bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1metabolic genes and risk of lung cancer in Asturias
Authors: López-Cima M Felicitas , Álvarez-Avellón Sara M , Pascual Teresa , Fernández-Somoano Ana , Tardón Adonina 
Published: September 2012

AbstractBackgroundMetabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of theCYP1A1 MspIT6235C,GSTM1 present/null,GSTT1 present/nullandGSTP1 Ile105Valpolymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain.MethodsA hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation.ResultsNo statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed.ConclusionsThese results suggest that genetic polymorphisms in theCYP1A1,GSTM1,GSTT1andGSTP1metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions ofCYP1A1 MspI T6235C,GSTM1present/null,GSTT1present/null andGSTP1Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.
Plasma concentrations of soluble cytokine receptors in euthymic bipolar patients with and without subsyndromal symptoms
Authors: Cetin Turan , Guloksuz Sinan , Cetin Esin Aktas , Gazioglu Sema Bilgic , Deniz Gunnur , Oral E Timucin , van Os Jim 
Published: September 2012

Abstract

Background
Current evidence suggests that high concentrations of pro-inflammatory markers are associated with bipolar disorder characterized by severe impairment during inter-episodic periods, reduced treatment response and persistent subsyndromal symptoms. We tested whether persistent subsyndromal symptoms in euthymic bipolar patients were associated with markers of an ongoing chronic pro-inflammatory process.

Methods
Forty-five euthymic bipolar patients (22 with subsyndromal symptoms (BD+) and 23 without subsyndromal symptoms (BD-) and 23 well controls (WC) were recruited for assessment of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R) and soluble interleukin-2 receptor (sIL-2R) concentrations. Soluble cytokine receptor concentrations were assessed using enzyme-linked immunosorbent assay.

Results
In comparison to WC, sTNF-R1 concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.34, p = 0.012 and β = 0.41, p = 0.003). Similarly, compared to WC, sIL-6R concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.44, p = 0.001 and β = 0.37, p = 0.008). There was no difference between BD- and BD+ in the concentration of either sTNF-R1 or sIL-6R; plasma concentration of sIL-2R was not analyzed as 75% percent of the samples were non-detectable.

Conclusions
Although bipolar patients present with a pro-inflammatory shift compared to well controls, subsyndromal symptoms are not associated with additive increasing effects. Longitudinal studies with larger samples are required to clarify the relationship between illness course and inflammatory markers in bipolar disorder.
Seven years of the field epidemiology training programme (FETP) at Chennai, Tamil Nadu, India: an internal evaluation
Authors:   The NIE FETP team (by alphabetical order), Bhatnagar Tarun , Gupte Mohan D , Hutin Yvan J , Kaur Prabhdeep , Kumaraswami Vasanthapuram , Manickam Ponnaiah , Murhekar Manoj , Ramachandran Vidya , Ramakrishnan Ramachandran 
Published: September 2012

Abstract

Background
During 2001–2007, the National Institute of Epidemiology (NIE), Chennai, Tamil Nadu, India admitted 80 trainees in its two-year Field Epidemiology Training Programme (FETP). We evaluated the first seven years of the programme to identify strengths and weaknesses.

Methods
We identified core components of the programme and broke them down into input, process, output and outcome. We developed critical indicators to reflect the logic model. We reviewed documents including fieldwork reports, abstracts listed in proceedings and papers published in Medline-indexed journals. We conducted an anonymous online survey of the graduates to collect information on self-perceived competencies, learning activities, field assignments, supervision, curriculum, relevance to career goals, strengths and weaknesses.

Results
Of the 80 students recruited during 2001–2007, 69 (86%) acquired seven core competencies (epidemiology, surveillance, outbreaks, research, human subjects protection, communication and management) and graduated through completion of at least six field assignments. The faculty-to-student ratio ranged between 0.4 and 0.12 (expected: 0.25). The curriculum was continuously adapted with all resources available on-line. Fieldwork led to the production of 158 scientific communications presented at international meetings and to 29 manuscripts accepted in indexed, peer-reviewed journals. The online survey showed that while most graduates acquired competencies, unmet needs persisted in laboratory sciences, data analysis tools and faculty-to-student ratio.

