bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection
Authors: Channappanavar Rudragouda , Fett Craig , Zhao Jincun , Meyerholz David K. , Perlman Stanley 
Published: July 2014

ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection.

IMPORTANCE
Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.
Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4
+
T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism
Authors: Arenaccio Claudia , Chiozzini Chiara , Columba-Cabezas Sandra , Manfredi Francesco , Affabris Elisabetta , Baur Andreas , Federico Maurizio 
Published: July 2014

ABSTRACT

Resting CD4
+
T lymphocytes resist human immunodeficiency virus (HIV) infection. Here, we provide evidence that exosomes from HIV-1-infected cells render resting human primary CD4
+
T lymphocytes permissive to HIV-1 replication. These results were obtained with transwell cocultures of HIV-1-infected cells with quiescent CD4
+
T lymphocytes in the presence of inhibitors of exosome release and were confirmed using exosomes purified from supernatants of HIV-1-infected primary CD4
+
T lymphocytes. We found that the expression of HIV-1 Nef in exosome-producing cells is both necessary and sufficient for cell activation as well as HIV-1 replication in target CD4
+
T lymphocytes. We also identified a Nef domain important for the effects we observed, i.e., the
62
EEEE
65
acidic cluster domain. In addition, we observed that ADAM17, i.e., a disintegrin and metalloprotease converting pro-tumor necrosis factor alpha (TNF-α) in its mature form, associates with exosomes from HIV-1-infected cells, and plays a key role in the HIV-1 replication in quiescent CD4
+
T lymphocytes. Treatment with an inhibitor of ADAM17 abolished both activation and HIV-1 replication in resting CD4
+
T lymphocytes. TNF-α is the downstream effector of ADAM17 since the treatment of resting lymphocytes with anti-TNF-α antibodies blocked the HIV-1 replication. The data presented here are consistent with a model where Nef induces intercellular communication through exosomes to activate bystander quiescent CD4
+
T lymphocytes, thus stimulating viral spread.

IMPORTANCE
Overall, our findings support the idea that HIV evolved to usurp the exosome-based intercellular communication network to favor its spread in infected hosts.
Short Self-Interacting N-Terminal Region of Rubella Virus Capsid Protein Is Essential for Cooperative Actions of Capsid and Nonstructural p150 Proteins
Authors: Sakata Masafumi , Otsuki Noriyuki , Okamoto Kiyoko , Anraku Masaki , Nagai Misato , Takeda Makoto , Mori Yoshio 
Published: July 2014

ABSTRACT
Nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral RNA synthesis via an unknown mechanism. The present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting N-terminal region of the capsid protein. Mutational analyses indicated that hydrophobic amino acids in this N-terminal region are essential for its N-terminal self-interaction, which is critical for the capsid-p150 association. An analysis based on a subgenomic replicon system demonstrated that the self-interacting N-terminal region of the capsid protein plays a key role in promoting viral gene expression. Analyses using a virus-like particle (VLP) system also showed that the self-interacting N-terminal region of the capsid protein is not essential for VLP production but is critical for VLP infectivity. These results demonstrate that the close cooperative actions of the capsid protein and p150 require the short self-interacting N-terminal region of the capsid protein during the life cycle of the rubella virus.

IMPORTANCE
The capsid protein of rubella virus promotes viral RNA replication via an unknown mechanism. This protein interacts with the nonstructural protein p150, but the importance of this interaction is unclear. In this study, we demonstrate that the short N-terminal region of the capsid protein forms a homo-oligomer that is critical for the capsid-p150 interaction. These interactions are required for the viral-gene-expression-promoting activity of the capsid protein, allowing efficient viral growth. These findings provide information about the mechanisms underlying the regulation of rubella virus RNA replication via the cooperative actions of the capsid protein and p150.
Careers in Virology: Teaching at a Primarily Undergraduate Institution
Authors: Kushner David B. 
Published: July 2014

ABSTRACT
A faculty position at a primarily undergraduate institution requires working with undergraduates in both the classroom and the research lab. Graduate students and postdoctoral fellows who are interested in such a career should understand that faculty at these institutions need to teach broadly and devise research questions that can be addressed safely and with limited resources compared to a research I university. Aspects of, and ways to prepare for, this career will be reviewed herein.
Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case–control study
Authors: Feng Xianjun , Zang Shuzhi , Yang Yanrong , Zhao Shasha , Li Yunxia , Gao Xinyuan , Zhang Ligong 
Published: July 2014

