bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of parvovirus B19 in the German population
Authors: RÖHRER C. , GÄRTNER B. , SAUERBREI A. , BÖHM S. , HOTTENTRÄGER B. , RAAB U. , THIERFELDER W. , WUTZLER P. , MODROW S. 
Published: January 2008

SUMMARYAcute parvovirus B19 infection is a risk for pregnant women. After vertical transmission the infected fetus may develop hydrops fetalis. Since B19 infection occurs mainly during childhood, children represent a main source for virus transmission. In order to determine whether certain groups in the German population show increased risks for B19 infection we analysed the seroprevalence using 6583 sera collected from adults in former Eastern and Western Germany during the German National Health Survey and 649 sera from healthy Thuringian children and adolescents. In adults the overall seroprevalence was 72·1%, rising from 20·4% in children (1–3 years) and 66·9% in adolescents (18–19 years) to 79·1% in the elderly (65–69 years). Significant differences were observed between females (73·3%) and males (70·9%) and between inhabitants of small (74·8%) and big cities (69·0%) but not between people of the former Eastern (72·8%) and Western states (72·0%) of Germany. For women during childbearing age (18–49 years) highest values were observed in those living together with two or more children (81·6%) and in women with occupational contact with children aged <6 years (88·9%). In contrast seroprevalence was significantly lower in age-matched female singles (64·8%) and in women with occupational contact with children aged >6 years and adolescents (63·8%).
Use of non-thermal atmospheric plasmas to reduce the viability ofBacillus subtilison spacecraft surfaces
Authors: Schuerger Andrew C. , Trigwell Steven , Calle Carlos I. 
Published: January 2008

AbstractAtmospheric pressure glow-discharge (APGD) plasmas have been proposed for sterilizing spacecraft surfaces prior to launch. The advantages of APGD plasmas for the sterilization of spacecraft surfaces include low temperatures at treatment sites, rapid inactivation kinetics of exposed microbial cells, physical degradation and removal of microbial cells, physical removal of organic biosignature molecules, and short exposure times for the materials. However, few studies have tested APGD plasmas on spacecraft materials for their effectiveness in both sterilizing surfaces and removal of microbial cells or spores. A helium (He)+oxygen (O2) APGD plasma was used to expose six spacecraft materials (aluminum 6061, polytetrafluoroethylene (PTFE), polycarbonate, Saf-T-Vu, Rastex, and Herculite 20) doped with spores of the common spacecraft contaminant,Bacillus subtilis, for periods of time up to 6 min. Results indicated that greater than six orders of magnitude reductions in viability were observed forB. subtilisspores in as short of time as 40 s exposure to the APGD plasmas. Spacecraft materials were not affected by exposures to the APGD plasmas. However, Saf-T-Vu was the only material in which spores ofB. subtilisadhered more aggressively to plasma-treated coupons when compared to non-plasma treated coupons; all other materials exhibited no significant differences between plasma and non-plasma treated coupons. In addition, spores ofB. subtiliswere physically degraded by exposures to the plasmas beginning at the terminal ends of spores, which appeared to be ruptured after only 30 s. After 300 s, most bacteria were removed from aluminium coupons, and only subtle residues of bacterial secretions or biofilms remained. Results support the conclusion that APGD plasmas can be used as a prelaunch cleaning and sterilization treatment on spacecraft materials provided that the biocidal and cleaning times are shorter than those required to alter surface properties of materials.
Impact of the Priority Follow-Up System on Quality of Life in Chinese Schizophrenia Patients
Authors: Xiang Yu-Tao , Leung Chi-Ming , Tang Wai-Kwong , Sandor Ungvari Gabor 
Published: January 2008

