bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clozapine Use in a Forensic Population in a New South Wales Prison Hospital
Authors: Martin Adam , O'Driscoll Colmán , Samuels Anthony 
Published: January 2008

Objective: To document and measure various parameters and outcomes in patients prescribed clozapine in a forensic psychiatric setting. Method: A retrospective file review was conducted on patients prescribed clozapine. Parameters and outcomes were recorded and compared against a group prescribed other antipsychotics, matched for sex and diagnosis. Results: Patients prescribed clozapine had higher rates of substance misuse syndromes and comorbidity when compared to patients prescribed other antipsychotics. Clozapine was found to be effective in treatment of psychosis. High rates of adverse effects were noted. Discontinuation of clozapine for a variety of reasons was common. Conclusion: Patients identified as treatment resistant who are prescribed clozapine are often more complex in the pattern of illness and subsequent needs. Clozapine is effective in the treatment of psychosis in this forensic service. Its benefits need to be balanced against the potential for adverse effects and problems ensuring adherence. Regular, objective monitoring of clinical and adverse effects would aid patient safety, clinical decision-making and future research.
Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood
Authors: Chatzi L , Torrent M , Romieu I , Garcia-Esteban R , Ferrer C , Vioque J , Kogevinas M , Sunyer J 
Published: January 2008

Introduction:Dietary intake of specific nutrients or food groups during pregnancy could play a role in the risk of asthma and atopy in offspring, but specific dietary patterns have not been implicated. The authors evaluated the impact of maternal (during pregnancy) and child adherence to a Mediterranean diet on asthma and atopy in childhood.Methods:Women presenting for antenatal care at all general practices in Menorca, a Mediterranean island in Spain, over a 12 month period starting in mid-1997 were recruited. 460 children were included in the analysis after 6.5 years of follow-up. Maternal dietary intake during pregnancy and children’s dietary intake at age 6.5 years were assessed by food frequency questionnaires, and adherence to a Mediterranean diet was evaluated by a priori defined scores. During follow-up, parents completed questionnaires on the child’s respiratory and allergic symptoms. Children underwent skin prick tests with six common aeroallergens.Results:The prevalence rates of persistent wheeze, atopic wheeze and atopy at age 6.5 years were 13.2%, 5.8% and 17.0%, respectively. One-third (36.1%) of mothers had a low quality Mediterranean diet during pregnancy according to the Mediterranean Diet Score, while the rest had a high score. A high Mediterranean Diet Score during pregnancy (at two levels, using “low” score as the reference) was found to be protective for persistent wheeze (OR 0.22; 95% CI 0.08 to 0.58), atopic wheeze (OR 0.30; 95% CI 0.10 to 0.90) and atopy (OR 0.55; 95% CI 0.31 to 0.97) at age 6.5 years after adjusting for potential confounders. Childhood adherence to a Mediterranean diet was negatively associated with persistent wheeze and atopy although the associations did not reach statistical significance.Conclusion:These results support a protective effect of a high level of adherence to a Mediterranean diet during pregnancy against asthma-like symptoms and atopy in childhood.
Cryptosporiopsisspecies isolated from the roots of aspen in central Alberta: identification, morphology, and interactions with the host, in vitroThis article is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Wang Wei , Tsuneda Akihiko , Gibas Connie Fe , Currah Randolph S. 
Published: January 2008

Cryptosporiopsis Bubák & Kabát isolates were obtained for the first time from roots of apparently healthy aspen seedlings in Alberta. These isolates were similar in all the major morphological features previously used to separate Cryptosporiopsis species, but sequencing data of the ITS1-5.8S-ITS2 region indicated that they were separated into two groups, one belonging to Cryptosporiopsis ericae Sigler and the other to Cryptosporiopsis radicicola Kowalski & Bartnik. Scanning electron microscopy of ex-type cultures and selected isolates from aspen roots revealed that C. ericae and C. radicicola differed in morphogenesis and structure of conidiomata: those of C. ericae were either synnematous or sporodochial, whereas those of C. radicicola possessed a peridium-like mycelial envelope bearing amorphous adhesive material. Phialides in the hymenium of C. radicicola were also embedded in amorphous matrix material but such material was absent in C. ericae. Microscopic examination of artificially inoculated aspen roots indicated that both species are endophytes of the host. Hyphal penetration by C. ericae was only occasional and confined to the host epidermis, whereas C. radicicola was more aggressive and its hyphal ingress extended to the cortical region.
Poplar research in Canada — a historical perspective with a view to the futureThis minireview is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Richardson J. , Cooke J. E.K. , Isebrands J. G. , Thomas B. R. , Van Rees K. C.J. 
Published: January 2008

