bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase Suppresses Formation of ALT-Associated Single-Stranded Telomeric C-Circles
Authors: Plantinga Matthew J. , Pascarelli Kara M. , Merkel Anna S. , Lazar Alexander J. , von Mehren Margaret , Lev Dina , Broccoli Dominique 
Published: March 2013

Abstract
Telomere maintenance is an essential characteristic of cancer cells, most commonly achieved by activation of telomerase. Telomeres can also be maintained by a recombination-based mechanism, alternative lengthening of telomeres (ALT). Cells using ALT are characterized by the presence of ALT-associated promyelocytic leukemia (PML) bodies (APB), long, heterogeneously sized telomeres, extrachromosomal telomeric circular DNA, and elevated telomeric recombination. Consistent with other reports, we found that liposarcomas containing APBs, but lacking telomerase expression, always contained C-rich circles (C-circles), and these C-circles were never present in the absence of APBs, indicating a tight link between these features in ALT cells. However, a rare subgroup of tumors showing evidence of telomere maintenance by both telomerase and ALT did not contain C-circles. To test the hypothesis that telomerase expression disrupts the tight link between APBs and C-circles, we used ALT cell lines that were engineered to express telomerase. Introduction of telomerase activity in these ALT cells resulted in, on average, shorter telomeres with retention of APBs. However, at high passage, the level of C-circles was significantly reduced, which was paralleled by a switch from C-strand overhangs to G-strand overhangs. We propose that by extending critically short telomeres in these cells, telomerase is disrupting a key step in the ALT pathway necessary for production and/or maintenance of C-circles. Mol Cancer Res; 11(6); 557–67. ©2013 AACR.
Tumor Suppressor microRNAs, miR-100 and -125b, Are Regulated by 1,25-dihydroxyvitamin D in Primary Prostate Cells and in Patient Tissue
Authors: Giangreco Angeline A. , Vaishnav Avani , Wagner Dennis , Finelli Antonio , Fleshner Neil , Van der Kwast Theodorus , Vieth Reinhold , Nonn Larisa 
Published: March 2013

AbstractMiR-100 and miR-125b are lost in many cancers and have potential function as tumor suppressors. Using both primary prostatic epithelial cultures and laser capture-microdissected prostate epithelium from 45 patients enrolled in a vitamin D3 randomized trial, we identified miR-100 and -125b as targets of 1,25-dihydroxyvitamin D3 (1,25D). In patients, miR-100 and -125b levels were significantly lower in tumor tissue than in benign prostate. Similarly, miR-100 and -125b were lower in primary prostate cancer cells than in cells derived from benign prostate. Prostatic concentrations of 1,25D positively correlated with these miRNA levels in both prostate cancer and benign epithelium, showing that patients with prostate cancer may still benefit from vitamin D3. In cell assays, upregulation of these miRNAs by 1,25D was vitamin D receptor dependent. Transfection of pre-miR-100 and pre-miR-125b in the presence or absence of 1,25D decreased invasiveness of cancer cell, RWPE-2. Pre-miR-100 and pre-miR-125b decreased proliferation in primary cells and cancer cells respectively. Pre-miR-125b transfection suppressed migration and clonal growth of prostate cancer cells, whereas knockdown of miR-125b in normal cells increased migration indicates a tumor suppressor function. 1,25D suppressed expression of previously bona fide mRNA targets of these miRNAs, E2F3 and Plk1, in a miRNA-dependent manner. Together, these findings show that vitamin D3 supplementation augments tumor suppressive miRNAs in patient prostate tissue, providing evidence that miRNAs could be key physiologic mediators of vitamin D3 activity in prevention and early treatment of prostate cancer. Cancer Prev Res; 6(5); 483–94. ©2013 AACR.
Association of Tooth Loss and Oral Hygiene with Risk of Gastric Adenocarcinoma
Authors: Shakeri Ramin , Malekzadeh Reza , Etemadi Arash , Nasrollahzadeh Dariush , Abedi-Ardekani Behnoush , Khoshnia Masoud , Islami Farhad , Pourshams Akram , Pawlita Michael , Boffetta Paolo , Dawsey Sanford M. , Kamangar Farin , Abnet Christian C. 
Published: March 2013

