bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection
Authors: Reynolds Tracy D. , Buonocore Linda , Rose Nina F. , Rose John K. , Robek Michael D. 
Published: August 2015

ABSTRACTMore than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus-like vesicles (VLVs) that contain VSV G but no other viral structural proteins. We report here that the evolved VLV vector engineered to additionally express the HBV middle surface envelope glycoprotein (MHBs) induces functional CD8 T cell responses in mice. These responses were greater in magnitude and broader in specificity than those obtained with other immunization strategies, including recombinant protein and DNA. Additionally, a single immunization with VLV-MHBs protected mice from HBV hydrodynamic challenge, and this protection correlated with the elicitation of a CD8 T cell recall response. In contrast to MHBs, a VLV expressing HBV core protein (HBcAg) neither induced a CD8 T cell response in mice nor protected against challenge. Finally, combining DNA and VLV-MHBs immunization led to induction of HBV-specific CD8 T cell responses in a transgenic mouse model of chronic HBV infection. The ability of VLV-MHBs to induce a multispecific T cell response capable of controlling HBV replication, and to generate immune responses in a tolerogenic model of chronic infection, indicates that VLV vaccine platforms may offer a unique strategy for HBV therapeutic vaccination.IMPORTANCEHBV infection is associated with significant morbidity and mortality. Furthermore, treatments for chronic infection are suboptimal and rarely result in complete elimination of the virus. Therapeutic vaccines represent a unique approach to HBV treatment and have the potential to induce long-term control of infection. Recently, a virus-based vector system that combines the nonstructural proteins of Semliki Forest virus with the VSV glycoprotein has been described. In this study, we used this system to construct a novel HBV vaccine and demonstrated that the vaccine is capable of inducing virus-specific immune responses in mouse models of acute and chronic HBV replication. These findings highlight the potential of this new vaccine system and support the idea that highly immunogenic vaccines, such as viral vectors, may be useful in the treatment of chronic hepatitis B.
Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations
Authors: Karakas Aram , Brumme Zabrina L. , Poon Art F. Y. 
Published: August 2015

ABSTRACT
Associations between HIV-1 cytotoxic T lymphocyte (CTL) escape mutations and their restricting human leukocyte antigen (HLA) alleles imply that HIV could adapt to divergent HLA repertoires of human populations globally. Using publicly available databases, we examine the relationship between the frequencies of 19 experimentally validated CTL escape mutations in HIV-1 reverse transcriptase and their restricting HLA alleles in 59 countries. From these extensive data, we find evidence of differential HIV adaptations to human populations at only a limited number of the studied epitope sites.
Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity
Authors: Turkington Hannah L. , Juozapaitis Mindaugas , Kerry Philip S. , Aydillo Teresa , Ayllon Juan , García-Sastre Adolfo , Schwemmle Martin , Hale Benjamin G. 
Published: August 2015

ABSTRACT
We demonstrate that novel bat HL17NL10 and HL18NL11 influenza virus NS1 proteins are effective interferon antagonists but do not block general host gene expression. Solving the RNA-binding domain structures revealed the canonical NS1 symmetrical homodimer, and RNA binding required conserved basic residues in this domain. Interferon antagonism was strictly dependent on RNA binding, and chimeric bat influenza viruses expressing NS1s defective in this activity were highly attenuated in interferon-competent cells but not in cells unable to establish antiviral immunity.
Infectious Risks of Traveling Abroad
Authors: Chen Lin H. , Blair Barbra M. 
Published: August 2015

