bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals
Authors: Liu Jun , Zhang Shihong , Tan Shuguang , Yi Yong , Wu Bin , Cao Bin , Zhu Fengcai , Wang Chen , Wang Hua , Qi Jianxun , Gao George F. 
Published: September 2012

ABSTRACTLack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24+population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11+and HLA-A24+donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11+population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.
Intrinsic Temperature Sensitivity of Influenza C Virus Hemagglutinin-Esterase-Fusion Protein
Authors: Takashita Emi , Muraki Yasushi , Sugawara Kanetsu , Asao Hironobu , Nishimura Hidekazu , Suzuki Koji , Tsuji Takashi , Hongo Seiji , Ohara Yoshihiro , Kawaoka Yoshihiro , Ozawa Makoto , Matsuzaki Yoko 
Published: September 2012

ABSTRACTInfluenza C virus replicates more efficiently at 33°C than at 37°C. To determine whether hemagglutinin-esterase-fusion protein (HEF), a surface glycoprotein of influenza C virus, is a restricting factor for this temperature sensitivity, we analyzed the biological and biochemical properties of HEF at 33°C and 37°C. We found that HEF exhibits intrinsic temperature sensitivities for surface expression and fusion activity.
In Vitro
and
In Vivo
Analysis of the Interaction between RNA Helicase A and HIV-1 RNA
Authors: Xing Li , Niu Meijuan , Kleiman Lawrence 
Published: September 2012

ABSTRACT

RNA helicase A (RHA) promotes multiple steps of HIV-1 RNA metabolism during viral replication, including transcription, translation, and the annealing of primer tRNA
3
Lys
to the viral RNA. RHA is a member of the DExH subclass of RNA helicases that uniquely contains two double-stranded RNA binding domains (dsRBDs) at its N terminus. Here, we performed a genome-wide analysis of the interaction of RHA with HIV-1 RNA both
in vitro
, using fluorescence polarization, and during viral replication, using an RNA-protein coprecipitation assay.
In vitro
, RHA binds to all the isolated regions of the HIV-1 RNA genome tested, with

K
d

(equilibrium dissociation constant) values ranging from 44 to 178 nM. In contrast, during viral replication, RNA-protein coprecipitation assays detected only a major interaction of RHA with the 5′-untranslated region (5′-UTR) and a minor interaction with the Rev response element (RRE) of HIV-1 RNA. Since RHA does not associate well with all the highly structured regions of HIV-1 RNA tested
in vivo
, the results suggest that other viral or cellular factors not present
in vitro
may modulate the direct interaction of RHA with HIV-1 RNA during virus replication. Nevertheless, a role for duplex RNA as a target for RHA binding
in vivo
is suggested by the fact that the deletion of either one or both dsRBDs eliminates the
in vivo
interaction of RHA with HIV-1 RNA. Furthermore, these mutant RHAs do not promote the
in vivo
annealing of tRNA
3
Lys
to viral RNA, nor are they packaged into virions, demonstrating that the dsRBDs are essential for the role of RHA in HIV-1 replication.
Intersubtype Differences in the Effect of a Rare p24 Gag Mutation on HIV-1 Replicative Fitness
Authors: Chopera Denis R. , Cotton Laura A. , Zawaira Alexander , Mann Jaclyn K. , Ngandu Nobubelo K. , Ntale Roman , Carlson Jonathan M. , Mlisana Koleka , Woodman Zenda , de Assis Rosa Debra , Martin Eric , Miura Toshiyuki , Pereyra Florencia , Walker Bruce D. , Gray Clive M. , Martin Darren P. , Ndung'u Thumbi , Brockman Mark A. , Karim Salim Abdool , Brumme Zabrina L. , Williamson Carolyn ,   the CAPRISA 002 Study Team
Published: September 2012

