bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice Lacking Functional STAT1 Are Highly Susceptible to Lethal Infection with Lassa Virus
Authors: Yun Nadezhda E. , Seregin Alexey V. , Walker David H. , Popov Vsevolod L. , Walker Aida G. , Smith Jeanon N. , Miller Milagros , de la Torre Juan C. , Smith Jennifer K. , Borisevich Viktoriya , Fair Joseph N. , Wauquier Nadia , Grant Donald S. , Bockarie Bayon , Bente Dennis , Paessler Slobodan 
Published: August 2013

ABSTRACT
Lassa fever (LF) is a potentially lethal human disease that is caused by the arenavirus Lassa virus (LASV). Annually, around 300,000 infections with up to 10,000 deaths occur in regions of Lassa fever endemicity in West Africa. Here we demonstrate that mice lacking a functional STAT1 pathway are highly susceptible to infection with LASV and develop lethal disease with pathology similar to that reported in humans.
Host Species Barriers to Jaagsiekte Sheep Retrovirus Replication and Carcinogenesis
Authors: Caporale Marco , Martineau Henny , De las Heras Marcelo , Murgia Claudio , Huang Robert , Centorame Patrizia , Di Francesco Gabriella , Di Gialleonardo Luigina , Spencer Thomas E. , Griffiths David J. , Palmarini Massimo 
Published: August 2013

ABSTRACT
Understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. In this study, in order to further clarify the pathogenesis of OPA, we investigated whether goats are resistant to JSRV replication and carcinogenesis. We found that JSRV induces lung tumors in goats with macroscopic and histopathological features that dramatically differ from those in sheep. However, the origins of the tumor cells in the two species are identical. Interestingly, in experimentally infected lambs and goat kids, we revealed major differences in the number of virus-infected cells at early stages of infection. These differences were not related to the number of available target cells for virus infection and cell transformation or the presence of a host-specific immune response toward JSRV. Indeed, we also found that goats possess transcriptionally active endogenous retroviruses (enJSRVs) that likely influence the host immune response toward the exogenous JSRV. Overall, these results suggest that goat cells, or at least those cells targeted for viral carcinogenesis, are not permissive to virus replication but can be transformed by JSRV.
Isolate-Specific Differences in the Conformational Dynamics and Antigenicity of HIV-1 gp120
Authors: Davenport Thaddeus M. , Guttman Miklos , Guo Wenjin , Cleveland Brad , Kahn Maria , Hu Shiu-Lok , Lee Kelly K. 
Published: August 2013

ABSTRACT
The HIV-1 envelope glycoprotein (Env) mediates viral entry into host cells and is the sole target of neutralizing antibodies. Much of the sequence diversity in the HIV-1 genome is concentrated within Env, particularly within its gp120 surface subunit. While dramatic functional diversity exists among HIV-1 Env isolates—observable even in the context of monomeric gp120 proteins as differences in antigenicity and immunogenicity—we have little understanding of the structural features that distinguish Env isolates and lead to isolate-specific functional differences, as crystal structures of truncated gp120 “core” proteins from diverse isolates reveal a high level of structural conservation. Because gp120 proteins are used as prospective vaccine immunogens, it is critical to understand the structural factors that influence their reactivity with antibodies. Here, we studied four full-length, glycosylated gp120 monomers from diverse HIV-1 isolates by using small-angle X-ray scattering (SAXS) to probe the overall subunit morphology and hydrogen/deuterium-exchange with mass spectrometry (HDX-MS) to characterize the local structural order of each gp120. We observed that while the overall subunit architecture was similar among isolates by SAXS, dramatic isolate-specific differences in the conformational stability of gp120 were evident by HDX-MS. These differences persisted even with the CD4 receptor bound. Furthermore, surface plasmon resonance (SPR) and enzyme-linked immunosorbance assays (ELISAs) showed that disorder was associated with poorer recognition by antibodies targeting conserved conformational epitopes. These data provide additional insight into the structural determinants of gp120 antigenicity and suggest that conformational dynamics should be considered in the selection and design of optimized Env immunogens.
Identification of a Region in the Stalk Domain of the Nipah Virus Receptor Binding Protein That Is Critical for Fusion Activation
Authors: Talekar Aparna , DeVito Ilaria , Salah Zuhair , Palmer Samantha G. , Chattopadhyay Anasuya , Rose John K. , Xu Rui , Wilson Ian A. , Moscona Anne , Porotto Matteo 
Published: August 2013