Conclusions
NIE adapted the international FETP model to India. However, further efforts are required to scale up the programme and to develop career tracks for field epidemiologists in the country.
Trion X+ in vertically coupled type II quantum dots in threading magnetic field
Authors: Horta-Piñeres Sindi , Escorcia-Salas Gene Elizabeth , Mikhailov Ilia D , Sierra-Ortega José 
Published: September 2012

Abstract
We analyze the energy spectrum of a positively charged exciton confined in a semiconductor heterostructure formed by two vertically coupled, axially symmetrical type II quantum dots located close to each other. The electron in the structure is mainly located inside the dots, while the holes generally move in the exterior region close to the symmetry axis. The solutions of the Schrödinger equation are obtained by a variational separation of variables in the adiabatic limit. Numerical results are shown for bonding and anti-bonding lowest-lying of the trion states corresponding to the different quantum dots morphologies, dimensions, separation between them, thicknesses of the wetting layers, and the magnetic field strength.
Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation
Authors: Halleskog Carina , Dijksterhuis Jacomijn Petronella , Kilander Michaela Brita Christina , Becerril-Ortega Javier , Villaescusa Juan Carlos , Lindgren Eva , Arenas Ernest , Schulte Gunnar 
Published: September 2012

Abstract

Background
WNT-5A signaling in the central nervous system is important for morphogenesis, neurogenesis and establishment of functional connectivity; the source of WNT-5A and its importance for cellular communication in the adult brain, however, are mainly unknown. We have previously investigated the inflammatory effects of WNT/β-catenin signaling in microglia in Alzheimer's disease. WNT-5A, however, generally recruits β-catenin-independent signaling. Thus, we aim here to characterize the role of WNT-5A and downstream signaling pathways for the inflammatory transformation of the brain's macrophages, the microglia.

Methods
Mouse brain sections were used for immunohistochemistry. Primary isolated microglia and astrocytes were employed to characterize the WNT-induced inflammatory transformation and underlying intracellular signaling pathways by immunoblotting, quantitative mRNA analysis, proliferation and invasion assays. Further, measurements of G protein activation by [γ-35 S]GTP binding, examination of calcium fluxes and cyclic AMP production were used to define intracellular signaling pathways.

Results
Astrocytes in the adult mouse brain express high levels of WNT-5A, which could serve as a novel astroglia-microglia communication pathway. The WNT-5A-induced proinflammatory microglia response is characterized by increased expression of inducible nitric oxide synthase, cyclooxygenase-2, cytokines, chemokines, enhanced invasive capacity and proliferation. Mapping of intracellular transduction pathways reveals that WNT-5A activates heterotrimeric Gi/o proteins to reduce cyclic AMP levels and to activate a Gi/o protein/phospholipase C/calcium-dependent protein kinase/extracellular signal-regulated kinase 1/2 (ERK1/2) axis. We show further that WNT-5A-induced ERK1/2 signaling is responsible for distinct aspects of the proinflammatory transformation, such as matrix metalloprotease 9/13 expression, invasion and proliferation.

Conclusions
Thus, WNT-5A-induced and G protein-dependent signaling to ERK1/2 is important for the regulation of proinflammatory responses in mouse primary microglia cells. We show for the first time that WNT-5A/G protein signaling mediates physiologically important processes in primary mammalian cells with natural receptor and G protein stochiometry. Consequently, WNT-5A emerges as an important means of astrocyte-microglia communication and we, therefore, suggest WNT-5A as a new player in neuroinflammatory conditions, such as neurodegenerative disease, hypoxia, stroke, injury and infection.
Annotate-it: a Swiss-knife approach to annotation, analysis and interpretation of single nucleotide variation in human disease
Authors: Sifrim Alejandro , Van Houdt Jeroen KJ , Tranchevent Leon-Charles , Nowakowska Beata , Sakai Ryo , Pavlopoulos Georgios A , Devriendt Koen , Vermeesch Joris R , Moreau Yves , Aerts Jan 
Published: September 2012

AbstractThe increasing size and complexity of exome/genome sequencing data requires new tools for clinical geneticists to discover disease-causing variants. Bottlenecks in identifying the causative variation include poor cross-sample querying, constantly changing functional annotation and not considering existing knowledge concerning the phenotype. We describe a methodology that facilitates exploration of patient sequencing data towards identification of causal variants under different genetic hypotheses. Annotate-it facilitates handling, analysis and interpretation of high-throughput single nucleotide variant data. We demonstrate our strategy using three case studies. Annotate-it is freely available and test data are accessible to all users at http://www.annotate-it.org.
Comparison of the low-frequency variations of the vertical and horizontal components of the electric background field at the sea bottom
Authors: Flekkøy Eirik G. , Håland Endre , Måløy Knut Jørgen 
Published: September 2012

Natural electric field variations are measured at the sea bottom over long periods of time by means of stationary, vertical, and horizontal galvanic antennas. We compare the power spectra of the vertical and horizontal field components and the extent to which they may be reduced by standard averaging techniques. Although the raw spectra of the vertical and horizontal components do not differ greatly, the difference in the spectra after averaging is significantly greater. Most significantly, in the frequency range between 0.0005 and 0.03 Hz, this averaging scheme suppresses the vertical electric field component more strongly than the horizontal component.
Lithologic imaging using complex conductivity: Lessons learned from the Hanford 300 Area
Authors: Mwakanyamale Kisa , Slater Lee , Binley Andrew , Ntarlagiannis Dimitrios 
Published: September 2012