ObjectivesTo further identify the single-nucleotide polymorphisms (SNPs) that contribute to the genetic susceptibility to sarcoidosis, we examined the potential association between sarcoidosis and 15 SNPs of the ANXA11 gene.DesignA case–control study.SettingA tuberculosis unit in a hospital of the university in China.ParticipantsParticipants included 412 patients with sarcoidosis and 418 healthy controls.MethodsThe selected SNPs were genotyped using the MALDI-TOF in the MassARRAY system.ResultsStatistically significant differences were found in the allelic or genotypic frequencies of the rs2789679, rs1049550 and rs2819941 in the ANXA11 gene between patients with sarcoidosis and controls. The rs2789679 A allele (p=0.00004, OR=1.42, 95% CI 1.17 to 1.73) and rs2819941 T allele (p=0.0006, OR=1.41, 95% CI 1.16 to 1.71) were significantly more frequent in patients with sarcoidosis compared with controls. The frequency of the rs1049550 T allele (p=0.000002, OR=0.61, 95% CI 0.49 to 0.74) in patients with sarcoidosis was significantly lower than that in controls. The multi-SNP model reveals that rs1049550 is the only independent SNP association effect after accounting for the other two marginally associated SNPs. In block 2 (rs1049550–rs2573351), the T–C haplotype occurred significantly less frequently (p=0.001), whereas the C–C haplotypes occurred more frequently (p=0.0001) in patients with sarcoidosis than controls. Furthermore, genotype frequency distribution revealed that, in rs1049550, the CC genotype was significantly more in patients with chest X-ray (CXR) stage I sarcoidosis than in patients with CXR stage II–IV sarcoidosis (p=0.012).ConclusionsThese findings point to a role for the polymorphisms of ANXA11 in sarcoidosis in a Chinese Han population, and may be informative for future genetic studies on sarcoidosis.
Patient and public involvement in the early stages of clinical trial development: a systematic cohort investigation
Authors: Gamble Carrol , Dudley Louise , Allam Alison , Bell Philip , Goodare Heather , Hanley Bec , Preston Jennifer , Walker Alison , Williamson Paula , Young Bridget 
Published: July 2014

BackgroundRandomised controlled trials (RCTs) are considered particularly likely to benefit from patient and public involvement (PPI). Decisions made by professional researchers at the outset may go on to have a significant impact on the potential for PPI contributions.ObjectiveTo increase knowledge of PPI within the early development of RCTs by systematically describing the reported level, nature and acceptability of proposed PPI to the funders.MethodsDocumentation from the outline application process for all RCTs that received funding from the Health Technology Assessment (HTA) Programme 2006–2010 was requested. For each application, data were extracted on trial characteristics, references to PPI in the development of the outline application and funding Board feedback, and plans for PPI in the full application and after the trial was funded.Results110 applications were eligible with outline applications available for 90 (82%). The cohort covered a wide range of interventions and conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated PPI within the development of the outline application itself; 32 (35.6%) planned involvement in the full application and 43 (48%) once the trial was funded. Recruitment at diagnosis and surgical interventions were less likely to describe PPI. Blinded trials and trials in which participants may receive placebo only, more frequently described PPI activity. The HTA commissioning Board feedback rarely referred to PPI.ConclusionsIncorporation of PPI within the development of the outline application or specification of plans for future involvement was low. Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research. Comments on PPI by reviewers should be directional rather than state that an increase is required. Challenges facing applicants in initiating PPI prior to funding need to be addressed.
Brazilian medicinal plants to treat upper respiratory tract and bronchial illness: systematic review and meta-analyses—study protocol
Authors: Lopes Luciane C , Silva Maria Carolina O , Motta Cristiane Bergamashi , Macho Quirós Antonio , Biavatti Maique Weber , de Oliveira Jardel Corrêa , Guyatt Gordon 
Published: July 2014

IntroductionRespiratory illness, often associated with cough and sputum, is frequent. In Brazil, herbal medicines are often recommended as a first-line treatment for respiratory illness. There exists uncertainty regarding the effectiveness of these treatments. No systematic review has evaluated Brazilian medicinal plants (BMP) to treat upper respiratory tract and bronchial illness (URTI).Methods and analysisWe will conduct a systematic review and, if appropriate, a series of meta-analyses evaluating the safety and effectiveness of BMP for URTI. Eligible randomised controlled trials and observational studies will enrol adult or paediatric patients presenting with URTI treated by BMP approved by the Brazilian Health Surveillance Agency compared with placebo, no treatment or an alternative therapy. Our search will include the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Illness Group's Specialized Register; MEDLINE; EMBASE; CINAHL (Cumulative Index to Nursing and Allied Health Literature); Web of Science; AMED; LILACS; CAB abstracts; clinical trial.gov; the WHO Trial Register and the Brazilian thesis database (CAPES) without any language restrictions. Outcomes of interest are time to resolution of clinical symptoms and/or signs (cough, sputum production or activity limitations), severity of symptoms prior to resolution and major/minor adverse events. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and the complete full text to determine eligibility. For eligible studies, reviewers will perform data abstraction and assess risk of bias of eligible trials. When appropriate, we will conduct meta-analyses. We will also assess the quality of body of evidence (confidence in estimates of effect) for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Ethics and disseminationThe systematic review will be published in a peer-reviewed journal. Brief reports of review findings will be disseminated directly to appropriate audiences via email and other modes of communication. The review will guide healthcare practice and policy in Brazil.Trial registration numberProspero CRD42014007057.
Perceptions of chronically ill and healthy consumers about electronic personal health records: a comparative empirical investigation
Authors: Cocosila Mihail , Archer Norm 
Published: July 2014

