bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients
Authors: Körner Christian , Riesner Katarina , Krämer Benjamin , Eisenhardt Marianne , Glässner Andreas , Wolter Franziska , Berg Thomas , Müller Tobias , Sauerbruch Tilman , Nattermann Jacob , Spengler Ulrich , Nischalke Hans Dieter 
Published: March 2012

Abstract

Background
Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.

Methods
Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population.

Results
Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049).

Conclusions
The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.
Increasing organ donation via anticipated regret (INORDAR): protocol for a randomised controlled trial
Authors: O'Carroll Ronan E , Ferguson Eamonn , Hayes Peter C , Shepherd Lee 
Published: March 2012

Abstract

Background
Throughout the world there is an insufficient supply of donor organs to meet the demand for organ transplantations. This paper presents a protocol for a randomised controlled trial, testing whether a simple, theory-based anticipated regret manipulation leads to a significant increase in posthumous organ donor registrations.

Methods
We will use a between-groups, prospective randomised controlled design. A random sample of 14,520 members of the adult Scottish general public will be contacted via post. These participants will be randomly allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group will simply receive a letter and donor registration form. The questionnaire control (QC) arm will receive a questionnaire measuring their emotions and non-cognitive affective attitudes towards organ donation. The theory of planned behavior (TPB) group will complete the emotions and affective attitudes questionnaire plus additional items assessing their cognitive attitudes towards organ donation, perceived control over registration and how they think significant others view this action. Finally, the anticipated regret (AR) group will complete the same indices as the TPB group, plus two additional anticipated regret items. These items will assess the extent to which the participant anticipates regret for not registering as an organ donor in the near future. The outcome variable will be NHS Blood and Transplant verified registrations as an organ donor within 6 months of receiving our postal intervention.

Discussion
This study will assess whether simply asking people to reflect on the extent to which they may anticipate regret for not registering as an organ donor increases organ donor registration 6 months later. If successful, this simple and easy to administer theory-based intervention has the potential to save lives and money for the NHS by reducing the number of people receiving treatments such as dialysis. This intervention may also be incorporated into future organ donor campaigns.

Trial registration number
ISRCTN: ISRCTN92204897
Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes
Authors: Chu Chih-Sheng , Lee Kun-Tai , Cheng Kai-Hong , Lee Min-Yi , Kuo Hsuan-Fu , Lin Tsung-Hsien , Su Ho-Ming , Voon Wen-Chol , Sheu Sheng-Hsiung , Lai Wen-Ter 
Published: March 2012

Abstract

Background
Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM).

Methods
Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT.

Results
Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 μ mol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis.

Conclusions
These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.
Saharan dust and association between particulate matter and case-specific mortality: a case-crossover analysis in Madrid (Spain)
Authors: Díaz Julio , Tobías Aurelio , Linares Cristina 
Published: March 2012

Abstract

Background
Saharan dust intrusions are a common phenomenon in the Madrid atmosphere, leading induce exceedances of the 50 μg/m3- EU 24 h standard for PM10.

Methods
We investigated the effects of exposure to PM10 between January 2003 and December 2005 in Madrid (Spain) on daily case-specific mortality; changes of effects between Saharan and non-Saharan dust days were assessed using a time-stratified case-crossover design.

Results
Saharan dust affected 20% of days in the city of Madrid. Mean concentration of PM10 was higher during dust days (47.7 μg/m3) than non-dust days (31.4 μg/m3). The rise of mortality per 10 μg/m3 PM10 concentration were always largely for Saharan dust-days. When stratifying by season risks of PM10, at lag 1, during Saharan dust days were stronger for respiratory causes during cold season (IR% = 3.34% (95% CI: 0.36, 6.41) versus 2.87% (95% CI: 1.30, 4.47)) while for circulatory causes effects were stronger during warm season (IR% = 4.19% (95% CI: 1.34, 7.13) versus 2.65% (95% CI: 0.12, 5.23)). No effects were found for cerebrovascular causes.