This paper provides a brief history of the development of poplar research in Canada within the broader North American context, as background to the present collection of papers on current Canadian poplar research. After the earliest times and European settlement, a few individual scientists played a pioneering role in early selection and breeding of poplars. The development of farm shelterbelts in the prairies over the last 100 years, including the widespread distribution of adapted poplars, has had a significant impact on the landscape. In the last 30 years, industrial strategies for the development and use of poplars have been the most important driver for poplar research. All of these components have in some way foreshadowed the present dramatic leading-edge research in poplar genomics. With the increasing diversity and sophistication of poplar research, particularly in recent years, a need is seen for identification of research priorities and coordination of research activities by disparate parties.
Natural dynamics-based silviculture for maintaining plant biodiversity in Populus tremuloides-dominated boreal forests of eastern CanadaThis article is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Haeussler Sybille , Bergeron Yves , Brais Suzanne , Harvey Brian D. 
Published: January 2008

Southern boreal forests dominated by trembling aspen ( Populus tremuloides Michx.) are notable for the biological richness of their plant communities. We used 12 plant community and plant functional group indicators to test the hypothesis that natural dynamics-based silvicultural systems better maintain biodiversity in aspen plant communities than conventional clear-cutting. Using CA ordination, box-and-whisker diagrams, and ANOVA, we compared the range of variability of our 12 bioindicators among five experimental stand types of the sylviculture et aménagement forestier écosystémiques (SAFE) project: mature (78 years) uncut; mature 1/3 partial-cut; mature 2/3 partial-cut; young (3 years) unburned clear-cut; young burned clear-cut; and three closely matched aspen stand types of northwest Quebec and northeast Ontario: old (105 years) uncut; young unburned clear-cut; young wildfire. Burned clearcuts partially emulated wildfires by reducing tall shrub abundance and regenerating post-fire specialists, but snags were lacking. The dual disturbance also retarded aspen regrowth and caused a 7-fold increase in non-native plants. Partial-cuts retained most attributes of mature uncut stands, but after 3 years showed little evidence of accelerating development of old stand characteristics. We concluded that SAFE natural dynamics-based silviculture better recreated the range of variability of naturally disturbed aspen plant communities than conventional clear-cutting. Improvements, including alternative burn prescriptions and snag or green tree retention in clearcuts, are nontheless warranted.
Cyclooxygenase-2 Expression during Immortalization and Breast Cancer Progression
Authors: Zhao Xiangshan , Goswami Monica , Pokhriyal Nidhi , Ma Hui , Du Hongyan , Yao Jun , Victor Thomas A. , Polyak Kornelia , Sturgis Charles D. , Band Hamid , Band Vimla 
Published: January 2008

Abstract
Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells. [Cancer Res 2008;68(2):467–75]
p19Arf Inhibits the Invasion of Hepatocellular Carcinoma Cells by Binding to C-terminal Binding Protein
Authors: Chen Ya-Wen , Paliwal Seema , Draheim Kyle , Grossman Steven R. , Lewis Brian C. 
Published: January 2008

