bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer
Authors: Ibragimova Ilsiya , Ibáñez de Cáceres Inmaculada , Hoffman Amanda M. , Potapova Anna , Dulaimi Essel , Al-Saleem Tahseen , Hudes Gary R. , Ochs Michael F. , Cairns Paul 
Published: August 2010

Abstract
Transcriptional silencing associated with aberrant promoter hypermethylation is a common mechanism of inactivation of tumor suppressor genes in cancer cells. To globally profile the genes silenced by hypermethylation in prostate cancer, we screened a whole genome expression microarray for genes reactivated in the LNCaP, DU-145, PC-3, and MDA2b prostate tumor cell lines after treatment with the demethylating drug 5-aza-2-deoxycytidine and the histone deacetylation–inhibiting drug trichostatin A. A total of 2,997 genes showed at least 2-fold upregulation of expression after drug treatment in at least one prostate tumor cell line. For validation, we examined the first 45 genes, ranked by upregulation of expression, which had a typical CpG island and were known to be expressed in the normal cell counterpart. Two important findings were, first, that several genes known to be frequently hypermethylated in prostate cancer were apparent, and, second, that validation studies revealed eight novel genes hypermethylated in the prostate tumor cell lines, four of which were unmethylated in normal prostate cells and hypermethylated in primary prostate tumors (SLC15A3, 66%; KRT7, 54%; TACSTD2, 17%; GADD45b, 3%). Thus, we established the utility of our screen for genes hypermethylated in prostate cancer cells. One of the novel genes was TACSTD2/TROP2, a marker of human prostate basal cells with stem cell characteristics. TACSTD2 was unmethylated in prostatic intraepithelial neoplasia and may have utility in emerging methylation-based prostate cancer tests. Further study of the hypermethylome will provide insight into the biology of the disease and facilitate translational studies in prostate cancer. Cancer Prev Res; 3(9); 1084–92. ©2010 AACR.
DNA Methylation Markers for Prostate Cancer with a Stem Cell Twist
Authors: Jerónimo Carmen , Esteller Manel 
Published: August 2010

Abstract
This perspective on Ibragimova et al. (beginning on page 1084 in this issue of the journal) highlights the potential role of DNA methylation–based markers in the early detection of prostate cancer (PCa), with a focus on the global reactivation of expression of genes epigenetically silenced in PCa cell lines. Novel findings of these investigators identified four genes methylated specifically in PCa, including the stem cell marker TACSTD2, which seems to discriminate PCa (methylated TACSTD2) from prostatic intraepithelial neoplasia (unmethylated). These genes add significantly to the list of epigenetic markers showing promise for clinical early detection of PCa in the near future. Cancer Prev Res; 3(9); 1053–5. ©2010 AACR.
The Role of Regional Advisory Councils in the European Common Fisheries Policy: Legal Constraints and Future Options
Authors: Long Ronán 
Published: August 2010

AbstractOne of the outcomes of the reform of the European common fisheries policy (CFP) in 2002 was the establishment of Regional Advisory Councils (RACs) to enable the European Commission to benefit from the knowledge and experience of stakeholders in the formulation and implementation of fisheries management measures by the European institutions. RACs are now in operation for the Baltic Sea, the North Sea, North-Western Waters, South-Western Waters, the High-Seas/Long-Distance Fleet, Pelagic Stocks, and the Mediterranean Sea. The CFP will be subject to further reform in 2011. This article reviews the legal constraints and future prospects for enhancing RAC participation in decision-making within the European institutions in light of the Commission’s proposals tabled in the 2009 Green Paper on Reform of the CFP and changes to European law resulting from the Lisbon Treaty.
International Treaties and U.S. Laws as Tools to Regulate the Greenhouse Gas Emissions from Ships and Ports
Authors: Torbitt Alison , Hildreth Richard 
Published: August 2010

AbstractRegulations on marine greenhouse gas emissions are possible, and some are in progress, using international treaty law and federal regulations. Under the United Nations Convention on the Law of the Sea (LOSC), port and coastal States have jurisdiction over ships entering their waters and have the ability to implement mitigation strategies, ranging from mandatory speed reduction to installing shore-side electricity or sequestration equipment. Under the International Convention for the Prevention of Pollution from Ships (MARPOL) Annex VI, the International Maritime Organization (IMO) is determining the feasibility of design, fuel, and operation reforms. Alternatively, the implementation may be usurped by a global cap-and-trade scheme from the United Nations Framework Convention on Climate Change. In the U.S., the Environmental Protection Agency (EPA) is tightening the Clean Air Act § 213 regulations governing marine vessels and U.S. waters were recently designated a SOx Emission Control Area. However, carbon dioxide emissions from marine vessels remain unregulated.
Between Integration Provision and Selection Mechanism. Party Politics, Judicial Constraints, and the Making of French and Dutch Policies of Civic Integration Abroad
Authors: Bonjour Saskia 
Published: August 2010