Objective: Priority follow up (PFU) is a particular aspect of mental health care in Hong Kong whereby psychiatric patients with a history of violence or suspected proclivity to violence are identified and their management is closely monitored. The aim of the present study was to determine the impact of a PFU system on quality of life (QOL) in schizophrenia patients. Methods: Two hundred and sixty-seven clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong using standardized assessment instruments that covered their clinical condition and QOL. Results: Patients with PFU status constituted 8.2% of the sample. PFU patients were more likely to be men, have a history of violence, and were poorer in the physical, psychological, social and environmental QOL domains than their non-PFU counterparts even after controlling for the effects of potential confounding variables. Conclusions: More effective measures should be taken to improve QOL in PFU schizophrenia patients who are prone to violent behavior.
Clustering of Psychosocial Symptoms in Overweight Children
Authors: Gibson Lisa Y. , Byrne Susan M. , Blair Eve , Davis Elizabeth A. , Jacoby Peter , Zubrick Stephen R. 
Published: January 2008

Objective: The aims of the present study were to (i) examine the relationship between children's degree of adiposity and psychosocial functioning; and (ii) compare patterns of clustering of psychosocial measures between healthy weight and overweight/obese children. Method: Cross-sectional data from a population-based cohort of 158 healthy weight, 77 overweight, and 27 obese children aged 8–13 years were analysed. Height, weight depression, quality of life, self-esteem, body dissatisfaction, eating disorder symptoms, peer relationships and behavioural and emotional problems were measured. Results: Multi-level analysis showed significant linear associations between child body mass index z-scores and the psychosocial variables, with increasing adiposity associated with increasing levels of psychosocial distress. Principal components analyses indicated subtle differences between the healthy weight and overweight/obese groups with regards to the clustering of psychosocial measures. In particular, in overweight/obese, but not in healthy weight children, global self-worth clustered with body image and eating disorder symptoms. Conclusions: The psychosocial burden of excess weight is significant and broad reaching, with overweight/obese children showing multiple significant psychosocial problems.
Nerve Growth Factor Is a Potential Therapeutic Target in Breast Cancer
Authors: Adriaenssens Eric , Vanhecke Elsa , Saule Pasquine , Mougel Alexandra , Page Adeline , Romon Rodrigue , Nurcombe Victor , Le Bourhis Xuefen , Hondermarck Hubert 
Published: January 2008

Abstract
We show here that nerve growth factor (NGF), the prototypic neurotrophin, can be targeted in breast cancer to inhibit tumor cell proliferation, survival, and metastasis. Analysis of a series of biopsies revealed widespread expression of NGF in the majority of human breast tumors, with anti-NGF immunoreactivity concentrated in the epithelial cancer cells. Moreover, immunodeficient mice xenografted with human breast cancer cells and treated with either anti-NGF antibodies or small interfering RNA against NGF displayed inhibited tumor growth and metastasis. Such treatments directed against NGF induced a decrease in cell proliferation with a concomitant increase in apoptosis of breast cancer cells and an inhibition of tumor angiogenesis. Together, these data indicate that targeting NGF in breast cancer may have therapeutic ramifications. [Cancer Res 2008;68(2):346–51]
Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44
Authors: Golshani Roozbeh , Lopez Luis , Estrella Veronica , Kramer Mario , Iida Naoko , Lokeshwar Vinata B. 
Published: January 2008

Abstract
Hyaluronic acid (HA) promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. HA is synthesized by HA synthases HAS1, HAS2, or HAS3. We have previously shown that HAS1 expression in tumor tissues is a predictor of bladder cancer recurrence and treatment failure. In this study, we stably transfected HT1376 bladder cancer cells with HAS1-sense (HAS1-S), HAS1-antisense (HAS1-AS), or vector cDNA constructs. Whereas HAS1-S transfectants produced ∼1.7-fold more HA than vector transfectants, HA production was reduced by ∼70% in HAS1-AS transfectants. HAS1-AS transfectants grew 5-fold slower and were ∼60% less invasive than vector and HAS1-S transfectants. HAS1-AS transfectants were blocked in G2-M phase of the cell cycle due to down-regulation of cyclin B1, cdc25c, and cyclin-dependent kinase 1 levels. These transfectants were also 5- to 10-fold more apoptotic due to the activation of the Fas-Fas ligand–mediated extrinsic pathway. HAS1-AS transfectants showed a ∼4-fold decrease in ErbB2 phosphorylation and down-regulation of CD44 variant isoforms (CD44-v3, CD44-v6, and CD44-E) both at the protein and mRNA levels. However, no decrease in RHAMM levels was observed. The decrease in CD44-v mRNA levels was not due to increased mRNA degradation. Whereas CD44 small interfering RNA (siRNA) transfection decreased cell growth and induced apoptosis in HT1376 cells, HA addition modestly increased CD44 expression and cell growth in HAS1-AS transfectants, which could be blocked by CD44 siRNA. In xenograft studies, HAS1-AS tumors grew 3- to 5-fold slower and had ∼4-fold lower microvessel density. These results show that HAS1 regulates bladder cancer growth and progression by modulating HA synthesis and HA receptor levels. [Cancer Res 2008;68(2):483–91]
Activating Transcription Factor 3 Is a Novel Repressor of the Nuclear Factor Erythroid-Derived 2–Related Factor 2 (Nrf2)–Regulated Stress Pathway
Authors: Brown Stephan L. , Sekhar Konjeti R. , Rachakonda Girish , Sasi Soumya , Freeman Michael L. 
Published: January 2008

