bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded Glucose Import Capability Affords Staphylococcus aureus Optimized Glycolytic Flux during Infection
Authors: Vitko Nicholas P. , Grosser Melinda R. , Khatri Dal , Lance Thurlow R. , Richardson Anthony R. 
Published: June 2016

ABSTRACT

Acquisition of numerous virulence determinants affords
Staphylococcus aureus
greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of
S. aureus
to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to
S. aureus
virulence. Specifically,
S. aureus
has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that
S. aureus
has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11
S. aureus
transporters were identified, and at least four of their genes encode
S. aureus
glucose transporters (
glcA
,
glcB
,
glcC
, and
glcU
). Moreover, two transporter genes (
glcA
and
glcC
) are unique to
S. aureus
and contribute disproportionately to the nonrespiratory growth of
S. aureus
on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated
S. aureus
in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of
S. aureus
to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows
S. aureus
to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion.

IMPORTANCE
The bacterial pathogen
Staphylococcus aureus
causes a wide range of human infections that are costly and difficult to treat.
S. aureus
differs from closely related commensal staphylococci in its ability to flourish following the invasion of deeper tissue from the skin surface. There,
S. aureus
primarily uses glucose to grow under respiration-limiting conditions imposed by the immune system. It was previously unclear how
S. aureus
thrives in this environment when other
Staphylococcus
species cannot. Our results provide evidence that
S. aureus
has acquired an expanded repertoire of carbohydrate transporters. In particular, four glucose transporters contribute to efficient
S. aureus
growth during infection. Thus,
S. aureus
has evolved to maximize its glucose uptake abilities for enhanced glycolytic flux during tissue invasion. This dependence on glucose acquisition for
S. aureus
virulence may also explain links between serious infectious complications associated with diabetic patients exhibiting elevated blood glucose levels.
Catalytic Subunit 1 of Protein Phosphatase 2A Is a Subunit of the STRIPAK Complex and Governs Fungal Sexual Development
Authors: Beier Anna , Teichert Ines , Krisp Christoph , Wolters Dirk A. , Kück Ulrich 
Published: June 2016

ABSTRACT

The generation of complex three-dimensional structures is a key developmental step for most eukaryotic organisms. The details of the molecular machinery controlling this step remain to be determined. An excellent model system to study this general process is the generation of three-dimensional fruiting bodies in filamentous fungi like
Sordaria macrospora
. Fruiting body development is controlled by subunits of the highly conserved striatin-interacting phosphatase and kinase (STRIPAK) complex, which has been described in organisms ranging from yeasts to humans. The highly conserved heterotrimeric protein phosphatase PP2A is a subunit of STRIPAK. Here, catalytic subunit 1 of PP2A was functionally characterized. The Δ
pp2Ac1
strain is sterile, unable to undergo hyphal fusion, and devoid of ascogonial septation. Further, PP2Ac1, together with STRIPAK subunit PRO22, governs vegetative and stress-related growth. We revealed
in vitro
catalytic activity of wild-type PP2Ac1, and our
in vivo
analysis showed that inactive PP2Ac1 blocks the complementation of the sterile deletion strain. Tandem affinity purification, followed by mass spectrometry and yeast two-hybrid analysis, verified that PP2Ac1 is a subunit of STRIPAK. Further, these data indicate links between the STRIPAK complex and other developmental signaling pathways, implying the presence of a large interconnected signaling network that controls eukaryotic developmental processes. The insights gained in our study can be transferred to higher eukaryotes and will be important for understanding eukaryotic cellular development in general.

IMPORTANCE
The striatin-interacting phosphatase and kinase (STRIPAK) complex is highly conserved from yeasts to humans and is an important regulator of numerous eukaryotic developmental processes, such as cellular signaling and cell development. Although functional insights into the STRIPAK complex are accumulating, the detailed molecular mechanisms of single subunits are only partially understood. The first fungal STRIPAK was described in
Sordaria macrospora
, which is a well-established model organism used to study the formation of fungal fruiting bodies, three-dimensional organ-like structures. We analyzed STRIPAK subunit PP2Ac1, catalytic subunit 1 of protein phosphatase PP2A, to study the importance of the catalytic activity of this protein during sexual development. The results of our yeast two-hybrid analysis and tandem affinity purification, followed by mass spectrometry, indicate that PP2Ac1 activity connects STRIPAK with other signaling pathways and thus forms a large interconnected signaling network.
Low socioeconomic status is associated with adverse events in children and teens on insulin pumps under a universal access program: a population-based cohort study
Authors: Shulman Rayzel , Stukel Therese A , Miller Fiona A , Newman Alice , Daneman Denis , Wasserman Jonathan D , Guttmann Astrid 
Published: June 2016

ObjectiveTo describe adverse events in pediatric insulin pump users since universal funding in Ontario and to explore the role of socioeconomic status and 24-hour support.Research design and methodsPopulation-based cohort study of youth (<19 years) with type 1 diabetes (n=3193) under a universal access program in Ontario, Canada, from 2006 to 2013. We linked 2012 survey data from 33 pediatric diabetes centers to health administrative databases. The relationship between patient and center-level characteristics and time to first diabetic ketoacidosis (DKA) admission or death was tested using a Cox proportional hazards model and the rate of diabetes-related emergency department visits and hospitalizations with a Poisson model, both using generalized estimating equations.ResultsThe rate of DKA was 5.28/100 person-years and mortality 0.033/100 person-years. Compared with the least deprived quintile, the risk of DKA or death for those in the most deprived quintile was significantly higher (HR 1.58, 95% CI 1.05 to 2.38) as was the rate of diabetes-related acute care use (RR 1.60, 95% CI 1.27 to 2.00). 24-hour support was not associated with these outcomes. Higher glycated hemoglobin, prior DKA, older age, and higher nursing patient load were associated with a higher risk of DKA or death.ConclusionsThe safety profile of pump therapy in the context of universal funding is similar to other jurisdictions and unrelated to 24-hour support. Several factors including higher deprivation were associated with an increased risk of adverse events and could be used to inform the design of interventions aimed at preventing poor outcomes in high-risk individuals.
Study protocol for screening and diagnosis of fetal alcohol spectrum disorders (FASD) among young people sentenced to detention in Western Australia
Authors: Passmore Hayley M , Giglia Roslyn , Watkins Rochelle E , Mutch Raewyn C , Marriott Rhonda , Pestell Carmela , Zubrick Stephen R , Rainsford Candice , Walker Noni , Fitzpatrick James P , Freeman Jacinta , Kippin Natalie , Safe Bernadette , Bower Carol 
Published: June 2016

IntroductionPrenatal alcohol exposure can cause lifelong disability, including physical, cognitive and behavioural deficits, known as fetal alcohol spectrum disorders (FASD). Among individuals with FASD, engagement with justice services is common. Little is known about the prevalence of FASD among young people engaged with the Australian justice system. This study aims to establish FASD prevalence among sentenced young people in detention in Western Australia (WA), and use the findings to develop a screening tool for use among young people entering detention. Translation of these results will guide the management and support of young people in detention and will have significant implications on the lives of young people with FASD and the future of Australian youth justice services.Methods and analysisAny sentenced young person in WA aged 10–17 years 11 months is eligible to participate. Young people are assessed for FASD by a multidisciplinary team. Standardised assessment tools refined for the Australian context are used, acknowledging the language and social complexities involved. Australian diagnostic guidelines for FASD will be applied. Information is obtained from young people, responsible adults, teachers and custodial officers. Individualised results and management plans for each young person are communicated to the young person and responsible adult. Prevalence of FASD will be reported and multivariate methods used to identify variables most predictive of FASD and to optimise the predictive value of screening.Ethics and disseminationApprovals have been granted by the WA Aboriginal Health Ethics Committee, University of WA Human Research Ethics Committee, Department of Corrective Services, and Department for Child Protection and Family Support. Anonymised findings will be disseminated through peer-reviewed manuscripts, presentations and the media. Extensive consultation with stakeholders (including government agencies, detention centre staff, community service providers, the young people and their families or carers) will be ongoing until findings are disseminated and translated.
Reviewing deaths in British and US hospitals: a study of two scales for assessing preventability
Authors: Manaseki-Holland Semira , Lilford Richard J , Bishop Jonathan R B , Girling Alan J , Chen Yen-Fu , Chilton Peter J , Hofer Timothy P ,   The UK Case Note Review Group
Published: June 2016

BackgroundStandardised mortality ratios do not provide accurate measures of preventable mortality. This has generated interest in using case notes to assess the preventable component of mortality. But, different methods of measurement have not been compared. We compared the reliability of two scales for assessing preventability and the correspondence between them.MethodsMedical specialists reviewed case notes of patients who had died in hospital, using two instruments: a five-point Likert scale and a continuous (0–100) scale of preventability. To enhance generalisability, we used two different hospital datasets with different types of acute medical patients across different epochs, and in two jurisdictions (UK and USA). We investigated the reliability of measurement and correspondence of preventability estimates across the two scales. Ordinal mixed effects regression methods were used to analyse the Likert scale and to calibrate it against the continuous scale. We report the estimates of the probability a death could have been prevented, accounting for reviewer inconsistency.ResultsCorrespondence between the two scales was strong; the Likert categories explained most of the variation (76% UK, 73% USA) in the continuous scale. Measurement reliability was low, but similar across the two instruments in each dataset (intraclass correlation: 0.27, UK; 0.23, USA). Adjusting for the inconsistency of reviewer judgements reduced the proportion of cases with high preventability, such that the proportion of all deaths judged probably or definitely preventable on the balance of probability was less than 1%.ConclusionsThe correspondence is high between a Likert and a continuous scale, although the low reliability of both would suggest careful measurement design would be needed to use either scale. Few to no cases are above the threshold when using a balance of probability approach to determining a preventable death, and in any case, there is little evidence supporting anything more than an ordinal correspondence between these reviewer estimates of probability and the true probability. Thus, it would be more defensible to use them as an ordinal measure of the quality of care received by patients who died in the hospital.
Multicenter assessment of morbidity associated with cerebral arteriovenous malformation hemorrhages
Authors: Fukuda Keiko , Majumdar Monica , Masoud Hesham , Nguyen Thanh , Honarmand Amir , Shaibani Ali , Ansari Sameer , Tan Lee A , Chen Michael 
Published: June 2016

BackgroundThe optimal management strategy for unruptured cerebral arteriovenous malformations (AVMs) is controversial since the ARUBA trial (A Randomized trial of Unruptured Brain AVMs). An accurate understanding of the morbidity associated with AVM hemorrhages may help clinicians to formulate the best treatment strategy for unruptured AVMs.ObjectiveTo determine the morbidity associated with initial cerebral AVM rupture in patients presenting to tertiary medical centers.MethodsRetrospective chart reviews from three tertiary academic medical centers were performed for the period between 2008 and 2014. All patients admitted with intracranial hemorrhage due to untreated AVMs were included in this study. Patient-specific variables, including demographics, imaging characteristics, neurologic examination results, and clinical outcome, were analyzed and recorded.Results101 Patients met the inclusion criteria. Admission National Institutes of Health Stroke Scale (NIHSS) scores were 0, 1–9, and ≥10 in 26%, 29%, and 45% of patients, respectively. Hematoma locations were subarachnoid, intraventricular, intraparenchymal, and combined in 5%, 11%, 32%, and 52% of patients, respectively. Deep venous drainage was present in 43% of AVMs; AVM-associated aneurysms were present in 44% of patients. Emergent hematoma evacuations were performed in 37% of patients and 8% of patients died while in hospital. At discharge, of those who survived, NIHSS scores of ≥1 and ≥10 were found in 69% and 23%, respectively. At the 90-day follow-up, 34% had a modified Rankin Scale (mRS) score >2. Patients with admission NIHSS score ≥10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥3 (p<0.05).ConclusionsThe morbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment strategy for unruptured cerebral AVMs.
Gaining insight into corrosion processes from numerical simulations of an integrated iron-claystone experiment
Authors: Bildstein Olivier , Lartigue Jean-Éric , Schlegel Michel L. , Bataillon Christian , Cochepin Benoît , Munier Isabelle , Michau Nicolas 
Published: June 2016

Abstract
Numerical simulations concerning iron–clay interactions in the conditions of an integrated experiment were conducted within a Callovo-Oxfordian claystone block at 90°C for 2 years. The calculations aim at determining the configurations and the parameters for which the simulation reproduce the mineral paragenesis observed at the end of the experiment. This paragenesis suggests that a thin magnetite layer precipitates at the surface of the corroding iron and dissolves on the claystone side to promote precipitation of Fe-silicate and Fe-carbonate minerals. The claystone is also altered close to the interface with iron via a significant precipitation of a Fe-carbonate mineral.
The results obtained using the coupled reactive transport code Crunchflow show that adjusting both the kinetics of magnetite dissolution/precipitation and the properties of the corroded layer (considered as a diffusive barrier) was required in order: (i) to model the destabilization of the magnetite layer formed at the original iron–claystone interface early in the corrosion process and the precipitation of other iron-bearing minerals; and (ii) to isolate the chemical conditions at the iron surface from the conditions in the clay environment in order to favour magnetite precipitation at the iron surface. With these assumptions, the model closely reproduced the mineral paragenesis observed in the experiment.
The gas permeability, breakthrough behaviour and re-sealing ability of Czech Ca–Mg bentonite
Authors: Smutek Jan , Hausmannova Lucie , Svoboda Jiri 
Published: June 2016

Abstract
The study's objectives were to test the gas permeability of unsaturated compacted bentonite, the gas-breakthrough behaviour of saturated bentonite, and the re-sealing ability compared with the material's dry density, hydraulic conductivity and swelling pressure. During the project's pilot phase, a series of laboratory experiments were conducted on samples of two Czech Ca–Mg bentonites (Bentonite 75 and Cerny Vrch). The testing procedure, employing repeated hydration and gas-breakthrough test phases, simulated conditions within deep geological repositories for radioactive waste, wherein the buffer will be progressively hydrated from the surrounding host rock and loaded with pressure exerted by gases created within the repository.
It was found that the gas permeability of the bentonites tested was affected by dry density and, as with the two materials (FEBEX and MX-80) used for comparison, it correlated well with the accessible void ratio. Gas-breakthrough tests revealed correlations between time to breakthrough and both dry density and sample height. The recorded repeated test breakthrough times on the same samples varied, which implies that the pathways created are complex and differ for repeated gas-injection cycles. However, no systematic deterioration in sample properties was detected, thus indicating the extensive re-sealing ability of the materials tested.
Regional aquifer hydrogeochemistry in the confined aquifer system below the Boom Clay (NE Belgium): data analysis and modelling
Authors: Vandersteen K. , Leterme B. , Gedeon M. 
Published: June 2016

Abstract

Geochemical data from the deep aquifer system below the Boom Clay in NE Belgium have been collected and reinterpreted. The data were obtained between 1980 and 2014 within the framework of radioactive waste disposal studies. Currently, groundwater in the deep aquifer system mainly ranges between NaHCO
3
type and NaCl type. Because of the low groundwater velocity in this aquifer system, re-equilibration with the mineralogical composition of the host formations generally occurs. The main geochemical indicators point out that the current formation waters are a mixture between the original saline marine porewaters and freshwater recharge. SE–NW gradients of increasing ion concentrations are observed and can be explained in agreement with the pattern of natural groundwater flow. Calcite dissolution and cation exchange are still ongoing in this freshening aquifer system. A low sulphate content in the deep aquifer system indicates sulphate reduction associated with organic matter degradation. Inverse modelling along a flow path using PHREEQC generally confirms the reactions that have been derived in the data analysis.
Stigma and discrimination experienced by people living with severe and persistent mental illness in assertive community treatment settings
Authors: Ye Jing , Chen Timothy F , Paul Diane , McCahon Rebecca , Shankar Sumitra , Rosen Alan , O’Reilly Claire L 
Published: June 2016

Aims: To describe the perceived experiences of stigma and discrimination among people living with severe and persistent mental illness in assertive community treatment (ACT teams) settings in New South Wales (NSW), Australia. Methods: The Discrimination and Stigma Scale (DISC) was used in this cross-sectional study with people living with severe and persistent mental illness. The DISC is a reliable and valid, quantitative and qualitative instrument used to explore and measure levels of negative, anticipated and positive discrimination. Relevant clinical history and socio-demographic information were also collected. Results: A total of 50 clients participated, with 40 (80%) reporting experienced negative discrimination in at least one life area. Negative discrimination was most commonly experienced in being avoided or shunned ( n=25, 50%), by neighbours ( n=24, 48%) and family ( n=23, 46%). Anticipated discrimination was common, with half of participants ( n=25, 50%) feeling the need to conceal their mental health diagnosis. Conclusion: Discrimination was highly prevalent in everyday aspects of life. While healthcare professionals often tend to increase perceived stigma and discrimination, this was only experienced in interactions with general health professionals, while interactions with ACT team members decreased perceived stigma and increased positive discrimination. This indicates that healthcare professionals potentially have a significant role in reducing stigma and discrimination in mental health and that such an effect may be optimised in an ACT team setting.
Infective endocarditis in patients on haemodialysis – possible strategies for prevention
Authors: Oun Hadi A , Price Andrew J , Traynor Jamie P 
Published: June 2016

Background and aims Infective endocarditis is an important cause of morbidity and mortality in patients receiving haemodialysis for established renal failure. We carried out a prospective audit of patients developing infective endocarditis in a single renal unit. Methods and results From 1 January 2000 to 31 December 2013, we collected data on all cases of endocarditis occurring in patients receiving haemodialysis at Monklands Hospital, Airdrie. Twenty-nine patients developed endocarditis during our audit period. Twenty-three (79.3%) of the patients had pre-existing cardiac valve abnormalities such as regurgitation or calcification. Staphylococcus aureus was the most common microorganism cultured from the blood of 22 patients (75.9%). MRSA bacteraemia was identified in eight of these patients and all eight patients died during that first presentation. Different strategies were introduced within the unit during the audit period aiming to reduce the rate of bacteraemia. Since 2011, a successful strategy has been introduced under the auspices of the Scottish Patient Safety Programme. This led to our Staph aureus bacteraemia rate related to non-tunnelled venous catheters going from an average of 15 days between episodes to having had no episodes between 2 December 2011 and the end of the study period (760 days). This also appears to have had a positive impact on reducing the rate of endocarditis. Conclusion Infective endocarditis remains a devastating consequence of bacteraemia in patients receiving haemodialysis. An effective strategy aimed at reducing the rate of bacteraemia appears to have a similar effect on the rate of endocarditis.