bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the Schmallenberg Virus Gc Glycoprotein Facilitate Cellular Protein Synthesis Shutoff and Restore Pathogenicity of NSs Deletion Mutants in Mice
Authors: Varela Mariana , Pinto Rute Maria , Caporale Marco , Piras Ilaria M. , Taggart Aislynn , Seehusen Frauke , Hahn Kerstin , Janowicz Anna , de Souza William Marciel , Baumgärtner Wolfgang , Shi Xiaohong , Palmarini Massimo 
Published: March 2016

ABSTRACTSerial passage of viruses in cell culture has been traditionally used to attenuate virulence and identify determinants of viral pathogenesis. In a previous study, we found that a strain of Schmallenberg virus (SBV) serially passaged in tissue culture (termed SBVp32) unexpectedly displayed increased pathogenicity in suckling mice compared to wild-type SBV. In this study, we mapped the determinants of SBVp32 virulence to the viral genome M segment. SBVp32 virulence is associated with the capacity of this virus to reach high titers in the brains of experimentally infected suckling mice. We also found that the Gc glycoprotein, encoded by the M segment of SBVp32, facilitates host cell protein shutoffin vitro. Interestingly, while the M segment of SBVp32 is a virulence factor, we found that the S segment of the same virus confers by itself an attenuated phenotype to wild-type SBV, as it has lost the ability to block the innate immune system of the host. Single mutations present in the Gc glycoprotein of SBVp32 are sufficient to compensate for both the attenuated phenotype of the SBVp32 S segment and the attenuated phenotype of NSs deletion mutants. Our data also indicate that the SBVp32 M segment does not act as an interferon (IFN) antagonist. Therefore, SBV mutants can retain pathogenicity even when they are unable to fully control the production of IFN by infected cells. Overall, this study suggests that the viral glycoprotein of orthobunyaviruses can compensate, at least in part, for the function of NSs. In addition, we also provide evidence that the induction of total cellular protein shutoff by SBV is determined by multiple viral proteins, while the ability to control the production of IFN maps to the NSs protein.IMPORTANCEThe identification of viral determinants of pathogenesis is key to the development of prophylactic and intervention measures. In this study, we found that the bunyavirus Gc glycoprotein is a virulence factor. Importantly, we show that mutations in the Gc glycoprotein can restore the pathogenicity of attenuated mutants resulting from deletions or mutations in the nonstructural protein NSs. Our findings highlight the fact that careful consideration should be taken when designing live attenuated vaccines based on deletions of nonstructural proteins since single mutations in the viral glycoproteins appear to revert attenuated mutants to virulent phenotypes.
Effect of serotonin modulating pharmacotherapies on body mass index and dysglycaemia among children and adolescents: a systematic review and network meta-analysis protocol
Authors: Al Khalifah Reem A , De Long Nicole E , Florez Ivan D , Mbuagbaw Lawrence , Morrison Katherine M 
Published: March 2016

IntroductionSerotonin-modulating medications are commonly prescribed for mental health issues. Currently, there is limited consensus on weight gain and dysglycaemia development among children using these medications. The objective of this study is to review and synthesise all the available evidence on serotonin-modulating medications and their effects on body mass index (BMI), weight and glycaemic control.Methods and analysisWe will conduct a systematic review of all randomised controlled trials evaluating the use of serotonin-modulating medications in the treatment of children 2–17 years with mental health conditions. The outcome measures are BMI, weight and dysglycaemia. We will perform literature searches through Ovid Medline, Ovid Embase, PsycINFO and grey literature resources. Two reviewers from the team will independently screen titles and abstracts, assess the eligibility of full-text trials, extract information from eligible trials and assess the risk of bias and quality of the evidence. Results of this review will be summarised narratively and quantitatively as appropriate. We will perform a multiple treatment comparison using network meta-analysis to estimate the pooled direct, indirect and network estimate for all serotonin-modulating medications on outcomes if adequate data are available.Ethics and disseminationSerotonin-modulating medications are widely prescribed for children with mental health diseases and are also used off-label. This network meta-analysis will be the first to assess serotonin modulating antidepressants and their effects on weight and glycaemic control. We anticipate that our results will help physicians and patients make more informed choices while considering the side effect profile. We will disseminate the results of the systematic review and network meta-analysis through peer-reviewed journals.PROSPERO registration numberCRD42015024367.
ECG risk markers for atrial fibrillation and sudden cardiac death in minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised trial
Authors: Schlatzer Christian , Bratton Daniel J , Craig Sonja E , Kohler Malcolm , Stradling John R 
Published: March 2016

