bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Products
Authors: Nan Yuchen , Yu Ying , Ma Zexu , Khattar Sunil K. , Fredericksen Brenda , Zhang Yan-Jin 
Published: August 2014

ABSTRACT
Hepatitis E virus (HEV) causes both endemic and epidemic human hepatitis by fecal-oral transmission in many parts of the world. Zoonotic transmission of HEV from animals to humans has been reported. Due to the lack of an efficient cell culture system, the molecular mechanisms of HEV infection remain largely unknown. In this study, we found that HEV replication in hepatoma cells inhibited poly(I·C)-induced beta interferon (IFN-β) expression and that the HEV open reading frame 1 (ORF1) product was responsible for this inhibition. Two domains, X and the papain-like cysteine protease domain (PCP), of HEV ORF1 were identified as the putative IFN antagonists. When overexpressed in HEK293T cells, the X domain (or macro domain) inhibited poly(I·C)-induced phosphorylation of interferon regulatory factor 3 (IRF-3), which is the key transcription factor for IFN induction. The PCP domain was shown to have deubiquitinase activity for both RIG-I and TBK-1, whose ubiquitination is a key step in their activation in poly(I·C)-induced IFN induction. Furthermore, replication of a HEV replicon containing green fluorescent protein (GFP) (E2-GFP) in hepatoma cells led to impaired phosphorylation of IRF-3 and reduced ubiquitination of RIG-I and TBK-1, which confirmed our observations of X and PCP inhibitory effects in HEK293T cells. Altogether, our study identified the IFN antagonists within the HEV ORF1 polyprotein and expanded our understanding of the functions of several of the HEV ORF1 products, as well as the mechanisms of HEV pathogenesis.

IMPORTANCE
Type I interferons (IFNs) are important components of innate immunity and play a crucial role against viral infection. They also serve as key regulators to evoke an adaptive immune response. Virus infection can induce the synthesis of interferons; however, viruses have evolved many strategies to antagonize the induction of interferons. There is little knowledge about how hepatitis E virus (HEV) inhibits induction of host IFNs, though the viral genome was sequenced more than 2 decades ago. This is the first report of identification of the potential IFN antagonists encoded by HEV. By screening all the domains in the open reading frame 1 (ORF1) polyprotein, we identified two IFN antagonists and performed further research to determine how and at which step in the IFN induction pathway they antagonize host IFN induction. Our work provides valuable information about HEV-cell interaction and pathogenesis.
Family-based interventions to increase physical activity in children: a meta-analysis and realist synthesis protocol
Authors: Brown Helen Elizabeth , Atkin Andrew J , Panter Jenna , Corder Kirsten , Wong Geoff , Chinapaw Mai J M , van Sluijs Esther 
Published: August 2014

IntroductionDespite the established relationship between physical activity and health, data suggest that many children are insufficiently active, and that levels decline into adolescence. Engaging the family in interventions may increase and maintain children's physical activity levels at the critical juncture before secondary school. Synthesis of existing evidence will inform future studies, but the heterogeneity in target populations recruited, behaviour change techniques and intervention strategies employed, and measurement conducted, may require a multifaceted review method. The primary objective of this work will therefore be to synthesis evidence from intervention studies that explicitly engage the family unit to increase children's physical activity using an innovative dual meta-analysis and realist approach.Methods and analysisPeer-reviewed studies will be independently screened by two authors for inclusion based on (1) including ‘healthy’ participants aged 5–12 years; (2) having a substantive intervention aim of increasing physical activity, by engaging the family and (3) reporting on physical activity. Duplicate data extraction and quality assessment will be conducted using a specially designed proforma and the Effective Public Health Practice Project Quality Assessment Tool respectively. STATA software will be used to compute effect sizes for meta-analyses, with subgroup analyses conducted to identify moderating characteristics. Realist syntheses will be conducted according to RAMESES quality and publication guidelines, including development of a programme theory and evidence mapping.DisseminationThis review will be the first to use the framework of a traditional review to conduct a dual meta-analysis and realist synthesis, examining interventions that engage the family to increase physical activity in children. The results will be disseminated through peer-reviewed publications, conferences, formal presentations to policy makers and practitioners and informal meetings. Evidence generated from this synthesis will also be used to inform the development of theory-driven, evidence-based interventions aimed at engaging the family to increase physical activity levels in children.Protocol registrationInternational Prospective Register for Systematic Reviews (PROSPERO): number CRD42013005780.
Non-vitamin K antagonist oral anticoagulants (NOACs): clinical evidence and therapeutic considerations
Authors: Saraf Karan , Morris Paul , Garg Pankaj , Sheridan Paul , Storey Robert 
Published: August 2014