Abstract
The transcription factor nuclear factor erythroid-derived 2–related factor 2 (Nrf2) regulates induction of an extensive cellular stress response network when complexed with the cAMP-responsive element binding protein (CBP) at antioxidant response elements (ARE) located in the promoter region of target genes. Activating transcription factor 3 (ATF3) can repress Nrf2-mediated signaling in a manner that is not well understood. Here, we show that ATF3-mediated suppression is a consequence of direct ATF3-Nrf2 protein-protein interactions that result in displacement of CBP from the ARE. This work establishes ATF3 as a novel repressor of the Nrf2-directed stress response pathway. [Cancer Res 2008;68(2):364–8]
Cyclooxygenase-2–Derived Prostaglandin E2 Activates β-Catenin in Human Cholangiocarcinoma Cells: Evidence for Inhibition of These Signaling Pathways by ω3 Polyunsaturated Fatty Acids
Authors: Lim Kyu , Han Chang , Xu Lihong , Isse Kumiko , Demetris Anthony J. , Wu Tong 
Published: January 2008

Abstract
Cholangiocarcinoma is a highly malignant neoplasm of the biliary tree. It has a high rate of mortality, and currently, there is no effective chemoprevention and treatment. This study was designed to investigate the potential effect of ω3 polyunsaturated fatty acids (ω3-PUFA) on human cholangiocarcinoma cell growth and to determine their mechanisms of actions. Treatment of three human cholangiocarcinoma cells (CCLP1, HuCCT1, SG231) with two ω3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for 12 to 72 h resulted in a dose- and time-dependent inhibition of cell growth; in contrast, arachidonic acid, a ω6-PUFA, had no significant effect. The ω3-PUFA effect is due to the induction of apoptosis, given that DHA induced the cleaved form of PARP, caspase-3, and caspase-9. DHA and EPA treatment caused dephosphorylation (and hence, the activation) of glycogen synthase kinase-3β (GSK-3β) with a decline of β-catenin protein. Accordingly, DHA treatment also decreased the β-catenin–mediated T cell factor/lymphoid enhancer factor (TCF/LEF) reporter activity, and inhibited the expression of c-Met, a β-catenin–controlled downstream gene implicated in cholangiocarcinogenesis. The GSK-3β inhibitor, SB216763, partially prevented DHA-induced reduction of β-catenin protein and TCF/LEF reporter activity, and restored cell growth, suggesting the involvement of GSK-3β dephosphorylation in ω3-PUFA–induced β-catenin degradation. In parallel, DHA treatment also induced the formation of the β-catenin/Axin/GSK-3β binding complex, further leading to β-catenin degradation. Moreover, DHA inhibited the expression of cyclooxygenase-2 (COX-2) and enhanced the expression of 15-hydroxyprostaglandin dehydrogenase, a physiologic COX-2 antagonist, in human cholangiocarcinoma cells. These findings suggest that ω3-PUFAs block cholangiocarcinoma cell growth at least in part through inhibition of Wnt/β-catenin and COX-2 signaling pathways. Thus, utilization of ω3-PUFAs may represent an effective and safe therapeutic approach for the chemoprevention and treatment of human cholangiocarcinoma. [Cancer Res 2008;68(2):553–60]
Impact of Common Epidermal Growth Factor Receptor and HER2 Variants on Receptor Activity and Inhibition by Lapatinib
Authors: Gilmer Tona M. , Cable Louann , Alligood Krystal , Rusnak David , Spehar Glenn , Gallagher Kathleen T. , Woldu Ermias , Carter H. Luke , Truesdale Anne T. , Shewchuk Lisa , Wood Edgar R. 
Published: January 2008

