bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor (TNF)‐α, soluble TNF receptors and endometrial cancer risk: The EPIC study
Authors: Dossus Laure , Becker Susen , Rinaldi Sabina , Lukanova Annekatrin , Tjønneland Anne , Olsen Anja , Overvad Kim , Chabbert‐Buffet Nathalie , Boutron‐Ruault Marie‐Christine , Clavel‐Chapelon Françoise , Teucher Birgit , Chang‐Claude Jenny , Pischon Tobias , Boeing Heiner , Trichopoulou Antonia , Benetou Vasiliki , Valanou Elisavet , Palli Domenico , Sieri Sabina , Tumino Rosario , Sacerdote Carlotta , Galasso Rocco , Redondo Maria‐Luísa , Bonet Catalina Bonet , Molina‐Montes Esther , Altzibar Jone M. , Chirlaque Maria‐Dolores , Ardanaz Eva , Bas Bueno‐de‐Mesquita H. , van Duijnhoven Fränzel J.B. , Peeters Petra H.M. , Charlotte Onland‐Moret N. , Lundin Eva , Idahl Annika , Khaw Kay‐Tee , Wareham Nicholas , Allen Naomi , Romieu Isabelle , Fedirko Veronika , Hainaut Pierre , Romaguera Dora , Norat Teresa , Riboli Elio , Kaaks Rudolf 
Published: December 2010

AbstractChronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor‐α (TNF‐α), one of the major pro‐inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case‐control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF‐α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two‐hundred‐seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two‐sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF‐α (odds ratio [OR]: 1.73, 95% CI: 1.09‐2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99‐2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92‐2.55, Ptrend = 0.03) after adjustment for body‐mass‐index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C‐peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF‐α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
Uptake of prostate‐specific antigen testing for early prostate cancer detection in Sweden
Authors: Jonsson Håkan , Holmström Benny , Duffy Stephen W. , Stattin Pär 
Published: December 2010

AbstractThe aim of our study was to estimate uptake of prostate‐specific antigen (PSA) testing in an entire country, including time trends and geographical differences. Data from the Swedish Cancer Register on prostate cancer incidence between 1980 and 2007 and published data from the Gothenburg branch of the European randomized study of screening for prostate cancer (ERSPC), a population‐based PSA screening study, were used in two models of changes in incidence of prostate cancer as a proxy for uptake of PSA testing in all 24 Swedish counties. The estimated annual PSA testing, irrespective of previous years' exposure, reached a peak of 12% of all men in 2004 and decreased thereafter to 6% in 2007 and varied from less than 5 to 20% between counties. Under the assumption that men who underwent annual PSA testing were previously unexposed to PSA testing, the cumulated uptake of PSA testing in men aged 55–69 years in Sweden increased from zero in 1997 to 56% in 2007. Our study shows that it is possible to estimate uptake of PSA testing in the population from the prostate cancer incidence pattern. There were large geographical variations in uptake of PSA testing despite a uniform health care system in Sweden and there was a substantial increase in the uptake of PSA testing during the study period, despite that there were no national recommendations for PSA‐based prostate cancer screening.
Sessile serrated adenomas and classical adenomas: An epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract
Authors: Dhir Mashaal , Yachida Shinichi , Neste Leander Van , Glöckner Sabine C. , Jeschke Jana , Pappou Emmanouil P. , Montgomery Elizabeth A. , Herman James G. , Baylin Stephen B. , Iacobuzio‐Donahue Christine , Ahuja Nita 
Published: December 2010

