bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Novel ASIC2 Locus Is Associated with Severe Gingival Inflammation
Authors: Zhang S. , Divaris K. , Moss K. , Yu N. , Barros S. , Marchesan J. , Morelli T. , Agler C. , Kim S.J. , Wu D. , North K.E. , Beck J. , Offenbacher S. 
Published: April 2016

An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4,077 European American adults, participants in the Dental Atherosclerosis Risk in Communities cohort. The severe GI trait was defined dichotomously with the 90th percentile of gingival index ≥2 extent score. Genotyping was performed with the Affymetrix 6.0 array platform, and an imputed set of 2.5 million markers, based on HapMap Phase II CEU build 36, was interrogated. Genetic models were based on logistic regression and controlled for ancestry (10 principal components), sex, age, and examination center. One locus on chromosome 17 met genome-wide statistical significance criteria—lead single-nucleotide polymorphism: rs11652874 (minor allele frequency = 0.06, intronic to ASIC2 [acid-sensing ionic channel 2, formerly named ACCN1]; odds ratio = 2.1, 95% confidence interval = 1.6 to 2.7, P = 3.9 × 10-8). This association persisted among subjects with severe periodontitis and was robust to adjustment for microbial plaque index. Moreover, the minor (G) allele was associated with higher levels of severe GI in stratified analyses among subsets of participants with high load of either “red” or “orange” complex pathogens, although this association was not statistically significant. While these results will require replication in independent samples and confirmation by mechanistic studies, this locus appears as a promising candidate for severe GI. Our findings suggest that genetic variation in ASIC2 is significantly associated with severe GI and that the association is plaque independent. Knowledge Transfer Statement: Persistent gingival inflammation reflected by bleeding usually precedes ongoing attachment loss or periodontal disease progression. Our findings suggest that genetic variation in ASIC2 that is associated with severe gingival inflammation might be used as a genetic marker to identify people at higher risk for periodontal disease. Ongoing studies to uncover the mechanistic link between ASIC2 and gingival inflammation could lead to novel therapeutic interventions.
The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis
Authors: Hartz Bernd , Marsh Rebecca , Rao Kanchan , Henter Jan-Inge , Jordan Michael , Filipovich Lisa , Bader Peter , Beier Rita , Burkhardt Birgit , Meisel Roland , Schulz Ansgar , Winkler Beate , Albert Michael H. , Greil Johann , Karasu Gülsün , Woessmann Wilhelm , Corbacioglu Selim , Gruhn Bernd , Holter Wolfgang , Kühl Jörn-Sven , Lang Peter , Seidel Markus G. , Veys Paul , Löfstedt Alexandra , Ammann Sandra , Ehl Stephan , Janka Gritta , Müller Ingo , Lehmberg Kai 
Published: April 2016

Key Points
Donor chimerism >20%-30% usually protects against late disease reactivation after day 180 post stem cell transplantation for primary HLH. Lower levels do not inevitably result in reactivations. The risks of intervention must be weighed against the risk of reactivation.
Using expected sequence features to improve basecalling accuracy of amplicon pyrosequencing data
Authors: Rask Thomas S. , Petersen Bent , Chen Donald S. , Day Karen P. , Pedersen Anders Gorm 
Published: April 2016

Abstract
Background
Amplicon pyrosequencing targets a known genetic region and thus inherently produces reads highly anticipated to have certain features, such as conserved nucleotide sequence, and in the case of protein coding DNA, an open reading frame. Pyrosequencing errors, consisting mainly of nucleotide insertions and deletions, are on the other hand likely to disrupt open reading frames. Such an inverse relationship between errors and expectation based on prior knowledge can be used advantageously to guide the process known as basecalling, i.e. the inference of nucleotide sequence from raw sequencing data.

Results
The new basecalling method described here, named Multipass, implements a probabilistic framework for working with the raw flowgrams obtained by pyrosequencing. For each sequence variant Multipass calculates the likelihood and nucleotide sequence of several most likely sequences given the flowgram data. This probabilistic approach enables integration of basecalling into a larger model where other parameters can be incorporated, such as the likelihood for observing a full-length open reading frame at the targeted region. We apply the method to 454 amplicon pyrosequencing data obtained from a malaria virulence gene family, where Multipass generates 20 % more error-free sequences than current state of the art methods, and provides sequence characteristics that allow generation of a set of high confidence error-free sequences.

