bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cigarette smoke condensate on pneumococcal biofilm formation and pneumolysin
Authors: Mutepe N. Daphney , Cockeran Riana , Steel Helen C. , Theron Annette J. , Mitchell Tim J. , Feldman Charles , Anderson Ronald 
Published: June 2012

Although the well-recognised predisposition of cigarette smokers to the development of severe pneumococcal disease may be attributable to impairment of local host defences, less is known about the direct effects of smoke exposure on airway pathogens, or their virulence factors. In the current study, we have investigated the effects of cigarette smoke condensate (CSC) on biofilm formation byStreptococcus pneumoniae, and on the pore-forming activity of its major toxin, pneumolysin.Biofilm formation following exposure of the pneumococcus to CSC (20–160 μg·mL−1) was measured using a crystal violet-based spectrophotometric procedure, while the pore-forming activity of recombinant pneumolysin was determined by a fura-2/acetoxymethyl ester-based spectrofluorimetric procedure to monitor the uptake of extracellular Ca2+by isolated human neutrophils.Exposure of the pneumococcus or pneumolysin to CSC resulted in significant dose-related augmentation of biofilm formation (p≤0.05 at 80 and 160 μg·mL−1) and substantial attenuation of the pore-forming interactions of pneumolysin, respectively.Augmentation of biofilm formation and inactivation of pneumolysin as a consequence of smoking are likely to favour microbial colonisation and persistence, both being essential precursors of pneumococcal disease.
A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma
Authors: Piper Edward , Brightling Christopher , Niven Robert , Oh Chad , Faggioni Raffaella , Poon Kwai , She Dewei , Kell Chris , May Richard D. , Geba Gregory P. , Molfino Nestor A. 
Published: June 2012

Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies.194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β2-agonist use and safety. Numerical end-points are reported as mean±sd.At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumabversus-0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV1) were 0.21±0.38 Lversus0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β2-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45versusplacebo -0.10±1.49 (p=0.020). The increase in FEV1following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab.No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.
Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism
Authors: Moores Lisa , Zamarro Celia , Gómez Vicente , Aujesky Drahomir , García Leticia , Nieto Rosa , Yusen Roger , Jiménez David 
Published: June 2012

Although the Pulmonary Embolism Severity Index (PESI) accurately identifies 35% of patients with acute pulmonary embolism (PE) as being low risk, some patients deemed high risk by the PESI on admission might be treated safely in the outpatient environment.This retrospective cohort study included a total of 304 consecutive patients with acute PE, classified at the time of hospital admission into PESI class III. The PESI was recalculated 48 h after admission (PESI48) and each patient reclassified into the corresponding risk category. The primary outcome of the study was all-cause mortality between day 2 and day 30 after PE diagnosis.26 (8.5%) patients (95% CI 5.4–11.7%) died between day 2 and day 30 after PE diagnosis. Investigators reclassified 83 (27.3%) patients (95% CI 22.3–32.3%) as low risk (classes I and II) at 48 h. 30-day mortality in these patients was 1.2% (95% CI 0–3.5%) as opposed to 11.3% (95% CI 7.1–15.5%) in those who remained high risk. The net improvement in reclassification was estimated at 54% (p<0.001).In a cohort of intermediate-risk patients with acute PE, calculation of the PESI48allows identification of those patients at very low risk of dying during the first month of follow-up.
Stage-specific embryonic antigen-4is expressed in basaloid lung cancer and associated with poor prognosis
Authors: Gottschling Sandra , Jensen Katrin , Warth Arne , Herth Felix J.F. , Thomas Michael , Schnabel Philipp A. , Herpel Esther 
Published: June 2012

