bluuebunny/crossref_metadata_2025_split huggingface dataset:
The epidemiology of travel-related Salmonella Enteritidis in Ontario, Canada, 2010–2011
Authors: Tighe Mary-Kathryn , Savage Rachel , Vrbova Linda , Toolan Miriam , Whitfield Yvonne , Varga Csaba , Lee Brenda , Allen Vanessa , Maki Anne , Walton Ryan , Johnson Caitlin , Dhar Badal , Ahmed Rafiq , Crowcroft Natasha S , Middleton Dean 
Published: April 2012

Abstract

Background
Increases in the number of salmonellosis cases due to Salmonella Enteritidis (SE) in 2010 and 2011 prompted a public health investigation in Ontario, Canada. In this report, we describe the current epidemiology of travel-related (TR) SE, compare demographics, symptoms and phage types (PTs) of TR and domestically-acquired (DA) cases, and estimate the odds of acquiring SE by region of the world visited.

Methods
All incident cases of culture confirmed SE in Ontario obtained from isolates and specimens submitted to public health laboratories were included in this study. Demographic and illness characteristics of TR and DA cases were compared. A national travel survey was used to provide estimates for the number of travellers to various destinations to approximate rates of SE in travellers. Multivariate logistic regression was used to estimate the odds of acquiring SE when travelling to various world regions.

Results
Overall, 51.9% of SE cases were TR during the study period. This ranged from 35.7% TR cases in the summer travel period to 65.1% TR cases in the winter travel period. Compared to DA cases, TR cases were older and were less likely to seek hospital care. For Ontario travellers, the adjusted odds of acquiring SE was the highest for the Caribbean (OR 37.29, 95% CI 17.87-77.82) when compared to Europe. Certain PTs were more commonly associated with travel (e.g., 1, 4, 5b, 7a, Atypical) than with domestic infection. Of the TR cases, 88.9% were associated with travel to the Caribbean and Mexico region, of whom 90.1% reported staying on a resort. Within this region, there were distinct associations between PTs and countries.

Conclusions
There is a large burden of TR illness from SE in Ontario. Accurate classification of cases by travel history is important to better understand the source of infections. The findings emphasize the need to make travellers, especially to the Caribbean, and health professionals who provide advice to travellers, aware of this risk. The findings may be generalized to other jurisdictions with travel behaviours in their residents similar to Ontario residents.
Exploring functionally related enzymes using radially distributed properties of active sites around the reacting points of bound ligands
Authors: Ueno Keisuke , Mineta Katsuhiko , Ito Kimihito , Endo Toshinori 
Published: April 2012

Abstract

Background
Structural genomics approaches, particularly those solving the 3D structures of many proteins with unknown functions, have increased the desire for structure-based function predictions. However, prediction of enzyme function is difficult because one member of a superfamily may catalyze a different reaction than other members, whereas members of different superfamilies can catalyze the same reaction. In addition, conformational changes, mutations or the absence of a particular catalytic residue can prevent inference of the mechanism by which catalytic residues stabilize and promote the elementary reaction. A major hurdle for alignment-based methods for prediction of function is the absence (despite its importance) of a measure of similarity of the physicochemical properties of catalytic sites. To solve this problem, the physicochemical features radially distributed around catalytic sites should be considered in addition to structural and sequence similarities.

Results
We showed that radial distribution functions (RDFs), which are associated with the local structural and physicochemical properties of catalytic active sites, are capable of clustering oxidoreductases and transferases by function. The catalytic sites of these enzymes were also characterized using the RDFs. The RDFs provided a measure of the similarity among the catalytic sites, detecting conformational changes caused by mutation of catalytic residues. Furthermore, the RDFs reinforced the classification of enzyme functions based on conventional sequence and structural alignments.

Conclusions
Our results demonstrate that the application of RDFs provides advantages in the functional classification of enzymes by providing information about catalytic sites.
Racial differences in the built environment—body mass index relationship? A geospatial analysis of adolescents in urban neighborhoods
Authors: Duncan Dustin T , Castro Marcia C , Gortmaker Steven L , Aldstadt Jared , Melly Steven J , Bennett Gary G 
Published: April 2012

