bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Host Susceptibility Gene, DR1, Facilitates Influenza A Virus Replication by Suppressing Host Innate Immunity and Enhancing Viral RNA Replication
Authors: Hsu Shih-Feng , Su Wen-Chi , Jeng King-Song , Lai Michael M. C. 
Published: January 2015

ABSTRACT
Influenza A virus (IAV) depends on cellular factors to complete its replication cycle; thus, investigation of the factors utilized by IAV may facilitate antiviral drug development. To this end, a cellular transcriptional repressor, DR1, was identified from a genome-wide RNA interference (RNAi) screen. Knockdown (KD) of DR1 resulted in reductions of viral RNA and protein production, demonstrating that DR1 acts as a positive host factor in IAV replication. Genome-wide transcriptomic analysis showed that there was a strong induction of interferon-stimulated gene (ISG) expression after prolonged DR1 KD. We found that beta interferon (IFN-β) was induced by DR1 KD, thereby activating the JAK-STAT pathway to turn on ISG expression, which led to a strong inhibition of IAV replication. This result suggests that DR1 in normal cells suppresses IFN induction, probably to prevent undesired cytokine production, but that this suppression may create a milieu that favors IAV replication once cells are infected. Furthermore, biochemical assays of viral RNA replication showed that DR1 KD suppressed viral RNA replication. We also showed that DR1 associated with all three subunits of the viral RNA-dependent RNA polymerase (RdRp) complex, indicating that DR1 may interact with individual components of the viral RdRp complex to enhance viral RNA replication. Thus, DR1 may be considered a novel host susceptibility gene for IAV replication via a dual mechanism, not only suppressing the host defense to indirectly favor IAV replication but also directly facilitating viral RNA replication.

IMPORTANCE
Investigations of virus-host interactions involved in influenza A virus (IAV) replication are important for understanding viral pathogenesis and host defenses, which may manipulate influenza virus infection or prevent the emergence of drug resistance caused by a high error rate during viral RNA replication. For this purpose, a cellular transcriptional repressor, DR1, was identified from a genome-wide RNAi screen as a positive regulator in IAV replication. In the current studies, we showed that DR1 suppressed the gene expression of a large set of host innate immunity genes, which indirectly facilitated IAV replication in the event of IAV infection. Besides this scenario, DR1 also directly enhanced the viral RdRp activity, likely through associating with individual components of the viral RdRp complex. Thus, DR1 represents a novel host susceptibility gene for IAV replication via multiple functions, not only suppressing the host defense but also enhancing viral RNA replication. DR1 may be a potential target for drug development against influenza virus infection.
Normal saline flushes performed once daily maintain peripheral intravenous catheter patency: a randomised controlled trial
Authors: Schreiber Silvana , Zanchi Chiara , Ronfani Luca , Delise Anna , Corbelli Alessandra , Bortoluzzi Rosamaria , Taddio Andrea , Barbi Egidio 
Published: January 2015

ObjectiveRecent evidence supports the use of normal saline flushes in place of heparin to maintain the patency of peripheral intravenous locks (IVLs); however, there are no data regarding the recommended flush frequency.Study designThis was an open, non-inferiority, randomised controlled trial. Children with IVLs, aged 1–17 years, were randomly assigned to receive saline flushing every 12 h (group A) or every 24 h (group B). The main outcome was the maintenance of catheter patency.ResultsFour hundred patients were randomised; 198 subjects were analysed in the 12 h group and 199 in the 24 h group (three patients were lost at follow-up). Occlusion occurred in 15 children (7.6%) in group A versus 9 (4.5%) in group B (p=0.21). The difference in catheter patency was +3.1% in favour of the 24 h group (95% CI −1.6% to 7.7%), showing the non-inferiority of the 24 h procedure (the non-inferiority margin was set at −4%). Catheter-related complications were not different between the two groups (12.1% in group A vs 9.5% in group B; p=0.42).ConclusionsA flushing procedure with one flush per day allows maintenance of catheter patency without an increase in catheter-related complications. We propose a simplification of the flushing procedure with only one flush per day, thereby reducing costs (materials use and nursing time), labour and unnecessary manipulation of the catheters which can cause distress in younger children and their parents.Trial registration numberThe study is registered in the international database ClinicalTrial.gov under registration number NCT02221024.
Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres
Authors: Gennatas S , Noble J , Stanway S , Gunapala R , Chowdhury R , Wotherspoon A , Benepal T , Popat S 
Published: January 2015