Conclusions
This novel method can be used to increase accuracy of existing and future amplicon sequencing data, particularly where extensive prior knowledge is available about the obtained sequences, for example in analysis of the immunoglobulin VDJ region where Multipass can be combined with a model for the known recombining germline genes. Multipass is available for Roche 454 data at http://www.cbs.dtu.dk/services/MultiPass-1.0, and the concept can potentially be implemented for other sequencing technologies as well.
Empirical estimation of sequencing error rates using smoothing splines
Authors: Zhu Xuan , Wang Jian , Peng Bo , Shete Sanjay 
Published: April 2016

Abstract
Background
Next-generation sequencing has been used by investigators to address a diverse range of biological problems through, for example, polymorphism and mutation discovery and microRNA profiling. However, compared to conventional sequencing, the error rates for next-generation sequencing are often higher, which impacts the downstream genomic analysis. Recently, Wang et al. (BMC Bioinformatics 13:185, 2012) proposed a shadow regression approach to estimate the error rates for next-generation sequencing data based on the assumption of a linear relationship between the number of reads sequenced and the number of reads containing errors (denoted as shadows). However, this linear read-shadow relationship may not be appropriate for all types of sequence data. Therefore, it is necessary to estimate the error rates in a more reliable way without assuming linearity. We proposed an empirical error rate estimation approach that employs cubic and robust smoothing splines to model the relationship between the number of reads sequenced and the number of shadows.

Results
We performed simulation studies using a frequency-based approach to generate the read and shadow counts directly, which can mimic the real sequence counts data structure. Using simulation, we investigated the performance of the proposed approach and compared it to that of shadow linear regression. The proposed approach provided more accurate error rate estimations than the shadow linear regression approach for all the scenarios tested. We also applied the proposed approach to assess the error rates for the sequence data from the MicroArray Quality Control project, a mutation screening study, the Encyclopedia of DNA Elements project, and bacteriophage PhiX DNA samples.

Conclusions
The proposed empirical error rate estimation approach does not assume a linear relationship between the error-free read and shadow counts and provides more accurate estimations of error rates for next-generation, short-read sequencing data.
Stochastic epigenetic outliers can define field defects in cancer
Authors: Teschendorff Andrew E. , Jones Allison , Widschwendter Martin 
Published: April 2016

Abstract
Background
There is growing evidence that DNA methylation alterations may contribute to carcinogenesis. Recent data also suggest that DNA methylation field defects in normal pre-neoplastic tissue represent infrequent stochastic “outlier” events. This presents a statistical challenge for standard feature selection algorithms, which assume frequent alterations in a disease phenotype. Although differential variability has emerged as a novel feature selection paradigm for the discovery of outliers, a growing concern is that these could result from technical confounders, in principle thus favouring algorithms which are robust to outliers.

Results
Here we evaluate five differential variability algorithms in over 700 DNA methylomes, including two of the largest cohorts profiling precursor cancer lesions, and demonstrate that most of the novel proposed algorithms lack the sensitivity to detect epigenetic field defects at genome-wide significance. In contrast, algorithms which recognise heterogeneous outlier DNA methylation patterns are able to identify many sites in pre-neoplastic lesions, which display progression in invasive cancer. Thus, we show that many DNA methylation outliers are not technical artefacts, but define epigenetic field defects which are selected for during cancer progression.

Conclusions
Given that cancer studies aiming to find epigenetic field defects are likely to be limited by sample size, adopting the novel feature selection paradigm advocated here will be critical to increase assay sensitivity.
Catheter-Related Bloodstream Infection in End-Stage Kidney Disease: A Canadian Narrative Review
Authors: Lata Chris , Girard Louis , Parkins Michael , James Matthew T. 
Published: April 2016

Purpose of the review: Patients with end-stage renal disease (ESRD) are at a high risk of bacterial infection. We reviewed publications on risk factors, prevention, and treatment paradigms, as well as outcomes associated with bacterial infection in end-stage kidney disease. We focused in particular on studies conducted in Canada where rates of haemodialysis catheter use are high. Sources of information: We included original research articles in English text identified from MEDLINE using search terms ‘chronic kidney failure’, ‘renal dialysis’, or ‘chronic renal insufficiency’, and ‘bacterial infection’. We focused on articles with Canadian study populations and included comparisons to international standards and outcomes where possible. Findings: Bacterial infections in this setting are most commonly due to Gram-positive skin flora, particularly Staphylococcus, with methicillin-resistant Staphylococcus aureus (MRSA) carrying a poorer prognosis. Interventions that may decrease mortality from sepsis include a collaborative care model that includes a nephrology team, an infectious disease specialist, and use of standardized care bundles that adhere to proven quality-of-care indicators. Decreased infectious mortality may be achieved by ensuring appropriate antibiotic selection and dosing as well as avoiding catheter salvage attempts. Reduction in bloodstream infection (BSI) incidence has been observed with the use of tPA catheter-locking solutions and the use of mupirocin or polysporin as a topical agent at the catheter exit site, as well as implementing standarized hygiene protocols during catheter use. Limitations: There has been a paucity of randomized controlled trials of prevention and treatment strategies for catheter-related BSIs in haemodialysis. Some past trials have been limited by lack of blinding and short duration of follow-up. Microbiological epidemiology, although well characterized, may vary by region and treatment centre. Implications: With the high prevalence of catheter use in Canadian haemodialysis units, further studies on long-term treatment and preventative strategies for BSI are warranted.
Results of the 2014–2015 Canadian Society of Nephrology Workforce Survey
Authors: Ward David R. , Manns Braden , Gil Sarah , Au Flora , Kappel Joanne E. 
Published: April 2016