AbstractThe diagnosis of sessile serrated adenomas (SSAs) is challenging, and there is a great deal of interobserver variability amongst pathologists in differentiating SSAs from hyperplastic polyps (HPPs). The aim of this study was (i) to assess the utility of epigenetic changes such as DNA methylation in differentiating SSAs from HPPs and (ii) to identify common methylation based molecular markers potentially useful for early detection of premalignant neoplastic lesions of gastrointestinal tract. A total of 97 primary patient adenoma samples were obtained from The Johns Hopkins Hospital pathology archive with IRB approval and HIPAA compliance. We analyzed the promoter associated CpG island methylation status of 17 genes using nested multiplex methylation specific PCR (MSP). Methylation of CDX2, hMLH1 and TLR2 was detected in SSAs and SSAs with dysplasia but not in HPPs. A subset of genes including EVL, GATAs (4 and 5), HIN‐1, SFRPs (1, 2, 4 and 5), SOX17 and SYNE1 were methylated frequently in all premalignant gastrointestinal adenomas including tubular adenomas, villous adenomas, SSAs and SSAs with dysplasia but infrequently in non‐premalignant polyps such as HPPs. Methylation of CDX2, hMLH1 and TLR2 may be of diagnostic utility in differentiating, histologically challenging cases of SSAs from HPPs. Genes such as EVL, GATAs, HIN‐1, SFRPs, SOX17 and SYNE1, which are frequently methylated in all types of tested premalignant adenomas, may be useful as biomarkers in stool‐based strategies for early detection of these adenomas and CRCs in future.
Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications
Authors: Mazumder (Indra) Dipanjana , Mitra Sraboni , Singh Ratnesh Kumar , Dutta Sankhadeep , Roy Anup , Mondal Ranajit Kumar , Basu Partha Sarathi , Roychoudhury Susanta , Panda Chinmay Kumar 
Published: December 2010

AbstractTo understand the importance of frequent deletion of chromosomal 11q23.3‐24.3 region in cervical carcinogenesis, alterations (deletion/methylation/mutation/expression) of the candidate genes LOH11CR2A, EI24 and CHEK1 located in the region were analyzed in 29 cervical intraepithelial neoplasia (CIN), 112 cervical carcinoma (CACX) samples and two CACX cell lines. The deletion frequency of these genes was low in CIN than in CACX [CIN: CHEK1: 28%, EI24: 21%, LOH11CR2A: 15% and CACX: CHEK1: 51%, EI24: 41%, LOH11CR2A: 36%]. Similar trend was seen in promoter methylation of these genes [CIN: CHEK1: 10%, EI24: 3%, LOH11CR2A: 3% and CACX: CHEK1: 55%, EI24: 31%, LOH11CR2A: 14%]. Mutations of the genes are a rare event. Overall alterations (deletion and methylation) of CHEK1 and EI24 were associated with progression of CACX. Quantitative mRNA expression analysis showed reduced expression of the three genes in concordance to their molecular alterations. A shorter isoform of CHEK1 lacking exon 8, hence impaired in substrate binding capacity, was found in two samples. Immunohistochemical analysis showed nuclear expression of Chek1, p‐Chek1 and Ei24 in tumor tissues, whereas the cell lines exhibited both nuclear and cytoplasmic expression of Chek1 and Ei24, as is also evident from Western blot analysis suggesting differential localization of the proteins. Alterations of CHEK1 and EI24 coupled with tumor stage and early sexual debut (≤19 years) predicted worst prognosis. Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX.
Induction of cytotoxic T lymphocytes against ovarian cancer‐initiating cells
Authors: Weng Desheng , Song Baizheng , Durfee John , Sugiyama Valerie , Wu Zhengrong , Koido Shigeo , Calderwood Stuart K. , Gong Jianlin 
Published: December 2010

AbstractThe majority of patients with stage III/IV ovarian carcinoma that respond initially to standard therapies ultimately undergo relapse due to the survival of small populations of cells with tumor‐initiating potential. These ovarian cancer (OVCA)‐initiating cells (OCIC) are sometimes called cancer stem cells (CSC) because they express stem cell markers, and can survive conventional therapies such as chemotherapy, which usually target rapidly replicating tumor cells, and give rise to recurrent tumors that are more chemo‐resistant and more aggressive. Thus, it would be desirable to develop a therapy that could selectively target OCIC and be used to complement the conventional therapies. In this study, we isolated a subset of OVCA cells with a CD44+ phenotype in samples from patients with OVCA that possess CSC properties including the formation of spheroids in culture, self‐renewal and the ability to be engrafted in immune‐compromised mice. We next explored the use of immunotherapy using fusions of dendritic cells and OCIC to specifically target the OCIC subpopulations. Fusion cells (FCs) prepared in this way activated T cells to express elevated levels of IFN‐γ with enhanced killing of CD44+ OVCA cells. We envision a combined approach where conventional therapies such as chemotherapy kill the bulk of tumor cells, whereas OCIC‐reactive cytotoxic T lymphocytes target the resistant OCIC fraction. A combined therapy such as this may represent a promising approach for the treatment of OVCA.
GC‐MS‐based metabolomics reveals mechanism of action for hydrazine induced hepatotoxicity in rats
Authors: Bando Kiyoko , Kunimatsu Takeshi , Sakai Jun , Kimura Juki , Funabashi Hitoshi , Seki Takaki , Bamba Takeshi , Fukusaki Eiichiro 
Published: December 2010