ABSTRACT
Paramyxoviruses, including the emerging lethal human Nipah virus (NiV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral and target cell membranes. For paramyxoviruses, membrane fusion is the result of the concerted action of two viral envelope glycoproteins: a receptor binding protein and a fusion protein (F). The NiV receptor binding protein (G) attaches to ephrin B2 or B3 on host cells, whereas the corresponding hemagglutinin-neuraminidase (HN) attachment protein of NDV interacts with sialic acid moieties on target cells through two regions of its globular domain. Receptor-bound G or HN via its stalk domain triggers F to undergo the conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We show that chimeric proteins containing the NDV HN receptor binding regions and the NiV G stalk domain require a specific sequence at the connection between the head and the stalk to activate NiV F for fusion. Our findings are consistent with a general mechanism of paramyxovirus fusion activation in which the stalk domain of the receptor binding protein is responsible for F activation and a specific connecting region between the receptor binding globular head and the fusion-activating stalk domain is required for transmitting the fusion signal.
Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses
Authors: Margine I. , Krammer F. , Hai R. , Heaton N. S. , Tan G. S. , Andrews S. A. , Runstadler J. A. , Wilson P. C. , Albrecht R. A. , García-Sastre A. , Palese P. 
Published: August 2013

ABSTRACT
Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.
Herpes Simplex Virus 1 Targets the Murine Olfactory Neuroepithelium for Host Entry
Authors: Shivkumar Maitreyi , Milho Ricardo , May Janet S. , Nicoll Michael P. , Efstathiou Stacey , Stevenson Philip G. 
Published: August 2013

ABSTRACT
Herpes simplex virus 1 (HSV-1) is a ubiquitous and important human pathogen. It is known to persist in trigeminal ganglia (TG), but how it reaches this site has been difficult to determine, as viral transmission is sporadic, pathogenesis is complicated, and early infection is largely asymptomatic. We used mice to compare the most likely natural HSV-1 host entry routes: oral and nasal. Intranasal infection was 100-fold more efficient than oral and targeted predominantly the olfactory neuroepithelium. Live imaging of HSV-1-expressed luciferase showed infection progressing from the nose to the TG and then reemerging in the facial skin. The brain remained largely luciferase negative throughout. Infected cell tagging by viral Cre recombinase expression in floxed reporter gene mice showed nasal virus routinely reaching the TG and only rarely reaching the olfactory bulbs. Thus, HSV-1 spread from the olfactory neuroepithelium to the TG and reemerged peripherally without causing significant neurological disease. This recapitulation of typical clinical infection suggests that HSV-1 might sometimes also enter humans via the respiratory tract.
AIDS Alters the Commensal Plasma Virome
Authors: Li Linlin , Deng Xutao , Linsuwanon Piyada , Bangsberg David , Bwana Mwebesa Bosco , Hunt Peter , Martin Jeffrey N. , Deeks Steven G. , Delwart Eric 
Published: August 2013

ABSTRACT

We compared the plasma viromes of HIV-infected subjects with low versus high CD4
+
T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.
How to treat Guyon's canal syndrome? Results from the European HANDGUIDE study: a multidisciplinary treatment guideline
Authors: Hoogvliet P , Coert J H , Fridén J , Huisstede B M A ,   the European HANDGUIDE group
Published: August 2013

