bluuebunny/crossref_metadata_2025_split huggingface dataset:
Varicella-Zoster Virus Downregulates Programmed Death Ligand 1 and Major Histocompatibility Complex Class I in Human Brain Vascular Adventitial Fibroblasts, Perineurial Cells, and Lung Fibroblasts
Authors: Jones Dallas , Blackmon Anna , Neff C. Preston , Palmer Brent E. , Gilden Don , Badani Hussain , Nagel Maria A. 
Published: September 2016

ABSTRACT
Varicella-zoster virus (VZV) vasculopathy produces stroke, giant cell arteritis, and granulomatous aortitis, and it develops after virus reactivates from ganglia and spreads transaxonally to arterial adventitia, resulting in persistent inflammation and pathological vascular remodeling. The mechanism(s) by which inflammatory cells persist in VZV-infected arteries is unknown; however, virus-induced dysregulation of programmed death ligand 1 (PD-L1) may play a role. Specifically, PD-L1 can be expressed on virtually all nucleated cells and suppresses the immune system by interacting with the programmed cell death protein receptor 1, found exclusively on immune cells; thus, downregulation of PD-L1 may promote inflammation, as seen in some autoimmune diseases. Both flow cytometry and immunofluorescence analyses to test whether VZV infection of adventitial cells downregulates PD-L1 showed decreased PD-L1 expression in VZV-infected compared to mock-infected human brain vascular adventitial fibroblasts (HBVAFs), perineural cells (HPNCs), and fetal lung fibroblasts (HFLs) at 72 h postinfection. Quantitative RT-PCR analyses showed no change in PD-L1 transcript levels between mock- and VZV-infected cells, indicating a posttranscriptional mechanism for VZV-mediated downregulation of PD-L1. Flow cytometry analyses showed decreased major histocompatibility complex class I (MHC-I) expression in VZV-infected cells and adjacent uninfected cells compared to mock-infected cells. These data suggest that reduced PD-L1 expression in VZV-infected adventitial cells contribute to persistent vascular inflammation observed in virus-infected arteries from patients with VZV vasculopathy, while downregulation of MHC-I prevents viral clearance.

IMPORTANCE
Here, we provide the first demonstration that VZV downregulates PD-L1 expression in infected HBVAFs, HPNCs, and HFLs, which, together with the noted VZV-mediated downregulation of MHC-I, might foster persistent inflammation in vessels, leading to pathological vascular remodeling during VZV vasculopathy and persistent inflammation in infected lungs to promote subsequent infection of T cells and hematogenous virus spread. Identification of a potential mechanism by which persistent inflammation in the absence of effective viral clearance occurs in VZV vasculopathy and VZV infection of the lung is a step toward targeted therapy of VZV-induced disease.
Marine Bacterial and Archaeal Ion-Pumping Rhodopsins: Genetic Diversity, Physiology, and Ecology
Authors: Pinhassi Jarone , DeLong Edward F. , Béjà Oded , González José M. , Pedrós-Alió Carlos 
Published: September 2016

SUMMARY
The recognition of a new family of rhodopsins in marine planktonic bacteria, proton-pumping proteorhodopsin, expanded the known phylogenetic range, environmental distribution, and sequence diversity of retinylidene photoproteins. At the time of this discovery, microbial ion-pumping rhodopsins were known solely in haloarchaea inhabiting extreme hypersaline environments. Shortly thereafter, proteorhodopsins and other light-activated energy-generating rhodopsins were recognized to be widespread among marine bacteria. The ubiquity of marine rhodopsin photosystems now challenges prior understanding of the nature and contributions of “heterotrophic” bacteria to biogeochemical carbon cycling and energy fluxes. Subsequent investigations have focused on the biophysics and biochemistry of these novel microbial rhodopsins, their distribution across the tree of life, evolutionary trajectories, and functional expression in nature. Later discoveries included the identification of proteorhodopsin genes in all three domains of life, the spectral tuning of rhodopsin variants to wavelengths prevailing in the sea, variable light-activated ion-pumping specificities among bacterial rhodopsin variants, and the widespread lateral gene transfer of biosynthetic genes for bacterial rhodopsins and their associated photopigments. Heterologous expression experiments with marine rhodopsin genes (and associated retinal chromophore genes) provided early evidence that light energy harvested by rhodopsins could be harnessed to provide biochemical energy. Importantly, some studies with native marine bacteria show that rhodopsin-containing bacteria use light to enhance growth or promote survival during starvation. We infer from the distribution of rhodopsin genes in diverse genomic contexts that different marine bacteria probably use rhodopsins to support light-dependent fitness strategies somewhere between these two extremes.
Epidemic of fractures during a period of snow and ice: has anything changed 33 years on?
Authors: Al-Azzani Waheeb , Adam Maliq Mak Danial , Hodgson Paul , Williams Rhodri 
Published: September 2016

