bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of human exposure pathways in an urban brownfield: Reduced risk from paving roads
Authors: James Kyle , Farrell Richard E. , Siciliano Steven D. 
Published: July 2012

Abstract
Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p &lt; 0.1) and PM10 (p &lt; 0.05) but not PM25. Consequently, the ingestion of inhaled soil particles was substantially reduced. The authors conclude that resuspended soil is likely an important source of risk for many northern communities and that paving roads is an effective method of reducing risk from the inhalation of soil particles. Environ. Toxicol. Chem. 2012; 31: 2423–2430. © 2012 SETAC
Nutritional status of community‐dwelling older people with dementia: associations with individual and family caregivers' characteristics
Authors: Rullier Laetitia , Lagarde Alexia , Bouisson Jean , Bergua Valérie , Barberger‐Gateau Pascale 
Published: July 2012

ObjectiveThe objective of this study was to explore the associations of individual characteristics of both older people with dementia and family caregivers with the nutritional status of older people with dementia.MethodsThis cross‐sectional study comprising 56 community‐dwelling older persons with dementia and 56 family caregivers was conducted at home by a psychogerontologist working for a community gerontological center. Older people with dementia were assessed with Mini mental state examination, Instrumental Activities of Daily Living, Activities of Daily Living (ADL), and NeuroPsychiatric Inventory (NPI) and family caregivers with the Burden Interview (Zarit scale), the State‐Trait Anxiety Inventory, the Center for Epidemiologic Studies Depression Scale, and the emotional impact measure of NPI. For both, nutritional status was evaluated using the Mini Nutritional Assessment (MNA).ResultsAmong older people with dementia, 58.9% were at risk of malnutrition and 23.2% presented a poor nutritional status, and among the family caregivers, 32.1% and 5.4%, respectively. The MNA score of older people with dementia was strongly and inversely associated with the ADL score and was strongly and positively associated with the MNA score of family caregiver. These two factors significantly explained 32% of variation of MNA score of older people with dementia.ConclusionsThese findings confirm the value of investigating nutritional deficiencies in dementia within the caregiving dyad and suggest that the functional status of older people with dementia and the nutritional status of family caregivers should be carefully assessed. Copyright © 2012 John Wiley & Sons, Ltd.
High-mobility group box 1 (HMGB1)-toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: Interaction of γδ T cells with macrophages
Authors: Wang Xuefu , Sun Rui , Wei Haiming , Tian Zhigang 
Published: July 2012

Abstract
Acetaminophen overdose causes acute liver inflammation with neutrophil infiltration; however, the mechanism of damage-associated inflammation has not been elucidated. In this study we found that the HMGB1-TLR4-IL-23-IL-17A axis played a crucial role in acetaminophen-induced infiltration of neutrophils and liver injury. Notably, interleukin (IL)-17A and IL-23 significantly increased after acetaminophen challenge. A neutralizing antibody against IL-17A attenuated the recruitment of neutrophils, accompanied by reduced liver injury. Only IL-17A+CD3+γδ T cell receptor (TCR)+ cells were significantly increased in the liver, and depletion of γδ T cells, but not CD4+ T cells or natural killer (NK)T cells significantly reduced IL-17A production, attenuated liver injury, and decreased the number of neutrophils in the liver. Furthermore, a neutralizing IL-23 p19 antibody or p40-deficiency significantly decreased the levels of IL-17A and infiltration of neutrophils. After in vitro stimulation, the percentage of IL-17A-producing γδ T cells and the levels of supernatant IL-17A from total hepatic lymphocytes or purified γδ T cells markedly increased in the presence with IL-23. Importantly, IL-23 and IL-17A were reduced after inhibition of macrophages and could not be induced in Toll-like receptor TLR4−/− mice after acetaminophen challenge. Meanwhile, serum high-mobility group box 1 (HMGB1), a damage-associated molecule released from necrotic hepatocytes, increased after acetaminophen challenge, and the HMGB1 inhibitor glycyrrhizin markedly reduced the production of IL-23 and IL-17A and the recruitment of hepatic neutrophils. HMGB1 stimulated the production of IL-23 by TLR4+/+ but not by TLR4−/− macrophages. Conclusion: The HMGB1-TLR4-IL-23 pathway in macrophages makes the generation of IL-17-producing γδ T cells, which mediates neutrophil infiltration and damage-induced liver inflammation. (Hepatology 2013)
Loss of SLC45A3 protein (prostein) expression in prostate cancer is associated with SLC45A3‐ERG gene rearrangement and an unfavorable clinical course
Authors: Perner Sven , Rupp Niels J. , Braun Martin , Rubin Mark A. , Moch Holger , Dietel Manfred , Wernert Nicolas , Jung Klaus , Stephan Carsten , Kristiansen Glen 
Published: July 2012

