bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells
Authors: Lin Zhen , Swan Kenneth , Zhang Xin , Cao Subing , Brett Zoe , Drury Stacy , Strong Michael J. , Fewell Claire , Puetter Adriane , Wang Xia , Ferris MaryBeth , Sullivan Deborah E. , Li Li , Flemington Erik K. 
Published: January 2016

ABSTRACT
In the oral epithelium, peripheral stores of Epstein-Barr virus (EBV) are transmitted from infiltrating B cells to epithelial cells. Once the virus is transmitted to epithelial cells, the highly permissive nature of this cell type for lytic replication allows virus amplification and exchange to other hosts. Since the initial transfer of EBV from B cells to epithelial cells requires transitioning of the B-cell to a state that induces virus reactivation, we hypothesized that there might be epithelium-specific signals that allow the infiltrating B cells to sense the appropriate environment to initiate reactivation and begin this exchange process. We previously found that the epithelium-specific miR-200 family of microRNAs promotes EBV lytic replication. Here we show that there are high levels of miR-200 family members in oral and tonsillar epithelia and in saliva. Analysis of cultured oral epithelial cells (OKF6) showed that they actively secrete membrane vesicles (exosomes) that are enriched with miR-200 family members. Coculturing of EBV-positive B cells with OKF6 cells induced viral reactivation. Further, treatment of EBV-positive B cells with OKF6 cell-derived membrane vesicles promoted reactivation. Using a cell system that does not naturally express miR-200 family members, we found that enforced expression of a miR-200 family member produced membrane vesicles that were able to induce the lytic cascade in EBV-positive B cells. We propose that membrane vesicles secreted by oral and tonsillar epithelial cells may serve as a tissue-specific environmental cue that initiates reactivation in B cells, promoting the transfer of virus from peripheral B-cell stores to the oral epithelium to facilitate virus amplification and exchange to other hosts.

IMPORTANCE
Epstein-Barr virus (EBV) is an important human pathogen that is causally associated with several lymphomas and carcinomas. The switch from latency to the lytic cycle is critical for successful host infection and for EBV pathogenesis. Although the EBV lytic cycle can be triggered by certain agents
in vitro
, the mechanisms that signal reactivation
in vivo
are poorly understood. We previously reported that endogenously expressed miR-200 family members likely play a role in facilitating the lytic tendencies of EBV in epithelial cells. Here we show that membrane vesicles secreted from oral epithelial cells contain miR-200 family members and that they can be transmitted to proximal EBV-positive B cells, where they trigger reactivation. We propose that this intercellular communication pathway may serve as a sensor mechanism for infiltrating B cells to recognize an appropriate environment to initiate reactivation, thereby allowing the exchange of virus to the oral epithelium.
Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site
Authors: Strauss Mike , Schotte Lise , Thys Bert , Filman David J. , Hogle James M. 
Published: January 2016

ABSTRACT
Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion.

IMPORTANCE
We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed.
Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population
Authors: Qvist Ina , Hendriks Jeroen M L , Møller Dorthe S , Albertsen Andi E , Mogensen Helle M , Oddershede Gitte D , Odgaard Annette , Mortensen Leif Spange , Johnsen Søren Paaske , Frost Lars 
Published: January 2016

ObjectiveA previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death.MethodsAll patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts.ResultsA total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23).ConclusionsStructured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings.
Linking outcrop analogue with flow simulation to reduce uncertainty in sub-surface carbon capture and storage: an example from the Sherwood Sandstone Group of the Wessex Basin, UK
Authors: Newell Andrew J. , Shariatipour Seyed M. 
Published: January 2016

Abstract

Modelling the behaviour of carbon dioxide (CO
2
) injected into sub-surface reservoirs as part of carbon capture and storage (CCS) strategies is often performed using models that incorporate very limited geological detail, particularly at the subseismic (metre to decametre) scale. Those modelling studies that incorporate varying degrees of geological realism show the inherent risks and uncertainties that can result from neglecting heterogeneity and reservoir–caprock topography along the migration path of an injected CO
2
plume. A key problem is that detailed geological data are often not available for the relatively deep saline aquifers that are an important target for CCS. Deep saline aquifers fall between the relatively data-rich environments of shallow freshwater aquifers and hydrocarbon reservoirs and it is in these settings that outcrop analogues may play an important part in reducing the risks and uncertainties associated with CCS. This study uses an example from the Sherwood Sandstone Group (Otter Sandstone Formation) of the Wessex Basin to show how an outcrop study can impart a much greater understanding of heterogeneity in critical reservoir–caprock zones. Here the transition from the Sherwood Sandstone Group (fluvial sandstone reservoir) to the Mercia Mudstone Group (playa lacustrine mudstone seal) is not simple, but includes a major change in fluvial style that introduces considerable heterogeneity at the top of the reservoir. The study shows how laser-scanned outcrop can be used to rapidly construct static geological models that are taken through to flow simulations. In combination, the use of appropriate outcrop analogues and flow modelling can reduce the risks and uncertainties associated with CCS.
SGEF Is Regulated via TWEAK/Fn14/NF-κB Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide
Authors: Ensign Shannon P. Fortin , Roos Alison , Mathews Ian T. , Dhruv Harshil D. , Tuncali Serdar , Sarkaria Jann N. , Symons Marc H. , Loftus Joseph C. , Berens Michael E. , Tran Nhan L. 
Published: January 2016

