bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Role for ERα: Silencing via DNA Methylation of Basal, Stem Cell, and EMT Genes
Authors: Ariazi Eric A. , Taylor John C. , Black Michael A. , Nicolas Emmanuelle , Slifker Michael J. , Azzam Diana J. , Boyd Jeff 
Published: November 2016

Abstract
Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α–positive (ERα+) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα+ status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα+ cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression. ERα-dependent DNA methylation targets (n = 39) were enriched for ERα-binding sites, basal-up/luminal-down markers, cancer stem cell, epithelial–mesenchymal transition, and inflammatory and tumor suppressor genes. Kaplan–Meier survival curve and Cox proportional hazards regression analyses indicated that these targets predicted poor distant metastasis–free survival among a large cohort of breast cancer patients. The basal breast cancer subtype markers LCN2 and IFI27 showed the greatest inverse relationship with ERα expression/activity and contain ERα-binding sites. Thus, genes that are methylated in an ERα-dependent manner may serve as predictive biomarkers in breast cancer.
Implications: ERα directs DNA methylation–mediated silencing of specific genes that have biomarker potential in breast cancer subtypes. Mol Cancer Res; 15(2); 152–64. ©2016 AACR.
Total Anomalous Pulmonary Venous Connection
Authors: Shi Guocheng , Zhu Zhongqun , Chen Jimei , Ou Yanqiu , Hong Haifa , Nie Zhiqiang , Zhang Haibo , Liu Xiaoqing , Zheng Jinghao , Sun Qi , Liu Jinfen , Chen Huiwen , Zhuang Jian 
Published: November 2016

Background:
Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China.

Methods:
This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO.

Results:

The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (
P
=0.001), mixed (
P
=0.004) and infracardiac (
P
=0.035) TAPVC, preoperative PVO (
P
=0.027), prolonged cardiopulmonary bypass time (
P
<0.001), and longer duration of ventilation (
P
=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1–112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (
P
<0.001), infracardiac TAPVC (
P
<0.001), mixed TAPVC (
P
=0.013), and prolonged cardiopulmonary bypass time (
P
<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (
P
=0.038), except in newborn patients (
P
=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II.

Conclusions:
Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.
Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus
Authors: Saito Yoshihiko , Okada Sadanori , Ogawa Hisao , Soejima Hirofumi , Sakuma Mio , Nakayama Masafumi , Doi Naofumi , Jinnouchi Hideaki , Waki Masako , Masuda Izuru , Morimoto Takeshi 
Published: November 2016

Background:
The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive.

Methods:
The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care–controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity.

Results:

The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91–1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83–1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction
P
>0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82–1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group (
P
=0.03), and the incidence of hemorrhagic stroke was not different between groups.

Conclusions:
Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00110448.
Neurological Injury in Intermediate‐Risk Transcatheter Aortic Valve Implantation
Authors: Fanning Jonathon P. , Wesley Allan J. , Walters Darren L. , Eeles Eamonn M. , Barnett Adrian G. , Platts David G. , Clarke Andrew J. , Wong Andrew A. , Strugnell Wendy E. , O'Sullivan Cliona , Tronstad Oystein , Fraser John F. 
Published: November 2016

Background

The application of transcatheter aortic valve implantation (
TAVI
) to intermediate‐risk patients is a controversial issue. Of concern, neurological injury in this group remains poorly defined. Among high‐risk and inoperable patients, subclinical injury is reported on average in 75% undergoing the procedure. Although this attendant risk may be acceptable in higher‐risk patients, it may not be so in those of lower risk.

