bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity at 11 Years of Age and Incidence of Mental Health Problems in Adolescence: Prospective Study
Authors: Hallal Pedro C. , Martínez-Mesa Jeovany , Coll Carolina V.N. , Mielke Grégore I. , Mendes Márcio A. , Peixoto Márcio B. , Munhoz Tiago N. , Ramires Virgilio V. , Assunção Maria Cecilia , Gonçalves Helen , Menezes Ana M. B. 
Published: October 2014

Aim:To evaluate the longitudinal association between physical activity behavior at 11 years of age and the incidence of mental health problems from 11 to 15 years of age.Methods:Individuals born in the city of Pelotas, Brazil, in 1993 have been followed up since birth. At 11 and 15 years of age, mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ). At 11 years of age, physical activity was assessed through a validated questionnaire. The continuous SDQ score at 15 years was used as the outcome variable. The main exposure was physical activity behavior at 11 years of age divided into 3 categories (0, 1−299, >300 min/wk).Results:The incidence of mental health problems from 11 to 15 years was 13.6% (95% CI, 12.4−14.9). At 11 years, 35.2% of the adolescents achieved 300 min/wk of physical activity. In the unadjusted analysis, physical activity was inversely related to mental health problems (P = .04). After adjustment for confounders, the association was no longer significant in the whole sample but was still significant among boys.Conclusion:Physical activity appears to be inversely related to mental health problems in adolescence, but the magnitude of the association is weak to moderate.
Correlates of Physical Activity Among People With Disabilities in South Korea: A Multilevel Modeling Approach
Authors: Kim Youngdeok , Cho Jaehoon , Fuller Dana K , Kang Minsoo 
Published: October 2014

Background:The purpose of this study was to examine the correlates of physical activity (PA) with personal and environmental factors among people with disabilities in South Korea.Methods:Data from the 2011 National Survey for Physical Activity and Exercise for the Disabled, conducted by Korea Sports Association for the Disabled, was used (n = 1478). The personal characteristics (age, gender, occupation, types of disabilities, family income) and the numbers of public PA-related facilities (welfare center, public indoor gym, and public outdoor facilities) and social sports/exercise clubs for people with disabilities across 16 local areas were also obtained. Hierarchical generalized linear model was used to examine subjectively measured PA in relation to personal and environmental factors.Results:The likelihood of engaging in PA was significantly lower for women with disabilities. People with hearing and intellectual disabilities were less likely to engage in PA compared with those with physical disabilities. The availability of sports/exercise clubs for people with disabilities was the only environmental factor that was significantly associated with PA.Conclusions:These findings suggest the need of systematic intervention strategies based upon personal characteristics of people with disabilities. Further public efforts to promote sports/exercise club activities should be encouraged in this population.
Efficacy and safety of a herbal medicinal product containing myrrh, chamomile and coffee charcoal for the treatment of gastrointestinal disorders: a non-interventional study
Authors: Albrecht Uwe , Müller Valentina , Schneider Berthold , Stange Rainer 
Published: October 2014

ObjectiveThis prospective observational postmarketing multicentre study was performed to collect data on the clinical efficacy, safety and tolerability of a licensed herbal combination of myrrh, coffee charcoal and chamomile extracts in patients with symptoms of acute diarrhoea.Material and methodsPatients aged 12 years and above with symptoms of acute diarrhoea due to acute inflammatory disorders (AID) of the gastrointestinal tract, inflammatory bowel diseases (IBD) or irritable bowel syndrome (IBS) were treated with the herbal preparation either as monotherapy, add-on therapy or with other therapies. The primary outcome parameter was the pre-post change of total mean symptom score. Secondary outcome parameters were changes of score of single symptoms, physician's assessment of the clinical course and efficacy, and patient's satisfaction.Results1062 patients (mean age 43.2±17.8 years, range 12–89, 42.3% men) were included. A decrease of the overall mean total symptom score was observed in all treatment groups (monotreatment: 1.33±0.51 to 0.15±0.34, add-on treatment: 1.39±0.41 to 0.30±0.37, other therapy: 1.31±0.43 to 0.24±0.33). No significant differences between three treatment options were observed within AID and IBD groups. However, in the IBS group, monotreatment with the herbal preparation resulted in a significantly better outcome when compared to either add-on treatment (mean difference 0.140; 95% CI 0.036 to 0.245; p=0.009) or other therapy (mean difference 0.217; 95% CI 0.085 to 0.349; p=0.001). Secondary efficacy criteria showed comparable results between different treatment options in the respective disorder groups. Patient satisfaction was generally higher with monotreatment in the AID and IBS groups, while add-on treatment was preferred in the IBD group.ConclusionsThe combination of myrrh, coffee charcoal and chamomile flower extract is effective, well tolerated and safe for use in patients with symptoms of acute diarrhoea. The effects are comparable to conventional therapies used in routine care.
MHD Equations with Regularity in One Direction
Authors: Zhang Zujin 
Published: October 2014

We consider the 3D MHD equations and prove that if one directional derivative of the fluid velocity, say, ∂3u∈Lp0, T;LqR3, with 2/p + 3/q = γ ∈ [1,3/2), 3/γ ≤ q ≤ 1/(γ - 1), then the solution is in fact smooth.  This improves previous results greatly.
The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials
Authors: Benes Jan , Giglio Mariateresa , Brienza Nicola , Michard Frederic 
Published: October 2014

Abstract
Introduction
Dynamic predictors of fluid responsiveness, namely systolic pressure variation, pulse pressure variation, stroke volume variation and pleth variability index have been shown to be useful to identify in advance patients who will respond to a fluid load by a significant increase in stroke volume and cardiac output. As a result, they are increasingly used to guide fluid therapy. Several randomized controlled trials have tested the ability of goal-directed fluid therapy (GDFT) based on dynamic parameters (GDFTdyn) to improve post-surgical outcome. These studies have yielded conflicting results. Therefore, we performed this meta-analysis to investigate whether the use of GDFTdyn is associated with a decrease in post-surgical morbidity.

Methods
A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through September 2013 was conducted. Data synthesis was obtained by using odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) by random-effects model.

Results
In total, 14 studies met the inclusion criteria (961 participants). Post-operative morbidity was reduced by GDFTdyn (OR 0.51; CI 0.34 to 0.75; P <0.001). This effect was related to a significant reduction in infectious (OR 0.45; CI 0.27 to 0.74; P = 0.002), cardiovascular (OR 0.55; CI 0.36 to 0.82; P = 0.004) and abdominal (OR 0.56; CI 0.37 to 0.86; P = 0.008) complications. It was associated with a significant decrease in ICU length of stay (WMD -0.75 days; CI -1.37 to -0.12; P = 0.02).

Conclusions
In surgical patients, we found that GDFTdyn decreased post-surgical morbidity and ICU length of stay. Because of the heterogeneity of studies analyzed, large prospective clinical trials would be useful to confirm our findings.
Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria
Authors: Zhu Quing , Wang Liqun , Tannenbaum Susan , Ricci Andrew , DeFusco Patricia , Hegde Poornima 
Published: October 2014

Abstract
Introduction
The purpose of this study is to develop a prediction model utilizing tumor hemoglobin parameters measured by ultrasound-guided near-infrared optical tomography (US-NIR) in conjunction with standard pathologic tumor characteristics to predict pathologic response before neoadjuvant chemotherapy (NAC) is given.

Methods
Thirty-four patients’ data were retrospectively analyzed using a multiple logistic regression model to predict response. These patients were split into 30 groups of training (24 tumors) and testing (12 tumors) for cross validation. Tumor vascularity was assessed using US-NIR measurements of total hemoglobin (tHb), oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) concentrations acquired before treatment. Tumor pathologic variables of tumor type, Nottingham score, mitotic index, the estrogen and progesterone receptors and human epidermal growth factor receptor 2 acquired before NAC in biopsy specimens were also used in the prediction model. The patients’ pathologic response was graded based on the Miller-Payne system. The overall performance of the prediction models was evaluated using receiver operating characteristic (ROC) curves. The quantitative measures were sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC).

Results
Utilizing tumor pathologic variables alone, average sensitivity of 56.8%, average specificity of 88.9%, average PPV of 84.8%, average NPV of 70.9% and average AUC of 84.0% were obtained from the testing data. Among the hemoglobin predictors with and without tumor pathological variables, the best predictor was tHb combined with tumor pathological variables, followed by oxyHb with pathological variables. When tHb was included with tumor pathological variables as an additional predictor, the corresponding measures improved to 79%, 94%, 90%, 86% and 92.4%, respectively. When oxyHb was included with tumor variables as an additional predictor, these measures improved to 77%, 85%, 83%, 83% and 90.6%, respectively. The addition of tHb or oxyHb significantly improved the prediction sensitivity, NPV and AUC compared with using tumor pathological variables alone.

Conclusions
These initial findings indicate that combining widely used tumor pathologic variables with hemoglobin parameters determined by US-NIR may provide a powerful tool for predicting patient pathologic response to NAC before the start of treatment.

Trial registration
ClincalTrials.gov ID: NCT00908609 (registered 22 May 2009)
Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations
Authors: Martelotto Luciano G , Ng Charlotte KY , De Filippo Maria R , Zhang Yan , Piscuoglio Salvatore , Lim Raymond S , Shen Ronglai , Norton Larry , Reis-Filho Jorge S , Weigelt Britta 
Published: October 2014

Abstract
Background
Massively parallel sequencing studies have led to the identification of a large number of mutations present in a minority of cancers of a given site. Hence, methods to identify the likely pathogenic mutations that are worth exploring experimentally and clinically are required. We sought to compare the performance of 15 mutation effect prediction algorithms and their agreement. As a hypothesis-generating aim, we sought to define whether combinations of prediction algorithms would improve the functional effect predictions of specific mutations.

Results
Literature and database mining of single nucleotide variants (SNVs) affecting 15 cancer genes was performed to identify mutations supported by functional evidence or hereditary disease association to be classified either as non-neutral (n = 849) or neutral (n = 140) with respect to their impact on protein function. These SNVs were employed to test the performance of 15 mutation effect prediction algorithms. The accuracy of the prediction algorithms varies considerably. Although all algorithms perform consistently well in terms of positive predictive value, their negative predictive value varies substantially. Cancer-specific mutation effect predictors display no-to-almost perfect agreement in their predictions of these SNVs, whereas the non-cancer-specific predictors showed no-to-moderate agreement. Combinations of predictors modestly improve accuracy and significantly improve negative predictive values.

Conclusions
The information provided by mutation effect predictors is not equivalent. No algorithm is able to predict sufficiently accurately SNVs that should be taken forward for experimental or clinical testing. Combining algorithms aggregates orthogonal information and may result in improvements in the negative predictive value of mutation effect predictions.
Mobster: accurate detection of mobile element insertions in next generation sequencing data
Authors: Thung Djie Tjwan , de Ligt Joep , Vissers Lisenka EM , Steehouwer Marloes , Kroon Mark , de Vries Petra , Slagboom Eline P , Ye Kai , Veltman Joris A , Hehir-Kwa Jayne Y 
Published: October 2014

AbstractMobile elements are major drivers in changing genomic architecture and can cause disease. The detection of mobile elements is hindered due to the low mappability of their highly repetitive sequences. We have developed an algorithm, called Mobster, to detect non-reference mobile element insertions in next generation sequencing data from both whole genome and whole exome studies. Mobster uses discordant read pairs and clipped reads in combination with consensus sequences of known active mobile elements. Mobster has a low false discovery rate and high recall rate for both L1 and Alu elements. Mobster is available at http://sourceforge.net/projects/mobster.
Enhancer variants: evaluating functions in common disease
Authors: Corradin Olivia , Scacheri Peter C 
Published: October 2014

AbstractGene enhancer elements are noncoding segments of DNA that play a central role in regulating transcriptional programs that control development, cell identity, and evolutionary processes. Recent studies have shown that noncoding single nucleotide polymorphisms (SNPs) that have been associated with risk for numerous common diseases through genome-wide association studies frequently lie in cell-type-specific enhancer elements. These enhancer variants probably influence transcriptional output, thereby offering a mechanistic basis to explain their association with risk for many common diseases. This review focuses on the identification and interpretation of disease-susceptibility variants that influence enhancer function. We discuss strategies for prioritizing the study of functional enhancer SNPs over those likely to be benign, review experimental and computational approaches to identifying the gene targets of enhancer variants, and highlight efforts to quantify the impact of enhancer variants on target transcript levels and cellular phenotypes. These studies are beginning to provide insights into the mechanistic basis of many common diseases, as well as into how we might translate this knowledge for improved disease diagnosis, prevention and treatments. Finally, we highlight five major challenges often associated with interpreting enhancer variants, and discuss recent technical advances that may help to surmount these challenges.
Reducing INDEL calling errors in whole genome and exome sequencing data
Authors: Fang Han , Wu Yiyang , Narzisi Giuseppe , ORawe Jason A , Barrón Laura T Jimenez , Rosenbaum Julie , Ronemus Michael , Iossifov Ivan , Schatz Michael C , Lyon Gholson J 
Published: October 2014

Abstract
Background
INDELs, especially those disrupting protein-coding regions of the genome, have been strongly associated with human diseases. However, there are still many errors with INDEL variant calling, driven by library preparation, sequencing biases, and algorithm artifacts.

Methods
We characterized whole genome sequencing (WGS), whole exome sequencing (WES), and PCR-free sequencing data from the same samples to investigate the sources of INDEL errors. We also developed a classification scheme based on the coverage and composition to rank high and low quality INDEL calls. We performed a large-scale validation experiment on 600 loci, and find high-quality INDELs to have a substantially lower error rate than low-quality INDELs (7% vs. 51%).

Results
Simulation and experimental data show that assembly based callers are significantly more sensitive and robust for detecting large INDELs (>5 bp) than alignment based callers, consistent with published data. The concordance of INDEL detection between WGS and WES is low (53%), and WGS data uniquely identifies 10.8-fold more high-quality INDELs. The validation rate for WGS-specific INDELs is also much higher than that for WES-specific INDELs (84% vs. 57%), and WES misses many large INDELs. In addition, the concordance for INDEL detection between standard WGS and PCR-free sequencing is 71%, and standard WGS data uniquely identifies 6.3-fold more low-quality INDELs. Furthermore, accurate detection with Scalpel of heterozygous INDELs requires 1.2-fold higher coverage than that for homozygous INDELs. Lastly, homopolymer A/T INDELs are a major source of low-quality INDEL calls, and they are highly enriched in the WES data.

Conclusions
Overall, we show that accuracy of INDEL detection with WGS is much greater than WES even in the targeted region. We calculated that 60X WGS depth of coverage from the HiSeq platform is needed to recover 95% of INDELs detected by Scalpel. While this is higher than current sequencing practice, the deeper coverage may save total project costs because of the greater accuracy and sensitivity. Finally, we investigate sources of INDEL errors (for example, capture deficiency, PCR amplification, homopolymers) with various data that will serve as a guideline to effectively reduce INDEL errors in genome sequencing.
Staphylococcus aureusgene expression in a rat model of infective endocarditis
Authors: Hanses Frank , Roux Christelle , Dunman Paul M , Salzberger Bernd , Lee Jean C 
Published: October 2014

Abstract
Background
Diabetes mellitus is a frequent underlying comorbidity in patients with Staphylococcus aureus endocarditis, and it represents a risk factor for complications and a negative outcome. The pathogenesis of staphylococcal endocardial infections in diabetic hosts has been poorly characterized, and little is known about S. aureus gene expression in endocardial vegetations.

Methods
We utilized a rat model of experimental S. aureus endocarditis to compare the pathogenesis of staphylococcal infection in diabetic and nondiabetic hosts and to study the global S. aureus transcriptome in endocardial vegetations in vivo.

Results
Diabetic rats had higher levels of bacteremia and larger endocardial vegetations than nondiabetic control animals. Microarray analyses revealed that 61 S. aureus genes were upregulated in diabetic rats, and the majority of these bacterial genes were involved in amino acid and carbohydrate metabolism. When bacterial gene expression in vivo (diabetic or nondiabetic endocardial vegetations) was compared to in vitro growth conditions, higher in vivo expression of genes encoding toxins and proteases was observed. Additionally, genes involved in the production of adhesins, capsular polysaccharide, and siderophores, as well as in amino acid and carbohydrate transport and metabolism, were upregulated in endocardial vegetations. To test the contribution of selected upregulated genes to the pathogenesis of staphylococcal endocarditis, isogenic deletion mutants were utilized. A mutant defective in production of the siderophore staphyloferrin B was attenuated in the endocarditis model, whereas the virulence of a surface adhesin (ΔsdrCDE) mutant was similar to that of the parental S. aureus strain.

Conclusions
Our results emphasize the relevance of diabetes mellitus as a risk factor for infectious endocarditis and provide a basis for understanding gene expression during staphylococcal infections in vivo.
PLD3 is accumulated on neuritic plaques in Alzheimer’s disease brains
Authors: Satoh Jun-ichi , Kino Yoshihiro , Yamamoto Yoji , Kawana Natsuki , Ishida Tsuyoshi , Saito Yuko , Arima Kunimasa 
Published: October 2014

Abstract
Introduction
Recently, a whole-exome sequencing (WES) study showed that a rare variant rs145999145 composed of p.Val232Met located in exon 7 of the phospholipase D3 (PLD3) gene confers a doubled risk for late-onset Alzheimer’s disease (AD). Knockdown of PLD3 elevates the levels of extracellular amyloid-beta (Aβ), suggesting that PLD3 acts as a negative regulator of Aβ precursor protein (APP) processing. However, the precise cellular location and distribution of PLD3 in AD brains remain largely unknown.

Methods
By quantitative RT-PCR (qPCR), western blot, immunohistochemistry, and bioinformatics analysis, we studied PLD3 expression patterns and levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson’s disease, multiple system atrophy, and non-neurological cases.

Results
The levels of PLD3 mRNA and protein expression were reduced modestly in AD brains, compared with those in non-AD brains. In all brains, PLD3 was expressed constitutively in cortical neurons, hippocampal pyramidal and granular neurons but not in glial cells. Notably, PLD3 immunoreactivity was accumulated on neuritic plaques in AD brains. We identified the human granulin (GRN) gene encoding progranulin (PRGN) as one of most significant genes coexpressed with PLD3 by bioinformatics database search. PLD3 was actually coexpressed and interacted with PGRN both in cultured cells in vitro and in AD brains in vivo.

Conclusions
We identified an intense accumulation of PLD3 on neuritic plaques coexpressed with PGRN in AD brains, suggesting that PLD3 plays a key role in the pathological processes of AD.
β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage
Authors: Portelius Erik , Dean Robert A , Andreasson Ulf , Mattsson Niklas , Westerlund Anni , Olsson Maria , Demattos Ronald Bradley , Racke Margaret M , Zetterberg Henrik , May Patrick C , Blennow Kaj 
Published: October 2014

Abstract
Introduction
The β-secretase enzyme, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in β-amyloid (Aβ) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer’s disease. In a previous exploratory Aβ biomarker study, we found that BACE1 inhibitor treatment resulted in decreased levels of Aβ1-34 together with increased Aβ5-40, suggesting that these Aβ species may be novel pharmacodynamic biomarkers in clinical trials. We have now examined whether the same holds true in humans.

Methods
In an investigator-blind, placebo-controlled and randomized study, healthy subjects (n =18) were randomly assigned to receive a single dose of 30 mg of LY2811376 (n =6), 90 mg of LY2811376 (n =6), or placebo (n =6). We used hybrid immunoaffinity-mass spectrometry (HI-MS) and enzyme-linked immunosorbent assays to monitor a variety of Aβ peptides.

Results
Here, we demonstrate dose-dependent changes in cerebrospinal fluid (CSF) Aβ1-34, Aβ5-40 and Aβ5-X after treatment with the BACE1-inhibitor LY2811376. Aβ5-40 and Aβ5-X increased dose-dependently, as reflected by two independent methods, while Aβ1-34 dose-dependently decreased.

Conclusion
Using HI-MS for the first time in a study where subjects have been treated with a BACE inhibitor, we confirm that CSF Aβ1-34 may be useful in clinical trials on BACE1 inhibitors to monitor target engagement. Since it is less hydrophobic than longer Aβ species, it is less susceptible to preanalytical confounding factors and may thus be a more stable marker. By independent measurement techniques, we also show that BACE1 inhibition in humans is associated with APP-processing into N-terminally truncated Aβ peptides via a BACE1-independent pathway.

Trial registration
ClinicalTrials.gov NCT00838084. Registered: First received: January 23, 2009, Last updated: July 14, 2009, Last verified: July 2009.