bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models
Authors: Sun Xiangjie , Belser Jessica A. , Pulit-Penaloza Joanna A. , Zeng Hui , Lewis Amanda , Shieh Wun-Ju , Tumpey Terrence M. , Maines Taronna R. 
Published: September 2016

ABSTRACT

Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate
in vitro
in human airway cells and
in vivo
in mouse and ferret models. Both H7N8 viruses replicated efficiently
in vitro
and
in vivo
, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health.

IMPORTANCE
H7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low-pathogenic avian influenza (LPAI) virus were recently isolated from commercial turkey farms in Indiana. To determine the risk that these influenza viruses pose to humans, we assessed their pathogenesis and transmission
in vitro
and in mammalian models. We found that the H7N8 HPAI virus exhibited enhanced virulence, and although transmission was only observed with the H7N8 LPAI virus, the ability of this H7 virus to transmit in a mammalian host and quickly evolve to a more virulent strain is cause for concern. Our findings offer important insight into the potential for emerging H7 avian influenza viruses to acquire the ability to cause disease and transmit among mammals.
Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells
Authors: Lacombe Benoît , Morel Marina , Margottin-Goguet Florence , Ramirez Bertha Cecilia 
Published: September 2016

ABSTRACT

Tat protein, the HIV transactivator, regulates transcription of the HIV genome by the host transcription machinery. Efficient inhibitors of HIV transcription that target Tat or the cellular cofactor NF-κB are well known. However, inhibition of HIV Tat-dependent transcription by targeting the general transcription and DNA repair factor II human (TFIIH) has not been reported. Here, we show that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4
+
T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat-dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection. Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy.

IMPORTANCE
Transcription from the HIV promoter is regulated by the combined activities of the host transcription machinery and the viral transactivator Tat protein. Here, we report that the drug spironolactone—an antagonist of aldosterone—blocks viral Tat-dependent transcription, thereby inhibiting both HIV-1 and HIV-2 infection of permissive T cells. This inhibition relies on the degradation of the cellular helicase XPB, a component of the TFIIH transcription factor complex. Consequently, XPB appears to be a novel HIV cofactor. Our discovery of the HIV-inhibitory activity of spironolactone opens the way for the development of novel anti-HIV strategies targeting a cellular cofactor without the limitations of antiretroviral therapy of drug resistance and high cost.
How many children and young people with life-limiting conditions are clinically unstable? A national data linkage study
Authors: Jarvis Stuart , Parslow Roger C , Carragher Pat , Beresford Bryony , Fraser Lorna K 
Published: September 2016

ObjectiveTo determine the clinical stage (stable, unstable, deteriorating or dying) for children and young people (CYP) aged 0–25 years in Scotland with life-limiting conditions (LLCs).DesignNational cohort of CYP with LLCs using linked routinely collected healthcare data.SettingScotland.Patients20 436 CYP identified as having LLCs and resident in Scotland between 1 April 2009 and 31 March 2014.Main outcomeClinical stage based on emergency inpatient and intensive care unit admissions and date of death.ResultsOver 2200 CYP with LLCs in Scotland were unstable, deteriorating or dying in each year. Compared with 1-year-olds to 5-year-olds, children under 1 year of age had the highest risk of instability (OR 6.4, 95% CI 5.7 to 7.1); all older age groups had lower risk. Girls were more likely to be unstable than boys (OR 1.15, 95% CI 1.06 to 1.24). CYP of South Asian (OR 1.61, 95% CI 1.28 to 2.01), Black (OR 1.58, 95% CI 1.04 to 2.41) and Other (OR 1.33, 95% CI 1.02 to 1.74) ethnicity were more likely to experience instability than White CYP. Deprivation was not a significant predictor of instability. Compared with congenital abnormalities, CYP with most other primary diagnoses had a higher risk of instability; only CYP with a primary perinatal diagnosis had significantly lower risk (OR 0.23, 95% CI 0.19 to 0.29).ConclusionsThe large number of CYP with LLCs who are unstable, deteriorating or dying may benefit from input from specialist paediatric palliative care. The age group under 1 and CYP of South Asian, Black and Other ethnicities should be priority groups.
Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study
Authors: Patel Riyaz S , Lagord Catherine , Waterall Jamie , Moth Martin , Knapton Mike , Deanfield John E 
Published: September 2016