AbstractThe goal of this study was to characterize the effects of non–small cell lung carcinoma (NSCLC)-associated mutations in epidermal growth factor receptor (EGFR/ErbB1) and HER2 (ErbB2) on interactions with the dual tyrosine kinase inhibitor lapatinib. Biochemical studies show that commonly observed variants of EGFR [G719C, G719S, L858R, L861Q, and Δ746–750 (del15)] are enzyme activating, increasing the tyrosine kinase Vmax and increasing the Km(app) for ATP. The point mutations G719C and L861Q had minor effects on lapatinib Kis, whereas EGFR mutations L858R and del15 had a higher Ki for lapatinib than wild-type EGFR. Structural analysis of wild-type EGFR-lapatinib complexes and modeling of the EGFR mutants were consistent with these data, suggesting that loss of structural flexibility and possible stabilization of the active-like conformation could interfere with lapatinib binding, particularly to the EGFR deletion mutants. Furthermore, EGFR deletion mutants were relatively resistant to lapatinib-mediated inhibition of receptor autophosphorylation in recombinant cells expressing the variants, whereas EGFR point mutations had a modest or no effect. Of note, EGFR T790M, a receptor variant found in patients with gefitinib-resistant NSCLC, was also resistant to lapatinib-mediated inhibition of receptor autophosphorylation. Two HER2 insertional variants found in NSCLC were less sensitive to lapatinib inhibition than two HER2 point mutants. The effects of lapatinib on the proliferation of human NSCLC tumor cell lines expressing wild-type or variant EGFR and HER2 cannot be explained solely on the basis of the biochemical activity or receptor autophosphorylation in recombinant cells. These data suggest that cell line genetic heterogeneity and/or multiple determinants modulate the role played by EGFR/HER2 in regulating cell proliferation. [Cancer Res 2008;68(2):571–9]
Mammalian Target of Rapamycin Is the Key Effector of Phosphatidylinositol-3-OH–Initiated Proliferative Signals in the Thyroid Follicular Epithelium
Authors: Yeager Nicole , Brewer Charlene , Cai Kathy Qi , Xu Xiang-Xi , Di Cristofano Antonio 
Published: January 2008

Abstract
Activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling cascade is becoming increasingly recognized as a common feature of thyroid follicular neoplasms. We have recently shown that conditional loss of Pten in the mouse thyroid follicular cells is sufficient to stimulate continuous autonomous growth, leading to a homogeneously hyperplastic gland and to the development of follicular adenomas. Because the PI3K/AKT cascade can activate a plethora of different signaling pathways, it is still unclear which of these may represent the key mitogenic output of PI3K-initiated signaling. Here, we show that the in vivo proliferative response to chronic PI3K activation profoundly relies on the activation of the mammalian target of rapamycin (mTOR)/S6K1 axis, and that mTOR inhibition in Pten mutant mice and cells restores virtually normal proliferation rates, despite the presence of still elevated Akt activity, at least in part by down-regulating cyclins D1 and D3, and without affecting cell survival. [Cancer Res 2008;68(2):444–9]
Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Authors: Coates Philip J. , Rundle Jana K. , Lorimore Sally A. , Wright Eric G. 
Published: January 2008

AbstractIn addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow–derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure. [Cancer Res 2008;68(2):450–6]
Vascular Endothelial Growth Factor–Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth
Authors: Ebos John M.L. , Lee Christina R. , Bogdanovic Elena , Alami Jennifer , Van Slyke Paul , Francia Giulio , Xu Ping , Mutsaers Anthony J. , Dumont Daniel J. , Kerbel Robert S. 
Published: January 2008

