bluuebunny/crossref_metadata_2025_split huggingface dataset:
HAPRAP: a haplotype-based iterative method for statistical fine mapping using GWAS summary statistics
Authors: Zheng Jie , Rodriguez Santiago , Laurin Charles , Baird Denis , Trela-Larsen Lea , Erzurumluoglu Mesut A , Zheng Yi , White Jon , Giambartolomei Claudia , Zabaneh Delilah , Morris Richard , Kumari Meena , Casas Juan P , Hingorani Aroon D ,   UCLEB Consortium, Evans David M , Gaunt Tom R , Day Ian N M 
Published: September 2016

AbstractMotivationFine mapping is a widely used approach for identifying the causal variant(s) at disease-associated loci. Standard methods (e.g. multiple regression) require individual level genotypes. Recent fine mapping methods using summary-level data require the pairwise correlation coefficients (r2) of the variants. However, haplotypes rather than pairwise r2, are the true biological representation of linkage disequilibrium (LD) among multiple loci. In this article, we present an empirical iterative method, HAPlotype Regional Association analysis Program (HAPRAP), that enables fine mapping using summary statistics and haplotype information from an individual-level reference panel.ResultsSimulations with individual-level genotypes show that the results of HAPRAP and multiple regression are highly consistent. In simulation with summary-level data, we demonstrate that HAPRAP is less sensitive to poor LD estimates. In a parametric simulation using Genetic Investigation of ANthropometric Traits height data, HAPRAP performs well with a small training sample size (N &lt; 2000) while other methods become suboptimal. Moreover, HAPRAP’s performance is not affected substantially by single nucleotide polymorphisms (SNPs) with low minor allele frequencies. We applied the method to existing quantitative trait and binary outcome meta-analyses (human height, QTc interval and gallbladder disease); all previous reported association signals were replicated and two additional variants were independently associated with human height. Due to the growing availability of summary level data, the value of HAPRAP is likely to increase markedly for future analyses (e.g. functional prediction and identification of instruments for Mendelian randomization).Availability and ImplementationThe HAPRAP package and documentation are available at http://apps.biocompute.org.uk/haprap/Supplementary informationSupplementary data are available at Bioinformatics online.
popSTR: population-scale detection of STR variants
Authors: Kristmundsdóttir Snædís , Sigurpálsdóttir Brynja D , Kehr Birte , Halldórsson Bjarni V 
Published: September 2016

Abstract

Motivation
Microsatellites, also known as short tandem repeats (STRs), are tracts of repetitive DNA sequences containing motifs ranging from two to six bases. Microsatellites are one of the most abundant type of variation in the human genome, after single nucleotide polymorphisms (SNPs) and Indels. Microsatellite analysis has a wide range of applications, including medical genetics, forensics and construction of genetic genealogy. However, microsatellite variations are rarely considered in whole-genome sequencing studies, in large due to a lack of tools capable of analyzing them.

Results
Here we present a microsatellite genotyper, optimized for Illumina WGS data, which is both faster and more accurate than other methods previously presented. There are two main ingredients to our improvements. First we reduce the amount of sequencing data necessary for creating microsatellite profiles by using previously aligned sequencing data. Second, we use population information to train microsatellite and individual specific error profiles. By comparing our genotyping results to genotypes generated by capillary electrophoresis we show that our error rates are 50% lower than those of lobSTR, another program specifically developed to determine microsatellite genotypes.

Availability and Implementation
Source code is available on Github: https://github.com/DecodeGenetics/popSTR
signeR: an empirical Bayesian approach to mutational signature discovery
Authors: Rosales Rafael A , Drummond Rodrigo D , Valieris Renan , Dias-Neto Emmanuel , da Silva Israel T 
Published: September 2016

Abstract

Motivation
Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. Current methods based on optimization techniques are strongly sensitive to initial conditions due to high dimensionality and nonconvexity of the NMF paradigm. In this context, an important question consists in the determination of the actual number of signatures that best represent the data. The extraction of mutational signatures from high-throughput data still remains a daunting task.

