bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live Attenuated Influenza Viruses Containing NS1 Truncations as Vaccine Candidates against H5N1 Highly Pathogenic Avian Influenza
Authors: Steel John , Lowen Anice C. , Pena Lindomar , Angel Matthew , Solórzano Alicia , Albrecht Randy , Perez Daniel R. , García-Sastre Adolfo , Palese Peter 
Published: December 2008

ABSTRACT
Due to the high mortality associated with recent, widely circulating strains of H5N1 influenza virus in poultry, the recurring introduction of H5N1 viruses from birds to humans, and the difficulties in H5N1 eradication by elimination of affected flocks, an effective vaccine against HPAI (highly pathogenic avian influenza) is highly desirable. Using reverse genetics, a set of experimental live attenuated vaccine strains based on recombinant H5N1 influenza virus A/Viet Nam/1203/04 was generated. Each virus was attenuated through expression of a hemagglutinin protein in which the polybasic cleavage site had been removed. Viruses were generated which possessed a full-length NS1 or a C-terminally truncated NS1 protein of 73, 99, or 126 amino acids. Viruses with each NS genotype were combined with a PB2 polymerase gene which carried either a lysine or a glutamic acid at position 627. We predicted that glutamic acid at position 627 of PB2 would attenuate the virus in mammalian hosts, thus increasing the safety of the vaccine. All recombinant viruses grew to high titers in 10-day-old embryonated chicken eggs but were attenuated in mammalian cell culture. Induction of high levels of beta interferon by all viruses possessing truncations in the NS1 protein was demonstrated by interferon bioassay. The viruses were each found to be highly attenuated in a mouse model. Vaccination with a single dose of any virus conferred complete protection from death upon challenge with a mouse lethal virus expressing H5N1 hemagglutinin and neuraminidase proteins. In a chicken model, vaccination with a single dose of a selected virus encoding the NS1 1-99 protein completely protected chickens from lethal challenge with homologous HPAI virus A/Viet Nam/1203/04 (H5N1) and provided a high level of protection from a heterologous virus, A/egret/Egypt/01/06 (H5N1). Thus, recombinant influenza A/Viet Nam/1203/04 viruses attenuated through the introduction of mutations in the hemagglutinin, NS1, and PB2 coding regions display characteristics desirable for live attenuated vaccines and hold potential as vaccine candidates in poultry as well as in mammalian hosts.
Herpes Simplex Virus Type 1 ICP27 Induces p38 Mitogen-Activated Protein Kinase Signaling and Apoptosis in HeLa Cells
Authors: Gillis Peter A. , Okagaki Laura H. , Rice Stephen A. 
Published: December 2008

ABSTRACT
The herpes simplex virus type 1 (HSV-1) protein ICP27 has been implicated in a variety of functions important for viral replication including host shutoff, viral gene expression, activation of mitogen-activated protein kinases p38 and Jun N-terminal protein kinase (JNK), and apoptosis inhibition. In the present study we sought to examine the functions of ICP27 in the absence of viral infection by creating stable HeLa cell lines that inducibly express ICP27. Here, we characterize two such cell lines and show that ICP27 expression is associated with a cellular growth defect. The observed defect is caused at least in part by the induction of apoptosis as indicated by caspase-3 activation, annexin V staining, and characteristic changes in cellular morphology. In an effort to identify the function of ICP27 responsible for inducing apoptosis, we show that ICP27 expression is sufficient to activate p38 signaling to a level that is similar to that observed during wild-type HSV-1 infection. However, ICP27 expression alone is unable to lead to a strong activation of JNK signaling. Using chemical inhibitors, we show that the ICP27-mediated activation of p38 signaling is responsible for the observed induction of apoptosis in the induced cell lines. Our findings suggest that during viral infection, ICP27 activates p38 and JNK signaling pathways via two distinct mechanisms. ICP27 directly activates p38 signaling, leading to stimulation of the host cell apoptotic pathways. In contrast, robust activation of JNK signaling by ICP27 requires one or more delayed early or late viral gene products and may be associated with the inhibition of apoptosis.
Attenuation of Rabies Virus Replication and Virulence by Picornavirus Internal Ribosome Entry Site Elements
Authors: Marschalek Adriane , Finke Stefan , Schwemmle Martin , Mayer Daniel , Heimrich Bernd , Stitz Lothar , Conzelmann Karl-Klaus 
Published: December 2008

