bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid growth of seed black holes in the early universe by supra-exponential accretion
Authors: Alexander Tal , Natarajan Priyamvada 
Published: August 2014

Sheltered black hole seeds grow faster
Astrophysicists have struggled to find a way to grow supermassive black holes within the first billion years of the universe, in the first 6% of its current age. These objects power the extremely bright and distant quasars whose light from that era has finally reached us. To grow a black hole so massive so quickly seemed to violate the expected balance of both radiation pressure and angular momentum. Alexander and Natarajan report that the predicted accretion rate can be exceeded with the help of a protective gas cloud at the heart of a star cluster. There, the radiation from accretion is reverted back onto the black hole, enabling a phase of supraexponential growth for a brief 10 million years.

Science
, this issue p.
1330
Complete Genome Sequence of a Tobacco-Infecting, Tomato-Blistering Mosaic Virus
Authors: Melo Fernando Lucas , Fernandes Jhon Eric Alves , Ribeiro Bergmann Morais , Ribeiro Simone Graça 
Published: August 2014

ABSTRACT

The complete genome sequence of a new tomato-blistering mosaic virus (ToBMV) isolate was determined. This tymovirus isolate was first described infecting tobacco during the 1980s, but it also infects other
Solanaceae
members experimentally. The genome has 6,257 nucleotides and shares 88% nucleotide identity with the ToBMV isolated from tomato.
Draft Genome Sequence of Linezolid-Resistant Enterococcus faecalis Clinical Isolate HS0914
Authors: Lin Dongfang , Guo Yan , Chen Chunhui , Fuzhu Yingjie , Xiao Shuxin , Zhu Demei , Wang Minggui , Xu Xiaogang 
Published: August 2014

ABSTRACT

We report the draft genome sequence of linezolid-resistant
Enterococcus faecalis
strain HS-0914 isolated from a teaching hospital in Shanghai, China. The draft genome sequence is composed of 61 contigs for 2,816,079 bp. Ribosomal RNA mutations and
cfr
, which mediates linezolid resistance, are not present.
Draft Genome Sequence of Hexachlorohexane (HCH)-Degrading Sphingobium lucknowense Strain F2
T
, Isolated from an HCH Dumpsite
Authors: Negi Vivek , Lata Pushp , Sangwan Naseer , Kumar Gupta Sanjay , Das Shreyasi , Rao D. L. N. , Lal Rup 
Published: August 2014

ABSTRACT

Sphingobium lucknowense
F2
T
, isolated from the hexachlorocylcohexane (HCH) dumpsite located in Ummari village, Lucknow, India, rapidly degrades HCH isomers. Here we report the draft genome of strain F2 (4.4 Mbp), consisting of 4,910 protein coding genes with an average G+C content of 64.3%.
Risk of overdose and death following codeine prescription among immigrants
Authors: Ray Joel G , Hollands Simon , Gomes Tara , Urquia Marcelo L , Macdonald Erin M , Li Ping , Mamdani Muhammad M , Juurlink David N 
Published: August 2014

BackgroundImmigrants may be at a higher risk of adverse drug reactions, in that poor language proficiency reduces individuals understanding of drug label instructions. Additionally, there are reports of severe or fatal toxicity due to CYP2D6 ultrarapid hepatic metabolism of codeine to morphine among some ethnic groups, especially those from Eastern Africa.MethodsBetween 2002 and 2012 we conducted a population-based cohort study among residents of Ontario, Canada. We used administrative health databases that linked immigrants and Canadian-born individuals to both prescription medication use and emergency department visits and hospital admissions. The primary composite outcome was the risk of drug overdose or all-cause mortality within 30 days of codeine prescription, comparing patients from various world regions to Canadian-born individuals. A secondary analysis stratified by codeine dose and ability to speak English and/or French.ResultsThere were 553 504 individuals exclusively prescribed codeine. Relative to an incidence rate of 57.1/100 000 person-days among Canadian-born codeine recipients, those who migrated from various world regions were at a lower risk of drug overdose or death. For example, Eastern Africans had an adjusted HR of 0.60 (95% CI 0.31 to 1.17) on controlling for potential confounders such as age, sex, income and physician visits. Patients unable to speak English or French who were prescribed codeine were at a lower risk of the composite outcome relative to those proficient in either language (adjusted HR 0.63, 95% CI 0.54 to 0.74).InterpretationOverdose and death following the institution of codeine therapy are not more commonly observed among immigrants from world regions with a high prevalence of ultrarapid CYP2D6 status relative to those born in Canada. Lower proficiency in English or French also did not appear to heighten the risk.
A Macrophage-Dominant PI3K Isoform Controls Hypoxia-Induced HIF1α and HIF2α Stability and Tumor Growth, Angiogenesis, and Metastasis
Authors: Joshi Shweta , Singh Alok R. , Zulcic Muamera , Durden Donald L. 
Published: August 2014