ObjectivesWe conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site.SettingWe have reviewed the outcomes of one of the largest data sets of consecutive patients with EPSCC identified from two major cancer centres.ParticipantsConsecutive patients with a histopathological diagnosis of EPSCC from the two institutions were retrospectively identified.Primary and secondary outcome measuresOutcomes were evaluated including stage at presentation, treatments given, sites of relapse, time to distant relapse, progression-free survival and overall survival (OS).ResultsFrom a total 159 patients, 114 received first-line chemotherapy, 80.5% being platinum-based. Response rate was 48%. Commonest primary sites were genitourinary and gynaecological. 44% of patients presented with metastatic disease. 55.9% relapsed with liver the commonest site, whereas only 2.5% developed brain metastases. Median OS was 13.4 months for all patients, 7.6 months and 19.5 months for those with metastatic and non-metastatic disease, respectively. Gynaecological and head and neck patients had significantly better OS compared to gastrointestinal patients.ConclusionsEPSCCs demonstrate high response rates to chemotherapy and high rates of distant metastases. Primary sites may influence prognosis, and survival is optimal with a radical strategy. Brain metastases are rare and we therefore do not recommend prophylactic cranial irradiation.
Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study
Authors: Fox Michael J , Ahuja Kiran D K , Robertson Iain K , Ball Madeleine J , Eri Rajaraman D 
Published: January 2015

ObjectiveTo estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children.Design and settingThis was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia.Participants and interventionsChildren (aged 1–12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containingLactobacillus rhamnosusGG (LGG),Bifidobacterium lactis(Bb-12) andLactobacillus acidophilus(La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment.OutcomesStool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis.Results72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥6, ≥3 stools/day for ≥2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p=0.025). There was also only one episode of minor diarrhoea (stool consistency ≥5, ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite and 1 had nausea).ConclusionsA yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children.Trial registration numberAustralian New Zealand Clinical Trials Registry ACTRN12609000281291
The African, Caribbean and European (ACE) Pathways to Care study: a qualitative exploration of similarities and differences between African-origin, Caribbean-origin and European-origin groups in pathways to care for psychosis
Authors: Ferrari Manuela , Flora Nina , Anderson Kelly K , Tuck Andrew , Archie Suzanne , Kidd Sean , McKenzie Kwame 
Published: January 2015

ObjectivesThis paper reports on a qualitative exploration of the reasons for differences in pathways to care and duration of untreated psychosis (DUP) in the African, Caribbean and European (ACE) Pathways to Care study from the perspective of respondents to the study and their families.SettingOntario, Canada.ParticipantsThirty-four participants in total. Twenty-five young people who had experienced a first episode of psychosis and nine family members. Participants were part of the ACE Pathways to Care study.DesignWe implemented six focus groups. Furthermore, we implemented four in-depth interviews with two African-origin young women, one Caribbean-origin woman, and one European-origin woman with lived experience of psychosis.ResultsFactors that influenced help-seeking delays across the three groups were: personal awareness of symptoms, family members’ knowledge of psychotic symptoms and knowledge of mental health services. Youth and their family members described how stigma played a key role in pathways to care by stopping them from asking for help. The way in which stigma operated on the three groups’ members, from feeling ashamed to feeling guilty for their mental illnesses, helped to explain differences in DUP between the groups. Guilt feelings emerged as a prominent theme among members from the African and Caribbean groups and it was not discussed in the European focus group. Delay in entering into first-episode psychosis programmes was also influenced by the stigma perceived by young people in healthcare settings. This had an impact on the therapeutic relationships, disclosure of symptoms and overall trust in the healthcare system.ConclusionsThe findings of this paper suggest that stigma, especially internalised stigma, may operate in different ways in European-origin, African-origin and Caribbean-origin groups. These findings could inform the development of more equitable services for people in early stages of psychosis.
Efficacy of metformin in pregnant obese women: a randomised controlled trial
Authors: Chiswick Carolyn A , Reynolds Rebecca M , Denison Fiona C , Whyte Sonia A , Drake Amanda J , Newby David E , Walker Brian R , Forbes Shareen , Murray Gordon D , Quenby Siobhan , Wray Susan , Norman Jane E 
Published: January 2015