BackgroundAlthough Guyon's canal syndrome is not highly prevalent, a considerable knowledge of anatomy is needed to localise and treat the pathology. Data on the effectiveness of interventions for this disorder are lacking.ObjectiveTo achieve consensus on a multidisciplinary treatment guideline for this disorder based on experts’ opinions.MethodsA European Delphi consensus strategy was initiated. In total, 35 experts (hand surgeons/hand therapists selected by the national member associations of their European federations and Physical Medicine and Rehabilitation physicians) participated in the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis and a feedback report.ResultsAfter three Delphi rounds, consensus was achieved on the description, symptoms and diagnosis of Guyon's canal syndrome. The experts agreed that patients with this disorder should always receive instructions and that these instructions should be combined with another form of treatment. Instructions combined with splinting or with surgery were considered as suitable treatment options. Details on the use of instructions, splinting and surgery were described. Main factors for selecting one of the aforementioned treatment options were identified: severity and duration of the syndrome and previous treatments given. A relation between the severity/duration and choice of therapy was indicated by the experts and reported in the guideline.ConclusionsAlthough this disorder is less prevalent and not easy to diagnose, this guideline may contribute to better insight into and treatment of Guyon's canal syndrome.
Fit and healthy Paralympians—medical care guidelines for disabled athletes: a study of the injuries and illnesses incurred by the Polish Paralympic team in Beijing 2008 and London 2012
Authors: Gawroński Wojciech , Sobiecka Joanna , Malesza Jacek 
Published: August 2013

BackgroundSuccessful performance in Paralympic Games (PGs) requires continuous monitoring of the athletes’ health and optimal medical care.ObjectiveTo present the health status and disability category of Polish athletes at the Beijing and London PGs, as well as to compare the injuries and illnesses incurred during both PGs in view of the more stringent healthcare guidelines implemented before London.MethodsThe preparticipation examination (PPE) involved general medical/orthopaedic examination, ECG, blood and urine tests. The mandatory periodic health evaluation (PHE) introduced before London comprised general medical/orthopaedic/dental examination, anthropometric measurement, ECG, stress test, laryngological and ophthalmological consultations, and blood and urine tests. The incidence rate (IR) for all injuries/illnesses with 95% CI, incidence proportion and exposure data (athlete-days) were calculated.ResultsThere were 91 Polish Paralympians in Beijing and 100 in London. Medical consultations decreased from 151 to 74 (injuries: 57 vs 24 and illnesses: 94 vs 50). In both PGs, respiratory tract infections (RTIs) were the most frequent: IR increased from 15.2 in Beijing to 18.1 in London/1000 athlete-days (95% CI 9.7 to 20.7 vs 11.5 to 24.7). In both PGs, most injuries/illnesses concerned Paralympians with spinal cord injuries. The PPE before both PGs confirmed the disability type according to the general medical classification and revealed no health-related contraindications. Only 6.6% of athletes before Beijing but 100% before London had undergone the multispecialist PHE.ConclusionsIn both PGs, illnesses were more frequent than injuries. RTIs presented a serious problem. Some groups of disabled athletes are at an increased risk of injury/illness. The more stringent medical care guidelines before London may have caused staggeringly better results.
A pilot randomised controlled trial of a preconsultation web-based intervention to improve the care quality and clinical outcomes of diabetes outpatients (DIAT)
Authors: Frost Julia , Anderson Rob , Argyle Catherine , Daly Mark , Harris-Golesworthy Faith , Harris Jim , Gibson Andy , Ingram Wendy , Pinkney Jon , Ukoumunne Obioha C , Vaidya Bijay , Vickery Jane , Britten Nicky 
Published: August 2013

