bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins as potential therapeutic drug for asthma?
Authors: Yuan Cheng , Zhou Lin , Cheng Jiyun , Zhang Jingying , Teng Yue , Huang Mao , Adcock Ian M , Barnes Peter J , Yao Xin 
Published: November 2012

Abstract

Background
Statins are lipid-lowering agents that also exhibit pleiotropic effects in decreasing oxidative stress and inflammation. There have been several published studies reporting the use of statins in the treatment of asthma patients, but their results are not consistent. The aim of this study is to determine whether statins are beneficial for asthma administration, and explore the potential covariables that may affect their clinical effectiveness.

Methods
A systematic literature search was performed in PubMed, Embase and Cochrane Center Register of Controlled Trials from inception to September 2012. Randomized controlled trials (RCT), retrospective studies and controlled clinical trials which reported the use of statins in the treatment of asthma patients were eligible. Quality evaluation was conducted for RCT using Jadad criteria.

Results
A total of 18 articles were included. In our study, we found no conclusive evidence to demonstrate that statins could enhance the lung function in asthmatics, although, they may reduce airway inflammation. Additionally, the results were not consistent across studies with respect to symptoms, quality of life, maintenance medication, asthma hospitalization/emergency department (ED) visits.

Conclusions
Statins may reduce airway inflammation in asthmatics, without having a significant effect on lung function. Further large sample and multicenter clinical trials are needed to confirm this and to see if there are more responsive phenotypes of asthma.
Local functional descriptors for surface comparison based binding prediction
Authors: Cipriano Gregory M , George Phillips N , Gleicher Michael 
Published: November 2012

Abstract

Background
Molecular recognition in proteins occurs due to appropriate arrangements of physical, chemical, and geometric properties of an atomic surface. Similar surface regions should create similar binding interfaces. Effective methods for comparing surface regions can be used in identifying similar regions, and to predict interactions without regard to the underlying structural scaffold that creates the surface.

Results
We present a new descriptor for protein functional surfaces and algorithms for using these descriptors to compare protein surface regions to identify ligand binding interfaces. Our approach uses descriptors of local regions of the surface, and assembles collections of matches to compare larger regions. Our approach uses a variety of physical, chemical, and geometric properties, adaptively weighting these properties as appropriate for different regions of the interface. Our approach builds a classifier based on a training corpus of examples of binding sites of the target ligand. The constructed classifiers can be applied to a query protein providing a probability for each position on the protein that the position is part of a binding interface. We demonstrate the effectiveness of the approach on a number of benchmarks, demonstrating performance that is comparable to the state-of-the-art, with an approach with more generality than these prior methods.

Conclusions
Local functional descriptors offer a new method for protein surface comparison that is sufficiently flexible to serve in a variety of applications.
Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics
Authors: Jaime Maria DLA , Lopez-Llorca Luis Vicente , Conesa Ana , Lee Anna Y , Proctor Michael , Heisler Lawrence E , Gebbia Marinella , Giaever Guri , Westwood J Timothy , Nislow Corey 
Published: November 2012

Abstract

Background
Chitosan oligosaccharide (COS), a deacetylated derivative of chitin, is an abundant, and renewable natural polymer. COS has higher antimicrobial properties than chitosan and is presumed to act by disrupting/permeabilizing the cell membranes of bacteria, yeast and fungi. COS is relatively non-toxic to mammals. By identifying the molecular and genetic targets of COS, we hope to gain a better understanding of the antifungal mode of action of COS.

