific marker of inflammation, is modestly positively associated with breast cancer risk.
Impact: Our findings provide support to the concept that inflammation can influence breast cancer development. Cancer Epidemiol Biomarkers Prev; 24(8); 1199–206. ©2015 AACR.
PIK3CA Somatic Mutation Status in Relation to Patient and Tumor Factors in Racial/Ethnic Minorities with Colorectal Cancer
Authors: Phipps Amanda I. , Ahnen Dennis J. , Cheng Iona , Newcomb Polly A. , Win Aung Ko , Burnett Terrilea 
Published: May 2015

Abstract
Background: Approximately 10% to 20% of colorectal cancers exhibit somatic mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PIK3CA). We evaluated the relationship of PIK3CA mutation status in colorectal cancer with race/ethnicity, colorectal cancer survival, and other patient and tumor factors.
Methods: This study comprised 377 racial/ethnic minorities with incident invasive colorectal cancer, enrolled in the Colon Cancer Family Registry via population-based cancer registries. Tumor specimens were tested for PIK3CA mutations in exon 9 and 20 hotspots, BRAF p.V600E mutations, and DNA mismatch repair (MMR). In logistic regression models, we evaluated the association between PIK3CA mutation status and race/ethnicity, overall, and by mutation site. Using Cox regression, we evaluated the association between PIK3CA mutation status and survival after colorectal cancer diagnosis.
Results: PIK3CA mutations were detected in 42 cases (11%), with a similar prevalence across racial/ethnic groups. Individuals with PIK3CA-mutated colorectal cancer were significantly more likely than those with PIK3CA-wildtype disease to have proximal colon cancer, MMR-deficient tumors, and a germline MMR mutation (P ≤ 0.01). There was no evidence for an association between PIK3CA and overall survival (HR, 0.77; 95% confidence interval, 0.43–1.39).
Conclusions: The prevalence of PIK3CA mutation status in colorectal cancer does not differ according to race/ethnicity, but may vary according to other relevant clinicopathologic and etiologic factors, including germline MMR mutation status, tumor MMR status, and tumor site.
Impact: These findings underscore the importance of PIK3CA mutation status in colorectal cancer epidemiology and provide evidence that the prevalence of such mutations is similar across several racial/ethnic groups. Cancer Epidemiol Biomarkers Prev; 24(7); 1046–51. ©2015 AACR.
Model Matters: Differences in Orthotopic Rat Hepatocellular Carcinoma Physiology Determine Therapy Response to Sorafenib
Authors: Groß Claudia , Steiger Katja , Sayyed Sufyan , Heid Irina , Feuchtinger Annette , Walch Axel , Heß Julia , Unger Kristian , Zitzelsberger Horst , Settles Marcus , Schlitter Anna Melissa , Dworniczak Juliane , Altomonte Jennifer , Ebert Oliver , Schwaiger Markus , Rummeny Ernst , Steingötter Andreas , Esposito Irene , Braren Rickmer 
Published: May 2015

Abstract
Purpose: Preclinical model systems should faithfully reflect the complexity of the human pathology. In hepatocellular carcinoma (HCC), the tumor vasculature is of particular interest in diagnosis and therapy. By comparing two commonly applied preclinical model systems, diethylnitrosamine induced (DEN) and orthotopically implanted (McA) rat HCC, we aimed to measure tumor biology noninvasively and identify differences between the models.
Experimental Design: DEN and McA tumor development was monitored by MRI and PET. A slice-based correlation of imaging and histopathology was performed. Array CGH analyses were applied to determine genetic heterogeneity. Therapy response to sorafenib was tested in DEN and McA tumors.
Results: Histologically and biochemically confirmed liver damage resulted in increased 18F-fluorodeoxyglucose (FDG) PET uptake and perfusion in DEN animals only. DEN tumors exhibited G1–3 grading compared with uniform G3 grading of McA tumors. Array comparative genomic hybridization revealed a highly variable chromosomal aberration pattern in DEN tumors. Heterogeneity of DEN tumors was reflected in more variable imaging parameter values. DEN tumors exhibited lower mean growth rates and FDG uptake and higher diffusion and perfusion values compared with McA tumors. To test the significance of these differences, the multikinase inhibitor sorafenib was administered, resulting in reduced volume growth kinetics and perfusion in the DEN group only.
Conclusions: This work depicts the feasibility and importance of in depth preclinical tumor model characterization and suggests the DEN model as a promising model system of multifocal nodular HCC in future therapy studies. Clin Cancer Res; 21(19); 4440–50. ©2015 AACR.
See related commentary by Weber et al., p. 4254
Transposon Mutagenesis Screen Identifies Potential Lung Cancer Drivers and CUL3 as a Tumor Suppressor
Authors: Dorr Casey , Janik Callie , Weg Madison , Been Raha A. , Bader Justin , Kang Ryan , Ng Brandon , Foran Lindsey , Landman Sean R. , O'Sullivan M. Gerard , Steinbach Michael , Sarver Aaron L. , Silverstein Kevin A.T. , Largaespada David A. , Starr Timothy K. 
Published: May 2015