ObjectiveTo develop a model of consumer perceptions of electronic personal health records (PHRs) and validate it in a comparative study between consumers who report having a chronic illness and those who report being well.Materials and methodsA model of PHR use motivators and barriers was built and tested through a national survey across Canada. Data were collected from 800 individuals, 18 years or older. Half reported having a chronic illness or disability and half reported being well. Analyses were performed with structural equation modelling techniques.ResultsA total of 389 answers from chronically ill and 383 from well participants were collected. Perceived usefulness was the key explanation of the intention to use PHRs for both ill and well people (total effect of 0.601 and 0.565, respectively) followed by security, privacy and trust in PHRs (total effect of 0.377 and 0.479, respectively). Conversely, computer anxiety was perceived as a significant barrier (total effect of −0.327 for ill individuals and −0.212 for well individuals).DiscussionThe model proposed was appropriate in explaining key consumer positive and negative perceptions on electronic PHR use. We found little difference in perceptions of electronic PHRs between chronically ill and well individuals, although self-reporting their health status might have influenced the results.ConclusionsTo increase the adoption rate of electronic PHRs among both chronically ill and well consumers it is necessary to reinforce consumer perceptions of the usefulness of and trust in these eHealth technologies while mitigating their anxieties about computer use in general.
Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK
Authors: Adams Elisabeth J , Ehrlich Alice , Turner Katherine M E , Shah Kunj , Macleod John , Goldenberg Simon , Meray Robin K , Pearce Vikki , Horner Patrick 
Published: July 2014

ObjectivesWe aimed to explore patient pathways using a chlamydia/gonorrhoea point-of-care (POC) nucleic acid amplification test (NAAT), and estimate and compare the costs of the proposed POC pathways with the current pathways using standard laboratory-based NAAT testing.Design/participantsWorkshops were conducted with healthcare professionals at four sexual health clinics representing diverse models of care in the UK. They mapped out current pathways that used chlamydia/gonorrhoea tests, and constructed new pathways using a POC NAAT. Healthcare professionals' time was assessed in each pathway.Outcome measureThe proposed POC pathways were then priced using a model built in Microsoft Excel, and compared to previously published costs for pathways using standard NAAT-based testing in an off-site laboratory.ResultsPathways using a POC NAAT for asymptomatic and symptomatic patients and chlamydia/gonorrhoea-only tests were shorter and less expensive than most of the current pathways. Notably, we estimate that POC testing as part of a sexual health screen for symptomatic patients, or as stand-alone chlamydia/gonorrhoea testing, could reduce costs per patient by as much as £16 or £6, respectively. In both cases, healthcare professionals' time would be reduced by approximately 10 min per patient.ConclusionsPOC testing for chlamydia/gonorrhoea in a clinical setting may reduce costs and clinician time, and may lead to more appropriate and quicker care for patients. Further study is warranted on how to best implement POC testing in clinics, and on the broader clinical and cost implications of this technology.
Clinical significance of low forced expiratory flow between 25% and 75% of vital capacity following treated pulmonary tuberculosis: a cross-sectional study
Authors: Pefura-Yone Eric Walter , Kengne Andre Pascal , Tagne-Kamdem Pierre Eugene , Afane-Ze Emmanuel 
Published: July 2014

