bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of early breast cancer patient survival using ensembles of hypoxia signatures
Authors: Gong Inna Y. , Fox Natalie S. , Boutros Paul C. 
Published: August 2017

AbstractBackgroundBiomarkers are a key component of precision medicine. However, full clinical integration of biomarkers has been met with challenges, partly attributed to analytical difficulties. It has been shown that biomarker reproducibility is susceptible to data preprocessing approaches. Here, we systematically evaluated machine-learning ensembles of preprocessing methods as a general strategy to improve biomarker performance for prediction of survival from early breast cancer.ResultsWe risk stratified breast cancer patients into either low-risk or high-risk groups based on four published hypoxia signatures (Buffa, Winter, Hu, and Sorensen), using 24 different preprocessing approaches for microarray normalization. The 24 binary risk profiles determined for each hypoxia signature were combined using a random forest to evaluate the efficacy of a preprocessing ensemble classifier. We demonstrate that the best way of merging preprocessing methods varies from signature to signature, and that there is likely no ‘best’ preprocessing pipeline that is universal across datasets, highlighting the need to evaluate ensembles of preprocessing algorithms. Further, we developed novel signatures for each preprocessing method and the risk classifications from each were incorporated in a meta-random forest model. Interestingly, the classification of these biomarkers and its ensemble show striking consistency, demonstrating that similar intrinsic biological information are being faithfully represented. As such, these classification patterns further confirm that there is a subset of patients whose prognosis is consistently challenging to predict.ConclusionsPerformance of different prognostic signatures varies with pre-processing method. A simple classifier by unanimous voting of classifications is a reliable way of improving on single preprocessing methods. Future signatures will likely require integration of intrinsic and extrinsic clinico-pathological variables to better predict disease-related outcomes.AbbreviationsAUCarea under the receiver operating characteristic curveGCRMAGeneChip Robust Multi-array AverageHG-U133AAffymetrix Human Genome U133AHG-U133 Plus 2.0Affymetrix Human Genome Plus 2.0HRhazard ratioMAS5MicroArray Suite 5.0MBEIModel-base Expression IndexNSCLCNon-small cell lung cancerRFRandom forestROCreceiver operator characteristicRMARobust Multi-array Average
Patterns of structural variation in human cancer
Authors: Li Yilong , Roberts Nicola D , Weischenfeldt Joachim , Wala Jeremiah A , Shapira Ofer , Schumacher Steven E. , Khurana Ekta , Korbel Jan , Imielinski Marcin , Beroukhim Rameen , Campbell Peter J ,   on behalf of the PCAWG-Structural Variation Working Group,   and the PCAWG Network
Published: August 2017

ABSTRACTA key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments ranging in size from kilobases to whole chromosomes. We developed methods to group, classify and describe structural variants, applied to >2,500 cancer genomes. Nine signatures of structural variation emerged. Deletions have trimodal size distribution; assort unevenly across tumour types and patients; enrich in late-replicating regions; and correlate with inversions. Tandem duplications also have trimodal size distribution, but enrich in early-replicating regions, as do unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy number gains and frequent inverted rearrangements. One prominent structure consists of 1-7 templates copied from distinct regions of the genome strung together within one locus. Such ‘cycles of templated insertions’ correlate with tandem duplications, frequently activating the telomerase gene,TERT,in liver cancer. Cancers access many rearrangement processes, flexibly sculpting the genome to maximise oncogenic potential.
A “Tug of War” maintains a dynamic protein-membrane complex as shown in all-atom simulations of C-Raf RBD-CRD bound to K-Ras4B at an anionic membrane
Authors: Li Zhen-Lu , Prakash Priyanka , Buck Matthias 
Published: August 2017

AbstractAssociation of Raf kinase with activated Ras triggers downstream signaling cascades, towards regulating transcription in the cells’ nucleus. Dysregulation of Ras: Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD and K-Ras4B- membrane interactions. This competition arises because the interaction between the RBD and K-Ras is strong and the linker between the RBD and CRD is short. This study reveals a mechanism that maintains a modest binding for the overall complex at the membrane to facilitate fast signaling processes. It is likely a common mechanism for other multi-protein, if not multidomain proteins at membranes.
Novel application of explicit dynamics occupancy models to ongoing aquatic invasions
Authors: Sepulveda Adam J. 
Published: August 2017

Abstract

Identification of suitable habitats, where invasive species can establish, is an important step towards controlling their spread. Accurate identification is difficult for new or slow invaders because unoccupied habitats may be suitable, given enough time for dispersal, while occupied habitats may prove to be unsuitable for establishment.

To identify the suitable habitat of a recent invader, I used an explicit dynamics occupancy modelling framework to evaluate habitat covariates related to successful and failed establishments of American Bullfrogs (Lithobates catesbeianus) within the Yellowstone River floodplain of Montana, USA, from 2012 to 2016.