Abstract
Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors. Despite surgical removal followed by concomitant radiation and chemotherapy with the alkylating agent temozolomide, GB tumors develop treatment resistance and ultimately recur. Impaired response to treatment occurs rapidly, conferring a median survival of just fifteen months. Thus, it is necessary to identify the genetic and signaling mechanisms that promote tumor resistance to develop targeted therapies to combat this refractory disease. Previous observations indicated that SGEF (ARHGEF26), a RhoG-specific guanine nucleotide exchange factor (GEF), is overexpressed in GB tumors and plays a role in promoting TWEAK-Fn14–mediated glioma invasion. Here, further investigation revealed an important role for SGEF in glioma cell survival. SGEF expression is upregulated by TWEAK-Fn14 signaling via NF-κB activity while shRNA-mediated reduction of SGEF expression sensitizes glioma cells to temozolomide-induced apoptosis and suppresses colony formation following temozolomide treatment. Nuclear SGEF is activated following temozolomide exposure and complexes with the DNA damage repair (DDR) protein BRCA1. Moreover, BRCA1 phosphorylation in response to temozolomide treatment is hindered by SGEF knockdown. The role of SGEF in promoting chemotherapeutic resistance highlights a heretofore unappreciated driver, and suggests its candidacy for development of novel targeted therapeutics for temozolomide-refractory, invasive GB cells.
Implication: SGEF, as a dual process modulator of cell survival and invasion, represents a novel target for treatment refractory glioblastoma. Mol Cancer Res; 14(3); 302–12. ©2016 AACR.
Radiofrequency Ablation of Persistent Atrial Fibrillation
Authors: Hussein Ayman A. , Saliba Walid I. , Barakat Amr , Bassiouny Mohammed , Chamsi-Pasha Mohammed , Al-Bawardy Rasha , Hakim Ali , Tarakji Khaldoun , Baranowski Bryan , Cantillon Daniel , Dresing Thomas , Tchou Patrick , Martin David O. , Varma Niraj , Bhargava Mandeep , Callahan Thomas , Niebauer Mark , Kanj Mohamed , Chung Mina , Natale Andrea , Lindsay Bruce D. , Wazni Oussama M. 
Published: January 2016

Background—
Various ablation strategies of persistent atrial fibrillation (PersAF) have had disappointing outcomes, despite concerted clinical and research efforts, which could reflect progressive atrial fibrillation–related atrial remodeling.

Methods and Results—

Two-year outcomes were assessed in 1241 consecutive patients undergoing first-time ablation of PersAF (2005–2012). The time intervals between the first diagnosis of PersAF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide and C-reactive protein before the procedures. The median diagnosis-to-ablation time was 3 years (25th–75th percentiles 1–6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in recurrence rates in addition to an increase in B-type natriuretic peptide levels (
P
=0.01), C-reactive protein levels (
P
<0.0001), and left atrial size (
P
=0.03). The arrhythmia recurrence rates over 2 years were 33.6%, 52.6%, 57.1%, and 54.6% in the first, second, third, and fourth quartiles, respectively (
P
categorical
<0.0001). In Cox Proportional Hazard analyses, B-type natriuretic peptide levels, C-reactive protein levels, and left atrial size were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with the ablation outcomes which persisted in multivariable Cox analyzes (hazard ratio for recurrence per +1Log diagnosis-to-ablation time 1.27, 95% confidence interval 1.14–1.43;
P
<0.0001; hazard ratio fourth versus first quartile 2.44, 95% confidence interval 1.68–3.65;
P
categorical
<0.0001).

