bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epistatic study reveals two genetic interactions in blood pressure regulation
Authors: Ndiaye Ndeye Coumba , Said El Shamieh , Stathopoulou Maria G , Siest Gérard , Tsai Michael Y , Visvikis-Siest Sophie 
Published: March 2013

Abstract

Background
Although numerous candidate gene and genome-wide association studies have been performed on blood pressure, a small number of regulating genetic variants having a limited effect have been identified. This phenomenon can partially be explained by possible gene-gene/epistasis interactions that were little investigated so far.

Methods
We performed a pre-planned two-phase investigation: in phase 1, one hundred single nucleotide polymorphisms (SNPs) in 65 candidate genes were genotyped in 1,912 French unrelated adults in order to study their two-locus combined effects on blood pressure (BP) levels. In phase 2, the significant epistatic interactions observed in phase 1 were tested in an independent population gathering 1,755 unrelated European adults.

Results
Among the 9 genetic variants significantly associated with systolic and diastolic BP in phase 1, some may act through altering the corresponding protein levels: SNPs rs5742910 (Padjusted≤0.03) and rs6046 (Padjusted =0.044) in F7 and rs1800469 (Padjusted ≤0.036) in TGFB1; whereas some may be functional through altering the corresponding protein structure: rs1800590 (Padjusted =0.028, SE=0.088) in LPL and rs2228570 (Padjusted ≤9.48×10-4) in VDR. The two epistatic interactions found for systolic and diastolic BP in the discovery phase: VCAM1 (rs1041163) * APOB (rs1367117), and SCGB1A1 (rs3741240) * LPL (rs1800590), were tested in the replication population and we observed significant interactions on DBP. In silico analyses yielded putative functional properties of the SNPs involved in these epistatic interactions trough the alteration of corresponding protein structures.

Conclusions
These findings support the hypothesis that different pathways and then different genes may act synergistically in order to modify BP. This could highlight novel pathophysiologic mechanisms underlying hypertension.
Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues
Authors: Rodrigues-Peres Raquel Mary , Cadore Solange , Febraio Stefanny , Heinrich Juliana Karina , Serra Katia Piton , Derchain Sophie F M , Vassallo Jose , Sarian Luis Otavio 
Published: March 2013

Abstract

Background
Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels.

Methods
A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS.

Results
The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02).

Conclusions
Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum concentration is related to the key genomic abnormalities associated with breast carcinogenesis.
The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption
Authors: Yasui Hironobu , Asanuma Taketoshi , Kino Junichi , Yamamori Tohru , Meike Shunsuke , Nagane Masaki , Kubota Nobuo , Kuwabara Mikinori , Inanami Osamu 
Published: March 2013

Abstract

Background
Glioblastoma is one of the intractable cancers and is highly resistant to ionizing radiation. This radioresistance is partly due to the presence of a hypoxic region which is widely found in advanced malignant gliomas. In the present study, we evaluated the effectiveness of the hypoxic cell sensitizer doranidazole (PR-350) using the C6 rat glioblastoma model, focusing on the status of blood brain barrier (BBB).

Methods
Reproductive cell death in the rat C6 glioma cell line was determined by means of clonogenic assay. An intracranial C6 glioma model was established for the in vivo experiments. To investigate the status of the BBB in C6 glioma bearing brain, we performed the Evans blue extravasation test. Autoradiography with [14C]-doranidazole was performed to examine the distribution of doranidazole in the glioma tumor. T2-weighted MRI was employed to examine the effects of X-irradiation and/or doranidazole on tumor growth.

Results
Doranidazole significantly enhanced radiation-induced reproductive cell death in vitro under hypoxia, but not under normoxia. The BBB in C6-bearing brain was completely disrupted and [14C]-doranidazole specifically penetrated the tumor regions. Combined treatment with X-irradiation and doranidazole significantly inhibited the growth of C6 gliomas.

Conclusions
Our results revealed that BBB disruption in glioma enables BBB-impermeable radiosensitizers to penetrate and distribute in the target region. This study is the first to propose that in malignant glioma the administration of hydrophilic hypoxic radiosensitizers could be a potent strategy for improving the clinical outcome of radiotherapy without side effects.
Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues
Authors: Raine Emma V A , Dodd Andrew W , Reynard Louise N , Loughlin John 
Published: March 2013