During this 5‐year period, bullfrogs failed to establish at most sites they colonized. Bullfrog establishment was most likely to occur and least likely to fail at sites closest to human‐modified ponds and lakes and those with emergent vegetation. These habitat covariates were generally associated with the presence of permanent water.

Suitable habitat for bullfrog establishment is abundant in the Yellowstone River floodplain, although many sites with suitable habitat remain uncolonized. Thus, the maximum distribution of bullfrogs is much greater than their current distribution.

Synthesis and applications. Focused control efforts on habitats with or proximate to permanent waters are most likely to reduce the potential for invasive bullfrog establishment and spread in the Yellowstone River. The novel application of explicit dynamics occupancy models is a useful and widely applicable tool for guiding management efforts towards those habitats where new or slow invaders are most likely to establish and persist.
Alcohol‐related presentations to the Royal Perth Hospital Emergency Department: A prospective study
Authors: McLay Stuart VB , MacDonald Ellen , Fatovich Daniel M ,   on behalf of the Alcohol Harm in Emergency Departments (AHED) Investigators
Published: August 2017

AbstractObjectiveTo quantify and describe alcohol‐related presentations to our ED, as part of the binational Alcohol Harm in Emergency Departments study.MethodsA prospective observational study at Royal Perth Hospital of every patient attending ED for the 168‐h period commencing 08.00 hours Monday 1 December 2014. Patient presentations were classified as alcohol‐related (alcohol‐positive) using predefined criteria. These patients were compared to alcohol‐negative patients on a range of demographic and clinical descriptors.ResultsTwo hundred and thirteen (15.2%) of 1403 patients screened were alcohol‐positive. Compared with alcohol‐negative patients, alcohol‐positive patients were more likely to be male (148/213, 69.5% vs 636/1190, 53.4%, P < 0.001) and younger (mean 38 years vs 48 years, P < 0.001). They were more likely to arrive in police custody (OR 3.7, 95% CI 1.3–9.5, P = 0.005), and be admitted to the State Adult Major Trauma Unit (OR 4.2, 95% CI 2.1–8.3, P < 0.001). Forty‐two (19.7%) of 213 patients had injuries suspected to be caused by an alcohol‐affected third party. The ED length of stay and admission rate were not significantly different between the groups.Conclusions15.2% of patient presentations over the study week were alcohol‐related. These patients were more likely to present with injury; one in five having injuries suspected to be caused by a third party affected by alcohol. This is a significant public health problem.
Ventilatory choices for intubated patients during helicopter stretcher winching
Authors: Hollott John 
Published: August 2017

AbstractIntroductionThe winching of intubated patients on a stretcher into a helicopter is a rare event. Intermittent positive pressure ventilation is mandatory, which can either be performed manually with a self‐inflating bag, or automatically using a portable ventilator. Theoretically automatic ventilation would provide improved oxygenation, more stable arterial carbon dioxide levels and a reduced risk of airway disconnection. Furthermore, the stretcher attendant may better perform winching procedures with higher situational awareness, contributing to crew and patient safety. However ventilator failure, and the diagnosis and management of such, is of concern.ObjectiveThe aim of this study is to compare automatic against manual ventilation during intubated helicopter stretcher winching.MethodThe trial had two phases. Initially a static winch on a hoist simulator was performed, followed by live winching into a helicopter. All stretcher attendants performed two winches with an intubated manikin. During one winch, the manikin was manually ventilated, and an automatic ventilator was used for the other. Airway pressures were measured.ResultsAutomatic ventilation did not fail. Compared with automatic ventilation, manual ventilation displayed significant pauses, inconsistent rates and both high and low airway pressures. Automatic ventilation permitted better situational awareness and performance in winching manoeuvres. One airway disconnection occurred during manual ventilation.ConclusionsDuring helicopter winching, automatic ventilation is superior in providing controlled, consistent and reliable ventilation for intubated patients. The stretcher attendant is also able to provide more attention to the winching manoeuvres with subsequent safety gains. The risk of automatic ventilator failure is low.
Water Quality Signals from Rural Land Use and Exurbanization in a Mountain Landscape: What's Clear and What's Confounded?
Authors: Jackson C. Rhett , Bahn Robert A. , Webster Jackson R. 
Published: August 2017