AbstractGas chromatography–mass spectrometry (GC‐MS) has great advantages for analyzing organic/amino acids, which are often targets in efficacy and/or toxicity studies. Although GC‐MS has been used for the detection of many metabolic disorders, applications of GC‐MS‐based metabolomics in pharmacology/toxicology are relatively underdeveloped. We intended to investigate applicability of a GC‐MS‐based metabolomics approach for toxicological evaluation, and tried to elucidate the mechanism of hydrazine‐induced hepatotoxicity. Rats were administered hydrazine chloride orally (120 and 240 mg kg−1), and urine, plasma and liver samples were collected at 24 or 48 h post‐dosing. Conventional clinical chemistry and liver histopathology were performed, urine and plasma were analyzed by GC‐MS, and metabolic profiles were assessed using chemometric techniques. Principal component analysis score plots showed clear separation of the groups, indicating dose‐dependent toxicity and recovery. The mechanism of toxicity was investigated based on semi‐quantification data of identified metabolites. Amino acid precursors of glutathione (cystein, glutamate and glycine) and a product of glutathione metabolism (5‐oxoproline) were elevated dose‐dependently, accompanied with elevation of ascorbate levels. In addition, intermediates of the TCA cycle were decreased, whereas participants of the urea cycle and other amino acids were increased. These alterations were associated with histopathological changes such as fatty degeneration and glycogen accumulation. Application of GC‐MS‐based metabolomics revealed that oxidative stress and GSH consumption play important roles in the etiology of hydrazine‐induced hepatotoxicity, demonstrating that this approach is a useful tool in pharmacology and toxicology for screening, elucidating mode of action and biomarker discovery. Copyright © 2010 John Wiley & Sons, Ltd.
Presence of pores and hydrogel composition influence tensile properties of scaffolds fabricated from well‐defined sphere templates
Authors: LaNasa Stephanie M. , Hoffecker Ian T. , Bryant Stephanie J. 
Published: December 2010

AbstractSphere templating is an attractive method to produce porous polymeric scaffolds with well‐defined and uniform pore structures for applications in tissue engineering. While high porosity is desired to facilitate cell seeding and enhance nutrient transport, the incorporation of pores will impact gross mechanical properties of tissue scaffolds and will likely be dependent on pore size. The goals of this study were to evaluate the effect of pores, pore diameter, and polymer composition on gross mechanical properties of hydrogels prepared from crosslinked poly(ethylene glycol) (PEG) and poly(2‐hydroxyethyl methacrylate) (pHEMA). Sphere templates were fabricated from uncrosslinked poly(methyl methacrylate) spheres sieved between 53–63 and 150–180 μm. Incorporating pores into hydrogels significantly decreased the quasi‐static modulus and ultimate tensile stress, but increased the ultimate tensile strain. For pHEMA, decreases in gel crosslinking density and increases in pore diameters followed similar trends. Interestingly, the mechanical properties of porous PEG hydrogels were less sensitive to changes in pore diameter for a given polymer composition. Additionally, pore diameter was shown to affect skeletal myoblast adhesion whereby many cells cultured in porous hydrogels with smaller pores were seen spanning across multiple pores, but lined the inside of larger pores. In summary, incorporation of pores and changes in pore diameter significantly affect the gross mechanical properties, but in a manner that is dependent on gel chemistry, structure, and composition. Together, these findings will help to design better hydrogel scaffolds for applications where gross mechanical properties and porosity are critical. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
An efficient synthesis of pyrazolo[3,4‐b]quinolin‐5(6H)‐one derivatives in ionic liquid
Authors: Shi Da‐Qing , Yang Fang 
Published: December 2010

