bluuebunny/crossref_metadata_2025_split huggingface dataset:
Casein Kinase I Isoform Hrr25 Is a Negative Regulator of Haa1 in the Weak Acid Stress Response Pathway in Saccharomyces cerevisiae
Authors: Collins Morgan E. , Black Joshua J. , Liu Zhengchang 
Published: April 2017

ABSTRACT

Haa1 is a transcription factor that adapts
Saccharomyces cerevisiae
cells to weak organic acid stresses by activating the expression of various genes. Many of these genes encode membrane proteins, such as
TPO2
and
YRO2
. How Haa1 is activated by weak acids is not clear. Here, we show that casein kinase I isoform Hrr25 is an important negative regulator of Haa1. Haa1 is known to be multiply phosphorylated. We found that mutations in
HRR25
lead to reduced Haa1 phosphorylation and increased expression of Haa1 target genes and that Hrr25 interacts with Haa1. The other three casein kinase I isoforms, Yck1, Yck2, and Yck3, do not seem to play critical roles in Haa1 regulation. Hrr25 has a 200-residue C-terminal region, including a proline- and glutamine-rich domain. Our data suggest that the C-terminal region of Hrr25 is required for normal inhibition of expression of Haa1 target genes
TPO2
and
YRO2
and is important for cell growth but is not required for cell morphogenesis. We propose that Hrr25 is an important regulator of cellular adaptation to weak acid stress by inhibiting Haa1 through phosphorylation.

IMPORTANCE
Our study has revealed the casein kinase I protein Hrr25 to be a negative regulator of Haa1, a transcription factor mediating the cellular response to stresses caused by weak acids. Many studies have focused on the target genes of Haa1 and their roles in weak acid stress responses, but little has been reported on the regulatory mechanism of Haa1. Weak acids, such as acetic acid, have long been used for food preservation by slowing down the growth of fungal species, including
S. cerevisiae
. In the biofuel industry, acetic acid in the lignocellulosic hydrolysates limits the production of ethanol, which is undesirable. By understanding how Haa1 is regulated, we can make advances in the field of food sciences to better preserve food and engineer acetic acid-resistant strains that will increase productivity in the biofuel industry.
Subduction-transition zone interaction: A review
Authors: Goes Saskia , Agrusta Roberto , van Hunen Jeroen , Garel Fanny 
Published: April 2017

AbstractAs subducting plates reach the base of the upper mantle, some appear to flatten and stagnate, while others seemingly go through unimpeded. This variable resistance to slab sinking has been proposed to affect long-term thermal and chemical mantle circulation. A review of observational constraints and dynamic models highlights that neither the increase in viscosity between upper and lower mantle (likely by a factor 20–50) nor the coincident endothermic phase transition in the main mantle silicates (with a likely Clapeyron slope of –1 to –2 MPa/K) suffice to stagnate slabs. However, together the two provide enough resistance to temporarily stagnate subducting plates, if they subduct accompanied by significant trench retreat. Older, stronger plates are more capable of inducing trench retreat, explaining why backarc spreading and flat slabs tend to be associated with old-plate subduction. Slab viscosities that are ∼2 orders of magnitude higher than background mantle (effective yield stresses of 100–300 MPa) lead to similar styles of deformation as those revealed by seismic tomography and slab earthquakes. None of the current transition-zone slabs seem to have stagnated there more than 60 m.y. Since modeled slab destabilization takes more than 100 m.y., lower-mantle entry is apparently usually triggered (e.g., by changes in plate buoyancy). Many of the complex morphologies of lower-mantle slabs can be the result of sinking and subsequent deformation of originally stagnated slabs, which can retain flat morphologies in the top of the lower mantle, fold as they sink deeper, and eventually form bulky shapes in the deep mantle.
International variations in clinical practice guidelines for palliative sedation: a systematic review
Authors: Abarshi Ebun , Rietjens Judith , Robijn Lenzo , Caraceni Augusto , Payne Sheila , Deliens Luc , Van den Block Lieve 
Published: April 2017