ObjectivesWe reproduced a frequently cited study that was published in theBritish Medical Journal(BMJ) in 1981 assessing the extent of ‘snow-and-ice’ fractures during the winter period.SettingThis study aims to provide an insight into how things have changed within the same emergency department (ED) by comparing the findings of theBMJpaper published 33 years ago with the present date.ParticipantsAs per the original study, all patients presenting to the ED with a radiological evidence of fracture during three different 4-day periods were included. The three 4-day periods included 4 days of snow-and-ice conditions and two control 4-day periods when snow and ice was not present; the first was 4 days within the same year, with a similar amount of sunshine hours, and the second was 4 days 1 calendar year later.Primary and secondary outcome measuresTo identify the frequency, distribution and pattern of fractures sustained in snow-and-ice conditions compared to control conditions as well as comparisons with the index study 33 years ago.ResultsA total of 293 patients with fractures were identified. Overall, there was a 2.20 (CI 1.7 to 3.0, p <0.01) increase in risk of fracture during snow-and-ice periods compared to control conditions. There was an increase (p <0.01) of fractures of the arm, forearm and wrist (RR 3.2 (CI 1.4 to 7.6) and 2.9 (CI 1.5 to 5.4) respectively).ConclusionsWhile the relative risk was not of the magnitude 33 years ago, the overall number of patients presenting with a fracture during snow-and-ice conditions remains more than double compared to control conditions. This highlights the need for improved understanding of the impact of increased fracture burden on hospitals and more effective preventative measures.
Development of an active behavioural physiotherapy intervention (ABPI) for acute whiplash-associated disorder (WAD) II management: a modified Delphi study
Authors: Wiangkham Taweewat , Duda Joan , Haque M Sayeed , Rushton Alison 
Published: September 2016

ObjectiveTo develop an active behavioural physiotherapy intervention (ABPI) for managing acute whiplash-associated disorder (WAD) II using a modified Delphi method to develop consensus for the basic features of the ABPI.DesignModified Delphi study. Our systematic review and meta-analysis evaluating conservative management for acute WADII found that a combined ABPI may be a useful intervention to prevent patients progressing to chronicity. No previous research has considered a combined behavioural approach and active physiotherapy in the management of acute WADII patients. The ABPI was therefore developed using a rigorous consensus method using international research and local clinical whiplash experts. Descriptive statistics were used to assess consensus in each round.SettingOnline international survey.ParticipantsA purposive sample of 97 potential participants (aiming to recruit n=30) consisting of international research whiplash experts, UK private physiotherapists and UK postgraduate musculoskeletal physiotherapy students were invited to participate via electronic mail with an attached participant information sheet and consent form.Results36 individuals signed and returned the consent form. In round 1, 32/36 participants (response rate=89%, mean age±SD=36.03±13.22 years) across 8 countries (Australia, Finland, Greece, India, Netherlands, Norway, Sweden and UK) contributed to round 1 questionnaire. Response rates were 78% and 75% for rounds 2 and 3, respectively. Following round 3, 12 underlying principles (eg, return to normal function as soon as possible, pain management, encouragement of self-management, reduce fear avoidance and anxiety) achieved consensus. The treatment components reaching consensus included behavioural (eg, education, reassurance, self-management) and physiotherapy components (eg, exercises for stability and mobility). No passive intervention achieved consensus.ConclusionsExperts suggested and agreed the underlying principles and treatment components of the ABPI for the management of acute WADII. The ABPI was underpinned by social cognitive theory focusing on self-efficacy enhancement prior to conducting a phase II trial.
Home-based versus centre-based cardiac rehabilitation: abridged Cochrane systematic review and meta-analysis
Authors: Buckingham S A , Taylor R S , Jolly K , Zawada A , Dean S G , Cowie A , Norton R J , Dalal H M 
Published: September 2016