ABSTRACT
A popular leisure activity, international travel can be associated with some infections. The most common travel-related illnesses appear to be gastrointestinal, dermatologic, respiratory, and systemic febrile syndromes. The pretravel medical consultation includes immunizations, malaria chemoprophylaxis, self-treatment for traveler’s diarrhea, and advice on the prevention of a myriad of other infectious causes including dengue, chikungunya, rickettsiosis, leptospirosis, schistosomiasis, and strongyloidiasis. Travel to locations experiencing outbreaks such as Ebola virus disease, Middle East respiratory syndrome, avian influenza, and chikungunya call for specific alerts on preventive strategies. After travel, evaluation of an ill traveler must explore details of exposure, including destinations visited; activities; ingestion of contaminated food or drinks; contact with vectors, animals, fresh water, or blood and body fluids; and other potential exposures. Knowledge of the geographic distribution of infectious diseases is important in generating the differential diagnoses and testing accordingly. Empiric treatment is sometimes necessary when suspicion of a certain diagnosis is strong and confirmatory tests are delayed or lacking, particularly for infections that are rapidly progressive (for example, malaria) or for which timing of testing is prolonged (such as leptospirosis).
Chemical Biology Strategies for Biofilm Control
Authors: Yang Liang , Givskov Michael 
Published: August 2015

ABSTRACT
Microbes live as densely populated multicellular surface-attached biofilm communities embedded in self-generated, extracellular polymeric substances (EPSs). EPSs serve as a scaffold for cross-linking biofilm cells and support development of biofilm architecture and functions. Biofilms can have a clear negative impact on humans, where biofilms are a common denominator in many chronic diseases in which they prime development of destructive inflammatory conditions and the failure of our immune system to efficiently cope with them. Our current assortment of antimicrobial agents cannot efficiently eradicate biofilms. For industrial applications, the removal of biofilms within production machinery in the paper and hygienic food packaging industry, cooling water circuits, and drinking water manufacturing systems can be critical for the safety and efficacy of those processes. Biofilm formation is a dynamic process that involves microbial cell migration, cell-to-cell signaling and interactions, EPS synthesis, and cell-EPS interactions. Recent progress of fundamental biofilm research has shed light on novel chemical biology strategies for biofilm control. In this article, chemical biology strategies targeting the bacterial intercellular and intracellular signaling pathways will be discussed.
Effects of Electroacupuncture at Gb Points on Markers of Osteoporosis and Bodyweight in Ovariectomised Rats
Authors: Wang Hong-Du , Chen Zhuang , Inoue Isao , Fu Shi-Jie , Shi Xiao-Lin , Tang Li , Zhang Feng-Zheng , Jiang Yang , Jiang Hua 
Published: August 2015

Background Based on a description of acupuncture to treat a bone disease resembling osteoporosis in the ancient text of Huangdi Neijing, we aimed to assess the effects of electroacupuncture (EA) at GB points in ovariectomised (OVX) rats. Methods 40 female Wistar rats were randomly divided into four groups (n=10 each): ovariectomised model group (OVX); ovariectomised group treated with EA at GB points (OVX+GB); ovariectomised group treated with EA at non-GB points (OVX+N) in the hindlimb; and a sham surgery group (Sham). Three months after ovariectomy, rats in the OVX+GB and OVX+N groups received EA treatment for 3 months. Urine, blood and femur samples were collected from each animal for analysis. Results Bodyweight (BW) in the OVX+GB group decreased after EA treatment, reaching a minimum of ∼12% below the OVX and OVX+N groups at 1 month. Concentrations of urine deoxypyridinoline, a bone resorption marker, were significantly elevated in the OVX and OVX+N groups but not the OVX+GB group. Concentrations of serum bone specific alkaline phosphatase, a bone formation marker, were significantly higher in the OVX+GB group versus the Sham and OVX groups. Bone mineral density (BMD) did not differ between the OVX, OVX+GB and OVX+N groups, but was ∼10% lower than the Sham group. However, BMD/BW in the OVX+GB group was significantly higher than in the OVX and OVX+N groups and similar to the Sham group. Histological assessment of the femur showed that EA at GB points improved the bone architecture. Conclusions EA treatment at GB points had anti-osteoporotic effects in a rat model of osteoporosis.
Injury data of major international field hockey tournaments
Authors: Theilen Till-Martin , Mueller-Eising Wiebke , Wefers Bettink Peter , Rolle Udo 
Published: August 2015

BackgroundDetailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.Materials and methodsFIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.ResultsThe average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.SummaryField hockey has a low incidence of acute injuries during competition.
Analyzing thoracic cavity gas during pneumothorax treatment to monitor the pneumothorax conditions in real time for updating the treatment strategy: A pilot study
Authors: Ma Hui , Jia Wei , Li Yuechuan 
Published: August 2015

Objectives To monitor the pneumothorax conditions in real time by analyzing thoracic cavity gas during pneumothorax treatment, and provide instructions for updating the treatment strategy. Methods The partial pressures of O2 and CO2 in the thoracic cavity from 49 pneumothorax patients was analyzed before the management and after chest tube clogging during the management. The pneumothorax type was differentially diagnosed according to the partial pressure results, and the treatment strategy was updated accordingly. Results The 49 pneumothorax patients were divided into four groups, as follows: Group A, 30 patients with a closed pneumothorax were confirmed to have a closed pneumothorax in the second analysis; Group B, 10 patients with an open pneumothorax were confirmed to have an open pneumothorax in the second analysis; Group C, three patients with a tension pneumothorax confirmed to have a tension pneumothorax in the second analysis; and Group D, six patients with a closed pneumothorax were re-diagnosed to have an open pneumothorax in the second analysis. The cure rates of the four groups after treatment were as follows: Group A (97%, 29/30), Group B (100%, 16/16), Group C (100%, 3/3) and Group D (100%, 6/6). Conclusions Analyzing thoracic cavity gas during pneumothorax treatment is suggested as an efficient way to monitor the pneumothorax conditions in real time and to provide instructions for updating the treatment strategy.
Nonlinear Stability of Periodic Traveling Wave Solutions for(n +1)-Dimensional Coupled Nonlinear Klein-Gordon Equations
Authors: Sun Cong , Jiang Bo 
Published: August 2015

We study the existence and orbital stability of smooth periodic traveling waves solutions of the(n +1)-dimensional coupled nonlinear Klein-Gordon equations. Such a system occurs in quantum mechanics, fluid mechanics, and optical fiber communication. Inspired by Angulo Pava’s results (2007), and by applying the stability theory established by Grillakis et al. (1987), we prove the existence of periodic traveling waves solutions and obtain the orbital stability of the solutions to this system.
A complementary role for tetraspanin superfamily member CD151 and ADP purinergic P2Y12 receptor in platelets
Authors: Makkawi Mohammed , Moheimani Fatemeh , Alserihi Raed , Howells David , Wright Mark , Ashman Leonie , Jackson Denise E. 
Published: August 2015

SummaryP2Y12 receptor is required for sustained activation of integrin αllbβ3, irreversible platelet aggregation and thrombus stabilisation. Tetraspanin superfamily member CD151 associates with integrin aNbp3 and plays critical roles in regulation of thrombus growth and stability in vivo. The possible functional relationship between P2Y12 and CD151 in a molecular cluster in platelets may affect thrombus formation. Hence our aim was to investigate the physical and functional requirements for this association in platelets. Our investigations reveal a specific and constitutive association between CD151 and P2Y12 receptor in human platelets shown by immunoprecipitation/western blot studies and by flow cytometry. Specifically, the prominent association involves CD151 with P2Y12 oligomers, and to a lesser extent P2Y12 monomers. This association is not altered by platelet aggregation induced by different agonists. There is also a distinct complex of tetraspanin CD151 with ADP purinergic receptor P2Y12 but not P2Y1. P2Y12 oligomer interaction with CD151 is selective as compared to other tetraspanins. To investigate the functional relationship between these receptors in platelets we used wild-type or CD151 knockout (KO) mice treated with either PBS or 50 mg/kg clopidogrel. CD151 KO mice treated with clopidogrel exhibited synergy in delayed kinetics of clot retraction, in PAR-4 and collagen-mediated platelet aggregation, platelet spreading on fibrinogen and without restricting cAMP inhibition. Clopidogrel treated CD151 KO arterioles showed smaller and less stable thrombi with increased tendency to embolise ex vivo and in vivo. These studies demonstrate a complementary role between CD151 and P2Y12 receptor in platelets in regulating thrombus growth and stability.
Aspirin for primary prevention in diabetes mellitus: from the calculation of cardiovascular risk and risk/benefit profile to personalised treatment
Authors: Santilli Francesca , Pignatelli Pasquale , Violi Francesco , Davì Giovanni 
Published: August 2015