Conclusions
We found evidence of strongest effects of particulate matter during Saharan dust days, providing a suggestion of effect modification, even though interaction terms were not statistically significant. Further investigation is needed to understand the mechanism by which Saharan dust increases mortality.
Superantigen profiles of emm and emm-like typeable and nontypeable pharyngeal streptococcal isolates of South India
Authors: Anand Thangarajan Durai , Rajesh Thangamani , Rajendhran Jeyaprakash , Gunasekaran Paramasamy 
Published: March 2012

AbstractBackgroundThe major virulence factors determining the pathogenicity of streptococcal strains include M protein encoded byemmandemm-like (emmL) genes and superantigens. In this study, the distribution ofemm, emmLand superantigen genes was analyzed among the streptococcal strains isolated from the patients of acute pharyngitis.MethodsThe streptococcal strains were isolated from the throat swabs of 1040 patients of acute pharyngitis. TheemmandemmLgenes were PCR amplified from each strain and sequenced to determine theemmtypes. The dot-blot hybridization was performed to confirm the pathogens as trueemmnontypeable strains. The presence of eleven currently known superantigens was determined in all the strains by multiplex PCR.ResultsTotally, 124 beta-hemolytic streptococcal strains were isolated and they were classified as group A streptococcus (GAS) [15.3% (19/124)], group C streptococcus (GCS) [59.7% (74/124)] and group G streptococcus (GGS) [25.0% (31/124)]. Among 124 strains, only 35 strains wereemmtypeable and the remaining 89 strains wereemmnontypeable. All GAS isolates were typeable, whereas most of the GCS and GGS strains were nontypeable. These nontypeable strains belong toS. anginosus[75.3% (67/89)] andS. dysgalactiaesubsp.equisimilis[24.7% (22/89)]. TheemmandemmLtypes identified in this study includeemm12.0(28.6%),stG643.0(28.6%),stC46.0(17.0%),emm30.11(8.5%),emm3.0(2.9%),emm48.0(5.7%),st3343.0(2.9%),emm107.0(2.9%) andstS104.2(2.9%). Various superantigen profiles were observed in typeable as well as nontypeable strains.ConclusionsMultiplex PCR analysis revealed the presence of superantigens in all the typeable strains irrespective of theiremmtypes. However, the presence of superantigen genes inemmandemmLnontypeable strains has not been previously reported. In this study, presence of at least one or a combination of superantigen coding genes was identified in all theemmandemmLnontypeable strains. Thus, the superantigens may inevitably play an important role in the pathogenesis of these nontypeable strains in the absence of the primary virulence factor, M protein.
IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors
Authors: Regel Ivonne , Eichenmüller Melanie , Joppien Saskia , Liebl Johanna , Häberle Beate , Müller-Höcker Josef , Vollmar Angelika , von Schweinitz Dietrich , Kappler Roland 
Published: March 2012

Abstract

Background
Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.

Results
The IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion.

Conclusion
This study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.
De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer
Authors: Wu Xiwei , Somlo George , Yu Yang , Palomares Melanie R , Li Arthur Xuejun , Zhou Weiying , Chow Amy , Yen Yun , Rossi John J , Gao Harry , Wang Jinhui , Yuan Yate-Ching , Frankel Paul , Li Sierra , Ashing-Giwa Kimlin Tam , Sun Guihua , Wang Yafan , Smith Robin , Robinson Kim , Ren Xiubao , Wang Shizhen Emily 
Published: March 2012

AbstractBackgroundMicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.MethodsThe pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.ResultsMore than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.ConclusionsOur study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy
Authors: Bowerman Melissa , Murray Lyndsay M , Boyer Justin G , Anderson Carrie L , Kothary Rashmi 
Published: March 2012

Abstract

Background
Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil.

Methods
Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P < 0.05. For the remaining analyses, the Student's two-tail t test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at P < 0.05.

Results
Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific.