Abstract
Non–small cell lung cancers (NSCLC) harbor thousands of passenger events that hide genetic drivers. Even highly recurrent events in NSCLC, such as mutations in PTEN, EGFR, KRAS, and ALK, are detected, at most, in only 30% of patients. Thus, many unidentified low-penetrant events are causing a significant portion of lung cancers. To detect low-penetrance drivers of NSCLC, a forward genetic screen was performed in mice using the Sleeping Beauty (SB) DNA transposon as a random mutagen to generate lung tumors in a Pten-deficient background. SB mutations coupled with Pten deficiency were sufficient to produce lung tumors in 29% of mice. Pten deficiency alone, without SB mutations, resulted in lung tumors in 11% of mice, whereas the rate in control mice was approximately 3%. In addition, thyroid cancer and other carcinomas, as well as the presence of bronchiolar and alveolar epithelialization, in mice deficient for Pten were also identified. Analysis of common transposon insertion sites identified 76 candidate cancer driver genes. These genes are frequently dysregulated in human lung cancers and implicate several signaling pathways. Cullin3 (Cul3), a member of a ubiquitin ligase complex that plays a role in the oxidative stress response pathway, was identified in the screen and evidence demonstrates that Cul3 functions as a tumor suppressor.
Implications: This study identifies many novel candidate genetic drivers of lung cancer and demonstrates that CUL3 acts as a tumor suppressor by regulating oxidative stress. Mol Cancer Res; 13(8); 1238–47. ©2015 AACR.
Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants
Authors: Michalski Franziska , Tittl Luise , Werth Sebastian , Hänsel Ulrike , Pannach Sven , Sahin Kurtulus , Weiss Norbert , Beyer-Westendorf Jan 
Published: May 2015

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.
Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction
Authors: Xian Ying , Wang Tracy Y. , McCoy Lisa A. , Effron Mark B. , Henry Timothy D. , Bach Richard G. , Zettler Marjorie E. , Baker Brian A. , Fonarow Gregg C. , Peterson Eric D. 
Published: May 2015

Background—
Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain.

Methods and Results—
We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85–1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium–defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06–1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05–1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87–1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor).

Conclusions—
Among percutaneous coronary intervention–treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.
Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors
Authors: Pironti Gianluigi , Strachan Ryan T. , Abraham Dennis , Mon-Wei Yu Samuel , Chen Minyong , Chen Wei , Hanada Kenji , Mao Lan , Watson Lewis J. , Rockman Howard A. 
Published: May 2015

Background—
Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin II type I receptor (AT1R).

Methods and Results—
Exosomes containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells exposed to osmotic stretch and from sera of mice undergoing cardiac pressure overload. The presence of AT1Rs in exosomes was confirmed by both electron microscopy and radioligand receptor binding assays and shown to require β-arrestin2, a multifunctional adaptor protein essential for receptor trafficking. We show that functional AT1Rs are transferred via exosomes in an in vitro model of cellular stretch. Using mice with global and cardiomyocyte conditional deletion of β-arrestin2, we show that under conditions of in vivo pressure overload the cellular source of the exocytosis of exosomes containing AT1R is the cardiomyocyte. Exogenously administered AT1R-enriched exosomes target cardiomyocytes, skeletal myocytes, and mesenteric resistance vessels and are sufficient to confer blood pressure responsiveness to angiotensin II infusion in AT1R knockout mice.

Conclusions—
AT1R-enriched exosomes are released from the heart under conditions of in vivo cellular stress to likely modulate vascular responses to neurohormonal stimulation. In the context of the whole organism, the concept of G protein–coupled receptor trafficking should consider circulating exosomes as part of the reservoir of functional AT1Rs.
Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction
Authors: Ishikawa Kiyotake , Aguero Jaume , Oh Jae Gyun , Hammoudi Nadjib , A. Fish Lauren , Leonardson Lauren , Picatoste Belén , Santos‐Gallego Carlos G. , M. Fish Kenneth , Hajjar Roger J. 
Published: May 2015

Background
It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis.

