bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Coronavirus HKU1 Spike Protein Uses
O
-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme
Authors: Huang Xingchuan , Dong Wenjuan , Milewska Aleksandra , Golda Anna , Qi Yonghe , Zhu Quan K. , Marasco Wayne A. , Baric Ralph S. , Sims Amy C. , Pyrc Krzysztof , Li Wenhui , Sui Jianhua 
Published: April 2015

ABSTRACT

Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-
O
-acetylated sialic acid (9-
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-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-
O
-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-
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-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the
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-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only
in vitro
replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits
O
-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-
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-acetylesterase RDE activity.

IMPORTANCE
Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an
O
-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of
O
-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-
O
-acetylesterase RDE activity.
Recombination Analysis of Herpes Simplex Virus 1 Reveals a Bias toward GC Content and the Inverted Repeat Regions
Authors: Lee Kyubin , Kolb Aaron W. , Sverchkov Yuriy , Cuellar Jacqueline A. , Craven Mark , Brandt Curtis R. 
Published: April 2015

ABSTRACT
Herpes simplex virus 1 (HSV-1) causes recurrent mucocutaneous ulcers and is the leading cause of infectious blindness and sporadic encephalitis in the United States. HSV-1 has been shown to be highly recombinogenic; however, to date, there has been no genome-wide analysis of recombination. To address this, we generated 40 HSV-1 recombinants derived from two parental strains, OD4 and CJ994. The 40 OD4-CJ994 HSV-1 recombinants were sequenced using the Illumina sequencing system, and recombination breakpoints were determined for each of the recombinants using the Bootscan program. Breakpoints occurring in the terminal inverted repeats were excluded from analysis to prevent double counting, resulting in a total of 272 breakpoints in the data set. By placing windows around the 272 breakpoints followed by Monte Carlo analysis comparing actual data to simulated data, we identified a recombination bias toward both high GC content and intergenic regions. A Monte Carlo analysis also suggested that recombination did not appear to be responsible for the generation of the spontaneous nucleotide mutations detected following sequencing. Additionally, kernel density estimation analysis across the genome found that the large, inverted repeats comprise a recombination hot spot.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) virus is the leading cause of sporadic encephalitis and blinding keratitis in developed countries. HSV-1 has been shown to be highly recombinogenic, and recombination itself appears to be a significant component of genome replication. To date, there has been no genome-wide analysis of recombination. Here we present the findings of the first genome-wide study of recombination performed by generating and sequencing 40 HSV-1 recombinants derived from the OD4 and CJ994 parental strains, followed by bioinformatics analysis. Recombination breakpoints were determined, yielding 272 breakpoints in the full data set. Kernel density analysis determined that the large inverted repeats constitute a recombination hot spot. Additionally, Monte Carlo analyses found biases toward high GC content and intergenic and repetitive regions.
A novel measure of socioeconomic status using individual housing data to assess the association of SES with rheumatoid arthritis and its mortality: a population-based case–control study
Authors: Ghawi Husam , Crowson Cynthia S , Rand-Weaver Jennifer , Krusemark Elizabeth , Gabriel Sherine E , Juhn Young J 
Published: April 2015

ObjectivesTo assess whether HOUSES (HOUsing-based index of socioeconomic status (SES)) is associated with risk of and mortality after rheumatoid arthritis (RA).DesignWe conducted a population-based case–control study which enrolled population-based RA cases and their controls without RA.SettingThe study was performed in Olmsted County, Minnesota.ParticipantsStudy participants were all residents of Olmsted County, Minnesota, with RA identified using the 1987 American College of Rheumatology criteria for RA from 1 January 1988, to 31 December 2007, using the auspices of the Rochester Epidemiology Project. For each patient with RA, one control was randomly selected from Olmsted County residents of similar age and gender without RA.Primary and secondary outcome measureThe disease status was RA cases and their matched controls in relation to HOUSES as an exposure. As a secondary aim, post-RA mortality among only RA cases was an outcome event. The associations of SES measured by HOUSES with the study outcomes were assessed using logistic regression and Cox models. HOUSES, as a composite index, was formulated based on a summed z-score for housing value, square footage and number of bedrooms and bathrooms.ResultsOf the eligible 604 participants, 418 (69%) were female; the mean age was 56±15.6 years. Lower SES, as measured by HOUSES, was associated with the risk of developing RA (0.5±3.8 for controls vs −0.2±3.1 for RA cases, p=0.003), adjusting for age, gender, calendar year of RA index date, smoking status and BMI. The lowest quartile of HOUSES was significantly associated with increased post-RA mortality compared to higher quartiles of HOUSES (HR 1.74; 95% CI 1.10 to 2.74; p=0.017) in multivariate analysis.ConclusionsLower SES, as measured by HOUSES, is associated with increased risk of RA and mortality after RA. HOUSES may be a useful tool for health disparities research concerning rheumatological outcomes when conventional SES measures are unavailable.
Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population
Authors: Haraoui Boulos , Jovaisas Algis , Bensen William G , Faraawi Rafat , Kelsall John , Dixit Sanjay , Rodrigues Jude , Sheriff Maqbool , Rampakakis Emmanouil , Sampalis John S , Lehman Allen J , Otawa Susan , Nantel Francois , Shawi May 
Published: April 2015

