bluuebunny/crossref_metadata_2025_split huggingface dataset:
General Molecular Strategy for Development of Arenavirus Live-Attenuated Vaccines
Authors: Iwasaki Masaharu , Ngo Nhi , Cubitt Beatrice , Teijaro John R. , de la Torre Juan C. 
Published: September 2015

ABSTRACT

Hemorrhagic fever arenaviruses (HFA) pose important public health problems in regions where they are endemic. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly in West Africa, causing a large number of Lassa fever cases associated with high morbidity and mortality. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. The Mopeia virus (MOPV)/LASV reassortant (ML29) is a LASV candidate live-attenuated vaccine (LAV) that has shown promising results in animal models. Nevertheless, the mechanism of ML29 attenuation remains unknown, which raises concerns about the phenotypic stability of ML29 in response to additional mutations. Development of LAVs based on well-defined molecular mechanisms of attenuation will represent a major step in combatting HFA. We used the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) to develop a general molecular strategy for arenavirus attenuation. Our approach involved replacement of the noncoding intergenic region (IGR) of the L genome segment with the IGR of the S genome segment to generate a recombinant LCMV, rLCMV(IGR/S-S), that was highly attenuated
in vivo
but induced protection against a lethal challenge with wild-type LCMV. Attenuation of rLCMV(IGR/S-S) was associated with a stable reorganization of the control of viral gene expression. This strategy can facilitate the rapid development of LAVs with the antigenic composition of the parental HFA and a mechanism of attenuation that minimizes concerns about increased virulence that could be caused by genetic changes in the LAV.

IMPORTANCE
Hemorrhagic fever arenaviruses (HFA) cause high morbidity and mortality, and pose important public health problems in the regions where they are endemic. Implementation of live-attenuated vaccines (LAV) will represent a major step in combatting HFA. Here we have used the prototypic arenavirus LCMV to document a general molecular strategy for arenavirus attenuation that can facilitate the rapid development of safe and effective, as well as stable, LAV to combat HFA.
Replication-Competent Influenza B Reporter Viruses as Tools for Screening Antivirals and Antibodies
Authors: Fulton Benjamin O. , Palese Peter , Heaton Nicholas S. 
Published: September 2015

ABSTRACT
Influenza B virus is a human pathogen responsible for significant health and economic burden. Research into this pathogen has been limited by the lack of reporter viruses. Here we describe the development of both a replication-competent fluorescent influenza B reporter virus and bioluminescent influenza B reporter virus. Furthermore, we demonstrate these reporter viruses can be used to quickly monitor viral growth and permit the rapid screening of antiviral compounds and neutralizing antibodies.
Single Neutralizing Monoclonal Antibodies Targeting the VP1 GH Loop of Enterovirus 71 Inhibit both Virus Attachment and Internalization during Viral Entry
Authors: Ku Zhiqiang , Ye Xiaohua , Shi Jinping , Wang Xiaoli , Liu Qingwei , Huang Zhong 
Published: September 2015

ABSTRACT
Antibodies play a critical role in immunity against enterovirus 71 (EV71). However, how EV71-specific antibodies neutralize infections remains poorly understood. Here we report the working mechanism for a group of three monoclonal antibodies (MAbs) that potently neutralize EV71. We found that these three MAbs (termed D5, H7, and C4, respectively) recognize the same conserved neutralizing epitope within the VP1 GH loop of EV71. Single MAbs in this group, exemplified by D5, could inhibit EV71 infection in cell cultures at both the pre- and postattachment stages in a cell type-independent manner. Specifically, MAb treatment resulted in the blockade of multiple steps of EV71 entry, including virus attachment, internalization, and subsequent uncoating and RNA release. Furthermore, we show that the D5 and C4 antibodies can interfere with EV71 binding to its key receptors, including heparan sulfate, SCARB2, and PSGL-1, thus providing a possible explanation for the observed multi-inhibitory function of the MAbs. Collectively, our study unravels the mechanism of neutralization by a unique group of anti-EV71 MAbs targeting the conserved VP1 GH loop. The findings should enhance our understanding of MAb-mediated immunity against enterovirus infections and accelerate the development of MAb-based anti-EV71 therapeutic drugs.