AbstractA series of 4‐aryl‐3,7,7‐trimethyl‐1‐phenyl‐7,8‐dihydro‐1H‐pyrazolo[3,4‐b]quinolin‐5(6H)‐ones were synthesized via the three‐component reaction of aromatic aldehydes, 5,5‐dimethyl‐1,3‐cyclohexandione and 5‐amino‐3‐methyl‐1‐phenylpyrazole in ionic liquid without using any catalyst. This protocol has the advantages of easier work‐up, milder reaction conditions, short reaction time, and environmentally benign procedure. J. Heterocyclic Chem., (2011).
Efficient preparation of 3‐substituted quinazolinediones directly from anthranilic acids and isocyanates
Authors: Koay Natalie , Campeau Louis‐Charles 
Published: December 2010

AbstractAn efficient and practical synthesis of 3‐substituted quinazolinediones is described. The protocol uses readily available isocyanates and anthranilic acids as precursors in a one‐pot operation and has been demonstrated on >50 g scale. Isolation of the products via filtration directly from the reaction media is facile, affording high‐purity material. This procedure was then applied to the synthesis of Zenarestat. J. Heterocyclic Chem., (2011).
Oogenesis of microlecithal oocytes in the viviparous teleost Heterandria formosa
Authors: Uribe Mari Carmen , Grier Harry J. 
Published: December 2010

AbstractViviparous teleosts exhibit two patterns of embryonic nutrition: lecithotrophy (when nutrients are derived from yolk that is deposited in the oocyte during oogenesis) and matrotrophy (when nutrients are derived from the maternal blood stream during gestation). Nutrients contained in oocytes of matrotrophic species are not sufficient to support embryonic development until term. The smallest oocytes formed among the viviparous poeciliid fish occur in the least killifish, Heterandria formosa, these having diameters of only 400 μm. Accordingly, H. formosa presents the highest level of matrotrophy among poeciliids. This study provides histological details occurring during development of its microlecithal oocytes. Five stages occur during oogenesis: oogonial proliferation, chromatin nucleolus, primary growth (previtellogenesis), secondary growth (vitellogenesis), and oocyte maturation. H. formosa, as in all viviparous poeciliids, has intrafollicular fertilization and gestation. Therefore, there is no ovulation stage. The full‐grown oocyte of H. formosa contains a large oil globule, which occupies most of the cell volume. The oocyte periphery contains the germinal vesicle, and ooplasm that includes cortical alveoli, small oil droplets and only a few yolk globules. The follicular cell layer is initially composed of a single layer of squamous cells during early previtellogenesis, but these become columnar during early vitellogenesis. They are pseudostratified during late vitellogenesis and reduce their height becoming almost squamous in full‐grown oocytes. The microlecithal oocytes of H. formosa represent an extreme in fish oogenesis typified by scarce yolk deposition, a characteristic directly related to matrotrophy. J. Morphol., 2011. © 2010 Wiley‐Liss, Inc.
Wintertime radiation and energy budget along an urbanization gradient in Montreal, Canada
Authors: Bergeron Onil , Strachan Ian B. 
Published: December 2010

AbstractThis study reports on the radiation and energy balance of three sites (rural, suburban, and urban) located along an urbanization gradient in the Montreal, QC, region for two winters (December–March) with contrasting snow regimes. The urban and suburban sites had similar albedo which was about half that at the rural site during the snow‐cover period. Temporal variability in albedo was attributable to the presence of snow on rooftops at the urban site and to a site‐specific response to cloudiness at the suburban site. As compared to the suburban site, the urban site showed higher albedo inducing lower net radiation (Q*) which was compensated for by greater anthropogenic heat flux (QF), so that the urban site had highest total available energy (Q* + QF). Hourly QF estimates were a significant term in the winter energy budget analysis. QF was dominated by building heating at both urbanized sites, while vehicular traffic contributed to rush hour peaks. Daytime total available energy was mostly dissipated as sensible heat flux (QH) at the beginning of the winter season and mostly stored (ΔQS) towards the end of the winter at both urbanized sites. Daytime energy partitioning into QH and ΔQS was correlated with air temperature with no significant differences between urbanized sites. On a daily time scale, available energy was mostly stored before noon and dissipated as QH in the afternoon at both urbanized sites. Urbanized sites showed differences in diurnal variability of QH and ΔQS occurring in the afternoon and evening. Latent heat flux (QE) was low throughout winter and accounted for 10% of the total available energy during daytime at the urbanized sites. Water vapour emissions showed intra‐urban differences in their response to wintertime climatic conditions. Copyright © 2010 Royal Meteorological Society
Development and analysis of a 50‐year high‐resolution daily gridded precipitation dataset over Spain (Spain02)
Authors: Herrera S. , Gutiérrez J. M. , Ancell R. , Pons M. R. , Frías M. D. , Fernández J. 
Published: December 2010

