bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life in patients with chronic obstructive pulmonary disease: the predictive validity of the BODE index
Authors: Medinas-Amorós M. , Alorda C. , Renom F. , Rubí M. , Centeno J. , Ferrer V. , Gorriz T. , Mas-Tous C. , Ramis F.
Published: February 2008

Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of mortality and morbility in the developed world. Patients with COPD experience a progressive deterioration of health-related quality of life (HRQOL). A new model of severity classification, the body mass index, bronchial obstruction, dyspnoea, exercise (BODE) index, has recently been proposed.

Objective: To evaluate the relationship between HRQOL and the BODE index, and the predictive ability of BODE on HRQOL measurements.

Methods: Two HRQOL questionnaires were administered, namely the Nottingham Health Profile (NHP) and St George's Respiratory Questionnaire (SGRQ), in a sample of 67 patients with severe COPD.

Results: Pearsonś correlation coefficient analysis shows a positive correlation between the BODE index and the total scores of the specific ( P < 0.001), and general HRQOL ( P < 0.001); the analysis shows a significant correlation between the BODE index and the subscales of symptoms, activity and impact of SGRQ ( P < 0.001) and the subscales energy and physical mobility of the NHP ( P < 0.001). The regression analysis shows that the BODE index is a significant predictor of HRQOL, explaining 46,1% of the total score of the SGRQ ( P < 0.001) and 14.8% of the total score of the NHP ( P < 0.001).

Conclusions: The BODE index is good at predicting the worsening of HRQOL in patients with severe COPD. Chronic Respiratory Disease 2008; 5: 7—11
Risk factors for increased need for intravenous antibiotics for pulmonary exacerbations in adult patients with cystic fibrosis
Authors: Jarad N. A. , Giles K.
Published: February 2008

Background: Pulmonary exacerbations (P Exs) are important in cystic fibrosis (CF). They are very common, and are associated with poor quality of life. P Exs are regarded as an important end point in clinical trials. Risk factors associated with increase in P Exs have not been examined at a large scale. This study investigates factors associated with P Exs in a large cohort of adolescent and adult patients.

Patients and methods: This is a cross-sectional study on data collected in the South and West Regions in England in 2002. Patients aged 16 years and over were included. Data on age, gender, FEV1, body mass index (BMI), infection with Pseudomonas aeruginosa (Pa) and on CF-related diabetes were included in the analysis. P Ex was defined as an episode treated with IV antibiotics. Forward stepwise multiple regression analysis was performed with the number of P Exs being the independent variable. The rest of the variables were considered to be the dependent variables.

Results: Data from 341 patients (194 female), mean age (SD), 24.9 (8.9) years were available. In 2002, a total of 599 P Exs were reported, median 1.00 range 0—16 P Exs. Using stepwise multiple regression analysis factors associated with increased number of P Exs were: infection with Pa ( t-value —5.0, P < 0.0001), FEV1, ( t-value —4.9, P < 0.0001) and diabetes mellitus, ( t-value —2.1, P = 0.04). Age, gender and BMI did not influence the annual number of exacerbations.

Conclusions: In this study, risk factors for P Exs were found to be as follows: growth of Pa in the sputum, reduced FEV1 and CF-related diabetes mellitus. Chronic Respiratory Disease 2008; 5: 29—33
Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease
Authors: Poulain M. , Doucet M. , Drapeau V. , Fournier G. , Tremblay A. , Poirier P. , Maltais F.
Published: February 2008

Background: Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD.

Methods: Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 ± 4.2 kg/m2] and normal weight group ( n = 12, BMI = 21.1 ± 2.6kg/m2). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured.

Results: Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume1: 51 ± 19% versus 31 ± 12% predicted, respectively, P < 0.01). The metabolic syndrome was diagnosed in 50% of overweight/obese patients and in none of the normal weight patients. TNF-α, IL-6 and leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight.

Conclusions: The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities. Chronic Respiratory Disease 2008; 5: 35—41
Efficacy of Closed Suction Drainage in Lower Limb Arterial Surgery: A Meta-Analysis of Published Clinical Trials
Authors: Karthikesalingam Alan , Walsh Stewart R. , Sadat Umar , Tang Tjun Y. , Koraen Linn , Varty Kevin
Published: February 2008

Background Suction drains are widely used in vascular surgery, despite the absence of specific evidence that they confer benefit to patients. There has been no systematic review of the available evidence, though drainage has been shown to confer no benefit, or indeed harm, across a variety of surgical disciplines. Accordingly, a systematic review and meta-analysis of the current evidence base for closed suction drainage following surgical lower limb revascularization was undertaken.