Field-scale lithologic applications of complex conductivity ([Formula: see text]) imaging have been hindered by the challenges of (1) acquiring reliable induced polarization (IP) measurements and (2) obtaining reliable [Formula: see text] images from the measurements. We performed a series of 2D time domain resistivity/IP surveys at the Hanford 300 Area (Richland, Washington) where the challenge was to image the spatial distribution of two lithologic units that control the exchange between groundwater and surface water of the Columbia River. Exploiting the equivalence between time domain and frequency domain measurements of polarization, a 2D [Formula: see text] inversion (real conductivity [Formula: see text], imaginary conductivity [Formula: see text], and phase angle [Formula: see text]) was used to image the spatial distribution of [Formula: see text] across the site. Synthetic studies were carried out to investigate the effects of noise on the resolution of [Formula: see text] images and to add confidence on the interpretation of possible paleochannels observed in the field data sets. The synthetic studies show that, with increasing representative noise levels, degradation of the resolution of lithologic structures in the parameters most controlled by the IP measurements ([Formula: see text] and [Formula: see text]) is significantly greater than degradation of resolution of [Formula: see text] images. However, the acquisition of IP measurements, and the analysis of changes in [Formula: see text] and [Formula: see text] constrains the lithological interpretation of the geoelectrical data set due to the strong dependency of [Formula: see text] on lithological properties. A threshold based on [Formula: see text] measurements from cores at the site was used to estimate the elevation of the contact between the two key units, which is consistent with boreholes at the site. Variation in the elevation of this contact provides evidence of a depression in the Hanford-Ringold contact connecting the aquifer and the Columbia River; this depression likely represents a paleochannel regulating flow and transport at the site.
Discovery of a Novel Glucagon-like Peptide (GCGL) and Its Receptor (GCGLR) in Chickens: Evidence for the Existence of GCGL and GCGLR Genes in Nonmammalian Vertebrates
Authors: Wang Yajun , Meng Fengyan , Zhong Yu , Huang Guian , Li Juan 
Published: September 2012

AbstractGlucagon (GCG), glucagon-related peptides, and their receptors have been reported to play important roles including the regulation of glucose homeostasis, gastrointestinal activity, and food intake in vertebrates. In this study, we identified genes encoding a novel glucagon-like peptide (named GCGL) and its receptor (GCGLR) from adult chicken brain using RACE and/or RT-PCR. GCGL was predicted to encode a peptide of 29 amino acids (cGCGL1–29), which shares high amino acid sequence identity with mammalian and chicken GCG (62–66%). GCGLR is a receptor of 430 amino acids and shares relatively high amino acid sequence identity (53–55%) with the vertebrate GCG receptor (GCGR). Using a pGL3-CRE-luciferase reporter system, we demonstrated that synthetic cGCGL1–29, but not its structurally related peptides, i.e. exendin-4 and GCG, could potently activate GCGLR (EC50: 0.10 nm) expressed in Chinese hamster ovary cells, indicating that GCGLR can function as a GCGL-specific receptor. RT-PCR assay revealed that GCGL expression is mainly restricted to several tissues including various brain regions, spinal cord, and testes, whereas GCGLR mRNA is widely expressed in adult chicken tissues with abundant expression noted in the pituitary, spinal cord, and various brain regions. Using synteny analysis, GCGL and GCGLR genes were also identified in the genomes of fugu, tetraodon, tilapia, medaka, coelacanth, and Xenopus tropicalis. As a whole, the discovery of GCGL and GCGLR genes in chickens and other nonmammalian vertebrates clearly indicates a previously unidentified role of GCGL-GCGLR in nonmammalian vertebrates and provides important clues to the evolutionary history of GCG and GCGL genes in vertebrates.
Mitochondrial hyperfusion induced by loss of the fission protein Drp1 causes ATM-dependent G2/M arrest and aneuploidy through DNA replication stress
Authors: Qian Wei , Choi Serah , Gibson Gregory A. , Watkins Simon C. , Bakkenist Christopher J. , Van Houten Bennett 
Published: September 2012

Summary
Mitochondrial fission and fusion cycles are integrated with cell cycle progression. In this paper, we demonstrate that the inhibition of mitochondrial fission protein Drp1 causes an unexpected delay in G2/M cell cycle progression and aneuploidy. In investigating the underlying molecular mechanism, we revealed that inhibiting Drp1 triggers replication stress, which is mediated by a hyperfused mitochondrial structure and unscheduled expression of cyclin E in the G2 phase. This persistent replication stress then induces an ATM-dependent activation of the G2 to M transition cell cycle checkpoint. Knockdown of ATR, an essential kinase in preventing replication stress, significantly enhanced DNA damage and cell death of Drp1-deficienct cells. Persistent mitochondrial hyperfusion also induces centrosomal overamplification and chromosomal instability, which are causes of aneuploidy. Analysis using cells depleted of mitochondrial DNA revealed that these events are not mediated by the defects in mitochondrial ATP production and reactive oxygen species (ROS) generation. Thus dysfunctional mitochondrial fission directly induces genome instability by replication stress, which then initiates the DNA damage response. Our findings provide a novel mechanism that contributes to the cellular dysfunction and diseases associated with altered mitochondrial dynamics.
The outcomes of navigation-assisted bone tumour surgery
Authors: Cho H. S. , Oh J. H. , Han I. , Kim H-S. 
Published: September 2012