Methods and Results

Forty patients undergoing
TAVI
with the Edwards
SAPIEN
‐
XT
™
prosthesis were prospectively studied. Patients were of intermediate surgical risk, with a mean±standard deviation Society of Thoracic Surgeons score of 5.1±2.5% and a Euro
SCORE II
of 4.8±2.4%; participant age was 82±7 years. Clinically apparent injury was assessed by serial National Institutes of Health Stroke Scale assessments, Montreal Cognitive Assessments (Mo
CA
), and with the Confusion Assessment Method. These identified 1 (2.5%) minor stroke, 1 (2.5%) episode of postoperative delirium, and 2 patients (5%) with significant postoperative cognitive dysfunction. Subclinical neurological injury was assessed using brain magnetic resonance imaging, including diffusion‐weighted imaging (
DWI
) sequences preprocedure and at 3±1 days postprocedure. This identified 68 new
DWI
lesions present in 60% of participants, with a median±interquartile range of 1±3 lesions/patient and volumes of infarction of 24±19 μL/lesion and 89±218 μL/patient.
DWI
lesions were associated with a statistically significant reduction in early cognition (mean ΔMo
CA
−3.5±1.7) without effect on cognition, quality of life, or functional capacity at 6 months.

Conclusions

Objectively measured subclinical neurological injuries remain a concern in intermediate‐risk patients undergoing
TAVI
and are likely to manifest with early neurocognitive changes.

Clinical Trial Registration

URL
:
http://www.anzctr.org.au
. Australian & New Zealand Clinical Trials Registry:
ACTRN
12613000083796.
THSD1
(Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage
Authors: Santiago-Sim Teresa , Fang Xiaoqian , Hennessy Morgan L. , Nalbach Stephen V. , DePalma Steven R. , Lee Ming Sum , Greenway Steven C. , McDonough Barbara , Hergenroeder Georgene W. , Patek Kyla J. , Colosimo Sarah M. , Qualmann Krista J. , Hagan John P. , Milewicz Dianna M. , MacRae Calum A. , Dymecki Susan M. , Seidman Christine E. , Seidman J.G. , Kim Dong H. 
Published: November 2016

Background and Purpose—
A ruptured intracranial aneurysm (IA) is the leading cause of a subarachnoid hemorrhage. This study seeks to define a specific gene whose mutation leads to disease.

Methods—

More than 500 IA probands and 100 affected families were enrolled and clinically characterized. Whole exome sequencing was performed on a large family, revealing a segregating
THSD1
(thrombospondin type 1 domain containing protein 1) mutation.
THSD1
was sequenced in other probands and controls. Thsd1 loss-of-function studies in zebrafish and mice were used for in vivo analyses and functional studies performed using an in vitro endothelial cell model.

Results—

A nonsense mutation in
THSD1
was identified that segregated with the 9 affected (3 suffered subarachnoid hemorrhage and 6 had unruptured IA) and was absent in 13 unaffected family members (LOD score 4.69). Targeted
THSD1
sequencing identified mutations in 8 of 507 unrelated IA probands, including 3 who had suffered subarachnoid hemorrhage (1.6% [95% confidence interval, 0.8%–3.1%]). These
THSD1
mutations/rare variants were highly enriched in our IA patient cohort relative to 89 040 chromosomes in Exome Aggregation Consortium (ExAC) database (
P
<0.0001). In zebrafish and mice, Thsd1 loss-of-function caused cerebral bleeding (which localized to the subarachnoid space in mice) and increased mortality. Mechanistically,
THSD1
loss impaired endothelial cell focal adhesion to the basement membrane. These adhesion defects could be rescued by expression of wild-type
THSD1
but not
THSD1
mutants identified in IA patients.

Conclusions—

This report identifies
THSD1
mutations in familial and sporadic IA patients and shows that
THSD1
loss results in cerebral bleeding in 2 animal models. This finding provides new insight into IA and subarachnoid hemorrhage pathogenesis and provides new understanding of
THSD1
function, which includes endothelial cell to extracellular matrix adhesion.
Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes
Authors: Kasasbeh Aimen S. , Christensen Søren , Straka Matus , Mishra Nishant , Mlynash Michael , Bammer Roland , Albers Gregory W. , Lansberg Maarten G. 
Published: November 2016

Background and Purpose—
The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature.

Methods—
We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time.

Results—

We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T
0
plus 1.6 times the width of the venous output function (
P
<0.001;
R
2
=0.49).