AbstractBackgroundThe single nucleotide polymorphism (SNP) rs2615977 is associated with osteoarthritis (OA) and is located in intron 31 ofCOL11A1, a strong candidate gene for this degenerative musculoskeletal disease. Furthermore, the common non-synonymousCOL11A1SNP rs1676486 is associated with another degenerative musculoskeletal disease, lumbar disc herniation (LDH). rs1676486 is a C-T transition mediating its affect on LDH susceptibility by modulatingCOL11A1expression. The risk T-allele of rs1676486 leads to reduced expression of theCOL11A1transcript, a phenomenon known as allelic expression imbalance (AEI). We were keen therefore to assess whether the effect that rs1676486 has onCOL11A1expression in LDH is also observed in OA and whether the rs2615977 association to OA also marked AEI.MethodsUsing RNA from OA cartilage, we assessed whether either SNP correlated withCOL11A1AEI by 1) measuringCOL11A1expression and stratifying the data by genotype at each SNP; and 2) quantifying the mRNA transcribed from each allele of the two SNPs. We also assessed whether rs1676486 was associated with OA susceptibility using a case–control cohort of over 18,000 individuals.ResultsWe observed significant AEI at rs1676486 (p < 0.0001) with the T-allele correlating with reducedCOL11A1expression. This corresponded with observations in LDH but the SNP was not associated with OA. We did not observe AEI at rs2615977.ConclusionsCOL11A1is subject to AEI in OA cartilage. AEI at rs1676486 is a risk factor for LDH, but not for OA. These two diseases therefore share a common functional phenotype, namely AEI ofCOL11A1, but this appears to be a disease risk only in LDH. Other functional effects onCOL11A1presumably account for the OA susceptibility that maps to this gene.
MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRα
Authors: Zhong Dan , Zhang Yan , Zeng Yi-jun , Gao Min , Wu Geng-ze , Hu Chang-jiang , Huang Gang , He Feng-tian 
Published: March 2013

Abstract

Background
MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor α (LXRα), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells.

Methods
HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXRα and its target genes involved in lipogenesis, binding site for miR-613 in 3′-untranslated region (3′-UTR) of LXRα mRNA and lipid droplet accumulation in the cells.

Results
MiR-613 dramatically suppressed the expression of LXRα and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3′-UTR of LXRα mRNA. Moreover, miR-613 significantly repressed LXRα-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXRα without 3′-UTR markedly attenuated the miR-613-mediated downregulation of LXRα’s target genes and LXRα-induced lipid droplet accumulation.

Conclusions
MiR-613 suppresses lipogenesis by directly targeting LXRα in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.
Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease
Authors: Dams Judith , Klotsche Jens , Bornschein Bernhard , Reese Jens P , Balzer-Geldsetzer Monika , Winter Yaroslav , Schrag Anette , Siderowf Andrew , Oertel Wolfgang H , Deuschl Günther , Siebert Uwe , Dodel Richard 
Published: March 2013

AbstractBackgroundClinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates.MethodsLinear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models.ResultsThe regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2of 0.60 and 0.67. The independent data confirmed the prediction models.ConclusionThe best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.
Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors
Authors: Diaz Claudia Marcela , Chiappori Alberto , Aurisicchio Luigi , Bagchi Ansuman , Clark Jason , Dubey Sheri , Fridman Arthur , Fabregas Jesus C , Marshall John , Scarselli Elisa , La Monica Nicola , Ciliberto Gennaro , Montero Alberto J 
Published: March 2013

Abstract

Background
DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease.

Methods
Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2).

Results
The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination.

Conclusion
V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2.

Trial registration
Study 1 – ClinicalTrials.gov, NCT00250419; Study 2 – ClinicalTrials.gov, NCT00647114.
A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior
Authors: Morris Gerwyn , Anderson George , Galecki Piotr , Berk Michael , Maes Michael 
Published: March 2013

AbstractIt is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.
Management of a female with recurrence of fibromatosis of the chest wall adjacent to the breast: a case report
Authors: Shen Cheng , Zhou Yubin , Che Guowei 
Published: March 2013

Abstract
Extra-abdominal desmoid tumor is a rare soft tissue tumor that is histologically benign, but may behave aggressively. This case report specifically describes the clinical, radiographic, and pathologic features of 27 year-old female who experienced a post-surgical recurrence of fibromatosis of the chest wall over a two-year period of time secondary to previous inadequate excision. The fibromatosis was found to be involving the lower-inner quadrant of her right breast and causing worsening pain. A surgical management strategy was successfully undertaken.
Molecular identification of microorganisms associated with the brine shrimp Artemia franciscana
Authors: Riddle Misty R , Baxter Bonnie K , Avery Brian J 
Published: March 2013

Abstract

Background
Prior research on the microorganisms associated with the brine shrimp, Artemia franciscana, has mainly been limited to culture-based identification techniques or feeding studies for aquaculture. Our objective was to identify bacteria and archaea associated with Artemia adults and encysted embryos to understand the role of microbes in the Artemia life cycle and, therefore, their importance in a hypersaline food chain.

