bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework
Authors: Jabra-Rizk Mary Ann , Kong Eric F. , Tsui Christina , Nguyen M. Hong , Clancy Cornelius J. , Fidel Paul L. , Noverr Mairi 
Published: July 2016

ABSTRACT

Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of
Candida albicans
, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably,
C. albicans
infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses.
Understanding HIV-positive patients' preferences for healthcare services: a protocol for a discrete choice experiment
Authors: Youssef Elaney , Cooper Vanessa , Miners Alec , Llewellyn Carrie , Pollard Alex , Lagarde Mylene , Sachikonye Memory , Sabin Caroline , Foreman Claire , Perry Nicky , Nixon Eileen , Fisher Martin 
Published: July 2016

IntroductionWhile the care of HIV-positive patients, including the detection and management of comorbidities, has historically been provided in HIV specialist outpatient clinics, recent years have seen a greater involvement of non-HIV specialists and general practitioners (GPs). The aim of this study is to determine whether patients would prefer to see their GP or HIV physician given general symptoms, and to understand what aspects of care influence their preferences.Methods/analysisWe have developed and piloted a discrete choice experiment (DCE) to better understand patients' preferences for care of non-HIV-related acute symptoms. The design of the DCE was informed by our exploratory research, including the findings of a systematic literature review and a qualitative study. Additional questionnaire items have been included to measure demographics, service use and experience of non-HIV illnesses and quality of life (EQ5D). We plan to recruit 1000 patients from 14 HIV clinics across South East England. Data will be analysed using random-effects logistic regression and latent class analysis. ORs and 95% CIs will be used to estimate the relative importance of each of the attribute levels. Latent class analysis will identify whether particular groups of people value the service attribute levels differently.Ethics/disseminationEthical approval for this study was obtained from the Newcastle and North Tyneside Research Ethics Committee (reference number 14/NE/1193). The results will be disseminated at national and international conferences and peer-reviewed publications. A study report, written in plain English, will be made available to all participants. The Patient Advisory Group will develop a strategy for wider dissemination of the findings to patients and the public.
Pain education in pre-registration professional health courses: a protocol for a scoping review
Authors: Thompson Kate , Milligan James , Johnson Mark I , Briggs Michelle 
Published: July 2016

IntroductionPain is a global health concern causing significant health and social problems with evidence that patients experiencing pain are receiving inadequate care. The content of pain education in pre-registration professional health courses is thought to be lacking both in the UK and internationally which is unacceptable considering the prevalence of pain. Evaluating the effect of education is complex in that the outcome (improved healthcare) is some distance from the educational approach. Best evidence medical education has been proposed as a continuum between ‘opinion-based teaching’ and ‘evidence-based teaching’. Searching for evidence to inform best practice in health education is complex. A scoping review provides a practical and comprehensive strategy to locate and synthesise literature of varied methodology including reports from a variety of sources. The aim of this article is to describe a protocol for a scoping review that will locate, map and report research, guidelines and policies for pain education in pre-registration professional health courses. The extent, range and nature of reports will be examined, and where possible titles for potential systematic review will be identified.Methods and analysisReports will be included for review that are directly relevant to the development of the pain curriculum in pre-registration professional health courses, eg nursing, medicine, physiotherapy. The search strategy will identify reports that include [pain] AND [pre-registration education or curriculum] AND [health professionals] in the title or abstract. Two authors will independently screen retrieved studies against eligibility criteria. A numerical analysis regarding the extent, nature and distribution of reports will be given along with a narrative synthesis to describe characteristics of relevant reports.Ethics and disseminationFormal ethical approval was not required to undertake this scoping review. Findings will be published in scientific peer-reviewed journals and via conference presentations.
Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis
Authors: Hackstein Carl-Philipp , Assmus Lisa Mareike , Welz Meike , Klein Sabine , Schwandt Timo , Schultze Joachim , Förster Irmgard , Gondorf Fabian , Beyer Marc , Kroy Daniela , Kurts Christian , Trebicka Jonel , Kastenmüller Wolfgang , Knolle Percy A , Abdullah Zeinab 
Published: July 2016

