bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection
Authors: Pinto Amelia K. , Brien James D. , Lam Chia-Ying Kao , Johnson Syd , Chiang Cindy , Hiscott John , Sarathy Vanessa V. , Barrett Alan D. , Shresta Sujan , Diamond Michael S. 
Published: September 2015

ABSTRACTWith over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (IfnarandIfngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion ofIfnarexpression on subsets of murine myeloid cells (LysM Cre+Ifnarflox/flox[denoted asIfnarf/fherein]) resulted in enhanced DENV replicationin vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre+Ifnarf/fmice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre+Ifnarf/fmice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents.IMPORTANCEAlthough dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features of severe human disease. Using animals lacking the type I interferon receptor only on myeloid cell subsets, we developed a more immunocompetent mouse model of severe DENV infection with characteristics of the human disease, including vascular leakage, hemoconcentration, thrombocytopenia, and liver injury. Using this model, we demonstrate that pathogenesis by two different DENV serotypes is inhibited by therapeutic administration of a genetically modified antibody or a RIG-I receptor agonist that stimulates innate immunity.
The psychological factor ‘self-blame’ predicts overuse injury among top-level Swedish track and field athletes: a 12-month cohort study
Authors: Timpka Toomas , Jacobsson Jenny , Dahlström Örjan , Kowalski Jan , Bargoria Victor , Ekberg Joakim , Nilsson Sverker , Renström Per 
Published: September 2015

BackgroundAthletes’ psychological characteristics are important for understanding sports injury mechanisms. We examined the relevance of psychological factors in an integrated model of overuse injury risk in athletics/track and field.MethodsSwedish track and field athletes (n=278) entering a 12-month injury surveillance in March 2009 were also invited to complete a psychological survey. Simple Cox proportional hazards models were compiled for single explanatory variables. We also tested multiple models for 3 explanatory variable groupings: an epidemiological model without psychological variables, a psychological model excluding epidemiological variables and an integrated (combined) model.ResultsThe integrated multiple model included the maladaptive coping behaviourself-blame(p=0.007; HR 1.32; 95% CI 1.08 to 1.61), and an interaction between athlete category and injury history (p<0.001). Youth female (p=0.034; HR 0.51; 95% CI 0.27 to 0.95) and youth male (p=0.047; HR 0.49; 95% CI 0.24 to 0.99) athletes with no severe injury the previous year were at half the risk of sustaining a new injury compared with the reference group. A training load index entered the epidemiological multiple model, but not the integrated model.ConclusionsThe coping behaviourself-blamereplaced training load in an integrated explanatory model of overuse injury risk in athletes. What seemed to be more strongly related to the likelihood of overuse injury was not the athletics load per se, but, rather, the load applied in situations when the athlete's body was in need of rest.
Melanoma mortality following skin cancer screening in Germany
Authors: Boniol Mathieu , Autier Philippe , Gandini Sara 
Published: September 2015

ObjectivesIn 2003, a skin cancer screening campaign based on total body skin examination was launched in the federal state of Schleswig-Holstein, Germany. 20% of adults aged 20 and over were screened. In 2008, a 48% decline in melanoma mortality was reported. In the same year, skin screening was extended to the rest of Germany. We evaluated whether melanoma mortality trends decreased in Germany as compared with surrounding countries where skin screening is uncommon. We also evaluated whether the initial decreasing mortality trend observed in Schleswig-Holstein was maintained with a longer follow-up.Setting and participantsRegional and national melanoma mortality data from 1995 to 2013 were extracted from the GEKID database and the Federal Statistical Office. Mortality data for Germany and surrounding countries from 1980 to 2012 were extracted from the WHO mortality database.Primary and secondary outcome measuresAge-adjusted (European Standard Population) mortality rates were computed and joinpoint analysis performed for Schleswig-Holstein, Germany and surrounding countries.ResultsIn Schleswig-Holstein, melanoma mortality rates declined by 48% from 2003 to 2008, and from 2009 to 2013 returned to levels observed before screening initiation. During the 5 years of the national programme (2008–2012), melanoma mortality rates increased by 2.6% (95% CI −0.1 to 5.2) in men and 0.02% (95% CI −1.8 to 1.8) in women. No inflexion point in trends was identified after 2008 that could have suggested a decreasing melanoma mortality. Trends of cutaneous melanoma mortality in Germany from 1980 to 2012 did not differ from those observed in surrounding countries.ConclusionsThe transient decrease mortality in Schleswig-Holstein followed by return to pre-screening levels could reflect a temporal modification in the reporting of death causes. An in-depth evaluation of the screening programme is required.
Individual patient data meta-analysis of self-monitoring of blood pressure (BP-SMART): a protocol
Authors: Tucker Katherine L , Sheppard James P , Stevens Richard , Bosworth Hayden B , Bove Alfred , Bray Emma P , Godwin Marshal , Green Beverly , Hebert Paul , Hobbs F D Richard , Kantola Ilkka , Kerry Sally , Magid David J , Mant Jonathan , Margolis Karen L , McKinstry Brian , Omboni Stefano , Ogedegbe Olugbenga , Parati Gianfranco , Qamar Nashat , Varis Juha , Verberk Willem , Wakefield Bonnie J , McManus Richard J 
Published: September 2015