Results
Three different chemogenomic fitness assays, haploinsufficiency (HIP), homozygous deletion (HOP), and multicopy suppression (MSP) profiling were combined with a transcriptomic analysis to gain insight in to the mode of action and mechanisms of resistance to chitosan oligosaccharides. The fitness assays identified 39 yeast deletion strains sensitive to COS and 21 suppressors of COS sensitivity. The genes identified are involved in processes such as RNA biology (transcription, translation and regulatory mechanisms), membrane functions (e.g. signalling, transport and targeting), membrane structural components, cell division, and proteasome processes. The transcriptomes of control wild type and 5 suppressor strains overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the presence and absence of COS. Some of the up-regulated transcripts in the suppressor overexpressing strains exposed to COS included genes involved in transcription, cell cycle, stress response and the Ras signal transduction pathway. Down-regulated transcripts included those encoding protein folding components and respiratory chain proteins. The COS-induced transcriptional response is distinct from previously described environmental stress responses (i.e. thermal, salt, osmotic and oxidative stress) and pre-treatment with these well characterized environmental stressors provided little or any resistance to COS.

Conclusions
Overexpression of the ARL1 gene, a member of the Ras superfamily that regulates membrane trafficking, provides protection against COS-induced cell membrane permeability and damage. We found that the ARL1 COS-resistant over-expression strain was as sensitive to Amphotericin B, Fluconazole and Terbinafine as the wild type cells and that when COS and Fluconazole are used in combination they act in a synergistic fashion. The gene targets of COS identified in this study indicate that COS’s mechanism of action is different from other commonly studied fungicides that target membranes, suggesting that COS may be an effective fungicide for drug-resistant fungal pathogens.
The effect of strand bias in Illumina short-read sequencing data
Authors: Guo Yan , Li Jiang , Li Chung-I , Long Jirong , Samuels David C , Shyr Yu 
Published: November 2012

Abstract

Background
When using Illumina high throughput short read data, sometimes the genotype inferred from the positive strand and negative strand are significantly different, with one homozygous and the other heterozygous. This phenomenon is known as strand bias. In this study, we used Illumina short-read sequencing data to evaluate the effect of strand bias on genotyping quality, and to explore the possible causes of strand bias.

Result
We collected 22 breast cancer samples from 22 patients and sequenced their exome using the Illumina GAIIx machine. By comparing the consistency between the genotypes inferred from this sequencing data with the genotypes inferred from SNP chip data, we found that, when using sequencing data, SNPs with extreme strand bias did not have significantly lower consistency rates compared to SNPs with low or no strand bias. However, this result may be limited by the small subset of SNPs present in both the exome sequencing and the SNP chip data. We further compared the transition and transversion ratio and the number of novel non-synonymous SNPs between the SNPs with low or no strand bias and those with extreme strand bias, and found that SNPs with low or no strand bias have better overall quality. We also discovered that the strand bias occurs randomly at genomic positions across these samples, and observed no consistent pattern of strand bias location across samples. By comparing results from two different aligners, BWA and Bowtie, we found very consistent strand bias patterns. Thus strand bias is unlikely to be caused by alignment artifacts. We successfully replicated our results using two additional independent datasets with different capturing methods and Illumina sequencers.

Conclusion
Extreme strand bias indicates a potential high false-positive rate for SNPs.
Weighted pedigree-based statistics for testing the association of rare variants
Authors: Shugart Yin Yao , Zhu Yun , Guo Wei , Xiong Momiao 
Published: November 2012