ObjectivePatients with liver cirrhosis suffer from increased susceptibility to life-threatening bacterial infections that cause substantial morbidity.MethodsExperimental liver fibrosis in mice induced by bile duct ligation or CCl4application was used to characterise the mechanisms determining failure of innate immunity to control bacterial infections.ResultsIn murine liver fibrosis, translocation of gut microbiota induced tonic type I interferon (IFN) expression in the liver. Such tonic IFN expression conditioned liver myeloid cells to produce high concentrations of IFN upon intracellular infection withListeriathat activate cytosolic pattern recognition receptors. Such IFN-receptor signalling caused myeloid cell interleukin (IL)-10 production that corrupted antibacterial immunity, leading to loss of infection-control and to infection-associated mortality. In patients with liver cirrhosis, we also found a prominent liver IFN signature and myeloid cells showed increased IL-10 production after bacterial infection. Thus, myeloid cells are both source and target of IFN-induced and IL-10-mediated immune dysfunction. Antibody-mediated blockade of IFN-receptor or IL-10-receptor signalling reconstituted antibacterial immunity and prevented infection-associated mortality in mice with liver fibrosis.ConclusionsIn severe liver fibrosis and cirrhosis, failure to control bacterial infection is caused by augmented IFN and IL-10 expression that incapacitates antibacterial immunity of myeloid cells. Targeted interference with the immune regulatory host factors IL-10 and IFN reconstitutes antibacterial immunity and may be used as therapeutic strategy to control bacterial infections in patients with liver cirrhosis.
Myristica fragransSuppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A
Authors: Kim Eun-Yeong , Choi Hee-Jung , Park Mi-Ju , Jung Yeon-Seop , Lee Syng-Ook , Kim Keuk-Jun , Choi Jung-Hye , Chung Tae-Wook , Ha Ki-Tae 
Published: July 2016

Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg’s effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity.
Mass limits for the chiral color symmetry G′-boson from LHC dijet data
Authors: Frolov I. V. , Smirnov A. D. 
Published: July 2016

The contributions of [Formula: see text]-boson predicted by the chiral color symmetry of quarks to the differential dijet cross-sections in pp-collisions at the large hadron collider (LHC) are calculated and analyzed in dependence on two free parameters of the model, the [Formula: see text] mass [Formula: see text] and mixing angle [Formula: see text]. The exclusion and consistency [Formula: see text] regions imposed by the ATLAS and CMS data on dijet cross-sections are found. Using the CT10 (MSTW2008) parton distribution function (PDF) set we show that the [Formula: see text]-boson for [Formula: see text], i.e. the axigluon, with the masses [Formula: see text] TeV and [Formula: see text] TeV is excluded at the probability level of 95% by the ATLAS and CMS dijet data, respectively. For the other values of [Formula: see text] the exclusion limits are more stringent. The [Formula: see text] regions consistent with these data at CL = 68% and CL = 90% are also found.
Rapid Conversion of Mutant IDH1 from Driver to Passenger in a Model of Human Gliomagenesis
Authors: Johannessen Tor-Christian Aase , Mukherjee Joydeep , Viswanath Pavithra , Ohba Shigeo , Ronen Sabrina M. , Bjerkvig Rolf , Pieper Russell O. 
Published: July 2016

Abstract
Missense mutations in the active site of isocitrate dehydrogenase 1 (IDH1) biologically and diagnostically distinguish low-grade gliomas and secondary glioblastomas from primary glioblastomas. IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of α-ketoglutarate (α-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. Although mutant IDH1 expression is thought to drive the gliomagenesis process, the extent to which it remains a viable therapeutic target remains unknown. To address this question, we exposed immortalized (p53/pRb deficient), untransformed human astrocytes to the mutant IDH1 inhibitor AGI-5198 prior to, concomitant with, or at intervals after, introduction of transforming mutant IDH1, then measured effects on 2-HG levels, histone methylation (H3K4me3, H3K9me2, H3K9me3, or H3K27me3), and growth in soft agar. Addition of AGI-5198 prior to, or concomitant with, introduction of mutant IDH1 blocked all mutant IDH1-driven changes, including cellular transformation. Addition at time intervals as short as 4 days following introduction of mutant IDH1 also suppressed 2-HG levels, but had minimal effects on histone methylation, and lost the ability to suppress clonogenicity in a time-dependent manner. Furthermore, in two different models of mutant IDH1–driven gliomagenesis, AGI-5198 exposures that abolished production of 2-HG also failed to decrease histone methylation, adherent cell growth, or anchorage-independent growth in soft agar over a prolonged period. These studies show although mutant IDH1 expression drives gliomagenesis, mutant IDH1 itself rapidly converts from driver to passenger.
Implications: Agents that target mutant IDH may be effective for a narrow time and may require further optimization or additional therapeutics in glioma. Mol Cancer Res; 14(10); 976–83. ©2016 AACR.
Celecoxib Alters the Intestinal Microbiota and Metabolome in Association with Reducing Polyp Burden
Authors: Montrose David C. , Zhou Xi Kathy , McNally Erin M. , Sue Erika , Yantiss Rhonda K. , Gross Steven S. , Leve Nitai D. , Karoly Edward D. , Suen Chen S. , Ling Lilan , Benezra Robert , Pamer Eric G. , Dannenberg Andrew J. 
Published: July 2016