Conclusions—
In patients with PersAF undergoing ablation, the time interval between the first diagnosis of PersAF and the catheter ablation procedure had a strong association with the ablation outcomes, such as shorter diagnosis-to-ablation times were associated with better outcomes and in direct association with markers of atrial remodeling.
MiR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis
Authors: Nagpal Varun , Rai Rahul , Place Aaron T. , Murphy Sheila B. , Verma Suresh K. , Ghosh Asish K. , Vaughan Douglas E. 
Published: January 2016

Background—
Cardiac fibrosis is the pathological consequence of stress-induced fibroblast proliferation and fibroblast-to-myofibroblast transition. MicroRNAs have been shown to play a central role in the pathogenesis of cardiac fibrosis. We identified a novel miRNA-driven mechanism that promotes cardiac fibrosis via regulation of multiple fibrogenic pathways.

Methods and Results—
Using a combination of in vitro and in vivo studies, we identified that miR-125b is a novel regulator of cardiac fibrosis, proliferation, and activation of cardiac fibroblasts. We demonstrate that miR-125b is induced in both fibrotic human heart and murine models of cardiac fibrosis. In addition, our results indicate that miR-125b is necessary and sufficient for the induction of fibroblast-to-myofibroblast transition by functionally targeting apelin, a critical repressor of fibrogenesis. Furthermore, we observed that miR-125b inhibits p53 to induce fibroblast proliferation. Most importantly, in vivo silencing of miR-125b by systemic delivery of locked nucleic acid rescued angiotensin II–induced perivascular and interstitial fibrosis. Finally, the RNA-sequencing analysis established that miR-125b altered the gene expression profiles of the key fibrosis-related genes and is a core component of fibrogenesis in the heart.

Conclusions—
In conclusion, miR-125b is critical for induction of cardiac fibrosis and acts as a potent repressor of multiple anti-fibrotic mechanisms. Inhibition of miR-125b may represent a novel therapeutic approach for the treatment of human cardiac fibrosis and other fibrotic diseases.
Response of Northern Hemisphere Midlatitude Circulation to Arctic Amplification in a Simple Atmospheric General Circulation Model
Authors: Wu Yutian , Smith Karen L. 
Published: January 2016

AbstractThis study examines the Northern Hemisphere midlatitude circulation response to Arctic amplification (AA) in a simple atmospheric general circulation model. It is found that, in response to AA, the tropospheric jet shifts equatorward and the stratospheric polar vortex weakens, robustly for various AA forcing strengths. Despite this, no statistically significant change in the frequency of sudden stratospheric warming events is identified. In addition, in order to quantitatively assess the role of stratosphere–troposphere coupling, the tropospheric pathway is isolated by nudging the stratospheric zonal mean state toward the reference state. When the nudging is applied, rendering the stratosphere inactive, the tropospheric jet still shifts equatorward but by approximately half the magnitude compared to that of an active stratosphere. The difference represents the stratospheric pathway and the downward influence of the stratosphere on the troposphere. This suggests that stratosphere–troposphere coupling plays a nonnegligible role in establishing the midlatitude circulation response to AA.
Advances in Geostationary-Derived Longwave Fluxes for the CERES Synoptic (SYN1deg) Product
Authors: Doelling David R. , Sun Moguo , Nguyen Le Trang , Nordeen Michele L. , Haney Conor O. , Keyes Dennis F. , Mlynczak Pamela E. 
Published: January 2016

AbstractThe Clouds and the Earth’s Radiant Energy System (CERES) project has provided the climate community 15 years of globally observed top-of-the-atmosphere fluxes critical for climate and cloud feedback studies. To accurately monitor the earth’s radiation budget, the CERES instrument footprint fluxes must be spatially and temporally averaged properly. The CERES synoptic 1° (SYN1deg) product incorporates derived fluxes from the geostationary satellites (GEOs) to account for the regional diurnal flux variations in between Terra and Aqua CERES measurements. The Edition 4 CERES reprocessing effort has provided the opportunity to reevaluate the derivation of longwave (LW) fluxes from GEO narrowband radiances by examining the improvements from incorporating 1-hourly versus 3-hourly GEO data, additional GEO infrared (IR) channels, and multichannel GEO cloud properties. The resultant GEO LW fluxes need to be consistent across the 16-satellite climate data record. To that end, the addition of the water vapor channel, available on all GEOs, was more effective than using a reanalysis dataset’s column-weighted relative humidity combined with the window channel radiance. The benefit of the CERES LW angular directional model to derive fluxes was limited by the inconsistency of the GEO cloud retrievals. Greater success was found in the direct conversion of window and water vapor channel radiances into fluxes. Incorporating 1-hourly GEO fluxes had the greatest impact on improving the accuracy of high-temporal-resolution fluxes, and normalizing the GEO LW fluxes with CERES greatly reduced the monthly regional LW flux bias.
Risk factors for repetition of a deliberate self-harm episode within seven days in adolescents and young adults: A population-level record linkage study in Western Australia
Authors: Hu Nan , Glauert Rebecca A , Li Jianghong , Taylor Catherine L 
Published: January 2016