Abstract
The INK4A/ARF tumor suppressor locus is frequently inactivated in hepatocellular carcinoma (HCC), yet the consequences of this remain unknown. We recently described a HCC mouse model in which loss of the Ink4a/Arf locus accelerates the development of metastasis and enhances tumor cell migration and invasion in cell culture assays. We show here that knockdown of p19Arf in an HCC cell line increases invasion in cell culture assays. Furthermore, reintroduction of p19Arf into HCC cell lines lacking Ink4a/Arf inhibits tumor cell invasion, without affecting cell proliferation, or cell transformation as measured by soft agar colony formation. Inhibition of cell invasion by p19Arf was dependent on its C-terminal binding protein (CtBP) interaction domain but independent of Mdm2 binding and nucleolar localization. Indeed, RNA interference–mediated knockdown of CtBP1 or CtBP2 decreased cell invasion, and ectopic expression of CtBP2 enhanced tumor cell migration and invasion. Thus, our data indicate a novel role for the Arf tumor suppressor protein in regulating phenotypes associated with tumor progression and metastasis in HCC cells. [Cancer Res 2008;68(2):476–82]
The Adenocarcinoma-Associated Antigen, AGR2, Promotes Tumor Growth, Cell Migration, and Cellular Transformation
Authors: Wang Zheng , Hao Ying , Lowe Anson W. 
Published: January 2008

Abstract
The AGR2 gene encodes a secretory protein that is highly expressed in adenocarcinomas of the esophagus, pancreas, breast, and prostate. This study explores the effect of AGR2 expression with well-established in vitro and in vivo assays that screen for cellular transformation and tumor growth. AGR2 expression in SEG-1 esophageal adenocarcinoma cells was reduced with RNA interference. Cellular transformation was examined using NIH3T3 cells that express AGR2 after stable transfection. The cell lines were studied in vitro with assays for density-dependent and anchorage-independent growth, and in vivo as tumor xenografts in nude mice. SEG-1 cells with reduced AGR2 expression showed an 82% decrease in anchorage-independent colony growth and a 60% reduction in tumor xenograft size. In vitro assays of AGR2-expressing NIH3T3 cells displayed enhanced foci formation and anchorage-independent growth. In vivo, AGR2-expressing NIH3T3 cells established tumors in nude mice. Thus, AGR2 expression promotes tumor growth in esophageal adenocarcinoma cells and is able to transform NIH3T3 cells. Immunohistochemistry of the normal mouse intestine detected AGR2 expression in proliferating and differentiated intestinal cells of secretory lineage. AGR2 may be important for the growth and development of the intestine as well as esophageal adenocarcinomas. [Cancer Res 2008;68(2):492–7]
Critical Role of the Stress Chaperone GRP78/BiP in Tumor Proliferation, Survival, and Tumor Angiogenesis in Transgene-Induced Mammary Tumor Development
Authors: Dong Dezheng , Ni Min , Li Jianze , Xiong Shigang , Ye Wei , Virrey Jenilyn J. , Mao Changhui , Ye Risheng , Wang Miao , Pen Ligaya , Dubeau Louis , Groshen Susan , Hofman Florence M. , Lee Amy S. 
Published: January 2008

Abstract
The unfolded protein response (UPR) is an evolutionarily conserved mechanism that activates both proapoptotic and survival pathways to allow eukaryotic cells to adapt to endoplasmic reticulum (ER) stress. Although the UPR has been implicated in tumorigenesis, its precise role in endogenous cancer remains unclear. A major UPR protective response is the induction of the ER chaperone GRP78/BiP, which is expressed at high levels in a variety of tumors and confers drug resistance in both proliferating and dormant cancer cells. To determine the physiologic role of GRP78 in in situ–generated tumor and the consequence of its suppression on normal organs, we used a genetic model of breast cancer in the Grp78 heterozygous mice where GRP78 expression level was reduced by about half, mimicking anti-GRP78 agents that achieve partial suppression of GRP78 expression. Here, we report that Grp78 heterozygosity has no effect on organ development or antibody production but prolongs the latency period and significantly impedes tumor growth. Our results reveal three major mechanisms mediated by GRP78 for cancer progression: enhancement of tumor cell proliferation, protection against apoptosis, and promotion of tumor angiogenesis. Importantly, although partial reduction of GRP78 in the Grp78 heterozygous mice substantially reduces the tumor microvessel density, it has no effect on vasculature of normal organs. Our findings establish that a key UPR target GRP78 is preferably required for pathophysiologic conditions, such as tumor proliferation, survival, and angiogenesis, underscoring its potential value as a novel therapeutic target for dual antitumor and antiangiogenesis activity. [Cancer Res 2008;68(2):498–505]
Development of a New Tracking Tool for the Human Monomeric Laminin-γ2 Chain In vitro and In vivo
Authors: Koshikawa Naohiko , Minegishi Tomoko , Nabeshima Kazuki , Seiki Motoharu 
Published: January 2008