AbstractThe majority of prostate cancer harbors recurrent gene fusions involving ETS transcription factors, most commonly ERG. The second most common 5′ fusion partner after TMPRSS2 is SLC45A3. The aim of our study was to quantify the protein expression of ERG, TMPRSS2 and SLC45A3 in prostate cancer to assess for diagnostic or prognostic utility. Six hundred and forty consecutive prostate cancer cases in tissue microarray format were immunohistochemically analyzed for ERG, TMPRSS2 and SLC45A3 protein. Resultant protein expression data was correlated to the respective gene rearrangement status and clinico‐pathological parameters including PSA follow up times. ERG showed no expression in benign prostate glands. In cancer tissue, ERG protein expression showed a high rate of concordance with an underlying ERG rearrangement (91.5%). SLC45A3 showed a weaker expression in cancer as compared to benign tissue, which was pronounced in cases with SLC45A3‐ERG fusion. Importantly, SLC45A3 down regulation was significantly associated with shorter PSA‐free survival times. In contrast, TMPRSS2 was neither differentially expressed nor did it show a correlation between protein expression and rearrangement status. This study provides first evidence that the expression of SLC45A3 protein is down regulated through SLC45A3‐ERG fusion in prostate cancer. Moreover, these cases may represent a distinct molecular subclass of ERG rearranged prostate cancer with distinct clinical features. This study also confirms that ERG protein expression is predominantly found in prostate carcinomas with ERG gene rearrangement and does not occur in benign glands.
Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark
Authors: Idorn Luise Winkel , Thieden Elisabeth , Philipsen Peter Alshede , Wulf Hans Christian 
Published: July 2012

AbstractThere is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM. Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16–75 in 2002–2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p < 0.001, 95% confidence interval (CI): 31–63) and risk of CMM of the extremities by 34% (p < 0.001, 95% CI: 20–49) among people with home gardens. Dosimeter study: During a summer season 194 participants living in the Capital area, Denmark, equally distributed in homes with and without a garden, wore personal electronic UVR dosimeters measuring time‐stamped UVR doses continuously and filled in sun exposure diaries. While no difference was found in estimated yearly UVR dose between groups, participants with a home garden had more days exposing shoulders or upper body, and upper extremities outdoors than those without a garden (p = 0.026, age adjusted). People with a home garden are at increased risk of CMM of the trunk and extremities—body sites that seems to be exposed to a higher extent among people with home gardens. People with a higher SES are more likely to have a home garden. This may partly explain the well‐known association of higher SES with CMM incidence.
Stroma‐directed imatinib therapy impairs the tumor‐promoting effect of bone marrow‐derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer
Authors: Shinagawa Kei , Kitadai Yasuhiko , Tanaka Miwako , Sumida Tomonori , Onoyama Mieko , Ohnishi Mayu , Ohara Eiji , Higashi Yukihito , Tanaka Shinji , Yasui Wataru , Chayama Kazuaki 
Published: July 2012

