bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levels of knowledge and perceived understanding among participants in cancer clinical trials – factors related to the informed consent procedure
Authors: Bergenmar Mia , Johansson Hemming , Wilking Nils 
Published: November 2010

Background An informed consent from patients participating in cancer clinical trials is mandatory according to international and national guidelines and laws. Insufficient knowledge and understanding by trial participants have been reported in several studies. Purpose The aims of this study were to investigate factors of importance for knowledge and understanding about cancer clinical trials among trial participants. Methods All patients consenting to a phase II or III clinical trial during 1 year were invited ( n = 325). Data on knowledge and perceived understanding were collected by a questionnaire, Quality of Informed Consent. Results are based on data from 268 patients (82%). Associations between knowledge and perceived understanding as well as clinical, socio-economic factors, and factors related to the informed consent procedure were tested. Results In the multivariate analysis no statistically significant associations were found between knowledge and any of the factors. Patients who reported longer time for trial information before their decision to participate, those who found the decision easy to take, and patients who reported use of other information sources had statistically significant higher perceived understanding. No differences in mean scores for knowledge or perceived understanding were found for any of the clinical factors (age, gender, diagnostic group, trial phase), socio-economic factors (education, marital status), and the following factors related to the informed consent procedure; presence of relative or nurse at information about the trial or previous participation in clinical trials. Limitations No study specific questions were included due to the number of trials ( n = 35). Conclusion Strategies to increase patients’ knowledge needs to be elaborated in order to improve the fulfilment of the requirements of informed consent in participants in cancer clinical trials.
Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease
Authors: Brodlie M. , McKean M.C. , Johnson G.E. , Anderson A.E. , Hilkens C.M.U. , Fisher A.J. , Corris P.A. , Lordan J.L. , Ward C. 
Published: November 2010

Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells.Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs.Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p = 0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells·mm−1compared with 9 cells·mm−1basement membrane, p = 0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor.In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.
House dust mite extract downregulates C/EBPα in asthmatic bronchial smooth muscle cells
Authors: Miglino N. , Roth M. , Tamm M. , Borger P. 
Published: November 2010

Reduced translation ofCEBPAmRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients.Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([3H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory proteins of CCAAT/enhancer-binding protein (C/EBP)α in human BSM cells of healthy controls and asthmatic patients.HDM extract significantly increased IL-6 protein and proliferation of BSM cells of asthma patients only. HDM extract reduced the C/EBPα expression in BSM cells of asthma patients, which coincided with significantly increased levels of calreticulin (CRT) protein, an inhibitor ofCEBPAmRNA translation. HDM extract elicited both protease-dependent and -independent responses, which were mediatedviaprotease-activated receptor (PAR)2 and CRT, respectively.In conclusion, HDM extract reducedCEBPAmRNA translation, specifically in asthmatic BSM cells, and 1) upregulated CRT, 2) activated PAR2, and increased 3) IL-6 expression and 4) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodelling by a nonimmune cell-mediated mechanismviaa direct interaction with BSM cells. These findings may potentially explain several pathological features of this disease, in particular BSM cell hyperplasia.
Childhood diet and asthma and atopy at 8 years of age: the PIAMA birth cohort study
Authors: Willers S.M. , Wijga A.H. , Brunekreef B. , Scholtens S. , Postma D.S. , Kerkhof M. , de Jongste J.C. , Smit H.A. 
Published: November 2010

Diet may affect the development of asthma. We investigated whether asthma or atopy outcomes at 8 yrs of age were associated with long-term dietary exposure, and whether associations were different for consumption at early or later age.The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort enrolled 4,146 participants at baseline, who were followed up to 8 yrs of age. Dietary intakes of interest were fruit, vegetables, brown/wholemeal bread, fish, milk, butter and margarine. Associations between food intake at early (2–3 yrs) and later (7–8 yrs) age, and long-term intake, asthma and atopy at 8 yrs of age were calculated by logistic regression.Complete longitudinal dietary data for at least one of the food groups were available for 2,870 children. Fruit consumption at early age was associated with reduced asthma symptoms (OR per 1 consumption day per week increase 0.93, 95% CI 0.85–1.00). Long-term fruit intake was inversely associated with asthma symptoms (OR 0.90, 95% CI 0.82–0.99) and sensitisation to inhaled allergens (OR 0.90, 95% CI 0.82–0.99). We found no consistent associations between diet and outcomes for other foods.This study indicates no consistent effects of increased early or late consumption, or long-term intake of certain foods on asthma and atopy in 8-yr-olds, with a possible exception for fruit.
Normative data for lung function and exhaled nitric oxide in unsedated healthy infants
Authors: Fuchs O. , Latzin P. , Thamrin C. , Stern G. , Frischknecht P. , Singer F. , Kieninger E. , Proietti E. , Riedel T. , Frey U. 
Published: November 2010