Methods Medline, Embase, trial registries, conference proceedings, and article reference lists were searched to identify randomized controlled trials of the use of surgical drains. The primary outcomes were wound infection, seroma/lymphocele formation, and hematoma formation. Pooled odds ratios were calculated for categorical outcomes.

Results Four trials containing 429 groin wounds were eligible for inclusion. There was no significant effect on wound infection, seroma/lymphocele formation, or hematoma formation.

Conclusion Our meta-analysis suggests that no benefit is conferred by wound drainage following lower limb revascularization. The practice incurs avoidable expense and should not be routinely used.
DDX3Y encodes a class I MHC–restricted H-Y antigen that is expressed in leukemic stem cells
Authors: Rosinski Kellie V. , Fujii Nobuharu , Mito Jeffrey K. , Koo Kevin K. W. , Xuereb Suzanne M. , Sala-Torra Olga , Gibbs James S. , Radich Jerald P. , Akatsuka Yoshiki , Van den Eynde Benoît J. , Riddell Stanley R. , Warren Edus H.
Published: February 2008

The Y chromosome encodes male-specific minor histocompatibility (H-Y) antigens that stimulate T- and B-lymphocyte responses after sex-mismatched allogeneic hematopoietic cell transplantation (HCT). A CD8+ cytotoxic T lymphocyte (CTL) clone that recognizes a novel HLA-B*2705–restricted H-Y antigen encoded by the DDX3Y gene was isolated from a male who had received a hematopoietic cell graft from his human leukocyte antigen (HLA)–identical sister. The antigenic peptide is a decamer that differs from the homologous DDX3X-encoded peptide at 4 positions. Expression of DDX3Y and of the H-Y epitope that it encodes was examined by quantitative polymerase chain reaction (PCR) and by CTL recognition assays. Expression of DDX3Y is detected in all myeloid and lymphoid leukemic cells that carry an intact Y chromosome. Moreover, the DDX3Y-encoded H-Y epitope is presented on the surface of both myeloid and lymphoid leukemic cells from male HLA-B*2705+ patients. DDX3Y-specific CTLs prevent engraftment of human acute leukemia in nonobese diabetic/severe combined immune deficient mice, demonstrating that the DDX3Y-encoded H-Y antigen is also expressed in leukemic stem cells. These results demonstrate that CD8+ T-cell responses against DDX3Y have the potential to contribute to graft-versus-leukemia (GVL) activity after female into male allogeneic HCT. This study is registered at http://clinicaltrials.gov as NCT00107354.
High-precision high-coverage functional inference from integrated data sources
Authors: Linghu Bolan , Snitkin Evan S , Holloway Dustin T , Gustafson Adam M , Xia Yu , DeLisi Charles
Published: February 2008

Background

Information obtained from diverse data sources can be combined in a principled manner using various machine learning methods to increase the reliability and range of knowledge about protein function. The result is a weighted functional linkage network (FLN) in which linked neighbors share at least one function with high probability. Precision is, however, low. Aiming to provide precise functional annotation for as many proteins as possible, we explore and propose a two-step framework for functional annotation (1) construction of a high-coverage and reliable FLN via machine learning techniques (2) development of a decision rule for the constructed FLN to optimize functional annotation.

Results

We first apply this framework to Saccharomyces cerevisiae. In the first step, we demonstrate that four commonly used machine learning methods, Linear SVM, Linear Discriminant Analysis, Naïve Bayes, and Neural Network, all combine heterogeneous data to produce reliable and high-coverage FLNs, in which the linkage weight more accurately estimates functional coupling of linked proteins than use individual data sources alone. In the second step, empirical tuning of an adjustable decision rule on the constructed FLN reveals that basing annotation on maximum edge weight results in the most precise annotation at high coverages. In particular at low coverage all rules evaluated perform comparably. At coverage above approximately 50%, however, they diverge rapidly. At full coverage, the maximum weight decision rule still has a precision of approximately 70%, whereas for other methods, precision ranges from a high of slightly more than 30%, down to 3%. In addition, a scoring scheme to estimate the precisions of individual predictions is also provided. Finally, tests of the robustness of the framework indicate that our framework can be successfully applied to less studied organisms.