Basaloid carcinoma represents a rare variant of nonsmall cell lung cancer (NSCLC), which has shown a poor prognosis in a number of studies. Although it is considered to derive from a pluri- or multipotent pulmonary stem cells, little is known about the expression and clinical significance of stem cell antigens in this variant.Stage-specific embryonic antigen-4(SSEA-4) was analysed by immunohistochemistry in 38 patients with resected early-stage basaloid NSCLC who had a median follow-up of 72.9 months. The expression ofSSEA-4was related to clinico-pathological characteristics, to the expression of the adult stem cell antigens CD117, CD133 andbreast cancer resistance protein 1(BCRP1), and to prognosis.SSEA-4was positive in 37% of the specimens and showed no association with clinico-pathological characteristics or the expression of adult stem cell antigens. Cox proportional hazards regression analysis revealed a 6.0-fold increased risk of relapse (p = 0.001) and a 4.2-fold increased risk of disease-related mortality (p = 0.017) inSSEA-4-positive patients, whileSSEA-4-negative patients showed a prognosis comparable with that of other early-stage NSCLC.SSEA-4is expressed in a fraction of basaloid NSCLC and is associated with poor prognosis.
MarVis: a tool for clustering and visualization of metabolic biomarkers
Authors: Kaever Alexander , Lingner Thomas , Feussner Kirstin , Göbel Cornelia , Feussner Ivo , Meinicke Peter 
Published: June 2012

Abstract

Background
A central goal of experimental studies in systems biology is to identify meaningful markers that are hidden within a diffuse background of data originating from large-scale analytical intensity measurements as obtained from metabolomic experiments. Intensity-based clustering is an unsupervised approach to the identification of metabolic markers based on the grouping of similar intensity profiles. A major problem of this basic approach is that in general there is no prior information about an adequate number of biologically relevant clusters.

Results
We present the tool MarVis (Marker Visualization) for data mining on intensity-based profiles using one-dimensional self-organizing maps (1D-SOMs). MarVis can import and export customizable CSV (Comma Separated Values) files and provides aggregation and normalization routines for preprocessing of intensity profiles that contain repeated measurements for a number of different experimental conditions. Robust clustering is then achieved by training of an 1D-SOM model, which introduces a similarity-based ordering of the intensity profiles. The ordering allows a convenient visualization of the intensity variations within the data and facilitates an interactive aggregation of clusters into larger blocks. The intensity-based visualization is combined with the presentation of additional data attributes, which can further support the analysis of experimental data.

Conclusion
MarVis is a user-friendly and interactive tool for exploration of complex pattern variation in a large set of experimental intensity profiles. The application of 1D-SOMs gives a convenient overview on relevant profiles and groups of profiles. The specialized visualization effectively supports researchers in analyzing a large number of putative clusters, even though the true number of biologically meaningful groups is unknown. Although MarVis has been developed for the analysis of metabolomic data, the tool may be applied to gene expression data as well.
Origin of a novel protein-coding gene family with similar signal sequence in Schistosoma japonicum
Authors: Mbanefo Evaristus Chibunna , Chuanxin Yu , Kikuchi Mihoko , Shuaibu Mohammed Nasir , Boamah Daniel , Kirinoki Masashi , Hayashi Naoko , Chigusa Yuichi , Osada Yoshio , Hamano Shinjiro , Hirayama Kenji 
Published: June 2012

Abstract

Background
Evolution of novel protein-coding genes is the bedrock of adaptive evolution. Recently, we identified six protein-coding genes with similar signal sequence from Schistosoma japonicum egg stage mRNA using signal sequence trap (SST). To find the mechanism underlying the origination of these genes with similar core promoter regions and signal sequence, we adopted an integrated approach utilizing whole genome, transcriptome and proteome database BLAST queries, other bioinformatics tools, and molecular analyses.

Results
Our data, in combination with database analyses showed evidences of expression of these genes both at the mRNA and protein levels exclusively in all developmental stages of S. japonicum. The signal sequence motif was identified in 27 distinct S. japonicum UniGene entries with multiple mRNA transcripts, and in 34 genome contigs distributed within 18 scaffolds with evidence of genome-wide dispersion. No homolog of these genes or similar domain was found in deposited data from any other organism. We observed preponderance of flanking repetitive elements (REs), albeit partial copies, especially of the RTE-like and Perere class at either side of the duplication source locus. The role of REs as major mediators of DNA-level recombination leading to dispersive duplication is discussed with evidence from our analyses. We also identified a stepwise pathway towards functional selection in evolving genes by alternative splicing. Equally, the possible transcription models of some protein-coding representatives of the duplicons are presented with evidence of expression in vitro.