Results
Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. While requiring minimal intervention from the user, our method addresses the determination of the number of signatures directly as a model selection problem. In addition, we introduce two new concepts of significant clinical relevance for evaluating the mutational profile. The advantages brought by our approach are shown by the analysis of real and synthetic data. The later is used to compare our approach against two alternative methods mostly used in the literature and with the same NMF parametrization as the one considered here. Our approach is robust to initial conditions and more accurate than competing alternatives. It also estimates the correct number of signatures even when other methods fail. Results on real data agree well with current knowledge.

Availability and Implementation
signeR is implemented in R and C ++, and is available as a R package at http://bioconductor.org/packages/signeR.

Supplementary information
Supplementary data are available at Bioinformatics online.
Technology and tuberculosis control: the OUT-TB Web experience
Authors: Guthrie Jennifer L , Alexander David C , Marchand-Austin Alex , Lam Karen , Whelan Michael , Lee Brenda , Furness Colin , Rea Elizabeth , Stuart Rebecca , Lechner Julia , Varia Monali , McLean Jennifer , Jamieson Frances B 
Published: September 2016

Objective: Develop a tool to disseminate integrated laboratory, clinical, and demographic case data necessary for improved contact tracing and outbreak detection of tuberculosis (TB).
Methods: In 2007, the Public Health Ontario Laboratories implemented a universal genotyping program to monitor the spread of TB strains within Ontario. Ontario Universal Typing of TB (OUT-TB) Web utilizes geographic information system (GIS) technology with a relational database platform, allowing TB control staff to visualize genotyping matches and microbiological data within the context of relevant epidemiological and demographic data.
Results: OUT-TB Web is currently available to the 8 health units responsible for &gt;85% of Ontario’s TB cases and is a valuable tool for TB case investigation. Users identified key features to implement for application enhancements, including an e-mail alert function, customizable heat maps for visualizing TB and drug-resistant cases, socioeconomic map layers, a dashboard providing TB surveillance metrics, and a feature for animating the geographic spread of strains over time.
Conclusion: OUT-TB Web has proven to be an award-winning application and a useful tool. Developed and enhanced using regular user feedback, future versions will include additional data sources, enhanced map and line-list filter capabilities, and development of a mobile app.
Are there two types of pulsars?
Authors: Contopoulos I. 
Published: September 2016

Abstract
In order to investigate the importance of dissipation in the pulsar magnetosphere, we decided to combine force-free with Aristotelian electrodynamics. We obtain solutions that are ideal (non-dissipative) everywhere except in an equatorial current sheet where Poynting flux from both hemispheres converges and is dissipated into particle acceleration and radiation. We find significant dissipative losses (up to about 50 per cent of the pulsar spin-down luminosity), similar to what is found in global Particle-In-Cell simulations in which particles are provided only on the stellar surface. We conclude that there might indeed exist two types of pulsars, strongly dissipative ones with particle injection only from the stellar surface, and ideal (weakly dissipative) ones with particle injection in the outer magnetosphere and in particular at the Y-point.
A strong-lensing elliptical galaxy in the MaNGA survey
Authors: Smith Russell J. 
Published: September 2016

Abstract
I report discovery of a new galaxy-scale gravitational lens system, identified using public data from the Mapping Galaxies at Apache Point Observatory (MaNGA) survey, as part of a systematic search for lensed background line emitters. The lens is SDSS J170124.01+372258.0, a giant elliptical galaxy with velocity dispersion σ = 256 km s−1, at a redshift of zl = 0.122. After modelling and subtracting the target galaxy light, the integral-field data cube reveals [O ii], [O iii] and Hβ emission lines corresponding to a source at zs = 0.791, forming an identifiable ring around the galaxy centre. If the ring is formed by a single lensed source, then the Einstein radius is REin ≈ 2.3 arcsec, projecting to ∼5 kpc at the distance of the lens. The total projected lensing mass is MEin = (3.6 ± 0.6) × 1011 Mȯ, and the total J-band mass-to-light ratio is 3.0 ± 0.7 solar units. Plausible estimates of the likely dark matter content could reconcile this with a Milky Way-like initial mass function (IMF), for which M/L ≈ 1.5 is expected, but heavier IMFs are by no means excluded with the present data. An alternative interpretation of the system, with a more complex source plane, is also discussed. The discovery of this system bodes well for future lens searches based on MaNGA and other integral-field spectroscopic surveys.
Sevoflurane Impairs Growth Cone Motility in Dissociated Murine Neurons
Authors: Ryu Yun Kyoung , Mathena Reilley P. , Lim Sanghee , Kwak Minhye , Xu Michael , Mintz Cyrus D. 
Published: September 2016

Background:
Early postnatal exposure to general anesthetic agents causes a lasting impairment in learning and memory in animal models. One hypothesis to explain this finding is that exposure to anesthetic agents during critical points in neural development disrupts the formation of brain circuitry. Here, we explore the effects of sevoflurane on the neuronal growth cone, a specialization at the growing end of axons and dendrites that is responsible for the targeted growth that underlies connectivity between neurons.