IntroductionIncreasing evidence suggests obesity has its origins prior to birth. There is clear correlation between maternal obesity, high birthweight and offspring risk of obesity in later life. It is also clear that women who are obese during pregnancy are at greater risk of adverse outcomes, including gestational diabetes and stillbirth. The mechanism(s) by which obesity causes these problems is unknown, although hyperglycaemia and insulin resistance are strongly implicated. We present a protocol for a study to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high birthweight babies and other pregnancy complications.Methods and analysisThe Efficacy of Metformin in Pregnant Obese Women, a Randomised controlled (EMPOWaR) trial is a double-masked randomised placebo-controlled trial to determine whether metformin given to obese (body mass index >30 kg/m2) pregnant women from 16 weeks’ gestation until delivery reduces the incidence of high birthweight babies. A secondary aim is to test the mechanism(s) of any effect. Obese women with a singleton pregnancy and normal glucose tolerance will be recruited prior to 16 weeks’ gestation and prescribed study medication, metformin or placebo, to be taken until delivery. Further study visits will occur at 28 and 36 weeks’ gestation for glucose tolerance testing and to record anthropometric measurements. Birth weight and other measurements will be recorded at time of delivery. Anthropometry of mother and baby will be performed at 3 months postdelivery. As of January 2014, 449 women had been randomised across the UK.Ethics and disseminationThe study will be conducted in accordance with the principles of Good Clinical Practice. A favourable ethical opinion was obtained from Scotland A Research Ethics Committee, reference number 10/MRE00/12. Results will be disseminated at conferences and published in peer-reviewed journals.Trial registration numberISRCTN51279843.
Value and treatment
Authors: Roger Paul 
Published: January 2015

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Value and treatment’, was submitted and is discussed by Paul Roger. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Fate of a severely lame cow’, which was published in the November/December issue of In Practice, appears on page 47.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Utility of bone marrow examination for workup of fever of unknown origin in patients with HIV/AIDS
Authors: Quesada Andrés E , Tholpady Ashok , Wanger Audrey , Nguyen Andy N D , Chen Lei 
Published: January 2015

AimsThe utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of debate. Because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of BMAB for this diagnostic purpose. To our knowledge, no such studies have been performed in Harris County which has the highest incidence of HIV in the state of Texas.MethodsWe reviewed all BMABs from patients with HIV/AIDS and FUO or persistent cytopenia(s) from 2007 to 2011.ResultsOf 57 evaluable patients, BMAB was positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates (31.6%), culture (21.0%) or a combination. Cultures demonstratedMycobacterium avium/intracellulare(4),M tuberculosis(2),M gordonae(1),Histoplasma capsulatum(3) andCryptococcus neoformans(2). There were three cases in which a pathogen was grown in culture but that had a negative of ‘direct examination’ on tissue sections (negative AFB and GMS special stains, no morphological evidence of granuloma/lymphohistiocytic infiltrates).ConclusionsThis study supports the use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and FUO in the proper clinical setting. BMAB demonstrated infection-related evidence prior to positive bone marrow culture in 75% of cases. Special stains and blood cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this procedure assists in clinical decision making and the refinement of treatment in a more timely manner.
Traditional serrated adenomas (TSAs) admixed with other serrated (so-called precursor) polyps and conventional adenomas: a frequent occurrence
Authors: Chetty Runjan , Hafezi-Bakhtiari Sara , Serra Stefano , Colling Richard , Wang Lai Mun 
Published: January 2015

BackgroundTraditional serrated adenoma (TSA) is a very characteristic type of serrated polyp that has a predilection for the left colon. Recent molecular advances have shown two molecular phenotypes of TSA: one associated with BRAF mutations and the other with KRAS mutations. The former is associated with hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs), while the latter is associated with more conventional adenomatous dysplasia.AimsThe association of TSAs with so-called precursor lesions (HPs and SSAs) is not well recognised and the purpose of this study was to explore the coexistent presence of HPs, SSAs and adenomatous polyps within a large cohort of TSAs.MethodsIn total 149 TSAs were examined for the presence of HP, SSA and adenomatous polyps.ResultsSeen in 83 men and 65 women ranging in age from 32 to 89 years and 127 were left sided with 22 in the right colon. Seventy-eight of the 149 TSAs showed evidence of another polyp (52.34%): 32 were low-grade tubular/tubulovillous adenomas (TAs/TVAs; 41%), 28 were HPs (36%) and 18 were SSAs (23%). Eleven of the 22 right-sided TSAs were associated with a precursor lesion (1 HP and 7 SSA). In addition, five TSAs showed more than one polyp type: TSA with TA/TVA and HP (3); TSA with TA/TVA and SSA (2). The TAs/TVAs were adjacent to the TSA but occurred as a separate discrete polyp, while HPs and SSAs were intermingled with the TSA and present at the base and surface of the lesion.ConclusionsMore than 50% of TSAs are associated with a precursor lesion or adjacent TA/TVA. Their recognition is important as this may have surveillance and management ramifications.
Narratives of HIV: measuring understanding of HIV and the law in HIV-positive patients
Authors: Phillips Matthew D , Schembri Gabriel 
Published: January 2015