AbstractBone marrow‐derived mesenchymal stem cells (MSCs) are reported to contribute to formation of tumor‐promoting stromal cells. We reported recently that, in an orthotopic nude mice model of colon cancer, MSCs traveled to tumor stroma, where they differentiated into carcinoma‐associated fibroblast (CAF)‐like cells. We also found that CAFs express platelet‐derived growth factor receptor (PDGFR) at a high level and that imatinib therapy targeting PDGFR in CAFs inhibits growth and metastasis of human colon cancer. These findings led us to examine whether the tumor‐promoting effect of MSCs is impaired by blockade of PDGFR signaling achieved with imatinib. Orthotopic transplantation and splenic injection of human MSCs along with KM12SM human colon cancer cells, in comparison with transplantation of KM12SM cells alone, resulted in significantly greater promotion of tumor growth and liver metastasis. The KM12SM + MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor‐bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+MSC xenograft, and survival in the mixed‐cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. In in vitro experiments, treatment with imatinib inhibited migration of MSCs. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow‐derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.
Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma
Authors: Funamizu Naotake , Hu Chaoxin , Lacy Curtis , Schetter Aaron , Zhang Geng , He Peijun , Gaedcke Jochen , Ghadimi Michael B. , Ried Thomas , Yfantis Harris G. , Lee Dong H. , Subleski Jeffrey , Chan Tim , Weiss Jonathan M. , Back Timothy C. , Yanaga Katsuhiko , Hanna Nader , Alexander H. Richard , Maitra Anirban , Hussain S. Perwez 
Published: July 2012

AbstractMIF is a proinflammatory cytokine and is implicated in cancer. A higher MIF level is found in many human cancer and cancer‐prone inflammatory diseases, including chronic pancreatitis and pancreatic cancer. We tested the hypothesis that MIF contributes to pancreatic cancer aggressiveness and predicts disease outcome in resected cases. Consistent with our hypothesis we found that an elevated MIF mRNA expression in tumors was significantly associated with poor outcome in resected cases. Multivariate Cox‐regression analysis further showed that MIF is independently associated with patients' survival (HR = 2.26, 95% CI = 1.17–4.37, p = 0.015). Mechanistic analyses revealed that MIF overexpression decreased E‐cadherin and increased vimentin mRNA and protein levels in pancreatic cancer cell lines, consistent with the features of epithelial‐to‐mesenchymal transition (EMT). Furthermore, MIF‐overexpression significantly increased ZEB1/2 and decreased miR‐200b expression, while shRNA‐mediated inhibition of MIF increased E‐cadherin and miR‐200b expression, and reduced the expression of ZEB1/2 in Panc1 cells. Re‐expression of miR‐200b in MIF overexpressing cells restored the epithelial characteristics, as indicated by an increase in E‐cadherin and decrease in ZEB1/2 and vimentin expression. A reduced sensitivity to the chemotherapeutic drug, gemcitabine, occurred in MIF‐overexpressing cells. Indicative of an increased malignant potential, MIF over‐expressing cells showed significant increase in their invasion ability in vitro, and tumor growth and metastasis in an orthotopic xenograft mouse model. These results support a role of MIF in disease aggressiveness, indicating its potential usefulness as a candidate target for designing improved treatment in pancreatic cancer.
Oncogenic mutations in extramammary Paget's disease and their clinical relevance
Authors: Kang Zhihua , Xu Feng , Zhang Qiao‐an , Wu Zhiyuan , Zhang Xinju , Xu Jinhua , Luo Yan , Guan Ming 
Published: July 2012