Conclusion
Our findings contribute to the accumulating evidence of the role of REs in the generation of evolutionary novelties in organisms’ genomes.
The immune gene repertoire of an important viral reservoir, the Australian black flying fox
Authors: Papenfuss Anthony T , Baker Michelle L , Feng Zhi-Ping , Tachedjian Mary , Crameri Gary , Cowled Chris , Ng Justin , Janardhana Vijaya , Field Hume E , Wang Lin-Fa 
Published: June 2012

Abstract

Background
Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity.

Results
Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts.

Conclusions
This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection.
Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report
Authors: Diserens Esther-Amélie , Bodenmann Patrick , N'Garambe Chantal , Ansermet-Pagot Anne , Vannotti Marco , Masserey Eric , Cavassini Matthias 
Published: June 2012

Abstract

Background
Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries.

Method
This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic.

Result
We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing.

Conclusion
This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.
Statin therapy in critical illness: an international survey of intensive care physicians’ opinions, attitudes and practice
Authors: Shankar-Hari Manu , Kruger Peter S , Di Gangi Stefania , Scales Damon C , Perkins Gavin D , McAuley Danny F , Terblanche Marius 
Published: June 2012

Abstract

Background
Pleotropic effects of statins on inflammation are hypothesised to attenuate the severity of and possibly prevent the occurrence of the host inflammatory response to pathogen and infection-related acute organ failure. We conducted an international survey of intensive care physicians in Australia, New Zealand (ANZ) and United Kingdom (UK). The aims of the survey were to assess the current prescribing practice patterns, attitudes towards prescribing statin therapy in critically ill patients and opinions on the need for an interventional trial of statin therapy in critically ill patients.

Methods
Survey questions were developed through an iterative process. An expert group reviewed the resulting 26 items for face and content validity and clarity. The questions were further refined following pilot testing by ICU physicians from Australia, Canada and the UK. We used the online Smart SurveyTM software to administer the survey.

Results
Of 239 respondents (62 from ANZ and 177 from UK) 58% worked in teaching hospitals; most (78.2%) practised in ‘closed’ units with a mixed medical and surgical case mix (71.0%). The most frequently prescribed statins were simvastatin (77.6%) in the UK and atorvastatin (66.1%) in ANZ. The main reasons cited to explain the choice of statin were preadmission prescription and pharmacy availability. Most respondents reported never starting statins to prevent (65.3%) or treat (89.1%) organ dysfunction. Only a minority (10%) disagreed with a statement that the risks of major side effects of statins when prescribed in critically ill patients were low. The majority (84.5%) of respondents strongly agreed that a clinical trial of statins for prevention is needed. More than half (56.5%) favoured rates of organ failure as the primary outcome for such a trial, while a minority (40.6%) favoured mortality.

Conclusions
Despite differences in type of statins prescribed, critical care physicians in the UK and ANZ reported similar prescription practices. Respondents from both communities agreed that a trial is needed to test whether statins can prevent the onset of new organ failure in patients with sepsis.
Reflections of students graduating from a transforming medical curriculum in South Africa: a qualitative study
Authors: Green-Thompson Lionel Patrick , McInerney Patricia , Manning Dianne Mary , Mapukata-Sondzaba Ntsiki , Chipamaunga Shalote , Maswanganyi Tlangelani 
Published: June 2012

Abstract

Background
The six year medical programme at the University of the Witwatersrand admits students into the programme through two routes – school entrants and graduate entrants. Graduates join the school entrants in the third year of study in a transformed curriculum called the Graduate Entry Medical Programme (GEMP). In years I and 2 of the GEMP, the curriculum is structured into system based blocks. Problem-based learning, using a three session format, is applied in these two years. The curriculum adopts a biopsychosocial approach to health care, which is implemented through spiral teaching and learning in four main themes – basic and clinical sciences, patient-doctor, community- doctor and personal and professional development. In 2010 this programme produced its fifth cohort of graduates.