ObjectivesPalliative sedation is a highly debated medical practice, particularly regarding its proper use in end-of-life care. Worldwide, guidelines are used to standardise care and regulate this practice. In this review, we identify and compare national/regional clinical practice guidelines on palliative sedation against the European Association for Palliative Care (EAPC) palliative sedation Framework and assess the developmental quality of these guidelines using the Appraisal Guideline Research and Evaluation (AGREE II) instrument.MethodsUsing the PRISMA criteria, we searched multiple databases (PubMed, CancerLit, CINAHL, Cochrane Library, NHS Evidence and Google Scholar) for relevant guidelines, and selected those written in English, Dutch and Italian; published between January 2000 and March 2016.ResultsOf 264 hits, 13 guidelines—Belgium, Canada (3), Ireland, Italy, Japan, the Netherlands, Norway, Spain, Europe, and USA (2) were selected. 8 contained at least 9/10 recommendations published in the EAPC Framework; 9 recommended ‘pre-emptive discussion of the potential role of sedation in end-of-life care’; 9 recommended ‘nutrition/hydration while performing sedation’ and 8 acknowledged the need to ‘care for the medical team’. There were striking differences in terminologies used and in life expectancy preceding the practice. Selected guidelines were conceptually similar, comparing closely to the EAPC Framework recommendations, albeit with notable variations.ConclusionsBased on AGREE II, 3 guidelines achieved top scores and could therefore be recommended for use in this context. Also, domains ‘scope and purpose’ and ‘editorial independence’ ranked highest and lowest, respectively—underscoring the importance of good reportage at the developmental stage.
A middle-aged woman with a heavy heart
Authors: Van de Bruaene Cedric , Crapé Lara , Surmont Veerle 
Published: April 2017

Clinical introductionA 51-year-old woman was referred to our hospital with a 4-month history of progressive dyspnoea on exertion (New York Heart Association Functional Classification III), chest heaviness, dry cough, weight loss and tiredness. She worked as cleaning woman and had no relevant medical history, apart from an Epstein-Barr Virus (EBV) infection 2 months before symptom onset. She did not smoke and family history was negative.On examination, blood pressure was 104/80 mm Hg and heart rate was regular at 145 bpm. On auscultation, heart sounds were distant, muffled and there was no murmur. Minimal, bilateral pitting oedema was observed. Laboratory findings were unremarkable. During hospitalisation, cardiac monitoring revealed paroxysmal new-onset atrial fibrillation.Chest radiography from a previous hospital had revealed cardiomegaly and subsequent echocardiography had shown pericardial effusion with diastolic dysfunction, for which she had received percutaneous pericardiocentesis. However, repeated echocardiography at our hospital showed recurrence of pericardial effusion with diastolic dysfunction and the presence of a pericardial mass. CT and Fluorine-18-fluorodeoxyglucose PET (18F-FDG PET) scanning were done (figure 1).Figure 1| Contrast-enhanced CT scanning and 18F-FDG PET scanning. (A) CT scan, sagittal view; (B) 18F-FDG PET scan, frontal view; (C) CT scan, axial view and (D) 18F-FDG PET scan, axial view.QuestionWhich of the following is the most likely diagnosis?And based on patient history and imaging, are further diagnostics needed?Benign pericardial lipomaFibrinofibrous pericarditis following EBV infectionInflammatory pseudotumorPrimary cardiac lymphomaPrimary malignant pericardial mesothelioma
Implications of the PEGASUS-TIMI 54 trial for US clinical practice
Authors: Bradley Steven M , Hess Gregory P , Stewart Patrick , Armstrong Ehrin J , Farmer Steven A , Wasfy Jason H , Valle Javier Alfonso , Sandhu Amneet , Maddox Thomas M 
Published: April 2017