Abstract
Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However, a small number of studies have tested these associations. We conducted a case–control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age, and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. ORs and 95% confidence intervals (95% CI) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree-of-freedom global test of the effect of adding oral hygiene variables to the model were also calculated. Our results showed apparent associations between tooth loss and decayed, missing, filled teeth (DMFT) score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma ORs (95% CI) of 5.6 (1.6–19.3). We found evidence for an association between oral health and gastric cancer, but the nonmonotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions. Cancer Prev Res; 6(5); 477–82. ©2013 AACR.
Preoperative Assessment of High-Risk Candidates to Predict Survival After Heart Transplantation
Authors: Schulze P. Christian , Jiang Jeffrey , Yang Jonathan , Cheema Faisal H. , Schaeffle Kenneth , Kato Tomoko S. , Farr Maryjane , Restaino Susan , Deng Mario , Maurer Mathew , Horn Evelyn , Latif Farhana , Colombo Paolo C. , Jorde Ulrich , Uriel Nir , Haythe Jennifer , Bijou Rachel , Drusin Ron , Lee Sun Hi , Takayama Hiroo , Naka Yoshifumi , Mancini Donna M. 
Published: March 2013

Background—
Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx.

Methods and Results—

We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years;
P
<0.001), had more renal dysfunction, prior cancer, and smoking. Survival analysis revealed lower post-HTx survival in high-risk recipients (82.2% versus 87.4% at 1-year; 59.8% versus 76.3% at 5-year post-HTx;
P
=0.0005). Prior cerebral vascular accident, albumin <3.5 mg/dL, re-HTx, renal dysfunction (glomerular filtration rate <40 mL/min), and >2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0–2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx;
P
<0.001). Low-risk alternate patients had survival comparable with regular patients (87.9% versus 87.0% at 1-year and 65.9% versus 74.5% at 5-year post-HTx;
P
=0.46).

Conclusions—
High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.
Galectin-3 and Cardiac Function in Survivors of Acute Myocardial Infarction
Authors: Weir Robin A.P. , Petrie Colin J. , Murphy C. Aengus , Clements Suzanne , Steedman Tracey , Miller Ashley M. , McInnes Iain B. , Squire Iain B. , Ng Leong L. , Dargie Henry J. , McMurray John J.V. 
Published: March 2013

Background—
Galectin-3 is a biomarker associated with inflammation and fibrosis that predicts adverse outcome and relates to biomarkers of extracellular matrix turnover in patients with heart failure, particularly when left ventricular (LV) systolic function is preserved. Whether galectin-3 is related to LV remodeling after acute myocardial infarction is unknown.

Methods and Results—

Circulating galectin-3 and various extracellular matrix biomarkers were measured in 100 patients (age, 58.9±12.0 years; 77% men) admitted with acute myocardial infarction and LV dysfunction, at baseline (mean 46 hours) and at 24 weeks, with cardiac MRI at each time-point. LV remodeling was defined as change in LV end-systolic volume index. Relationships among galectin-3, biomarkers, and LV remodeling were analyzed across the entire cohort, then according to median baseline LV ejection fraction. Galectin-3 levels were elevated in 22 patients (22%) at baseline and increased significantly over time from 14.7±5.5 to 16.3±6.6 ng/mL (
P
=0.007). Baseline galectin-3 did not correlate with any LV parameters at baseline or change in any parameter over time. Galectin-3 was positively associated with remodeling in patients with supramedian baseline LV ejection fraction (ie, >49.2%;
r
=0.40;
P
=0.01) but not when LV ejection fraction was ≤49.2%. Galectin-3 correlated significantly with matrix metalloproteinase-3 and monocyte chemoattractant protein-1 at baseline, biomarkers that have been shown to relate to LV remodeling in this cohort.

Conclusions—
Galectin-3 correlated significantly with certain biomarkers involved in extracellular matrix turnover, although no definite relationship was identified with LV remodeling. Whether galectin-3 plays a pathological role in remodeling remains unclear but merits further study.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00132093.
Vorapaxar in Patients With Peripheral Artery Disease
Authors: Bonaca Marc P. , Scirica Benjamin M. , Creager Mark A. , Olin Jeffrey , Bounameaux Henri , Dellborg Mikael , Lamp Jessica M. , Murphy Sabina A. , Braunwald Eugene , Morrow David A. 
Published: March 2013

Background—
Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for peripheral revascularization.

Methods and Results—

The Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with stable atherosclerotic vascular disease (myocardial infarction, stroke, or peripheral artery disease). Patients with qualifying peripheral artery disease (n=3787) had a history of claudication and an ankle-brachial index of <0.85 or prior revascularization for limb ischemia. The primary efficacy end point was cardiovascular death, myocardial infarction, or stroke, and the principal safety end point was Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) bleeding. In the peripheral artery disease cohort, the primary end point did not differ significantly with vorapaxar (11.3% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.78–1.14;
P
=0.53). However, rates of hospitalization for acute limb ischemia (2.3% versus 3.9%; hazard ratio, 0.58; 95% confidence interval, 0.39–0.86;
P
=0.006) and peripheral artery revascularization (18.4% versus 22.2%; hazard ratio, 0.84; 95% confidence interval, 0.73–0.97;
P
=0.017) were significantly lower in patients randomized to vorapaxar. Bleeding occurred more frequently with vorapaxar compared with placebo (7.4% versus 4.5%; hazard ratio, 1.62; 95% confidence interval, 1.21–2.18;
P
=0.001).