AbstractIn this paper, we present a new publicly available high‐resolution daily precipitation gridded dataset developed for peninsular Spain and the Balearic islands using 2756 quality‐controlled stations (this dataset is referred to as Spain02). The grid has a regular 0.2° (approx. 20 km) horizontal resolution and spans the period from 1950 to 2003. Different interpolation methods were tested using a cross‐validation approach to compare the resulting interpolated values against station data: kriging, angular distance weighting, and thin plane splines. Finally, the grid was produced applying the kriging method in a two‐step process. First, the occurrence was interpolated using a binary kriging and, in a second step, the amounts were interpolated by applying ordinary kriging to the occurrence outcomes. This procedure is similar to the interpolation method used to generate the E‐OBS gridded data—the state‐of‐the‐art publicly available high‐resolution daily dataset for Europe—which was used in this study for comparison purposes. Climatological statistics and extreme value indicators from the resulting grid were compared to those from the 25 km E‐OBS dataset using the observed station records as a reference. Spain02 faithfully reproduces climatological features such as annual precipitation occurrence, accumulated amounts and variability, whereas E‐OBS has some deficiencies in the southern region. When focusing on upper percentiles and other indicators of extreme precipitation regimes, Spain02 accurately reproduces the amount and spatial distribution of the observed extreme indicators, whereas E‐OBS data present serious limitations over Spain due to the sparse data used in this region. As extreme values are more sensitive to interpolation, the dense station coverage of this new data set was crucial to get an accurate reproduction of the extremes. Copyright © 2010 Royal Meteorological Society
A test for network‐wide trends in rainfall extremes
Authors: Burauskaite‐Harju Agne , Grimvall Anders , Brömssen Claudia von 
Published: December 2010

AbstractTemporal trends in meteorological extremes are often examined by first reducing daily data to annual index values, such as the 95th or 99th percentiles. Here, we report how this idea can be elaborated to provide an efficient test for trends at a network of stations. The initial step is to make separate estimates of tail probabilities of precipitation amounts for each combination of station and year by fitting a generalised Pareto distribution (GPD) to data above a user‐defined threshold. The resulting time series of annual percentile estimates are subsequently fed into a multivariate Mann‐Kendall (MK) test for monotonic trends. We performed extensive simulations using artificially generated precipitation data and noted that the power of tests for temporal trends was substantially enhanced when ordinary percentiles were substituted for GPD percentiles. Furthermore, we found that the trend detection was robust to misspecification of the extreme value distribution. An advantage of the MK test is that it can accommodate non‐linear trends, and it can also take into account the dependencies between stations in a network. To illustrate our approach, we used long time series of precipitation data from a network of stations in The Netherlands. Copyright © 2010 Royal Meteorological Society
Building effective virtual teams: How to overcome the problems of trust and identity in virtual teams
Authors: Kimble Chris 
Published: December 2010

AbstractThis article explores some of the challenges faced when managing virtual teams, in particular the role played by trust and identity in virtual teams. It outlines why teams and virtual teams have become a valuable part of the modern organization and presents ten short case studies that illustrate the range of activities in which virtual teams can be found. Following this, the article examines some of the common problems encountered in virtual team working. It discusses two broad classes of solutions. The first are solutions that are essentially technical in nature (i.e., where changes to or improvements in technology would help to solve or ameliorate the problem); the second are more organizationally based (i.e., where the root of the problem is in people and how they are managed). The article concludes that both the technical and the organizational solutions need to be considered in parallel if an attempt to build an effective virtual team is to be successful. © 2011 Wiley Periodicals, Inc.