ObjectiveTo update the Cochrane review comparing the effects of home-based and supervised centre-based cardiac rehabilitation (CR) on mortality and morbidity, quality of life, and modifiable cardiac risk factors in patients with heart disease.MethodsSystematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL were searched up to October 2014, without language restriction. Randomised trials comparing home-based and centre-based CR programmes in adults with myocardial infarction, angina, heart failure or who had undergone coronary revascularisation were included.Results17 studies with 2172 patients were included. No difference was seen between home-based and centre-based CR in terms of: mortality (relative risk (RR) 0.79, 95% CI 0.43 to 1.47); cardiac events; exercise capacity (mean difference (MD) −0.10, −0.29 to 0.08); total cholesterol (MD 0.07 mmol/L, −0.24 to 0.11); low-density lipoprotein cholesterol (MD −0.06 mmol/L, −0.27 to 0.15); triglycerides (MD −0.16 mmol/L, −0.38 to 0.07); systolic blood pressure (MD 0.2 mm Hg, −3.4 to 3.8); smoking (RR 0.98, 0.79 to 1.21); health-related quality of life and healthcare costs. Lower high-density lipoprotein cholesterol (MD −0.07 mmol/L, −0.11 to −0.03, p=0.001) and lower diastolic blood pressure (MD −1.9 mm Hg, −0.8 to −3.0, p=0.009) were observed in centre-based participants. Home-based CR was associated with slightly higher adherence (RR 1.04, 95% CI 1.01 to 1.07).ConclusionsHome-based and centre-based CR provide similar benefits in terms of clinical and health-related quality of life outcomes at equivalent cost for those with heart failure and following myocardial infarction and revascularisation.
Design and implementation of flexible TWDM-PON with PtP WDM overlay based on WSS for next-generation optical access networks
Authors: Wu Bin , Yin Hongxi , Qin Jie , Liu Chang , Liu Anliang , Shao Qi , Xu Xiaoguang 
Published: September 2016

Aiming at the increasing demand of the diversification services and flexible bandwidth allocation of the future access networks, a flexible passive optical network (PON) scheme combining time and wavelength division multiplexing (TWDM) with point-to-point wavelength division multiplexing (PtP WDM) overlay is proposed for the next-generation optical access networks in this paper. A novel software-defined optical distribution network (ODN) structure is designed based on wavelength selective switches (WSS), which can implement wavelength and bandwidth dynamical allocations and suits for the bursty traffic. The experimental results reveal that the TWDM-PON can provide 40 Gb/s downstream and 10 Gb/s upstream data transmission, while the PtP WDM-PON can support 10 GHz point-to-point dedicated bandwidth as the overlay complement system. The wavelengths of the TWDM-PON and PtP WDM-PON are allocated dynamically based on WSS, which verifies the feasibility of the proposed structure.
Lurbinectedin Specifically Triggers the Degradation of Phosphorylated RNA Polymerase II and the Formation of DNA Breaks in Cancer Cells
Authors: Santamaría Nuñez Gema , Robles Carlos Mario Genes , Giraudon Christophe , Martínez-Leal Juan Fernando , Compe Emmanuel , Coin Frédéric , Aviles Pablo , Galmarini Carlos María , Egly Jean-Marc 
Published: September 2016