AbstractTumor growth, progression, and response to the hypoxic tumor microenvironment involve the action of hypoxia-inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFα subunit and a constitutively expressed HIFβ subunit. The signaling pathways operational in macrophages regulating hypoxia-induced HIFα stabilization remain the subject of intense investigation. Here, it was discovered that the PTEN/PI3K/AKT signaling axis controls hypoxia-induced HIF1α (HIF1A) and HIF2α (EPAS1) stability in macrophages. Using genetic mouse models and pan-PI3K as well as isoform-specific inhibitors, inhibition of the PI3K/AKT pathway blocked the accumulation of HIFα protein and its primary transcriptional target VEGF in response to hypoxia. Moreover, blocking the PI3K/AKT signaling axis promoted the hypoxic degradation of HIFα via the 26S proteasome. Mechanistically, a macrophage-dominant PI3K isoform (p110γ) directed tumor growth, angiogenesis, metastasis, and the HIFα/VEGF axis. Moreover, a pan-PI3K inhibitor (SF1126) blocked tumor-induced angiogenesis and inhibited VEGF and other proangiogenic factors secreted by macrophages. These data define a novel molecular mechanism by which PTEN/PI3K/AKT regulates the proteasome-dependent stability of HIFα under hypoxic conditions, a signaling pathway in macrophages that controls tumor-induced angiogenesis and metastasis.Implications: This study indicates that PI3K inhibitors are excellent candidates for the treatment of cancers where macrophages promote tumor progression. Mol Cancer Res; 12(10); 1520–31. ©2014 AACR.
Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStar and Innovance
Authors: Maistre Emmanuel de , Volot Fabienne , Mourey Guillaume , Aho Ludwig , Ternisien Catherine , Briquel Marie-Elisabeth , Bertrand Marie-Anne , Tardy Brigitte , Frotscher Birgit , Nguyen Philippe , Dumont Laure , Vandroux David , Hezard Nathalie , Trossaërt Marc 
Published: August 2014

SummaryThe ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20–30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the “gold standard” VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
Relationship Between MDCT‐Imaged Myocardial Fat and Ventricular Tachycardia Substrate in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Komatsu Yuki , Jadidi Amir , Sacher Frederic , Denis Arnaud , Daly Matthew , Derval Nicolas , Shah Ashok , Lehrmann Heiko , Park Chan‐Il , Weber Reinhold , Arentz Thomas , Pache Gregor , Sermesant Maxime , Ayache Nicholas , Relan Jatin , Montaudon Michel , Laurent François , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre , Cochet Hubert 
Published: August 2014

Background

Myocardial fibrofatty infiltration is a milieu for ventricular tachycardia (
VT
) in arrhythmogenic right ventricular cardiomyopathy (
ARVC
) and can be depicted as myocardial hypodensity on contrast‐enhanced multidetector computed tomography (
MDCT
) with high spatial and temporal resolution. This study aimed to assess the relationship between
MDCT
‐imaged myocardial fat and
VT
substrate in
ARVC
.

Methods and Results

We studied 16 patients with
ARVC
who underwent ablation and preprocedural
MDCT
. High‐resolution imaging data were processed and registered to high‐density endocardial and epicardial maps in sinus rhythm on 3‐dimensional electroanatomic mapping (3D‐
EAM
) (626±335 and 575±279 points/map, respectively). Analysis of the locations of low‐voltage and fat segmentation included the following endocardial and epicardial regions: apex, mid (anterior, lateral, inferior), and basal (anterior, lateral, inferior). The location of local abnormal ventricular activities (
LAVA
) was compared with fat distribution.
RV
myocardial fat was successfully segmented and integrated with 3D‐
EAM
in all patients. The κ agreement test demonstrated a good concordance between the epicardial low voltage and fat (κ=0.69, 95%
CI
0.54 to 0.84), but fair concordance with the endocardium (κ=0.41, 95%
CI
0.27 to 0.56). The majority of
LAVA
(520/653 [80%]) were located within the
RV
fat segmentation, of which 90% were not farther than 20 mm from its border. Registration of
MDCT
allowed direct visualization of the coronary arteries, thus avoiding coronary damage during epicardial radiofrequency delivery.

Conclusions

The integration of
MDCT
‐imaged myocardial fat with 3D‐
EAM
provides valuable information on the extent and localization of
VT
substrate and demonstrates ablation targets clustering in its border region.
Association of Cognitive Functioning, Incident Stroke, and Mortality in Older Adults
Authors: Rajan Kumar B. , Aggarwal Neelum T. , Wilson Robert S. , Everson-Rose Susan A. , Evans Denis A. 
Published: August 2014

Background and Purpose—
Stroke increases the risk of dementia; however, bidirectional association of incident stroke and cognitive decline below dementia threshold is not well established. Also, both cognitive decline and stroke increase mortality risk.

