bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis
Authors: Yu Yiting , Kim H Stanley , Chua Hui Hoon , Lin Chi Ho , Sim Siew Hoon , Lin Daoxun , Derr Alan , Engels Reinhard , DeShazer David , Birren Bruce , Nierman William C , Tan Patrick 
Published: May 2006

Abstract

Background
The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 and B. thailandensis (Bt) E264, a closely related but avirulent relative.

Results
We found the Bp and Bt genomes to be broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands, which we experimentally validated to be differentially present in multiple Bt isolates. By examining species-specific genomic regions, we derived molecular explanations for previously-known metabolic differences, discovered potentially new ones, and found that the acquisition of a capsular polysaccharide gene cluster in Bp, a key virulence component, is likely to have occurred non-randomly via replacement of an ancestral polysaccharide cluster. Virulence related genes, in particular members of the Type III secretion needle complex, were collectively more divergent between Bp and Bt compared to the rest of the genome, possibly contributing towards the ability of Bp to infect mammalian hosts. An analysis of pseudogenes between the two species revealed that protein inactivation events were significantly biased towards membrane-associated proteins in Bt and transcription factors in Bp.

Conclusion
Our results suggest that a limited number of horizontal-acquisition events, coupled with the fine-scale functional modulation of existing proteins, are likely to be the major drivers underlying Bp virulence. The extensive genomic similarity between Bp and Bt suggests that, in some cases, Bt could be used as a possible model system for studying certain aspects of Bp behavior.
Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses
Authors: Adams Vera J , Markus Miles B , Kwitshana Zilungile L , Dhansay Muhammad A , van der Merwe Lize , Walzl Gerhard , Fincham John E 
Published: May 2006

Abstract

Background
Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs.

Methods
Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons.

Results
In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas.

Conclusion
There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.
Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation
Authors: Zhang Zhuangyu , Machac Josef , Helft Gerard , Worthley Stephen G , Tang Cheuk , Zaman Azfar G , Rodriguez Oswaldo J , Buchsbaum Monte S , Fuster Valentin , Badimon Juan J 
Published: May 2006

Abstract

Background
Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model.

Methods
Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta.

Results
Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity.

Conclusion
PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.
Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease
Authors: Fahim Magid M , Haji Shamim , Koonapareddy Chakravarthy V , Fan Vincent C , Asbell Penny A 
Published: May 2006

Abstract

Background
Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients.

Methods
Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master (TradeMark). Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls.

Results
Ten minutes after fluorescein installition, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 ± 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 ± 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 ± 52.83 ng/ml) compared with that of controls (mean = 40.64 ± 7.96 ng/ml), averaging a three-fold increase.

Conclusion
Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.
The air quality impacts of road closures associated with the 2004 Democratic National Convention in Boston
Authors: Levy Jonathan I , Baxter Lisa K , Clougherty Jane 
Published: May 2006

Abstract

Background
The Democratic National Convention (DNC) in Boston, Massachusetts in 2004 provided an opportunity to evaluate the impacts of a localized and short-term but potentially significant change in traffic patterns on air quality, and to determine the optimal monitoring approach to address events of this nature. It was anticipated that the road closures associated with the DNC would both influence the overall air pollution level and the distribution of concentrations across the city, through shifts in traffic patterns.

Methods
To capture these effects, we placed passive nitrogen dioxide badges at 40 sites around metropolitan Boston before, during, and after the DNC, with the goal of capturing the array of hypothesized impacts. In addition, we continuously measured elemental carbon at three sites, and gathered continuous air pollution data from US EPA fixed-site monitors and traffic count data from the Massachusetts Highway Department.