AbstractExtramammary Paget's disease (EMPD) is a rare cutaneous malignant neoplasm. The genetic alterations underlying its pathogenesis have less been described. Therefore, we analyzed the possible mutations in the KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, PIK3CA, AKT1, CTNNB1 and APC genes as well as methylation and expression of CDH1 in 144 EMPD cases and 42 matched normal skin tissues. A distinct mutation profile was identified in EMPDs with 27 (19%) cases mutant for RAS and RAF genes and 50 (35%) cases harboring oncogenic mutations in PIK3CA and AKT1. Moreover, a mutually exclusive pattern was observed in the genetic variants in these two signaling pathways. No mutation was detected in CTNNB1 and APC genes. High prevalence of low expression and hypermethylation of CDH1 gene was detected in 33 and 48% of the EMPD cases, respectively. Furthermore, PIK3CA and AKT1 mutations were significantly correlated with CDH1 hypermethylation which could explain why the majority of EMPD cases with mutant PIK3CA and AKT1 were invasive. Our study demonstrates that genetic variants associated with constitutive activation of RAS/RAF and PI3K/AKT pathways are involved in the pathogenesis of EMPD. This may represent novel therapeutic targets for this skin cancer.
A novel RT‐PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis
Authors: Gao Ge , Chernock Rebecca D. , Gay Hiram A. , Thorstad Wade L. , Zhang Tian R. , Wang Hongwei , Ma Xiao‐Jun , Luo Yuling , Lewis James S. , Wang Xiaowei 
Published: July 2012

AbstractOropharyngeal squamous cell carcinoma (SCC) is strongly associated with human papillomavirus (HPV) infection, which is distinctively different from most other head and neck cancers. However, a robust quantitative reverse transcription PCR (RT‐qPCR) method for comprehensive expression profiling of HPV genes in routinely fixed tissues has not been reported. To address this issue, we have established a new real‐time RT‐PCR method for the expression profiling of the E6 and E7 oncogenes from 13 high‐risk HPV types. This method was validated in cervical cancer and by comparison with another HPV RNA detection method (in situ hybridization) in oropharyngeal tumors. In addition, the expression profiles of selected HPV‐related human genes were also analyzed. HPV E6 and E7 expression profiles were then analyzed in 150 archived oropharyngeal SCC samples and compared with other variables and with patient outcomes. Our study showed that RT‐qPCR and RNA in situ hybridization were 100% concordant in determining HPV status. HPV transcriptional activity was found in most oropharyngeal SCC (81.3%), a prevalence that is higher than in previous studies. Besides HPV16, three other HPV types were also detected, including 33, 35 and 18. Furthermore, HPV and p16 had essentially identical expression signatures, and both HPV and p16 were prognostic biomarkers for the prediction of disease outcome. Thus, p16 mRNA or protein expression signature is a sensitive and specific surrogate marker for HPV transcriptional activity (all genotypes combined).
Italian mediterranean index and risk of colorectal cancer in the Italian section of the EPIC cohort
Authors: Agnoli Claudia , Grioni Sara , Sieri Sabina , Palli Domenico , Masala Giovanna , Sacerdote Carlotta , Vineis Paolo , Tumino Rosario , Giurdanella Maria Concetta , Pala Valeria , Berrino Franco , Mattiello Amalia , Panico Salvatore , Krogh Vittorio 
Published: July 2012

AbstractColorectal cancer is among the commonest cancers worldwide. Dietary factors have been linked to colorectal cancer risk, however, few studies have evaluated the relationship between a priori dietary patterns and colorectal cancer risk. We evaluated the effect of adherence to a Mediterranean dietary pattern, as measured by the Italian Mediterranean Index, on the risk of colorectal cancer in the 45,275 participants of the Italian section of the EPIC study who completed a dietary questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) for colorectal cancer in relation to categories of Italian Mediterranean Index score were estimated by multivariate Cox models adjusted for known risk factors, on the whole cohort, on men and women and according to cancer subsite. During a mean follow‐up of 11.28 years, 435 colorectal cancer cases were identified. The Italian Mediterranean Index was inversely associated with colorectal cancer risk (HR: 0.50; 95% CI: 0.35–0.71 for the highest category compared to the lowest, P‐trend: 0.043). Results did not differ by sex. Highest Italian Mediterranean Index score was also significantly associated with reduced risks of any colon cancer (HR: 0.54, 95% CI: 0.36–0.81), distal colon cancer (HR: 0.44, 95% CI: 0.26–0.75) and rectal cancer (HR: 0.41, 95% CI: 0.20–0.81), but not of proximal colon cancer. These findings suggest that adherence to a Mediterranean diet (as measured by the Italian Mediterranean Index) protects against colorectal cancer in general but not against cancer developing in the proximal colon.
Biocompatibility of an experimental MTA sealer implanted in the rat subcutaneous: Quantitative and immunohistochemical evaluation
Authors: Viana Viola Naiana , Maria Guerreiro‐Tanomaru Juliane , Ferreira da Silva Guilherme , Sasso‐Cerri Estela , Tanomaru‐Filho Mario , Cerri Paulo Sérgio 
Published: July 2012