AbstractBackgroundWith the advent of next-generation sequencing (NGS) technologies, researchers are now generating a deluge of data on high dimensional genomic variations, whose analysis is likely to reveal rare variants involved in the complex etiology of disease. Standing in the way of such discoveries, however, is the fact that statistics for rare variants are currently designed for use with population-based data. In this paper, we introduce a pedigree-based statistic specifically designed to test for rare variants in family-based data. The additional power of pedigree-based statistics stems from the fact that while rare variants related to diseases or traits of interest occur only infrequently in populations, in families with multiple affected individuals, such variants are enriched. Note that while the proposed statistic can be applied with and without statistical weighting, our simulations show that its power increases when weighting (WSS and VT) are applied.ResultsOur working hypothesis was that, since rare variants are concentrated in families with multiple affected individuals, pedigree-based statistics should detect rare variants more powerfully than population-based statistics. To evaluate how well our new pedigree-based statistics perform in association studies, we develop a general framework for sequence-based association studies capable of handling data from pedigrees of various types and also from unrelated individuals. In short, we developed a procedure for transforming population-based statistics into tests for family-based associations. Furthermore, we modify two existing tests, the weighted sum-square test and the variable-threshold test, and apply both to our family-based collapsing methods. We demonstrate that the new family-based tests are more powerful than corresponding population-based test and they generate a reasonable type I error rate.To demonstrate feasibility, we apply the newly developed tests to a pedigree-based GWAS data set from the Framingham Heart Study (FHS). FHS-GWAS data contain approximately 5000 uncommon variants with frequencies less than 0.05. Potential association findings in these data demonstrate the feasibility of the software PB-STAR (note, PB-STAR is now freely available to the public).ConclusionOur tests show that when analyzing for rare variants, a pedigree-based design is more powerful than a population-based case–control design. We further demonstrate that a pedigree-based statistic’s power to detect rare variants increases in direct relation to the proportion of affected individuals within the pedigree.
Forward chemical genetic screens in Arabidopsis identify genes that influence sensitivity to the phytotoxic compound sulfamethoxazole
Authors: Schreiber Karl J , Austin Ryan S , Gong Yunchen , Zhang Jianfeng , Fung Pauline , Wang Pauline W , Guttman David S , Desveaux Darrell 
Published: November 2012

Abstract

Background
The sulfanilamide family comprises a clinically important group of antimicrobial compounds which also display bioactivity in plants. While there is evidence that sulfanilamides inhibit folate biosynthesis in both bacteria and plants, the complete network of plant responses to these compounds remains to be characterized. As such, we initiated two forward genetic screens in Arabidopsis in order to identify mutants that exhibit altered sensitivity to sulfanilamide compounds. These screens were based on the growth phenotype of seedlings germinated in the presence of the compound sulfamethoxazole (Smex).

Results
We identified a mutant with reduced sensitivity to Smex, and subsequent mapping indicated that a gene encoding 5-oxoprolinase was responsible for this phenotype. A mutation causing enhanced sensitivity to Smex was mapped to a gene lacking any functional annotation.

Conclusions
The genes identified through our forward genetic screens represent novel mediators of Arabidopsis responses to sulfanilamides and suggest that these responses extend beyond the perturbation of folate biosynthesis.
Spreading brain lesions in a familial Creutzfeldt-Jakob disease with V180I mutation over 4 years
Authors: Deguchi Kentaro , Takamiya Motonori , Deguchi Shoko , Morimoto Nobutoshi , Kurata Tomoko , Ikeda Yoshio , Abe Koji 
Published: November 2012

Abstract

Background
We report a female patient with familial Creutzfeldt-Jakob disease with V180I mutation (fCJD with V180I), who was serially followed up with magnetic resonance imaging (MRI) and electroencephalogram (EEG) for up to four years.

Case presentation
At 6 months after the onset, diffusion-weighted images (DWI) and fluid-attenuated inversion recovery (FLAIR) of brain MRI revealed an increased signal intensity in the bilateral frontal, temporal, and parietal cerebral cortex with left dominancy except for the occipital lobe. However, her follow-up MRI at four years showed the high-signal regions spreading to the occipital cerebral cortex in DWI and FLAIR images, and bilateral frontal cerebral white matter in FLAIR images. EEG showed a progressive and general slow high-voltage rhythm from 7–8 to 3–5 c/s over four years, without evidence of periodic synchronous discharge. These findings correspond to the symptom progression even after akinetic mutism at 18 months.