ObjectiveA modified version of the Joint British Societies (JBS3) ‘heart age’ tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk.DesignObservational, retrospective analysis of online tool use.SettingBetween February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages.ResultsThe online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid ‘heart age’ result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over-represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks.ConclusionsThese data suggest a high level of public interest in self-assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention.
How close are we to standardised extendedRASgene mutation testing? The UK NEQAS evaluation
Authors: Richman Susan D , Fairley Jennifer , Butler Rachel , Deans Zandra C 
Published: September 2016

AimsSince 2008,KRASmutation status in exon 2 has been used to predict response to anti-EGFR therapies. Recent evidence has demonstrated thatNRASstatus is also predictive of response. Several retrospective ‘extendedRAS’ analyses have been performed on clinical trial material. Despite this, are we really moving towards such extended screening practice in reality?MethodsData were analysed from four consecutive UK National External Quality Assessment Service for Molecular Genetics Colorectal cancer External Quality Assessment schemes (during the period 2014–2016), with up to 110 laboratories (worldwide) participating in each scheme. Testing of four or five tumour samples is required per scheme. Laboratories provided information on which codons were routinely screened, and provided genotyping and interpretation results for each sample.ResultsAt least 85% of laboratories routinely testedKRAScodons 12, 13 and 61. Over the four schemes, an increasing number of laboratories routinely testedKRAScodons 59, 117 and 146. Furthermore, more laboratories were introducing next generation sequencing technologies. The pattern of ‘extended testing’ was reassuringly similar forNRAS, although fewer laboratories currently test for mutations in this gene. Alarmingly, still only 36.1% and 24.1% of participating laboratories met the ACP Molecular Pathology and Diagnostics Group and American Society of Clinical Oncology guidelines, respectively, for extendedRAStesting in the latest assessment.ConclusionsDespite recommendations in the UK and USA on extendedRAStesting, there has clearly been, based on these results, a delay in implementation. Inadequate testing results in patients being subjected to harmful treatment regimens, which would not be the case, were routine practice altered, in line with evidence-based guidelines.
Regression grading in neoadjuvant treated pancreatic cancer: an interobserver study
Authors: N Kalimuthu Sangeetha , Serra Stefano , Dhani Neesha , Hafezi-Bakhtiari Sara , Szentgyorgyi Eva , Vajpeyi Rajkumar , Chetty Runjan 
Published: September 2016

AimSeveral regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems.MethodsFour gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7–20 slides from each case) of neoadjuvant chemoradiation-treated PDAC. A postscoring discussion with each pathologist was conducted. The results were entered into a standardised data collection form and statistical analyses were performed.ResultsThere was little concordance across the three systems. The Kendall coefficient of concordance agreement scores were: CAP: 2-poor, 2-fair; Evans: 1-fair, 1-moderate, 2-good; MDA: 1-poor, 2-moderate, 1-good. Interpretation in all three grades in the CAP grading system was a source of discrepancy. Furthermore, using fibrosis as a criterion to assess regression was contentious. In the Evans system, quantifying tumour destruction using arbitrary percentage cut-offs (ie, 9% vs 10%; 50% vs 51%, etc) was imprecise and subjective. Although the MDA system generated greatest concordance, this was due to ‘oversimplification’ surrounding wide, arbitrarily assigned thresholds of </> 5% of tumour.ConclusionsAll systems lacked precision and clarity for accurate regression grading. Presently the clinical utility and impact of histological regression grading in patient management is questionable. There is a need to re-evaluate regression grading in the pancreas and establish a reproducible, clinically relevant grading system.
Explaining socioeconomic inequalities in self-rated health: a systematic review of the relative contribution of material, psychosocial and behavioural factors
Authors: Moor Irene , Spallek Jacob , Richter Matthias 
Published: September 2016