Methods—
A longitudinal population-based cohort of 7217 older adults without a history of stroke from a biracial community was interviewed at 3-year intervals. Cognitive function was assessed using a standardized global cognitive score. Stroke was determined by linkage with Medicare claims, and mortality was ascertained via the National Death Index. We used a Cox model to assess the risk of incident stroke, a joint model with a piecewise linear mixed model with incident stroke as a change point for cognitive decline process, and a time-dependent relative risk regression model for mortality risk.

Results—
During follow-up, 1187 (16%) subjects had incident stroke. After adjusting for known confounders, lower baseline cognitive function was associated with a higher risk of incident stroke (hazard ratio, 1.61; 95% confidence interval, 1.46–1.77). Cognitive function declined by 0.064 U per year before incident stroke occurrence and 0.122 U per year after stroke, a nearly 1.9-fold increase in cognitive decline (95% confidence interval, 1.78–2.03). Both stroke (hazard ratio, 1.17; 95% confidence interval, 1.08–1.26) and cognitive decline (hazard ratio, 1.90; 95% confidence interval, 1.81–1.98) increased mortality risk.

Conclusions—
Baseline cognitive function was associated with incident stroke. Cognitive decline increased significantly after stroke relative to before stroke. Cognitive decline increased mortality risk independent of the risk attributable to stroke and should be followed as a marker for both stroke and mortality.
A Unified Convection Scheme (UNICON). Part II: Simulation
Authors: Park Sungsu 
Published: August 2014

Abstract
A unified convection scheme (UNICON) is implemented into the Community Atmosphere Model, version 5 (CAM5), and tested in single-column and global simulations forced by observed sea surface temperature. Compared to CAM5, UNICON substantially improves the single-column simulations of stratocumulus-to-cumulus transition and shallow and deep convection cases. The global performance of UNICON is similar to CAM5 with a relative spatiotemporal root-mean-square error (RMSE) of 0.777 (0.755 in CAM5) against the earlier version of the model (CCSM3.5). The notable improvements in the UNICON-simulated climatologies over CAM5 are seasonal precipitation patterns (i.e., monsoon) over the western Pacific and South Asia, reduced biases of cloud radiative forcing in the tropical deep convection regions, aerosol optical depth in the tropical and subtropical regions, and cumulus fraction and in-cumulus condensate. One notable degradation is that UNICON simulates warmer near-surface air temperature over the United States during summer.
In addition to the climatology, UNICON significantly improves the simulation of the diurnal cycle of precipitation and the Madden–Julian oscillation (MJO). The surface precipitation simulated by UNICON is a maximum in the late afternoon (early afternoon in CAM5) over the summer continents and in the early morning (predawn in CAM5) over the ocean with a fairly realistic amplitude of the diurnal cycle. Sensitivity simulations indicate that the key for successful MJO simulation in UNICON is a seamless parameterization of the updraft plume dilution rate as convection evolves from shallow to deep convection. The mesoscale perturbation of the vertical velocity and the thermodynamic scalars of convective updrafts is an additional requirement for simulating the observed diurnal cycle of precipitation.
WRF Model Sensitivity to Land Surface Model and Cumulus Parameterization under Short-Term Climate Extremes over the Southern Great Plains of the United States
Authors: Pei Lisi , Moore Nathan , Zhong Shiyuan , Luo Lifeng , Hyndman David W. , Heilman Warren E. , Gao Zhiqiu 
Published: August 2014

Abstract
Extreme weather and climate events, especially short-term excessive drought and wet periods over agricultural areas, have received increased attention. The Southern Great Plains (SGP) is one of the largest agricultural regions in North America and features the underlying Ogallala-High Plains Aquifer system worth great economic value in large part due to production gains from groundwater. Climate research over the SGP is needed to better understand complex coupled climate–hydrology–socioeconomic interactions critical to the sustainability of this region, especially under extreme climate scenarios. Here the authors studied growing-season extreme conditions using the Weather Research and Forecasting (WRF) Model. The six most extreme recent years, both wet and dry, were simulated to investigate the impacts of land surface model and cumulus parameterization on the simulated hydroclimate. The results show that under short-term climate extremes, the land surface model plays a more important role modulating the land–atmosphere water budget, and thus the entire regional climate, than the cumulus parameterization under current model configurations. Between the two land surface models tested, the more sophisticated land surface model produced significantly larger wet bias in large part due to overestimation of moisture flux convergence, which is attributed mainly to an overestimation of the surface evapotranspiration during the simulated period. The deficiencies of the cumulus parameterizations resulted in the model’s inability to depict the diurnal rainfall variability. Both land surface processes and cumulus parameterizations remain the most challenging parts of regional climate modeling under extreme climates over the SGP, with the former strongly affecting the precipitation amount and the latter strongly affecting the precipitation pattern.
Subtalar Joint Axis in Patients With Symptomatic Peritalar Subluxation Compared to Normal Controls
Authors: Apostle Kelly L. , Coleman Nathan W. , Sangeorzan Bruce J. 
Published: August 2014