AbstractBackgroundBuilt environment features of neighborhoods may be related to obesity among adolescents and potentially related to obesity-related health disparities. The purpose of this study was to investigate spatial relationships between various built environment features and body mass index (BMI) z-score among adolescents, and to investigate if race/ethnicity modifies these relationships. A secondary objective was to evaluate the sensitivity of findings to the spatial scale of analysis (i.e. 400- and 800-meter street network buffers).MethodsData come from the 2008 Boston Youth Survey, a school-based sample of public high school students in Boston, MA. Analyses include data collected from students who had georeferenced residential information and complete and valid data to compute BMI z-score (n = 1,034). We built a spatial database using GIS with various features related to access to walking destinations and to community design. Spatial autocorrelation in key study variables was calculated with the Global Moran’sIstatistic. We fit conventional ordinary least squares (OLS) regression and spatial simultaneous autoregressive error models that control for the spatial autocorrelation in the data as appropriate. Models were conducted using the total sample of adolescents as well as including an interaction term for race/ethnicity, adjusting for several potential individual- and neighborhood-level confounders and clustering of students within schools.ResultsWe found significant positive spatial autocorrelation in the built environment features examined (Global Moran’sImost ≥ 0.60; allp = 0.001) but not in BMI z-score (Global Moran’sI = 0.07,p = 0.28). Because we found significant spatial autocorrelation in our OLS regression residuals, we fit spatial autoregressive models. Most built environment features were not associated with BMI z-score. Density of bus stops was associated with a higher BMI z-score among Whites (Coefficient: 0.029,p < 0.05). The interaction term for Asians in the association between retail destinations and BMI z-score was statistically significant and indicated an inverse association. Sidewalk completeness was significantly associated with a higher BMI z-score for the total sample (Coefficient: 0.010,p < 0.05). These significant associations were found for the 800-meter buffer.ConclusionSome relationships between the built environment and adolescent BMI z-score were in the unexpected direction. Our findings overall suggest that the built environment does not explain a large proportion of the variation in adolescent BMI z-score or racial disparities in adolescent obesity. However, there are some differences by race/ethnicity that require further research among adolescents.
Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades
Authors: Kunigal Sateesh , Ponnusamy Moorthy P , Momi Navneet , Batra Surinder K , Chellappan Srikumar P 
Published: April 2012

Abstract

Background
The membrane-bound mucins are thought to play an important biological role in cell–cell and cell–matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3.

Results
Chromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer.

Conclusions
Our studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that targeting these signaling pathways might inhibit the expression of MUC4 and prevent the proliferation and invasion of pancreatic cancer cells.
Radiation effect on viscous flow of a nanofluid and heat transfer over a nonlinearly stretching sheet
Authors: Hady Fekry M , Ibrahim Fouad S , Abdel-Gaied Sahar M , Eid Mohamed R 
Published: April 2012

Abstract
In this work, we study the flow and heat transfer characteristics of a viscous nanofluid over a nonlinearly stretching sheet in the presence of thermal radiation, included in the energy equation, and variable wall temperature. A similarity transformation was used to transform the governing partial differential equations to a system of nonlinear ordinary differential equations. An efficient numerical shooting technique with a fourth-order Runge-Kutta scheme was used to obtain the solution of the boundary value problem. The variations of dimensionless surface temperature, as well as flow and heat-transfer characteristics with the governing dimensionless parameters of the problem, which include the nanoparticle volume fraction ϕ, the nonlinearly stretching sheet parameter n, the thermal radiation parameter N

R
, and the viscous dissipation parameter Ec, were graphed and tabulated. Excellent validation of the present numerical results has been achieved with the earlier nonlinearly stretching sheet problem of Cortell for local Nusselt number without taking the effect of nanoparticles.
Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia
Authors: Tamayev Robert , D’Adamio Luciano 
Published: April 2012

Abstract

Background
A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). BRI2 is an inhibitor of amyloid-β precursor protein (APP) processing, which is genetically linked to Alzheimer’s disease (AD) pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI). β-cleavage of APP yields the β-carboxyl-terminal (β-CTF) and the amino-terminal-soluble APPβ (sAPPβ) fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss.

Results
Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI) results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity.