Conclusions—
Vorapaxar did not reduce the risk of cardiovascular death, myocardial infarction, or stroke in patients with peripheral artery disease; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of protease-activated receptor-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00526474.
Reporting and Representation: Intra-EU Diplomacy and Dutch Bilateral Embassies
Authors: Uilenreef Arjan D. 
Published: March 2013

Summary
Embassies of the Netherlands within the European Union operate in another political and diplomatic environment than Dutch embassies in other parts of the world. There is a lack of comprehensive studies on the change dynamics of bilateral diplomacy within the EU. This article aims to contribute to the study of intra-EU diplomacy by looking at one of the key tasks of embassies abroad, namely reporting back to the capital. An analysis of the addressees, the type of reporting, and the interlocutors of embassy staff across Europe, reveals characteristics of the work of representations in a ‘post-Westphalian’ order. The results show that the diplomatic environment of Dutch bilateral embassies within the European Union does in several important ways indeed differ from that of Dutch embassies outside the Union.
CMIP5 Simulations of Low-Level Tropospheric Temperature and Moisture over the Tropical Americas
Authors: Carvalho Leila M. V. , Jones Charles 
Published: March 2013

Abstract
Global warming has been linked to systematic changes in North and South America's climates and may severely impact the North American monsoon system (NAMS) and South American monsoon system (SAMS). This study examines interannual-to-decadal variations and changes in the low-troposphere (850 hPa) temperature (T850) and specific humidity (Q850) and relationships with daily precipitation over the tropical Americas using the NCEP–NCAR reanalysis, the Climate Forecast System Reanalysis (CFSR), and phase 5 of the Coupled Model Intercomparison Project (CMIP5) simulations for two scenarios: “historic” and high-emission representative concentration pathway 8.5 (RCP8.5). Trends in the magnitude and area of the 85th percentiles were distinctly examined over North America (NA) and South America (SA) during the peak of the respective monsoon season. The historic simulations (1951–2005) and the two reanalyses agree well and indicate that significant warming has occurred over tropical SA with a remarkable increase in the area and magnitude of the 85th percentile in the last decade (1996–2005). The RCP8.5 CMIP5 ensemble mean projects an increase in the T850 85th percentile of about 2.5°C (2.8°C) by 2050 and 4.8°C (5.5°C) over SA (NA) by 2095 relative to 1955. The area of SA (NA) with T850 ≥ the 85th percentile is projected to increase from ~10% (15%) in 1955 to ~58% (~33%) by 2050 and ~80% (~50%) by 2095. The respective increase in the 85th percentile of Q850 is about 3 g kg−1 over SAMS and NAMS by 2095. CMIP5 models project variable changes in daily precipitation over the tropical Americas. The most consistent is increased rainfall in the intertropical convergence zone in December–February (DJF) and June–August (JJA) and decreased precipitation over NAMS in JJA.
Seasonal Forecasts of the Pan-Arctic Sea Ice Extent Using a GCM-Based Seasonal Prediction System
Authors: Chevallier Matthieu , Salas y Mélia David , Voldoire Aurore , Déqué Michel , Garric Gilles 
Published: March 2013

Abstract
An ocean–sea ice model reconstruction spanning the period 1990–2009 is used to initialize ensemble seasonal forecasts with the Centre National de Recherches Météorologiques Coupled Global Climate Model version 5.1 (CNRM-CM5.1) coupled atmosphere–ocean general circulation model. The aim of this study is to assess the skill of fully initialized September and March pan-Arctic sea ice forecasts in terms of climatology and interannual anomalies. The predictions are initialized using “full field initialization” of each component of the system. In spite of a drift due to radiative biases in the coupled model during the melt season, the full initialization of the sea ice cover on 1 May leads to skillful forecasts of the September sea ice extent (SIE) anomalies. The skill of the prediction is also significantly high when considering anomalies of the SIE relative to the long-term linear trend. It confirms that the anomaly of spring sea ice cover in itself plays a role in preconditioning a September SIE anomaly. The skill of predictions for March SIE initialized on 1 November is also encouraging, and it can be partly attributed to persistent features of the fall sea ice cover. The present study gives insight into the current ability of state-of-the-art coupled climate systems to perform operational seasonal forecasts of the Arctic sea ice cover up to 5 months in advance.
Uncertainty in Ranking the Hottest Years of U.S. Surface Temperatures
Authors: Guttorp Peter , Kim Tae Yen 
Published: March 2013