Abstract
Vascular endothelial growth factor (VEGF) is a potent proangiogenic protein that activates VEGF receptor (VEGFR) tyrosine kinases expressed by vascular endothelial cells. We previously showed that one of these receptors, VEGFR-2, has a truncated soluble form (sVEGFR-2) that can be detected in mouse and human plasma. Because activation of VEGFR-2 plays an important role in tumor angiogenesis, clinical interest in monitoring plasma sVEGFR-2 levels in cancer patients has focused on its potential exploitation as a surrogate biomarker for disease progression as well as assessing efficacy/activity of antiangiogenic drugs, particularly those that target VEGF or VEGFR-2. However, no preclinical studies have been done to study sVEGFR-2 during tumor growth or the mechanisms involved in its modulation. Using spontaneously growing tumors and both localized and metastatic human tumor xenografts, we evaluated the relationship between sVEGFR-2 and tumor burden as well as underlying factors governing protein level modulation in vivo. Our results show an inverse relationship between the levels of sVEGFR-2 and tumor size. Furthermore, using various methods of VEGF overexpression in vivo, including cell transfection and adenoviral delivery, we found plasma sVEGFR-2 decreases to be mediated largely by tumor-derived VEGF. Finally, in vitro studies indicate VEGF-mediated sVEGFR-2 modulation is the result of ligand-induced down-regulation of the VEGFR-2 from the cell surface. Taken together, these findings may be pertinent to further clinical exploitation of plasma sVEGFR-2 levels as a surrogate biomarker of VEGF-dependent tumor growth as well as an activity indicator of antiangiogenic drugs that target the VEGFR system. [Cancer Res 2008;68(2):521–9]
Prediction of Prostate-Specific Antigen Recurrence in Men with Long-term Follow-up Postprostatectomy Using Quantitative Nuclear Morphometry
Authors: Veltri Robert W. , Miller M. Craig , Isharwal Sumit , Marlow Cameron , Makarov Danil V. , Partin Alan W. 
Published: January 2008

AbstractBackground: Nuclear morphometric signatures can be calculated using nuclear size, shape, DNA content, and chromatin texture descriptors [nuclear morphometric descriptor (NMD)]. We evaluated the use of a patient-specific quantitative nuclear grade (QNG) alone and in combination with routine pathologic features to predict biochemical [prostate-specific antigen (PSA)] recurrence-free survival in patients with prostate cancer.Methods: The National Cancer Institute Cooperative Prostate Cancer Tissue Resource (NCI-CPCTR) tissue microarray was prepared from radical prostatectomy cases treated in 1991 to 1992. We assessed 112 cases (72 nonrecurrences and 40 PSA recurrences) with long-term follow-up. Images of Feulgen DNA–stained nuclei were captured and the NMDs were calculated using the AutoCyte system. Multivariate logistic regression was used to calculate QNG and pathology-based solutions for prediction of PSA recurrence. Kaplan-Meier survival curves and predictive probability graphs were generated.Results: A QNG signature using the variance of 14 NMDs yielded an area under the receiver operator characteristic curve (AUC-ROC) of 80% with a sensitivity, specificity, and accuracy of 75% at a predictive probability threshold of ≥0.39. A pathology model using the pathologic stage and Gleason score yielded an AUC-ROC of 67% with a sensitivity, specificity, and accuracy of 70%, 50%, and 57%, respectively, at a predictive probability threshold of ≥0.35. Combining QNG, pathologic stage, and Gleason score yielded a model with an AUC-ROC of 81% with a sensitivity, specificity, and accuracy of 75%, 78%, and 77%, respectively, at a predictive probability threshold of ≥0.34.Conclusions: PSA recurrence is more accurately predicted using the QNG signature compared with routine pathology information alone. Inclusion of a morphometry signature, routine pathology, and new biomarkers should improve the prognostic value of information collected at surgery. (Cancer Epidemiol Biomarkers Prev 2008;17(1):102–10)