Conclusion

We provide a general two-step function-annotation framework, and show that high coverage, high precision annotations can be achieved by constructing a high-coverage and reliable FLN via data integration followed by applying a maximum weight decision rule.
SciDBMaker: new software for computer-aided design of specialized biological databases
Authors: Hammami Riadh , Zouhir Abdelmajid , Naghmouchi Karim , Ben Hamida Jeannette , Fliss Ismail
Published: February 2008

Background

The exponential growth of research in molecular biology has brought concomitant proliferation of databases for stocking its findings. A variety of protein sequence databases exist. While all of these strive for completeness, the range of user interests is often beyond their scope. Large databases covering a broad range of domains tend to offer less detailed information than smaller, more specialized resources, often creating a need to combine data from many sources in order to obtain a complete picture. Scientific researchers are continually developing new specific databases to enhance their understanding of biological processes.

Description

In this article, we present the implementation of a new tool for protein data analysis. With its easy-to-use user interface, this software provides the opportunity to build more specialized protein databases from a universal protein sequence database such as Swiss-Prot. A family of proteins known as bacteriocins is analyzed as 'proof of concept'.

Conclusion

SciDBMaker is stand-alone software that allows the extraction of protein data from the Swiss-Prot database, sequence analysis comprising physicochemical profile calculations, homologous sequences search, multiple sequence alignments and the building of new and more specialized databases. It compiles information with relative ease, updates and compares various data relevant to a given protein family and could solve the problem of dispersed biological search results.
Annotation of expressed sequence tags for the East African cichlid fish Astatotilapia burtoni and evolutionary analyses of cichlid ORFs
Authors: Salzburger Walter , Renn Susan CP , Steinke Dirk , Braasch Ingo , Hofmann Hans A , Meyer Axel
Published: February 2008

Background

The cichlid fishes in general, and the exceptionally diverse East African haplochromine cichlids in particular, are famous examples of adaptive radiation and explosive speciation. Here we report the collection and annotation of more than 12,000 expressed sequence tags (ESTs) generated from three different cDNA libraries obtained from the East African haplochromine cichlid species Astatotilapia burtoni and Metriaclima zebra.

Results

We first annotated more than 12,000 newly generated cichlid ESTs using the Gene Ontology classification system. For evolutionary analyses, we combined these ESTs with all available sequence data for haplochromine cichlids, which resulted in a total of more than 45,000 ESTs. The ESTs represent a broad range of molecular functions and biological processes. We compared the haplochromine ESTs to sequence data from those available for other fish model systems such as pufferfish (Takifugu rubripes and Tetraodon nigroviridis), trout, and zebrafish. We characterized genes that show a faster or slower rate of base substitutions in haplochromine cichlids compared to other fish species, as this is indicative of a relaxed or reinforced selection regime. Four of these genes showed the signature of positive selection as revealed by calculating Ka/Ks ratios.

Conclusion

About 22% of the surveyed ESTs were found to have cichlid specific rate differences suggesting that these genes might play a role in lineage specific characteristics of cichlids. We also conclude that the four genes with a Ka/Ks ratio greater than one appear as good candidate genes for further work on the genetic basis of evolutionary success of haplochromine cichlid fishes.
A non-parametric meta-analysis approach for combining independent microarray datasets: application using two microarray datasets pertaining to chronic allograft nephropathy
Authors: Kong Xiangrong , Mas Valeria , Archer Kellie J
Published: February 2008

Background

With the popularity of DNA microarray technology, multiple groups of researchers have studied the gene expression of similar biological conditions. Different methods have been developed to integrate the results from various microarray studies, though most of them rely on distributional assumptions, such as the t-statistic based, mixed-effects model, or Bayesian model methods. However, often the sample size for each individual microarray experiment is small. Therefore, in this paper we present a non-parametric meta-analysis approach for combining data from independent microarray studies, and illustrate its application on two independent Affymetrix GeneChip studies that compared the gene expression of biopsies from kidney transplant recipients with chronic allograft nephropathy (CAN) to those with normal functioning allograft.