Results
We used small subunit (SSU) 16S ribosomal RNA gene sequencing to identify bacteria and archaea associated with adults and encysted Artemia embryos from one of their natural environments – Great Salt Lake (GSL), Utah, USA. We found that bacterial sequences most closely related to the genera Halomonas and Vibrio were commonly extracted from GSL adult Artemia, while bacterial sequences most similar to the genera Halomonas, Psychroflexus and Alkalilimnicola dominate in GSL water. Encysted embryos (cysts) yielded bacterial sequences from the genera Idiomarina and Salinivibrio, which were absent from adults and water. Common archaeal sequences in adults were most closely related to the genera Haloterrigena and Haloarcula, while all of the archaeal sequences from GSL water were most similar to the genus Halogeometricum. Cyst derived archaeal sequences were most closely related to the genera Halorubrum and Haloarcula.

Conclusions
In addition to identifying microbial rRNA sequences that are specific to different stages of the Artemia life cycle, we observed striking differences in the sequences associated with the adult Artemia population in samples collected from GSL at different times and locations. While our study was limited in scope and the sample was small, our findings provide a foundation for future research into how the bacteria and archaea associated with Artemia influence the Artemia life cycle, and GSL food web.
Attitudes among healthcare professionals to the reporting of adverse drug reactions in Nepal
Authors: KC Santosh , Tragulpiankit Pramote , Gorsanan Sarun , Edwards I Ralph 
Published: March 2013

Abstract

Background
Healthcare professional’s knowledge and attitudes to adverse drug reaction (ADR) and ADR reporting play vital role to report any cases of ADR. Positive attitudes may favour ADR reporting by healthcare professionals. This study was aimed to investigate the attitudes towards and ways to improve adverse drug reaction (ADR) reporting among healthcare professionals working at four Regional Pharmacovigilance Centres (RPCs) of Nepal.

Methods
A cross sectional study was done by survey using a self-administered structured questionnaire. The questionnaire was distributed to 450 healthcare professionals working at four RPCs.

Results
The overall response rate was 74.0%. There were 74.8% of healthcare professionals who had seen patient experiencing an ADR; however, only 20.1% had reported. Reporting form not available (48.1%) and other colleagues not reporting ADR cases (46.9%) would significantly discourage the ADR reporting among healthcare professionals working at four RPCs. Healthcare professionals perceived that seriousness of the reaction (75.6%); unusual reaction (64.6%); reaction to new product (71.2%); new reaction to existing product (70.2%); and confidence in diagnosis of ADR (60.8%) were important factors on the decision to report ADR. Awareness among healthcare professionals (85.9%), training (76.0%), collaboration (67.0%), and involve pharmacist for ADR reporting (63.1%) were mostly recognized ways to improve reporting. Regular newsletter on current awareness in drug safety (71.2%), information on new ADR (65.8%), and international drug safety information (64.0%) were the identified feedbacks they would like to receive from the Nepal pharmacovigilance programme.

Conclusion
Healthcare professionals working at four RPCs of Nepal have positive attitudes towards ADR reporting. Awareness among healthcare professionals, training and collaboration would likely improve reporting provided they would receive appropriate feedback from the national pharamcovigilance programme.
Electrospun eri silk fibroin scaffold coated with hydroxyapatite for bone tissue engineering applications
Authors: Andiappan Muthumanickkam , Sundaramoorthy Subramanian , Panda Niladrinath , Meiyazhaban Gowri , Winfred Sofi Beaula , Venkataraman Ganesh , Krishna Pramanik 
Published: March 2013

Abstract
Natural biomaterials such as collagen, silk fibroin, and chitosan, and synthetic biopolymers such as polylactic acid, polycaprolactone, polyglycolic acid, and their copolymers are being used as scaffold for tissue engineering applications. In the present work, a fibrous mat was electrospun from eri silk fibroin (ESF). A composite of hydroxyapatite (Hap) and the ESF scaffold was prepared by soaking the ESF scaffold in a solution of calcium chloride and then in sodium diammonium phosphate. The average tensile stress of the pure ESF and hydroxyapatite-coated ESF scaffold (ESF-Hap) was found to be 1.84 and 0.378 MPa, respectively. Pure ESF and ESF-Hap scaffolds were evaluated for their characteristics by a themogravimetric analyzer and Fourier transform infrared spectroscope. The crystallinity and thermal stability of the ESF-Hap scaffold were found to be more than that of uncoated eri silk nanofiber scaffold. The water uptake of the pure ESF and ESF-Hap scaffolds was found to be 69% and 340%, respectively, in distilled water as well as phosphate buffer saline. The hemolysis percentage of both scaffolds was less than 5%, which indicate their good blood compatibility. The cytocompatibility studied by 3-(4,5-dimethyl) thiazol-2-yl-2,5-dimethyl tetrazolium bromide assay showed that the scaffold is biocompatible. To assess cell attachment and growth on the scaffold, human mesenchymal stem cells were cultured on the scaffolds. The results from scanning electron microscopy and fluorescent microscopy showed a notable cellular growth and favorable morphological features. Hence, the ESF-Hap scaffold is better suited for cell growth than the pure ESF scaffold.