bluuebunny/crossref_metadata_2025_split huggingface dataset:
Number of Nevi and Early-Life Ambient UV Exposure Are Associated with BRAF-Mutant Melanoma
Authors: Thomas Nancy E. , Edmiston Sharon N. , Alexander Audrey , Millikan Robert C. , Groben Pamela A. , Hao Honglin , Tolbert Dawn , Berwick Marianne , Busam Klaus , Begg Colin B. , Mattingly Dianne , Ollila David W. , Tse Chiu Kit , Hummer Amanda , Lee-Taylor Julia , Conway Kathleen 
Published: May 2007

Abstract
Malignant melanomas often contain BRAF or NRAS mutations, but the relationship of these mutations to ambient UV exposure in combination with phenotypic characteristics is unknown. In a population-based case series from North Carolina, 214 first primary invasive melanoma patients in the year 2000 were interviewed regarding their risk factors. Ambient solar UV exposures were estimated using residential histories and a satellite-based model. Cases were grouped on the basis of BRAF and NRAS somatic mutations, determined using single-strand conformation polymorphism analysis and radiolabeled DNA sequencing, and the risk profiles of these groups were compared. Mutually exclusive BRAF-mutant and NRAS-mutant cases occurred at frequencies of 43.0% and 13.6% with mean ages at diagnosis of 47.3 and 62.1 years, respectively. Tumors from patients with &gt;14 back nevi were more likely to harbor either a BRAF mutation [age-adjusted odds ratio (OR), 3.2; 95% confidence interval (95% CI), 1.4-7.0] or an NRAS mutation (age-adjusted OR, 1.7; 95% CI, 0.6-4.8) compared with patients with 0 to 4 back nevi. However, BRAF-mutant and NRAS-mutant tumors were distinctive in that BRAF-mutant tumors were characteristic of patients with high early-life ambient UV exposure (adjusted OR, 2.6; 95% CI, 1.2-5.3). When ambient UV irradiance was analyzed by decadal age, high exposure at ages 0 to 20 years was associated with BRAF-mutant cases, whereas high exposure at ages 50 and 60 years was characteristic of NRAS-mutant cases. Our results suggest that although nevus propensity is important for the occurrence of both BRAF and NRAS-mutant melanomas, ambient UV irradiance influences risk differently based on the age of exposure. The association of BRAF mutations with early-life UV exposure provides evidence in support of childhood sun protection for melanoma prevention. (Cancer Epidemiol Biomarkers Prev 2007;16(5):991–7)
Serum Levels of Insulin-like Growth Factor-I and Insulin-like Growth Factor-I Binding Protein-3: Quality Control for Studies of Stored Serum
Authors: Berrigan David , Potischman Nancy , Dodd Kevin W. , Nicar Michael , McQuillan Geraldine , Lavigne Jackie A. , Barrett J. Carl , Ballard-Barbash Rachel 
Published: May 2007

AbstractThe insulin-like growth factor (IGF) axis, particularly IGF-I and IGF binding protein-3 (IGFBP-3), has been the subject of much attention because of its role in juvenile growth and their association with cancers at several sites. However, epidemiologic studies of IGF-I and IGFBP-3 have had mixed results and several authors have speculated that quality control (QC), sample storage history, and other methodologic concerns could play a role in this heterogeneity. This article documents the results of storage history and QC efforts for a study of IGF-I and IGFBP-3 in 6,226 serum samples from the National Health and Nutrition Examination Survey III (NHANES III). The study was carried out on site at Diagnostic Systems Laboratories in Webster, Texas, using the IGF-I ELISA (DSL 10-5600) and the IGFBP-3 immunoradiometric assay (DSL 6600). A run-in study of assay performance suggested that plates, days, and weeks significantly affected the variance of both assays. Analysis of samples with different storage histories also indicated strong effects of storage history. Serum samples disbursed to laboratories for measurement of diverse analytes and then returned for storage showed reductions in serum IGF-I level averaging 43% and reductions in IGFBP-3 of 25% compared with samples shipped immediately to the repository for long-term storage at −80°C. Therefore, the main study was carried out using samples that had been shipped directly to the National Center for Health Statistics/NHANES collection center for storage. Laboratory analyses of NHANES III and QC samples were carried out over ∼10 months. QC was monitored through repeated testing of blood samples from six individuals, with two individuals tested twice on each plate. Assay performance was stable over the entire study and coefficients of variation averaged 2% to 3% within plates and ∼14% for IGF-I and ∼11.5% for IGFBP-3 over the entire study. Coefficients of variation varied significantly among individual QC subjects, ranging from 12.3% to 17.6% for IGF-I and 8.9% to 12.8% for IGFBP-3. Based on Levy-Jennings plots, ∼5% of the plates used for IGF-I in the main study were out of compliance. Finally, location on a plate had small but significant effects on IGF-I level. Together, these results highlight the need for care in large studies of putative biomarkers for cancer risk and illustrate some probable sources of heterogeneity in past epidemiologic studies of the IGF axis and cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(5):1017–22)
Recurrent tuberculosis from 1992 to 2004 in a metropolitan area
Authors: Cacho J. , Pérez Meixeira A. , Cano I. , Soria T. , Ramos Martos A. , Sánchez Concheiro M. , Samper S. , Gavin P. , Martín C. 
Published: May 2007