Results

The simulation study comparing the non-parametric meta-analysis approach to a commonly used t-statistic based approach shows that the non-parametric approach has better sensitivity and specificity. For the application on the two CAN studies, we identified 309 distinct genes that expressed differently in CAN. By applying Fisher's exact test to identify enriched KEGG pathways among those genes called differentially expressed, we found 6 KEGG pathways to be over-represented among the identified genes. We used the expression measurements of the identified genes as predictors to predict the class labels for 6 additional biopsy samples, and the predicted results all conformed to their pathologist diagnosed class labels.

Conclusion

We present a new approach for combining data from multiple independent microarray studies. This approach is non-parametric and does not rely on any distributional assumptions. The rationale behind the approach is logically intuitive and can be easily understood by researchers not having advanced training in statistics. Some of the identified genes and pathways have been reported to be relevant to renal diseases. Further study on the identified genes and pathways may lead to better understanding of CAN at the molecular level.
The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse
Authors: Eriksson Krister S , Zhang Shengwen , Lin Ling , Larivière Roxanne C , Julien Jean-Pierre , Mignot Emmanuel
Published: February 2008

Background

Peripherin, a type III neuronal intermediate filament, is widely expressed in neurons of the peripheral nervous system and in selected central nervous system hindbrain areas with projections towards peripheral structures, such as cranial nerves and spinal cord neurons. Peripherin appears to play a role in neurite elongation during development and axonal regeneration, but its exact function is not known. We noticed high peripherin expression in the posterior hypothalamus of mice, and decided to investigate further the exact location of expression and function of peripherin in the mouse posterior hypothalamus.

Results

In situ hybridization indicated expression of peripherin in neurons with a distribution reminiscent of the histaminergic neurons, with little signal in any other part of the forebrain. Immunocytochemical staining for histidine decarboxylase and peripherin revealed extensive colocalization, showing that peripherin is produced by histaminergic neurons in all parts of the tuberomammillary nucleus. We next used histamine immunostaining in peripherin knockout, overexpressing and wild type mice to study if altered peripherin expression affects these neurons, but could not detect any visible difference in the appearance of these neurons or their axons.

Peripherin knockout mice and heterozygotic littermates were used for measurement of locomotor activity, feeding, drinking, and energy expenditure. Both genotypes displayed diurnal rhythms with all the parameters higher during the dark period. The respiratory quotient, an indicator of the type of substrate being utilized, also exhibited a significant diurnal rhythm in both genotypes. The diurnal patterns and the average values of all the recorded parameters for 24 h, daytime and night time were not significantly different between the genotypes, however.

Conclusion

In conclusion, we have shown that peripherin is expressed in the tuberomammillary neurons of the mouse hypothalamus. Monitoring of locomotor activity, feeding, drinking, and energy expenditure in mice either lacking or overexpressing peripherin did not reveal any difference, so the significance of peripherin in these neurons remains to be determined. The complete overlap between histidine decarboxylase and peripherin, both the protein and its mRNA, renders peripherin a useful new marker for histaminergic neurons in the hypothalamus.
Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models
Authors: Shue Eveline H , Carson-Walter Eleanor B , Liu Yang , Winans Bethany N , Ali Zarina S , Chen Jun , Walter Kevin A
Published: February 2008

Background

Plasmalemmal vesicle associated protein-1 (PV-1) is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS) diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state.

Results

We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated.

Conclusion

Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.
Parental and infant characteristics and childhood leukemia in Minnesota
Authors: Johnson Kimberly J , Soler John T , Puumala Susan E , Ross Julie A , Spector Logan G
Published: February 2008

Background

Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL), few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology.

Methods

We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML) diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR) and 95% confidence intervals (CIs).

Results

Male sex (HR = 1.41, 95% CI 1.16–1.70), white race (HR = 2.32, 95% CI 1.13–4.76), and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70) increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47). Higher birth weights (>3798 grams) (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65), and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60) increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education.

Conclusion

We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.
Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping
Authors: Zaharieva Irina , Georgieva Lyudmila , Nikolov Ivan , Kirov George , Owen Michael J , O'Donovan Michael C , Toncheva Draga
Published: February 2008

Background

Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.

Methods

We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.

Results

Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within the SPRY4 gene.