IMPORTANCE
Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which has caused significant morbidities and mortalities in young children. Neither a vaccine nor an antiviral drug is available. Neutralizing antibodies are major protective components in EV71 immunity. Here, we unraveled an unusual mechanism of EV71 neutralization by a group of three neutralizing monoclonal antibodies (MAbs). All of these MAbs bound the same conserved epitope located at the VP1 GH loop of EV71. Interestingly, mechanistic studies showed that single antibodies in this MAb group could block EV71 attachment and internalization during the viral entry process and interfere with EV71 binding to heparan sulfate, SCARB2, and PSGL-1 molecules, which are key receptors involved in different steps of EV71 entry. Our findings greatly enhance the understanding of the interplays among EV71, neutralizing antibodies, and host receptors, which in turn should facilitate the development of an MAb-based anti-EV71 therapy.
Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans
Authors: Ashe Alyson , Sarkies Peter , Le Pen Jérémie , Tanguy Mélanie , Miska Eric A. 
Published: September 2015

ABSTRACT

Antiviral RNA-mediated silencing (RNA interference [RNAi]) acts as a powerful innate immunity defense in plants, invertebrates, and mammals. In
Caenorhabditis elegans
, RNAi is systemic; i.e., RNAi silencing signals can move between cells and tissues. Furthermore, RNAi effects can be inherited transgenerationally and may last for many generations. Neither the biological relevance of systemic RNAi nor transgenerational RNAi is currently understood. Here we examined the role of both pathways in the protection of
C. elegans
from viral infection. We studied the Orsay virus, a positive-strand RNA virus related to
Nodaviridae
and the first and only virus known to infect
C. elegans
. Immunity to Orsay virus infection requires the RNAi pathway. Surprisingly, we found that genes required for systemic or transgenerational RNAi did not have a role in antiviral defense. Furthermore, we found that Orsay virus infection did not elicit a systemic RNAi response even when a target for RNAi was provided by using transgenes. Finally, we show that viral siRNAs, the effectors of RNAi, are not inherited to a level that provides any significant resistance to viral infection in the next generation. We conclude that systemic or transgenerational RNAi does not play a role in the defense against natural Orsay virus infection. Furthermore, our data suggest that there is a qualitative difference between experimental RNAi and antiviral RNAi. Our data are consistent with a model of systemic and transgenerational RNAi that requires a nuclear or germ line component that is lacking in almost all RNA virus infections.

IMPORTANCE
Since its discovery in
Caenorhabditis elegans
, RNAi has proven a valuable scientific tool in many organisms. In
C. elegans
, exogenous RNAi spreads throughout the organism and can be passed between generations; however, there has been controversy as to the endogenous role(s) that the RNAi pathway plays. One endogenous role for which spreading both within the infected organism and between generations would be advantageous is a role in viral defense. In plants, antiviral RNAi is systemic and the spread of RNAi between cells provides protection against subsequent viral infection. Here we investigated this by using the only naturally occurring virus known to infect
C. elegans
, Orsay virus, and surprisingly found that, in contrast to the exogenous RNAi pathway, the antiviral RNAi response targeted against this virus does not spread systemically throughout the organism and cannot be passed between generations. These results suggest that there are differences between the two pathways that remain to be discovered.
Improving preparedness of medical students and junior doctors to manage patients with diabetes
Authors: Kelly Narcie A A , Brandom Kevin G , Mattick Karen L 
Published: September 2015

ObjectiveNew medical graduates are the front-line staff in many hospital settings and manage patients with diabetes frequently. Prescribing is an area of concern for junior doctors, however, with insulin prescribing reported as a particular weakness. This study aimed to produce an educational intervention which aimed to improve preparedness to manage patients with diabetes and evaluate it using a mixed methods approach.Research design and methodsAn e-resource (http://www.diabetesscenariosforjuniordoctors.co.uk) was created to contain commonplace and authentic diabetes decision-making scenarios. –32 junior doctors (n=20) and year 5 students (n=12) in South West England worked through the scenarios while ‘thinking aloud’ and then undertook a semistructured interview. Qualitative data were transcribed verbatim and analyzed thematically. Participant confidence to manage patients with diabetes before, immediately after, and 6 weeks after the educational intervention was also measured using a self-rating scale.ResultsParticipants reported that patients with diabetes were daunting to manage because of the wide array of insulin products, their lack of confidence with chronic disease management and the difficulty of applying theory to practice. The e-resource was described as authentic, practical, and appropriate for the target audience. Junior doctors’ self-rated confidence to manage patients with diabetes increased from 4.7 (of 10) before using the e-resource, to 6.4 immediately afterwards, and 6.8 6 weeks later. Medical students’ confidence increased from 5.1 before, to 6.4 immediately afterwards, and 6.4 6 weeks later.ConclusionsProviding opportunities to work with authentic scenarios in a safe environment can help to ameliorate junior doctors’ lack of confidence to manage patients with diabetes.
Using an internet intervention to support self-management of low back pain in primary care: protocol for a randomised controlled feasibility trial (SupportBack)
Authors: Geraghty Adam W A , Stanford Rosie , Little Paul , Roberts Lisa , Foster Nadine E , Hill Jonathan C , Hay Elaine , Stuart Beth , Turner David , Yardley Lucy 
Published: September 2015

