bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenovirus-Based Vaccines against Rhesus Lymphocryptovirus EBNA-1 Induce Expansion of Specific CD8
+
and CD4
+
T Cells in Persistently Infected Rhesus Macaques
Authors: Leskowitz R. , Fogg M. H. , Zhou X. Y. , Kaur A. , Silveira E. L. V. , Villinger F. , Lieberman P. M. , Wang F. , Ertl H. C. 
Published: February 2014

ABSTRACT

The impact of Epstein-Barr virus (EBV) on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA-1) is an important target for vaccination because it is the only protein expressed in all EBV-associated malignancies. We have designed and tested two therapeutic EBV vaccines that target the rhesus (rh) lymphocryptovirus (LCV) EBNA-1 to determine if ongoing T cell responses during persistent rhLCV infection in rhesus macaques can be expanded upon vaccination. Vaccines were based on two serotypes of E1-deleted simian adenovirus and were administered in a prime-boost regimen. To further modulate the response, rhEBNA-1 was fused to herpes simplex virus glycoprotein D (HSV-gD), which acts to block an inhibitory signaling pathway during T cell activation. We found that vaccines expressing rhEBNA-1 with or without functional HSV-gD led to expansion of rhEBNA-1-specific CD8
+
and CD4
+
T cells in 33% and 83% of the vaccinated animals, respectively. Additional animals developed significant changes within T cell subsets without changes in total numbers. Vaccination did not increase T cell responses to rhBZLF-1, an immediate early lytic phase antigen of rhLCV, thus indicating that increases of rhEBNA-1-specific responses were a direct result of vaccination. Vaccine-induced rhEBNA-1-specific T cells were highly functional and produced various combinations of cytokines as well as the cytolytic molecule granzyme B. These results serve as an important proof of principle that functional EBNA-1-specific T cells can be expanded by vaccination.

IMPORTANCE
EBV is a common human pathogen that establishes a persistent infection through latency in B cells, where it occasionally reactivates. EBV infection is typically benign and is well controlled by the host adaptive immune system; however, it is considered carcinogenic due to its strong association with lymphoid and epithelial cell malignancies. Latent EBNA-1 is a promising target for a therapeutic vaccine, as it is the only antigen expressed in all EBV-associated malignancies. The goal was to determine if rhEBNA-1-specific T cells could be expanded upon vaccination of infected animals. Results were obtained with vaccines that target EBNA-1 of rhLCV, a virus closely related to EBV. We found that vaccination led to expansion of rhEBNA-1 immune cells that exhibited functions fit for controlling viral infection. This confirms that rhEBNA-1 is a suitable target for therapeutic vaccines. Future work should aim to generate more-robust T cell responses through modified vaccines.
A Host-Oriented Inhibitor of Junin Argentine Hemorrhagic Fever Virus Egress
Authors: Lu Jianhong , Han Ziying , Liu Yuliang , Liu Wenbo , Lee Michael S. , Olson Mark A. , Ruthel Gordon , Freedman Bruce D. , Harty Ronald N. 
Published: February 2014

ABSTRACT

There are currently no U.S. Food and Drug Administration (FDA)-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as a National Institute of Allergy and Infectious Disease/Centers for Disease Control and Prevention category A priority pathogen. The PTAP late (L) domain motif within JUNV Z protein facilitates virion egress and transmission by recruiting host Tsg101 and other ESCRT complex proteins to promote scission of the virus particle from the plasma membrane. Here, we describe a novel compound (compound 0013) that blocks the JUNV Z-Tsg101 interaction and inhibits budding of virus-like particles (VLPs) driven by ectopic expression of the Z protein and live-attenuated JUNV Candid-1 strain in cell culture. Since inhibition of the PTAP-Tsg101 interaction inhibits JUNV egress, compound 0013 serves as a prototype therapeutic that could reduce virus dissemination and disease progression in infected individuals. Moreover, since PTAP
l
-domain-mediated Tsg101 recruitment is utilized by other RNA virus pathogens (e.g., Ebola virus and HIV-1), PTAP inhibitors such as compound 0013 have the potential to function as potent broad-spectrum, host-oriented antiviral drugs.