ObjectiveTo describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care.MethodsBiological naïve patients with RA followed in theBiologicTreatmentRegistryAcrossCanada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression.Results838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28(95% CI) 1.40 (0.95 to 2.06); HRCDAI1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28(95% CI) 1.78 (1.00 to 3.19); HRCDAI2.38 (1.14 to 4.99)).ConclusionsOral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered.Trial registration numberNCT00741793.
Radiation biophysical aspects of charged particles: From the nanoscale to therapy
Authors: Scifoni Emanuele 
Published: April 2015

Charged particle applications for radiotherapy are motivated by their specific advantages in terms of dose delivery and biological effect. These advantages have to a large extent originated from the peculiarities of ion beam energy deposition patterns in the medium on a microscopic, down to a nanoscopic scale. A large amount of research was conducted in this direction, especially in the last two decades, profiting also from the parallel investigations going on in radiation protection for space exploration. The main biophysical aspects of charged particles, which are relevant to hadrontherapy are shortly reviewed in the present contribution, namely focusing on relative biological effectiveness (RBE), oxygen enhancement ratio (OER) and combination with radiosensitizers. A summary of present major research direction on both microscopic and macroscopic assessment of the specific mechanism of radiation damage will be given, as well as several open challenges for a better understanding of the whole process, which still limit the full exploitation of ion beams for radiotherapy.
Gantries and dose delivery systems
Authors: Meer David , Psoroulas Serena 
Published: April 2015

Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.
On Finsler manifolds of negative flag curvature
Authors: Fang Yong , Foulon Patrick 
Published: April 2015

One of the key differences between Finsler metrics and Riemannian metrics is the non-reversibility, i.e. given two points p and q, the Finsler distance d(p, q) is not necessarily equal to d(q, p). In this paper, we build the main tools to investigate the non-reversibility in the context of large-scale geometry of uniform Finsler Cartan–Hadamard manifolds. In the second part of this paper, we use the large-scale geometry to prove the following dynamical theorem: Let φ be the geodesic flow of a closed negatively curved Finsler manifold. If its Anosov splitting is C2, then its cohomological pressure is equal to its Liouville metric entropy. This result generalizes a previous Riemannian result of U. Hamenstädt.
A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer
Authors: Small Eric J. , Lance Raymond S. , Gardner Thomas A. , Karsh Lawrence I. , Fong Lawrence , McCoy Candice , DeVries Todd , Sheikh Nadeem A. , GuhaThakurta Debraj , Chang Nancy , Redfern Charles H. , Shore Neal D. 
Published: April 2015

Abstract
Purpose: This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients.
Experimental Design: mCRPC patients received sipuleucel-T followed by AA + P 1 day (concurrent) or 10 weeks (sequential) after the first sipuleucel-T infusion. AA + P treatment continued for 26 weeks. The primary endpoint was cumulative antigen presenting cell (APC) activation, and secondary endpoints included cumulative APC number and total nucleated cell counts. Additional endpoints included in vivo peripheral immune responses to sipuleucel-T (T-cell responses, T-cell proliferation, humoral responses, and antigen spread) as well as safety.
Results: Sixty-nine mCRPC patients were enrolled, with 35 and 34 patients randomized to the concurrent and sequential arms, respectively. Ex vivo APC activation was significantly greater at the second and third infusions compared with baseline in both arms (P &lt; 0.05), indicative of an immunologic prime-boost effect. In both arms, sipuleucel-T product parameter profiles and peripheral immune responses were consistent with previously conducted sipuleucel-T phase III trials. Antigen spread was similarly observed in both arms and consistent with the other immunologic endpoints.
Conclusions: These data suggest that sipuleucel-T can be successfully manufactured during concurrent administration of AA + P without blunting immunologic effects or altering immune parameters that correlate with sipuleucel-T's clinical benefit. Combination of these agents was well tolerated, with no new safety signals emerging. Clin Cancer Res; 21(17); 3862–9. ©2015 AACR.
Role of Alternative Interventional Procedures When Endo- and Epicardial Catheter Ablation Attempts for Ventricular Arrhythmias Fail
Authors: Kumar Saurabh , Barbhaiya Chirag R. , Sobieszczyk Piotr , Eisenhauer Andrew C. , Couper Gregory S. , Nagashima Koichi , Mahida Saagar , Baldinger Samuel H. , Choi Eue-Keun , Epstein Laurence M. , Koplan Bruce A. , John Roy M. , Michaud Gregory F. , Stevenson William G. , Tedrow Usha B. 
Published: April 2015

Background—
Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group.

Methods and Results—

Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1;
P
<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%.