Conclusion
This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI is a valuable mouse model to study AD pathogenesis and predict the clinical outcome of therapeutic agents for AD.
Brain structure and joint hypermobility: Relevance to the
expression of psychiatric symptoms
Authors: Eccles J. A. , Beacher F. D. C. , Gray M. A. , Jones C. L. , Minati L. , Harrison N. A. , Critchley H. D. 
Published: April 2012

SummaryJoint hypermobility is overrepresented among people with anxiety and can be
associated with abnormal autonomic reactivity. We tested for associations
between regional cerebral grey matter and hypermobility in 72 healthy
volunteers using voxel-based morphometry of structural brain scans.
Strikingly, bilateral amygdala volume distinguished those with from those
without hypermobility. The hypermobility group scored higher for
interoceptive sensitivity yet were not significantly more anxious. Our
findings specifically link hypermobility to the structural integrity of a
brain centre implicated in normal and abnormal emotions and physiological
responses. Our observations endorse hypermobility as a multisystem phenotype
and suggest potential mechanisms mediating clinical vulnerability to
neuropsychiatric symptoms.
Androgens Inhibit the Stimulatory Action of 17β-Estradiol on Normal Human Breast Tissue in Explant Cultures
Authors: Eigėlienė Natalija , Elo Teresa , Linhala Mari , Hurme Saija , Erkkola Risto , Härkönen Pirkko 
Published: April 2012

Abstract

Background:
The data concerning the effects and safety of androgen in human breast tissue are conflicting.

Objective:
Our aim was to analyze the effects of androgens on normal human breast tissue (HBT).

Approach:
We cultured explants of HBT (obtained from reduction mammoplasty operations of postmenopausal women) with or without testosterone (T) and 5α-dihydrotestosterone (DHT) or in combination with 17β-estradiol (E2) for 7 and 14 d to study the effects of androgens on proliferation, apoptosis, target gene expression, and steroid receptors. The androgen receptor (AR) and estrogen receptor (ER) dependences of the effects were studied with the antihormones bicalutamide and fulvestrant, respectively.

Results:
The hormone responsiveness of cultured breast tissue was assessed by assaying apolipoprotein-D and prostate-specific antigen expression increased by androgens and amphiregulin and trefoil factor-1 expression induced by E2 treatment. T and DHT reduced proliferation and increased apoptosis in breast epithelium, the effects of which were reversed by bicalutamide. In combination with E2, they suppressed E2-stimulated proliferation and cell survival. DHT also inhibited basal (P &lt; 0.05) and E2-induced expression of cyclin-D1 mRNA (P &lt; 0.05). Immunohistochemistry showed that T (P &lt; 0.05) and DHT (P &lt; 0.05) increased the relative number of AR-positive cells, whereas ERα-positive (P &lt; 0.001) cell numbers were strongly decreased. The percentage of ERβ-positive cells remained unchanged. E2 treatment increased ERα-positive (P &lt; 0.01) cells, whereas AR- (P &lt; 0.05) and ERβ-expressing (P &lt; 0.001) cells diminished. These effects were repressed in combination cultures of E2 with T and DHT.

Conclusion:
T and DHT inhibited proliferation and increased apoptosis in the epithelium of cultured normal HBT and opposed E2-stimulated proliferation and cell survival in an AR-dependent manner. These effects were associated with changes in the proportions of ERα- and AR-positive epithelial cells.
Metabolic Slowing with Massive Weight Loss despite Preservation of Fat-Free Mass
Authors: Johannsen Darcy L. , Knuth Nicolas D. , Huizenga Robert , Rood Jennifer C. , Ravussin Eric , Hall Kevin D. 
Published: April 2012

AbstractContext:An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in substantial loss of FFM potentially slowing metabolic rate.Objective:Our objective was to determine whether a weight loss program consisting of diet restriction and vigorous exercise helped to preserve FFM and maintain resting metabolic rate (RMR).Participants and Intervention:We measured body composition by dual-energy x-ray absorptiometry, RMR by indirect calorimetry, and total energy expenditure by doubly labeled water at baseline (n = 16), wk 6 (n = 11), and wk 30 (n = 16).Results:At baseline, participants were severely obese (×± sd; body mass index 49.4 ± 9.4 kg/m2) with 49 ± 5% body fat. At wk 30, more than one third of initial body weight was lost (−38 ± 9%) and consisted of 17 ± 8% from FFM and 83 ± 8% from fat. RMR declined out of proportion to the decrease in body mass, demonstrating a substantial metabolic adaptation (−244 ± 231 and −504 ± 171 kcal/d at wk 6 and 30, respectively, P &lt; 0.01). Energy expenditure attributed to physical activity increased by 10.2 ± 5.1 kcal/kg·d at wk 6 and 6.0 ± 4.1 kcal/kg·d at wk 30 (P &lt; 0.001 vs. zero).Conclusions:Despite relative preservation of FFM, exercise did not prevent dramatic slowing of resting metabolism out of proportion to weight loss. This metabolic adaptation may persist during weight maintenance and predispose to weight regain unless high levels of physical activity or caloric restriction are maintained.
Accuracy of MRI with an endorectal coil for staging endometrial cancer
Authors: Alt Céline D , Brocker Kerstin A , Eichbaum Michael , Sohn Christof , Kopp-Schneider Annette , Kauczor Hans-Ulrich , Hallscheidt Peter 
Published: April 2012

