bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4 T Cells Promote CD8 T Cell Immunity at the Priming and Effector Site during Viral Encephalitis
Authors: Phares Timothy W. , Stohlman Stephen A. , Hwang Mihyun , Min Booki , Hinton David R. , Bergmann Cornelia C. 
Published: December 2011

ABSTRACTCD4 T cell activation during peripheral infections not only is essential in inducing protective CD8 T cell memory but also promotes CD8 T cell function and survival. However, the contributions of CD4 T cell help to antiviral CD8 T cell immunity during central nervous system (CNS) infection are not well established. Encephalitis induced by the sublethal coronavirus JHMV was used to identify when CD4 T cells regulate CD8 T cell responses following CNS infection. Peripheral expansion of virus-specific CD8 T cells was impaired when CD4 T cells were ablated prior to infection but not at 4 days postinfection. Delayed CD4 T cell depletion abrogated CD4 T cell recruitment to the CNS but only slightly diminished CD8 T cell recruitment. Nevertheless, the absence of CNS CD4 T cells was associated with reduced gamma interferon (IFN-γ) and granzyme B expression by infiltrating CD8 T cells, increased CD8 T cell apoptosis, and impaired control of infectious virus. CD4 T cell depletion subsequent to CD4 T cell CNS migration restored CD8 T cell activity and virus control. Analysis of γc-dependent cytokine expression indicated interleukin-21 (IL-21) as a primary candidate optimizing CD8 T cell activity within the CNS. These results demonstrate that CD4 T cells play critical roles in both enhancing peripheral activation of CD8 T cells and prolonging their antiviral function within the CNS. The data highlight the necessity for temporally and spatially distinct CD4 T cell helper functions in sustaining CD8 T cell activity during CNS infection.
Evidence for a Common Evolutionary Origin of Coronavirus Spike Protein Receptor-Binding Subunits
Authors: Li Fang 
Published: December 2011

ABSTRACT
Among different coronavirus genera, the receptor-binding S1 subunits of their spike proteins differ in primary, secondary, and tertiary structures. This study identified shared structural topologies (connectivity of secondary structural elements) in S1 domains of different coronavirus genera. The results suggest that coronavirus S1 subunits share a common evolutionary origin but have attained diverse sequences and structures following extensive divergent evolution. The results also increase understanding of the structures and functions of coronavirus S1 domains whose tertiary structures are currently unknown.
Combined Endocardial and Epicardial Catheter Ablation in Arrhythmogenic Right Ventricular Dysplasia Incorporating Scar Dechanneling Technique
Authors: Berruezo Antonio , Fernández-Armenta Juan , Mont Lluís , Zeljko Hrvojka , Andreu David , Herczku Csaba , Boussy Tim , Tolosana Jose María , Arbelo Elena , Brugada Josep 
Published: December 2011

Background—
Ventricular tachycardia (VT) ablation in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has a low success rate. A more extensive epicardial (Epi) arrhythmogenic substrate could explain the low efficacy. We report the results of combined endocardial (Endo) and Epi VT ablation and conducting channel (CC) elimination.

Methods and Results—

Eleven consecutive patients with ARVD/C were included in the study. A high-density 3D Endo (321±93 sites mapped) and Epi (302±158 sites mapped) electroanatomical voltage map was obtained during sinus rhythm to define scar areas (<1.5 mV) and CCs inside the scars, between scars, or between the tricuspid annulus and a scar. The end point of the ablation procedure was the elimination of all identified CCs (scar dechanneling) and the abolition of all inducible VTs. The mean procedure and fluoroscopy time were 177±63 minutes and 20±8 minutes, respectively. Epi scar area was larger in all cases (26±18 versus 94±45 cm
2
,
P
<0.01). The combined Endo and Epi VT ablation eliminated all clinical and induced VTs, and the addition of scar dechanneling resulted in noninducibility in all cases. Seven patients continued on sotalol. During a median follow-up of 11 months (6–24 months), only 1 (9%) patient had a VT recurrence. There was a single major bleeding event that did not preclude a successful procedure.