ObjectivesThis study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, to characterise their current use of P2Y12inhibitors and to explore the estimated costs and ischaemic event consequences of increasing P2Y12inhibitor use among these patients.MethodsIn the US national ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines), we identified 273 328 patients with MI and determined the proportion that would have met the eligibility criteria for the PEGASUS trial. We described longitudinal P2Y12inhibitor use among patients eligible for PEGASUS and estimated the cost and ischaemic consequences of increasing P2Y12use among eligible patients.ResultsA total of 112 222 (41.1%) patients with MI in ACTION Registry–GWTG met eligibility for the PEGASUS trial. Among 83 871 eligible patients with pharmacy claims data, 23 042 (27.5%) were on a P2Y12inhibitor at 1 year, 9661 (11.5%) at 2 years and 5246 (6.3%) at 3 years, with the majority (79.2%) of these patients on clopidogrel. The use of ticagrelor in eligible patients not yet on a P2Y12inhibitor at 1 year post-MI would cost an estimated US$885 000 per MI, stroke or cardiovascular death averted over a 3-year time horizon, while the use of clopidogrel would cost an estimated US$19 800 per ischaemic event averted.ConclusionIn contemporary clinical practice, a minority of patients are on a P2Y12inhibitor beyond 1-year post-MI. Applying PEGASUS trial findings to clinical practice would result in a large increase in P2Y12inhibitor use, with a cost per ischaemic event averted that is strongly influenced by the choice of therapy.
Tobacco retail availability and risk of relapse among smokers who make a quit attempt: a population-based cohort study
Authors: Chaiton Michael O , Mecredy Graham , Cohen Joanna 
Published: April 2017

IntroductionThe availability of tobacco is thought to influence smoking behaviour, but there are few longitudinal studies examining if the location and number of tobacco outlets has a prospective impact on smoking cessation.MethodsThe Ontario Tobacco Survey, a population-representative sample of Ontario adult smokers who were followed every 6 months for up to 3 years, was linked with tobacco outlet location data from the Ontario Ministry of Health. Proximity (distance), threshold (at least one outlet within 500 m) and density (number of outlets within 500 m) with respect to a smokers’ home were calculated among urban and suburban current smokers (n=2414). Quit attempts and risk of relapse were assessed using logistic regression and survival analysis, adjusted for neighbourhood effects and individual characteristics.ResultsIncreased density of tobacco outlets was associated with decreased odds of making a quit attempt (OR: 0.54; 95% CI 0.35 to 0.85) in high-income neighbourhoods, but not in lower income ones. There was an increased risk of relapse among those who had at least one store within 500 m (HR: 1.41 (95% CI 1.06 to 1.88). Otherwise, there was no association of proximity with quit attempts or relapse.ConclusionsThe existence of a tobacco retail outlet within walking distance from home was associated with difficulty in succeeding in a quit attempt, while the increased density of stores was associated with decreased attempts in higher income neighbourhoods. The availability of tobacco may influence tobacco use through multiple mechanisms.
Recruiting and retaining youth and young adults: challenges and opportunities in survey research for tobacco control
Authors: Cantrell Jennifer , Hair Elizabeth C , Smith Alexandria , Bennett Morgane , Rath Jessica Miller , Thomas Randall K , Fahimi Mansour , Dennis J Michael , Vallone Donna 
Published: April 2017