The proportion of recurrent tuberculosis (TB) cases caused by re-infection has varied widely in previous studies. The aim of the present study was to determine the relative frequency of relapse and exogenous re-infection in patients with second episodes of TB, using DNA fingerprinting.A population-based retrospective longitudinal descriptive study was conducted in Madrid (Spain) during 1992–2004. The study consisted of 645 patients with culture-confirmed TB. Of these, 20 (3.1%) were retained because they presented with a second isolate ofMycobacterium tuberculosis. Finally, 12 of these cases were excluded because they did not complete the full treatment prescribed. All strains were typed by restriction fragment length polymorphism analysis and some by mycobacterial interspersed repetitive unit-variable number of tandem repeats analysis. The patients with recurrent TB were compared with those without recurrent TB.For seven out of the eight patients, the restriction fragment length polymorphism patterns of theMycobacterium tuberculosisstrains from the episodes of recurrent disease showed identical initial and final genotypes, indicating relapse; the remaining recurrent case showed different genotypes, suggesting exogenous re-infection.Re-infection is possible among people in developed countries, but the rates are lower than those occurring in high-risk areas. The risk factors for recurrent tuberculosis should be taken into account in the follow-up of treatment and tuberculosis control strategies.
Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis
Authors: Fridlender Z. G. , Cohen P. Y. , Golan O. , Arish N. , Wallach-Dayan S. , Breuer R. 
Published: May 2007

Epithelial cell injury and apoptosis are recognised as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosis-alleviating factor.The role of telomerase was studied during bleomycin-induced lung epithelial cell (LEC) apoptosisin vitroin a mouse LEC line, andin vivoin LECs isolated from bleomycin-treated mice.The current authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA levels and changes in telomerase activity with the TRAPeze Detection Kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain.There was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity 24 h afterin vitrobleomycin treatment. At 72 h, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted.In vivo, telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days.In conclusion, telomerase activity may play a protective role against robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.
Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD
Authors: Powrie D. J. , Wilkinson T. M. A. , Donaldson G. C. , Jones P. , Scrine K. , Viel K. , Kesten S. , Wedzicha J. A. 
Published: May 2007

Chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation. Tiotropium has been shown to reduce exacerbation frequency, but its effect on airway inflammation is unknown. The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency.Patients (n = 142) were randomised to receive tiotropium or placebo in addition to their usual medication for 1 yr. Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary.There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups, but sputum IL-8 level was increased in the tiotropium arm. There was no difference between start and end of study in serum IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction in exacerbation frequency (1.17versus2.46 exacerbations·yr−1). Of patients on tiotropium, 43% experienced at least one exacerbation, compared with 64% on placebo. The total number of exacerbation days was reduced compared with placebo (17.3versus34.5 days).Tiotropium reduces exacerbation frequency in chronic obstructive pulmonary disease, but this effect does not appear to be due to a reduction in airway or systemic inflammation.
Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion
Authors: Su C-F. , Liu D. D. , Kao S. J. , Chen H. I. 
Published: May 2007

Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung.I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-α and interleukin-1β in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue.Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg·kg−1body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression.The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.
Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD
Authors: Hill K. , Jenkins S. C. , Philippe D. L. , Shepherd K. L. , Hillman D. R. , Eastwood P. R. 
Published: May 2007

The aim of the present study was to determine the relative value of incremental and constant load tests in detecting changes in inspiratory muscle endurance following high-intensity inspiratory muscle training (H-IMT) in chronic obstructive pulmonary disease.In total, 16 subjects (11 males; forced expiratory volume in one second (FEV1) 37.4±12.5%) underwent H-IMT. In addition, 17 subjects (11 males; FEV136.5±11.5%) underwent sham inspiratory muscle training (S-IMT). Training took place three times a week for 8 weeks. Baseline and post-training measurements were obtained of maximum threshold pressure sustained during an incremental load test (Pth,max) and time breathing against a constant load (tlim). Breathing pattern was unconstrained.H-IMT increasedPth,maxandtlimrelative to baseline and to any change seen following S-IMT. The effect size forPth,maxwas greater than fortlim. Post-training tests were accompanied by changes in breathing pattern, including decreased duty cycle, which may have served to decrease inspiratory work and thereby contribute to the increase inPth,maxandtlimin both groups.When assessing inspiratory muscle function in chronic obstructive pulmonary diseaseviatests in which the pattern of breathing is unconstrained, the current authors recommend incremental load tests be used in preference to constant load tests. However, to attribute changes in these tests to improvements in inspiratory muscle endurance, breathing pattern should be controlled.
Cost-effectiveness of interferon-γ release assay testing for the treatment of latent tuberculosis
Authors: Diel R. , Wrighton-Smith P. , Zellweger J-P. 
Published: May 2007

The aim of the present study was to assess the cost-effectiveness of the new T-SPOT.TBassayversusthe tuberculin skin test (TST) for screening contacts for latent tuberculosis (TB) infection in Switzerland.Health and economic outcomes of isoniazid treatment of 20- and 40-yr-old close contacts were compared in a Markov model over a 20-yr period following screening with TST only (at three cut-off values) and T-SPOT.TBalone or in combination with the TST.T-SPOT.TB-based treatment was cost-effective at \#8342;11,621 and \#8342;23,692 per life-year-gained (LYG) in the younger and older age group, respectively. No TST-based programmes were cost-effective, except at a 15-mm cut-off in the younger group only, where the cost-effectiveness (\#8342;26,451·LYG−1) fell just below the willingness-to-pay threshold. Combination of the TST with T-SPOT.TBslightly reduced the total cost compared with the T-SPOT.TBalone by 4.4 and 5.0% in the younger and older groups respectively. The number of contacts treated to avoid one case of TB decreased from 50 (95% confidence interval 32–106) with the TST (10-mm cut-off) to 18 (95%CI 11–43) if T-SPOT.TBwas used.Using T-SPOT.TBalone or in combination with the tuberculin skin test for screening of close contacts before latent tuberculosis infection treatment is highly cost-effective in reducing the disease burden of tuberculosis.
Increased airway iron as a potential factor in the persistence ofPseudomonas aeruginosainfection in cystic fibrosis
Authors: Reid D. W. , Carroll V. , O'May C. , Champion A. , Kirov S. M. 
Published: May 2007