ObjectiveObstructive sleep apnoea (OSA), atrial fibrillation (AF) and sudden cardiac death (SCD) may occur concomitantly, and are of considerable epidemiological interest, potentially leading to morbidity and mortality. Effective treatment of OSA with continuous positive airway pressure (CPAP) could prevent progression and/or recurrence of AF and factors leading to SCD. Recently, a randomised controlled trial showed a statistically and clinically significant prolongation of measures of cardiac repolarisation after CPAP withdrawal in symptomatic patients with moderate to severe OSA. Whether or not CPAP therapy improves ECG risk markers of AF and SCD in patients with minimally symptomatic OSA as well, is unknown.Methods3 centres taking part in the MOSAIC (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular) trial randomisd 303 patients with minimally symptomatic OSA to receive either CPAP or standard care for 6 months. Treatment effects of CPAP on P-wave duration, P-wave dispersion, QT interval, QT dispersion, Tpeak-to-Tend (TpTe) and TpTe/QT ratio were analysed.ResultsParticipants were primarily men (83%). Mean age was 57.8 (7.2) and mean ODI (Oxygen Desaturation Index) at baseline was 13.1/h (12.3). Full 12-lead ECG data was available in 250 patients. Mean (SD) baseline intervals of P-wave duration, P-wave dispersion, QTcinterval, QT dispersion, TpTe and TpTe/QT ratio in ms were 87.4 (8.3), 42.3 (11.9), 397.8 (22.7), 43.1 (16.7), 73.5 (13.7) and 0.19 (0.0), respectively. No treatment effect of CPAP on risk markers for AF and SCD was found.ConclusionsThere seems to be no effect of CPAP on ECG measures of arrhythmia risk in patients with minimally symptomatic OSA.Trial registration numberISRCTN34164388; Post-results.
Information transfer in multidisciplinary operating room teams: a simulation-based observational study
Authors: Cumin David , Skilton Carmen , Weller Jennifer 
Published: March 2016

BackgroundCommunication of clinically relevant information between members of the operating room (OR) team is critical for safe patient care. Formal communication processes, such as briefing, sign in and time out, are designed to promote this.AimsWe investigated patterns of communication of clinically relevant information between OR staff in simulated surgical scenarios, to identify factors associated with effective information sharing. We focused on the influence of precase briefing, sign in and time out, which we defined as formal team communications.MethodTwenty teams of six participated in two scenarios during a day-long course. Participants each received unique, clinically relevant items of information (information probes) prior to simulations and were tested postscenario on recall of the information in the probe. Using videos of the simulations, we coded each time an information probe was mentioned against a structured framework.ResultsOf the 145 instances where a probe was mentioned at least once, 75 (51.7%) were mentioned during a formal team communication. However, there were 89 instances of a possible 234 (38%) where a probe was never mentioned. Some team members were more likely to mention the information than others. When probes were mentioned during formal team communications, significantly more team members were attentive (1.4 vs 2.3; p<0.001), the information was significantly more likely to be recalled and the team was five times more likely (p=0.01) to recall the information than if the information was only mentioned outside of a formal communication.ConclusionsWhile our study supports the value of formal team communications during precase briefing, sign in and time out in the Surgical Safety Checklist, our findings suggest suboptimal transmission of information between team members and unequal contributions of information by different professional groups.
Concussed athletes are more prone to injury both before and after their index concussion: a data base analysis of 699 concussed contact sports athletes
Authors: Burman Erik , Lysholm Jack , Shahim Pashtun , Malm Christer , Tegner Yelverton 
Published: March 2016