Abstract
We have defined the mechanism of action of lurbinectedin, a marine-derived drug exhibiting a potent antitumor activity across several cancer cell lines and tumor xenografts. This drug, currently undergoing clinical evaluation in ovarian, breast, and small cell lung cancer patients, inhibits the transcription process through (i) its binding to CG-rich sequences, mainly located around promoters of protein-coding genes; (ii) the irreversible stalling of elongating RNA polymerase II (Pol II) on the DNA template and its specific degradation by the ubiquitin/proteasome machinery; and (iii) the generation of DNA breaks and subsequent apoptosis. The finding that inhibition of Pol II phosphorylation prevents its degradation and the formation of DNA breaks after drug treatment underscores the connection between transcription elongation and DNA repair. Our results not only help to better understand the high specificity of this drug in cancer therapy but also improve our understanding of an important transcription regulation mechanism. Mol Cancer Ther; 15(10); 2399–412. ©2016 AACR.
Cardiac Abnormalities in First-Degree Relatives of Unexplained Cardiac Arrest Victims
Authors: Steinberg Christian , Padfield Gareth J. , Champagne Jean , Sanatani Shubhayan , Angaran Paul , Andrade Jason G. , Roberts Jason D. , Healey Jeffrey S. , Chauhan Vijay S. , Birnie David H. , Janzen Mikyla , Gerull Brenda , Klein George J. , Leather Richard , Simpson Christopher S. , Seifer Colette , Talajic Mario , Gardner Martin , Krahn Andrew D. 
Published: September 2016

Background—
Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities.

Methods and Results—

Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims’ relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%;
P
=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%;
P
=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%).

Conclusions—
Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00292032.
Outcome of the Swedish Nationwide Abdominal Aortic Aneurysm Screening Program
Authors: Wanhainen Anders , Hultgren Rebecka , Linné Anneli , Holst Jan , Gottsäter Anders , Langenskiöld Marcus , Smidfelt Kristian , Björck Martin , Svensjö Sverker , Lyttkens Linda , Pihl Ewa , Wetterling Tomas , Kjellin Per , Eliasson Ken , Wellander Erik , Narbani Azin , Skagius Elisabet , Hollsten Alexandra , Welander Martin , Länne Toste , Fröst Bibbi , Korman David , Persson Sven-Erik , Sigvant Birgitta , Troëng Thomas , Palm Markus , Ansgarius Eva , Gilgen Nils-Peter , Sjöström Christina , Gidlund Khatereh Djavani , Danielsson Peter , Bersztel Adam , Jonasson Tomas 
Published: September 2016

Background:
A general abdominal aortic aneurysm (AAA) screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006 and reached nationwide coverage in 2015. The aim of this study was to determine the outcome of this program.

Methods:
Data on the number of invited and examined men, screening-detected AAAs, AAAs operated on, and surgical outcome were retrieved from all 21 Swedish counties for the years 2006 through 2014. AAA-specific mortality data were retrieved from the Swedish Cause of Death Registry. A linear regression analysis was used to estimate the effect on AAA-specific mortality among all men ≥65 years of age for the observed time period. The long-term effects were projected by using a validated Markov model.

Results:

Of 302 957 men aged 65 years invited, 84% attended. The prevalence of screening-detected AAA was 1.5%. After a mean of 4.5 years, 29% of patients with AAA had been operated on, with a 30-day mortality rate of 0.9% (1.3% after open repair and 0.3% after endovascular repair,
P
<0.001). The introduction of screening was associated with a significant reduction in AAA-specific mortality (mean, 4.0% per year of screening,
P
=0.020). The number needed to screen and the number needed to operate on to prevent 1 premature death were 667 and 1.5, respectively. With a total population of 9.5 million, the Swedish national AAA-screening program was predicted to annually prevent 90 premature deaths from AAA and to gain 577 quality-adjusted life-years. The incremental cost-efficiency ratio was estimated to be €7770 per quality-adjusted life-years.