Results
There were significant reductions in traffic volume on the highway with closures north of Boston, with relatively little change along other highways, indicating a more isolated traffic reduction rather than an across-the-board decrease. For our nitrogen dioxide samples, while there was a relatively small change in mean concentrations, there was significant heterogeneity across sites, which corresponded with our a priori classifications of road segments. The median ratio of nitrogen dioxide concentrations during the DNC relative to non-DNC sampling periods was 0.58 at sites with hypothesized traffic reductions, versus 0.88 for sites with no changes hypothesized and 1.15 for sites with hypothesized traffic increases. Continuous monitors measured slightly lower concentrations of elemental carbon and nitrogen dioxide during road closure periods at monitors proximate to closed highway segments, but not for PM2.5 or further from major highways.

Conclusion
We conclude that there was a small but measurable influence of DNC-related road closures on air quality patterns in the Boston area, and that a low-cost monitoring study combining passive badges for spatial heterogeneity and continuous monitors for temporal heterogeneity can provide useful insight for community air quality assessments.
Exposure assessment in investigations of waterborne illness: a quantitative estimate of measurement error
Authors: Jones Andria Q , Dewey Catherine E , Doré Kathryn , Majowicz Shannon E , McEwen Scott A , Waltner-Toews David 
Published: May 2006

Abstract
Background
Exposure assessment is typically the greatest weakness of epidemiologic studies of disinfection by-products (DBPs) in drinking water, which largely stems from the difficulty in obtaining accurate data on individual-level water consumption patterns and activity. Thus, surrogate measures for such waterborne exposures are commonly used. Little attention however, has been directed towards formal validation of these measures.

Methods
We conducted a study in the City of Hamilton, Ontario (Canada) in 2001–2002, to assess the accuracy of two surrogate measures of home water source: (a) urban/rural status as assigned using residential postal codes, and (b) mapping of residential postal codes to municipal water systems within a Geographic Information System (GIS). We then assessed the accuracy of a commonly-used surrogate measure of an individual's actual drinking water source, namely, their home water source.

Results
The surrogates for home water source provided good classification of residents served by municipal water systems (approximately 98% predictive value), but did not perform well in classifying those served by private water systems (average: 63.5% predictive value). More importantly, we found that home water source was a poor surrogate measure of the individuals' actual drinking water source(s), being associated with high misclassification errors.

Conclusion
This study demonstrated substantial misclassification errors associated with a surrogate measure commonly used in studies of drinking water disinfection byproducts. Further, the limited accuracy of two surrogate measures of an individual's home water source heeds caution in their use in exposure classification methodology. While these surrogates are inexpensive and convenient, they should not be substituted for direct collection of accurate data pertaining to the subjects' waterborne disease exposure. In instances where such surrogates must be used, estimation of the misclassification and its subsequent effects are recommended for the interpretation and communication of results. Our results also lend support for further investigation into the quantification of the exposure misclassification associated with these surrogate measures, which would provide useful estimates for consideration in interpretation of waterborne disease studies.
Causal criteria and counterfactuals; nothing more (or less) than scientific common sense
Authors: Phillips Carl V , Goodman Karen J 
Published: May 2006

AbstractTwo persistent myths in epidemiology are that we can use a list of "causal criteria" to provide an algorithmic approach to inferring causation and that a modern "counterfactual model" can assist in the same endeavor. We argue that these are neither criteria nor a model, but that lists of causal considerations and formalizations of the counterfactual definition of causation are nevertheless useful tools for promoting scientific thinking. They set us on the path to the common sense of scientific inquiry, including testing hypotheses (really putting them to a test, not just calculating simplistic statistics), responding to the Duhem-Quine problem, and avoiding many common errors. Austin Bradford Hill's famous considerations are thus both over-interpreted by those who would use them as criteria and under-appreciated by those who dismiss them as flawed. Similarly, formalizations of counterfactuals are under-appreciated as lessons in basic scientific thinking. The need for lessons in scientific common sense is great in epidemiology, which is taught largely as an engineering discipline and practiced largely as technical tasks, making attention to core principles of scientific inquiry woefully rare.
Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats
Authors: Diaz Heijtz Rochellys , Castellanos F Xavier 
Published: May 2006