ABSTRACT

Gene expression of nonsegmented negative-strand RNA viruses is regulated at the transcriptional level and relies on the canonical 5′-end-dependent translation of capped viral mRNAs. Here, we have used internal ribosome entry sites (IRES) from picornaviruses to control the expression level of the phosphoprotein P of the neurotropic rabies virus (RV;
Rhabdoviridae
), which is critically required for both viral replication and escape from the host interferon response. In a dual luciferase reporter RV, the IRES elements of poliovirus (PV) and human rhinovirus type 2 (HRV2) were active in a variety of cell lines from different host species. While a generally lower activity of the HRV2 IRES was apparent compared to the PV IRES, specific deficits of the HRV2 IRES in neuronal cell lines were not observed. Recombinant RVs expressing P exclusively from a bicistronic nucleoprotein (N)-IRES-P mRNA showed IRES-specific reduction of replication in cell culture and in neurons of organotypic brain slice cultures, an increased activation of the beta interferon (IFN-β) promoter, and increased sensitivity to IFN. Intracerebral infection revealed a complete loss of virulence of both PV- and HRV2 IRES-controlled RV for wild-type mice and for transgenic mice lacking a functional IFN-α receptor (IFNAR
−/−
). The virulence of HRV2 IRES-controlled RV was most severely attenuated and could be demonstrated only in newborn IFNAR
−/−
mice. Translational control of individual genes is a promising strategy to attenuate replication and virulence of live nonsegmented negative-strand RNA viruses and vectors and to study the function of IRES elements in detail.
Effect of Preexisting Immunity on Oncolytic Adenovirus Vector INGN 007 Antitumor Efficacy in Immunocompetent and Immunosuppressed Syrian Hamsters
Authors: Dhar Debanjan , Spencer Jacqueline F. , Toth Karoly , Wold William S. M. 
Published: December 2008

ABSTRACT
Immune responses against adenovirus (Ad) vectors pose a possible concern for the outcome of treatment efficacy. To address the role of preexisting immunity in oncolytic Ad vector antitumor efficacy following intratumoral injection of vector as well as tumor-to-tissue spread of the vector, we employed the Syrian hamster model. These animals are immunocompetent, and their tumors and tissues are permissive for replication of Ad type 5 (Ad5). We used the adenovirus death protein-overexpressing Ad5-based vector INGN 007. Subcutaneous tumors were established in groups of hamsters that were or were not immunized with Ad5. Half of the hamsters in these groups were immunosuppressed with cyclophosphamide. For all groups, tumors injected with INGN 007 grew significantly more slowly than those injected with buffer. Under immunocompetent conditions, there was no significant effect of preexisting immunity on vector antitumor efficacy. Soon after the tumors in naïve animals were injected with vector, the hamsters developed neutralizing antibody (NAb) and the difference in NAb titers between the naïve and immunized groups diminished. Under immunosuppressed conditions, preexisting NAb did significantly reduce vector efficacy. Thus, NAb do reduce vector efficacy to some extent, but immunosuppression is required to observe the effect. Regarding vector toxicity, there was spillover of vector from the tumor to the liver and lungs in naïve immunocompetent hamsters, and this was nearly eliminated in the immunized hamsters. Thus, preexisting immunity to Ad5 does not affect INGN 007 antitumor efficacy following intratumoral injection, but immunity prevents vector spillover from the tumor to the liver and lungs.
Role of Heparan Sulfate in Attachment to and Infection of the Murine Female Genital Tract by Human Papillomavirus
Authors: Johnson Katherine M. , Kines Rhonda C. , Roberts Jeffrey N. , Lowy Douglas R. , Schiller John T. , Day Patricia M. 
Published: December 2008