AbstractBoth the Netherlands and France have recently introduced civic integration abroad policies, which stipulate that family migrants are to learn about the language and customs of the host society, before being admitted to the country. The Dutch program however is much more stringent than the French. While France requires only participation in an evaluation and course that are organised and financed by the French state, the Dutch government has made entry conditional upon passing a test and does not offer courses. In this article, I propose two explanations for the significant differences between the modalities of the Dutch and French civic integration abroad programs. The first is related to party politics, that is to the positions adopted by political parties and the relations between them; the second to the different judicial constraints that weigh upon family migration policies in France and in the Netherlands.
Gracilis Autograft for Recurrent Posttraumatic Instability of the Superior Tibiofibular Joint
Authors: Maffulli Nicola , Spiezia Filippo , Oliva Francesco , Testa Vittorino , Capasso Giovanni , Denaro Vincenzo 
Published: August 2010

Background Several reconstruction procedures have been proposed to manage recurrent dislocation of the superior tibiofibular joint. Hypothesis Reconstruction of the superior tibiofibular joint using a gracilis tendon autograft is effective in recurrent dislocation of the superior tibiofibular joint. Study Design Case series; Level of evidence, 4. Methods Eight patients with recurrent dislocation of the superior tibiofibular joint without anatomical predisposing factors and who practiced sports were included in the study. Evaluation included the modified Cincinnati rating system and the Kujala score, anthropometry, plain radiography, and isokinetic dynamometry. Results The average follow-up was 44 ± 13 months. The mean modified Cincinnati score increased from 54 preoperatively to 92 (P = .01). The mean Kujala scores increased from 48 preoperatively to 85 (P = .05). The muscle volume of the thigh of the operated limb remained less well developed than the muscle volume of the nonoperated limb (P = .05). Significant isokinetic strength differences were found between the operated and the contralateral limb (P = .02) even at the latest follow-up. Conclusion Gracilis autograft for posttraumatic instability of the superior tibiofibular joint is a safe, reliable management option for recurrent dislocation of the superior tibiofibular joint in patients without any predisposing factors.
Treatment adherence of cancer patients to orally administered chemotherapy: Insights from a Greek study using a self-reported questionnaire
Authors: Saratsiotou Ioanna , Kordoni Maria , Bakogiannis Charalampos , Livadarou Eleftheria , Skarlos Dimosthenis , Kosmidis Paris A , Razis Evangelia 
Published: August 2010

Purpose. The aim of this prospective observational study was to investigate the patterns of treatment adherence to orally administered chemotherapy of patients being treated for cancer. Methods. Patients were asked to participate in the survey during their visits to the study centers’ pharmacists or doctors to obtain their oral medication from April 2008 until May 2009. The data were collected using a self-reported anonymous 7-page long questionnaire, which contained questions about their demographic profile, disease and treatment characteristics, and side-effects and adherence information, both intentional and nonintentional. Results. 99 Patients completed the questionnaire. Missing values ranged from 1% to 8%. Unintended nonadherence to therapy was reported by 19 patients. The most important factor correlating with unintended nonadherence was the patient’s belief regarding treatment effectiveness since only 16.7% of the patients believing that their treatment is effective reported nonadherence as opposed to 62.5% for those that did not believe that treatment is effective ( p = 0.03). Intentional nonadherence was reported by 14 patients The most important factor correlating to intentional nonadherence was time since disease diagnosis, as nonadherence was reported by 33.3% of the patients having the disease less than 6 months, compared to 16.7% for those between 6 and 24 months and 8.3% for those between 2 and 5 years ( p = 0.01). Conclusion. Greek patients seem to have similar nonadherence pattern as in other countries. Confidence in treatment efficacy appeared as a significant adherence determinant.
Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan
Authors: Yoshida Jin , Koda Shigeki , Nishida Shozo , Yoshida Toshiaki , Miyajima Keiko , Kumagai Shinji 
Published: August 2010

Purpose. The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Methods. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A—E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Results. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. Conclusion. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.
Highly-multiplexed SNP genotyping for genetic mapping and germplasm diversity studies in pea
Authors: Deulvot Chrystel , Charrel Hélène , Marty Amandine , Jacquin Françoise , Donnadieu Cécile , Lejeune-Hénaut Isabelle , Burstin Judith , Aubert Grégoire 
Published: August 2010

Abstract

Background
Single Nucleotide Polymorphisms (SNPs) can be used as genetic markers for applications such as genetic diversity studies or genetic mapping. New technologies now allow genotyping hundreds to thousands of SNPs in a single reaction.
In order to evaluate the potential of these technologies in pea, we selected a custom 384-SNP set using SNPs discovered in Pisum through the resequencing of gene fragments in different genotypes and by compiling genomic sequence data present in databases. We then designed an Illumina GoldenGate assay to genotype both a Pisum germplasm collection and a genetic mapping population with the SNP set.

Results
We obtained clear allelic data for more than 92% of the SNPs (356 out of 384). Interestingly, the technique was successful for all the genotypes present in the germplasm collection, including those from species or subspecies different from the P. sativum ssp sativum used to generate sequences. By genotyping the mapping population with the SNP set, we obtained a genetic map and map positions for 37 new gene markers.