Conclusion
We suggest that serial MRI and EEG examinations are useful for early diagnosis of fCJD with V180I and for monitoring disease progression.
Over prescription of antibiotics for adult pharyngitis is prevalent in developing countries but can be reduced using McIsaac modification of Centor scores: a cross-sectional study
Authors: Palla Amber Hanif , Khan Rafeeq Alam , Gilani Anwar H , Marra Fawziah 
Published: November 2012

AbstractBackgroundAlthoughGroup A beta hemolytic streptococcus (GABHS)can cause bacterial pharyngitis, the most common etiology is viral; despite this viral etiology, antibiotics are commonly prescribed for this infection in industrialized countries. We investigated the prevalence ofGABHSin adult pharyngitis patients from lower socioeconomic settings in Karachi, Pakistan, how often antibiotics are prescribed for pharyngitis and if appropriate agents were used in a developing world setting. Finally, we wanted to see the usefulness of modified McIsaac scores in predicting positive cultures.MethodsAdult patients were recruited from three local hospital outpatient dispensaries (OPDs). All patients aged 14–65 years who were suspected of having bacterial pharyngitis had throat swabs taken. Laboratory results forGABHSpharyngitis were then compared with their prescriptions. Appropriateness (using the World Health Organization’s definition) and type of antibiotic prescribed were assessed.ResultsOf 137 patients,30 patients each were studied for scores of 0, 1, 2 and 3; 17 patients were studied for score 4. Although 6 (4.4%) patients wereGABHS+, for a prevalence of 43.8 per 1000 population, antibiotics were prescribed to 135 patients (98.5%). Of these, only 11.1% received appropriate antibiotics while 88.9%received inappropriate antibiotics.Penicillins were prescribed most (34.1%), especially amoxicillin/clavulanate; followed by macrolides (31.1%), especially the second-generation agents, and fluoroquinolones (14.8%). McIsaac scores were found to be 100% sensitive and 68.7% specific, giving a positive predictive value (PPV) of 12.7% and a negative predictive value (NPV) of 100%.ConclusionsAntibiotics were prescribed irrationally to adult pharyngitis patients, as most cultures were negative for bacterial infection. McIsaac modification of Centor scores related directly to culture results. We would therefore highly recommend its use to help family physicians make treatment decisions for adult pharyngitis patients.
Strengthening and stretching for rheumatoid arthritis of the hand (SARAH): design of a randomised controlled trial of a hand and upper limb exercise intervention - ISRCTN89936343
Authors:   Sarah Trial Team, Adams Jo , Bridle Chris , Dosanjh Sukhdeep , Heine Peter , Lamb Sarah E , Lord Joanne , McConkey Christopher , Nichols Vivien , Toye Francine , Underwood Martin R , Williams Mark A , Williamson Esther M 
Published: November 2012

AbstractBackgroundRheumatoid Arthritis (RA) commonly affects the hands and wrists with inflammation, deformity, pain, weakness and restricted mobility leading to reduced function. The effectiveness of exercise for RA hands is uncertain, although evidence from small scale studies is promising. The Strengthening And Stretching for Rheumatoid Arthritis of the Hand (SARAH) trial is a pragmatic, multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of adding an optimised exercise programme for hands and upper limbs to best practice usual care for patients with RA.Methods/design480 participants with problematic RA hands will be recruited through 17 NHS trusts. Treatments will be provided by physiotherapists and occupational therapists. Participants will be individually randomised to receive either best practice usual care (joint protection advice, general exercise advice, functional splinting and assistive devices) or best practice usual care supplemented with an individualised exercise programme of strengthening and stretching exercises. The study assessors will be blinded to treatment allocation and will follow participants up at four and 12 months. The primary outcome measure is the Hand function subscale of the Michigan Hand Outcome Questionnaire, and secondary outcomes include hand and wrist impairment measures, quality of life, and resource use. Economic and qualitative studies will also be carried out in parallel.DiscussionThis paper describes the design and development of a trial protocol of a complex intervention study based in therapy out-patient departments. The findings will provide evidence to support or refute the use of an optimised exercise programme for RA of the hand in addition to best practice usual care.Trial registrationCurrent Controlled Trials ISRCTN89936343
FSH prevents depletion of the resting follicle pool by promoting follicular number and morphology in fresh and cryopreserved primate ovarian tissues following xenografting
Authors: von Schönfeldt Viktoria , Chandolia Ramesh , Ochsenkühn Robert , Nieschlag Eberhard , Kiesel Ludwig , Sonntag Barbara 
Published: November 2012

Abstract

Background
Cryopreservation and transplantation of ovarian tissue is one option for re-establishing ovarian function, but optimal conditions for graft sustainment and follicular survival are still considered experimental. The present study aims to analyze the effect of FSH treatment on the resting follicle pool in fresh and cryopreserved primate ovarian tissues following xenografting.