BackgroundMaterial, psychosocial and behavioural factors are important explanatory pathways for socioeconomic inequalities in health. The aim of this systematic review was to summarise the available evidence on empirical studies and to analyse the relative contribution of these factors for explaining inequalities in self-rated health.MethodsThe study was performed in compliance with PRISMA guidelines. The literature search was conducted in the electronic databases PubMed and Web of Science (1996–2016) as well as by screening of reference lists of obtained articles. Two reviewers performed the search and critical appraisal of the studies. All studies that focus on explaining socioeconomic inequalities in self-rated health, including at least 2 of the 3 main pathways and analysing the relative contribution of these approaches in separate and joint models, were included.ResultsEleven publications were included. Separate analyses showed that material, psychosocial and behavioural factors contribute to the explanation of socioeconomic inequalities in self-rated health. However, the combined analyses revealed that material factors contributed most to differences in self-rated health because of their higher independent (direct) effect and additional shared (indirect) effect (through psychosocial and behavioural factors). These results were largely independent of age, gender and indicator of socioeconomic status.ConclusionsThe evidence presented might be used for policymakers to identify and to justify prioritisation in terms of prevention and health promotion. The findings show that multiple factors are important for tackling social inequalities in health. Strategies for reducing these inequalities should focus on material/structural living conditions as they shape conditions of psychosocial resources and health behaviour.
Republished: Use of aspirin as sole oral antiplatelet therapy in acute flow diversion for ruptured dissecting aneurysms
Authors: Chiu Albert Ho Yuen , Ramesh Rajalakshmi , Wenderoth Jason , Davies Mark , Cheung Andrew 
Published: September 2016

Subarachnoid hemorrhage secondary to rupture of a circumferential dissecting aneurysm continues to be a treatment dilemma. Vessel sacrifice, when possible, continues to be the safest option but in certain cases this is not possible due to lack of collateral supply. In such cases, coil assisted endovascular flow diversion has become a potential option but the requirement for dual antiplatelet therapy in an unsecured intracranial aneurysm continues to raise concern.We present a 48-year-old man with a World Federation of Neurological Surgeons grade 5 subarachnoid hemorrhage, secondary to a ruptured intradural left vertebral artery dissecting aneurysm, who was treated successfully with a pipeline embolization device with Shield technology using aspirin and a single intravenous loading dose of abciximab. To our knowledge, this is the first case of an acute flow diversion performed using only aspirin as the sole oral antiplatelet agent.
Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes
Authors: Fares Hassan , DiNicolantonio James J , O'Keefe James H , Lavie Carl J 
Published: September 2016

ObjectivesHypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers. One of the oldest groups of antihypertensives, the calcium channel blockers are a heterogeneous group of medications.MethodsThis review paper will focus on amlodipine, a dihydropyridine calcium channel blockers, which has been widely used for 2 decades.ResultsAmlodipine has good efficacy and safety, in addition to strong evidence from large randomised controlled trials for cardiovascular event reduction.ConclusionsAmlodipine should be considered a first-line antihypertensive agent.
Clinical characteristics of canine fibrocartilaginous embolic myelopathy (FCE): a systematic review of 393 cases (1973–2013)
Authors: Bartholomew K. A. , Stover K. E. , Olby N. J. , Moore S. A. 
Published: September 2016