Methods
We undertook a qualitative, descriptive and contextual study to explore the graduating students’ perceptions of the programme. Interviews were conducted with a total of 35 participants who volunteered to participate in the study. The majority of the participants interviewed participated in focus group discussions. The interviews were transcribed verbatim and analysed thematically, using Tesch’s eight steps. Ethics approval for the study was obtained from the Human Research Ethics Committee of the University of the Witwatersrand. Participants provided written consent to participate in the interviews and for the interviews to be audio-taped.

Results
Six themes were identified. These were: two separate programmes, problem-based learning and Garmins® (navigation system), see patients for real, being seen as doctors, assessment: of mice and MCQ’s, a cry for support and personal growth and pride. Participants were vocal in their reflections of experiences encountered during the programme and made several insightful suggestions for curriculum transformation. The findings suggest that graduates are exiting the programme confident and ready to begin their internships.

Conclusions
The findings of this study have identified a number of areas which need attention in the curriculum. Specifically attention needs to be given to ensuring that assessment is standardized; student support structures and appropriate levels of teaching. The study demonstrated the value of qualitative methods in obtaining students’ perceptions of a curriculum.
Computational synchronization of microarray data with application to Plasmodium falciparum
Authors: Zhao Wei , Dauwels Justin , Niles Jacquin C , Cao Jianshu 
Published: June 2012

AbstractBackgroundMicroarrays are widely used to investigate the blood stage ofPlasmodium falciparuminfection. Starting with synchronized cells, gene expression levels are continually measured over the 48-hour intra-erythrocytic cycle (IDC). However, the cell population gradually loses synchrony during the experiment. As a result, the microarray measurements are blurred. In this paper, we propose a generalized deconvolution approach to reconstruct the intrinsic expression pattern, and apply it toP. falciparumIDC microarray data.MethodsWe develop a statistical model for the decay of synchrony among cells, and reconstruct the expression pattern through statistical inference. The proposed method can handle microarray measurements with noise and missing data. The original gene expression patterns become more apparent in the reconstructed profiles, making it easier to analyze and interpret the data. We hypothesize that reconstructed gene expression patterns represent better temporally resolved expression profiles that can be probabilistically modeled to match changes in expression level to IDC transitions. In particular, we identify transcriptionally regulated protein kinases putatively involved in regulating theP. falciparumIDC.ResultsBy analyzing publicly available microarray data sets for theP. falciparumIDC, protein kinases are ranked in terms of their likelihood to be involved in regulating transitions between the ring, trophozoite and schizont developmental stages of theP. falciparumIDC. In our theoretical framework, a few protein kinases have high probability rankings, and could potentially be involved in regulating these developmental transitions.ConclusionsThis study proposes a new methodology for extracting intrinsic expression patterns from microarray data. By applying this method toP. falciparummicroarray data, several protein kinases are predicted to play a significant role in theP. falciparumIDC. Earlier experiments have indeed confirmed that several of these kinases are involved in this process. Overall, these results indicate that further functional analysis of these additional putative protein kinases may reveal new insights into how theP. falciparumIDC is regulated.
Ion annotation-assisted analysis of LC-MS based metabolomic experiment
Authors: Varghese Rency S , Zhou Bin , Nezami Ranjbar Mohammad R , Zhao Yi , Ressom Habtom W 
Published: June 2012

Abstract

Background
Analysis of multiple LC-MS based metabolomic studies is carried out to determine overlaps and differences among various experiments. For example, in large metabolic biomarker discovery studies involving hundreds of samples, it may be necessary to conduct multiple experiments, each involving a subset of the samples due to technical limitations. The ions selected from each experiment are analyzed to determine overlapping ions. One of the challenges in comparing the ion lists is the presence of a large number of derivative ions such as isotopes, adducts, and fragments. These derivative ions and the retention time drifts need to be taken into account during comparison.

Results
We implemented an ion annotation-assisted method to determine overlapping ions in the presence of derivative ions. Following this, each ion is represented by the monoisotopic mass of its cluster. This mass is then used to determine overlaps among the ions selected across multiple experiments.

Conclusion
The resulting ion list provides better coverage and more accurate identification of metabolites compared to the traditional method in which overlapping ions are selected on the basis of individual ion mass.