ABSTRACT

Certain immune-driven mutations in HIV-1, such as those arising in p24
Gag
, decrease viral replicative capacity. However, the intersubtype differences in the replicative consequences of such mutations have not been explored. In HIV-1 subtype B, the p24
Gag
M250I mutation is a rare variant (0.6%) that is enriched among elite controllers (7.2%) (
P
= 0.0005) and appears to be a rare escape variant selected by HLA-B58 supertype alleles (
P
< 0.01). In contrast, in subtype C, it is a relatively common minor polymorphic variant (10 to 15%) whose appearance is not associated with a particular HLA allele. Using site-directed mutant viruses, we demonstrate that M250I reduces
in vitro
viral replicative capacity in both subtype B and subtype C sequences. However, whereas in subtype C downstream compensatory mutations at p24
Gag
codons 252 and 260 reduce the adverse effects of M250I, fitness costs in subtype B appear difficult to restore. Indeed, patient-derived subtype B sequences harboring M250I exhibited
in vitro
replicative defects, while those from subtype C did not. The structural implications of M250I were predicted by protein modeling to be greater in subtype B versus C, providing a potential explanation for its lower frequency and enhanced replicative defects in subtype B. In addition to accounting for genetic differences between HIV-1 subtypes, the design of cytotoxic-T-lymphocyte-based vaccines may need to account for differential effects of host-driven viral evolution on viral fitness.
Loss of the Protease Dimerization Inhibition Activity of Tipranavir (TPV) and Its Association with the Acquisition of Resistance to TPV by HIV-1
Authors: Aoki Manabu , Danish Matthew L. , Aoki-Ogata Hiromi , Amano Masayuki , Ide Kazuhiko , Das Debananda , Koh Yasuhiro , Mitsuya Hiroaki 
Published: September 2012

ABSTRACT

Tipranavir (TPV), a protease inhibitor (PI) inhibiting the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-PI-resistant HIV-1 isolates. When a mixture of 11 multi-PI-resistant (but TPV-sensitive) clinical isolates (HIV
11MIX
), which included HIV
B
and HIV
C
, was selected against TPV, HIV
11MIX
rapidly (by 10 passages [HIV
11MIX
P10
]) acquired high-level TPV resistance and replicated at high concentrations of TPV. HIV
11MIX
P10
contained various amino acid substitutions, including I54V and V82T. The intermolecular FRET-based HIV-1 expression assay revealed that TPV's dimerization inhibition activity against cloned HIV
B
(cHIV
B
) was substantially compromised. The introduction of I54V/V82T into wild-type cHIV
NL4-3
(cHIV

NL4-3
I54V/V82T

) did not block TPV's dimerization inhibition or confer TPV resistance. However, the introduction of I54V/V82T into cHIV
B
(cHIV
B
I54V/V82T
) compromised TPV's dimerization inhibition and cHIV
B
I54V/V82T
proved to be significantly TPV resistant. L24M was responsible for TPV resistance with the cHIV
C
genetic background. The introduction of L24M into cHIV
NL4-3
(cHIV

NL4-3
L24M

) interfered with TPV's dimerization inhibition, while L24M increased HIV-1's susceptibility to TPV with the HIV
NL4-3
genetic background. When selected with TPV, cHIV

NL4-3
I54V/V82T

most readily developed TPV resistance and acquired E34D, which compromised TPV's dimerization inhibition with the HIV
NL4-3
genetic background. The present data demonstrate that certain amino acid substitutions compromise TPV's dimerization inhibition and confer TPV resistance, although the loss of TPV's dimerization inhibition is not always associated with significantly increased TPV resistance. The findings that TPV's dimerization inhibition is compromised with one or two amino acid substitutions may explain at least in part why the genetic barrier of TPV against HIV-1's development of TPV resistance is relatively low compared to that of darunavir.
Review of quality assessment tools for the evaluation of pharmacoepidemiological safety studies
Authors: Neyarapally George A , Hammad Tarek A , Pinheiro Simone P , Iyasu Solomon 
Published: September 2012