IntroductionSelf-monitoring of blood pressure is effective in reducing blood pressure in hypertension. However previous meta-analyses have shown a considerable amount of heterogeneity between studies, only part of which can be accounted for by meta-regression. This may be due to differences in design, recruited populations, intervention components or results among patient subgroups. To further investigate these differences, an individual patient data (IPD) meta-analysis of self-monitoring of blood pressure will be performed.Methods and analysisWe will identify randomised trials that have compared patients with hypertension who are self-monitoring blood pressure with those who are not and invite trialists to provide IPD including clinic and/or ambulatory systolic and diastolic blood pressure at baseline and all follow-up points where both intervention and control groups were measured. Other data requested will include measurement methodology, length of follow-up, cointerventions, baseline demographic (age, gender) and psychosocial factors (deprivation, quality of life), setting, intensity of self-monitoring, self-monitored blood pressure, comorbidities, lifestyle factors (weight, smoking) and presence or not of antihypertensive treatment. Data on all available patients will be included in order to take an intention-to-treat approach. A two-stage procedure for IPD meta-analysis, stratified by trial and taking into account age, sex, diabetes and baseline systolic BP will be used. Exploratory subgroup analyses will further investigate non-linear relationships between the prespecified variables. Sensitivity analyses will assess the impact of trials which have and have not provided IPD.Ethics and disseminationThis study does not include identifiable data. Results will be disseminated in a peer-reviewed publication and by international conference presentations.ConclusionsIPD analysis should help the understanding of which self-monitoring interventions for which patient groups are most effective in the control of blood pressure.
Gender differences between WOMAC index scores, health-related quality of life and physical performance in an elderly Taiwanese population with knee osteoarthritis
Authors: Fang Wen-Hui , Huang Guo-Shu , Chang Hsien-Feng , Chen Ching-Yang , Kang Chi-Yu , Wang Chih-Chien , Lin Chin , Yang Jia-Hwa , Su Wen , Kao SenYeong , Su Sui-Lung 
Published: September 2015

ObjectiveTo investigate the importance of the WOMAC index score, health-related quality of life and physical performance in each domain affected by knee osteoarthritis (OA) and to identify gender differences in the importance of these domains and physical performances.Material and methodsWe performed a population-based study for radiographic knee OA among participants aged more than 65 years. Demographic data were collected and anthropometric measurement, radiographic assessment, the WOMAC index score, the short-form 12 (SF-12), the Timed and Up to Go Test (TUGT) and the Five Times Sit to Stand Test (FTSST) were performed.ResultThere were 901 individuals (409 males and 492 females) aged 74.04±6.92 (male: 76.35±7.33; female: 72.12±5.92) years included in this study. The WOMAC scores of participants with OA were higher than those without OA in males and females (male: 11.97±15.79 vs 8.23±12.84, p<0.001; female: 10.61±14.97 vs 7.59±3.31, p=0.032). The physical component summary (PCS) score was only significant in females with knee OA (62.14±24.66 vs 66.59±23.85, p=0.043), while the mental component summary (MCS) score was only significant in males with knee OA (78.02±18.59 vs 81.98±15.46, p=0.02). The TUGT and FTSST were not significant in individuals with and without OA in males and females. Moreover, the multivariate results for the WOMAC score were significant for females (3.928 (95% CI 1.287 to 6.569), p=0.004).ConclusionsThe PCS domains of SF-12 and MCS domains of SF-12 are crucial in Taiwanese females and elderly males, respectively, with knee OA. Different evaluation and treatment strategies based on gender differences should be considered in elderly Taiwanese patients with knee OA to improve their quality of life.
The CHICO (Children's Cough) Trial protocol: a feasibility randomised controlled trial investigating the clinical and cost-effectiveness of a complex intervention to improve the management of children presenting to primary care with acute respiratory tract infection
Authors: Turnbull Sophie L , Redmond Niamh M , Lucas Patricia , Cabral Christie , Ingram Jenny , Hollinghurst Sandra , Hay Alastair D , Peters Tim J , Horwood Jeremy , Little Paul , Francis Nick , Blair Peter S 
Published: September 2015

IntroductionWhile most respiratory tract infections (RTIs) will resolve without treatment, many children will receive antibiotics and some will develop severe symptoms requiring hospitalisation. There have been calls for evidence to reduce uncertainty regarding the identification of children who will and will not benefit from antibiotics. The aim of this feasibility trial is to test recruitment and the acceptance of a complex behavioural intervention designed to reduce antibiotic prescribing, and to inform how best to conduct a larger trial.Methods and analysisThe CHICO (Children's Cough) trial is a single-centre feasibility cluster randomised controlled trial (RCT) comparing a web-based, within-consultation, behavioural intervention with usual care for children presenting to general practitioner practices with RTI and acute cough. The trial aims to recruit at least 300 children between October 2014 and April 2015, in a single area in South West England. Following informed consent, demographic information will be recorded, and symptoms and signs measured. Parents/carers of recruited children will be followed up on a weekly basis to establish symptom duration, resource use and cost of the illness to the parent until the child's cough has resolved or up to 8 weeks, whichever occurs earlier. A review of medical notes, including clinical history, primary care reconsultations and hospitalisations will be undertaken 2 months after recruitment. The trial feasibility will be assessed by: determining acceptability of the intervention to clinicians and parent/carers; quantifying differential recruitment and follow-up; determining intervention fidelity; the success in gathering the data necessary to conduct a cost-effectiveness analysis; and collecting data about antibiotic prescribing rates to inform the sample size needed for a fully powered RCT.Ethics and disseminationThe study was approved by the North West—Haydock Research Ethics Committee, UK (reference number: 14/NW/1034). The findings from this feasibility trial will be disseminated through research conferences and peer-reviewed journals.Trial registration numberISRCTN23547970.
Design of a superconducting linear synchronous motor with YBCO coil magnet
Authors: Li Jing , Tang Junjie , Zhang Ya 
Published: September 2015

The forces of the flat single-sided linear motor with four superconducting coils on the excitation system were presented by experimental method. The influences of the coil height and number of turns on the forces were investigated by the simulation method. Although the maximum thrust increased monotonically with the value of turns, the corresponding increment of the thrust decreased with the value of turns. The thrust reaches a certain saturation value with increasing the height of the superconducting coil. Continuing to increase the height of the coil could lead to an increase of the normal force. The superconducting linear motor is finally designed with the capability to generate thrust of 1 kN/m.
Chapter 10 Distribution and significance of basaltic eruptive centres: São Miguel, Azores
Authors: Ferreira T. , Gomes A. , Gaspar J. L. , Guest J. 
Published: September 2015

Abstract
Basaltic volcanism occurs at all the active volcanic systems of São Miguel. For the last 30 ka, the eruption of basaltic magma has been particularly significant in the areas between the three polygenetic volcanoes – Sete Cidades, Fogo and Furnas – and two basaltic fields have developed: the Picos Fissural Volcanic System (PFVS) and the Congro Fissural Volcanic System (CFVS). About 5 ka ago volcanic activity at CFVS ended abruptly and since then almost all basaltic activity has been concentrated at the PFVS, where about 30 eruptions have taken place. Despite the absence of eruptive activity, the Congro system represents one of the most active seismic areas in the archipelago. It shows episodes of volcanic deformation that are indicative of magma ascent, which halted beneath the volcanic system. Two historical eruptions are associated with the PFVS. The 1563 eruption at Pico do Sapateiro was of basaltic composition, whereas that of the 1652 eruption was, for almost two centuries, also considered to be basaltic. This event had, however, a Vulcanian style and involved the production of large amounts of fine ash and the growth of three trachyte domes with associated coulées. It was accurately described in contemporary historical accounts.
Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors
Authors: Hawinkels Lukas J.A.C. , de Vinuesa Amaya Garcia , Paauwe Madelon , Kruithof-de Julio Marianna , Wiercinska Eliza , Pardali Evangelia , Mezzanotte Laura , Keereweer Stijn , Braumuller Tanya M. , Heijkants Renier C. , Jonkers Jos , Löwik Clemens W. , Goumans Marie-José , ten Hagen Timo L. , ten Dijke Peter 
Published: September 2015

Abstract
Purpose: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor–like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap.
Experimental Design: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis.
Results: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. An immunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone.
Conclusions: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc. Clin Cancer Res; 22(1); 96–106. ©2015 AACR.
Multidomain Lifestyle Interventions for the Prevention of Cognitive Decline After Ischemic Stroke
Authors: Matz Karl , Teuschl Yvonne , Firlinger Bernadette , Dachenhausen Alexandra , Keindl Magdalena , Seyfang Leonhard , Tuomilehto Jaakko , Brainin Michael ,   Participants in the ASPIS Study Group in addition to the authors named, Schnider Peter , Bancher Christian , Pinter Michaela , Kepplinger Berthold , Asenbaum-Nan Susanne , Oberndorfer Stefan , Heiss Wolf-Dieter 
Published: September 2015

Background and Purpose—
Cognitive impairment occurs in ≤30% of all stroke survivors. However, effective therapies aimed at preventing poststroke cognitive decline are lacking. We assessed the efficacy of a multidomain intervention on preventing cognitive decline after stroke.

Methods—
In this randomized, observer-blind trial patients were recruited within 3 months after an acute stroke in 5 Austrian neurological centers. Patients were assigned to a 24-month lifestyle-based multidomain intervention or standard stroke care. Primary outcomes were the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and occurrence of cognitive decline in the composite scores of at least 2 of 5 cognitive domains at 24 months.

Results—

A total of 101 patients were randomized into multi-intervention and 101 into standard care during June 2010 and November 2012. Of them, 76 patients in the intervention group and 83 in the control group were included in the final intention-to-treat analysis. At 24 months, 8 of 76 (10.5%) patients in the intervention group and 10 of 83 (12.0%) patients in the control group showed cognitive decline corresponding to a relative risk reduction of 0.874 (95% confidence interval, 0.364–2.098). The change in ADAS-cog from baseline to 24 months was not different either (median 0 [IQR, −1 to 2] in both groups;
P
=0.808).

Conclusions—
This trial found no benefit of 24-month multidomain intervention with focus on improvement in lifestyle and vascular risk factors on the incidence of poststroke cognitive decline in comparison with standard stroke care. Studies with a larger sample size are needed.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01109836.
Effects of Dynamic Crop Growth on the Simulated Precipitation Response to Irrigation*
Authors: Harding Keith J. , Twine Tracy E. , Lu Yaqiong 
Published: September 2015

Abstract
The rapid expansion of irrigation since the 1950s has significantly depleted the Ogallala Aquifer. This study examines the warm-season climate impacts of irrigation over the Ogallala using high-resolution (6.33 km) simulations of a version of the Weather Research and Forecasting (WRF) Model that has been coupled to the Community Land Model with dynamic crop growth (WRF-CLM4crop). To examine how dynamic crops influence the simulated impact of irrigation, the authors compare simulations with dynamic crops to simulations with a fixed annual cycle of crop leaf area index (static crops). For each crop scheme, simulations were completed with and without irrigation for 9 years that represent the range of observed precipitation. Reduced temperature and precipitation biases occur with dynamic versus static crops. Fundamental differences in the precipitation response to irrigation occur with dynamic crops, as enhanced surface roughness weakens low-level winds, enabling more water from irrigation to remain over the region. Greater simulated rainfall increases (12.42 mm) occur with dynamic crops compared to static crops (9.08 mm), with the greatest differences during drought years (+20.1 vs +5.9 mm). Water use for irrigation significantly impacts precipitation with dynamic crops (R2 = 0.29), but no relationship exists with static crops. Dynamic crop growth has the largest effect on the simulated impact of irrigation on precipitation during drought years, with little impact during nondrought years, highlighting the need to simulate the dynamic response of crops to environmental variability within Earth system models to improve prediction of the agroecosystem response to variations in climate.