Background: Nephrology was previously identified as a subspecialty with few Canadian employment opportunities, and in recent years, fewer trainees are choosing nephrology. Objective: The objective of this study is to better understand the current Canadian adult nephrology workforce and the expected workforce trends over the next 5 years. Design: This is an online self-administered survey. Setting: This study is set in Canada. Survey participants: Survey participants are Canadian adult nephrologists, including self-identified division heads. Measurements: The measurements of this study are demographics, training, current practice characteristics, work hours, and projected workforce needs. Methods: Survey questions were based on previous workforce surveys. Ethics approval was obtained through the University of Saskatchewan. The survey was piloted in both English and French and modified based on the feedback to ensure that responses accurately reflected the information desired. It was circulated to all identified Canadian nephrologists via an anonymous e-mail link for self-administration. Categorical data was aggregated, and free-text answers were thematically analyzed. Additional descriptive analysis was conducted by all authors. Results: Five hundred ninety-two Canadian nephrologists were contacted and 48 % responded, with representation from all Canadian provinces. One third of the respondents were female, and the largest age cohort was 41–50 years. Most nephrologists are trained in Canada and 61 % completed additional training. The majority of the respondents (69.1 %) began working as a nephrologist immediately upon completion of fellowship training. Younger nephrologists reported more challenges in finding a job. Eighty percent of responding nephrologists were satisfied with their current work hours, 13.1 % will reduce work hours within 3 years, an additional 8.2 % will reduce work hours within 5 years, and a further 14.2 % will reduce work hours within 10 years. Nephrology division heads forecasted the number of clinical and academic nephrologists needed for the next 3 and 5 years. Limitations: The response rate was 48 %. Forecasted workforce needs are not indicative of guaranteed future positions. Conclusions: This Canadian Society of Nephrology workforce survey demonstrated the current workforce demographics, individual nephrologist future workforce plans, and projected nephrology division requirements for the next 3 and 5 years. Further work will need to be done to refine Canadian nephrology workforce planning with the development of a robust strategy that encompasses both societal and nephrologists' needs with the realities of employment.
Be ready at any time: postprandial synthesis of salivary proteins in salivary gland cells of the haematophagous leech Hirudo verbana
Authors: Lemke Sarah , Müller Christian , Hildebrandt Jan-Peter 
Published: April 2016

ABSTRACT
Sanguivorous leeches are ectoparasites having access to body fluids of potential hosts only infrequently. During feeding, salivary proteins are released from unicellular salivary glands into the wound. These substances, among them anti-coagulants, anti-inflammatory or anti-microbial agents, allow these animals proper feeding and long-term storage of host blood in their crops for several months. Using histological, protein biochemical and molecular techniques, we investigated whether synthesis of salivary proteins and refilling of salivary gland cells occur immediately after feeding or later when stored nutrients in the crop are getting scarce. The results of the histological analyses showed that gland cell area was significantly smaller right after feeding when compared with those in unfed animals. This parameter recovered quickly and reached the control level at 1 week after feeding. 2D gel electrophoresis and analysis of the abundance of individual proteins in extracts of leech tissues revealed that a subset of proteins that had been present in extracts of unfed animals virtually disappeared during feeding, but re-appeared within 1 week of feeding (most probably secretory proteins) while another subset did not change during the experimental period (most probably housekeeping proteins). Semi-quantitative PCR analysis of hirudin cDNA prepared from leech RNA samples revealed that the amount of hirudin transcripts increased immediately after feeding, peaked at 5 days after feeding and declined to control values thereafter. Our results indicate that bloodsucking leeches synthesize salivary proteins and refill their salivary gland cell reservoirs within a week of a blood meal to be prepared for another feeding opportunity.
Predation risk modifies behaviour by shaping the response of identified brain neurons
Authors: Magani Fiorella , Luppi Tomas , Nuñez Jesus , Tomsic Daniel 
Published: April 2016