ObjectivesPharmacoepidemiological studies are an important hypothesis-testing tool in the evaluation of postmarketing drug safety. Despite the potential to produce robust value-added data, interpretation of findings can be hindered due to well-recognised methodological limitations of these studies. Therefore, assessment of their quality is essential to evaluating their credibility. The objective of this review was to evaluate the suitability and relevance of available tools for the assessment of pharmacoepidemiological safety studies.DesignWe created an a priori assessment framework consisting of reporting elements (REs) and quality assessment attributes (QAAs). A comprehensive literature search identified distinct assessment tools and the prespecified elements and attributes were evaluated.Primary and secondary outcome measuresThe primary outcome measure was the percentage representation of each domain, RE and QAA for the quality assessment tools.ResultsA total of 61 tools were reviewed. Most tools were not designed to evaluate pharmacoepidemiological safety studies. More than 50% of the reviewed tools considered REs under the research aims, analytical approach, outcome definition and ascertainment, study population and exposure definition and ascertainment domains. REs under the discussion and interpretation, results and study team domains were considered in less than 40% of the tools. Except for the data source domain, quality attributes were considered in less than 50% of the tools.ConclusionsMany tools failed to include critical assessment elements relevant to observational pharmacoepidemiological safety studies and did not distinguish between REs and QAAs. Further, there is a lack of considerations on the relative weights of different domains and elements. The development of a quality assessment tool would facilitate consistent, objective and evidence-based assessments of pharmacoepidemiological safety studies.
A national cross-sectional study on effects of fluoride-safe water supply on the prevalence of fluorosis in China
Authors: Wang Cheng , Gao Yanhui , Wang Wei , Zhao Lijun , Zhang Wei , Han Hepeng , Shi Yuxia , Yu Guangqian , Sun Dianjun 
Published: September 2012

ObjectiveTo assess the effects of provided fluoride-safe drinking-water for the prevention and control of endemic fluorosis in China.DesignA national cross-sectional study in China.SettingIn 1985, randomly selected villages in 27 provinces (or cities and municipalities) in 5 geographic areas all over China.ParticipantsInvolved 81 786 children aged from 8 to 12 and 594 698 adults aged over 16.Main outcome measureThe prevalence of dental fluorosis and clinical skeletal fluorosis, the fluoride concentrations in the drinking-water in study villages and in the urine of subjects.ResultsThe study showed that in the villages where the drinking-water fluoride concentrations were higher than the government standard of 1.2 mg/l, but no fluoride-safe drinking-water supply scheme was provided (FNB areas), the prevalence rate and index of dental fluorosis in children, and prevalence rate of clinical skeletal fluorosis in adults were all significantly higher than those in the historical endemic fluorosis villages after the fluoride-safe drinking-water were provided (FSB areas). Additionally, the prevalence rate of dental fluorosis as well as clinical skeletal fluorosis, and the concentration of fluoride in urine were found increased with the increase of fluoride concentration in drinking-water, with significant positive correlations in the FNB areas. While, the prevalence rate of dental fluorosis and clinical skeletal fluorosis in different age groups and their degrees of prevalence were significantly lower in the FSB areas than those in the FNB areas.ConclusionsThe provision of fluoride-safe drinking-water supply schemes had significant effects on the prevention and control of dental fluorosis and skeletal fluorosis. The study also indicated that the dental and skeletal fluorosis is still prevailing in the high-fluoride drinking-water areas in China.
Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial
Authors: Hansson Anna , Hajek Peter , Perfekt Roland , Kraiczi Holger 
Published: September 2012

ObjectiveA new nicotine mouth spray was shown to be an effective stop-smoking treatment. This study was set up to examine the speed with which it relieves urges to smoke, and how it compares with nicotine lozenge in this respect.DesignRandomised, cross-over trial that compared nicotine mouth spray 2 mg versus nicotine lozenge 2 or 4 mg.SettingClinical pharmacology research unit.Participants200 Volunteer smokers who smoked their first cigarette of the day within 30 min of waking.InterventionsSubjects abstained from smoking the night before the morning they attended the laboratory. Treatment was administered following 5 h of witnessed abstinence.Primary and secondary outcome measuresUrge to smoke was rated before and at 1, 3, 5, 10, 15, 25, 30, 45 min and 1, 1.5, and 2 h after treatment administration. The primary outcome concerned change during the first 1, 3 and 5 min after treatment administration.ResultsNicotine mouth spray achieved greater reductions in craving than either lozenge during the first 1, 3 and 5 min postadministration. After using mouth spray, half of the users experienced 50% reduction in craving within 3.40 min, while the same treatment effect was achieved within 9.92 and 9.20 min for the 2 and 4 mg lozenge, respectively. Adverse events with both mouth spray and lozenge were mostly mild. Hiccups, local irritation, nausea and dyspepsia were more frequent with spray than lozenge.ConclusionsNicotine mouth spray provides a faster relief of cravings than nicotine lozenge.
Managing the after effects of serious patient safety incidents in the NHS: an online survey study
Authors: Pinto Anna , Faiz Omar , Vincent Charles 
Published: September 2012