Conclusion

Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.
Enhanced gene expression from retroviral vectors
Authors: Blø Magnus , Micklem David R , Lorens James B
Published: February 2008

Background

Retroviruses are widely used to transfer genes to mammalian cells efficiently and stably. However, genetic elements required for high-level gene expression are incompatible with standard systems. The retroviral RNA genome is produced by cellular transcription and post-transcriptional processing within packaging cells: Introns present in the retroviral genomic transcript are removed by splicing, while polyadenylation signals lead to the production of ineffective truncated genomes. Furthermore strong enhancer/promoters within the retroviral payload lead to detrimental competition with the retroviral enhancer/promoter.

Results

By exploiting a new method of producing the retroviral genome in vitro it is possible to produce infectious retroviral particles carrying a high-level expression cassette that completely prohibits production of infectious retroviral particles by conventional methods.

We produced an expression cassette comprising a strong enhancer/promoter, an optimised intron, the GFP open reading frame and a strong polyadenylation signal. This cassette was cloned into both a conventional MMLV retroviral vector and a vector designed to allow in vitro transcription of the retroviral genome by T7 RNA polymerase.

When the conventional retroviral vector was transfected into packaging cells, the expression cassette drove strong GFP expression, but no infectious retrovirus was produced. Introduction of the in vitro produced uncapped retroviral genomic transcript into the packaging cells did not lead to any detectable GFP expression. However, infectious retrovirus was easily recovered, and when used to infect target primary human cells led to very high GFP expression – up to 3.5 times greater than conventional retroviral LTR-driven expression.

Conclusion

Retroviral vectors carrying an optimized high-level expression cassette do not produce infectious virions when introduced into packaging cells by transfection of DNA. Infectious retrovirus carrying the same cassette is readily produced when packaging cells are transfected with in vitro transcribed retroviral genomic RNA. The applications of this technique are not limited to producing the higher levels of transgene expression demonstrated here. For example, novel reporters with alternatively spliced exon-intron configurations could readily be transduced into virtually any cell. Furthermore, because the in vitro transcripts are not translated within the packaging cells, retroviruses carrying genes lethal to the packaging cells can also be produced.
Quantitative urban classification for malaria epidemiology in sub-Saharan Africa
Authors: Siri Jose G , Lindblade Kim A , Rosen Daniel H , Onyango Bernard , Vulule John , Slutsker Laurence , Wilson Mark L
Published: February 2008

Background

Although sub-Saharan Africa (SSA) is rapidly urbanizing, the terms used to classify urban ecotypes are poorly defined in the context of malaria epidemiology. Lack of clear definitions may cause misclassification error, which likely decreases the accuracy of continent-wide estimates of malaria burden, limits the generalizability of urban malaria studies, and makes identification of high-risk areas for targeted interventions within cities more difficult. Accordingly, clustering techniques were applied to a set of urbanization- and malaria-related variables in Kisumu, Kenya, to produce a quantitative classification of the urban environment for malaria research.

Methods

Seven variables with a known or expected relationship with malaria in the context of urbanization were identified and measured at the census enumeration area (EA) level, using three sources: a) the results of a citywide knowledge, attitudes and practices (KAP) survey; b) a high-resolution multispectral satellite image; and c) national census data. Principal components analysis (PCA) was used to identify three factors explaining higher proportions of the combined variance than the original variables. A k-means clustering algorithm was applied to the EA-level factor scores to assign EAs to one of three categories: "urban," "peri-urban," or "semi-rural." The results were compared with classifications derived from two other approaches: a) administrative designation of urban/rural by the census or b) population density thresholds.

Results

Urban zones resulting from the clustering algorithm were more geographically coherent than those delineated by population density. Clustering distributed population more evenly among zones than either of the other methods and more accurately predicted variation in other variables related to urbanization, but not used for classification.

Conclusion

Effective urban malaria epidemiology and control would benefit from quantitative methods to identify and characterize urban areas. Cluster analysis techniques were used to classify Kisumu, Kenya, into levels of urbanization in a repeatable and unbiased manner, an approach that should permit more relevant comparisons among and within urban areas. To the extent that these divisions predict meaningful intra-urban differences in malaria epidemiology, they should inform targeted urban malaria interventions in cities across SSA.
Sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines
Authors: Fadlelmola Faisal M , Zhou Minglong , de Leeuw Ronald J , Dosanjh Nirpjit S , Harmer Karynn , Huntsman David , Lam Wan L , Banerjee Diponkar
Published: February 2008

Background

Hodgkin lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL), are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428) and ALCL cell lines (DEL and SR-786) in order to identify disease-associated gene copy number gains and losses.