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards.Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean±sdage of 5.1±0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow–volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5–10 acceptable interruption resistance (Rint) measurements.Acceptable measurements were obtained in ≤285 infants with high variability. Mean values were 7.48 mL·kg−1(95% limits of agreement 4.95–10.0 mL·kg−1) for tidal volume, 14.3 ppb (2.6–26.1 ppb) for eNO, 23.9 mL·kg−1(16.0–31.8 mL·kg−1) for functional residual capacity, 6.75 (5.63–7.87) for lung clearance index and 3.78 kPa·s·L−1(1.14–6.42 kPa·s·L−1) forRint. In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section.This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.
Improvements to previous algorithms to predict gene structure and isoform concentrations using Affymetrix Exon arrays
Authors: Anton Miguel A , Aramburu Ander , Rubio Angel 
Published: November 2010

Abstract

Background
Exon arrays provide a way to measure the expression of different isoforms of genes in an organism. Most of the procedures to deal with these arrays are focused on gene expression or on exon expression. Although the only biological analytes that can be properly assigned a concentration are transcripts, there are very few algorithms that focus on them. The reason is that previously developed summarization methods do not work well if applied to transcripts. In addition, gene structure prediction, i.e., the correspondence between probes and novel isoforms, is a field which is still unexplored.

Results
We have modified and adapted a previous algorithm to take advantage of the special characteristics of the Affymetrix exon arrays. The structure and concentration of transcripts -some of them possibly unknown- in microarray experiments were predicted using this algorithm. Simulations showed that the suggested modifications improved both specificity (SP) and sensitivity (ST) of the predictions. The algorithm was also applied to different real datasets showing its effectiveness and the concordance with PCR validated results.

Conclusions
The proposed algorithm shows a substantial improvement in the performance over the previous version. This improvement is mainly due to the exploitation of the redundancy of the Affymetrix exon arrays. An R-Package of SPACE with the updated algorithms have been developed and is freely available.
β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis
Authors: Mirando Anthony J , Maruyama Takamitsu , Fu Jiang , Yu Hsiao-Man Ivy , Hsu Wei 
Published: November 2010

Abstract

Background
Mouse genetic study has demonstrated that Axin2 is essential for calvarial development and disease. Haploid deficiency of β-catenin alleviates the calvarial phenotype caused by Axin2 deficiency. This loss-of-function study provides evidence for the requirement of β-catenin in exerting the downstream effects of Axin2.

Results
Here we utilize a gain-of-function analysis to further assess the role of β-catenin. A transgenic expression system permitting conditional activation of β-catenin in a spatiotemporal specific manner has been developed. Aberrant stimulation of β-catenin leads to increases in expansion of skeletogenic precursors and the enhancement of bone ossification reminiscent to the loss of Axin2. The constitutively active signal promotes specification of osteoprogenitors, but prevents their maturation into terminally differentiated osteoblasts, along the osteoblast lineage. However, the prevention does not interfere with bone synthesis, suggesting that mineralization occurs without the presence of mature osteoblasts. β-catenin signaling apparently plays a key role in suture development through modulation of calvarial morphogenetic signaling pathways. Furthermore, genetic inactivation of the β-catenin transcriptional target, cyclin D1, impairs expansion of the skeletogenic precursors contributing to deficiencies in calvarial ossification. There is a specific requirement for cyclin D1 in populating osteoprogenitor cell types at various developmental stages.