Methods:
Dissociated neuronal cultures were prepared from embryonic mouse neocortex. Time-lapse images of live growth cones exposed to anesthetics were taken using differential interference contrast microscopy, and the rate of change of the area of the lamellipodia and the speed of the filopodial tip were quantified as measures of motility. The involvement of the p75 neurotropin receptor (p75NTR) was tested using inhibitors applied to the media and by a coimmunoprecipitation assay.

Results:
The rate of lamellipodial area change and filopodial tip velocity in both axonal and dendritic growth cones was significantly reduced with sevoflurane exposure between 2% and 6%. Motility could be substantially restored by treatment with Y27632 and TAT-peptide 5, which are inhibitors of Rho Kinase and p75NTR, respectively. Sevoflurane results in reduced coimmunoprecipitation of Rho-Guanosine-5′-diphosphate dissociation inhibitor after pulldown with p75NTR.

Conclusions:
Sevoflurane interferes with growth cone motility, which is a critical process in brain circuitry formation. Our data suggest that this may occur through an action on the p75NTR, which promotes growth inhibitory signaling by the Rho pathway.
Use of Patient-reported Outcome Measures in Pediatric Orthopaedic Literature
Authors: Phillips Lisa , Carsen Sasha , Vasireddi Anisha , Mulpuri Kishore 
Published: September 2016

Background:
Patient-reported outcomes are increasingly used as primary measures of success and impact of health care services. There is no current consensus on the efficacy of functional health status (FHS) or health-related quality of life (HRQoL) evaluation in pediatric orthopaedic surgery. The purpose of this study was to quantify and characterize the use of such patient-reported outcomes in the pediatric orthopaedic literature over the last several years.

Methods:
A cross-sectional review of 6 orthopaedic journals—Journal of Bone and Joint Surgery, Bone and Joint Journal, Spine, Journal of Pediatric Orthopaedics A, Journal of Pediatric Orthopaedics B, and Journal of Children’s Orthopaedics, was conducted by 2 independent reviewers. Articles were analyzed for patient-reported outcome usage over the time periods of 2000 to 2001, 2007 to 2008, and 2012 to 2013.

Results:
A total of 189 articles (2.7%) were identified that used patient-reported outcomes in pediatric populations. A total of 71 (37.5%) of these articles used FHS tools, 95 (50.3%) used HRQoL tools and 23 (12.2%) used a combination of both. The use of FHS and HRQoL tools has increased over time, with 8 FHS and 2 HRQoL publications in the year 2000 expanding to 19 and 28, respectively, in 2013. Journal of Bone and Joint Surgery American Volume published both the highest total number of articles containing patient-reported outcome measures (57/189) and the highest number of articles specifically using FHS measures (28/71). Spine published the highest number of articles using HRQoL measures (43/95). The most frequently used FHS and HRQoL tools were the Lysholm knee score and the Scoliosis Research Society tools, respectively. Only 33/73 identified patient-based outcome instruments had been validated in a pediatric population.

Conclusions:
Patient-reported outcome measures are underutilized in the pediatric orthopaedic literature. Instruments are frequently used that are neither designed nor validated for a pediatric population. Consequently, further work is necessary to develop, validate, and implement pediatric-specific FHS and HRQoL tools to fully understand the impact of a clinical intervention on all aspects of patient quality of life.
Intraoperative Hypothermia is Common, but not Associated With Blood Loss or Transfusion in Pediatric Posterior Spinal Fusion
Authors: Schur Mathew D. , Blumstein Gideon W. , Seehausen Derek A. , Ross Patrick A. , Andras Lindsay M. , Skaggs David L. 
Published: September 2016

Background:
Intraoperative hypothermia may be associated with increased blood loss due to the effects of temperature on clotting but this has not been evaluated in the setting of pediatric posterior spinal fusion (PSF). The purpose of this study was to determine if a correlation exists between intraoperative hypothermia and estimated blood loss (EBL) or transfusion requirements in pediatric patients undergoing PSF.