Conclusion
Our results show that the Illumina GoldenGate assay can be used successfully for high-throughput SNP genotyping of diverse germplasm in pea. This genotyping approach will simplify genotyping procedures for association mapping or diversity studies purposes and open new perspectives in legume genomics.
Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion
Authors: de Backer Marijke WA , Brans Maike AD , Luijendijk Mieneke CM , Garner Keith M , van den Heuvel Dianne MA , Pasterkamp R Jeroen , Adan Roger AH 
Published: August 2010

AbstractBackgroundMultiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.ResultsWe fused the signal peptide from the Von Willebrand Factor (VWF) to a furin site followed by a processed form of the Agouti related protein (AgRP), AgRP83-132or α-melanocyte stimulating hormone.In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release.In vivoadministration of VWF-AgRP83-132, using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector.ConclusionsThis study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.
YAO is a nucleolar WD40-repeat protein critical for embryogenesis and gametogenesis in Arabidopsis
Authors: Li Hong-Ju , Liu Nai-You , Shi Dong-Qiao , Liu Jie , Yang Wei-Cai 
Published: August 2010

Abstract

Background
In flowering plants, gametogenesis generates multicellular male and female gametophytes. In the model system Arabidopsis, the male gametophyte or pollen grain contains two sperm cells and a vegetative cell. The female gametophyte or embryo sac contains seven cells, namely one egg, two synergids, one central cell and three antipodal cells. Double fertilization of the central cell and egg produces respectively a triploid endosperm and a diploid zygote that develops further into an embryo. The genetic control of the early embryo patterning, especially the initiation of the first zygotic division and the positioning of the cell plate, is largely unknown.

Results
Here we report the characterization of a mutation, yaozhe (yao), that causes zygote arrest and misplacement of cell plate of the zygote, leading to early embryo lethality. In addition, gametophyte development is partially impaired. A small portion of the mutant embryo sacs are arrested at four-nucleate stage with aberrant nuclear positioning. Furthermore, the competence of male gametophytes is also compromised. YAO encodes a nucleolar protein with seven WD-repeats. Its homologues in human and yeast have been shown to be components of the U3 snoRNP complex and function in 18S rRNA processing. YAO is expressed ubiquitously, with high level of expression in tissues under active cell divisions, including embryo sacs, pollen, embryos, endosperms and root tips.

Conclusions
Phenotypic analysis indicated that YAO is required for the correct positioning of the first zygotic division plane and plays a critical role in gametogenesis in Arabidopsis. Since YAO is a nucleolar protein and its counterparts in yeast and human are components of the U3 snoRNP complex, we therefore postulate that YAO is most likely involved in rRNA processing in plants as well.
"Sleep disparity" in the population: poor sleep quality is strongly associated with poverty and ethnicity
Authors: Patel Nirav P , Grandner Michael A , Xie Dawei , Branas Charles C , Gooneratne Nalaka 
Published: August 2010

Abstract

Background
Little is known about the social determinants of sleep attainment. This study examines the relationship of race/ethnicity, socio-economic status (SES) and other factors upon sleep quality.

Methods
A cross-sectional survey of 9,714 randomly selected subjects was used to explore sleep quality obtained by self-report, in relation to socioeconomic factors including poverty, employment status, and education level. The primary outcome was poor sleep quality. Data were collected by the Philadelphia Health Management Corporation.

Results
Significant differences were observed in the outcome for race/ethnicity (African-American and Latino versus White: unadjusted OR = 1.59, 95% CI 1.24-2.05 and OR = 1.65, 95% CI 1.37-1.98, respectively) and income (below poverty threshold, unadjusted OR = 2.84, 95%CI 2.41-3.35). In multivariable modeling, health indicators significantly influenced sleep quality most prominently in poor individuals. After adjusting for socioeconomic factors (education, employment) and health indicators, the association of income and poor sleep quality diminished, but still persisted in poor Whites while it was no longer significant in poor African-Americans (adjusted OR = 1.95, 95% CI 1.47-2.58 versus OR = 1.16, 95% CI 0.87-1.54, respectively). Post-college education (adjusted OR = 0.47, 95% CI 0.31-0.71) protected against poor sleep.

Conclusions
A "sleep disparity" exists in the study population: poor sleep quality is strongly associated with poverty and race. Factors such as employment, education and health status, amongst others, significantly mediated this effect only in poor subjects, suggesting a differential vulnerability to these factors in poor relative to non-poor individuals in the context of sleep quality. Consideration of this could help optimize targeted interventions in certain groups and subsequently reduce the adverse societal effects of poor sleep.
Diet as prophylaxis and treatment for venous thromboembolism?
Authors: Cundiff David K , Agutter Paul S , Malone P Colm , Pezzullo John C 
Published: August 2010

AbstractBackgroundBoth prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.Methods and FindingsThe literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment.Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.ConclusionsBecause of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.
Simulation methods with extended stability for stiff biochemical Kinetics
Authors: Rué Pau , Villà-Freixa Jordi , Burrage Kevin 
Published: August 2010

Abstract

Background
With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows.

Results
In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.

Conclusions
The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.