Conclusion
These findings advance our knowledge base of Wnt signaling in calvarial morphogenesis, suggesting a key regulatory pathway of Axin2/β-catenin/cyclin D1 in development of the suture mesenchyme.
No evidence for increased extinction proneness with decreasing effective population size in a parasitoid with complementary sex determination and fertile diploid males
Authors: Elias Jan , Dorn Silvia , Mazzi Dominique 
Published: November 2010

Abstract

Background
In species with single locus complementary sex determination (sl-CSD), the sex of individuals depends on their genotype at one single locus with multiple alleles. Haploid individuals are always males. Diploid individuals are females when heterozygous, but males when homozygous at the sex-determining locus. Diploid males are typically unviable or effectively sterile, hence imposing a genetic load on populations. Diploid males are produced from matings of partners that share an allele at the sex-determining locus. The lower the allelic diversity at the sex-determining locus, the more diploid males are produced, ultimately impairing the growth of populations and jeopardizing their persistence. The gregarious endoparasitoid wasp Cotesia glomerata is one of only two known species with sl-CSD and fertile diploid males.

Results
By manipulating the relatedness of the founders, we established replicated experimental populations of the parasitoid C. glomerata differing in their genetic effective size, and thus in allelic richness at the sex-determining locus and in the expected magnitude of diploid male production. Our long-term survey of population welfare and persistence did not provide evidence for increased proneness to population extinction with decreasing initial genetic effective population size. Most recorded surrogates of fitness nevertheless decayed over time and most experimental populations eventually went extinct, suggesting that the negative effects of inbreeding outweighed any premium from the fertility of diploid males.

Conclusions
The fertility of diploid males may have evolved as an adaptation prompted by the risk of extinction looming over small isolated populations of species with sl-CSD. However, fertility of diploid males does not negate the costs imposed by their production, and although it may temporarily stave off extinction, it is not sufficient to eradicate the negative effects of inbreeding.
The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa
Authors: Ioerger Thomas R , Feng Yicheng , Chen Xiaohua , Dobos Karen M , Victor Thomas C , Streicher Elizabeth M , Warren Robin M , Gey van Pittius Nicolaas C , Van Helden Paul D , Sacchettini James C 
Published: November 2010

AbstractBackgroundThe Beijing genotype ofM. tuberculosisis a virulent strain that is disseminating worldwide and has a strong association with drug resistance. In the Western Cape of South Africa, epidemiological studies have identified the R220 cluster of the Beijing genotype as a major contributor to a recent outbreak of drug-resistant tuberculosis. Although the outbreak is considered to be due to clonal transmission, the relationship among drug resistant isolates has not yet been established.ResultsTo better understand the evolution of drug resistance among these strains, 14 drug-resistant clinical isolates of the Beijing genotype were sequenced by whole-genome sequencing, including eight from R220 and six from a more ancestral Beijing cluster, R86, for comparison. While each cluster shares a distinct resistance mutation for isoniazid, mapping of other drug-resistance mutations onto a phylogenetic tree constructed from single nucleotide polymorphisms shows that resistance mutations to many drugs have arisen multiple times independently within each cluster of isolates. Thus, drug resistance among these isolates appears to be acquired, not clonally derived. This observation suggests that, although the Beijing genotype as a whole might have selective advantages enabling its rapid dissemination, the XDR isolates are relatively less fit and do not propagate well. Although it has been hypothesized that the increased frequency of drug resistance in some Beijing lineages might be caused by a mutator phenotype, no significant shift in synonymous substitution patterns is observed in the genomes.ConclusionWhile MDR-TB is spreading by transmission in the Western Cape, our data suggests that further drug resistance (i.e. XDR-TB) at this stage is acquired.
Characterization of JG024, a pseudomonas aeruginosa PB1-like broad host range phage under simulated infection conditions
Authors: Garbe Julia , Wesche Andrea , Bunk Boyke , Kazmierczak Marlon , Selezska Katherina , Rohde Christine , Sikorski Johannes , Rohde Manfred , Jahn Dieter , Schobert Max 
Published: November 2010

Abstract

Background

Pseudomonas aeruginosa causes lung infections in patients suffering from the genetic disorder Cystic Fibrosis (CF). Once a chronic lung infection is established, P. aeruginosa cannot be eradicated by antibiotic treatment. Phage therapy is an alternative to treat these chronic P. aeruginosa infections. However, little is known about the factors which influence phage infection of P. aeruginosa under infection conditions and suitable broad host range phages.