Abstract
Treatment with celecoxib, a selective COX-2 inhibitor, reduces formation of premalignant adenomatous polyps in the gastrointestinal tracts of humans and mice. In addition to its chemopreventive activity, celecoxib can exhibit antimicrobial activity. Differing bacterial profiles have been found in feces from colon cancer patients compared with those of normal subjects. Moreover, preclinical studies suggest that bacteria can modulate intestinal tumorigenesis by secreting specific metabolites. In the current study, we determined whether celecoxib treatment altered the luminal microbiota and metabolome in association with reducing intestinal polyp burden in mice. Administration of celecoxib for 10 weeks markedly reduced intestinal polyp burden in APCMin/+ mice. Treatment with celecoxib also altered select luminal bacterial populations in both APCMin/+ and wild-type mice, including decreased Lactobacillaceae and Bifidobacteriaceae as well as increased Coriobacteriaceae. Metabolomic analysis demonstrated that celecoxib caused a strong reduction in many fecal metabolites linked to carcinogenesis, including glucose, amino acids, nucleotides, and lipids. Ingenuity Pathway Analysis suggested that these changes in metabolites may contribute to reduced cell proliferation. To this end, we showed that celecoxib reduced cell proliferation in the base of normal appearing ileal and colonic crypts of APCMin/+ mice. Consistent with this finding, lineage tracing indicated that celecoxib treatment reduced the rate at which Lgr5-positive stem cells gave rise to differentiated cell types in the crypts. Taken together, these results demonstrate that celecoxib alters the luminal microbiota and metabolome along with reducing epithelial cell proliferation in mice. We hypothesize that these actions contribute to its chemopreventive activity. Cancer Prev Res; 9(9); 721–31. ©2016 AACR.
Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects
Authors: Smit Roelof A.J. , Trompet Stella , Sabayan Behnam , le Cessie Saskia , van der Grond Jeroen , van Buchem Mark A. , de Craen Anton J.M. , Jukema J. Wouter 
Published: July 2016

Background:
Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy.

Methods:
We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors.

Results:

Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention (
P
=0.017 and
P
=0.11, respectively), processing speed (
P
=0.20 and
P
=0.029), and memory (immediate recall,
P
=0.002 and
P
=0.006; delayed recall,
P
=0.001 and
P
≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms (
P
=0.031 and
P
=0.050) and with greater white matter hyperintensity load in the pravastatin arm (
P
=0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes.

Conclusions:
We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.
Forecasting Conditional Probabilities of Binary Outcomes under Misspecification
Authors: Elliott Graham , Ghanem Dalia , Krüger Fabian 
Published: July 2016

AbstractWe consider constructing probability forecasts from a parametric binary choice model under a large family of loss functions (“scoring rules”). Scoring rules are weighted averages over the utilities that heterogeneous decision makers derive from a publicly announced forecast (Schervish, 1989). Using analytical and numerical examples, we illustrate howdifferent scoring rules yield asymptotically identical results if the model is correctly specified. Under misspecification, the choice of scoring rule may be inconsequential under restrictive symmetry conditions on the data-generating process. If these conditions are violated, typically the choice of a scoring rule favors some decision makers over others.
Stochastic Parameterization: Toward a New View of Weather and Climate Models
Authors: Berner Judith , Achatz Ulrich , Batté Lauriane , Bengtsson Lisa , Cámara Alvaro de la , Christensen Hannah M. , Colangeli Matteo , Coleman Danielle R. B. , Crommelin Daan , Dolaptchiev Stamen I. , Franzke Christian L. E. , Friederichs Petra , Imkeller Peter , Järvinen Heikki , Juricke Stephan , Kitsios Vassili , Lott François , Lucarini Valerio , Mahajan Salil , Palmer Timothy N. , Penland Cécile , Sakradzija Mirjana , von Storch Jin-Song , Weisheimer Antje , Weniger Michael , Williams Paul D. , Yano Jun-Ichi 
Published: July 2016