IMPORTANCE
There are currently no FDA-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as an NIAID/CDC category A priority pathogen. Here, we describe a prototype therapeutic that blocks budding of JUNV and has the potential to function as a broad-spectrum antiviral drug.
Associations between environmental exposures and asthma control and exacerbations in young children: a systematic review
Authors: Dick Smita , Doust Emma , Cowie Hilary , Ayres Jon G , Turner Steve 
Published: February 2014

ObjectiveTo complete a systematic review of the literature describing associations between all environmental exposures and asthma symptoms and exacerbations in children up to mean age of 9 years.DesignSystematic review.SettingReference lists of identified studies and reviews were searched for all articles published until November 2013 in electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Controls Trials Register).ParticipantsStudies were selected which examined a link between exposure to environmental factors and asthma symptoms and exacerbations where the study participants were children with a mean age of ⩽9 years.Primary and secondary outcome measuresIndices of asthma symptoms, control and exacerbations.ResultsA total of 27 studies were identified including eight where inhaled allergens and four where environmental tobacco smoke (ETS) were the exposures of interest. There was evidence that exposure to allergen, ETS, poor air quality and unflued heaters had a modest magnitude of effect (ORs between 2 and 3). There was also evidence of interactions observed between exposures such as allergen and ETS.ConclusionsExposure to inhaled allergens, ETS, unflued heaters and poor air quality has an important effect on exacerbations in young children with asthma and should be minimised or, ideally, avoided. Better understanding of the effect of exposure to damp housing, air conditioning and dietary factors plus interactions between environmental exposures associated with exacerbations is required.
The direct and indirect impact of comorbidity on the survival of patients with non-small cell lung cancer: a combination of survival, staging and resection models with missing measurements in covariates
Authors: Iachina Maria , Green Anders , Jakobsen Erik 
Published: February 2014

ObjectiveTo examine the direct and indirect impact of comorbidity on the survival.DesignA historical cohort study.SettingDenmark.ParticipantsAll patients with non-small cell lung cancer who were registered in the Danish Lung Cancer Registry in 2010.Main outcome measuresThe influence of comorbidity on stage misclassification, probability of resection and survival.ResultsIt was estimated that the comorbidity influences the probability of resection with OR 0.65 and 95% credible interval (0.54; 0.79), the staging process with OR 1.08 and 95% credible interval (0.96; 1.20), and the survival process with HR 1.08 and 95% credible interval (1.02; 1.14).ConclusionsWe found that comorbidity has a significant indirect effect on survival mediated by the resection process and a slightly direct effect on mortality.
Positive and negative reasons for sickness presenteeism in Norway and Sweden: a cross-sectional survey
Authors: Johansen Vegard , Aronsson Gunnar , Marklund Staffan 
Published: February 2014