Conclusions—
Combined Endo and Epi mapping reveals a wider Epi VT substrate in patients with ARVD/C with clinical VTs. As a first-line therapy, combined Endo and Epi VT ablation incorporating scar dechanneling achieves a very good short- and midterm success rate.
Comparing Large-Scale Hydrological Model Simulations to Observed Runoff Percentiles in Europe
Authors: Gudmundsson Lukas , Tallaksen Lena M. , Stahl Kerstin , Clark Douglas B. , Dumont Egon , Hagemann Stefan , Bertrand Nathalie , Gerten Dieter , Heinke Jens , Hanasaki Naota , Voss Frank , Koirala Sujan 
Published: December 2011

AbstractLarge-scale hydrological models describing the terrestrial water balance at continental and global scales are increasingly being used in earth system modeling and climate impact assessments. However, because of incomplete process understanding and limits of the forcing data, model simulations remain uncertain. To quantify this uncertainty a multimodel ensemble of nine large-scale hydrological models was compared to observed runoff from 426 small catchments in Europe. The ensemble was built within the framework of the European Union Water and Global Change (WATCH) project. The models were driven with the same atmospheric forcing data. Models were evaluated with respect to their ability to capture the interannual variability of spatially aggregated annual time series of five runoff percentiles—derived from daily time series—including annual low and high flows. Overall, the models capture the interannual variability of low, mean, and high flows well. However, errors in the mean and standard deviation, as well as differences in performance between the models, became increasingly pronounced for low runoff percentiles, reflecting the uncertainty associated with the representation of hydrological processes, such as the depletion of soil moisture stores. The large spread in model performance implies that any single model should be applied with caution as there is a great risk of biased conclusions. However, this large spread is contrasted by the good overall performance of the ensemble mean. It is concluded that the ensemble mean is a pragmatic and reliable estimator of spatially aggregated time series of annual low, mean, and high flows across Europe.
Ethanol Lock Therapy in Reducing Catheter‐Related Bloodstream Infections in Adult Home Parenteral Nutrition Patients
Authors: John Bijo K. , Khan Maqsood A. , Speerhas Rex , Rhoda Kristen , Hamilton Cindy , DeChicco Robert , Lopez Rocio , Steiger Ezra , Kirby Donald F. 
Published: December 2011

BackgroundEquivocal data demonstrate the efficacy of ethanol lock therapy (ELT) in preventing catheter‐related bloodstream infections (CRBSIs) in home parenteral nutrition (HPN) patients, but it is not currently a standard of practice. The objective of this study is to investigate the efficacy of ELT in reducing the incidence of CRBSIs in HPN patients.MethodsMedical records from the Cleveland Clinic database of adult HPN patients with CRBSIs placed on prophylactic ELT were retrospectively studied from January 2006 to August 2009 (n = 31). Outcomes were compared pre‐ and post‐ELT with the patients serving as their own controls. Medical‐grade (70%) ethanol was instilled daily into each lumen of the central venous catheter (CVC) between PN infusion cycles. Comparative analysis was performed using McNemar's test and Wilcoxon ranked tests.ResultsThirty‐one patients had 273 CRBSI‐related admissions prior to ELT in comparison to 47 CRBSI‐related admissions post‐ELT. Adjusted data for only tunneled CVC pre‐ and post‐ELT showed a similar reduction of CRBSI‐related admissions from 10.1 to 2.9 per 1000 catheter days (P < .001). There was also a statistically significant reduction in culture‐positive CRBSIs and number of catheters changed pre‐ and post‐ELT. There were no reported side effects or complications in any patient undergoing ELT.ConclusionsThis study supports the efficacy and safety of ELT in reducing CRBSI‐related admissions in HPN patients and potentially helps reduce the burden of CRBSI‐related healthcare costs. This novel technique shows great promise as a standard prophylaxis for CRBSI in HPN patients and must be incorporated in routine practice.
Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis
Authors: Yuan Hongfeng , Wang Zhiqiang , Li Ling , Zhang Hao , Modi Hardik , Horne David , Bhatia Ravi , Chen WenYong 
Published: December 2011

Abstract
The tyrosine kinase inhibitor imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but primary and acquired resistance of CML cells to the drug offset its efficacy. Molecular mechanisms for resistance of CML to tyrosine kinase inhibitors are not fully understood. In the present study, we show that BCR-ABL activates the expression of the mammalian stress response gene SIRT1 in hematopoietic progenitor cells and that this involves STAT5 signaling. SIRT1 activation promotes CML cell survival and proliferation associated with deacetylation of multiple SIRT1 substrates, including FOXO1, p53, and Ku70. Imatinib-mediated inhibition of BCR-ABL kinase activity partially reduces SIRT1 expression and SIRT1 inhibition further sensitizes CML cells to imatinib-induced apoptosis. Knockout of SIRT1 suppresses BCR-ABL transformation of mouse BM cells and the development of a CML-like myeloproliferative disease, and treatment of mice with the SIRT1 inhibitor tenovin-6 deters disease progression. The combination of SIRT1 gene knockout and imatinib treatment further extends the survival of CML mice. Our results suggest that SIRT1 is a novel survival pathway activated by BCR-ABL expression in hematopoietic progenitor cells, which promotes oncogenic transformation and leukemogenesis. Our findings suggest further exploration of SIRT1 as a therapeutic target for CML treatment to overcome resistance.
Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system
Authors: Worsøe Jonas , Fynne Lotte , Gregersen Tine , Schlageter Vincent , Christensen Lisbet A , Dahlerup Jens F , Rijkhoff Nico JM , Laurberg Søren , Krogh Klaus 
Published: December 2011

AbstractBackgroundTracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system.MethodsA small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position:x, y, z, and angle: θ, ϕ). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state.ResultsExperiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1vs. 10.53 min-1) (p = 0.03).ConclusionMTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.
The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers
Authors: Tulah Asif S , Parker Stuart G , Moffatt Miriam F , Wardlaw Andrew J , Connolly Martin J , Sayers Ian 
Published: December 2011

Abstract

Background
We have previously shown evidence that polymorphisms within genes controlling leukotriene B4 (LTB4) production (ALOX5AP and LTA4H) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB4 in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB4 (LTB4R1 and LTB4R2) influence baseline lung function and COPD susceptibility/severity in smokers.

Methods
Eight ALOX5AP, six LTA4H and six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV1 and FEV1/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389).

Results
No association with ALOX5AP, LTA4H or LTB4R survived correction for multiple testing. However, we showed modest association with LTA4H rs1978331C (intron 11) with increased FEV1 (p = 0.029) and with increased FEV1/FVC ratio (p = 0.020).

Conclusions
These data suggest that polymorphisms spanning ALOX5AP, LTA4H and the LTB4R locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for LTA4H rs1978331C (intron 11) in determining baseline FEV1 and FEV1/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.
A survey of engagement and competence levels in interventions and activities in a community mental health workforce in England
Authors: Lang Linda , Orton Sophie , Sallah David , Hewitt-Moran Teresa , Zhang Dongmei , Cullen Sean , Dixon Sheila , Bell Brian , Bell David , Meeson Lesley , Chen Ruoling 
Published: December 2011

Abstract

Background
National Health Service (NHS) mental health workforce configuration is at the heart of successful delivery, and providers are advised to produce professional development strategies. Recent policy changes in England have sharpened the focus on competency based role development. We determined levels of intervention activities, engagement and competence and their influencing factors in a community-setting mental health workforce.

Methods
Using a modified questionnaire based on the Yorkshire Care Pathways Model we investigated 153 mental health staff working in Coventry and Warwickshire NHS Trust. A median score of competence was computed across 10 cluster activities. Low engagement and competence levels were examined in a logistic regression model.

Results
In 220 activities, Monitoring risk was the highest rate of engagement (97.6%) and Group psychological therapy/Art/Drama therapy was the lowest engagement (3.6%). The median competence level based on all activities was 3.95 (proficient). There were significant differences in the competence level among professional groups; non-qualified support group (3.00 for competent), Counsellor/Psychologist/Therapist (3.38), Occupational therapists (3.76), Nurses (4.01), Medical staff (4.05), Social workers (4.25) and Psychologists (4.62 for proficient/expert). These levels varied with activity clusters; the lowest level was for Counsellor/Psychologist/Therapist in the accommodation activity (1.44 novice/advance beginner) and the highest for Occupational therapists in personal activity (4.94 expert). In a multivariate analysis, low competence was significantly related to non-qualified community support professions, late time of obtaining first qualification, more frequencies of clinical training, and training of cognitive behavioural therapy. The associations were similar in the analysis for 10 activity clusters respectively.

Conclusions
There was a reasonable competence level in the community-setting mental health workforce, but competence varied with professional groups and cluster activities. New staff and other non-qualified support professions need to receive efficient training, and the training content is more important than frequency to increase level of competence.
Earlier surgical intervention in congenital heart disease results in better outcome and resource utilization
Authors: Panni Roheena Z , Ashfaq Awais , Amanullah Muhammad M 
Published: December 2011

Abstract

Background
Congenital heart disease (CHD) accounts for a major proportion of disease in the pediatric age group. The objective of the study was to estimate the cost of illness associated with CHD pre, intra and postoperatively; among patients referred to a tertiary care hospital in Karachi, Pakistan. This is the first study conducted to estimate the cost of managing CHD in Pakistan.

Methods
A prevalence based cost of illness study design was used to estimate the cost of cardiac surgery (corrective & palliative) for congenital heart defects in children ≤ 5 years of age from June 2006 to June 2009. A total of 120 patients were enrolled after obtaining an informed consent and the data was collected using a pre-tested questionnaire.