AbstractIn mountainous landscapes with high climatic and geomorphic variability, how do rural land uses and exurbanization alter hydrology and water quality? We evaluated effects of rural land use and exurbanization on streamflows, suspended sediment concentrations and loads, specific conductance, and summer water temperatures in 12 streams and rivers within the Upper Little Tennessee River basin in the southern Appalachian Mountains. Eleven streams featured low levels of development (>61% forest cover) but differed in land use patterning, basin size, annual precipitation, and watershed morphology. One urban stream, located within the largest town in the basin, provided the high development comparative endpoint. Even low levels of rural development and exurbanization were associated with substantial increases in suspended sediment concentrations, sediment loads, and summer stream temperature daily maxima and diurnal variation. Observed summer temperature increases were much larger than would be expected due to global climate change over the next century. Specific conductance was idiosyncratic among the smaller streams. These water quality changes were not accompanied by streamflow changes that were discernible amid the high natural variation in precipitation and geomorphology. The water quality findings suggest the need for applying the best management practices, including riparian buffers, to even low levels of rural development.
Mannequin‐based Telesimulation: Increasing Access to Simulation‐based Education
Authors: Hayden Emily M. , Khatri Avni , Kelly Hillary R. , Yager Phoebe H. , Salazar Gloria M. 
Published: August 2017

AbstractA telesimulation platform utilizes communications technology to provide mannequin‐based simulation education between learners and instructors located remotely from one another. Specifically, the instructor controls the mannequin and moderates the debriefing remotely. During these sessions, the instructor observes the learners in real time and provides immediate feedback during the debriefing. This platform obviates the need to have instructors, learners, and mannequins in the same place at the same time, potentially allowing simulation‐based educational sessions to occur with greater frequency for institutions not located proximate to formal simulation centers. Additionally, the telesimulation platform enables an experienced simulation instructor to observe and directly help new simulation instructors at remote simulation locations. Readily available Web‐conferencing, screen‐sharing software, microphones, and webcams makes telesimulation possible. Mannequin‐based telesimulation is relatively new and not well represented in the literature, but could facilitate systems changes, providing educational experiences to health care professionals in locations not currently benefiting from mannequin‐based simulation opportunities. Several research questions need to be addressed in future studies to better develop this educational approach, including technical feasibility, logistic issues, a comparison of telesimulation to other simulation approaches, and assessing limitations of the telesimulation platform.
“What Do People Do If They Don't Have Insurance?”: ED‐to‐ED Referrals
Authors: Medford‐Davis Laura N. , Prasad Siddharth , Rhodes Karin V. 
Published: August 2017

AbstractObjectiveUp to 20% of patients seen in public emergency departments (EDs) have already been seen for the same complaint at another ED, but little is known about the origin or impact of these duplicate ED visits. The goals of this investigation were to explore 1) whether patients making a repeat ED visit are self‐referred or indirectly referred from the other ED and 2) gather the perspective of affected patients on the health, social, and financial consequences of these duplicate ED visits.MethodsThis mixed‐methods study conducted over a 10‐week period during 2016 in a large public hospital ED in Texas prospectively surveyed patients seen in another ED for the same chief complaint. Selected patients presenting with fractures were then enrolled for semistructured qualitative interviews, which were audiotaped, transcribed, and independently coded by two team members until thematic saturation was reached.ResultsA total of 143 patients were identified as being recently seen at another local ED for the same chief complaint prior to presenting to the public hospital; 94% were uninsured and 61% presented with fractures. A total of 27% required admission at the public ED and 95% of those discharged required further outpatient follow‐up. Fifty‐one percent of patients completed a survey and qualitative interviews were conducted with 23 fracture patients. Fifty‐three percent of patients reported that staff at the first hospital told them to go the public hospital ED, and 23% reported referral from a follow‐up physician associated with the first hospital. Seventy‐three percent reported receiving the same tests at both EDs. Interview themes identified multiple health care visits for the same injury, concern about complications, disrespectful treatment at the first ED, delayed care, problems accessing needed follow‐up care without insurance, loss of work, and financial strain.ConclusionsThe majority of patients presenting to a public hospital ED after treatment for the same complaint in another local ED were indirectly referred to the public ED without transferring paperwork or records, incurring duplicate testing and patient anxiety.
Association between the antioxidant uric acid and depression and antidepressant medication use in 96 989 individuals
Authors: Wium‐Andersen M. K. , Kobylecki C. J. , Afzal S. , Nordestgaard B. G. 
Published: August 2017