ABSTRACT
Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs Neohelice granulata from two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome.
Debt Covenants and Cross-Sectional Equity Returns
Authors: Helwege Jean , Huang Jing-Zhi , Wang Yuan 
Published: April 2016

This paper investigates the impact of debt covenant protection on the cross section of equity returns with a firm-level covenant index and four subindices. We find that firms with weaker covenant protection (lower covenant index levels) earn significantly higher risk-adjusted equity returns than do those firms with greater covenant protection. These results are stronger for covenant indices that are related to investments, subsequent financing, and event risk. The difference between high and low covenant index stocks is more pronounced when agency problems between shareholders and debtholders are more severe, suggesting that the covenant effect arises from an inability to control shareholder risk taking. This paper was accepted by Wei Jiang, finance.
The unstable total hip arthroplasty
Authors: Ullmark Gösta 
Published: April 2016

One of the most common causes for revision surgery following total hip arthroplasty (THA) is dislocation. Dislocation is associated with a considerable amount of suffering and risks for the patient, and extra costs for the health care system. Compared with degenerative arthritis, the dislocation rate is doubled for avascular necrosis and multiplied by three times for congenital dislocation, four for fracture, five for nonunion, malunion or a failed hip arthroplasty, and eleven times after surgery for prosthetic instability. In analysing instability the cause may be assessed as 1) locally caused within the hip with explanatory radiographic findings, 2) locally caused without explanatory radiographic findings or 3) non-locally caused, i.e. non-compliant patient, neuromuscular or cognitive disorders. Revision strategies for instability are typically directed to correct the underlying aetiology, but also to strive for an upsizing of the head and liner.Cite this article: Ullmark G. The unstable total hip arthroplasty. EFORT Open Rev 2016;1:83-88. DOI: 10.1302/2058-5241.1.000022.
Perceived Autonomy Support Scale for Exercise Settings: Validity and reliability study for Turkish<p>Egzersizde Algılanan Özerklik Desteği Ölçeği: Türkçe geçerlik ve güvenirlik çalışması
Authors: Muftuler Mine 
Published: April 2016

The purpose of this study was to examine the validity and reliability of Perceived Autonomy Support Scale for Exercise Settings (PASSES; Hagger et al., 2007) from teacher and from peers in Turkish context. It was conducted with volunteer university students. 230 university students completed PASSES from teacher, and 142 university students completed PASSES from peers. Each scale has 12 items with a unidimension structure. The items were rated on a 7-point Likert type scale from totally disagree (1) to totally agree (7). Each scale was analyzed by using confirmatory factor analysis (CFA) to determine validity and by using Cronbach alpha value to determine reliability. The validity analyses for each scale showed good fit indexes in Turkish context. The reliability analyses also showed high reliability scores for each scale. Results were consistent with previous studies. It was suggested that PASSES from teacher and from peers can be used in Turkish context. ÖzetBu araştırmanın amacı “Egzersizde Algılanan Özerklik Desteği Ölçeğinin” (Perceived Autonomy Support Scale for Exercise Settings; Hagger ve diğ., 2007) hem öğretmen hem de arkadaşlar versiyonunu Türkçeye uyarlamak ve her iki ölçeğin geçerlik ve güvenirliğini incelemektir. Bu amaçla Türkçeye çevrilen ölçekler bir grup üniversite öğrencisine uygulanmıştır (öğretmen versiyonu için n = 230; arkadaşlar versiyonu için n = 142). Tek boyutlu olan ölçekler 12 ifadeden oluşmaktadır ve ifadeler tamamen katılmıyorum (1)’dan tamamen katılıyorum (7)’a doğru sıralanan yedili Likert üzerinden değerlendirilmektedir. Ölçeğin yapı geçerliğini belirlemek için doğrulayıcı faktör analizi uygulanmış, iç güvenirliğini tespit etmek için de Cronbach alfa kat sayısı hesaplanmıştır. Her iki ölçeğin yapı geçerliği bulguları iyi uyum indeksleri göstermiştir. Her iki ölçeğin iç güvenirlik kat sayıları da oldukça yüksek olarak hesaplanmıştır. Elde edilen bulgular alan yazında ilgili araştırmalarla benzerlik göstermektedir. Egzersizde Algılanan Özerklik Desteği Ölçeğinin hem öğretmen hem de arkadaşlar versiyonunun Türkçede ilgili araştırmalarda kullanılabileceği önerilmektedir.