Results
We isolated and characterized a phage, named JG024, which infects a broad range of clinical and environmental P. aeruginosa strains. Sequencing of the phage genome revealed that the phage JG024 is highly related to the ubiquitous and conserved PB1-like phages. The receptor of phage JG024 was determined as lipopolysaccharide. We used an artificial sputum medium to study phage infection under conditions similar to a chronic lung infection. Alginate production was identified as a factor reducing phage infectivity.

Conclusions
Phage JG024 is a suitable broad host range phage which could be used in phage therapy. Phage infection experiments under simulated chronic lung infection conditions showed that alginate production reduces phage infection efficiency.
Predominant porB1A and porB1B genotypes and correlation of gene mutations with drug resistance in Neisseria gonorrhoeae isolates in Eastern China
Authors: Sun Aihua , Fan Xingli , Gu Ye , Du Peng , Tang Renxian , Mao Yafei , Lin Xuai , Yan Jie 
Published: November 2010

Abstract

Background
Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance.

Methods
The β-lactamase production of N. gonorrhoeae isolates was determined by paper acidometric test and nitrocefin discs. The porB1A and porB1B genes of 315 non-penicillinase-producting N. gonorrhoeae (non-PPNG) strains were amplified by PCR for sequencing to determine serotypes and site mutations. A duplex PCR was designed to simultaneously detect both porB1A and porB1B genes. Penicillin and tetracycline resistance was assessed by an in vitro drug sensitivity test.

Results
Of the N. gonorrhoeae isolates, 31.1% tested positive for porB1A and 68.9% for porB1B genes. All the 98 porB1A
+ isolates belonging to IA6 serotype with either no mutation at the 120 and 121 sites (88.8%) or a D120G (11.2%) mutation and were no resistance to both penicillin and tetracycline. Among the 217 porB1B
+ isolates, 26.7%, 22.6% and 11.5% belonged to IB3, IB3/6 and IB4 serotypes, respectively. Particularly, two novel chimeric serotypes, IB3/6-IB2 and IB2-IB4-IB2, were found in 77 and 8 porB1B
+ isolates. Two hundred and twelve (97.7%) of the porB1B
+ isolates were presented G120 and/or A121 mutations with 163 (76.9%) at both sites. Interestingly, within the 77 porB1B
+ isolates belonging to IB3/6-IB2 serotype, 15 were discovered to possess novel deletions at both A121 and N122 sites. All the replacement mutations at these sites in PorB1B were correlated with resistance and the deletion mutation showed the highest resistance.

Conclusion

N. gonorrhoeae isolates circulating in Eastern China include a sole PorB1A serotype (IA6) and five PorB1B serotypes. Multiple mutations in porB1B genes, including novel A121 and N122 deletions, are correlated with high levels of penicillin and tetracycline resistance.
Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study
Authors: Zhang Donghong , Zhang Qingying , Zhou Li , Huo Leijun , Zhang Yi , Shen Zhongying , Zhu Yi 
Published: November 2010

Abstract

Background
Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain.

Methods
Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining.

Results
The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027).

Conclusions
High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.
Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol
Authors: Habl Gregor , Jensen Alexandra D , Potthoff Karin , Uhl Matthias , Hof Holger , Hajda Jacek , Simon Christian , Debus Jürgen , Krempien Robert , Münter Marc W 
Published: November 2010

Abstract

Background
Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation therapy (RT) is carried out as intensity-modulated RT (IMRT) to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues.

Methods/Design
The REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU) and the monoclonal epidermal growth factor-receptor (EGFR) antibody cetuximab (Erbitux®) as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx.
Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16) to a total dose of 69,9 Gy.

Discussion
Primary endpoint of the trial is local-regional control (LRC). Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer.

Trial registration
ISRCTN87356938