ObjectivesThis article investigates various reasons for sickness presenteeism (SP), that is, going to work despite illness. The research questions asked is: What are the main reported reasons for SP in Norway and Sweden?DesignCross-sectional survey in Norway and Sweden. Use of binomial logistic regression analysis.ParticipantsA random sample of people aged between 20 and 60 years was obtained from complete and updated databases of the Norwegian and Swedish populations. A postal questionnaire was sent to the selected individuals, with response rate 33% (n=2843). 2533 workers responded to questions about SP during the last 12 months.Primary and secondary outcome measuresThe article informs about the distribution of reasons for SP in Norway and Sweden, selected by the respondents from a closed list. The article also examines which factors influence the most often reported reasons for SP.Results56% of the Norwegian and Swedish respondents experienced SP in the previous year. The most frequently reported reasons for SP include not burden colleagues (43%), enjoy work (37%) and feeling indispensable (35%). A lower proportion of Norwegians state that they cannot afford taking sick leave adjusted OR (aOR 0.16 (95% CI 0.10 to 0.22)), while a higher proportion of Norwegians refer to that they enjoy their work (aOR=1.64 (95% CI 1.28 to 2.09)). Women and young workers more often report that they do not want to burden their colleagues. Managers (aOR=2.19 (95% CI 1.67 to 2.86)), highly educated persons and the self-employed more often report that they are indispensable.ConclusionsPositive and negative reasons for SP are reported, and there are significant differences between respondents from the two countries. The response rate is low and results must be interpreted with caution.Study designCross-sectional study.
Perceptions and experiences of financial incentives: a qualitative study of dialysis care in England
Authors: Abma Inger , Jayanti Anuradha , Bayer Steffen , Mitra Sandip , Barlow James 
Published: February 2014

ObjectiveThe objective of the study was to understand the extent to which financial incentives such as Payment by Results and other payment mechanisms motivate kidney centres in England to change their practices.DesignThe study followed a qualitative design. Data collection involved 32 in-depth semistructured interviews with healthcare professionals and managers, focusing on their subjective experience of payment structures.ParticipantsParticipants were kidney healthcare professionals, clinical directors, kidney centre managers and finance managers. Healthcare commissioners from different parts of England were also interviewed.SettingParticipants worked at five kidney centres from across England. The selection was based on the prevalence of home haemodialysis, ranging from low (<3%), medium (5–8%) and high (>8%) prevalence, with at least one centre in each one of these categories at the time of selection.ResultsWhile the tariff for home haemodialysis is not a clear incentive for its adoption due to uncertainty about operational costs, Commissioning for Quality and Innovation (CQUIN) targets and the Best Practice Tariff for vascular access were seen by our case study centres as a motivator to change practices.ConclusionsThe impact of financial incentives designed at a policy level is influenced by the understanding of cost and benefits at the local operational level. In a situation where costs are unclear, incentives which are based on the improvement of profit margins have a smaller impact than incentives which provide an additional direct payment, even if this extra financial support is relatively small.
Bone mineral density, rib pain and other features of the female athlete triad in elite lightweight rowers
Authors: Dimitriou Lygeri , Weiler Richard , Lloyd-Smith Rebecca , Turner Antony , Heath Luke , James Nic , Reid Anna 
Published: February 2014

ObjectiveTo determine bone mineral density (BMD) and the associations among BMD, menstrual history, disordered eating (DE), training history, intentional weight loss (IWL) and rib pain for the first time in female lightweight rowers.Setting9 lightweight rowing clubs, UK.Participants29 Caucasian female lightweight rowers volunteered. 21 (12 active, 9 retired) completed the study. Inclusion criteria: female lightweight rowers aged over 18 years. Exclusion criteria: participants with a history of bone disease, used medications known to influence BMD or if they were pregnant, lactating or postmenopausal.Main outcome measuresDual-energy X-ray absorptiometry measured total body (TB) composition and BMD at the spine, femoral neck (FN), radius and TB. DE, oligomenorrhoea/amenorrhoea years; rib pain and training history.ResultsDE was reported in six of the rowers. The active with DE started rowing younger (p<0.05) than those without, and their amount of IWL was associated with Eating Attitudes Test-26 score (p<0.05). Some participants reported a history of oligomenorrhoea/amenorrhoea 17 (76%) and/or rib pain 7 (32%) with those with rib pain having lower spine and TB Z-scores (p<0.05) than those without. Those with oligomenorrhoea/amenorrhoea had lower spine Z-scores (p<0.01) than those without. Twelve participants had low BMD; three at spine; one at FN; and eight at radius. Thirteen per cent of mean total training hours (18.6±9.1 h/week) were spent strength training (2.4±2.2 h/week).ConclusionsUpper body exercises incorporating multidimensional high peak bone strain were not reported and may need to be considered in their strength training to improve radial BMD. Results suggest IWL and high-level training at a young age increases the likelihood of DE and there may be a lack of quality nutritional support for these athletes. Thus, multidisciplinary sport science support should be offered at a young age and perhaps also to consider changing the weight rules to prevent the development of the Triad.
On site assessment of cardiac function and neural regulation in amateur half marathon runners
Authors: Dalla Vecchia Laura , Traversi Egidio , Porta Alberto , Lucini Daniela , Pagani Massimo 
Published: February 2014