Background The very good results of magnetic resonance imaging (MRI) using an endorectal coil in staging prostate cancer at 1.5T suggested that this imaging technique might be able to be used to stage endometrial cancer, the most common tumor in postmenopausal women. Purpose To evaluate the accuracy of MRI with an endorectal surface coil for staging primary endometrial carcinoma. Material and Methods A total of 33 consecutive patients with biopsy-proven endometrial cancer underwent 1.5T MRI with an endorectal surface coil (eMRI) using sagittal and axial T2-weighted (T2w) turbo spin echo (TSE), axial T1 gradient echo 2D fat-saturated (fs), sagittal T1 gradient echo 3D with and without contrast enhancement (CE), and axial T1 TSE fs CE sequence. Evaluation of local tumor extension was based on the revised standard TNM classification for endometrial cancer. eMRI staging was compared with the histopathological results after surgery. Results A total of 33 consecutive patients underwent eMRI for staging endometrial cancer, and 21 of these underwent primary surgery. The histological stages were as follows: T1a ( n = 8), T1b ( n = 10), T2b ( n = 2), and T3a ( n = 1). Overall staging accuracy by eMRI was 71% (15 of 21). With regard to depth of myometrial invasion, eMRI correctly diagnosed stage T1a in 75% (6/8) and stage T1b in 80% (8/10). eMRI overstaged the tumor in four patients and understaged it in two. Conclusion eMRI is highly accurate in staging myometrial invasion. However, eMRI at 1.5T does not seem to be significantly more accurate than pelvic MRI without an endorectal coil at 1.5T for staging primary endometrial cancer. eMRI for endometrial carcinoma therefore might not meet expectations compared with the results obtained using eMRI for staging prostate cancer at 1.5T.
In-phase and out-of-phase gradient-echo imaging in abdominal studies: intra-individual comparison of three different techniques
Authors: Ramalho Miguel , Herédia Vasco , de Campos Rafael OP , Dale Brian M , Azevedo Rafael M , Semelka Richard C 
Published: April 2012

Background T1-weighted gradient-echo in-phase and out-of-phase imaging is an essential component of comprehensive abdominal MR exams. It is useful for the study of fat-containing lesions and to identify various disease states related to the presence of fat in the liver. Purpose To compare three T1-weighted in-phase and out-of-phase (IP/OP) gradient-echo imaging sequences in an intra-individual fashion, and to determine whether advantages exist for each of these sequences for various patient types. Material and Methods One hundred and eighteen consecutive subjects (74 men, 44 women; mean age 53.9 ± 13.8 years) who had MRI examinations containing all three different IP/OP sequences (two-dimensional spoiled gradient-echo [2D-GRE], three-dimensional gradient-echo [3D-GRE], and magnetization-prepared gradient-recall echo [MP-GRE]) were included. Two different reviewers independently and blindly qualitatively evaluated IP/OP sequences to determine image quality, extent of artifacts, lesion detectability and conspicuity, and subjective grading of liver steatosis for the various sequences. Quantitative analysis was also performed. Qualitative and quantitative data were subjected to statistical analysis. Results Respiratory ghosting, parallel imaging, and truncation artifacts as well as shading and blurring were more pronounced with 3D-GRE IP/OP imaging. Overall image quality was higher with 2D-GRE ( P < 0.05). Detectability of low-fluid content lesions was lower with IP/OP MP-GRE sequences. MP-GRE sequences had the lowest SNRs ( P < 0.001). Liver-to-spleen and liver-to-lesion CNRs were significantly lower with 3D-GRE and MP-GR, respectively ( P < 0.001). Fat liver indexes showed strongly positive correlation between all sequences. Conclusion Currently, 2D-GRE remains the best approach for clinical IP/OP imaging. The good image quality of MP-GRE sequences acquired in a free-breathing manner should recommend its use in patients unable to suspend breathing.