IntroductionLow back pain (LBP) is a prevalent and costly condition. The majority of patients experiencing LBP are managed in primary care, where first-line care recommendations consist of advice to self-manage and remain active. Internet interventions present a potential means of providing patients with tailored self-management advice and evidence-based support for increasing physical activity.Methods/analysisThis protocol describes a single-blind, randomised controlled feasibility trial of an internet intervention developed to support the self-management of LBP in primary care. Patients are being randomised to 1 of 3 groups receiving either usual primary care, usual primary care with the addition of an internet intervention or an internet intervention with physiotherapist telephone support. Patients are followed up at 3 months. Primary outcomes are the feasibility of (1) the trial design/methods, (2) the delivery of the internet intervention and (3) the provision of telephone support by physiotherapists. Secondary outcomes will include exploratory analysis of estimates and variation in clinical outcomes of pain and disability, in order to inform a future main trial.Ethics/disseminationThis feasibility trial has undergone ethical scrutiny and been approved by the National Health Service (NHS) Research Ethics Committee, REC Reference 13/SC/0202. The feasibility findings will be disseminated to the research community through presentations at conferences and publication in peer review journals. Broader dissemination will come following a definitive trial.Trial registration numberISRCTN 31034004.
Did the Global Financial Crisis of 2007-2009 Impact Economic Growth in North Africa?
Authors: Aly Hassan Y. , Strazicich Mark C. 
Published: September 2015

Abstract
In this paper, we utilize time series tests with structural breaks to test for evidence of an impact on economic growth rates in North African countries following the 2007−2009 U.S. and global financial crisis. One or two breaks in economic growth are identified in each country, except for Morocco where no break is found. However, breaks that coincide with the financial crisis are found in only two of the six countries (Libya and Mauritania), while other breaks coincide most often with earlier U.S. and EU recessions. To further examine the impact of shocks, impulse response functions are estimated from Vector Auto-Regression models with structural breaks. We again find no evidence that shocks from the financial crisis had a significant impact on economic growth in North Africa. We conclude that shocks from the 2007−2009 financial crisis had only a temporary and relatively small impact on economic growth rates in North Africa.
Procambarus (Girardiella) holifieldi, a new species of crayfish (Decapoda: Cambaridae) from Alabama with a revision of the Hagenianus Group in the subgenus Girardiella
Authors: SCHUSTER GUENTER A. , TAYLOR CHRISTOPHER A. , ADAMS SUSAN B. 
Published: September 2015

Procambarus (Girardiella) holifieldi, new species, is a primary burrowing crayfish from a low-lying field in Perry County, Alabama. It belongs to the Hagenianus Group in the subgenus Girardiella. The new species is morphologically most similar to Procambarus (Girardiella) barbiger. They differ in the size and shape of the caudal processes. Procambarus barbiger has a beard along the mesial margin of the palm of the chela, while the new species lacks the beard. In addition to the description of the new species, the Hagenianus Group is reviewed and new synonymies are provided. We demonstrate that a cephalic process is indeed present in the Hagenianus Group.
Sawflies of Ethiopia (Hymenoptera: Argidae, Tenthredinidae)
Authors: Koch FRANK , Pauly Alain , Hora Zewdu A. , Boevé Jean-Luc 
Published: September 2015