Conclusions:
Screening 65-year-old men for AAA is an effective preventive health measure and is highly cost-effective in a contemporary setting. These findings confirm the results from earlier randomized controlled trials and model studies in a large population-based setting of the importance for future healthcare decision making.
Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans
Authors: Shishido Koki , Antoniadis Antonios P. , Takahashi Saeko , Tsuda Masaya , Mizuno Shingo , Andreou Ioannis , Papafaklis Michail I. , Coskun Ahmet U. , O'Brien Caroline , Feldman Charles L. , Saito Shigeru , Edelman Elazer R. , Stone Peter H. 
Published: September 2016

Background

In‐stent hyperplasia (
ISH
) may develop in regions of low endothelial shear stress (
ESS
), but the relationship between the magnitude of low
ESS
, the extent of
ISH,
and subsequent clinical events has not been investigated.

Methods and Results

We assessed the association of poststent
ESS
with neointimal
ISH
and clinical outcomes in patients treated with percutaneous coronary interventions (
PCI
). Three‐dimensional coronary reconstruction was performed in 374 post‐
PCI
patients at baseline and 6 to 10 months follow‐up as part of the
PREDICTION
Study. Each vessel was divided into 1.5‐mm‐long segments, and we calculated the local
ESS
within each stented segment at baseline. At follow‐up, we assessed
ISH
and the occurrence of a clinically indicated repeat
PCI
for in‐stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare‐metal stents (
BMS
), 104 (42.3%) sirolimus‐eluting stents, and 42 (17.1%) paclitaxel‐eluting stents. In
BMS
, low
ESS
post‐
PCI
at baseline was independently associated with
ISH
(β=1.47 mm
2
per 1‐Pa decrease; 95%
CI
, 0.38–2.56;
P
<0.01).
ISH
was minimal in drug‐eluting stents. During follow‐up, repeat
PCI
in
BMS
was performed in 21 stents (8.5%). There was no significant association between post‐
PCI ESS
and in‐stent restenosis requiring
PCI
.

Conclusions

Low
ESS
after
BMS
implantation is associated with subsequent
ISH
.
ISH
is strongly inhibited by drug‐eluting stents. Post‐
PCI ESS
is not associated with in‐stent restenosis requiring repeat
PCI
.
ESS
is an important determinant of
ISH
in
BMS
, but
ISH
of large magnitude to require
PCI
for in‐stent restenosis is likely attributed to factors other than
ESS
within the stent.
Facility‐Level Percutaneous Coronary Intervention Readmission Rates Are Not Associated With Facility‐Level Mortality: Insights From the VA Clinical Assessment, Reporting, and Tracking (CART) Program
Authors: Hegeman Timothy W. , Glorioso Thomas J. , Hess Edward , Barón Anna E. , Ho P. Michael , Maddox Thomas M. , Bradley Steven M. , Burke Robert E. 
Published: September 2016

Background

Thirty‐day readmission after percutaneous coronary intervention (
PCI
) is common, costly, and linked to poor patient outcomes. Accordingly, facility‐level 30‐day readmission rates have been considered as a potential quality measure. However, it is unknown whether facility‐level 30‐day readmission rates are associated with facility‐level mortality. We sought to determine the effect of 30‐day readmissions after
PCI
on mortality at both the patient and facility level in the Veterans Administration hospital system.

Methods and Results

We included all patients who underwent
PCI
in the Veterans Administration hospital system nationally from October 2007 through August 2012, comparing all‐cause mortality rates between patients with and without 30‐day readmissions following
PCI
. Patients were then aggregated at the hospital level to evaluate the correlation between hospital‐level readmission rates with hospital‐level 1‐year mortality rates. Among 41 069 patients undergoing
PCI
at 62 sites, 12.2% were readmitted within 30 days of discharge. Patients with 30‐day readmission had higher risk‐adjusted mortality (hazard ratio 1.53, 95%
CI
1.44–1.63,
P
<0.0001). Facilities varied widely in 30‐day readmission rates (systemwide range of 6.6–19.4%, median 11.8%, interquartile range 10.0–13.2%); however, adjusted facility‐level readmission rates were not correlated with adjusted 1‐year mortality rates.

Conclusions

Thirty‐day readmissions after
PCI
are common and are a significant risk factor for mortality for individual patients even after robust statistical adjustment for clinical confounding. However, lack of correlation between readmission and mortality at the facility level suggests that quality improvement based on facility‐level readmission rates will not modify mortality in this high‐risk group.