Abstract
Warfarin, a vitamin K antagonist, is the most widely used oral anticoagulant in the world. It is cheap and effective, but its use is limited in many patients by unpredictable levels of anticoagulation, which increases the risk of thromboembolic or haemorrhagic complications. It also requires regular blood monitoring and dose adjustment. New classes of drugs, non-vitamin K antagonist oral anticoagulants (NOACs), are now supported as alternatives to warfarin. Three NOACs are licensed: dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. NOACs do not require routine blood monitoring or dose adjustment. They have a rapid onset and offset of action and fewer food and drug interactions. Current indications include treatment and prophylaxis of venous thromboembolism and prevention of cardioembolic disease in non-valvular atrial fibrillation. Effective antidotes are lacking and some caution must be used in severe renal impairment, but favourable trial evidence has led to their widespread adoption. Research is ongoing, and an increase in their use and indications is expected in the coming years.
X-RAY PHOTOEMISSION ELECTRON MICROSCOPE DETERMINATION OF ORIGINS OF ROOM TEMPERATURE FERROMAGNETISM AND PHOTOLUMINESCENCE IN HIGHCo-CONTENTCoxZn1-xOFILMS
Authors: CAO WEI , PANKRATOV VLADIMIR , HUTTULA MARKO , SHIRMANE LIANA , NIU YU RAN , WANG FENG 
Published: August 2014

In this paper, we reported on the X-ray photoemission electron microscope (XPEEM) determination of magnetic and luminescence origins for two CoxZn1-xO films. The cobalt fraction x of radio frequency co-sputtered samples were 0.86(2) and 0.92(2), respectively. Films were ferromagnetic and semiconductive. Unique narrow green color lines beside the ZnO intrinsic emissions were found with a decay time in microsecond range at room temperature. Origins of magnetic and luminescence properties were determined with XPEEM. The X-ray absorption near edge structure at the Co L3-edge denoted that Co was partially oxidized, and phase-contrast images together with chemical composition identification further proved that Co and CoO co-existed in the samples. The ferromagnetism was attributed to ferromagnetism of Co clusters partially canceled by the antiferromagnetism of its oxide, and the photoluminescence to bound exciton in ZnO nanoclusters and defect related centers of ZnO nanoclusters in a Co -rich matrix. Present results show possibilities for adjusting magnetic and luminescence properties of Co – ZnO compounds by changing the cobalt concentration.
Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer
Authors: Walsh Alex J. , Cook Rebecca S. , Sanders Melinda E. , Aurisicchio Luigi , Ciliberto Gennaro , Arteaga Carlos L. , Skala Melissa C. 
Published: August 2014

Abstract
There is a need for technologies to predict the efficacy of cancer treatment in individual patients. Here, we show that optical metabolic imaging of organoids derived from primary tumors can predict the therapeutic response of xenografts and measure antitumor drug responses in human tumor–derived organoids. Optical metabolic imaging quantifies the fluorescence intensity and lifetime of NADH and FAD, coenzymes of metabolism. As early as 24 hours after treatment with clinically relevant anticancer drugs, the optical metabolic imaging index of responsive organoids decreased (P &lt; 0.001) and was further reduced when effective therapies were combined (P &lt; 5 × 10−6), with no change in drug-resistant organoids. Drug response in xenograft-derived organoids was validated with tumor growth measurements in vivo and staining for proliferation and apoptosis. Heterogeneous cellular responses to drug treatment were also resolved in organoids. Optical metabolic imaging shows potential as a high-throughput screen to test the efficacy of a panel of drugs to select optimal drug combinations. Cancer Res; 74(18); 5184–94. ©2014 AACR.
MicroRNA-26a/b Regulate DNA Replication Licensing, Tumorigenesis, and Prognosis by Targeting CDC6 in Lung Cancer
Authors: Zhang Xin , Xiao Dakai , Wang Ziyi , Zou Yongxin , Huang Liyan , Lin Weixuan , Deng Qiuhua , Pan Hui , Zhou Jiangfen , Liang Chun , He Jianxing 
Published: August 2014

Abstract
Cancer is characterized by mutations, genome rearrangements, epigenetic changes, and altered gene expression that enhance cell proliferation, invasion, and metastasis. To accommodate deregulated cellular proliferation, many DNA replication-initiation proteins are overexpressed in human cancers. However, the mechanism that represses the expression of these proteins in normal cells and the cellular changes that result in their overexpression are largely unknown. One possible mechanism is through miRNA expression differences. Here, it is demonstrated that miR26a and miR26b inhibit replication licensing and the proliferation, migration, and invasion of lung cancer cells by targeting CDC6. Importantly, miR26a/b expression is significantly decreased in human lung cancer tissue specimens compared with the paired adjacent normal tissues, and miR26a/b downregulation and the consequential upregulation of CDC6 are associated with poorer prognosis of patients with lung cancer. These results indicate that miR26a/b repress replication licensing and tumorigenesis by targeting CDC6.
Implications: The current study suggests that miR26a, miR26b, and CDC6 and factors regulating their expression represent potential cancer diagnostic and prognostic markers as well as anticancer targets.
Visual Overview: http://mcr.aacrjournals.org/content/12/11/1535/F1.large.jpg.
Mol Cancer Res; 12(11); 1535–46. ©2014 AACR.
Whole Exome Sequencing for Familial Bicuspid Aortic Valve Identifies Putative Variants
Authors: Martin Lisa J. , Pilipenko Valentina , Kaufman Kenneth M. , Cripe Linda , Kottyan Leah C. , Keddache Mehdi , Dexheimer Phillip , Weirauch Matthew T. , Benson D. Woodrow 
Published: August 2014

Background—
Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation. Although highly heritable, few causal variants have been identified. The purpose of this study was to identify genetic variants underlying BAV by whole exome sequencing a multiplex BAV kindred.

Methods and Results—
Whole exome sequencing was performed on 17 individuals from a single family (BAV=3; other cardiovascular malformation, 3). Postvariant calling error control metrics were established after examining the relationship between Mendelian inheritance error rate and coverage, quality score, and call rate. To determine the most effective approach to identifying susceptibility variants from among 54 674 variants passing error control metrics, we evaluated 3 variant selection strategies frequently used in whole exome sequencing studies plus extended family linkage. No putative rare, high-effect variants were identified in all affected but no unaffected individuals. Eight high-effect variants were identified by ≥2 of the commonly used selection strategies; however, these were either common in the general population (>10%) or present in the majority of the unaffected family members. However, using extended family linkage, 3 synonymous variants were identified; all 3 variants were identified by at least one other strategy.

Conclusions—
These results suggest that traditional whole exome sequencing approaches, which assume causal variants alter coding sense, may be insufficient for BAV and other complex traits. Identification of disease-associated variants is facilitated by the use of segregation within families.
Soil Moisture Droughts under the Retrospective and Projected Climate in India*
Authors: Mishra Vimal , Shah Reepal , Thrasher Bridget 
Published: August 2014

Abstract
Changes in precipitation, air temperature, and model-simulated soil moisture were examined for the observed (1950–2008) and projected (2010–99) climate for the sowing period of Kharif and Rabi [KHARIF_SOW (May–July) and RABI_SOW (October–December)] and the entire Kharif and Rabi [KHARIF (May–October) and RABI (October–April)] crop-growing periods in India. During the KHARIF_SOW and KHARIF periods, precipitation declined significantly in the Gangetic Plain, which in turn resulted in declines in soil moisture. Statistically significant warming trends were noticed as all-India-averaged air temperature increased by 0.40°, 0.90°, and 0.70°C in the KHARIF, RABI_SOW, and RABI periods, respectively, during 1950–2008. Frequency and areal extent of soil moisture–based droughts increased substantially during the latter half (1980–2008) of the observed period. Under the projected climate (2010–99), precipitation, air temperature, and soil moisture are projected to increase in all four crop-growing seasons. In the projected climate, all-India ensemble mean precipitation, air temperature, and soil moisture are projected to increase up to 39% (RABI_SOW period), 2.3°C, and 5.3%, respectively, in the crop-growing periods. While projected changes in air temperature are robust across India, robust increases in precipitation and soil moisture are projected to occur in the end-term (2070–99) climate. Frequency and areal extents of soil moisture–based severe, extreme, and exceptional droughts are projected to increase in the near- (2010–39) and midterm (2040–69) climate in the majority of crop-growing seasons in India. However, frequency and areal extent of droughts during the crop-growing period are projected to decline in the end-term climate in the entire crop-growing period because of projected increases in the monsoon season precipitation.
Spatial and Temporal Scales of Sverdrup Balance*
Authors: Thomas Matthew D. , De Boer Agatha M. , Johnson Helen L. , Stevens David P. 
Published: August 2014

Abstract
Sverdrup balance underlies much of the theory of ocean circulation and provides a potential tool for describing the interior ocean transport from only the wind stress. Using both a model state estimate and an eddy-permitting coupled climate model, this study assesses to what extent and over what spatial and temporal scales Sverdrup balance describes the meridional transport. The authors find that Sverdrup balance holds to first order in the interior subtropical ocean when considered at spatial scales greater than approximately 5°. Outside the subtropics, in western boundary currents and at short spatial scales, significant departures occur due to failures in both the assumptions that there is a level of no motion at some depth and that the vorticity equation is linear. Despite the ocean transport adjustment occurring on time scales consistent with the basin-crossing times for Rossby waves, as predicted by theory, Sverdrup balance gives a useful measure of the subtropical circulation after only a few years. This is because the interannual transport variability is small compared to the mean transports. The vorticity input to the deep ocean by the interaction between deep currents and topography is found to be very large in both models. These deep transports, however, are separated from upper-layer transports that are in Sverdrup balance when considered over large scales.
Lateral Heat Exchange after the Labrador Sea Deep Convection in 2008
Authors: Zhang Weiwei , Yan Xiao-Hai 
Published: August 2014

Abstract
The mechanisms through which convected water restratifies in the Labrador Sea are still under debate. The Labrador Sea restratification after deep convection in the 2007/08 winter is studied with an eddy-resolving numerical model. The modeled mixed layer depth during wintertime resembles the Argo observed mixed layer very well, and the lateral heat flux during the subsequent restratification is in line with observations. The Irminger rings (IRs) are reproduced with fresher caps above the 300-m depths, and they are identified and tracked automatically. The model underestimates both the number of IRs in the convection area and the heat they carry. The underestimation is most likely caused by the errors in the direction of the west Greenland currents in the model, which causes more IRs propagating westward, and only the IRs originating south of 61.5°N are able to propagate southward, yet with speed much slower than observed speed. The model still observed three eddies propagating into the convection area during the restratification phase in 2008, and their thermal contribution ranges from 1% to 4% if the estimation is made at the time when they enter the convection area. If all newly generated eddies are considered, then the ensemble-mean contributions by the IRs become 5.3%. The more detailed and direct heat flux by IRs is difficult to derive because of the strong fluctuation of the identified eddy radius. Nevertheless, the modeled lateral heat flux is largely composed of the boundary current eddies and convective eddies, thus it is possible for the model to maintain an acceptable thermal balance.
Contextual influences on nurses’ decision-making in cases of physical restraint
Authors: de Casterlé Bernadette Dierckx , Goethals Sabine , Gastmans Chris 
Published: August 2014

Background: In order to fully understand nurses’ ethical decision-making in cases of physical restraint in acute older people care, contextual influences on the process of decision-making should be clarified. Research questions: What is the influence of context on nurses’ decision-making process in cases of physical restraint, and what is the impact of context on the prioritizing of ethical values when making a decision on physical restraint? Research design: A qualitative descriptive study inspired by the Grounded Theory approach was carried out. Participants and research context: In total, 21 in-depth interviews were carried out with nurses working on acute geriatric wards in Flanders, Belgium. Ethical considerations: The research protocol was approved by the Ethics Committee of the Faculty of Medicine, Leuven. Findings: Relationships with nursing colleagues and the patient’s family form an inter-personal network. Nurses also point to the importance of the procedural–legal context as expressed in an institutional ethics policy and procedures, or through legal requirements concerning physical restraint. Furthermore, the architectural structure of a ward, the availability of materials and alternatives for restraint use can be decisive in nurses’ decision-making. All interviewed nurses highlighted the unquestionable role of the practical context of care. Context can have a guiding, supportive, or decisive role in decision-making concerning the application of physical restraint. Discussion: The discussion focuses on the role of the inter-personal network of nurses on the process of decision-making. Conclusion: An institutional ethics policy and a value-supportive care environment can support nurses in their challenge to take ethically sound decisions.
Women and the European crisis
Authors: Harcourt Wendy 
Published: August 2014

AbstractThe article raises questions about how the economic crisis is being played out ‘in place’, taking an embodied, generational and gender perspective. ‘Place’ is used in a political context by examining how global realities are experienced in place, and the author argues the need to look at the everyday realities of the crisis from a gendered ontological perspective in order to counter grand narratives of gloom and doom where women (whether old, young, migrant, heterosexual or otherwise) are particular victims. By discussing local contexts of the gendered realities of the crisis in three southern Europe areas, the author shows the possibility of changing the crisis narrative from one of overwhelming paralysis to one of potential transformation. The focus is on the rise of resistance, solidarity economies and new types of communities in the search by women in southern Europe for alternatives to neoliberal capitalism.
A cohort study of duplex Doppler examinations of the carotid artery in primary open angle glaucoma
Authors: Marmion Vincent J , Aldoori Munther I , Woodcock John P , Stephenson John 
Published: August 2014

Objectives To explore the possibility of pathological change in the common carotid artery at the bifurcation and in the internal carotid artery beyond the bifurcation which could contribute to a reduced diastolic pressure as observed in primary open angle glaucoma. Design Duplex ultrasonic examinations of carotid bifurcations were conducted on 80 patients. Carotid artery defects were allocated into three types: no demonstrable flow defects, internal carotid artery abnormalities and disease in the carotid bulb. Setting Bristol Royal Infirmary Vascular Laboratory. Participants Eighty patients (mean age 69.6 years) providing a total of 160 sides to the analysis. Main outcome measures An estimated central retinal artery pressure, intraocular pressure and field loss were recorded for each side measured. Results Doppler investigations revealed significant levels of pathological change in the internal carotid distinct from changes at the carotid bulb. The disease revealed in the internal carotid artery was significantly associated with intraocular pressure ( p = 0.032), with an effect small to medium in magnitude. The Q2 measure, derived from mean arterial pressure and intraocular pressure, was also substantively associated with disease in the internal carotid artery. Both intraocular pressure and the Q2 measure effectively discriminated between groups, with field loss providing rather less discriminating capability. There was a strong trend towards a higher intraocular pressures and a greater visual field loss with internal carotid artery disease. Conclusions Pathological changes in the extra cranial carotid artery in primary open angle glaucoma exceed those in the arteries classified as normal. The presence of disease specifically in the internal carotid artery emphasised the need for a mechanism for the evaluation of the internal carotid apart from the carotid bulb. A basis for clarifying the presence of an ischaemic zone is proposed.