ObjectiveStrenuous exercise variably modifies cardiovascular function. Only few data are available on intermediate levels of effort. We therefore planned a study in order to address the hypothesis that a half marathon distance would result in transient changes of cardiac mechanics, neural regulation and biochemical profile suggestive of a complex, integrated adaptation.MethodsWe enrolled 35 amateur athletes (42±7 years). Supine and standing heart rate variability and a complete echocardiographic evaluation were assessed on site after the completion of a half marathon (postrace) and about 1 month after (baseline). Biochemical tests were also measured postrace.ResultsCompared to baseline, the postrace left ventricular end-diastolic volume was smaller, peak velocity of E wave was lower, peak velocity of A wave higher, and accordingly the E/A ratio lower. The postrace heart and respiratory rate were higher and variance of RR interval lower, together with a clear shift towards a sympathetic predominance in supine position and a preserved response to orthostasis. At baseline, athletes were characterised by a lower, although still predominant, sympathetic drive with a preserved physiological response to standing.ConclusionsImmediately after a half marathon there are clear marks that an elevated sympathetic cardiac drive outlasts the performance, together with decreased left ventricular diastolic volumes and slight modifications of the left ventricular filling pattern without additional signs of diastolic dysfunction or indices of transient left or right ventricular systolic abnormalities. Furthermore, no biochemical indices of any permanent cardiac damage were found.
Feasibility and outcomes of ajmaline provocation testing for Brugada syndrome in children in a specialist paediatric inherited cardiovascular diseases centre
Authors: McMillan Merlin Ranald , Day Thomas George , Bartsota Margarita , Mead-Regan Sarah , Bryant Rory , Mangat Jasveer , Abrams Dominic , Lowe Martin , Kaski Juan Pablo 
Published: February 2014

ObjectivesBrugada syndrome (BrS) is an inherited arrhythmia syndrome that causes sudden cardiac death in the young. The class Ia antiarrhythmic ajmaline can be used to provoke the diagnostic ECG pattern. Its use has been established in adults, but little data exist on the ajmaline provocation test in children. This study aims to determine the safety and feasibility of ajmaline provocation testing in a large paediatric cohort in a specialist paediatric inherited cardiac diseases centre.Methods98 consecutive ajmaline tests were performed in 95 children between September 2004 and July 2012 for family history of BrS (n=46 (48%)); family history of unexplained sudden cardiac death (n=39 (41%); symptoms with suspicious ECG abnormalities (n=9 (10%)). Three patients were retested with age, due to the possibility of age-related penetrance. ECG parameters were measured at baseline and during maximal ajmaline effect.ResultsThe mean patient age was 12.55 years, 43% were female. Nineteen patients (20%) had a positive ajmaline test. There were no arrhythmias or adverse events during testing. Ajmaline provoked significant prolongation of the PR, QRS and QTc in all patients. Mean follow-up was 3.62 years with no adverse outcomes reported in any patients with BrS. There were no predictors of a positive ajmaline provocation test on multivariable analysis. One patient who tested negative at 12 years of age, subsequently tested positive at 15 years of age.ConclusionsAjmaline testing appears safe and feasible in children when performed in an appropriate setting by an experienced team. Test positivity may change with age in individuals, suggesting that the test should be repeated in the late teenage years or early adulthood.
Assessment of a blood preservation protocol for use in ferrets before transfusion
Authors: Pignon C. , Donnelly T. M. , Todeschini C. , Deschamps J. Y. , Roux F. A. 
Published: February 2014