Abstract
Laminin-5 (Ln-5), a heterotrimer composed of three different laminin chains [laminin-α3 (Ln-α3), laminin-β3 (Ln-β3), and laminin-γ2 (Ln-γ2)], is a major component of the basement membrane in most adult tissues. One of the chains, Ln-γ2, is a specific marker of invasive tumors because it is frequently expressed as a monomer in malignant tumors. However, there is no simple and direct method to detect the monomeric form of Ln-γ2 selectively in the presence of Ln-5 because all available antibodies recognize both monomeric and heterotrimeric forms of Ln-γ2. In this study, we developed a new monoclonal antibody (mAb) termed 1H3 that reacts specifically with human Ln-γ2 monomers during immunoprecipitation, ELISA, Western blotting, and immunostaining. Ln-5 was not recognized by mAb 1H3 after denaturation with detergents under nonreducing conditions, but reactivity was recovered when denaturation was done under reducing conditions. The epitope of the antibody was mapped to region on the coiled-coil structure formed between Ln-γ2 and its partner chains Ln-α3 and Ln-β3 in Ln-5, whose structure is further stabilized by disulfide bonds. In normal tissue samples, the basement membrane was stained with conventional antibody against Ln-γ2 but not by mAb 1H3. In contrast, tumor cells in tissue sections could be stained with mAb 1H3 as efficiently as with conventional antibody. Thus, mAb 1H3 holds promise as a powerful tracking tool for the specific detection of monomeric Ln-γ2 in vivo and in vitro and is potentially useful as a diagnostic tool for detecting tumors and as a vehicle for drug delivery to cancer tissues. [Cancer Res 2008;68(2):530–6]
Chronic Hypoxia Decreases Synthesis of Homologous Recombination Proteins to Offset Chemoresistance and Radioresistance
Authors: Chan Norman , Koritzinsky Marianne , Zhao Helen , Bindra Ranjit , Glazer Peter M. , Powell Simon , Belmaaza Abdellah , Wouters Brad , Bristow Robert G. 
Published: January 2008

Abstract
Hypoxic and/or anoxic tumor cells can have increased rates of mutagenesis and altered DNA repair protein expression. Yet very little is known regarding the functional consequences of any hypoxia-induced changes in the expression of proteins involved in DNA double-strand break repair. We have developed a unique hypoxic model system using H1299 cells expressing an integrated direct repeat green fluorescent protein (DR-GFP) homologous recombination (HR) reporter system to study HR under prolonged chronic hypoxia (up to 72 h under 0.2% O2) without bias from altered proliferation, cell cycle checkpoint activation, or severe cell toxicity. We observed decreased expression of HR proteins due to a novel mechanism involving decreased HR protein synthesis. Error-free HR was suppressed 3-fold under 0.2% O2 as measured by the DR-GFP reporter system. This decrease in functional HR resulted in increased sensitivity to the DNA cross-linking agents mitomycin C and cisplatin but not to the microtubule-interfering agent, paclitaxel. Chronically hypoxic H1299 cells that had decreased functional HR were relatively radiosensitive [oxygen enhancement ratio (OER), 1.37] when compared with acutely hypoxic or anoxic cells (OER, 1.96–2.61). Using CAPAN1 cells isogenic for BRCA2 and siRNA to RAD51, we confirmed that the hypoxia-induced radiosensitivity was due to decreased HR capacity. Persistent down-regulation of HR function by the tumor microenvironment could result in low-fidelity DNA repair and have significant implications for response to therapy and genetic instability in human cancers. [Cancer Res 2008;68(2):605–14]
A Rapid Outcomes Ascertainment System Improves the Quality of Prognostic and Pharmacogenetic Outcomes from Observational Studies
Authors: Bradbury Penelope A. , Heist Rebecca Suk , Kulke Matthew H. , Zhou Wei , Marshall Ariela L. , Miller David P. , Su Li , Park Sohee , Temel Jennifer , Fidias Panos , Sequist Lecia , Lynch Thomas J. , Wain John C. , Shepherd Frances A. , Christiani David C. , Liu Geoffrey 
Published: January 2008