Abstract
The last decade has seen the success of stochastic parameterizations in short-term, medium-range, and seasonal forecasts: operational weather centers now routinely use stochastic parameterization schemes to represent model inadequacy better and to improve the quantification of forecast uncertainty. Developed initially for numerical weather prediction, the inclusion of stochastic parameterizations not only provides better estimates of uncertainty, but it is also extremely promising for reducing long-standing climate biases and is relevant for determining the climate response to external forcing. This article highlights recent developments from different research groups that show that the stochastic representation of unresolved processes in the atmosphere, oceans, land surface, and cryosphere of comprehensive weather and climate models 1) gives rise to more reliable probabilistic forecasts of weather and climate and 2) reduces systematic model bias. We make a case that the use of mathematically stringent methods for the derivation of stochastic dynamic equations will lead to substantial improvements in our ability to accurately simulate weather and climate at all scales. Recent work in mathematics, statistical mechanics, and turbulence is reviewed; its relevance for the climate problem is demonstrated; and future research directions are outlined.
Local and Remote Impacts of Aerosol Species on Indian Summer Monsoon Rainfall in a GCM
Authors: Guo Liang , Turner Andrew G. , Highwood Eleanor J. 
Published: July 2016

Abstract
The HadGEM2 AGCM is used to determine the most important anthropogenic aerosols in the Indian monsoon using experiments in which observed trends in individual aerosol species are imposed. Sulfur dioxide (SD) emissions are shown to impact rainfall more strongly than black carbon (BC) aerosols, causing reduced rainfall especially over northern India. Significant perturbations due to BC are not noted until its emissions are scaled up in a sensitivity test, resulting in rainfall increases over northern India due to the elevated heat pump mechanism, enhancing convection during the premonsoon, and bringing forward the monsoon onset. Second, the impact of anthropogenic aerosols is compared to that of increasing greenhouse-gas concentrations and observed sea surface temperature (SST) warming. The tropospheric temperature gradient driving the monsoon shows weakening when forced by either SD or imposed SST trends. However, the observed SST trend is dominated by warming in the deep tropics; when the component of SST trend related to aerosol emissions is removed, further warming is found in the extratropical Northern Hemisphere that tends to offset monsoon weakening. This suggests caution is needed when using SST forcing as a proxy for greenhouse warming. Finally, aerosol emissions are decomposed into those from the Indian region and those elsewhere in pairs of experiments with SD and BC. Both local and remote aerosol emissions are found to lead to rainfall changes over India; for SD, remote aerosols contribute around 75% of the rainfall decrease over India, while for BC the remote forcing is even more dominant.
Reflection of Linear Internal Tides from Realistic Topography: The Tasman Continental Slope
Authors: Klymak Jody M. , Simmons Harper L. , Braznikov Dmitry , Kelly Samuel , MacKinnon Jennifer A. , Alford Matthew H. , Pinkel Robert , Nash Jonathan D. 
Published: July 2016

AbstractThe reflection of a low-mode internal tide on the Tasman continental slope is investigated using simulations of realistic and simplified topographies. The slope is supercritical to the internal tide, which should predict a large fraction of the energy reflected. However, the response to the slope is complicated by a number of factors: the incoming beam is confined laterally, it impacts the slope at an angle, there is a roughly cylindrical rise directly offshore of the slope, and a leaky slope-mode wave is excited. These effects are isolated in simulations that simplify the topography. To separate the incident from the reflected signal, a response without the reflector is subtracted from the total response to arrive at a reflected signal. The real slope reflects approximately 65% of the mode-1 internal tide as mode 1, less than two-dimensional linear calculations predict, because of the three-dimensional concavity of the topography. It is also less than recent glider estimates, likely as a result of along-slope inhomogeneity. The inhomogeneity of the response comes from the Tasman Rise that diffracts the incoming tidal beam into two beams: one focused along beam and one diffracted to the north. Along-slope inhomogeneity is enhanced by a partially trapped, superinertial slope wave that propagates along the continental slope, locally removing energy from the deep-water internal tide and reradiating it into the deep water farther north. This wave is present even in a simplified, straight slope topography; its character can be predicted from linear resonance theory, and it represents up to 30% of the local energy budget.