ObjectiveIn the last decade, several studies have suggested that depression is accompanied by increased oxidative stress and decreased antioxidant defenses. We tested the hypothesis that high levels of the antioxidant uric acid are associated with lower risk of hospitalization with depression and use of prescription antidepressant medication.MethodWe examined plasma levels of the antioxidant uric acid in 96 989 individuals from two independent cohort studies. Logistic regression and Cox proportional hazards regression models were multivariable adjusted for age, gender, alcohol, smoking, income, body mass index, C‐reactive protein, hemoglobin, triglycerides, cardiovascular disease, diabetes, and intake of meat and vegetables. Results were performed separately in each study and combined in a meta‐analysis.ResultsIn both studies, high uric acid was associated with lower risk of hospitalization as in‐patient or out‐patient with depression and antidepressant medication use. A doubling in uric acid was associated with an effect estimate of 0.57 (95% CI 0.49–0.65) and 0.77 (0.73–0.81) for hospitalization with depression and antidepressant medication use. The association was consistent across strata of all covariates. Results were attenuated in Cox regression analyses with less statistical power.ConclusionHigh plasma levels of uric acid were associated with low risk of depression hospitalization and antidepressant medication use.
Attraction of red turpentine beetle and otherScolytinae to ethanol, 3‐carene or ethanol + 3‐carene in anOregon pine forest
Authors: Kelsey Rick G. , Westlind Douglas J. 
Published: August 2017

AbstractRed turpentine beetleDendroctonus valensLeConte is a non‐aggressive bark beetle inNorthAmerica that attacks weakened or recently dead pines, as well as their fresh logs or stumps. Fire‐injured ponderosa pines releasing stress‐induced ethanol are often attacked. The oleoresin from these trees frequently contains 3‐carene as a major component mixed with α‐ or β‐pinene. 3‐Carene lures usually attract moreD. valensthan α‐ or β‐pinene lures or 1 : 1 : 1 mixtures, whereas the attraction of ethanol + 3‐carene lures has never been tested.Funnel traps with ethanol, 3‐carene or ethanol + 3‐carene lures, and a no lure blank, were set‐up as a randomized complete block design in a pine forest nearLaPine,Oregon,U.S.A.,from 23April until 11June 2015.Dendroctonus valens,Hylastes nigrinus,Hylurgops reticulatus,Hylurgops porosusandHylastes gracilisexhibited similar responses, with highest numbers captured in traps with ethanol + 3‐carene. The response by the first three species was confirmed as synergistic.Ipsspp.,Pityogenesspp.,Gnathotrichusspp.,Pachysquamus subcostulatusandHylastes macercomposed a second group whose numbers captured with ethanol lures were similar or greater than the 3‐carene or ethanol + 3‐carene lures. A reducedH. macerresponse to ethanol + 3‐carene was confirmed as an interruption.
Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first‐trimester trophoblast cells
Authors: Smith Arianna , Witte Elizabeth , McGee Devin , Knott Jason , Narang Kavita , Racicot Karen 
Published: August 2017

ProblemHeightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes.Methods of StudyStudies were performed using the first‐trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5‐azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan‐acetyl histone‐3 antibody. Invasion assays used Matrigel chambers.ResultsCortisol inhibited expression of CSF2 (GM‐CSF) and CSF3 (G‐CSF) in trophoblast cells. Cortisol‐associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs.ConclusionIn first‐trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol‐associated changes in trophoblast function could increase the risk for immune‐mediated abortion or other adverse pregnancy outcomes.
Source‐to‐sink analysis in an active extensional setting: Holocene erosion and deposition in the Sperchios rift, central Greece
Authors: Pechlivanidou Sofia , Cowie Patience A. , Hannisdal Bjarte , Whittaker Alexander C. , Gawthorpe Robert L. , Pennos Christos , Riiser Ole S. 
Published: August 2017

AbstractWe present a source‐to‐sink analysis to explain sediment supply variations and depositional patterns over the Holocene within an active rift setting. We integrate a range of modelling approaches and data types with field observations from the Sperchios rift basin, Central Greece that allow us to analyse and quantify (1) the size and characteristics of sediment source areas, (2) the dynamics of the sediment routing system from upstream fluvial processes to downstream deposition at the coastline, and (3) the depositional architecture and volumes of the Holocene basin fill. We demonstrate that the Sperchios rift comprises a ‘closed’ system over the Holocene and that erosional and depositional volumes are thus balanced. Furthermore, we evaluate key controls in the development of this source‐to‐sink system, including the role of pre‐existing topography, bedrock erodibility and lateral variations in the rate of tectonic uplift/subsidence. We show that tectonic subsidence alone can explain the observed grain size fining along the rift axis resulting in the downstream transition from a braided channel to an extensive meander belt (>15 km long) that feeds the fine‐grained Sperchios delta. Additionally, we quantify the ratios of sediment storage to bypass for the two main footwall‐sourced alluvial fan systems and relate the fan characteristics to the pattern and rates of fault slip. Finally, we show that ≥40% of the sediment that builds the Sperchios delta is supplied by ≤22% of the entire source area and that this can be primarily attributed to a longer‐term (~106 years) transient landscape response to fault segment linkage. Our multidisciplinary approach allows us to quantify the relative importance of multiple factors that control a complex source‐to‐sink system and thus improve our understanding of landscape evolution and stratigraphic development in active extensional tectonic settings.