SummaryType 2 diabetes mellitus is characterised by persistent thromboxane (TX)-dependent platelet activation, regardless of disease duration. Low-dose aspirin, that induces a permanent inactivation of platelet cyclooxygenase (COX)-1, thus inhibiting TXA2 biosynthesis, should be theoretically considered the drug of choice. The most up-to-date meta-analysis of aspirin prophylaxis in this setting, which includes three trials conducted in patients with diabetes and six other trials in which such patients represent a subgroup within a broader population, reported that aspirin is associated with a non-significant decrease in the risk of vascular events, although the limited amount of available data precludes a precise estimate of the effect size. An increasing body of evidence supports the concept that less-than-expected response to aspirin may underlie mechanisms related to residual platelet hyper-reactivity despite anti-platelet treatment, at least in a fraction of patients. Among the proposed mechanisms, the variable turnover rate of the drug target (platelet COX-1) appears to represent the most convincing determinant of the inter-individual variability in aspirin response. This review intends to develop the idea that the understanding of the determinants of less-than-adequate response to aspirin in certain individuals, although not changing the paradigm of the indication to low-dose aspirin prescription in primary prevention, may help identifying, in terms of easily detectable clinical or biochemical characteristics, individuals who would attain inadequate protection from aspirin, and for whom different strategies should be challenged.
Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC
Authors: Katholing Anja , Wallenhorst Christopher , Freedman Saul Benedict , Martinez Carlos 
Published: August 2015

SummaryEfforts to reduce stroke in atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines, but high early vitamin K antagonist (VKA) discontinuation is a limitation. We compared persistence of non-VKA OAC (NOAC) with VKA treatment in the first year after OAC inception for incident AF in real-world practice. We studied 27,514 anticoagulant-naïve patients with incident non-valvular AF between January 2011 and May 2014 in the UK primary care Clinical Practice Research Datalink, with full medication use linkage: mean age 74.2 ± 12.4, 45.7 % female, mean follow-up 1.9 ± 1.1 years. After treatment initiation and follow-up until 1/2015, the proportion remaining on OAC at one year (persistence) was estimated using competing risk survival analyses. OAC was commenced ≤90 days after incident AF in 13,221 patients (48.1 %): 12,307 VKA and 914 NOAC (apixaban, dabigatran, rivaroxaban). Amongst those treated with OAC, the proportion commencing NOAC increased from zero in 1/2011 to 27.0 % in 5/2014, and OAC prescriptions for CHA2DS2VASc score ≥2 (guideline adherence) increased from 41.2 % to 65.5 %. Persistence with OAC declined over 12 months to 63.6 % for VKA and 79.2 % for NOAC (p< 0.0001). Persistence for those with CHA2DS2VASc ≥2 was significantly greater for NOAC (83.0 %) than VKA (65.3 %, p< 0.0001) at one year and all earlier time points. Comparison of VKA and NOAC cohorts matched on individual CHA2DS2VASc components showed consistent results. In conclusion, persistence was significantly higher with NOAC than VKA, and could alone lead to fewer cardioembolic strokes. Increased guideline adherence following NOAC introduction could further decrease AF stroke burden.Supplementary Material to this article is available online at www.thrombosis-online.com.
Mechanistic Insights into Sympathetic Neuronal Regeneration
Authors: Bravo Paco E. , Lautamäki Riikka , Carter Debra , Holt Daniel P. , Nekolla Stephan G. , Dannals Robert F. , Russell Stuart D. , Bengel Frank M. 
Published: August 2015

Background—
Post-transplant reinnervation is a unique model to study sympathetic neuronal regeneration in vivo. The differential role of subcellular mechanisms of catecholamine handling in nerve terminals has not been investigated.