Conclusions
Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA and for other degenerative diseases characterized by muscular atrophy and postsynaptic immaturity.
Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges
Authors: Konold Timm , Bone Gemma E , Clifford Derek , Chaplin Melanie J , Cawthraw Saira , Stack Michael J , Simmons Marion M 
Published: March 2012

AbstractBackgroundThe majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes.ResultsTwo groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry.ConclusionsThe prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and methods that are currently in use.
NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C) stimulation
Authors: Lian Ling , Ciraci Ceren , Chang Guobin , Hu Jingdong , Lamont Susan J 
Published: March 2012

Abstract

Background
NLRC5 is a member of the CARD domain containing, nucleotide-binding oligomerization (NOD)-like receptor (NLR) family, which recognizes pathogen-associated molecular patterns (PAMPs) and initiates an innate immune response leading to inflammation and/or cell death. However, the specific role of NLRC5 as a modulator of the inflammatory immune response remains controversial. It has been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene. But no study on NLRC5 function has been reported to date in chickens. In the current study, we investigated the role of NLRC5 in the regulation of IFNA, IFNB, IL-6, and MHC class I in the chicken HD11 macrophage cell line, by using RNAi technology. HD11 cells were transfected with one of five siRNAs (s1, s2, s3, negative-siRNA, or a mixture of s1, s2, s3-siRNAs). After 24 hours, cells were exposed to LPS or poly (I:C) or a vehicle control. Gene expression of NLRC5, IFNA, IFNB, IL-6, and MHC class I at 2, 4, 6, and 8 hours post stimulation (hps) was quantified by qPCR.

Results
The expression of NLRC5, IFNA, IFNB, and IL-6 genes in negative irrelevant transfection controls was up-regulated at 2 hps after LPS treatment compared to the vehicle controls. S3-siRNA effectively knocked down NLRC5 expression at 4 hps, and the expression of IFNA and IFNB (but not IL-6 and MHC class I) was also down-regulated at 4 hps in s3-siRNA transfected cells, compared to negative irrelevant transfection controls. Stimulation by LPS appeared to relatively restore the decrease in NLRC5, IFNA, and IFNB expression, but the difference is not significant.

Conclusions
Functional characterization of chicken NLRC5 in an in vitro system demonstrated its importance in regulating intracellular molecules involved in inflammatory response. The knockdown of NLRC5 expression negatively mediates gene expression of IFNA and IFNB in the chicken HD11 cell line; therefore, NLRC5 likely has a role in positive regulation of IFNA and IFNB expression. No direct relationship was found between NLRC5 knockdown and IL-6 and MHC class I expression. Future studies will further clarify the roles of NLRC5 and other NLRs in infectious diseases of chickens and may increase the efficacy of antiviral vaccine design.
Random generation of RNA secondary structures according to native distributions
Authors: Nebel Markus E , Scheid Anika , Weinberg Frank 
Published: March 2012

Abstract

Background
Random biological sequences are a topic of great interest in genome analysis since, according to a powerful paradigm, they represent the background noise from which the actual biological information must differentiate. Accordingly, the generation of random sequences has been investigated for a long time. Similarly, random object of a more complicated structure like RNA molecules or proteins are of interest.

Results
In this article, we present a new general framework for deriving algorithms for the non-uniform random generation of combinatorial objects according to the encoding and probability distribution implied by a stochastic context-free grammar. Briefly, the framework extends on the well-known recursive method for (uniform) random generation and uses the popular framework of admissible specifications of combinatorial classes, introducing weighted combinatorial classes to allow for the non-uniform generation by means of unranking. This framework is used to derive an algorithm for the generation of RNA secondary structures of a given fixed size. We address the random generation of these structures according to a realistic distribution obtained from real-life data by using a very detailed context-free grammar (that models the class of RNA secondary structures by distinguishing between all known motifs in RNA structure). Compared to well-known sampling approaches used in several structure prediction tools (such as SFold) ours has two major advantages: Firstly, after a preprocessing step in time

O

(

n

2

)

for the computation of all weighted class sizes needed, with our approach a set of m random secondary structures of a given structure size n can be computed in worst-case time complexity

O

m
⋅
n
⋅
log

(

n

)

while other algorithms typically have a runtime in

O

(

m
⋅

n

2

)

. Secondly, our approach works with integer arithmetic only which is faster and saves us from all the discomforting details of using floating point arithmetic with logarithmized probabilities.

Conclusion
A number of experimental results shows that our random generation method produces realistic output, at least with respect to the appearance of the different structural motifs. The algorithm is available as a webservice at http://wwwagak.cs.uni-kl.de/NonUniRandGen and can be used for generating random secondary structures of any specified RNA type. A link to download an implementation of our method (in Wolfram Mathematica) can be found there, too.