Background: The etiology of peritalar subluxation (PTS) is poorly understood and likely mutifactorial. An anatomic predisposition for posterolateral subluxation of the hindfoot has not been previously described or investigated. The aim of the current study was to describe the morphology of the subtalar joint axis (STJA) in patients with symptomatic PTS compared to normal controls. Methods: We identified patients with symptomatic PTS who had undergone operative correction from hospital records. The angle of the axis of the posterior facet of the subtalar joint was made on simulated weight-bearing CT (SWBCT) scans. A control group of patients who had no foot deformity on standing films was used for comparison. The STJA was defined as the angle between the superior talar dome and the posterior facet of the talus on coronal CT scan. The mean, maximum, and minimum STJAs were calculated for each cut from anterior to posterior across the posterior facet. The trend in progression across the posterior facet was also examined. Results: After exclusions, 22 feet in 20 patients were included in the study group and compared to 20 control subjects. It was seen that patients with PTS had an increased valgus orientation of the subtalar joint. In patients with PTS the STJA began in valgus and progressed to even greater valgus from anterior to posterior across the posterior facet. The STJA in control subjects was seen instead to begin in slight varus and transition to valgus at the junction of the anterior and middle third and then increase in valgus as the joint progressed posteriorly. Conclusions: The valgus orientation of the coronal plane of the subtalar joint may represent an anatomic contribution to the etiology of PTS. Level of Evidence: Level III, comparative series.
The dynamic range of circulating tumor DNA in metastatic breast cancer
Authors: Heidary Maryam , Auer Martina , Ulz Peter , Heitzer Ellen , Petru Edgar , Gasch Christin , Riethdorf Sabine , Mauermann Oliver , Lafer Ingrid , Pristauz Gunda , Lax Sigurd , Pantel Klaus , Geigl Jochen B , Speicher Michael R 
Published: August 2014

Abstract
Introduction
The management of metastatic breast cancer needs improvement. As clinical evaluation is not very accurate in determining the progression of disease, the analysis of circulating tumor DNA (ctDNA) has evolved to a promising noninvasive marker of disease evolution. Indeed, ctDNA was reported to represent a highly sensitive biomarker of metastatic cancer disease directly reflecting tumor burden and dynamics. However, at present little is known about the dynamic range of ctDNA in patients with metastatic breast cancer.

Methods
In this study, 74 plasma DNA samples from 58 patients with metastasized breast cancer were analyzed with a microfluidic device to determine the plasma DNA size distribution and copy number changes in the plasma were identified by whole-genome sequencing (plasma-Seq). Furthermore, in an index patient we conducted whole-genome, exome, or targeted deep sequencing of the primary tumor, metastases, and circulating tumor cells (CTCs). Deep sequencing was done to accurately determine the allele fraction (AFs) of mutated DNA fragments.

Results
Although all patients had metastatic disease, plasma analyses demonstrated highly variable AFs of mutant fragments. We analyzed an index patient with more than 100,000 CTCs in detail. We first conducted whole-genome, exome, or targeted deep sequencing of four different regions from the primary tumor and three metastatic lymph node regions, which enabled us to establish the phylogenetic relationships of these lesions, which were consistent with a genetically homogeneous cancer. Subsequent analyses of 551 CTCs confirmed the genetically homogeneous cancer in three serial blood analyses. However, the AFs of ctDNA were only 2% to 3% in each analysis, neither reflecting the tumor burden nor the dynamics of this progressive disease. These results together with high-resolution plasma DNA fragment sizing suggested that differences in phagocytosis and DNA degradation mechanisms likely explain the variable occurrence of mutated DNA fragments in the blood of patients with cancer.

Conclusions
The dynamic range of ctDNA varies substantially in patients with metastatic breast cancer. This has important implications for the use of ctDNA as a predictive and prognostic biomarker.
A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD
Authors: Davidsen Peter K , Herbert John M , Antczak Philipp , Clarke Kim , Ferrer Elisabet , Peinado Victor I , Gonzalez Constancio , Roca Josep , Egginton Stuart , Barberá Joan A , Falciani Francesco 
Published: August 2014

Abstract
Background
A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology.
Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting.

Methods
We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting.

Results
We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle.

Conclusions
We conclude that CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis.