bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT2-Dependent Immune Responses Ensure Host Survival despite the Presence of a Potent Viral Antagonist
Authors: Le-Trilling Vu Thuy Khanh , Wohlgemuth Kerstin , Rückborn Meike U. , Jagnjic Andreja , Maaßen Fabienne , Timmer Lejla , Katschinski Benjamin , Trilling Mirko 
Published: May 2018

ABSTRACT

A pathogen encounter induces interferons, which signal via Janus kinases and STAT transcription factors to establish an antiviral state. However, the host and pathogens are situated in a continuous arms race which shapes host evolution toward optimized immune responses and the pathogens toward enhanced immune-evasive properties. Mouse cytomegalovirus (MCMV) counteracts interferon responses by pM27-mediated degradation of STAT2, which directly affects the signaling of type I as well as type III interferons. Using MCMV mutants lacking
M27
and mice lacking STAT2, we studied the opposing relationship between antiviral activities and viral antagonism in a natural host-pathogen pair
in vitro
and
in vivo
. In contrast to wild-type (wt) MCMV, ΔM27 mutant MCMV was efficiently cleared from all organs within a few days in BALB/c, C57BL/6, and 129 mice, highlighting the general importance of STAT2 antagonism for MCMV replication. Despite this effective and relevant STAT2 antagonism, wt and STAT2-deficient mice exhibited fundamentally different susceptibilities to MCMV infections. MCMV replication was increased in all assessed organs (e.g., liver, spleen, lungs, and salivary glands) of STAT2-deficient mice, resulting in mortality during the first week after infection. Taken together, the results of our study reveal the importance of cytomegaloviral interferon antagonism for viral replication as well as a pivotal role of the remaining STAT2 activity for host survival. This mutual influence establishes a stable evolutionary standoff situation with fatal consequences when the equilibrium is disturbed.

IMPORTANCE
The host limits viral replication by the use of interferons (IFNs), which signal via STAT proteins. Several viruses evolved antagonists targeting STATs to antagonize IFNs (e.g., cytomegaloviruses, Zika virus, dengue virus, and several paramyxoviruses). We analyzed infections caused by MCMV expressing or lacking the STAT2 antagonist pM27 in STAT2-deficient and control mice to evaluate its importance for the host and the virus
in vitro
and
in vivo
. The inability to counteract STAT2 directly translates into exaggerated IFN susceptibility
in vitro
and pronounced attenuation
in vivo
. Thus, the antiviral activity mediated by IFNs via STAT2-dependent signaling drove the development of a potent MCMV-encoded STAT2 antagonist which became indispensable for efficient virus replication and spread to organs required for dissemination. Despite this clear impact of viral STAT2 antagonism, the host critically required the remaining STAT2 activity to prevent overt disease and mortality upon MCMV infection. Our findings highlight a remarkably delicate balance between host and virus.
Dengue Virus Induces Increased Activity of the Complement Alternative Pathway in Infected Cells
Authors: Cabezas Sheila , Bracho Gustavo , Aloia Amanda L. , Adamson Penelope J. , Bonder Claudine S. , Smith Justine R. , Gordon David L. , Carr Jillian M. 
Published: May 2018

ABSTRACTSevere dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infectionin vitrowere investigated. mRNA for factor H (FH), a major negative regulator of the AP, was significantly increased in DENV-infected endothelial cells (EC) and macrophages, but, in contrast, production of extracellular FH protein was not. This discord was not seen for the AP activator factor B (FB), with DENV induction of both FB mRNA and protein, nor was it seen with Toll-like receptor 3 or 4 stimulation of EC and macrophages, which induces both FH and FB mRNA and protein. Surface-bound and intracellular FH protein was, however, induced by DENV, but only in DENV antigen-positive cells, while in two other DENV-susceptible immortalized cell lines (ARPE-19 and human retinal endothelial cells), FH protein was induced both intracellularly and extracellularly by DENV infection. Regardless of the cell type, there was an imbalance in AP components and an increase in markers of complement AP activity associated with DENV-infected cells, with lower FH relative to FB protein, an increased ability to promote AP-mediated lytic activity, and increased deposition of complement component C3b on the surface of DENV-infected cells. For EC in particular, these changes are predicted to result in higher complement activity in the local cellular microenvironment, with the potential to induce functional changes that may result in increased vascular permeability, a hallmark of dengue disease.IMPORTANCEDengue virus (DENV) is a significant human viral pathogen with a global medical and economic impact. DENV may cause serious and life-threatening disease, with increased vascular permeability and plasma leakage. The pathogenic mechanisms underlying these features remain unclear; however, overactivity of the complement alternative pathway has been suggested to play a role. In this study, we investigate the molecular events that may be responsible for this observed alternative pathway overactivity and provide novel findings of changes in the complement system in response to DENV infection in primary cell types that are a major target for DENV infection (macrophages) and pathogenesis (endothelial cells)in vivo. Our results suggest a new dimension of cellular events that may influence endothelial cell barrier function during DENV infection that could expand strategies for developing therapeutics to prevent or control DENV-mediated vascular disease.
Aerobic exercise interventions reduce blood pressure in patients after stroke or transient ischaemic attack: a systematic review and meta-analysis
Authors: Wang Cheng , Redgrave Jessica , Shafizadeh Mohsen , Majid Arshad , Kilner Karen , Ali Ali N 
Published: May 2018

Objective
Secondary vascular risk reduction is critical to preventing recurrent stroke. We aimed to evaluate the effect of exercise interventions on vascular risk factors and recurrent ischaemic events after stroke or transient ischaemic attack (TIA).

Design
Intervention systematic review and meta-analysis.

Data sources
OVID MEDLINE, PubMed, The Cochrane Library, Web of Science, The National Institute for Health and Care Excellence, TRIP Database, CINAHL, PsycINFO, SCOPUS, UK Clinical Trials Gateway and the China National Knowledge Infrastructure were searched from 1966 to October 2017.

Eligibility criteria
Randomised controlled trials evaluating aerobic or resistance exercise interventions on vascular risk factors and recurrent ischaemic events among patients with stroke or TIA, compared with control.

Results
Twenty studies (n=1031) were included. Exercise interventions resulted in significant reductions in systolic blood pressure (SBP) −4.30 mm Hg (95% CI −6.77 to −1.83) and diastolic blood pressure −2.58 mm Hg (95% CI −4.7 to −0.46) compared with control. Reduction in SBP was most pronounced among studies initiating exercise within 6 months of stroke or TIA (−8.46 mm Hg, 95% CI −12.18 to −4.75 vs −2.33 mm Hg, 95% CI −3.94 to −0.72), and in those incorporating an educational component (−7.81 mm Hg, 95% CI −14.34 to −1.28 vs −2.78 mm Hg, 95% CI −4.33 to −1.23). Exercise was also associated with reductions in total cholesterol (−0.27 mmol/L, 95% CI −0.54 to 0.00), but not fasting glucose or body mass index. One trial reported reductions in secondary vascular events with exercise, but was insufficiently powered.

Summary
Exercise interventions can result in clinically meaningful blood pressure reductions, particularly if initiated early and alongside education.
YB-1 Expression and Phosphorylation Regulate Tumorigenicity and Invasiveness in Melanoma by Influencing EMT
Authors: Kosnopfel Corinna , Sinnberg Tobias , Sauer Birgit , Busch Christian , Niessner Heike , Schmitt Anja , Forchhammer Stephan , Grimmel Cornelia , Mertens Peter R. , Hailfinger Stephan , Dunn Sandra E. , Garbe Claus , Schittek Birgit 
Published: May 2018

Abstract
Cutaneous melanoma represents one of the most aggressive human tumor entities possessing a high tendency to metastasize. Cancer cells frequently exploit a highly conserved developmental program, the epithelial-to-mesenchymal transition (EMT), to gain migratory and invasive properties promoting their metastatic spread. Cytoplasmic localization of the oncogenic transcription and translation factor Y-box binding protein 1 (YB-1) is a powerful inducer of EMT in breast carcinoma cells. Interestingly, EMT-like processes have also been observed in cutaneous melanoma despite its neural crest origin. Here, increased expression of YB-1 negatively affects patient survival in malignant melanoma and promotes melanoma cell tumorigenicity both in vitro and in vivo. Intriguingly, this effect seems to be mainly mediated by cytoplasmic YB-1 that does not exhibit phosphorylation at serine-102 (S102). Moreover, S102 unphosphorylated YB-1 enhances the migratory and invasive potential of human melanoma cells in two-dimensional (2D) and three-dimensional (3D) culture systems and facilitates acquisition of a mesenchymal-like invasive phenotype in the chick embryo model. Collectively, these data demonstrate that the cytoplasmic activity of YB-1 stimulates tumorigenicity and metastatic potential of melanoma cells by promoting EMT-like properties.
Implications: This study reveals for the first time that YB-1 efficiently drives tumorigenicity and invasiveness of melanoma cells in its S102 unphosphorylated cytoplasmic state and that YB-1 expression represents a negative prognostic factor in primary melanoma patients. Mol Cancer Res; 16(7); 1149–60. ©2018 AACR.
Courtship behaviour and male sexual competition of the Taliang crocodile newt, Liangshantriton taliangensis
Authors: Gong Yuzhou , Shu Guocheng , Huang Feng , He Liuyang , Li Cheng , Xie Feng 
Published: May 2018

Abstract
The Taliang crocodile newt, Liangshantriton taliangensis, which is endemic to south-western China, is a rare salamandrid species with a distinct evolutionary history. Using combined field observations and captive experiments, we studied the courtship behaviour and male sexual interference of this species and composed a complete ethogram of its courtship behaviour. Unlike previous reports on sperm transfer, male L. taliangensis did not deposit spermatophores during ventral amplexus and females did not pick up sperm masses in this courtship phase. Sperm transfer was only performed during arm-hooking pin-wheel circling, which distinguishes L. taliangensis from Tylototriton species and supports the validity of genus Liangshantriton. Whether L. taliangensis shows bimodality in sperm transfer needs to be explored in additional populations. In the presence of sexual competitors, male L. taliangensis adjusted the duration of their behaviour. We found that males with longer snout-vent length, heavier mass, and higher tailfins may have an advantage in intrasexual competition.
Quantifying direct and indirect contacts for the potential transmission of infection between species using a multilayer contact network
Authors: Silk Matthew J. , Drewe Julian A. , Delahay Richard J. , Weber Nicola , Steward Lucy C. , Wilson-Aggarwal Jared , Boots Mike , Hodgson David J. , Croft Darren P. , McDonald Robbie A. 
Published: May 2018

Abstract
Detecting opportunities for between-species transmission of pathogens can be challenging, particularly if rare behaviours or environmental transmission are involved. We present a multilayer network framework to quantify transmission potential in multi-host systems, incorporating environmental transmission, by using empirical data on direct and indirect contacts between European badgers Meles meles and domestic cattle. We identify that indirect contacts via the environment at badger latrines on pasture are likely to be important for transmission within badger populations and between badgers and cattle. We also find a positive correlation between the role of individual badgers within the badger social network, and their role in the overall badger-cattle-environment network, suggesting that the same behavioural traits contribute to the role of individual badgers in within- and between-species transmission. These findings have implications for disease management interventions in this system, and our novel network approach can provide general insights into transmission in other multi-host disease systems.
Gap-Filling Mobile Radar Observations of a Snow Squall in the San Luis Valley
Authors: Rosenow Andrew A. , Howard Kenneth , Meitín José 
Published: May 2018

Abstract
On 24 January 2017, a convective snow squall developed in the San Luis Valley of Colorado. This squall produced rapidly varying winds at San Luis Valley airport in Alamosa, Colorado, with gusts up to 12 m s−1, and an associated visibility drop to 1.4 km from unlimited in less than 10 min. This snow squall was largely undetected by the operational WSR-88D network because of the Sangre de Cristo Range of the Rocky Mountains lying between the valley and the nearest WSR-88D in Pueblo, Colorado. This study presents observations of the snow squall from the X-band NOAA X-Pol radar, which was deployed in the San Luis Valley during the event. These observations document the squall developing from individual convective cells and growing upscale into a linear squall, with peak radial velocities of 15 m s−1. The environment conducive to the development of this snow squall is examined using data from the High-Resolution Rapid Refresh model, which shows an environment unstable to ascending surface-based parcels, with surface-based convective available potential energy (SBCAPE) values up to 600 J kg−1 in the San Luis Valley. The mobile radar data are integrated into the Multi-Radar Multi-Sensor (MRMS) mosaic to illustrate both the large improvement in detectability of this event gained from a gap-filling radar as well as the capability of MRMS to incorporate data from new radars designed to fill gaps in the current radar network.
Ecological Interface Design for Computer Network Defense
Authors: Bennett Kevin B. , Bryant Adam , Sushereba Christen 
Published: May 2018

Objective: A prototype ecological interface for computer network defense (CND) was developed. Background: Concerns about CND run high. Although there is a vast literature on CND, there is some indication that this research is not being translated into operational contexts. Part of the reason may be that CND has historically been treated as a strictly technical problem, rather than as a socio-technical problem. Methods: The cognitive systems engineering (CSE)/ecological interface design (EID) framework was used in the analysis and design of the prototype interface. A brief overview of CSE/EID is provided. EID principles of design (i.e., direct perception, direct manipulation and visual momentum) are described and illustrated through concrete examples from the ecological interface. Results: Key features of the ecological interface include (a) a wide variety of alternative visual displays, (b) controls that allow easy, dynamic reconfiguration of these displays, (c) visual highlighting of functionally related information across displays, (d) control mechanisms to selectively filter massive data sets, and (e) the capability for easy expansion. Cyber attacks from a well-known data set are illustrated through screen shots. Conclusion: CND support needs to be developed with a triadic focus (i.e., humans interacting with technology to accomplish work) if it is to be effective. Iterative design and formal evaluation is also required. The discipline of human factors has a long tradition of success on both counts; it is time that HF became fully involved in CND. Application: Direct application in supporting cyber analysts.
Differences between early and late involvement of palliative home care in oncology care: A focus group study with palliative home care teams
Authors: Dhollander Naomi , Deliens Luc , Van Belle Simon , De Vleminck Aline , Pardon Koen 
Published: May 2018

Background: To date, no randomised controlled trials on the integration of specialised palliative home care into oncology care have been identified. Information on whether existing models of integrated care are applicable to the home care system and how working procedures and skills of the palliative care teams might require adaptation is missing. Aim: To gain insight into differences between early and late involvement and the effect on existing working procedures and skills as perceived by palliative home care teams. Design: Qualitative study – focus group interviews. Setting/participants: Six palliative home care teams in Flanders, Belgium. Participants included physicians, nurses and psychologists. Results: Differences were found concerning (1) reasons for initiation, (2) planning of care process, (3) focus on future goals versus problems, (4) opportunity to provide holistic care, (5) empowerment of patients and (6) empowerment of professional caregivers. A shift from a medical approach to a more holistic approach is the most noticeable. Being involved earlier also results in a more structured follow-up and in empowering the patient to be part of the decision-making process. Early involvement creates the need for transmural collaboration, which leads to the teams taking on more supporting and coordinating tasks. Discussion: Being involved earlier leads to different tasks and working procedures and to the need for transmural collaboration. Future research might focus on the development of an intervention model for the early integration of palliative home care into oncology care. To develop this model, components of existing models might need to be adapted or extended.
Effect of Intraoperative Platelet-Rich Plasma Treatment on Postoperative Donor Site Knee Pain in Patellar Tendon Autograft Anterior Cruciate Ligament Reconstruction: A Double-Blind Randomized Controlled Trial
Authors: Walters Brian L. , Porter David A. , Hobart Sarah J. , Bedford Benjamin B. , Hogan Daniel E. , McHugh Malachy M. , Klein Devon A. , Harousseau Kendall , Nicholas Stephen J. 
Published: May 2018

Background: Donor site morbidity in the form of anterior knee pain is a frequent complication after bone–patellar tendon–bone (BPTB) autograft anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to examine the effect of the intraoperative administration of platelet-rich plasma (PRP) on postoperative kneeling pain. It was hypothesized that PRP treatment would reduce knee pain. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Fifty patients (mean ± SD age, 30 ± 12 years) undergoing BPTB ACL autograft reconstruction were randomized to the PRP (n = 27) or sham (n = 23) treatment. In either case, 10 mL of venous blood was drawn before the induction of anesthesia and either discarded (sham) or processed (PRP) for preparation of a PRP gel to be later mixed with donor site bone chips and inserted into the patellar defect. At 12 weeks, 6 months, 1 year, and 2 years after surgery, patients completed International Knee Documentation Committee (IKDC) forms and visual analog scale pain scores for activities of daily living and kneeling. Healing indices at the donor site were assessed by routine noncontrast magnetic resonance imaging (MRI) at 6 months. Mixed-model analysis of variance was used to assess the effect of PRP on patient symptoms and MRI indices of donor site healing, as measured by the width of the donor site defect. Results: Kneeling pain, pain with activities of daily living, and IKDC scores were not different between treatment groups at any of the time intervals ( P = .08-.83). Kneeling pain improved from 12 weeks to 6 months and from 1 to 2 years ( P < .05). IKDC scores improved substantially from 12 weeks to 6 months ( P < .001) and continued to improve to 2 years (PRP, 86 ± 19; sham, 89 ± 10). MRI indices of donor site healing were not different between treatment groups ( P = .53-.90). Conclusion: Whether randomized to receive PRP in their patellar defect or not, patients continued to have similar levels of kneeling pain and patellar defect sizes after autograft BPTB ACL reconstruction. Registration: NCT01765712 ( ClinicalTrials.gov identifier).
Living Alone and Dementia Incidence: A Clinical-Based Study in People With Mild Cognitive Impairment
Authors: Grande Giulia , Vetrano Davide Liborio , Cova Ilaria , Pomati Simone , Mattavelli Daniele , Maggiore Laura , Cucumo Valentina , Ghiretti Roberta , Vanacore Nicola , Mariani Claudio , Rizzuto Debora 
Published: May 2018

Introduction: Social isolation and living alone have been associated with negative outcomes, especially in the older population. We aim to investigate the effect of living alone on the development of dementia in people with mild cognitive impairment (MCI). Materials and Methods: In this longitudinal study, we enrolled 345 outpatients with MCI evaluated at baseline through a clinical and neuropsychological protocol. Data on living situation (living alone vs. living with someone) were also collected. The development of dementia at follow-up was the outcome of the study. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression analyses. Laplace regression was used to model the time-to-dementia diagnosis as a function of living situation. Results: During the follow-up time (mean [SD]: 2.8 [2.2] years), 172 (50%) participants developed dementia. After controlling for age, sex, years of education, MCI subtype, presence of comorbidities, and antidepressant therapy, people with MCI living alone were more likely to develop dementia (HR: 1.5; 95% CI: 1.1-2.1), when compared to those living with someone. In addition, participants with MCI living alone were diagnosed with dementia 1 year earlier than those living with someone ( P = .012). Conclusion: Living alone increases by 50% the risk of developing dementia and anticipates by 1 year the diagnosis in people with MCI. These results, in line with findings of previous population-based studies, emphasize the pivotal role of the living situation in identifying a frailer share of the population at higher risk of dementia to which devote ad hoc assessment and care.