Objective: The risk of repetition of deliberate self-harm peaks in the first 7 days after a deliberate self-harm episode. However, thus far no studies have examined the risk factors for repeating deliberate self-harm during this short-term period. We aimed to investigate the effects of socio-demographic factors, self-harm method and mental health factors in adolescents (10–19 years old) and young adults (20–29 years old). Methods: We used data linkage of population-wide administrative records from hospital inpatients and emergency departments to identify all the deliberate self-harm–related episodes that occurred in adolescents and young adults in Western Australia from 2000 to 2011. Logistic regression with generalised estimating equations was used for the analyses. Results: The incidence of repeating deliberate self-harm within the first 7 days after an index episode was 6% (403/6,768) in adolescents and 8% (842/10,198) in young adults. Socio-demographic risk factors included female gender and socioeconomic disadvantage. Compared with non-poisoning, self-poisoning predicted increased risk of having a repeated deliberate self-harm episode in males, but not in females. Borderline personality, impulse-control and substance use disorders diagnosed within one week before and one week after an index deliberate self-harm episode conferred the highest risk, followed by depressive and anxiety disorders. Having a preceding deliberate self-harm episode up to 7 days before an index episode was a strong predictor for the future repetition of a deliberate self-harm episode. Conclusion: Having a repeated deliberate self-harm episode within the first 7 days was related to a wide range of factors present at an index deliberate self-harm episode including socio-demographic characteristics, deliberate self-harm method and co-existing psychiatric conditions. These factors can inform risk assessments tailored to adolescents and young adults respectively to reduce the repetition of deliberate self-harm within a short but critical period, potentially contributing to reduce the repetition of deliberate self-harm in the long term.
Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant
Authors: Felsky Daniel , De Jager Philip L , Schneider Julie A , Arfanakis Konstantinos , Fleischman Debra A , Arvanitakis Zoe , Honer William G , Pouget Jennie G , Mizrahi Romina , Pollock Bruce G , Kennedy James L , Bennett David A , Voineskos Aristotle N ,   for the authors of the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2016

The translocator protein, a microglial-expressed marker of neuroinflammation, has been implicated in Alzheimer’s disease, which is characterized by alterations in vascular and inflammatory states. A TSPO variant, rs6971, determines binding affinity of exogenous radioligands in vivo; however, the effect of these altered binding characteristics on inflammatory and cerebrovascular biomarkers has not been assessed. In 2345 living subjects (Alzheimer’s Disease Neuroimaging Initiative, n = 1330) and postmortem brain samples (Religious Orders Study and Memory and Aging Project, n = 1015), we analyzed effects of rs6971 on white matter hyperintensisites, cerebral infarcts, circulating inflammatory biomarkers, amyloid angiopathy, and microglial activation. We found that rs6971 does not alter translocator protein in a way that impacts cerebrovascular and inflammatory states known to be affected in dementia.
Pharmacists’ Perceptions Regarding Optimization of Antibiotic Prescribing in the Community
Authors: Res Rebecca , Hoti Kreshnik , Charrois Theresa L. 
Published: January 2016

Background and Objective: The overuse of antibiotics in the community is a primary cause of antibiotic resistance. Community pharmacists are the most accessible health professionals and so they are in an ideal position to implement interventions to ensure the appropriate use of antibiotics. This study aimed to explore the role of community pharmacists in the optimization of antibiotic prescribing and utilization. Method: Four focus groups were conducted with community pharmacists in Perth, Western Australia. Audio-recorded data were compared with field notes, transcribed, and thematically analyzed. Results: There were twenty-four participants in four focus group sessions. Four main themes were identified: patient perceptions and behaviors, prescribing behaviors, pharmacists’ roles and responsibilities, and health care system interventions in relation to antibiotic utilization. A number of interventions that could be implemented by community pharmacists were identified. In addition to interventions that are currently in place in Australia, forward dispensing, improved interprofessional collaboration, an expansion of current prescribing role, and vaccination capabilities were also suggested. Conclusions: This study indicated that current scope of pharmacists’ roles has room for more intervention strategies aimed at improving antibiotic prescribing and utilization in the community.