AbstractThe tissue reaction promoted by an experimental mineral trioxide aggregate sealer (MTAS) in the rat subcutaneous was evaluated by morphological and morphometric analyses. In the animals from each group (n = 20), polyethylene tubes filled with MTAS, Portland cement (PC) or MTA were implanted in the dorsal subcutaneous. In the control group, empty tubes were implanted. After 7, 14, 30, and 60 days, the specimens were fixed and embedded in paraffin. In the HE‐stained sections, the numerical density of inflammatory cells (IC) in the capsule was evaluated and statistical analyses performed (p ≤ 0.05). The expression of osteopontin (OPN) was evaluated by immunohistochemistry. The von Kossa method for detection of calcified structures was also performed. A moderate inflammatory process in the capsule was seen in all groups, at 7 and 14 days. At 60 days, significant reduction in the number of IC was verified in comparison to initial periods; however, significant differences were not verified among the groups. OPN immunolabeling was observed in the fibroblasts cytoplasm of the capsule next to the implants. Structures von Kossa‐positive were observed in the capsule adjacent to all materials implanted at 7, 14, and 30 days. The results strongly indicate that MTAS presents biocompatibility similarly to MTA and PC. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Extension of the CHARMM general force field to sulfonyl‐containing compounds and its utility in biomolecular simulations
Authors: Yu Wenbo , He Xibing , Vanommeslaeghe Kenno , MacKerell Alexander D. 
Published: July 2012

AbstractPresented is an extension of the CHARMM General Force Field (CGenFF) to enable the modeling of sulfonyl‐containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used as the basis for the parameter optimization. Targeting high‐level quantum mechanical and experimental crystal data, the new parameters were optimized in a hierarchical fashion designed to maintain compatibility with the remainder of the CHARMM additive force field. The optimized parameters satisfactorily reproduced equilibrium geometries, vibrational frequencies, interactions with water, gas phase dipole moments, and dihedral potential energy scans. Validation involved both crystalline and liquid phase calculations showing the newly developed parameters to satisfactorily reproduce experimental unit cell geometries, crystal intramolecular geometries, and pure solvent densities. The force field was subsequently applied to study conformational preference of a sulfonamide based peptide system. Good agreement with experimental IR/NMR data further validated the newly developed CGenFF parameters as a tool to investigate the dynamic behavior of sulfonyl groups in a biological environment. CGenFF now covers sulfonyl group containing moieties allowing for modeling and simulation of sulfonyl‐containing compounds in the context of biomolecular systems including compounds of medicinal interest. © 2012 Wiley Periodicals, Inc.
Preparation and Characterization of Sulfonated Polyacrylamide from Polyacrylonitrile for Proton Conductive Membranes
Authors: Touheed Azra , Maab Husnul 
Published: July 2012

AbstractPolyacrylonitrile (PAN) was sulfonated and the membranes prepared were then characterized by the FTIR‐ATR, Elemental Analyzer EA, TGA, DSC, SEM, Tensile, Water uptake and Impedance tests. FTIR‐ATR spectra show the substitution of the sulfonic group (SO3) to the main stem of the chain and also the hydrolysis of the cyanide group to amide group confirm the conversion of polyacrylonitrile to sulfonated polyacrylamide. Increase in water uptake property as compared to pure PAN also confirms the sulfonation process has occurred. Thermal properties also confirm the enhancement of the materials after sulfonation reaction.