Conclusions—

This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T
0
) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended.
Historical Land-Cover Change Impacts on Climate: Comparative Assessment of LUCID and CMIP5 Multimodel Experiments
Authors: Lejeune Quentin , Seneviratne Sonia I. , Davin Edouard L. 
Published: November 2016

Abstract
During the industrial period, many regions experienced a reduction in forest cover and an expansion of agricultural areas, in particular North America, northern Eurasia, and South Asia. Here, results from the Land-Use and Climate, Identification of Robust Impacts (LUCID) and CMIP5 model intercomparison projects are compared in order to investigate how land-cover changes (LCC) in these regions have locally impacted the biophysical land surface properties, like albedo and evapotranspiration, and how this has affected seasonal mean temperature as well as its diurnal cycle. The impact of LCC is extracted from climate simulations, including all historical forcings, using a method that is shown to capture well the sign and the seasonal cycle of the impacts diagnosed from single-forcing experiments in most cases.
The model comparison reveals that both the LUCID and CMIP5 models agree on the albedo-induced reduction of mean winter temperatures over midlatitudes. In contrast, there is less agreement concerning the response of the latent heat flux and, subsequently, mean temperature during summer, when evaporative cooling plays a more important role. Overall, a majority of models exhibit a local warming effect of LCC during this season, contrasting with results from the LUCID studies. A striking result is that none of the analyzed models reproduce well the changes in the diurnal cycle identified in present-day observations of the effect of deforestation. However, overall the CMIP5 models better simulate the observed summer daytime warming effect compared to the LUCID models, as well as the winter nighttime cooling effect.
Abyssal Upwelling and Downwelling Driven by Near-Boundary Mixing
Authors: McDougall Trevor J. , Ferrari Raffaele 
Published: November 2016

AbstractA buoyancy and volume budget analysis of bottom-intensified mixing in the abyssal ocean reveals simple expressions for the strong upwelling in very thin continental boundary layers and the interior near-boundary downwelling in the stratified ocean interior. For a given amount of Antarctic Bottom Water that is upwelled through neutral density surfaces in the abyssal ocean (between 2000 and 5000 m), up to 5 times this volume flux is upwelled in narrow, turbulent, sloping bottom boundary layers, while up to 4 times the net upward volume transport of Bottom Water flows downward across isopycnals in the near-boundary stratified ocean interior. These ratios are a direct result of a buoyancy budget with respect to buoyancy surfaces, and these ratios are calculated from knowledge of the stratification in the abyss along with the assumed e-folding height that characterizes the decrease of the magnitude of the turbulent diapycnal buoyancy flux away from the seafloor. These strong diapycnal upward and downward volume transports are confined to a few hundred kilometers of the continental boundaries, with no appreciable diapycnal motion in the bulk of the interior ocean.
Absolute Velocity Estimates from Autonomous Underwater Gliders Equipped with Doppler Current Profilers
Authors: Todd Robert E. , Rudnick Daniel L. , Sherman Jeffrey T. , Owens W. Brechner , George Lawrence 
Published: November 2016

AbstractDoppler current profilers on autonomous underwater gliders measure water velocity relative to the moving glider over vertical ranges of O(10) m. Measurements obtained with 1-MHz Nortek acoustic Doppler dual current profilers (AD2CPs) on Spray gliders deployed off Southern California, west of the Galápagos Archipelago, and in the Gulf Stream are used to demonstrate methods of estimating absolute horizontal velocities in the upper 1000 m of the ocean. Relative velocity measurements nearest to a glider are used to infer dive-dependent flight parameters, which are then used to correct estimates of absolute vertically averaged currents to account for the accumulation of biofouling during months-long glider missions. The inverse method for combining Doppler profiler measurements of relative velocity with absolute references to estimate profiles of absolute horizontal velocity is reviewed and expanded to include additional constraints on the velocity solutions. Errors arising from both instrumental bias and decreased abundance of acoustic scatterers at depth are considered. Though demonstrated with measurements from a particular combination of platform and instrument, these techniques should be applicable to other combinations of gliders and Doppler current profilers.
Polar Fourier Transform Processing of Marine Radar Signals
Authors: Lyzenga David R. 
Published: November 2016

AbstractThis paper describes a method of processing marine radar signals for the purpose of generating phase-resolved surface elevation maps as well as statistical measures of ocean surface wave fields. The method is well suited to the processing of data collected by marine radars because it allows for the incorporation of effects dependent on the radar look direction relative to the propagation direction of ocean waves. Applications to Doppler radar and backscattered power measurements are described, and example results are presented using simulated radar data.
A New Characterization within the Spatial Verification Framework for False Alarms, Misses, and Overall Patterns
Authors: Gilleland Eric 
Published: November 2016