ABSTRACT
The host factors required for in vivo infection have not been investigated for any papillomavirus. Using a recently developed murine cervicovaginal challenge model, we evaluated the importance of heparan sulfate proteoglycans (HSPGs) in human papillomavirus (HPV) infection of the murine female genital tract. We examined HPV type 16 (HPV16) as well as HPV31 and HPV5, for which some evidence suggests that they may differ from HPV16 in their utilization of HSPGs as their primary attachment factor in vitro. Luciferase-expressing pseudovirus of all three types infected the mouse genital tract, although HPV5, which normally infects nongenital epidermis, was less efficient. Heparinase III treatment of the genital tract significantly inhibited infection of all three types by greater than 90% and clearly inhibited virion attachment to the basement membrane and cell surfaces, establishing that HSPGs are the primary attachment factors for these three viruses in vivo. However, the pseudoviruses differed in their responses to treatment with various forms of heparin, a soluble analog of heparan sulfate. HPV16 and HPV31 infections were effectively inhibited by a highly sulfated form of heparin, but HPV5 was not, although it bound the compound. In contrast, a N-desulfated and N-acylated variant preferentially inhibited HPV5. Inhibition of infection paralleled the relative ability of the variants to inhibit basement membrane and cell surface binding. We speculate that cutaneous HPVs, such as HPV5, and genital mucosal HPVs, such as HPV16 and -31, may have evolved to recognize different forms of HSPGs to enable them to preferentially infect keratinocytes at different anatomical sites.
Limited Effects of Fasting on Hepatitis B Virus (HBV) Biosynthesis in HBV Transgenic Mice
Authors: Li Lie , Oropeza Claudia E. , Kaestner Klaus H. , McLachlan Alan 
Published: December 2008

ABSTRACT
Nuclear receptors have a unique role in governing hepatitis B virus (HBV) transcription and replication. Hepatocyte nuclear factor 4α (HNF4α) and retinoid X receptor α (RXRα) plus peroxisome proliferator-activated receptor α (PPARα) have been shown to support viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. However, the in vivo importance of these nuclear receptors in HBV biosynthesis has been investigated only to a limited extent. Fasting has been shown to activate gluconeogenesis, in part, by activating PPARγ coactivator 1 α, which in turn leads to activation of HNF4α- and RXRα/PPARα-mediated transcription. As HBV pregenomic RNA synthesis is primarily believed to be regulated by HNF4α under normal physiological conditions, it was of interest to determine the effect of fasting on the levels of HBV RNA and DNA synthesis. Fasting was shown to rather modestly increase the levels of viral proteins, transcripts, and replication intermediates in the HBV transgenic mouse model of chronic viral infection, suggesting that caloric restriction may modulate viremia to some extent during natural infection.
Injury and social determinants among in-school adolescents in six African countries
Authors: Peltzer K 
Published: December 2008

Background:There is a lack of data on injury and its social correlates among in-school adolescents in Africa.Objectives:To estimate the prevalence of injury among adolescents in six African countries, and to examine the consistency of associations cross-nationally between sociodemographics, social risk factors, and the occurrence of adolescent injury in Africa.Design:Cross-sectional national data from the Global School-based Health Survey (GSHS) conducted in six African countries between 2003 and 2004.Setting:Surveys administered in classrooms.Subjects:The sample included 20 765 students aged 13–15 years from six African countries (Kenya, Namibia, Swaziland, Uganda, Zambia, Zimbabwe) chosen by a two-stage cluster sample design to represent all students in grades 6, 7, 8, 9, and 10 in each country.Results:The mean percentage over all the countries of adolescents reporting one or more serious injuries within the past 12 months was 68.2%, ranging from 38.6% in Swaziland to 71.5% in Zambia. In multivariate regression analysis, risk behaviors were associated with annual injury prevalence, with the highest odds for loneliness, followed by hunger, truancy, depression, smoking, and drug use. The observed risk for all injuries, as well as injuries related to sports, motor vehicles, fighting, and burns, increased consistently with increasing number of risk behaviors.Conclusions:A high annual injury prevalence was found, and risk-taking played a role in the etiology of injury. There is a need to consider an integrated approach to injury etiology in planning injury prevention and safety promotion activities for schoolchildren, paying particular attention to lifestyle factors that have the potential to influence risk of injury.
What is lost when searching only one literature database for articles relevant to injury prevention and safety promotion?
Authors: Lawrence D W 
Published: December 2008