We evaluated the oncological and functional outcome of 18 patients, whose malignant bone tumours were excised with the assistance of navigation, and who were followed up for more than three years. There were 11 men and seven women, with a mean age of 31.8 years (10 to 57). There were ten operations on the pelvic ring and eight joint-preserving limb salvage procedures. The resection margins were free of tumour in all specimens. The tumours, which were stage IIB in all patients, included osteosarcoma, high-grade chondrosarcoma, Ewing’s sarcoma, malignant fibrous histiocytoma of bone, and adamantinoma. The overall three-year survival rate of the 18 patients was 88.9% (95% confidence interval (CI) 75.4 to 100). The three-year survival rate of the patients with pelvic malignancy was 80.0% (95% CI 55.3 to 100), and of the patients with metaphyseal malignancy was 100%. The event-free survival was 66.7% (95% CI 44.9 to 88.5). Local recurrence occurred in two patients, both of whom had a pelvic malignancy. The mean Musculoskeletal Tumor Society functional score was 26.9 points at a mean follow-up of 48.2 months (22 to 79).We suggest that navigation can be helpful during surgery for musculoskeletal tumours; it can maximise the accuracy of resection and minimise the unnecessary sacrifice of normal tissue by providing precise intra-operative three-dimensional radiological information.
The clinical and radiological outcome of pulsed electromagnetic field treatment for acute scaphoid fractures
Authors: Hannemann P. F. W. , Göttgens K. W. A. , van Wely B. J. , Kolkman K. A. , Werre A. J. , Poeze M. , Brink P. R. G. 
Published: September 2012

The use of pulsed electromagnetic fields (PEMF) to stimulate bone growth has been recommended as an alternative to the surgical treatment of ununited scaphoid fractures, but has never been examined in acute fractures. We hypothesised that the use of PEMF in acute scaphoid fractures would accelerate the time to union by 30% in a randomised, double-blind, placebo-controlled, multicentre trial. A total of 53 patients in three different medical centres with a unilateral undisplaced acute scaphoid fracture were randomly assigned to receive either treatment with PEMF (n = 24) or a placebo (n = 29). The clinical and radiological outcomes were assessed at four, six, nine, 12, 24 and 52 weeks. A log-rank analysis showed that neither time to clinical and radiological union nor the functional outcome differed significantly between the groups. The clinical assessment of union indicated that at six weeks tenderness in the anatomic snuffbox (p = 0.03) as well as tenderness on longitudinal compression of the scaphoid (p = 0.008) differed significantly in favour of the placebo group. We conclude that stimulation of bone growth by PEMF has no additional value in the conservative treatment of acute scaphoid fractures.
Proximal interphalangeal joint replacement in patients with arthritis of the hand
Authors: Adams J. , Ryall C. , Pandyan A. , Metcalf C. , Stokes M. , Bradley S. , Warwick D. J. 
Published: September 2012

We systematically reviewed all the evidence published in the English language on proximal interphalangeal joint (PIPJ) replacement, to determine its effectiveness on the function of the hand and the associated post-operative complications. Original studies were selected if they reported clinical outcome with a minimum of one year’s follow-up. Quality was assessed using the Cowley systematic review criteria modified for finger-joint replacements. Of 319 articles identified, only five were adequately reported according to our quality criteria; there were no randomised controlled trials. PIPJ replacements had a substantial effect size on hand pain of -23.2 (95% confidence interval (CI) -27.3 to -19.1) and grip strength 1.2 (95% CI -10.7 to 13.1), and a small effect on range of movement 0.2 (95% CI -0.4 to 0.8). A dorsal approach was most successful. Post-operative loosening occurred in 10% (95% CI 3 to 30) of ceramic and 12.5% (95% CI 7 to 21) of pyrocarbon replacements. Post-operative complications occurred in 27.8% (95% CI 20 to 37). We conclude that the effectiveness of PIPJ replacement has not been established. Small observational case studies and short-term follow-up, together with insufficient reporting of patient data, functional outcomes and complications, limit the value of current evidence. We recommend that a defined core set of patients, surgical and outcome data for this intervention be routinely and systematically collected within the framework of a joint registry.