Results

Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55%) were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45%) were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23.

Conclusion

This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3) in KMH2 and L428 (HL) and DEL (ALCL) cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and aggressive NHL, similar to those described in epithelial tumors.
NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols
Authors: Bratasz Anna , Selvendiran Karuppaiyah , Wasowicz Tomasz , Bobko Andrey , Khramtsov Valery V , Ignarro Louis J , Kuppusamy Periannan
Published: February 2008

Background

Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied.

Methods

NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies.

Results

Cells treated with NCX-4040 (25 μM) showed a significant reduction of cell viability (A2780 WT, 34.9 ± 8.7%; A2780 cDDP, 41.7 ± 7.6%; p < 0.05). Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 ± 11.8% versus NCX-4040+cisplatin, 26.4 ± 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 ± 4.4% versus NCX-4040+cisplatin, 56.4 ± 7.8%; p < 0.05), to cisplatin treatment. EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression.

Conclusion

The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.
A prospective study of decline in lung function in relation to welding emissions
Authors: Christensen Sigve W , Bonde Jens Peter , Omland Øyvind
Published: February 2008

Background

Numerous cross-sectional studies have reported reduced lung function among welders but limitations of exposure assessment and design preclude causal inference. The aim of this study was to investigate if long-term exposure to welding fume particulates accelerates the age-related decline in lung function.

Methods

Lung function was measured by spirometry in 1987 and 2004 among 68 steel welders and 32 non-welding production workers. The decline in forced expiratory volume (FEV1) was analysed in relation to cumulated exposure to fume particulates among welders during the follow-up period.

Results

Among smokers the decline in FEV1through follow-up period was in average 150 ml larger among welders than non-welders while the difference was negligible among non-smokers. The results did not reach statistical significance and within welders the decline in lung function was not related to the cumulated welding particulate exposure during follow-up period

Conclusion

Long-term exposure to welding emissions may accelerate the age-related decline of lung function but at exposure levels in the range of 1.5 to 6.5 mg/m3the average annual excess loss of FEV1is unlikely to exceed 25 ml in smokers and 10 ml in non-smokers.
Clinical implications of granulomatous inflammation detected by endobronchial ultrasound transbronchial needle aspiration in patients with suspected cancer recurrence in the mediastinum
Authors: Kennedy Marcus P , Jimenez Carlos A , Mhatre Ashwini D , Morice Rodolfo C , Eapen Georgie A
Published: February 2008

Background

Granulomatous inflammation has been previously reported in association with cancer. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a new minimally invasive test for investigating mediastinal lymphadenopathy. The identification of granulomatous inflammation by EBUS-TBNA and the clinical implications of such detection in a series of patients with previously treated cancer and new mediastinal lymphadenopathy has not previously been performed.

Methods

All 153 consecutive patients undergoing EBUS-TBNA in an academic cancer institution for suspected cancer in the mediastinum (mediastinal lymphadenopathy by CT imaging) were reviewed. Patients with non-caseating granuloma identified by EBUS-TBNA were included.

Results

EBUS-TBNA identified non-caseating granuloma in 17/153 (11%) patients. A subset of 8/153 (5.2%) had sarcoid like lymphadenopathy mimicking cancer recurrence (5/5 PET positive). Another 8/153 (5.2%) patients with new mediastinal lymphadenopathy and no prior history of cancer had a clinical syndrome consistent with sarcoidosis. One other patient with a history of breast cancer was diagnosed with non-tuberculous mycobacteria infection. No patient required mediastinoscopy and there were no complications.

Conclusion

In an academic cancer institute, at least 5% of patients undergoing EBUS-TBNA have sarcoid-like lymphadenopathy mimicking cancer recurrence. Further studies to define the precise etiology, natural history and prognosis of this phenomenon are warranted.
Reconstruction and analysis of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis
Authors: Goelzer Anne , Bekkal Brikci Fadia , Martin-Verstraete Isabelle , Noirot Philippe , Bessières Philippe , Aymerich Stéphane , Fromion Vincent
Published: February 2008

Background

Few genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation. In particular, the regulations involving metabolite pools are often neglected. However, metabolite pools link the metabolic to the genetic network through genetic regulations, including those involving effectors of transcription factors or riboswitches. Consequently, they play pivotal roles in the global organization of the genetic and metabolic regulatory networks.