Methods:
A retrospective review of consecutive patients undergoing PSF for scoliosis at a single institution between 6/2004 and 3/2012 was performed. Exclusion criteria were fewer than 10 levels fused, anterior spinal fusion, and patients below 9 years old at time of surgery. Temperature was measured every 15 seconds using esophageal temperature probe. Input variable of hypothermia was analyzed as a binary variable T
min ≤35°C at any point during anesthesia and as integrated temperature area under the curve (TAUC).

Results:
A total of 510 with an average age of 14.6 years (range, 9.0 to 24.3 y) met inclusion criteria. Totally, 56% (287/510) had idiopathic scoliosis (IS) and 44% (223/510) were non-IS. Hypothermia (T
min≤35°C) was experienced by 45% (230/510) of all patients [48% (137/287) of IS; 42% (93/223) of non-IS]. A total of 63% (323/510) of patients were transfused with packed red blood cells (PRBC) [49% (141/287) of IS patients; 82% (182/223) of non-IS patients]. There was no correlation between T
min≤35°C and transfusion of PRBC in all included patients (P=0.49); (IS patients P=0.45, non-IS patients P=0.61). There was no significant difference in EBL between patients who experienced hypothermia and those who did not (P=0.33; IS patients P=0.21, non-IS patients P=0.87). There was no significant correlation between TAUC and transfusion of PRBC for all patients (P=0.35), IS patients (P=0.26) and non-IS patients (P=0.54) or between TAUC and EBL (P=0.80); (IS patients P=0.57. non-IS patients P=0.62).

Conclusions:
There was no significant correlation between intraoperative hypothermia and EBL or transfusion of PRBC in pediatric patients undergoing PSF.

Level of Evidence:
Level III.
Subcapital Shortening Osteotomy for Severe Slipped Capital Femoral Epiphysis: Preliminary Results of the French Multicenter Study
Authors: Ilharreborde Brice , Cunin Vincent , Abu-Amara Saad 
Published: September 2016

Background:
There is growing evidence that symptomatic femoroacetabular impingement (FAI) can develop after severe slipped capital femoral epiphysis (SCFE) fixed in situ. Realignment procedures have therefore gained popularity, but complication rates remain controversial. Among them, the subcapital shortening osteotomy without hip dislocation has been progressively adopted in France, but results have never been assessed to date.

Methods:
All cases performed in 23 French university hospitals between January 2010 and March 2014 were reviewed to (1) describe the surgical procedure, (2) assess the radiologic and functional outcomes, and (3) report complications and more specifically the avascular necrosis rate (AVN) according to initial stability. Stable and unstable SCFE were distinguished following Loder’s definition. Radiologic outcomes were assessed by the 3 authors to determine FAI and osteonecrosis rates. Functional outcomes were evaluated at follow-up and complications were reported.

Results:
A total of 82 cases (45 unstable and 37 stable), performed in 10 institutions, were included with a mean follow-up of 25 months. No intraoperative complication occurred but 2 patients (2.4%) underwent unplanned early revision. Slip angle was significantly reduced (87%) without loss of correction. Overall AVN rate was 9.7%, reaching 13.3% in unstable slips. However, preoperative magnetic resonance imaging showed that most of the unstable epiphyses (4/6) were already hypoperfused before surgery.

Conclusions:
The procedure is a reliable option for the treatment of severe SCFE. AVN rates are lower than previously reported in multicenter series of modified Dunn technique, especially in unstable slips. However, the risk of AVN in severe stable SCFE (5.4%) must still be balanced with the functional outcomes of potential future FAI.

Level of Evidence:
Level IV—therapeutic study.
Soft Tissue Injury Severity is Associated With Neurovascular Injury in Pediatric Supracondylar Humerus Fractures
Authors: Ho Christine A. , Podeszwa David A. , Riccio Anthony I. , Wimberly Robert L. , Ramo Brandon A. 
Published: September 2016

Background:
Neurovascular injury in pediatric supracondylar fractures (SCHFx) has been associated with fracture classification but not with soft tissue injury. The purpose of this study is to correlate clinical soft tissue damage to neurovascular injuries in SCHFx.