BackgroundIce hockey and football players suffering concussions might have an increased risk for injuries afterwards. We aimed to investigate if concussions predisposed athletes for subsequent sport injuries.MethodsPatient data were obtained from a data base established at the University Hospital in Umea, Sweden. Athletes who had suffered a concussion were included if they had been aged between 15 and 35 years of age, and played ice hockey, football (soccer), floorball and handball. They were studied in terms of all new or previous injuries during 24 months before and after their concussion. Results were compared with a control group of athletes from the same four sports with an ankle injury.ResultsAthletes with a concussion were more likely to sustain injuries compared with the control group, both before (OR 1.98. 95% CI 1.45 to 2.72) and after the concussion (OR 1.72. 95% CI 1.26 to 2.37). No increase in frequency of injury was found after a concussion compared with before. This was true for athletes in all four sports and for both sexes.ConclusionsThis study indicates that athletes sustaining a concussion may have a more aggressive or risk-taking style of play than their counterparts. Our data do not suggest that a concussion injury, per se, leads to subsequent injuries.
Patient-initiated appointments compared with standard outpatient care for rheumatoid arthritis: a randomised controlled trial
Authors: Fredriksson Cecilia , Ebbevi David , Waldheim Eva , Lindblad Staffan , Ernestam Sofia 
Published: March 2016

ObjectivesTo test the hypothesis that implementing a patient-initiated system of care could improve clinical outcome in rheumatoid arthritis (RA) using disease activity guided management.MethodsAn 18-month controlled blinded end point two-centre study with 131 patients with RA randomised to intervention (n=64) or control (n=67). The intervention group participants were guaranteed appointments to a rheumatologist within 10 working days if they subjectively experienced a flare in disease activity. The control group participants were booked in advance according to guidelines. Independent assessments were performed in the two groups at 0, 3, 6, 12 and 18 months. Outcome measures included: Disease Activity Score 28 (DAS28), a Visual Analogue Scale (satisfaction with care, confidence in care), number of appointments with a rheumatologist.ResultsDAS28 decreased. Median satisfaction and confidence in care were >90 mm on Visual Analog Scale. Median number of appointments was 3. There were no significant differences between the groups among these outcomes. Visits in the intervention group more often resulted in change of treatment than in the control group (p<0.001).ConclusionsPatient-initiated care was neither better nor inferior to traditional care in terms of outcomes analysed. Patient-initiated appointments can safely be used in everyday outpatient care of RA to empower the patient, if disease activity guided management is applied. Further research should investigate if this intervention can target a subgroup of patients and hence also result in released resources.
Investigation of insulin-like growth factor-1 gene with egg-laying traits in the Muscovy duck (Cairina moschata)
Authors: Wu X. , Liu X.T. , Lan J.J. , Wan X.P. , Yan M.J. , Lian S.Y. , Li A. 
Published: March 2016

Muscovy duck (Cairina moschata) is characterized by broodiness, and egg-laying traits in this species should be of primary concern. As a member of the IGF superfamily of proteins, insulin-like growth factor-1 (IGF-1) is an important positive regulator of growth and gonad development in vertebrates. To explore the effect of IGF-1 on the growth hormone/insulin-like growth factors (GH/IGF) axis, we cloned and characterized IGF-1 of Muscovy duck. The expression level of IGF-1 was widely expressed in all the tested tissues, and the highest level was detected in the liver. In laying ducks, IGF-1 expression levels in the hypothalamus, pituitary, and ovary were very significantly higher (P < 0.01) than that in the tissues of nesting duck, and IGF-1 expression levels in the heart and liver were significantly higher (P < 0.05) than that in nesting duck tissues. Furthermore, a single nucleotide polymorphism (SNP) (A/G) was found and significantly (P < 0.05) associated with age at first egg and egg number at 300 d. This study provides the first evidence that IGF-1 promote egg-laying traits of Muscovy duck through two axes, involving GH/IGF and hypothalamic–pituitary–gonadal axes. These findings enrich the information of IGF-1 of Muscovy duck and demonstrate for the first time the ability of IGF-1 to promote reproduction, indicating that IGF-1 could be used as an important marker gene.
Net energy system of feed formulation with or without enzyme supplementation in growing-finishing pigs fed barley-based diets with alternative feed ingredients
Authors: Velayudhan D.E. , Nyachoti C.M. 
Published: March 2016

