bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐200c/Bmi1 axis and epithelial–mesenchymal transition contribute to acquired resistance to BRAF inhibitor treatment
Authors: Liu Shujing , Tetzlaff Michael T. , Wang Tao , Yang Ruifeng , Xie Lin , Zhang Gao , Krepler Clemens , Xiao Min , Beqiri Marilda , Xu Wei , Karakousis Giorgos , Schuchter Lynn , Amaravadi Ravi K. , Xu Weiting , Wei Zhi , Herlyn Meenhard , Yao Yuan , Zhang Litao , Wang Yingjie , Zhang Lin , Xu Xiaowei 
Published: April 2015

SummaryResistance to BRAF inhibitors (BRAFi) is one of the major challenges for targeted therapies for BRAF‐mutant melanomas. However, little is known about the role of microRNAs in conferring BRAFi resistance. Herein, we demonstrate that miR‐200c expression is significantly reduced whereas miR‐200c target genes including Bmi1, Zeb2, Tubb3, ABCG5, and MDR1 are significantly increased in melanomas that acquired BRAFi resistance compared to pretreatment tumor biopsies. Similar changes were observed in BRAFi‐resistant melanoma cell lines. Overexpression of miR‐200c or knock‐down of Bmi1 in resistant melanoma cells restores their sensitivities to BRAFi, leading to deactivation of the PI3K/AKT and MAPK signaling cascades, and acquisition of epithelial–mesenchymal transition‐like phenotypes, including upregulation of E‐cadherin, downregulation of N‐cadherin, and ABCG5 and MDR1 expression. Conversely, knock‐down of miR‐200c or overexpression of Bmi1 in BRAFi‐sensitive melanoma cells activates the PI3K/AKT and MAPK pathways, upregulates N‐cadherin, ABCG5, and MDR1 expression, and downregulates E‐cadherin expression, leading to BRAFi resistance. Together, our data identify miR‐200c as a critical signaling node in BRAFi‐resistant melanomas impacting the MAPK and PI3K/AKT pathways, suggesting miR‐200c as a potential therapeutic target for overcoming acquired BRAFi resistance.
Comparison of tuberculin skin test and QuantiFERON®‐TB Gold In‐Tube for the diagnosis of childhood tuberculosis
Authors: Uzunhan Ozan , Törün Selda Hançerli , Somer Ayper , Salman Nuran , Köksalan Kaya 
Published: April 2015

AbstractBackgroundTuberculosis (TB) is an important worldwide ongoing health issue. To be able to control TB, one should not only cure active TB but also identify childhood TB patients who have the possibility to develop active disease in the future. The aim of this study was to compare a century‐old tuberculin skin test (TST) and QuantiFERON‐TB Gold In‐Tube (QFT‐GIT) test, developed as an alternative to TST and which has been claimed to be superior to TST in several ways, in the diagnosis of childhood TB.MethodsFifty‐three children with TB between 5 months and 17.5 years of age and 92 healthy children from the same age group with no risk factors for TB were recruited into the study. All children underwent TST and QFT‐GIT test and their demographic, clinic and laboratory data were recorded. Data were analyzed using SPSS 14.ResultsA total of 53 patients were diagnosed with TB. Mean patient age was 8.5 ± 4.3 years (range, 5 months–17.5 years). A total of 41.7% of the patients were female. Sixteen of 53 patients had confirmation on culture. QFT‐GIT test was positive in 16 and TST was positive in 15 among 16 children with culture‐confirmed TB. The sensitivity of TST and QFT‐GIT were 93.8% and 100.0%, and the specificity of TST and QFT‐GIT were 100.0% and 97.8%, respectively. With regard to the 53 TB children including those without bacteriological confirmation, QFT‐GIT was positive in 33 children, and TST was positive in 44 children. The sensitivity of TST and QFT‐GIT was then 83.0% and 62.3%, and the specificity, 100.0% and 97.8%, respectively.ConclusionAlthough positive QFT‐GIT test is very significant for TB, negative results will not exclude TB infection. TST and QFT‐GIT used together may provide more efficient results.
HRCT of fibrosing lung disease
Authors: Jacob Joseph , Hansell David M. 
Published: April 2015

AbstractThe use of high‐resolution computed tomography (HRCT) has brought increased diagnostic discrimination to the evaluation of lung disease, particularly fibrosing lung diseases. Once the presence of a predominantly fibrosing lung disease has been established on evaluation of a HRCT, a stepwise approach is proposed that can refine the potential HRCT diagnoses from a list of over 100 different interstitial lung diseases to one of only five fibrosing lung diseases. Within the category of the fibrosing lung diseases, the recognition of idiopathic pulmonary fibrosis (IPF) is key. IPF is the most prevalent idiopathic interstitial pneumonia and has a mortality greater than any of the other diffuse lung diseases. Several diagnostic dilemmas are explored including challenges with the recent IPF diagnosis and management guidelines (2011), as well as with the ‘difficult to characterize’ fibrosing diseases such as smoking‐related lung fibrosis, unclassifiable disease and acute exacerbations of fibrosing lung disease.
Externalities of National Pharmaceutical Policy when Markets are Integrated through Parallel Trade
Authors: Birg Laura 
Published: April 2015

AbstractThis paper studies externalities of nationally determined cost‐sharing systems, in particular coinsurance rates, under pharmaceutical parallel trade in a two‐country model with a vertical distributor relationship. Parallel trade generates a price‐decreasing competition effect in the destination country of the parallel import and a price‐increasing double marginalization effect in the source country. An increase of the coinsurance rate in the destination country mitigates the double marginalization effect in the source country. An increase of the coinsurance rate in the source country reinforces the competition effect in the destination country. This may be a case for policy coordination in the European Union.
Nationalism and Linguistic Purism in ContemporaryJapan: National Sentiment Expressed through Public Attitudes towards Foreignisms
Authors: Hosokawa Naoko 
Published: April 2015

AbstractLinguistic purism is a term that refers to the urge to preserve a ‘desirable’ language form while eliminating ‘undesirable’ linguistic elements – a drive profoundly intertwined with nationalism. A particularly salient manifestation of this phenomenon is the controversy on the use of foreign loanwords. This article examines the contrasting expressions and metaphors used to describe the national language and foreignisms found in newspaper articles published in contemporaryJapan and argues that the growing tendency to discuss national language in contrast to foreignisms can be understood as a particular manifestation of ongoing (re)negotiation of national identity. Criticisms and praises of the use of loanwords are found to be grounded upon a desire to establish specific understandings of Japaneseness in reference to the otherness felt within a society that is symbolized by loanwords, constructing an ‘internal Other’ to a Japanese ‘Self’, the identity of which is neither autonomous nor clearly delineated.
Blinded by Beauty? Physical Attractiveness and Candidate Selection in the U.S. House of Representatives
Authors: Stockemer Daniel , Praino Rodrigo 
Published: April 2015

ObjectiveIn this article we show that physical attractiveness matters as a heuristic device for uninformed voters but not for politically savvy voters.MethodsDrawing on a two‐step experiment, we first ask over 100 students to rank the physical attractiveness of candidates to the U.S. House of Representatives. Second, we create a treatment and a control group comprising each of 1,200 research different subjects. We ask the first group to indicate their vote choice by merely looking at the picture of candidates for the 2008 U.S. House of Representatives elections, while the second group has a picture and a detailed description of the political/professional competence of the contenders at their disposal.ResultsWe find that our first group of study subjects representing all those voters who are politically uninformed tend to cast their ballot for the better‐looking candidate, whereas the second group, representing politically knowledgeable individuals, choose the more competent candidate.ConclusionOur experimental study provides evidence that uninformed or politically unknowledgeable voters use political appearance as a heuristic device in casing their ballot at elections.
A resource for characterizing genome‐wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus
Authors: Liu Lijun , Ramsay Trevor , Zinkgraf Matthew , Sundell David , Street Nathaniel Robert , Filkov Vladimir , Groover Andrew 
Published: April 2015

SummaryIdentifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP‐seq) resource consisting of genome‐wide binding regions and associated putative target genes for four Populus homeodomain transcription factors expressed during secondary growth and wood formation. Software code (programs and scripts) for processing the Populus ChIP‐seq data are provided within a publically available iPlant image, including tools for ChIP‐seq data quality control and evaluation adapted from the human Encyclopedia of DNA Elements (ENCODE) project. Basic information for each transcription factor (including members of Class I KNOX, Class III HD ZIP, BEL1‐like families) binding are summarized, including the number and location of binding regions, distribution of binding regions relative to gene features, associated putative target genes, and enriched functional categories of putative target genes. These ChIP‐seq data have been integrated within the Populus Genome Integrative Explorer (PopGenIE) where they can be analyzed using a variety of web‐based tools. We present an example analysis that shows preferential binding of transcription factor ARBORKNOX1 to the nearest neighbor genes in a pre‐calculated co‐expression network module, and enrichment for meristem‐related genes within this module including multiple orthologs of Arabidopsis KNOTTED‐like Arabidopsis 2/6.
Impacts of cropping system and management practices on the assembly of weed communities
Authors: Barroso J , Miller Z J , Lehnhoff E A , Hatfield P G , Menalled F D 
Published: April 2015

SummaryUnderstanding how weed communities assemble as a function of biotic and abiotic filters and transform through time has important implications for the sustainable management of agronomic systems. In a three‐year study, we evaluated weed community responses to lucerne (Medicago sativa, perennial) vs. continuous spring wheat (Triticum aestivum, annual, CSW) and weed management practices where weeds in the CSW system were managed with three contrasting approaches (herbicide, tillage or sheep grazing). Our results indicated no differences in weed diversity between the perennial and annual crops or across the different management practices in CSW. However, there were differences in weed community composition. Lucerne, with the exception of the establishing year, impeded the growth and reproduction of several annual weeds, including Amaranthus retroflexus, Thlaspi arvense, Lamium amplexicaule and Chenopodium album, but favoured perennial broad‐leaved weeds such as Taraxacum officinale and Cirsium arvense. The replacement of herbicide treatments in pre‐plant and post‐harvest in CSW with soil tillage or sheep grazing selected for different weed communities beyond the second year of establishment. The weed species driving the differences in CSW systems were Androsace occidentalis, more common in CSW managed chemically; Asperugo procumbens, more common in CSW managed with tillage; and T. officinale and Lactuca serriola, more common in CSW managed with sheep grazing. Understanding how cropping systems modify weed communities is a necessary step to shift from reactive weed control programmes to predictive management strategies.
Burden of ocular and visual disorders among pupils in special schools in Nepal
Authors: Puri Sudan , Bhattarai Dipesh , Adhikari Prakash , Shrestha Jyoti Baba , Paudel Nabin 
Published: April 2015

ObjectivesTo determine detailed oculo-visual characteristics of children with intellectual disability studying in special schools and explore the burden of visual impairment.Design of the studyDetailed ophthalmic examination was carried out in all pupils studying at the seven special needs schools of Kathmandu valley, Nepal. Ophthalmic examination included case history, presenting distance visual acuity, cycloplegic refraction, binocular vision examination, contrast sensitivity and anterior and posterior segment evaluation.Main outcome measuresOcular and visual status of children.ResultsRefractive errors (40%) and strabismus (17%) were the commonest visual disorders in our study children. Ninety-five per cent of the children who had clinically significant refractive errors presented without any correction. Visual impairment was present in 25% of the children. Severe visual impairment or worse was present in 3% of the children. Other common ocular findings were conjunctivitis, blepharitis, chalazion and ectropion.ConclusionsHigh prevalence of preventable visual impairment in this population requires immediate attention. It is hoped that the formulation of proper vision care guidelines at a national level may help in early detection and management of visual disorders in this special population and enhance their quality of life.
First medical contact in patients with STEMI and its impact on time to diagnosis; an explorative cross-sectional study
Authors: Thylén Ingela , Ericsson Maria , Hellström Ängerud Karin , Isaksson Rose-Marie , Sederholm Lawesson Sofia 
Published: April 2015