IntroductionDiabetes is a chronic condition associated with many long-term complications. People with diabetes need to actively manage their condition, which can be complex. In consultations with healthcare professionals, patients receive advice about their diabetes but do not always discuss things which concern them, perhaps because of the perceived limited time or embarrassment. We want to test a ‘preconsultation’ intervention in which the patient is supported by a healthcare assistant to complete a web-based intervention aimed at producing an agenda to help them identify important areas for discussion in the consultation. Use of this agenda may enable the patient to play a more active role in that consultation and consequently become more confident, and hence more successful, in managing their condition.Methods and analysisIn this pilot randomised controlled trial, 120 people with diabetes will be randomised with equal allocation to receive the intervention or usual clinical care. The primary outcome is reduction in glycosylated haemoglobin(HbA1c). Secondary outcomes are patient-reported communication, enablement, self-care activity, diabetes-dependent quality of life, empowerment, satisfaction, health-related quality of life and resource use. The aim of the pilot study was to estimate parameters to inform the design of the definitive trial. Follow-up on quantitative outcomes will be at 3 and 6 months. A nested qualitative study will collect data on the patients’ experiences of producing an agenda. Resource use data and medication use will also be collected via a review of medical records for a sample of participants.Ethics and disseminationApproval was granted by the NHS Research Ethics Committee North West—Preston (13/NW/0123). Dissemination will include publication of quantitative and qualitative findings, and experience of public involvement in peer-reviewed journals. Results will also be disseminated to trial participants via workshops led by lay coapplicants.Trial RegistrationISRCTN75070242.
Predicting human papillomavirus vaccination behaviour among adolescent girls in England: results from a prospective survey
Authors: Bowyer Harriet L , Forster Alice S , Marlow Laura A V , Waller Jo 
Published: August 2013

BackgroundTo maximise the benefits of human papillomavirus (HPV) vaccination, uptake needs to be high. We examined psychosocial predictors of HPV vaccine uptake and the association between vaccine intention and uptake 1 year later in adolescent girls (aged 16–17 years) in England.MethodAdolescent girls in the catch-up cohort were recruited from colleges in the South East of England in 2009 and 2010. Participants completed a questionnaire 6 months before (n=606) and 6 months after (n=214) being offered the vaccine, which assessed vaccine intention, vaccine uptake, demographics and attitudes based on the Health Belief Model and Theory of Planned Behaviour.ResultsA number of demographic and psychological factors, including intention, showed associations with vaccine uptake in uni-variable analyses. In multi-variable analyses, only ethnicity was independently associated with vaccine uptake. Participants from Black or ‘Other’ ethnic backgrounds were less likely to have received the HPV vaccine than White participants.ConclusionsMore research is needed to help understand variation in vaccine coverage between ethnic groups.
Hounsfield unit value and clot length in the acutely occluded vessel and time required to achieve thrombectomy, complications and outcome
Authors: Spiotta Alejandro M , Vargas Jan , Hawk Harris , Turner Raymond , Chaudry M Imran , Battenhouse Holly , Turk Aquilla S 
Published: August 2013

IntroductionIntra-arterial therapy for acute ischemic stroke (AIS) now has an established role. We investigated if Hounsfield Units (HU) quantification on non-contrast CT is associated with ease and efficacy of mechanical thrombectomy and outcomes.MethodsWe retrospectively studied a prospectively maintained database of cases of AIS given intra-arterial therapy between May 2008 and August 2012. Functional outcome was assessed by 90-day follow-up modified Rankin Scale (mRS). Patients were dichotomized based on time to recanalization. HU were calculated on head CT and thrombus location and length were determined on CT angiography. Simple linear regression was used to analyze the association between clot length, average HU and other clinical variables.Results141 patients were included. There was no difference in clot length or average HU among patients with good recanalization achieved within 1 h and those in which the procedures extended beyond 1 h. There was no relationship between clot length or density and recanalization. The thrombus length and density were not significantly different between patients with procedural complications and those without. Neither the presence of post-procedure intracranial hemorrhage nor the 90-day mRS was associated with thrombus length or density.ConclusionsWe have not found any significant associations between either thrombus length or density and likelihood of recanalization, time to achieve recanalization, intraprocedural complications, postprocedural hemorrhage or functional outcome at 90 days. These results do not support a predictive value for thrombus quantification in the evaluation of AIS.
The Villain Team-Up or howTrichomonas vaginalisand bacterial vaginosis alter innate immunity in concert
Authors: Fichorova Raina N , Buck Olivia R , Yamamoto Hidemi S , Fashemi Titilayo , Dawood Hassan Y , Fashemi Bisiayo , Hayes Gary R , Beach David H , Takagi Yuko , Delaney Mary L , Nibert Max L , Singh Bibhuti N , Onderdonk Andrew B 
Published: August 2013