ObjectivesThe aim of this study was to assess the prevalence and determinants of post-tuberculosis chronic respiratory signs, as well as the clinical impact of a low forced expiratory flow between 25% and 75% (FEF25–75%) in a group of individuals previously treated successfully for pulmonary tuberculosis.DesignThis was a cross-sectional study involving individuals in their post-tuberculosis treatment period. They all underwent a spirometry following the 2005 criteria of the American Thoracic Society/European Respiratory Society. Distal airflow obstruction (DAO) was defined by an FEF25–75%<65% and a ratio forced expiratory volume during the first second (FEV1)/forced vital capacity (FVC) ≥ 0.70. Logistic regression models were used to investigate the determinants of persisting respiratory symptoms following antituberculous treatment.SettingThis study was carried out in the tuberculosis diagnosis and treatment centre at Yaounde Jamot Hospital, which serves as a referral centre for tuberculosis and respiratory diseases for the capital city of Cameroon (Yaounde) and surrounding areas.ParticipantsAll consecutive patients in their post-tuberculosis treatment period were consecutively enrolled between November 2012 and April 2013.ResultsOf the 177 patients included, 101 (57.1%) were men, whose median age (25th-75th centiles) was 32 (24–45.5) years. At least one chronic respiratory sign was present in 110 (62.1%) participants and DAO was found in 67 (62.9%). Independent determinants of persisting respiratory signs were the duration of symptoms prior to tuberculosis diagnosis higher than 12 weeks (adjusted OR 2.91; 95% CI 1.12 to 7.60, p=0.029) and presence of DAO (2.22; 1.13 to 4.38, p=0.021).ConclusionsFEF25–75%<65% is useful for the assessment and diagnosis of post-tuberculous DAO. Mass education targeting early diagnosis of pulmonary tuberculosis can potentially reduce the prevalence of post-tuberculosis respiratory signs and distal airflow obstruction.
Are we exposing patients with a mildly elevated faecal calprotectin to unnecessary investigations?
Authors: Seenan J P , Thomson F , Rankin K , Smith K , Gaya D R 
Published: July 2014

ObjectiveFaecal calprotectin (FC) is a non-invasive marker used to differentiate irritable bowel syndrome from inflammatory bowel disease (IBD). However, false positives are common. We sought to determine the diagnostic yield of investigation in patients presenting with new lower gastrointestinal (GI) symptoms and a mildly elevated FC (100–200 µg/g).DesignRetrospective study of electronic patient records.PatientsPatients aged 16–50 years with new lower GI symptoms and an FC 100–200 µg/g were identified from our biochemistry laboratory database between September 2009 and 2011. Patients were excluded if they had a previous FC >200 µg/g, were taking non-steroidal anti-inflammatory drugs (NSAIDs), had IBD, positive stool cultures or ‘alarm’ symptoms.SettingSecondary care gastroenterology clinics.Results161 patients (103 female patients) were identified. Mean age was 37.3 years with a mean FC of 147 µg/g. 398 endoscopic, radiological and histological investigations were undertaken in 141 patients (an average of 2.8 investigations per patient). 131 colonoscopies were performed with abnormalities in only 24 (18.3%). In patients with a macroscopically normal upper GI endoscopy and colonoscopy, the diagnostic yield of any further investigation was only 7.3%. The negative predictive value (NPV) of an FC 100–200 µg/g was 86.7% for any pathology and 97.5% for significant luminal pathology (IBD, advanced adenoma or colorectal carcinoma). After a mean follow-up of 172.4 weeks, IBD was the final diagnosis in only 4 (2.5%) of patients.ConclusionsIn adult patients under 50 years old presenting with new lower GI symptoms, the NPV of an FC between 100 and 200 µg/g in excluding significant organic GI disease is high.
Pregnancy intentions among female sex workers: recognising their rights and wants as mothers
Authors: Duff Putu , Shoveller Jeannie , Feng Cindy , Ogilvie Gina , Montaner Julio , Shannon Kate 
Published: July 2014

ObjectiveTo better understand the prevalence and correlates of pregnancy intentions among female sex workers (FSWs).DesignCross-sectional analysis using data from an open prospective cohort of street and off-street FSWs in Vancouver, Canada, in partnership with local sex work and community agencies.MethodsFSWs were recruited through outreach to street and off-street locations (e.g. massage parlours, micro-brothels) and completed interviewer-administered questionnaires and HIV/sexually transmitted infection testing. Bivariable and multivariable logistic regression was used to evaluate correlates of pregnancy intention, based on a ‘yes’ or ‘no’ response to the question “Are you planning on have any (any more) children in the future?”.ResultsOf the 510 women, 394 (77.3%) reported prior pregnancy, with 140 (27.5%) of the entire sample reporting positive pregnancy intentions. Regarding ethnicity, 35.3% were Caucasian and 26.3% were Asian/visible minority, with no differences in pregnancy intention by ethnicity or HIV status; 38.4% reported Canadian Aboriginal ancestry. In our final multivariable model, servicing clients in formal indoor settings, inconsistent condom use by clients, younger age, and intimate partner violence (IPV) were associated with pregnancy intention.ConclusionsFSWs may have pregnancy intention levels similar to that of women in other occupations. Policy changes are needed to improve FSWs’ access to integrated HIV and reproductive health services and harm reduction services, particularly for FSWs experiencing IPV.