ObjectiveTo examine the current state of practice in English NHS Trusts in relation to the communication of serious patient safety incidents to patients and families and support for all parties involved.DesignCross-sectional design using online surveys.Participants209 patient safety managers, responsible for the ‘Being Open’ policy (54% response rate).SettingEnglish NHS Trusts.Results98% of the participants reported that they are familiar with the National Patient Safety Agency Being Open guidance and 82% that they implement it more than half the time when incidents occur. However, provision of timely information was not reported as routine, with two-thirds of the discussions taking place 3–6 weeks after the investigation. The frequency of taking responsibility for harm was low for incidents of different severity levels but significantly lower for less serious ones (p<0.001). Follow-ups of patients in the long term and ex gratia payments were provided less than half the time. The most highly rated barriers to being open were clinical staff's fear of negative reactions from patients or their families and anxiety about litigation. Support practices for staff, such as debriefing and training on being open, were acknowledged as highly important but not always available.ConclusionsAwareness of the importance of being open is high among patient safety managers in English NHS Trusts, but there is still considerable scope for improvement in the management of the after effects of patient safety incidents. More research is needed on patients' and healthcare professionals' preferences for support after patient safety incidents.
Applicability of the CATCH, CHALICE and PECARN paediatric head injury clinical decision rules: pilot data from a single Australian centre
Authors: Lyttle Mark D , Cheek John A , Blackburn Carol , Oakley Ed , Ward Brenton , Fry Amanda , Jachno Kim , Babl Franz E 
Published: September 2012

BackgroundClinical decision rules (CDRs) for paediatric head injury (HI) exist to identify children at risk of traumatic brain injury. Those of the highest quality are the Canadian assessment of tomography for childhood head injury (CATCH), Children's head injury algorithm for the prediction of important clinical events (CHALICE) and Pediatric Emergency Care Applied Research Network (PECARN) CDRs. They target different cohorts of children with HI and have not been compared in the same setting. We set out to quantify the proportion of children with HI to which each CDR was applicable.MethodsConsecutive children presenting to an Australian paediatric Emergency Department with HIs were enrolled. Published inclusion/exclusion criteria and predictor variables from the CDRs were collected prospectively. Using these we determined the frequency with which each CDR was applicable.Results1012 patients (69.9%) were enrolled with 949 available for analysis. Mean age was 6.8 years (21% <2 years). 95% had initial Glasgow Coma Scale 15. CT rate was 12.8% and neurosurgery rate was 0.7%. No CDR was applicable to all patients. CHALICE was applicable to the most (97%, 95% CI 96% to 98%) and CATCH to the fewest (26%, 95% CI 24% to 29%). PECARN was applicable to 76% (95% CI 70% to 82%) aged <2 years, and 74% (95% CI 71% to 77%) aged 2–<18 years.ConclusionsEach CDR is applicable to a different proportion of children with HI. This makes a direct comparison of the CDRs difficult. Prior to selection of any for implementation they should undergo validation outside the derivation setting coupled with an analysis of their performance accuracy, usability and cost effectiveness.
Utilisation of fluorescent multiplex PCR and laser-induced capillary electrophoresis for the diagnosis of Ewing family of tumours in formalin-fixed paraffin-embedded tissues
Authors: Patócs Barbara , Németh Krisztina , Garami Miklós , Arató Gabriella , Kovalszky Ilona , Szendrői Miklós , Fekete György 
Published: September 2012