Objective:To assess what is lost if only one literature database is searched for articles relevant to injury prevention and safety promotion (IPSP) topics.Method:Serial textword (keyword, free-text) searches using multiple synonym terms for five key IPSP topics (bicycle-related brain injuries, ethanol-impaired driving, house fires, road rage, and suicidal behaviors among adolescents) were conducted in four of the bibliographic databases that are most used by IPSP professionals: EMBASE, MEDLINE, PsycINFO, and Web of Science. Through a systematic procedure, an inventory of articles on each topic in each database was conducted to identify the total unduplicated count of all articles on each topic, the number of articles unique to each database, and the articles available if only one database is searched.Results:No single database included all of the relevant articles on any topic, and the database with the broadest coverage differed by topic. A search of only one literature database will return 16.7–81.5% (median 43.4%) of the available articles on any of five key IPSP topics. Each database contributed unique articles to the total bibliography for each topic.Conclusion:A literature search performed in only one database will, on average, lead to a loss of more than half of the available literature on a topic.
The Operational Use of QuikSCAT Ocean Surface Vector Winds at the National Hurricane Center
Authors: Brennan Michael J. , Hennon Christopher C. , Knabb Richard D. 
Published: December 2008

Abstract
The utility and shortcomings of near-real-time ocean surface vector wind retrievals from the NASA Quick Scatterometer (QuikSCAT) in operational forecast and analysis activities at the National Hurricane Center (NHC) are described. The use of QuikSCAT data in tropical cyclone (TC) analysis and forecasting for center location/identification, intensity (maximum sustained wind) estimation, and analysis of outer wind radii is presented, along with shortcomings of the data due to the effects of rain contamination and wind direction uncertainties. Automated QuikSCAT solutions in TCs often fail to show a closed circulation, and those that do are often biased to the southwest of the NHC best-track position. QuikSCAT winds show the greatest skill in TC intensity estimation in moderate to strong tropical storms. In tropical depressions, a positive bias in QuikSCAT winds is seen due to enhanced backscatter by rain, while in major hurricanes rain attenuation, resolution, and signal saturation result in a large negative bias in QuikSCAT intensity estimates.
QuikSCAT wind data help overcome the large surface data void in the analysis and forecast area of NHC’s Tropical Analysis and Forecast Branch (TAFB). These data have resulted in improved analyses of surface features, better definition of high wind areas, and improved forecasts of high-wind events. The development of a climatology of gap wind events in the Gulf of Tehuantepec has been possible due to QuikSCAT wind data in a largely data-void region.
The shortcomings of ocean surface vector winds from QuikSCAT in the operational environment at NHC are described, along with requirements for future ocean surface vector wind missions. These include improvements in the timeliness and quality of the data, increasing the wind speed range over which the data are reliable, and decreasing the impact of rain to allow for accurate retrievals in all-weather conditions.
The Hydrometeor Classification Algorithm for the Polarimetric WSR-88D: Description and Application to an MCS
Authors: Park Hyang Suk , Ryzhkov A. V. , Zrnić D. S. , Kim Kyung-Eak 
Published: December 2008

Abstract
This paper contains a description of the most recent version of the hydrometeor classification algorithm for polarimetric Weather Surveillance Radar-1988 Doppler (WSR-88D). This version contains several modifications and refinements of the previous echo classification algorithm based on the principles of fuzzy logic. These modifications include the estimation of confidence factors that characterize the possible impacts of all error sources on radar measurements, the assignment of the matrix of weights that characterizes the classification power of each variable with respect to every class of radar echo, and the implementation of a class designation system based on the distance from the radar and the parameters of the melting layer that are determined as functions of azimuth with polarimetric radar measurements. These additions provide considerable flexibility and improve the discrimination between liquid and frozen hydrometeors. The new classification scheme utilizes all available polarimetric variables and discerns 10 different classes of radar echoes. Furthermore, a methodology for the new fuzzy logic classification scheme is discussed and the results are illustrated using polarimetric radar data collected with the Norman, Oklahoma (KOUN), WSR-88D prototype radar during a mesoscale convective system event on 13 May 2005.
Using videotelephony to support paediatric oncology-related palliative care in the home: from abandoned RCT to acceptability study
Authors: Bensink ME , Armfield NR , Pinkerton R , Irving H , Hallahan AR , Theodoros DG , Russell T , Barnett AG , Scuffham PA , Wootton R 
Published: December 2008