AbstractBackgroundMolecular genetic studies suggest the dopamine D1 receptor (D1R) may be implicated in attention-deficit/hyperactivity disorder (ADHD). As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue.MethodsWe investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg), on motor behaviour and expression of the plasticity-associated gene,c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR), the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived).ResultsSHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing) in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increasedc-fosmRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels ofc-fosmRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum) of SHR when compared to WKY rats.ConclusionThe present results suggest a potential alteration in D1R neurotransmission within the frontal-striatal circuitry of SHR involved in motor control. These findings extend our understanding of the molecular alterations in SHR, a heuristically useful model of ADHD.
Identifying Individuals at High Risk of Melanoma: A Practical Predictor of Absolute Risk
Authors: Fears Thomas R. , Guerry DuPont , Pfeiffer Ruth M. , Sagebiel Richard W. , Elder David E. , Halpern Allan , Holly Elizabeth A. , Hartge Patricia , Tucker Margaret A. 
Published: May 2006

Purpose We developed a model to estimate the 5-year absolute risk of melanoma to efficiently identify individuals at increased risk of melanoma for potential interventions. Patients and Methods We used data from a case-control study with 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia, PA and San Francisco, CA; matched controls were 945 patients from outpatient clinics with similar catchment areas. All participants underwent extensive interviews and skin examinations. We selected easily obtained clinical characteristics and responses to simple questions for study in order to develop sex-specific relative risk models. These models were combined with incidence and mortality rates by United States geographic areas to develop estimates of the absolute risk of developing melanoma within 5 years. Results Relative risk models yielded an attributable risk of 86% for men and 89% for women, using at most seven variables. Attributable risks did not vary by age, ultraviolet B flux or hours outdoors. The absolute individual risks varied widely, depending on age, other host characteristics, and geographic area. Individual absolute risk can be estimated using a program available online. Conclusion Our procedures allow for estimating the absolute risk of developing melanoma to assist in the identification of patients at high risk. Such high-risk individuals could undergo interventions including a complete skin examination, counseling to avoid sun exposures, regular self and professional surveillance, or participation in prevention trials. It is important to emphasize that these projections are not intended to identify current melanoma cases.
Sim1 Haploinsufficiency Impairs Melanocortin-Mediated Anorexia and Activation of Paraventricular Nucleus Neurons
Authors: Kublaoui Bassil M. , Holder J. Lloyd , Gemelli Terry , Zinn Andrew R. 
Published: May 2006

Abstract
Single-minded 1 (SIM1) is one of only six genes implicated in human monogenic obesity. Haploinsufficiency of this hypothalamic transcription factor is associated with hyperphagic obesity and increased linear growth in both humans and mice. Additionally, Sim1 heterozygous mice show enhanced hyperphagia and obesity in response to a high-fat diet. Thus the phenotype of Sim1 haploinsufficiency is similar to that of agouti yellow (Ay), and melanocortin 4 receptor (Mc4r) knockout mice, both of which are defective in hypothalamic melanocortin signaling. Sim1 and Mc4r are both expressed in the paraventricular nucleus (PVN). Here we report that Sim1 heterozygous mice, which have normal energy expenditure, are hyperphagic despite having elevated hypothalamic proopiomelanocortin (Pomc) expression. In response to the melanocortin agonist melanotan-2 (MTII) they exhibit a blunted suppression of feeding yet increase their energy expenditure normally. They also fail to activate PVN neurons in response to the drug at a dose that induces robust c-Fos expression in a subset of Sim1 PVN neurons in wild-type mice. The resistance to melanocortin signaling in Sim1 heterozygotes is not due to a reduced number of Sim1 neurons in the PVN. Hypothalamic Sim1 gene expression is induced by leptin and MTII treatment. Our results demonstrate that Sim1 heterozygotes are resistant to hypothalamic melanocortin signaling and suggest that Sim1-expressing PVN neurons regulate feeding, but not energy expenditure, in response to melanocortin signaling.