ObjectivesComplex interactions of vaginal microorganisms with the genital tract epithelium shape mucosal innate immunity, which holds the key to sexual and reproductive health. Bacterial vaginosis (BV), a microbiome-disturbance syndrome prevalent in reproductive-age women, occurs commonly in concert with trichomoniasis, and both are associated with increased risk of adverse reproductive outcomes and viral infections, largely attributable to inflammation. To investigate the causative relationships among inflammation, BV and trichomoniasis, we established a model of human cervicovaginal epithelial cells colonised by vaginalLactobacillusisolates, dominant in healthy women, and common BV species (Atopobium vaginae,Gardnerella vaginalisandPrevotella bivia).MethodsColonised epithelia were infected withTrichomonas vaginalis(TV) or exposed to purified TV virulence factors (membrane lipophosphoglycan (LPG), its ceramide-phosphoinositol-glycan core (CPI-GC) or the endosymbiont Trichomonas vaginalis virus (TVV)), followed by assessment of bacterial colony-forming units, the mucosal anti-inflammatory microbicide secretory leucocyte protease inhibitor (SLPI), and chemokines that drive pro-inflammatory, antigen-presenting and T cells.ResultsTV reduced colonisation byLactobacillusbut not by BV species, which were found inside epithelial cells. TV increased interleukin (IL)-8 and suppressed SLPI, likely via LPG/CPI-GC, and upregulated IL-8 and RANTES, likely via TVV as suggested by use of purified pathogenic determinants. BV speciesA vaginaeandG vaginalisinduced IL-8 and RANTES, and also amplified the pro-inflammatory responses to both LPG/CPI-GC and TVV, whereasP biviasuppressed the TV/TVV-induced chemokines.ConclusionsThese molecular host–parasite–endosymbiont–bacteria interactions explain epidemiological associations and suggest a revised paradigm for restoring vaginal immunity and preventing BV/TV-attributable inflammatory sequelae in women.
ON THE DYNAMICS OF A BEAM PARTIALLY SUPPORTED BY AN ELASTIC FOUNDATION: AN EXACT SOLUTION-SET
Authors: CAZZANI ANTONIO 
Published: August 2013

Free vibrations of straight beams which are partially supported by an elastic foundation are analyzed. For the sake of simplicity, only the Euler–Bernoulli beam model coupled with a Winkler-type elastic foundation is considered. This structural system can be used to study, in a rather accurate way, the dynamic response of partially embedded piles (like those used for telecommunications) when dealing with the problem of identifying their mechanical properties during operative conditions. The study makes clear that different kinds of vibration modes may occur in the part of the beam which is supported by the continuous elastic foundation: indeed apart from the classical modes, corresponding to the dynamics of a free beam, it is possible to have vibration modes which are similar to the static deflection of a beam on an elastic support or even corresponding to rigid-body modes. For the same beam it is shown that transition between these vibration modes can appear when switching from the fundamental natural frequency to subsequent ones. This effect is the focus of the presented numerical examples. In particular, the analytic expression of the transcendental functions governing the vibration modes, and of the coefficients of the eigenfunctions for all occurring cases, are given here — to the best of the author's knowledge — for the first time. From the practical point of view, the reported results allow to define a suitable range of the elastic stiffness parameter such that the behavior of a partially supported beam can be conveniently approximated with that of a single-span beam, having one built-in end and the other free.