Methods and Results

Yorkshire pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months after surgery, and cardiac function was assessed comprehensively by invasive pressure–volume measurements, 3‐dimensional echocardiography, echocardiographic speckle‐tracking strain, and postmortem molecular and histological analyses. Pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end‐diastolic pressure–volume relationship β: 0.053±0.017 versus 0.028±0.009 mm Hg/mL,
P
=0.007); however, all other parameters corresponding to systolic function, including ejection fraction, end‐systolic pressure–volume relationship, preload recruitable stroke work, echocardiographic circumferential strain, and longitudinal strain, were not impaired in pigs with aortic banding. Relaxation parameters were also similar between groups. Sarcoplasmic reticulum calcium (Ca
2+
)
ATP
ase protein levels in the left ventricle were similar. There were significant increases in 3‐dimensional echocardiographic left atrial volumes, suggesting the usefulness of these indexes to detect increased stiffness. Right atrial pacing with a heart rate of 120 beats per minute induced increased end‐diastolic pressure in pigs with aortic banding in contrast to decreased end‐diastolic pressure in the control pigs. Histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis.

Conclusion
Increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis.
The Sensitivity of Simulated Shallow Cumulus Convection and Cold Pools to Microphysics
Authors: Li Zhujun , Zuidema Paquita , Zhu Ping , Morrison Hugh 
Published: May 2015

Abstract
The sensitivity of nested WRF simulations of precipitating shallow marine cumuli and cold pools to microphysical parameterization is examined. The simulations differ only in their use of two widely used double-moment rain microphysical schemes: the Thompson and Morrison schemes. Both simulations produce similar mesoscale variability, with the Thompson scheme producing more weak cold pools and the Morrison scheme producing more strong cold pools, which are associated with more intense shallow convection. The most robust difference is that the cloud cover and LWP are significantly larger in the Morrison simulation than in the Thompson simulation. One-dimensional kinematic simulations confirm that dynamical feedbacks do not mask the impact of microphysics. These also help elucidate that a slower autoconversion process along with a stronger accretion process explains the Morrison scheme’s higher cloud fraction for a similar rain mixing ratio. Differences in the raindrop terminal fall speed parameters explain the higher evaporation rate of the Thompson scheme at moderate surface rain rates. Given the implications of the cloud-cover differences for the radiative forcing of the expansive trade wind regime, the microphysical scheme should be considered carefully when simulating precipitating shallow marine cumulus.
The Role of Whitecapping in Thickening the Ocean Surface Boundary Layer
Authors: Gerbi Gregory P. , Kastner Samuel E. , Brett Genevieve 
Published: May 2015

AbstractThe effects of wind-driven whitecapping on the evolution of the ocean surface boundary layer are examined using an idealized one-dimensional Reynolds-averaged Navier–Stokes numerical model. Whitecapping is parameterized as a flux of turbulent kinetic energy through the sea surface and through an adjustment of the turbulent length scale. Simulations begin with a two-layer configuration and use a wind that ramps to a steady stress. This study finds that the boundary layer begins to thicken sooner in simulations with whitecapping than without because whitecapping introduces energy to the base of the boundary layer sooner than shear production does. Even in the presence of whitecapping, shear production becomes important for several hours, but then inertial oscillations cause shear production and whitecapping to alternate as the dominant energy sources for mixing. Details of these results are sensitive to initial and forcing conditions, particularly to the turbulent length scale imposed by breaking waves and the transfer velocity of energy from waves to turbulence. After 1–2 days of steady wind, the boundary layer in whitecapping simulations has thickened more than the boundary layer in simulations without whitecapping by about 10%–50%, depending on the forcing and initial conditions.
How is the Balance of a Forecast Ensemble Affected by Adaptive and Nonadaptive Localization Schemes?
Authors: Bannister Ross N. 
Published: May 2015

Abstract
This paper investigates the effect on balance of a number of Schur product–type localization schemes that have been designed with the primary function of reducing spurious far-field correlations in forecast error statistics. The localization schemes studied comprise a nonadaptive scheme (where the moderation matrix is decomposed in a spectral basis), and two adaptive schemes: a simplified version of Smoothed Ensemble Correlations Raised to a Power (SENCORP) and Ensemble Correlations Raised to a Power (ECO-RAP). The paper shows, the author believes for the first time, how the degree of balance (geostrophic and hydrostatic) implied by the error covariance matrices localized by these schemes can be diagnosed. Here it is considered that an effective localization scheme is one that reduces spurious correlations adequately, but also minimizes disruption of balance (where the “correct” degree of balance or imbalance is assumed to be possessed by the unlocalized ensemble). By varying free parameters that describe each scheme (e.g., the degree of truncation in the schemes that use the spectral basis, the “order” of each scheme, and the degree of ensemble smoothing), it is found that a particular configuration of the ECO-RAP scheme is best suited to the convective-scale system studied. According to the diagnostics this ECO-RAP configuration still weakens geostrophic and hydrostatic balance, but overall this is less so than for other schemes.