Results

We report the manually curated reconstruction of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis (transcriptional, translational and post-translational regulations and modulation of enzymatic activities). We provide a systematic graphic representation of regulations of each metabolic pathway based on the central role of metabolites in regulation. We show that the complex regulatory network of B. subtilis can be decomposed as sets of locally regulated modules, which are coordinated by global regulators.

Conclusion

This work reveals the strong involvement of metabolite pools in the general regulation of the metabolic network. Breaking the metabolic network down into modules based on the control of metabolite pools reveals the functional organization of the genetic and metabolic regulatory networks of B. subtilis.
Pulmonary manifestations in a pediatric patient with ulcerative colitis: a case report
Authors: Carvalho Ryan S , Wilson Lindsay , Cuffari Carmen
Published: February 2008

Introduction

Although respiratory involvement has been described in patients with IBD, well-defined interstitial lung disease has not been reported, especially among children with ulcerative colitis.

Case presentation

Herein, we present a case of an adolescent female with ulcerative colitis and extra-intestinal complications involving the lungs that were effectively treated with anti-metabolite therapy.

Conclusion

Children with UC may manifest either interstitial or large airway pulmonary involvement. All children with suspected lung involvement should be screened for tuberculosis prior to starting immunosuppressive therapy.
Determinants of tracheostomy decannulation: an international survey
Authors: Stelfox Henry Thomas , Crimi Claudia , Berra Lorenzo , Noto Alberto , Schmidt Ulrich , Bigatello Luca M , Hess Dean
Published: February 2008

Background

Although tracheostomy is probably the most common surgical procedure performed on critically ill patients, it is unknown when a tracheostomy tube can be safely removed.

Methods

We performed a cross-sectional survey of physicians and respiratory therapists with expertise in the management of tracheostomized patients at 118 medical centers to characterize contemporary opinions about tracheostomy decannulation practice and to define factors that influence these practices.

Results

We surveyed 309 clinicians, of whom 225 responded (73%). Clinicians rated patient level of consciousness, ability to tolerate tracheostomy tube capping, cough effectiveness, and secretions as the most important factors in the decision to decannulate a patient. Decannulation failure was defined as the need to reinsert an artificial airway within 48 hours (45% of respondents) to 96 hours (20% of respondents) of tracheostomy removal, and 2% to 5% was the most frequent recommendation for an acceptable recannulation rate (44% of respondents). In clinical scenarios, clinicians who worked in chronic care facilities (30%) were less likely to recommend decannulation than clinicians who worked in weaning (47%), rehabilitation (53%), or acute care (55%) facilities (p = 0.015). Patients were most likely to be recommended for decannulation if they were alert and interactive (odds ratio [OR] 4.76, 95% confidence interval [CI] 3.27 to 6.90; p < 0.001), had a strong cough (OR 3.84, 95% CI 2.66 to 5.54; p < 0.001), had scant thin secretions (OR 2.23, 95% CI 1.56 to 3.19; p < 0.001), and required minimal supplemental oxygen (OR 2.04, 95% CI 1.45 to 2.86; p < 0.001).

Conclusion

Patient level of consciousness, cough effectiveness, secretions, and oxygenation are important determinants of clinicians' tracheostomy decannulation opinions. Most surveyed clinicians defined decannulation failure as the need to reinsert an artificial airway within 48 to 96 hours of planned tracheostomy removal.
Copulsing tumor antigen-pulsed dendritic cells with zoledronate efficiently enhance the expansion of tumor antigen-specific CD8+ T cells via Vγ9γδ T cell activation
Authors: Takahara Masashi , Miyai Manami , Tomiyama Mai , Mutou Masato , Nicol Andrew J , Nieda Mie
Published: February 2008