Blood transfusion has been described in ferrets as a treatment for oestrus‐associated anaemia and as a life‐saving therapy following trauma, iatrogenic (usually surgery‐induced) anaemia, autoimmune haemolytic anaemia and pure red cell aplasia. Although blood banking is a common method for storage of feline and canine blood it is not currently done with ferret blood. The aim of this study was to determine the shelf‐life of ferret blood using the anticoagulant citrate‐phosphate‐dextrose‐solution with adenine (CPDA). Two male ferrets were used as blood donors. From each ferret, 6 ml of blood was taken from the cranial vena cava and stored in 10 ml polyethylene terephthalate (PET) blood tubes containing 1 ml of CPDA solution. Blood was taken from each ferret once per month for five months. These 10 blood samples were stored in a laboratory refrigerator at 4°C for four weeks. Biochemical (glucose, pH, lactate, potassium, sodium) and haematological (haematocrit, light microscopic blood smear examination) analyses were performed on the stored blood at days 0, 7, 14, 21 and 28. Biochemical analyses revealed a progressive decrease from day seven in the stored blood pH, glucose and sodium, with a concomitant increase in lactate and potassium. These results are attributable to the ongoing metabolism and deterioration of the red blood cells (RBC) while in storage, and are more rapid than described for human or canine stored blood. Haematological analyses revealed a progressive elevation of the haematocrit due to the appearance of hypochromic red blood cells and echinocytes beginning at day 7. Haemolysis was observed in the microhaematocrit capillary tube sample by day 21, and microscopic clots were visible on the blood smear by day 28. The low blood pH and the appearance of many hypochromic RBCs and some echinocytes from day 7 in CPDA‐stored ferret blood, suggest stored ferret blood has a short shelf‐life when compared with stored human or canine blood. We recommend that ferret blood stored in CPDA should not be used for transfusion after seven days of storage at 4°C.
QUALITY SYSTEM FOR PRODUCTION SOFTWARE (QSPS): AN INNOVATIVE APPROACH TO IMPROVE THE QUALITY OF PRODUCTION SOFTWARE
Authors: KIFOR C. V. , TUDOR N. , BARAL LAL MOHAN 
Published: February 2014

A quality system for production software should be part of the quality management system of an organization and can be expressed as objectives in the form of processes, procedures, tools and responsibilities, designed and developed to fulfil the quality requirements. These usually are addressing the customers (external or internal), compliance with standards (effectiveness) waste reduction and better use of resources (efficiency) for continual improvement. Such systems are designed according to the requirements of the standards for quality management, software engineering and information security. Quality systems themselves could not provide all necessary means for driving the organization to the quality and excellence of a product. Still there are some gaps in the processes which are not covered by too generic standards and it is the organizational ability to cover the gaps in an appropriate way. The aim of this paper is to examine the effectiveness of our proposed conceptual QSPS model to reduce the gaps in the processes of an organization by enhancing the quality of production software. In order to achieve that goal, a mathematical representation of QSPS has been derived and an evaluation has been realized among different software quality methods. The reliability and validity of the QSPS has been examined through the practical application to the automotive industry considering the elements like: (i) Planning, time and cost evaluation (ii) Software requirements (management, risk, quality and security) (iii) Validation and verification of the implemented software before release (iv) Internal release of the software (v) Client release of the software (vi) Functional monitoring after release in the production and continuous improvement process (vii) Customer satisfaction. The results of mathematical simulation and practical application revealed that the proposed QSPS model showed superior phenomena compared with other known software quality methods and also expressed significant advantages, while using it on the production software. So, an effective application of QSPS would result in the smooth running of the production software to get a high quality product according to customer and standard requirements.