Results
The mean age at the time of surgery in group A (1-12 mo age) was 6.08 ± 2.80 months and in group B (1-5 yrs) was 37.10 ± 19.94 months. The cost of surgical admission was found to be significantly higher in the older group, p = 0.001. The total number and cost of post-operative outpatient visits was also higher in group B, p = 0.003. Pre and post operative hospital admissions were not found to be significantly different among the two groups, p = 0.166 and 0.627, respectively. The number of complications were found to be different between the two groups (p = 0.019). Majority of these were contributed by hemorrhage and post-operative seizures.

Conclusion
This study concluded that significant expenditure is incurred by people with CHD; with the implication that resources could be saved by earlier detection and awareness campaigns.
The effects of varying protein and energy intakes on the growth and body composition of very low birth weight infants
Authors: Costa-Orvay Juan Antonio , Figueras-Aloy Josep , Romera Gerardo , Closa-Monasterolo Ricardo , Carbonell-Estrany Xavier 
Published: December 2011

AbstractObjectiveTo determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants.Study designThirty-eight VLBW infants whose weights were appropriate for their gestational ages were assessed for when they could tolerate oral intake for all their nutritional needs. Thirty-two infants were included in a longitudinal, randomized clinical trial over an approximate 28-day period. One control diet (standard preterm formula, group A, n = 8, 3.7 g/kg/d of protein and 129 kcal/kg/d) and two high-energy and high-protein diets (group B, n = 12, 4.2 g/kg/d and 150 kcal/kg/d; group C, n = 12, 4.7 g/kg/d and 150 kcal/kg/d) were compared. Differences among groups in anthropometry and body composition (measured with bioelectrical impedance analysis) were determined. An enriched breast milk group (n = 6) served as a descriptive reference group.ResultsGroups B and C displayed greater weight gains and higher increases in fat-free mass than group A.ConclusionAn intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants.
Orf virus DNA vaccines expressing ORFV 011 and ORFV 059 chimeric protein enhances immunogenicity
Authors: Zhao Kui , He Wenqi , Gao Wei , Lu Huijun , Han Tiesuo , Li Jing , Zhang Ximu , Zhang Bingbing , Wang Gaili , Su Gaoli , Zhao Zhihui , Song Deguang , Gao Feng 
Published: December 2011

Abstract

Background
ORFV attenuated live vaccines have been the main prophylactic measure against contagious ecthyma in sheep and goats in the last decades, which play an important role in preventing the outbreak of the disease. However, the available vaccines do not induce lasting immunity in sheep and goats. On the other hand, variation in the terminal genome of Orf virus vaccine strains during cell culture adaptation may affect the efficacy of a vaccine. Currently, there are no more effective antiviral treatments available for contagious ecthyma.

Results
We constructed three eukaryotic expression vectors pcDNA3.1-ORFV011, pcDNA3.1-ORFV059 and pcDNA3.1-ORFV011/ORFV059 and tested their immunogenicity in mouse model. High level expression of the recombinant proteins ORFV011, ORFV059 and ORFV011/ORFV059 was confirmed by western blotting analysis and indirect fluorescence antibody (IFA) tests. The ORFV-specific antibody titers and serum IgG1/IgG2a titers, the proliferation of lymphocytes and ORFV-specific cytokines (IL-2, IL-4, IL-6, IFN-γ, and TNF-α) were examined to evaluate the immune responses of the vaccinated mice. We found that mice inoculated with pcDNA3.1-ORFV 011/ORFV059 had significantly stronger immunological responses than those inoculated with pcDNA3.1-ORFV011, pcDNA3.1-ORFV059, or pcDNA3.1-ORFV011 plus pcDNA3.1-ORFV059. Compared to other vaccine plasmids immunized groups, pcDNA3.1-ORFV011/ORFV059 immunized group enhances immunogenicity.

Conclusions
We concluded that DNA vaccine pcDNA3.1-ORFV011/ORFV059 expressing ORFV011 and ORFV059 chemeric-proteins can significantly improve the potency of DNA vaccination and could be served as more effective and safe approach for new vaccines against ORFV.
Reconciling research and implementation in micro health insurance experiments in India: study protocol for a randomized controlled trial
Authors: Doyle Conor , Panda Pradeep , Van de Poel Ellen , Radermacher Ralf , Dror David M 
Published: December 2011

Abstract

Background
Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes.

Methods/Design
Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation.

Discussion
When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment.