bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between transforming growth factor β1 polymorphisms and atrial fibrillation in essential hypertensive subjects
Authors: Wang Yongzheng , Hou Xuwei , Li Yuliang 
Published: April 2010

Abstract

Background
The association of TGF β1 polymorphisms and atrial fibrillation (AF) in essential hypertensive (EH) subjects remains unknown. Methods EH subjects with AF (EH+AF+) and sinus rhythm (EH+AF-) were enrolled. The polymorphisms of +869 T → C at codon 10 and + 915 G → C at codon 25, were genotyped. The clinical characteristics including serum TGF β1 levels were detected.

Results
The GG genotypes of TGF β1 +915 G → C at codon 25 were more prevalent in subjects from EH+AF+ group than those from EH+AF- group (P = 0.009). The subjects with GG genotype from EH+AF+ group had the highest mean serum TGF β1 level, which was significantly higher than that of GG genotype subjects from EH+AF- group (3.18 ± 0.24 ng/dl vs.2.29 ± 0.14 ng/dl, P < 0.05). Multiple analyses revealed that the TGF β1 GG genotype of +915 G → C at codon 25 presented a 3.09 times higher risk in developing AF in the multivariate model after adjusting for age and gender.

Conclusion
The polymorphisms of TGF β1 +915 G → C at codon 25 were associated with occurrence of AF and serum TGF β1 level in EH subjects.
Predicting conserved protein motifs with Sub-HMMs
Authors: Horan Kevin , Shelton Christian R , Girke Thomas 
Published: April 2010

AbstractBackgroundProfile HMMs (hidden Markov models) provide effective methods for modeling the conserved regions of protein families. A limitation of the resulting domain models is the difficulty to pinpoint their much shorter functional sub-features, such as catalytically relevant sequence motifs in enzymes or ligand binding signatures of receptor proteins.ResultsTo identify these conserved motifs efficiently, we propose a method for extracting the most information-rich regions in protein families from their profile HMMs. The method was used here to predict a comprehensive set of sub-HMMs from the Pfam domain database. Cross-validations with the PROSITE and CSA databases confirmed the efficiency of the method in predicting most of the known functionally relevant motifs and residues. At the same time, 46,768 novel conserved regions could be predicted. The data set also allowed us to link at least 461 Pfam domains of known and unknown function by their common sub-HMMs. Finally, the sub-HMM method showed very promising results as an alternative search method for identifying proteins that share only short sequence similarities.ConclusionsSub-HMMs extend the application spectrum of profile HMMs to motif discovery. Their most interesting utility is the identification of the functionally relevant residues in proteins of known and unknown function. Additionally, sub-HMMs can be used for highly localized sequence similarity searches that focus on shorter conserved features rather than entire domains or global similarities. The motif data generated by this study is a valuable knowledge resource for characterizing protein functions in the future.
G-stack modulated probe intensities on expression arrays - sequence corrections and signal calibration
Authors: Fasold Mario , Stadler Peter F , Binder Hans 
Published: April 2010

Abstract

Background
The brightness of the probe spots on expression microarrays intends to measure the abundance of specific mRNA targets. Probes with runs of at least three guanines (G) in their sequence show abnormal high intensities which reflect rather probe effects than target concentrations. This G-bias requires correction prior to downstream expression analysis.

Results
Longer runs of three or more consecutive G along the probe sequence and in particular triple degenerated G at its solution end ((GGG)1-effect) are associated with exceptionally large probe intensities on GeneChip expression arrays. This intensity bias is related to non-specific hybridization and affects both perfect match and mismatch probes. The (GGG)1-effect tends to increase gradually for microarrays of later GeneChip generations. It was found for DNA/RNA as well as for DNA/DNA probe/target-hybridization chemistries. Amplification of sample RNA using T7-primers is associated with strong positive amplitudes of the G-bias whereas alternative amplification protocols using random primers give rise to much smaller and partly even negative amplitudes.
We applied positional dependent sensitivity models to analyze the specifics of probe intensities in the context of all possible short sequence motifs of one to four adjacent nucleotides along the 25meric probe sequence. Most of the longer motifs are adequately described using a nearest-neighbor (NN) model. In contrast, runs of degenerated guanines require explicit consideration of next nearest neighbors (GGG terms). Preprocessing methods such as vsn, RMA, dChip, MAS5 and gcRMA only insufficiently remove the G-bias from data.

Conclusions
Positional and motif dependent sensitivity models accounts for sequence effects of oligonucleotide probe intensities. We propose a positional dependent NN+GGG hybrid model to correct the intensity bias associated with probes containing poly-G motifs. It is implemented as a single-chip based calibration algorithm for GeneChips which can be applied in a pre-correction step prior to standard preprocessing.
Effect of TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards
Authors: Veloso Sergi , Olona Montserrat , García Felipe , Domingo Pere , Alonso-Villaverde Carlos , Broch Montserrat , Peraire Joaquim , Viladés Consuelo , Plana Montserrat , Pedrol Enric , López-Dupla Miguel , Aguilar Carmen , Gutiérrez Mar , Leon Agathe , Tasias Mariona , Ma Gatell Josep , Richart Cristóbal , Vidal Francesc 
Published: April 2010

AbstractBackgroundTumor necrosis factor alpha (TNF-α) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.MethodsWe aimed to determine whether carriage of theTNF-α-238G>A, -308G>Aand-863 C>Agene promoter single nucleotide polymorphisms (SNP) and theCCR5Δ32variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration).TNF-αSNP and theCCR5Δ32allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the χ 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.ResultsThe distribution ofTNF-α-238G>A, -308G>Aand-863 C>Agenetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals:-238G>A, p = 0.7 and p = 0.3;-308G>A, p = 0.05 and p = 0.07;-863 C>A, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the threeTNF-αgenetic variants assessed was non-significantly different between TP and LTNP:-238G>A, p = 0.35 and p = 0.7;-308G>A, p = 0.7 and p = 0.6:-863 C>A, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset indicated that theTNF-α-238Avariant allele was significantly overrepresented in patients who spontaneously controlled plasma viremia compared with those who had a detectable plasma viral load (genotype comparisons, p = 0.02; allele comparisons, p = 0.03). TheCCR5Δ32distribution was non-significantly different in HIV-1-infected patients with respect to the uninfected population (p = 0.15 and p = 0.2 for genotype and allele comparisons, respectively) and in LTNP vs TP (p = 0.4 and p = 0.5 for genotype and allele comparisons, respectively).ConclusionsIn our cohort of Caucasian Spaniards,TNF-αgenetic variants could be involved in the vulnerability to HIV-1 infection.TNF-αgenetic variants were unrelated to disease progression in infected subjects. The-238G>ASNP may modulate the control of viremia in LTNP. Carriage of theCCR5Δ32variant allele had no effect on the risk of infection and disease progression.
Understanding young adult physical activity, alcohol and tobacco use in community colleges and 4-year post-secondary institutions: A cross-sectional analysis of epidemiological surveillance data
Authors: VanKim Nicole A , Laska Melissa Nelson , Ehlinger Edward , Lust Katherine , Story Mary 
Published: April 2010

Abstract

Background
Young adults experience many adverse health behavior changes as they transition from adolescence into adulthood. A better understanding of the relationships between health promoting and risky health behaviors may aid in the development of health promotion interventions for various types of young adult post-secondary students. Therefore, the purpose of this study was to examine associations between alcohol and tobacco use and physical activity among 2-year and 4-year college students.

Methods
Cross-sectional analyses were conducted using 2007 survey data, collected as part of an on-going post-secondary health surveillance system in Minnesota. Students were randomly selected to participant from 14 Minnesota colleges and universities (six 2-year community and/or technical colleges, eight 4-year post-secondary institutions). The 2007 surveillance data included 9,931 respondents.

Results
The prevalence of demographic characteristics and health behaviors (e.g., physical activity, tobacco use) differed between young adults attending 2-year and 4-year post-secondary institutions; in general, those attending 2-year institutions are representative of more at-risk populations. Overall, higher levels of moderate, vigorous and strengthening physical activity were associated with higher levels of alcohol consumption and lower levels of smoking. In general, despite the disparities in the prevalence of these risk behaviors, the associations between the behaviors did not differ substantially between 2-year and 4-year post-secondary populations.

Conclusions
These findings illustrate links between leading risk behaviors. Interventions targeting multiple risk behaviors among young adults may warrant further consideration. Overall, future research is needed to support and inform young adult health promotion efforts that may be implemented in a wide array of post-secondary institutions.
A patient survey of the impact of fibromyalgia and the journey to diagnosis
Authors: Choy Ernest , Perrot Serge , Leon Teresa , Kaplan Joan , Petersel Danielle , Ginovker Anna , Kramer Erich 
Published: April 2010

Abstract

Background
Fibromyalgia is a painful, debilitating illness with a prevalence of 0.5-5.0% that affects women more than men. It has been shown that the diagnosis of fibromyalgia is associated with improved patient satisfaction and reduced healthcare utilization. This survey examined the patient journey to having their condition diagnosed and studied the impact of the condition on their life.

Methods
A questionnaire survey of 800 patients with fibromyalgia and 1622 physicians in 6 European countries, Mexico and South Korea. Patients were recruited via their physician.

Results
Over half the patients (61%) were aged 36-59 years, 84% were women, and the mean time since experiencing fibromyalgia symptoms was 6.5 years. Patients had experienced multiple fibromyalgia symptoms (mean of 7.3 out of 14), with pain, fatigue, sleeping problems and concentration difficulties being the most commonly reported. Most patients rated their chronic widespread pain as moderate or severe and fibromyalgia symptoms were on average "fairly" to "very" disruptive, and had a "moderate" to "strong" impact on patients' lives. 22% were unable to work and 25% were not able to work all the time because of their fibromyalgia. Patients waited on average almost a year after experiencing symptoms before presenting to a physician, and it took an average of 2.3 years and presenting to 3.7 different physicians before receiving a diagnosis of fibromyalgia. Patients rated receiving a diagnosis as somewhat difficult on average and had difficulties communicating their symptoms to the physician. Over one third (35%) felt their chronic widespread pain was not well managed by their current treatment.

Conclusions
This survey provides further evidence that fibromyalgia is characterized by multiple symptoms and has a notable impact on quality of life and function. The diagnosis of fibromyalgia is delayed. Patients wait a significant period of time before presenting to a physician, adding to the prolonged time to diagnosis. Patients typically present with a multitude of symptoms, all resulting in a delay in diagnosis and eventual management. Helping clinicians to diagnose and manage patients with fibromyalgia should benefit both patients and funders of healthcare.
Stepwise engineering of a Pichia pastoris D-amino acid oxidase whole cell catalyst
Authors: Abad Sandra , Nahalka Jozef , Bergler Gabriele , Arnold S Alison , Speight Robert , Fotheringham Ian , Nidetzky Bernd , Glieder Anton 
Published: April 2010

AbstractBackgroundTrigonopsis variabilisD-amino acid oxidase (TvDAO) is a well characterized enzyme used for cephalosporin C conversion on industrial scale. However, the demands on the enzyme with respect to activity, operational stability and costs also vary with the field of application. Processes that use the soluble enzyme suffer from fast inactivation ofTvDAO while immobilized oxidase preparations raise issues related to expensive carriers and catalyst efficiency. Therefore, oxidase preparations that are more robust and active than those currently available would enable a much broader range of economically viable applications of this enzyme in fine chemical syntheses. A multi-step engineering approach was chosen here to develop a robust and highly activePichia pastoris TvDAO whole-cell biocatalyst.ResultsAs compared to the nativeT. variabilishost, a more than seven-fold enhancement of the intracellular level of oxidase activity was achieved inP. pastoristhrough expression optimization by codon redesign as well as efficient subcellular targeting of the enzyme to peroxisomes. Multi copy integration further doubled expression and the specific activity of the whole cell catalyst. From a multicopy production strain, about 1.3 × 103U/g wet cell weight (wcw) were derived by standard induction conditions feeding pure methanol. A fed-batch cultivation protocol using a mixture of methanol and glycerol in the induction phase attenuated the apparent toxicity of the recombinant oxidase to yield final biomass concentrations in the bioreactor of ≥ 200 g/L compared to only 117 g/L using the standard methanol feed. Permeabilization ofP. pastorisusing 10% isopropanol yielded a whole-cell enzyme preparation that showed 49% of the total available intracellular oxidase activity and was notably stabilized (by three times compared to a widely usedTvDAO expressingEscherichia colistrain) under conditions ofD-methionine conversion using vigorous aeration.ConclusionsStepwise optimization using a multi-level engineering approach has delivered a newP. pastoriswhole cellTvDAO biocatalyst showing substantially enhanced specific activity and stability under operational conditions as compared to previously reported preparations of the enzyme. The production of the oxidase through fed-batch bioreactor culture and subsequent cell permeabilization is high-yielding and efficient. Therefore thisP. pastoriscatalyst has been evaluated for industrial purposes.
Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers
Authors: Wu Alan HB , Drees Julia C , Wang Hangpin , VandenBerg Scott R , Lal Anita , Henner William D , Pillai Raji 
Published: April 2010

Abstract

Background
Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients.

Methods
Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed.

Results
Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases.

Discussion
This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.
Interventions aimed at improving the nursing work environment: a systematic review
Authors: Schalk Donna MJ , Bijl Marloes LP , Halfens Ruud JG , Hollands Louk , Cummings Greta G 
Published: April 2010

Abstract

Background
Nursing work environments (NWEs) in Canada and other Western countries have increasingly received attention following years of restructuring and reported high workloads, high absenteeism, and shortages of nursing staff. Despite numerous efforts to improve NWEs, little is known about the effectiveness of interventions to improve NWEs. The aim of this study was to review systematically the scientific literature on implemented interventions aimed at improving the NWE and their effectiveness.

Methods
An online search of the databases CINAHL, Medline, Scopus, ABI, Academic Search Complete, HEALTHstar, ERIC, Psychinfo, and Embase, and a manual search of Emerald and Longwoods was conducted. (Quasi-) experimental studies with pre/post measures of interventions aimed at improving the NWE, study populations of nurses, and quantitative outcome measures of the nursing work environment were required for inclusion. Each study was assessed for methodological strength using a quality assessment and validity tool for intervention studies. A taxonomy of NWE characteristics was developed that would allow us to identify on which part of the NWE an intervention targeted for improvement, after which the effects of the interventions were examined.

Results
Over 9,000 titles and abstracts were screened. Eleven controlled intervention studies met the inclusion criteria, of which eight used a quasi-experimental design and three an experimental design. In total, nine different interventions were reported in the included studies. The most effective interventions at improving the NWE were: primary nursing (two studies), the educational toolbox (one study), the individualized care and clinical supervision (one study), and the violence prevention intervention (one study).

Conclusions
Little is known about the effectiveness of interventions aimed at improving the NWE, and published studies on this topic show weaknesses in their design. To advance the field, we recommend that investigators use controlled studies with pre/post measures to evaluate interventions that are aimed at improving the NWE. Thereby, more evidence-based knowledge about the implementation of interventions will become available for healthcare leaders to use in rebuilding nursing work environments.
Decrease in the expression of the type 1 PTH/PTHrP receptor (PTH1R) on chondrocytes in animals with osteoarthritis
Authors: Becher Christoph , Szuwart Thomas , Ronstedt Philipp , Ostermeier Sven , Skwara Adrian , Fuchs-Winkelmann Susanne , Tibesku Carsten O 
Published: April 2010

AbstractBackgroundTo evaluate the expression of the type 1 PTH/PTHrP receptor (PTH1R) on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).MethodsIn 12 NZW rabbits, the anterior cruciate ligament (ACL) was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for PTH1R.ResultsThere was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed significantly less expression of PTH1R in the experimental compared to the control group after 6 (P < 0.05) and 12 weeks (P < 0.01). In the experimental group, a negative linear correlation between PTH1R expression and macroscopic and histologic grades was found.ConclusionsThe results show an in vivo decrease in the expression of PTH1R on chondrocytes over the time course of OA. Further studies are needed to evaluate whether new treatment approaches could evolve from this knowledge.