IntroductionEvaluation studies of population-based tobacco control interventions often rely on large-scale survey data from numerous respondents across many geographic areas to provide evidence of their effectiveness. Significant challenges for survey research have emerged with the evolving communications landscape, particularly for surveying hard-to-reach populations such as youth and young adults. This study combines the comprehensive coverage of an address-based sampling (ABS) frame with the timeliness of online data collection to develop a nationally representative longitudinal cohort of young people aged 15-21.MethodsWe constructed an ABS frame, partially supplemented with auxiliary data, to recruit this hard-to-reach sample. Branded and tested mail-based recruitment materials were designed to bring respondents online for screening, consent and surveying. Once enrolled, respondents completed online surveys every 6 months via computer, tablet or smartphone. Numerous strategies were utilized to enhance retention and representativenessResultsResults detail sample performance, representativeness and retention rates as well as device utilization trends for survey completion among youth and young adult respondents. Panel development efforts resulted in a large, nationally representative sample with high retention rates.ConclusionsThis study is among the first to employ this hybrid ABS-to-online methodology to recruit and retain youth and young adults in a probability-based online cohort panel. The approach is particularly valuable for conducting research among younger populations as it capitalizes on their increasing access to and comfort with digital communication. We discuss challenges and opportunities of panel recruitment and retention methods in an effort to provide valuable information for tobacco control researchers seeking to obtain representative, population-based samples of youth and young adults in the U.S. as well as across the globe.
Genomic Instability in Cancer: Teetering on the Limit of Tolerance
Authors: Andor Noemi , Maley Carlo C. , Ji Hanlee P. 
Published: April 2017

Abstract
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold. This has been observed in clonal subpopulations of larger size, especially when genomic instability is shared among a limited number of clones. We hypothesize that cancers with extreme levels of genomic instability may be teetering on the brink of a threshold where so much of their genome is adversely altered that cells rarely replicate successfully. Another possibility is that tumors with high levels of genomic instability are more immunogenic than other cancers with a less extensive burden of genetic aberrations. Regardless of the exact mechanism, but hinging on our ability to quantify how a tumor's burden of genetic aberrations is distributed among coexisting clones, genomic instability has important therapeutic implications. Herein, we explore the possibility that a high genomic instability could be the basis for a tumor's sensitivity to DNA-damaging therapies. We primarily focus on studies of epithelial-derived solid tumors. Cancer Res; 77(9); 2179–85. ©2017 AACR.
Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign on Susceptibility-Weighted Magnetic Resonance Imaging
Authors: Kang Dong-Wan , Jeong Han-Gil , Kim Do Yeon , Yang Wookjin , Lee Seung-Hoon 
Published: April 2017

Background and Purpose—
The susceptibility vessel sign (SVS) is a hypointense signal visualized because of the susceptibility effect of thrombi, sensitively detected on susceptibility-weighted magnetic resonance imaging. The relationship of SVS parameters with the stroke subtype and recanalization status after endovascular treatment remains uncertain.

Methods—
The data from 89 patients with acute stroke caused by anterior circulation infarcts who underwent susceptibility-weighted magnetic resonance imaging before endovascular treatment were examined. Independent reviewers, blinded to the stroke subtype and recanalization status, measured the SVS diameter, length, and estimated volume. The intra- and interrater agreements of the SVS parameters were assessed.

Results—

The SVS was identified in 78% of the patients. SVS was more commonly associated with cardioembolism than with noncardioembolism (
P
=0.01). The SVS diameter (
P
<0.01) and length (
P
=0.01) were larger in the cardioembolism group. The SVS diameter was larger in the recanalization group (thrombolysis in cerebral infarction ≥2b) than in the nonrecanalization group (
P
=0.04). Multivariable analysis revealed that the SVS diameter was an independent predictor of cardioembolism (adjusted odds ratio, 1.97; 95% confidence interval, 1.34–2.90;
P
<0.01). There was no significant association between the SVS volume and the recanalization status (adjusted odds ratio, 1.003; 95% confidence interval, 0.999–1.006;
P
=0.12). The optimal cutoff value of the SVS diameter for the cardioembolism was 5.5 mm (sensitivity, 45.6%; specificity, 93.8%).