ObjectiveThis study aimed to identify the understanding of people living with HIV and AIDS (PLWHA) regarding the application of the law around transmission of HIV in England and Wales.DesignA questionnaire was designed to prompt participants attending a large HIV department to discuss their understanding of the law with reference to HIV transmission. The design focused on qualitative analysis as there were insufficient data available to inform a metric reflecting quantitative data on PLWHA's understanding of the legal implications of transmission.MethodsThe data were collected from PLWHA attending their HIV outpatient appointment to ensure relevance of population to the analysis. The answers were analysed using grounded theory and thematic analysis to identify key themes and theories for further testing.ResultsAnalysis demonstrated that understanding of legal obligations and outcomes of prosecutions was poor and patchy, with behavioural restrictions often overstated. There was a strong theme of ownership of responsibility amongst PLWHA, and of reference to principles of morality beyond legal restrictions.ConclusionsPLWHA remain at risk of prosecution through poor understanding of the law. Clinical services and advocacy agencies should strive to increase understanding in order to enable PLWHA to comprehend the law and negotiate it successfully. This information should be shared as a process, not an isolated event.
Influence of Sm3+ doping on microstructure and electrical properties of ((Nd0.7Yb0.3)1-xSmx)2Zr2O7
Authors: Ouyang Jia-Hu , Zhu Cheng , Liu Zhan-Guo , Ren Zhe , Jing Lin 
Published: January 2015

( Nd 0.7 Yb 0.3)2 Zr 2 O 7 and (( Nd 0.7 Yb 0.3)1-x Sm x)2 Zr 2 O 7 (0 < x ≤ 0.25) ceramics have been synthesized by pressureless sintering by tailoring the chemical compositions. Microstructure and electrical conductivity of (( Nd 0.7 Yb 0.3)1-x Sm x)2 Zr 2 O 7 were investigated by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and AC impedance spectroscopy. ( Nd 0.7 Yb 0.3)2 Zr 2 O 7 ceramic exhibits a mixed crystal structure of defect fluorite and pyrochlore. After doping with Sm 3+ cations, the structure changes from a mixed type of ( Nd 0.7 Yb 0.3)2 Zr 2 O 7 to a single pyrochlore type of (( Nd 0.7 Yb 0.3)1-x Sm x)2 Zr 2 O 7, as the addition of Sm 3+ reduces the difference in ionic radius between Nd 3+ and Yb 3+. However, (( Nd 0.7 Yb 0.3)1-x Sm x)2 Zr 2 O 7 ceramics contain the localized short-range disorder despite the structural order overall in the pyrochlore. The measured total conductivities of (( Nd 0.7 Yb 0.3)1-x Sm x)2 Zr 2 O 7 obey the Arrhenius relation. Doping of Sm 3+ enhances the electrical conductivity of ( Nd 0.7 Yb 0.3)2 Zr 2 O 7 ceramic significantly, which is closely related to the variations in the concentration of oxygen vacancies at 48f sites, relatively low activation energy and high pre-exponential factor caused by the long-range order and short-range disorder.
Numerical 3D-modeling of spall and shear fractures in shells of austenitic 12Kh18N10T steel and 30KhGSA steel under their spherical and quasi-spherical explosive loading
Authors: Kozlov Evgeny A. , Ol'khov Oleg V. , Shuvalova Ekaterina V. 
Published: January 2015

To pursue VNIIEF–VNIITF joint investigations, this paper briefly describes the experimental setup and provides numerical 3D-computation results (LEGAK-3D technique) on special features in the convergence dynamics of steel shells under their quasi-spherical explosive loading in the system with the 40-mm outer radius of the explosive layer. The computation results were compared with the data experimentally registered for shells of the 30KhGSA steel, both as-received and quenched to HRC 35…40, and the austenitic 12Kh18N10T stainless steel. The comparison was also made with laser-interferometry results obtained directly under explosive loading, as well as with gamma-tomography and scanning electron microscopy investigations of the recovered shells.