Methods:
This is an institutional review board approved prospective study from January 2010 through December 2013 of 748 operatively treated pediatric SCHFx. Prospective data were gathered both preoperatively and intraoperatively regarding detailed neurovascular examination as well as soft tissue status, with qualitative descriptives for swelling (mild/moderate/severe), ecchymosis, abrasions, skin tenting, and skin puckering.

Results:
A total of 7.8% of patients (41/526) had a nonpalpable radial pulse preoperatively. Compared with those with a palpable pulse, a nonpalpable pulse was associated with severe elbow swelling (P<0.0001), tenting (P=0.0085), puckering (P=0.0011), ecchymoses (P<0.0001), and open fracture (P=0.044). Ten patients had a loss of a palpable pulse from initial orthopaedic consult to time of surgery, and when compared with the patients who did not have a loss of pulse, this was associated with swelling severity (P=0.0001) and ecchymosis (P=0.053). A total of 14% of patients (71/526) had a neurological injury preoperatively, and this was associated with severe elbow swelling (P<0.0001), tenting (P=0.0008), puckering (P=0.0077), and ecchymoses (P<0.0001) when compared with patients who did not have a neurological injury. In total, 17 patients had a decline in their neurological examination from the time of initial orthopaedic consult to the time of surgery, and this was associated with severe elbow swelling (P=0.0054) and ecchymoses (P=0.011). After multivariate logistic regression analysis, severe swelling and ecchymoses were significantly associated with a nonpalpable pulse as well as neurological injury (P<0.05). No patient had compartment syndrome.

Conclusions:
Soft tissue injury, as measured by swelling, ecchymosis, puckering, and tenting, had a clinically significant association with neurovascular compromise in pediatric SCHFx, and assessment of soft tissue injury is as important as the radiographic appearance when examining these patients. The physical examination signs of soft tissue injury may play a factor in determining urgency of surgical treatment in these fractures.

Level of Evidence:
Level II—therapeutic.
Complication Rates After Bone Morphogenetic Protein (BMP) Use in Orthopaedic Surgery in Children: A Concise Multicenter Retrospective Cohort Study
Authors: Garg Sumeet , McCarthy James J. , Goodwin Ryan , Kolmodin Joel , Sankar Wudbhav N. , Franklin Corinna , Armstrong Douglas , Fryzel David , Hassenbein Susan , Meder Cara 
Published: September 2016

Background:
The use of bone morphogenetic protein (BMP) has been associated with a number of complications in adult patients. However, this association is less established in children. The aim of this study was to evaluate the safety of BMP use in children by determining the complication rates after BMP use at multiple institutions.

Methods:
In a retrospective study (2000 to 2013), the medical records of all patients who received BMP at any of the 5 institutions were reviewed. Demographic information, preoperative data, and postoperative follow-up data were collected on those patients who were under the age of 18 at the time of surgery.

Results:
A total of 312 pediatric patients underwent surgery with BMP application during the study period. The surgical procedures consisted of 228 spinal fusions, 39 pars repairs, 33 nonunion repair, and 12 other various procedures. Overall 21% (65/312) of patients who had BMP utilized had a complication. Fifty-five percent (36/65) of patients with a complication required a revision surgery. The average follow-up was 27 months (range, 3 to 96 mo); 80% of patients had a follow-up period of >12 months. The average age at the time of surgery was 13 years (range, 1 to 17 y). Males and females were almost equally represented in the study: 143 males (46%) and 168 females (54%). Of the patients who received BMP, 9% had minor complications and 13% had major complications. Wound dehiscence without infection was the most common minor complication and occurred in 59% (16/27) of patients with minor complications. Infection and implant failures were the most frequent major complications, occurring in 38% (15/39) and 33% (13/39) of patients with major complications, respectively. Five of 312 (2%) patients had neurological injury, 3 of which were only temporary.

Conclusions:
This multicenter study demonstrates a relatively high rate of complications after the use of BMP in children. However, further study is needed to attribute the complications directly to the use of BMP.

Level of Evidence:
Level IV.