Abstract
Ranking years based on statistical estimates of regional and temporal averages is subject to uncertainty. This uncertainty can in fact be quite substantial and can be described by the rank distribution of an ensemble of such averages. The authors develop a method for estimating it using simulation. The effect of temporal correlation is quite limited in the case studied in this paper: the contiguous United States' annual-mean temperature. The method also allows assessment of derived quantities such as the probability of a given year being one of the 10 warmest in the historical record.
The Influence of the Amundsen–Bellingshausen Seas Low on the Climate of West Antarctica and Its Representation in Coupled Climate Model Simulations
Authors: Hosking J. Scott , Orr Andrew , Marshall Gareth J. , Turner John , Phillips Tony 
Published: March 2013

Abstract
In contrast to earlier studies, the authors describe the climatological deep low pressure system that exists over the South Pacific sector of the Southern Ocean, referred to as the Amundsen–Bellingshausen Seas low (ABSL), in terms of its relative (rather than actual) central pressure by removing the background area-averaged mean sea level pressure (MSLP). Doing so removes much of the influence of large-scale variability across the ABSL sector region (e.g., due to the southern annular mode), allowing a clearer understanding of ABSL variability and its effect on the regional climate of West Antarctica. Using ECMWF Interim Re-Analysis (ERA-Interim) fields, the annual cycle of the relative central pressure of the ABSL for the period from 1979 to 2011 shows a minimum (maximum) during winter (summer), differing considerably from the earlier studies based on actual central pressure, which suggests a semiannual oscillation. The annual cycle of the longitudinal position of the ABSL is insensitive to the background pressure, and shows it shifting westward from ∼250° to ∼220°E between summer and winter, in agreement with earlier studies. The authors demonstrate that ABSL variability, and in particular its longitudinal position, play an important role in controlling the surface climate of West Antarctica and the surrounding ocean by quantifying its influence on key meteorological parameters. Examination of the ABSL annual cycle in 17 CMIP5 climate models run with historical forcing shows that the majority of them have definite biases, especially in terms of longitudinal position, and a correspondingly poor representation of West Antarctic climate.
Diagnosing Surface Mixed Layer Dynamics from High-Resolution Satellite Observations: Numerical Insights
Authors: Ponte Aurelien L. , Klein Patrice , Capet Xavier , Le Traon Pierre-Yves , Chapron Bertrand , Lherminier Pascale 
Published: March 2013

Abstract
High-resolution numerical experiments of ocean mesoscale eddy turbulence show that the wind-driven mixed layer (ML) dynamics affects mesoscale motions in the surface layers at scales lower than O(60 km). At these scales, surface horizontal currents are still coherent to, but weaker than, those derived from sea surface height using geostrophy. Vertical motions, on the other hand, are stronger than those diagnosed using the adiabatic quasigeotrophic (QG) framework. An analytical model, based on a scaling analysis and on simple dynamical arguments, provides a physical understanding and leads to a parameterization of these features in terms of vertical mixing. These results are valid when the wind-driven velocity scale is much smaller than that associated with eddies and the Ekman number (related to the ratio between the Ekman and ML depth) is not small. This suggests that, in these specific situations, three-dimensional ML motions (including the vertical velocity) can be diagnosed from high-resolution satellite observations combined with a climatological knowledge of ML conditions and interior stratification.
Adiabatic Eastern Boundary Currents
Authors: Cessi Paola , Wolfe Christopher L. 
Published: March 2013

AbstractThe dynamics of the eastern boundary current of a high-resolution, idealized model of oceanic circulation are analyzed and interpreted in terms of residual mean theory. In this framework, it is clear that the eastern boundary current is adiabatic and inviscid. Nevertheless, the time-averaged potential vorticity is not conserved along averaged streamlines because of the divergence of Eliassen–Palm fluxes, associated with buoyancy and momentum eddy fluxes. In particular, eddy fluxes of buoyancy completely cancel the mean downwelling or upwelling, so that there is no net diapycnal residual transport. The eddy momentum flux acts like a drag on the mean velocity, opposing the acceleration from the eddy buoyancy flux: in the potential vorticity budget this results in a balance between the divergences of eddy relative vorticity and buoyancy fluxes, which leads to a baroclinic eastern boundary current whose horizontal scale is the Rossby deformation radius and whose vertical extent depends on the eddy buoyancy transport, the Coriolis parameter, and the mean surface buoyancy distribution.