Sawflies were collected in Ethiopia during 2010–2013. Three species represent new records for the country: Arge deckerti Koch, 2005, Athalia excisa Koch, 2006 and Xenapates nigrifrons Koch, 2012. Arge flavifrons Mocsáry, 1909, syn. n. and A. transvaalensis Cameron, 1911, syn. n. are subjective synonyms of A. micheli (Buysson, 1900) that is re-described here. Athalia fumosa Gribodo, 1879 sp. rev. is recognized as a valid species and is removed from synonymy with A. scioensis Gribodo, 1879. Distega braunsi Enslin, 1911 syn. n. and D. brunniventris Enslin, 1913 syn. n. are subjective synonyms of D. montium Konow, 1907. Pseudoneacidiophora Koch, 1998 is a new junior synonym of Kivua Forsius, 1934 (syn. n.), resulting in the new combination Kivua pleuritica (comb. n.) for Athalia pleuritica Forsius, 1927. Kivua camerunensis nom. n. is proposed for P. bicolor Koch, 1998 (preoccupied in Kivua by K. bicolor (Pasteels, 1949) (Bicrista bicolor Pasteels)), the second species formerly included in Pseudoneacidiophora. The female of Distega abyssinica Pasteels, 1955 is described for the first time. An annotated and illustrated list including six distribution maps is given for Ethiopian sawflies. It is composed of 34 species belonging to the genus Arge (Argidae), and seven genera of Tenthredinidae: Athalia (Athaliinae), Kivua, Neacidiophora, Xenapates (Allantinae), Distega, Trisodontophyes (Blennocampinae), and Dulophanes (Selandriinae). Some ecological aspects of Athalia species are discussed, especially for the most abundantly collected A. vollenhoveni Gribodo, 1879.
The Role of Convective Heating in Tropical Cyclone Eyewall Ring Evolution
Authors: Wu Chun-Chieh , Wu Shun-Nan , Wei Ho-Hsuan , Abarca Sergio F. 
Published: September 2015

Abstract
The purpose of this study is to analyze the role of diabatic heating in tropical cyclone ring structure evolution. A full-physics three-dimensional modeling framework is used to compare the results with two-dimensional modeling approaches and to point to limitations of the barotropic instability theory in predicting the storm vorticity structure configuration. A potential vorticity budget analysis reveals that diabatic heating is a leading-order term and that it is largely offset by potential vorticity advection. Sawyer–Eliassen integrations are used to diagnose the secondary circulation (and corresponding vorticity tendency) forced by prescribed heating. These integrations suggest that diabatic heating forces a secondary circulation (and associated vorticity tendency) that helps maintain the original ring structure in a feedback process. Sensitivity experiments of the Sawyer–Eliassen model reveal that the magnitude of the vorticity tendency is proportional to that of the prescribed heating, indicating that diabatic heating plays a critical role in adjusting and maintaining the eyewall ring.
Contribution of Extreme Convective Storms to Rainfall in South America
Authors: Rasmussen K. L. , Chaplin M. M. , Zuluaga M. D. , Houze R. A. 
Published: September 2015

Abstract
The contribution of extreme convective storms to rainfall in South America is investigated using 15 years of high-resolution data from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR). Precipitation from three specific types of storms with extreme horizontal and vertical dimensions have been calculated and compared to the climatological rain. The tropical and subtropical regions of South America differ markedly in the influence of storms with extreme dimensions. The tropical regions, especially the Amazon basin, have aspects similar to oceanic convection. Convection in the subtropical regions, centered on La Plata basin, exhibits patterns consistent with storm life cycles initiating in the foothills of the Andes and growing into larger mesoscale convective systems that propagate to the east. In La Plata basin, convective storms with a large horizontal dimension contribute ~44% of the rain and the accumulated influence of all three types of storms with extreme characteristics produce ~95% of the total precipitation in the austral summer.
Hyperbilirubinemia after cardiac surgery: An observational study
Authors: Sharma Pranav , Ananthanarayanan Chandrasekaran , Vaidhya Nikunj , Malhotra Amber , Shah Komal , Sharma Ramanand 
Published: September 2015