Conclusions—
A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.
Temperature Variation over East Asia during the Lifecycle of Weak Stratospheric Polar Vortex
Authors: Woo Sung-Ho , Kim Baek-Min , Kug Jong-Seong 
Published: April 2015

Abstract
The authors investigate the circulation change during the life cycle of a weak stratospheric polar vortex (WSV) event and its impact on temperature variation over East Asia. The lower-tropospheric temperature over East Asia strongly fluctuates despite the slow decay of stratospheric circulation and the continuously negative Arctic Oscillation (AO) pattern during the WSV event. The temperature fluctuation is critically influenced by the variation of the East Asian upper-level coastal trough (EAT), which may be coupled to the stratospheric circulation during the WSV events. The EAT is deepened anomalously during the Peak phase (from lag −5 to lag 5 day) of the WSV, and East Asian temperature is lowest during this phase. During the next period (Decay-1 phase: from lag 6 to lag 16 day), in spite of the slowly decaying WSV condition, the cold temperature anomaly over East Asia is suddenly weakened; this change is caused by a westward-propagating signal of an anticyclonic anomaly from the North Pacific to East Asia. After about two weeks (Decay-2 phase: from lag 17 to lag 27 day), the cold conditions over East Asia are restrengthened by an intensification of EAT, which is related to the eastward propagation of a large-scale wave packet originating from a negative North Atlantic Oscillation (NAO)-type structure in the Decay-1 phase and its delayed influence on the East Asia region.
Governing the smart city: a review of the literature on smart urban governance
Authors: Meijer Albert , Bolívar Manuel Pedro Rodríguez 
Published: April 2015

Academic attention to smart cities and their governance is growing rapidly, but the fragmentation in approaches makes for a confusing debate. This article brings some structure to the debate by analyzing a corpus of 51 publications and mapping their variation. The analysis shows that publications differ in their emphasis on (1) smart technology, smart people or smart collaboration as the defining features of smart cities, (2) a transformative or incremental perspective on changes in urban governance, (3) better outcomes or a more open process as the legitimacy claim for smart city governance. We argue for a comprehensive perspective: smart city governance is about crafting new forms of human collaboration through the use of ICTs to obtain better outcomes and more open governance processes. Research into smart city governance could benefit from previous studies into success and failure factors for e-government and build upon sophisticated theories of socio-technical change. This article highlights that smart city governance is not a technological issue: we should study smart city governance as a complex process of institutional change and acknowledge the political nature of appealing visions of socio-technical governance. Points for practitioners The study provides practitioners with an in-depth understanding of current debates about smart city governance. The article highlights that governing a smart city is about crafting new forms of human collaboration through the use of information and communication technologies. City managers should realize that technology by itself will not make a city smarter: building a smart city requires a political understanding of technology, a process approach to manage the emerging smart city and a focus on both economic gains and other public values.
Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine
Authors: Ho Tony W , Ho Andrew P , Ge Yang (Joy) , Assaid Christopher , Gottwald Regina , MacGregor E Anne , Mannix Lisa K , van Oosterhout Willebrordus PJ , Koppenhaver Janelle , Lines Christopher , Ferrari Michel D , Michelson David 
Published: April 2015

Aim The aim of this article is to evaluate the safety and efficacy of perimenstrual telcagepant, a CGRP receptor antagonist, for headache prophylaxis. Methods We conducted a randomized, double-blind, placebo-controlled, six-month trial in women with migraine for ≥3 months who experienced perimenstrual headaches. Women were randomized to telcagepant 140 mg or placebo (2:1 ratio) for seven consecutive days perimenstrually. Safety was assessed by adverse events and laboratory tests. The primary efficacy endpoint was mean monthly headache days in the subset of women reporting perimenstrual migraine (−2 days to +3 days of menses onset) and ≥5 moderate or severe migraines per month prior to entering the trial. Results Telcagepant was generally well tolerated: 66/2660 (2.5%) on telcagepant and 36/1326 (2.7%) on placebo discontinued because of a clinical adverse event. The percentages of patients with clinical adverse events, laboratory adverse events, or discontinuation because of a laboratory adverse event were also similar between treatments. Alanine aminotransferase elevations ≥3× normal occurred in 0.6% of women on telcagepant and 0.4% on placebo. Three women on telcagepant vs none on placebo had alanine aminotransferase elevations ≥8× normal. In the efficacy subset there was no significant effect of telcagepant ( n = 887) vs placebo ( n = 447) in mean monthly headache days (treatment difference −0.5 day (95% CI: −1.1, 0.1)). However, telcagepant was associated with a reduction in on-drug headache days (treatment difference −0.4 day (95% CI: –0.5, –0.2), nominal p < 0.001). Conclusions Telcagepant 140 mg taken perimenstrually for seven days was generally well tolerated, but was associated with transaminase elevations . Telcagepant did not reduce monthly headache frequency, but did reduce perimenstrual headaches.