The aim of this study was to determine the growth performance and carcass characteristics of growing-finishing pigs fed diets formulated on net energy (NE) basis with or without exogenous enzyme supplementation. Twenty-four pigs with an initial body weight (BW) of 25 kg were randomly allotted one of three treatments; a barley-based control diet formulated on a digestible energy (DE) basis (Diet A), control diet formulated on an NE basis (Diet B), and Diet B + multicarbohydrase enzyme (Diet C). Pigs were offered their respective diets in a 3-phase feeding program. Individual pig BW and feed disappearance were monitored once every 2 wk. Pigs were slaughtered when they reached 100 kg BW to determine carcass characteristics. During phase 1, an improvement (P = 0.02) in feed intake was observed in pigs fed Diet C compared with Diet B. In phase 3, pigs fed Diet B showed improvement in daily gain (P = 0.02) and feed efficiency (P = 0.05) compared with Diet A. Overall, when compared with control diet, pigs fed Diet B showed significant improvement in daily gain (P = 0.05) and feed efficiency (P = 0.01). In conclusion, the results indicate a better growth performance with diets formulated using the NE system. Moreover, enzyme supplementation had no effect on the overall performance of pigs.
Evidence of a union between organic carbon and water content in soil
Authors: Manns Hida R. , Parkin Gary W. , Martin Ralph C. 
Published: March 2016

Soil organic matter, comprising ∼58% soil organic carbon (SOC), is attributed with increased water holding capacity in the surface horizon of agricultural soil. This paper addresses the role of SOC as a component of a common functional unit in soil from analysis within a single field and over multiple fields. Soil data measured on the fields during the SMAPVEX12 satellite prelaunch algorithm development campaign exhibited high correlation among SOC, field-mean soil water content (SWC), bulk density, and soil texture. The analysis extended over a wide range of soil texture and wetness in the top 5 cm of soil over 50 agricultural fields covering ∼400 km2 of southern Manitoba. Data collected over a much smaller area from Ontario silt loam soils at the Elora Research Centre demonstrated a similar correlation between SOC and SWC in intensive field sampling. This intercorrelation of SOC and SWC is examined with partial least-squares regression, principal component analysis, and geostatistical semivariograms. A model is proposed to interpret the feedback process between SOC and SWC to explain the persistent correlation. Further work to substantiate the strengths and limits of the relationship between SOC and SWC may be beneficial for estimating SWC for remote sensing, agriculture, hydrology, and ecosystem function.
Unanticipated Software Evolution: Evaluating the Impact on Development Cost and Quality
Authors: Vilar Rodrigo A. , Lima Anderson A. , Almeida Hyggo O. , Perkusich Angelo 
Published: March 2016

Unanticipated Software Evolution (USE) techniques enable developers to easily change any element of the software without being obligated to anticipate and isolate extension points. However, we have not found empirical validations of the impact of USE on development cost and quality. In this work, we design and execute an experiment for USE, in order to compare its resulting metrics — time, lines of code, test coverage and complexity — using OO systems as baseline. 30 undergraduate students were subjects in this experiment. The results suggest that USE has significant impact on the lines of code and complexity metrics, reducing the amount of lines changed and the McCabe cyclomatic complexity on software evolution.
CLIMATE IMPACT ON ENERGY DEMAND FOR SPACE HEATING IN ICELAND
Authors: FAZELI REZA , DAVIDSDOTTIR BRYNHILDUR , HALLGRIMSSON JONAS HLYNUR 
Published: March 2016

A major impact of climate change is expected to materialize on energy demand for space heating and cooling needs in the residential sector. To quantify this impact, a set of regression models were tested to study the relation between residential energy demand for space heating in Iceland and explanatory variables such as Heating Degree Days and GDP per capita. Considering the nonstationarity of the time-series, three methods were studied to cope with this condition: Cointegration, differencing and detrending.The evaluation statistics of the three models for the validation period showed that the modified detrending approach is the most reliable method. It became obvious that including the seasonal dummy variables and AR component significantly improve the power of the model to predict monthly energy demand for residential space heating in Iceland. The developed model can be used to project climate related changes in demand for low-geothermal heat.
Interaction of crustal heterogeneity and lithospheric processes in determining passive margin architecture on the southern Namibian margin
Authors: Mohammed M. , Paton D. , Collier R. E. L. , Hodgson N. , Negonga M. 
Published: March 2016

Abstract

The influence of pre-rift crustal heterogeneity and structure on the evolution of a continental rift and its subsequent passive margin is explored. The absence of thick Aptian salts in the Namibian South Atlantic allows imaging of sufficient resolution to distinguish different pre-rift basement seismic facies. Aspects of the pre-rift basement geometry were characterized and compared with the geometries of the Cretaceous rift basin structure and with subsequent post-rift margin architectural elements. Half-graben depocentres migrated westwards within the continental synrift phase at the same time as basin-bounding faults became established as hard-linked arrays with lengths of
c.
100 km. The rift–drift transition phase, marked by seaward-dipping reflectors, gave way to the early post-rift progradation of clastic sediments off the Namibian coast. In the Late Cretaceous, these shelf clastic sediments were much thicker in the south, reflecting the dominance of the newly formed Orange River catchment as the main entry point for sediments on the South African–Namibian margin. Tertiary clastic sediments largely bypassed the pre-existing shelf area, revealing a marked basinwards shift in sedimentation. The thickness of post-rift megasequences does not vary simply according to the location of synrift half-graben and thinned continental crust. Instead, the Namibian margin exemplifies a margin influenced by a complex interplay of crustal thinning, pre-rift basement heterogeneity, volcanic bodies and transient dynamic uplift events on the evolution of lithospheric strain and depositional architecture.
HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors
Authors: Budina-Kolomets Anna , Webster Marie R. , Leu Julia I-Ju , Jennis Matthew , Krepler Clemens , Guerrini Anastasia , Kossenkov Andrew V. , Xu Wei , Karakousis Giorgos , Schuchter Lynn , Amaravadi Ravi K. , Wu Hong , Yin Xiangfan , Liu Qin , Lu Yiling , Mills Gordon B. , Xu Xiaowei , George Donna L. , Weeraratna Ashani T. , Murphy Maureen E. 
Published: March 2016

AbstractThe stress-inducible chaperone protein HSP70 (HSPA1) is implicated in melanoma development, and HSP70 inhibitors exert tumor-specific cytotoxic activity in cancer. In this study, we documented that a significant proportion of melanoma tumors express high levels of HSP70, particularly at advanced stages, and that phospho-FAK (PTK2) and BRAF are HSP70 client proteins. Treatment of melanoma cells with HSP70 inhibitors decreased levels of phospho-FAK along with impaired migration, invasion, and metastasis in vitro and in vivo. Moreover, the HSP70 inhibitor PET-16 reduced levels of mutant BRAF, synergized with the BRAF inhibitor PLX4032 in vitro, and enhanced the durability of response to BRAF inhibition in vivo. Collectively, these findings provide strong support for HSP70 inhibition as a therapeutic strategy in melanoma, especially as an adjuvant approach for overcoming the resistance to BRAF inhibitors frequently observed in melanoma patients. Cancer Res; 76(9); 2720–30. ©2016 AACR.