Fibrocartilaginous embolic myelopathy (FCE) is common in dogs; however, there is conflicting information in the veterinary literature regarding clinical characteristics and data on recovery in severe cases is sparse. A systematic review of canine FCE was performed to delineate the natural history of this disease. 322 previously reported cases and 71 previously unreported cases were identified for inclusion. Source publications were identified via PubMed central search and by references from review articles. Previously unreported cases were identified via computerised medical records search at two veterinary institutions. FCE was most common in middle‐aged large breed dogs (30 per cent); however, the miniature schnauzer was the most frequently reported individual breed and small breeds comprised 24 per cent of all reported cases. The most common neuroanatomical localisation was a T3‐L3 myelopathy (33.1 per cent). Prognosis for recovery of ambulation was good to excellent with 85 per cent of cases regaining the ability to walk unassisted, most within 3 weeks. Persistent neurological deficits were common in patients that recovered ambulation (49.1 per cent). When nociception was absent in the affected limbs at initial presentation, rate of recovery was lower (10 per cent); however, this data is likely biased by limited follow‐up in more severe cases. Future prospective studies should evaluate prognosis for more severely affected patients.
Great Lakes Water Levels: Decomposing Time Series for Attribution
Authors: Pietrafesa Leonard J. , Bao Shaowu , Huang Norden E. , Gayes Paul T. , Yan Tingzhuang , Slattery Michael P. 
Published: September 2016

Great Lakes water levels have been trending downwards throughout the 20th and into the 21st centuries. Potential causes are numerous. There have been dredging and water diversion projects over the last 110 years, increasing demand for fresh water consumption from a rising population, and considerable variations in environmental factors (rainfall, snowfall, air temperature, and wind), all causal in nature. A thorough assessment of the National Ocean and Atmospheric Administration (NOAA) National Center for Environmental Information (NCEI) and the NOAA National Centers for Environmental Prediction and the National Center for Atmospheric Research (NCEP/NCAR) — Reanalysis Project (RP) archives of time series of winds, air temperatures, rainfall and snowfall, and water level data, reveals that falling lake levels can be linked to rising air temperatures. Nonuniform, post-glacial, isostatic adjustments of the entire Great Lakes region has further complicated the system as land mass tilting causes localized uplift or subsidence that has also altered relative water levels. A mathematical decomposition of the various data sets and accessory calculations strongly indicate regional atmospheric temperature increases over the entire 20th century and the early 21st century resulting in increased evaporation, appears to be the dominant driving factor in the continued downward trend of water levels in the Great Lakes. Moreover, a high degree of correlation was discovered in comparing water level in the Great Lakes with the comparable temporal variability and record length trends evident both the Global (Land and Ocean) Surface Temperature Anomaly (GSTA) time series and the Atlantic Multidecadal Oscillation (the AMO). It is of note that there have been several water level events since 2013 from which the long term losses of fresh water have undergone a change and the lakes have gained fresh water. This presents an apparent quandary to our nearly 120 year, record length study which revealed downward trends in water levels. To wit, this recent upward movement begs the question: Is the two-year change a precursor to increases in water levels or is it just a local blip? We will focus on data up to 2013, but comment upon recently reported increases as part of our analyses.
Geological map fusion: OneGeology-Europe and INSPIRE
Authors: Laxton J. L. 
Published: September 2016

Abstract
Geological maps can be seen as a type of model and can be implemented in digital systems as geological spatial databases. In this context, geological map fusion can be implemented at different levels: harmonization of the conceptual data model describing the map objects; the use of shared concepts to describe properties in the model to give semantic harmonization; and ensuring geometric consistency. GeoSciML has been developed as an interchange language for geosciences information, derived from a common conceptual data model, along with common vocabularies of concepts to populate the object properties. GeoSciML and the vocabularies were used in the OneGeology-Europe project where a 1:1 million scale geological map of Europe was delivered using disseminated web services from 20 different data providers. The lessons learnt from the OneGeology-Europe project informed the development of the INSPIRE Geology Data Specification. The INSPIRE data specification is used to define what information must be made available through web services under the INSPIRE legislation, so has to be kept simple. The INSPIRE data model can be extended with GeoSciML and will provide a basis for geological map fusion.