ObjectiveIt is unknown into what extent patients with ST-elevation myocardial infarction (STEMI) utilise a joint service number (Swedish Healthcare Direct, SHD) as first medical contact (FMC) instead of Emergency Medical Services (EMS) and how this impact time to diagnosis. We aimed to (1) describe patients’ FMC; (2) find explanatory factors influencing their FMC (ie, EMS and SHD) and (3) explore the time interval from symptom onset to diagnosis.SettingMulticentred study, Sweden.MethodsCross-sectional, enrolling patients with consecutive STEMI admitted within 24 h from admission.ResultsWe included 109 women and 336 men (mean age 66±11 years). Although 83% arrived by ambulance to the hospital, just half of the patients (51%) called EMS as their FMC. Other utilised SHD (21%), contacted their primary healthcare centre (14%), or went directly to the emergency room (14%). Reasons for not contacting EMS were predominantly; (1) my transport mode was faster (40%), (2) did not consider myself sick enough (30%), and (3) it was easier to be driven or taking a taxi (25%). Predictors associated with contacting SHD as FMC were female gender (OR 1.92), higher education (OR 2.40), history of diabetes (OR 2.10), pain in throat/neck (OR 2.24) and pain intensity (OR 0.85). Predictors associated with contacting EMS as FMC were history of MI (OR 2.18), atrial fibrillation (OR 3.81), abdominal pain (OR 0.35) and believing the symptoms originating from the heart (OR 1.60). Symptom onset to diagnosis time was significantly longer when turning to the SHD instead of the EMS as FMC (1:59 vs 1:21 h, p<0.001).ConclusionsUsing other forms of contacts than EMS, significantly prolong delay times, and could adversely affect patient prognosis. Nevertheless, having the opportunity to call the SHD might also, in some instances, lower the threshold for taking contact with the healthcare system, and thus lowers the number that would otherwise have delayed even longer.
Junior doctors’ views on reporting concerns about patient safety: a qualitative study
Authors: Hooper Patricia , Kocman David , Carr Sue , Tarrant Carolyn 
Published: April 2015

ABSTRACT

Background
Enabling healthcare staff to report concerns is critical for improving patient safety. Junior doctors are one of the groups least likely to engage in incident reporting. This matters both for the present and for the future, as many will eventually be in leadership positions. Little is known about junior doctors’ attitudes towards formally reporting concerns.

Aims
To explore the attitudes and barriers to junior doctors formally reporting concerns about patient safety to the organisations in which they are training.

Methods
A qualitative study comprising three focus groups with 10 junior doctors at an Acute Teaching Hospital Trust in the Midlands, UK, conducted in 2013. Focus group discussions were transcribed verbatim and analysed using a thematic approach, facilitated by NVivo 10.

Results
Participants were supportive of the idea of playing a role in helping healthcare organisations become more aware of risks to patient safety, but identified that existing incident reporting systems could frustrate efforts to report concerns. They described barriers to reporting, including a lack of role modelling and senior leadership, a culture within medicine that was not conducive to reporting concerns, and a lack of feedback providing evidence that formal reporting was worthwhile. They reported a tendency to rely on informal ways of dealing with concerns as an alternative to engaging with formal reporting systems.