Abstract
Purpose: Case-control and observational studies are popular choices for evaluating molecular prognostic/pharmacogenetic outcomes, but data quality is rarely tested. Using clinical trial and epidemiologic methods, we assessed the quality of prognostic and outcomes data obtainable from a large case-control study of lung cancer.
Methods: We developed an explicit algorithm (set of standard operating procedures forming a rapid outcomes ascertainment system) that encompassed multiple tests of quality assurance, and quality of data for a range of prognostic and outcomes variables, in several cancers, across several centers and two countries were assessed. Based on these assessments, the algorithm was revised and physicians' clinical practice changed. We reevaluated the quality of outcomes after these revisions.
Results: Development of an algorithm with internal quality controls showed specific patterns of data collection errors, which were fixable. Although the major discrepancy rate in retrospective data collection was low (0.6%) when compared with external validated sources, complete data were found in &lt;50% of patients for treatment response rate, toxicity, and documentation of patient palliative symptoms. Prospective data collection and changes to clinical practice led to significantly improved data quality. Complete data on response rate increased from 45% to 76% (P = 0.01, Fisher's exact test), for toxicity data, from 26% to 56% (P = 0.02), and for palliative symptoms, from 25% to 70% (P &lt; 0.05), in one large lung cancer case-control study.
Conclusions: Observational studies can be a useful source for studying molecular prognostic and pharmacogenetic outcomes. A rapid outcomes ascertainment system with strict ongoing quality control measures is an excellent means of monitoring key variables. (Cancer Epidemiol Biomarkers Prev 2008;17(1):204–11)
Regular Adult Aspirin Use Decreases the Risk of Non-Small Cell Lung Cancer among Women
Authors: Van Dyke Alison L. , Cote Michele L. , Prysak Geoffrey , Claeys Gina B. , Wenzlaff Angie S. , Schwartz Ann G. 
Published: January 2008

Abstract
Background: Prior studies indicate that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of non-small cell lung cancer (NSCLC); however, results have been contradictory in part because of variation in study design. Few studies have examined the use of aspirin or other NSAIDs on risk of NSCLC in women.
Methods: Through a case-control study of African American and Caucasian women with and without NSCLC, we examined the relationship between use of aspirin, NSAIDs, and acetaminophen and risk of NSCLC. Risk was estimated by calculating odds ratios and 95% confidence intervals for ever/never use, duration of use, and duration of use category (never, 1-5 years, &gt;5 years) after adjusting for major risk factors for lung cancer. Risk estimates were stratified by race, age, smoking history, and body mass index.
Results: Ever use of adult-strength aspirin was associated with a significant reduction in risk of NSCLC (odds ratio, 0.66; 95% confidence interval, 0.46-0.94). Additionally, there was a significant trend toward a reduced risk of NSCLC in adult-strength aspirin users with increasing duration of use (Ptrend = 0.02). In stratified analyses, aspirin use was associated with a significantly reduced risk of lung cancer among Caucasians and 55- to 64-year-olds. Baby aspirin and NSAID use was associated with a significant reduction in risk of NSCLC only among 65- to 74-year-olds.
Conclusion: Our results suggest that long-term use of adult-strength aspirin may reduce the risk of NSCLC in women. (Cancer Epidemiol Biomarkers Prev 2008;17(1):148–57)