Conclusions—
Increased SVS diameter on susceptibility-weighted magnetic resonance imaging may predict cardioembolism. No clear association was found between SVS volume and endovascular recanalization.
Biological considerations of plasma-derived and recombinant factor VIII immunogenicity
Authors: Lai Jesse , Hough Christine , Tarrant Julie , Lillicrap David 
Published: April 2017

AbstractIn hemophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the formation of FVIII neutralizing antibodies, also known as inhibitors, in 25% to 30% of patients. This adverse event is associated with a significant increase in morbidity and economic burden, thus highlighting the need to identify methods to limit FVIII immunogenicity. Inhibitor development is regulated by a complex balance of genetic factors, such as FVIII genotype, and environmental variables, such as coexistent inflammation. One of the hypothesized risk factors of inhibitor development is the source of the FVIII concentrate, which could be either recombinant or plasma derived. Differential immunogenicity of these concentrates has been documented in several recent epidemiologic studies, thus generating significant debate within the hemophilia treatment community. To date, these discussions have been unable to reach a consensus regarding how these outcomes might be integrated into enhancing clinical care. Moreover, the biological mechanistic explanations for the observed differences are poorly understood. In this article, we complement the existing epidemiologic investigations with an overview of the range of possible biochemical and immunologic mechanisms that may contribute to the different immune outcomes observed with plasma-derived and recombinant FVIII products.
The impact of HLA matching on outcomes of unmanipulated haploidentical HSCT is modulated by GVHD prophylaxis
Authors: Lorentino Francesca , Labopin Myriam , Fleischhauer Katharina , Ciceri Fabio , Mueller Carlheinz R. , Ruggeri Annalisa , Shimoni Avichai , Bornhäuser Martin , Bacigalupo Andrea , Gülbas Zafer , Koc Yener , Arcese William , Bruno Benedetto , Tischer Johanna , Blaise Didier , Messina Giuseppe , Beelen Dietrich W. , Nagler Arnon , Mohty Mohamad 
Published: April 2017

Key PointsIn unmanipulated haplo-HSCT, antigenic HLA-DRB1 match, stem cell source, conditioning, and donor sex are associated with GVHD. The role of HLA-matching status and other factors influencing alloreactivity is more prominent with PTCy compared to ATG GVHD prophylaxis.
Subsurface fluid flow focused by buried volcanoes in sedimentary basins: Evidence from 3D seismic data, Bass Basin, offshore southeastern Australia
Authors: Holford Simon P. , Schofield Nick , Reynolds Peter 
Published: April 2017

There is growing evidence that intrusive magmatic bodies such as sills and dikes can influence the migration of fluids in the deep subsurface. This influence is largely due to permeability contrasts with surrounding sedimentary rocks or because of interconnected open fractures within and around intrusions acting as conduits for migrating fluids. The role of buried volcanoes in influencing crossstratal fluid migration in sedimentary basins is less well-established. However, several studies have highlighted spatial linkages between extinct hydrothermal vent complexes and fluid seepage, suggesting that buried extrusive features can also influence subsurface fluid-flow pathways, potentially leading to migration of hydrocarbon fluids between the source and reservoir. We have developed 3D seismic reflection data from the Bass Basin in offshore southeastern Australia that image an early Miocene volcanic complex with exceptional clarity. This volcanic complex is now buried by [Formula: see text] of younger sediments. The largest volcano within this complex is directly overlain by a vertical feature interpreted to be a fluid escape pipe, which extends vertically for approximately 700 m across the late Miocene-Pliocene succession. We suggest that the buried volcanic complex was able to focus vertical fluid migration to the base of the pipe because its bulk permeability was higher than that of the overlying claystone sequence. The fluid escape pipe may have initiated through either (1) hydraulic fracturing following fluid expulsion from a deep, overpressured subvolcanic source region, (2) differential compaction and doming of the overlying claystones, or (3) a combination of these processes. Our results suggest a hitherto unrecognized role for buried volcanoes in influencing dynamic subsurface processes in sedimentary basins. In particular, our study highlights that buried volcanoes may facilitate cross-stratal migration of hydrocarbons from source to reservoir, or through sealing horizons.