Videotelephony (real-time audio-visual communication) has been used successfully in adult palliative home care. This paper describes two attempts to complete an RCT (both of which were abandoned following difficulties with family recruitment), designed to investigate the use of videotelephony with families receiving palliative care from a tertiary paediatric oncology service in Brisbane, Australia. To investigate whether providing videotelephone-based support was acceptable to these families, a 12-month non-randomised acceptability trial was completed. Seventeen palliative care families were offered access to a videotelephone support service in addition to the 24 hours ‘on-call’ service already offered. A 92% participation rate in this study provided some reassurance that the use of videotelephones themselves was not a factor in poor RCT participation rates. The next phase of research is to investigate the integration of videotelephone-based support from the time of diagnosis, through outpatient care and support, and for palliative care rather than for palliative care in isolation. Trial registration ACTRN 12606000311550
The Association of Transient Ischemic Attack Symptoms With Memory Impairment Among Elderly Participants of the Third US National Health and Nutrition Examination Survey
Authors: Takahashi Paul Y. , Dyrbye Liselotte N. , Thomas Kris G. , Quirindongo Cedeno Onelis , North Frederick , Stroebel Robert J. , DeJesus Ramona S. , Targonski Paul V. 
Published: December 2008

Background and Purpose: Stroke is a well-known risk factor for vascular dementia. However, the association of transient ischemic attacks with cognitive impairment is less well-established. Methods: Records from Third National Health and Nutrition Examination Survey were abstracted for demographic and medical information for participants with an age !60 years who reported being free of stroke. Five self-reported symptoms (weakness, numbness, loss of vision, inability to speak, and severe dizziness) were used as surrogates representing transient ischemic attacks. Information on conventional risk factors for vascular dementia was also obtained. Multivariable logistic regression was used to examine risk factors for memory impairment. Results: 4617 participants were included with a sample-weighted prevalence of memory impairment of 6.6% (1417 participants). The final multivariable analysis revealed a significant association between transient weakness and memory impairment (odds ratio 1.52, 95% CI 1.11-2.07). The other 4 transient ischemic attacks symptoms were not significantly associated with memory impairment in the final model. Systolic blood pressure >140 was most strongly associated with prevalent memory impairment (odds ratio, 9.78, 95% CI 1.49-64.3). Other associated risk factors included non-white race, male gender, age, education ≤12 years, and history of any alcohol use. Conclusion: Among transient ischemic attacks symptoms, self-reported weakness in the face, arm, or leg was significantly associated with memory impairment. This study indicates that transient ischemic attacks symptoms are, even in the absence of stroke, associated with memory impairment. Aggressive risk factor modification in patients with TIA symptoms may be warranted to prevent potential future memory loss.
Lupus-associated pancreatitis complicated by pancreatic pseudocyst and central nervous system vasculitis
Authors: Myung DS , Kim TJ , Lee SJ , Park SC , Kim JS , Kim JC , Yoon W , Lee SS , Park YW 
Published: December 2008

Pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE), but this can occasionally cause major complications. We report in this article, a case of 33-year-old female patient who developed lupus-associated pancreatitis that was subsequently complicated by pancreatic pseudocyst and central nervous system (CNS) vasculitis. Abdominal computed tomography (CT) showed an oedematous swelling of the pancreas and a pseudocyst measuring 4 × 3 cm2. Brain magnetic resonance imaging (MRI) showed multiple high–signal intensity lesions in both cerebral hemispheres. The pseudocyst did not completely resolve with high-dose steroid therapy, and it was later complicated by infection and rupture. After a surgical drainage for the complicated pseudocyst, her clinical symptoms and signs were markedly improved. This case shows the importance of performing early drainage rather than conservative treatment for a pancreatic pseudocyst in a patient with lupus-associated pancreatitis.