Conclusions
If healthcare organisations are to be able to gather and learn from intelligence about risks to patient safety from junior doctors, this will require attention to the features of reporting systems, as well as the implications of hierarchies and the wider cultural context in which junior doctors work.
Instruction-Cache Locking for Improving Embedded Systems Performance
Authors: Anand Kapil , Barua Rajeev 
Published: April 2015

Cache memories in embedded systems play an important role in reducing the execution time of applications. Various kinds of extensions have been added to cache hardware to enable software involvement in replacement decisions, improving the runtime over a purely hardware-managed cache. Novel embedded systems, such as Intel’s XScale and ARM Cortex processors, facilitate locking one or more lines in cache; this feature is called
cache locking
. We present a method in for instruction-cache locking that is able to reduce the average-case runtime of a program. We demonstrate that the optimal solution for instruction cache locking can be obtained in polynomial time. However, a fundamental lack of correlation between cache hardware and software program points renders such optimal solutions impractical.

Instead, we propose two practical heuristics-based approaches to achieve cache locking. First, we present a static mechanism for locking the cache, in which the locked contents of the cache are kept fixed over the execution of the program. Next, we present a dynamic mechanism that accounts for changing program requirements at runtime. We devise a cost--benefit model to discover the memory addresses that should be locked in the cache. We implement our scheme inside a binary rewriter, widening the applicability of our scheme to binaries compiled using any compiler.
Results obtained on a suite of MiBench benchmarks show that our static mechanism results in 20% improvement in the instruction-cache miss rate on average and up to 18% improvement in the execution time on average for applications having instruction accesses as a bottleneck, compared to no cache locking. The dynamic mechanism improves the cache miss rate by 35% on average and execution time by 32% on instruction-cache-constrained applications.
Single-Call Mechanisms
Authors: Wilkens Christopher A. , Sivan Balasubramanian 
Published: April 2015

Truthfulness is fragile and demanding. It is oftentimes harder to guarantee truthfulness when solving a problem than it is to solve the problem itself. Even worse, truthfulness can be utterly destroyed by small uncertainties in a mechanism’s outcome. One obstacle is that truthful payments depend on outcomes other than the one realized, such as the lengths of non-shortest-paths in a shortest-path auction. Single-call mechanisms are a powerful tool that circumvents this obstacle: they implicitly charge truthful payments, guaranteeing truthfulness in expectation using only the outcome realized by the mechanism. The cost of such truthfulness is a trade-off between the expected quality of the outcome and the risk of large payments.
We study two of the most general domains for truthful mechanisms and largely settle when and to what extent single-call mechanisms are possible. The first single-call construction was discovered by Babaioff et al. [2010] in single-parameter domains. They give a transformation that turns any monotone, single-parameter allocation rule into a truthful-in-expectation single-call mechanism. Our first result is a natural complement to Babaioff et al. [2010]: we give a new transformation that produces a single-call VCG mechanism from any allocation rule for which VCG payments are truthful. Second, in both the single-parameter and VCG settings, we precisely characterize the possible transformations, showing that a wide variety of transformations are possible but that all take a very simple form. Finally, we study the inherent trade-off between the expected quality of the outcome and the risk of large payments. We show that our construction and that of Babaioff et al. [2010] simultaneously optimize a variety of metrics in their respective domains.
Our study is motivated by settings where uncertainty in a mechanism renders other known techniques untruthful, and we offer a variety of examples where such uncertainty can arise. In particular, we analyze pay-per-click advertising auctions, where the truthfulness of the standard VCG-based auction is easily broken when the auctioneer’s estimated click-through-rates are imprecise.
Brain Magnetic Resonance Imaging Findings Fail to Suspect Fabry Disease in Young Patients With an Acute Cerebrovascular Event
Authors: Fazekas Franz , Enzinger Christian , Schmidt Reinhold , Grittner Ulrike , Giese Anne-Katrin , Hennerici Michael G. , Huber Roman , Jungehulsing Gerhard J. , Kaps Manfred , Kessler Christof , Martus Peter , Putaala Jukka , Ropele Stefan , Tanislav Christian , Tatlisumak Turgut , Thijs Vincent , von Sarnowski Bettina , Norrving Bo , Rolfs Arndt 
Published: April 2015

Background and Purpose—
Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD.

Methods—
The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18–55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality.

Results—

A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%;
P
<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients.

Conclusions—
Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00414583.