Iron availability is critical to many bacteria and increased iron has been described in airway secretions in cystic fibrosis (CF). The main aim of the present study was to assess the relationship between iron in CF sputum and the quantitative bacterial burden.Iron, ferritin and total cell counts (TCC) were assessed in sputum samples obtained from 15 clinically stable CF patients chronically infected withPseudomonas aeruginosa. Sputum samples were also obtained at the commencement of episodes of acute exacerbation in 10 subjects and analyses were repeated in six of these exacerbation cases afteri.v.antibiotic treatment. The relationship between iron indices and the presence ofP. aeruginosa, as well as total anaerobic bacterial load, was determined. Sputum was also obtained from 10 CF patients with no evidence of infection withP. aeruginosaand 11 normal healthy controls.Sputum iron, ferritin and TCC were significantly elevated in all CF patients, even in those not infected withP. aeruginosa, compared with healthy controls. There was a strong positive relationship between sputum iron andP. aeruginosain clinically stable patients, but not in samples obtained during an acute exacerbation. There was no relationship between sputum iron and anaerobic bacterial load. Antibiotic treatment significantly reduced sputum TCC and anaerobic bacterial load, but not iron, ferritin or the presence ofP. aeruginosaduring an exacerbation.In conclusion, the present study suggests that increased airway iron may be important toPseudomonas aeruginosapersistence in cystic fibrosis.
Ventilator-associated pneumonia due to colistin susceptible-only microorganisms
Authors: Rios F. G. , Luna C. M. , Maskin B. , Valiente A. Saenz. , Lloria M. , Gando S. , Sosa C. , Baquero S. , Llerena C. , Petrati C. , Apezteguia C. 
Published: May 2007

Acinetobacter spp. andPseudomonas aeruginosaare common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. andP. aeruginosasusceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units.A total of 61 episodes of VAP caused by Acinetobacter spp. orP. aeruginosawere studied, of which 30 isolates were Carb-S and 31 were Col-S.Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy.Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.
Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal
Authors: Greber Boris , Lehrach Hans , Adjaye James 
Published: May 2007

Abstract

Background
Despite their distinct origins, human embryonic stem (hES) and embryonic carcinoma (hEC) cells share a number of similarities such as surface antigen expression, growth characteristics, the ability to either self-renew or differentiate, and control of the undifferentiated state by the same core transcription factors. To obtain further insights into the regulation of self-renewal, we have silenced hES/hEC cell-specific genes in NCCIT hEC cells and analysed the downstream effects by means of microarrays.

Results
RNAi-mediated silencing of OCT4 and SOX2 induced differentiation with mesodermal characteristics. Markers of trophoblast induction were only transiently up-regulated in the OCT4 knock-down. Independent knock-downs of NANOG produced a proliferation rather than a differentiation phenotype, which may be due to high NANOG expression levels in the cell line used. Published ChIP-chip data from hES cells were used to identify putative direct targets. RNAi-mediated differentiation was accompanied by direct down-regulation of known hES/hEC cell markers. This included all three core transcription factors in the case of the OCT4 and SOX2 knock-downs, confirming previous findings of reciprocal activation in ES cells. Furthermore, large numbers of histone genes as well as epigenetic regulators were differentially expressed, pointing at chromatin remodeling as an additional regulatory level in the differentiation process. Moreover, loss of self-renewal was accompanied by the down-regulation of genes involved in FGF signaling. FGF receptor inhibition for short and prolonged periods of time revealed that the ERK/MAPK cascade is activated by endogenously expressed fibroblast growth factors and that FGF signaling is cruicial for maintaining the undifferentiated state of hEC cells, like in hES cells.

Conclusion
Control of self-renewal appears to be very similar in hEC and hES cells. This is supported by large numbers of common transcription factor targets and the requirement for autocrine FGF signaling.
A mechanism for the sharp transition of morphogen gradient interpretation in Xenopus
Authors: Saka Yasushi , Smith James C 
Published: May 2007

Abstract
Background
One way in which positional information is established during embryonic development is through the graded distribution of diffusible morphogens. Unfortunately, little is known about how cells interpret different concentrations of morphogen to activate different genes or how thresholds are generated in a morphogen gradient.

Results
Here we show that the concentration-dependent induction of the T-box transcription factor Brachyury (Xbra) and the homeobox-containing gene Goosecoid (Gsc) by activin in Xenopus can be explained by the dynamics of a simple network consisting of three elements with a mutual negative feedback motif that can function to convert a graded signal (activin) into a binary output (Xbra on and Gsc off, or vice versa). Importantly, such a system can display sharp thresholds. Consistent with the predictions of our model, Xenopus ectodermal cells display a binary response at the single cell level after treatment with activin.

Conclusion
This kind of simple network with mutual negative feedback might provide a general mechanism for selective gene activation in response to different levels of a single external signal. It provides a mechanism by which a sharp boundary might be created between domains of different cell types in response to a morphogen gradient.