Methods
Ovarian tissues from adult marmosets were grafted freshly or following cryopreservation to ovarectomized nude mice treated with FSH 25 IU twice daily post transplantation or left untreated as controls. Grafts were retrieved 2 or 4 weeks after transplantation to evaluate the number and morphological appearance of follicles.

Results
Early start of FSH treatment within 1 week following transplantation partly prevents primordial follicle loss in fresh and frozen-thawed tissues, whereas after a 3 weeks time interval this effect is present only in fresh tissues. A similar positive effect of early, but not later FSH treatment on primary follicles is seen in fresh tissues compared to only marginal effects in frozen-thawed tissues. The percentage of morphologically normal follicles is generally increased in FSH treated tissues, whereas the percentage of primary follicles over all primordial and primary follicles is increased by FSH only in freshly-grafted tissues.

Conclusions
FSH treatment alleviates depletion of the resting follicle pool and promotes normal follicular morphology both in freshly and frozen-thawed grafted tissues. In previously cryopreserved tissues, applying to most of the tissues intended for clinical use in fertility preservation attempts, its positive effect on primordial follicle numbers and potential graft sustainment is dependent on an early start of treatment within one week of transplantation.
Association of genome variations in the renin-angiotensin system with physical performance
Authors: Sgourou Argyro , Fotopoulos Vassilis , Kontos Vassilis , Patrinos George P , Papachatzopoulou Adamantia 
Published: November 2012

Abstract

Background
The aim of this study was to determine the genotype distribution and allelic frequencies of ACE (I/D), AGTR1 (A +1166 C), BDKRB2 (+9/−9) and LEP (G–2548A) genomic variations in 175 Greek athletes who excelled at a national and/or international level and 169 healthy Greek adults to identify whether some particular combinations of these loci might serve as predictive markers for superior physical condition.

Results
The D/D genotype of the ACE gene (p = 0.034) combined with the simultaneous existence of BDKRB2 (+9/−9) (p = 0.001) or LEP (G/A) (p = 0.021) genotypes was the most prevalent among female athletes compared to female controls. A statistical trend was also observed in BDKRB2 (+9/−9) and LEP (G–2548A) heterozygous genotypes among male and female Greek athletes, and in ACE (I/D) only in male athletes. Finally, both male and female athletes showed the highest rates in the AGTR1 (A/A) genotype.

Conclusions
Our results suggest that the co-existence of ACE (D/D), BDKRB2 (+9/−9) or LEP (G/A) genotypes in female athletes might be correlated with a superior level of physical performance.
Multilayer porous silicon diffraction gratings operating in the infrared
Authors: Lai Meifang , Sridharan Gayathri M , Parish Giacinta , Bhattacharya Shanti , Keating Adrian 
Published: November 2012

Abstract
Transmission diffraction gratings operating at 1,565 nm based on multilayer porous silicon films are modeled, fabricated, and tested. Features down to 2 μm have been patterned into submicron-thick mesoporous films using standard photolithographic and dry etching techniques. After patterning of the top porous film, a second anodization can be performed, allowing an under-layer of highly uniform porosity and thickness to be achieved. High transmission greater than 40% is measured, and modeling results suggest that a change in diffraction efficiency of 1 dB for a 1% change in normalized refractive index can be achieved. Preliminary measurement of solvent vapor shows a large signal change from the grating sensor in agreement with models.