Methods and Results—

Three different carbon-11–labeled catecholamines were used for positron emission tomography of transport (C-11 m-hydroxyephedrine, HED), vesicular storage (C-11 epinephrine, EPI), and metabolic degradation (C-11 phenylephrine). A 2-day protocol was used, including quantification of myocardial blood flow by N-13 ammonia. Resting myocardial blood flow and EPI, HED and phenylephrine retention were homogeneous in healthy volunteers (n=7). Washout was only observed for phenylephrine (
T
1/2
49±6 min). In nonrejecting, otherwise healthy heart transplant recipients (>1 year after surgery, n=10), resting myocardial blood flow was also homogenous. Regional catecholamine uptake of varying degrees was observed in the anterior left ventricular wall and septum. Overall, 24±19% of left ventricle showed HED uptake levels comparable with healthy volunteers, whereas it was only 8±7% for EPI (
P
=0.004 versus HED). Phenylephrine washout was not different from healthy volunteers in the area with restored EPI and HED retention (
T
1/2
41±7 min;
P
>0.05), but was significantly enhanced in the EPI/HED mismatch area (
T
1/2
36±8 min;
P
=0.008), consistent with inefficient vesicular storage and enhanced metabolic degradation.

Conclusions—
Regeneration of subcellular components of sympathetic nerve terminal function does not occur simultaneously. In the reinnervating transplanted heart, a region with normal catecholamine transport and vesicular storage is surrounded by a borderzone, where transport is already restored but vesicular storage remains inefficient, suggesting that vesicular storage is a more delicate mechanism. This observation may have implications for other pathologies involving cardiac autonomic innervation.
Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study
Authors: O’Brien Emily C. , Greiner Melissa A. , Xian Ying , Fonarow Gregg C. , Olson DaiWai M. , Schwamm Lee H. , Bhatt Deepak L. , Smith Eric E. , Maisch Lesley , Hannah Deidre , Lindholm Brianna , Peterson Eric D. , Pencina Michael J. , Hernandez Adrian F. 
Published: August 2015

Background—
In patients with ischemic stroke, data on the real-world effectiveness of statin therapy for clinical and patient-centered outcomes are needed to better inform shared decision making.

Methods and Results—

Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient-Centered Outcomes Research Institute–funded research program designed with stroke survivors to evaluate the effectiveness of poststroke therapies. We linked data on patients
≥
65 years of age enrolled in the Get With The Guidelines–Stroke Registry to Medicare claims. Two-year to postdischarge outcomes of those discharged on a statin versus not on a statin were adjusted through inverse probability weighting. Our coprimary outcomes were major adverse cardiovascular events and home time (days alive and out of a hospital or skilled nursing facility). Secondary outcomes included all-cause mortality, all-cause readmission, cardiovascular readmission, and hemorrhagic stroke. From 2007 to 2011, 77 468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard of major adverse cardiovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87–0.94), 28 more home-time days after discharge (
P
<0.001), and lower all-cause mortality and readmission. Statin therapy at discharge was not associated with increased risk of hemorrhagic stroke (hazard ratio, 0.94; 95% confidence interval, 0.72–1.23). Among statin-treated patients, 31% received a high-intensity dose; after risk adjustment, these patients had outcomes similar to those of recipients of moderate-intensity statin.

Conclusion—
In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of major adverse cardiovascular events and nearly 1 month more home time during the 2-year period after hospitalization.