AimsThe localisation of the translocation breakpoint of the Ewing sarcoma family of tumours shows significant variability on relatively large regions of fusion partner genes. As a consequence, many alternative forms of EWSR1-ETS translocation exist which make the RNA-based molecular diagnostics of Ewing sarcoma family of tumours complicated. In addition to the heterogeneity of fusion transcripts, the degradation of RNA also presents a significant difficulty in the molecular analysis of formalin-fixed paraffin-embedded (FFPE) tissues. Our aim was to establish a sensitive method which is able to identify all combinatorially possible EWSR1-FLI1 and EWSR1-ERG translocation transcripts in FFPE tissue samples despite significant RNA-degradation.MethodsThe combination of fluorescent multiplex PCR with laser-induced capillary electrophoresis was used to detect and identify EWSR1-FLI1 and EWSR1-ERG chimeric transcripts on the basis of amplicon size, and forward primers labelled by distinct fluorophores.ResultsUsing this method, we processed 60 FFPE samples of Ewing sarcoma family of tumours, and identified six types EWSR1-FLI1 and one type EWSR1-ERG chimeric transcripts acceptable for RT-PCR analysis in 27 out of 45 samples. This result shows 60% sensitivity for detecting the most frequent Ewing family of tumour (EFT)-related fusion transcripts.ConclusionsThe utilisation of fluorescent multiplex PCR and laser-induced fluorescent capillary electrophoresis is effective for the diagnosis of EFT in FFPE tissue, and after the defined modifications it can offer a sensitive method to overcome the diagnostic difficulties connected with heterogeneity of the variant translocations in EFT.
Magnetic resonance spectroscopy of the brain
Authors: Currie Stuart , Hadjivassiliou Marios , Craven Ian J , Wilkinson Iain D , Griffiths Paul D , Hoggard Nigel 
Published: September 2012

Abstract
Proton magnetic resonance (MR) spectroscopy of the brain is a non-invasive, in vivo technique that allows investigation into regional chemical environments. Its complementary use with MR imaging sequences provides valuable insights into brain tumour characteristics, progression and response to treatment. Additionally, its sensitivity to brain dysfunction in the presence of apparently normal structural imaging has galvanised interest in its use as a biomarker of neurodegenerative disorders such as Alzheimer's disease. Accordingly, its integration into clinical imaging protocols within many neuroscience centres throughout the world is increasing. This growing attention is encouraging but if the potential of MR spectroscopy is to be realised, fundamental questions need to be addressed, such as reproducibility of the technique and the biochemistry that underpins the neurometabolites measured. Failure to resolve these issues will continue to hinder the extent and accuracy of conclusions that can be drawn from its data. In this review we discuss the issues regarding MR spectroscopy in the brain with particular attention paid to its technique. Key examples of current clinical applications are provided and future directions are discussed.
Synthesis and Thermal Characterization of Lanthanide(III)Complexes with Mercaptosuccinic Acid and Hydrazine as Ligands
Authors: Devipriya S. , Arunadevi N. , Vairam S. 
Published: September 2012

Reaction of hydrazine and mercaptosuccinic acid with metal ions forms	complexes with general formula [Ln(N2H4)2{CH2(COO)CH(SH)(COO)}1.5]·(H2O), where Ln = La(III), Pr(III), Nd(III), Sm(III), and Gd(III) at pH 5. The complexes have been characterized by elemental analysis, IR and UV‐visible spectroscopic, thermal and X‐ray diffraction studies. The IR data reveal that the acid moiety in the complexes is present as dianion due to the deprotonation of COOH groups by lanthanides in these complexes, leaving –SH group unionized and hydrazine as bidental neutral ligand showing absorptions in the range of 945–948 cm−1. The thermoanalytical data evince that the complexes are stable up to 103°C and undergo complete decomposition in the range of 550–594°C resulting in metal oxides. SEM images of La2O3 and Gd2O3 residues show their nano sized clusters suggesting that the complexes may be used as precursors for nano La2O3 and Gd2O3, respectively. X‐ray powder diffraction patterns show isomorphism among the complexes. The kinetic parameters of the decomposition of the complexes have been computed by Coats‐Redfern equation.