Abstract
This paper proposes new diagnostic plots that take advantage of the lack of symmetry in the mean-error distance measure (MED) for binary images to yield a new concept of false alarms and misses appropriate to the spatial setting where the measure does not require perfect matching to be a hit or correct negative. Additionally, three previously proposed geometric indices that provide complementary information about forecast performance are used to produce useful diagnostic plots for forecast performance. The diagnostics are applied to previously analyzed case studies from the spatial forecast verification Intercomparison Project (ICP) to facilitate a comparison with more complicated methods. Relatively new test cases from the Mesoscale Verification Intercomparison over Complex Terrain (MesoVICT) project are also employed for future comparisons. It is found that the proposed techniques provide useful information about forecast model behavior by way of a succinct, easy-to-implement method that can be complementary to other measures of forecast performance.
CDE Perspectives of Providing New-Onset Type 1 Diabetes Education Using Formal Vignettes and Simulation
Authors: Ramchandani Neesha , Johnson Kim , Cullen Karen , Hamm Terri , Bisordi Jean , Sullivan-Bolyai Susan 
Published: November 2016

Purpose The purpose of this article is to describe the 4 Parent Education Through Simulation-Diabetes (PETS-D) nurse certified diabetes educators’ (CDEs) perspectives of teaching parents of children with newly diagnosed type 1 diabetes mellitus (T1DM) early diabetes management skills using formal vignettes and a human patient simulator/human patient simulation (HPS) to augment/enhance the teaching–learning process. Methods A qualitative descriptive approach was used. Four CDEs were interviewed by phone about their teaching experiences. Meticulous notes were taken. Data were analyzed using qualitative content analysis. Results The vignettes (and use of HPS) provided structure, especially for parents who were struggling to learn. Certified diabetes educators described a short learning curve to master the use of the HPS manikin. Human patient simulation-enhanced education was described as helpful for teaching multiple caregivers about diabetes. Certified diabetes educators also described factors that affect parent learning, mechanical issues with the HPS, and additional space requirements for HPS-enhanced education. Conclusion Vignettes and HPS-enhanced education can successfully be used to educate parents of children with new-onset T1DM and were preferred by the CDEs when compared with previous teaching strategies. The results of this study support the use of both vignette-based and HPS-enhanced education when a child is newly diagnosed with T1DM. Further studies need to be done to see if these effects persist with different populations, during different stages of the disease, and for individuals with other chronic illnesses.
An Adult Health Care–Based Pediatric to Adult Transition Program for Emerging Adults With Type 1 Diabetes
Authors: Agarwal Shivani , Raymond Jennifer K. , Schutta Mark H. , Cardillo Serena , Miller Victoria A. , Long Judith A. 
Published: November 2016

Purpose The purpose of the study was to evaluate an adult health care program model for emerging adults with type 1 diabetes transitioning from pediatric to adult care. Methods Evaluation of the Pediatric to Adult Diabetes Transition Clinic at the University of Pennsylvania included a cohort of 72 emerging adults with type 1 diabetes, ages 18 to 25 years. Data were extracted from transfer summaries and the electronic medical record, including sociodemographic, clinical, and follow-up characteristics. Pre- and postprogram assessment at 6 months included mean daily blood glucose monitoring frequency (BGMF) and glycemic control (A1C). Paired t tests were used to examine change in outcomes from baseline to 6 months, and multiple linear regression was utilized to adjust outcomes for baseline A1C or BGMF, sex, diabetes duration, race, and insulin regimen. Open-ended survey responses were used to assess acceptability amongst participants. Results From baseline to 6 months, mean A1C decreased by 0.7% (8 mmol/mol), and BGMF increased by 1 check per day. Eighty-eight percent of participants attended ≥2 visits in 6 months, and the program was rated highly by participants and providers (pediatric and adult). Conclusions This study highlights the promise of an adult health care program model for pediatric to adult diabetes transition.