We demonstrate that Vγ9γδ T cells activated by zoledronate can link innate and acquired immunity through crosstalk with dendritic cells (DCs) in a way that can amplify activation and proliferation of tumor antigen-specific CD8+ T cells. DCs pulsed with antigen alone or antigen plus zoledronate were used to stimulate the in vitro expansion of antigen-specific CD8+ T cells. MART-1-modified peptide (A27L peptide) and apoptotic HLA-A∗0201-positive, MART-1-positive JCOCB tumor cell lines were used as tumor antigen sources. The percentage of A27L-specific CD8+ T cells within the responding lymphocytes on Day 7 when immature DCs (imDCs) were cultured in the presence of A27L peptide and 0.01 μM zoledronate was significantly higher (P=0.002, n=11) than that observed when imDCs were cultured with the lymphocytes in the presence of the A27L peptide alone. This enhancing effect of zoledronate was significantly reduced when γδ T cells were depleted from responding lymphocytes (P=0.030, n=5), indicating that the effect is mediated mainly through Vγ9γδ T cells activated by zoledronate-pulsed imDCs. When imDCs copulsed with zoledronate and apoptotic JCOCB tumor cell lines were used, the percentage of A27L-specific CD8+ T cells was higher than that observed using imDCs with the apoptotic JCOCB lines alone, suggesting that zoledronate treatment of imDCs enhances the cross-presentation ability of DCs. These findings suggest a potentially valuable role for Vγ9γδ T cell activation for expanding antigen-specific CD8+T cells using DCs copulsed with tumor antigen and zoledronate in the design of vaccine therapies for malignancy.
Sensing danger—Hsp72 and HMGB1 as candidate signals
Authors: Williams John H H , Ireland H Elyse
Published: February 2008

Molecules that behave as danger signals are produced when the body is perceived to be under attack, and they alert the immune system to the problem. The immune system can then mount an appropriate response. Two molecules that have received attention as potential danger signals are heat shock protein 72 (Hsp72) and high mobility group box 1 (HMGB1), which are intracellular proteins but are released when cells are under stress, in particular, when necrosis occurs. This review considers the similarities between these two molecules and then contrasts their mechanism of action and problems that can arise when they are overpresented in the extracellular environment. It is proposed that Hsp72 and HMGB1 are members of a suite of danger molecules that provide a fingerprint of the threat, or stressor, to tissue or organism integrity.
Cigarette smoke stimulates the production of chemokines in mast cells
Authors: Mortaz Esmaeil , Redegeld Frank A , Sarir Hadi , Karimi Khalil , Raats Danielle , Nijkamp Frans P , Folkerts Gert
Published: February 2008

Chronic obstructive pulmonary disease is a major health problem and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular, cigarette smoke (CS), causes the progressive airflow limitation, in which macrophages and neutrophils are attracted by chemokines, leading to oxidative stress, emphysema, small airways fibrosis, and mucus hypersecretion. Smoking is also associated with an increase in mast cell numbers in bronchial mucosa. This study was conducted to determine the direct effects of CS on mast cell function, using murine bone marrow-derived mast cells (BMMC) as an in vitro model. BMMC were cultured from BALB/cBy mice for 3 weeks. Cells were treated with CS medium (CSM) for 30 min or 16 h. The effects of CSM on mast cell degranulation and chemokine production were measured. Moreover, we investigated the effect of CSM on IκB-α degradation and p38, Erk1/2, p65, and CREB expression by Western blotting. We found that CSM stimulated the release of chemokines in a noncytotoxic manner but did not induce mast cell degranulation. CSM induced phosphorylation of Erk1/2, p38, and CREB and increased translocation of p65 without degradation of IκB-α NF-κB in mast cells. The induction of chemokine production by CSM in mast cells could promote and prolong the inflammatory process. Our observations suggest that mast cells may contribute to the pathogenesis of emphysema through a direct effect of CS on the production of proinflammatory chemokines.
The Sounds of Black Laughter and the Harlem Renaissance: Claude McKay, Sterling Brown, Langston Hughes
Authors: Chasar Mike
Published: February 2008

In the first three decades of the twentieth century, a new and modern type of African American laughter was increasingly and aggressively sounded in the sonic landscape of the United States. Praised by poet Helene Johnson as an “arrogant and bold” laugh that did not synchronize with the acoustics of white power, this laughter also found a significant place in the poetry of Claude McKay, Sterling Brown, and Langston Hughes. In what Emily Thompson has called an “increasingly `sound-conscious'” era, these poets registered and analyzed the emergence of this new, combative black laugh and recognized that, in many cases, it could go where the physical black body could not and thus could uniquely challenge white control of public space while also mapping that space as a field for further political action.