Background We aimed to assess the incidence and perioperative risk factors for hyperbilirubinemia after cardiac surgery, and determine its influence on early operative outcome. Methods This prospective observational study was conducted on 476 patients who underwent cardiac surgical procedures from January 2014 to March 2014. Postoperative hyperbilirubinemia was defined as serum total bilirubin >2.0 mg dL−1. Results The overall incidence of postoperative hyperbilirubinemia was 25% (119 patients). Patients undergoing valve repair or replacement had the highest incidence of hyperbilirubinemia (36.2%), followed by coronary artery bypass grafting with concomitant valve surgery (34.1%), congenital heart surgery (23.1%), and coronary artery bypass alone (12.7%). Postoperative hyperbilirubinemia was associated with increased duration of inotropic support ( p = 0.0001), mechanical ventilation ( p = 0.0001), intensive care unit stay ( p = 0.001), hospital stay ( p = 0.006), and mortality ( p = 0.014). The perioperative factors associated with postoperative hyperbilirubinemia were increased preoperative bilirubin level ( p < 0.0001), preoperative prothrombin time ( p < 0.0001), cardiopulmonary bypass time ( p = 0.028), aortic crossclamp time ( p = 0.004), and blood transfusion units ( p = 0.0001). Conclusions Postoperative hyperbilirubinemia is common in patients undergoing cardiopulmonary bypass and is associated with high hospital mortality. The factors associated with its occurrence are increased preoperative bilirubin level, preoperative prothrombin time, cardiopulmonary bypass time, aortic crossclamp time, and blood transfusion units. Persistent hyperbilirubinemia is associated with a worse outcome than early transient hyperbilirubinemia.
Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercise in the management of hip osteoarthritis
Authors: Brosseau Lucie , Wells George A , Pugh Arlanna G , Smith Christine AM , Rahman Prinon , Àlvarez Gallardo Inmaculada C , Toupin-April Karine , Loew Laurianne , De Angelis Gino , Cavallo Sabrina , Taki Jade , Marcotte Rachel , Fransen Marlene , Hernandez-Molina Gabriela , Kenny Glen P , Regnaux Jean-Philippe , Lefevre-Colau Marie-Martine , Brooks Sydney , Laferriere Lucie , McLean Linda , Longchamp Guy 
Published: September 2015

Objectives: The primary objective is to identify effective land-based therapeutic exercise interventions and provide evidence-based recommendations for managing hip osteoarthritis. A secondary objective is to develop an Ottawa Panel evidence-based clinical practice guideline for hip osteoarthritis. Methods: The search strategy and modified selection criteria from a Cochrane review were used. Studies included hip osteoarthritis patients in comparative controlled trials with therapeutic exercise interventions. An Expert Panel arrived at a Delphi survey consensus to endorse the recommendations. The Ottawa Panel hierarchical alphabetical grading system (A, B, C+, C, D, D+, or D-) considered the study design (level I: randomized controlled trial and level II: controlled clinical trial), statistical significance ( p < 0.5), and clinical importance (⩾15% improvement). Results: Four high-quality studies were included, which demonstrated that variations of strength training, stretching, and flexibility exercises are generally effective for improving the management of hip osteoarthritis. Strength training exercises displayed the greatest improvements for pain (Grade A), disability (Grades A and C+), physical function (Grade A), stiffness (Grade A), and range of motion (Grade A) within a short time period (8–24 weeks). Stretching also greatly improved physical function (Grade A), and flexibility exercises improved pain (Grade A), range of motion (Grade A), physical function (Grade A), and stiffness (Grade C+). Conclusion: The Ottawa Panel recommends land-based therapeutic exercise, notably strength training, for management of hip osteoarthritis in reducing pain, stiffness and self-reported disability, and improving physical function and range of motion.
Self-amputation of the hand: issues in diagnosis and general hospital management
Authors: Crawford Alison , Wand Anne PF , Smith Michelle A 
Published: September 2015

Objectives: To detail a diagnostic dilemma of intentional hand amputation in a man with a history of substance misuse and associated psychosis, depression and traumatic brain injury and to highlight issues in joint psychiatric and surgical management of such a complex patient in a general hospital setting. Conclusions: Deliberate limb self-amputation is a rare event with the majority of reported cases occurring during an episode of psychosis. This case illustrates the diagnostic utility of the literature supporting that a person who has self-inflicted amputation of a limb should be treated as psychotic until proven otherwise. The presence of a traumatic brain injury, with associated cognitive and psychosocial sequelae, affected diagnosis and management. Early and ongoing involvement of consultation-liaison psychiatry collaborating with a multidisciplinary general hospital team may improve mental and physical health outcomes for such patients.