bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking the next generation of homology inference tools
Authors: Saripella Ganapathi Varma , Sonnhammer Erik L. L. , Forslund Kristoffer 
Published: June 2016

Abstract
Motivation: Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the ‘next generation’ of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA.
Method: We generated challenging benchmark datasets based on protein domain architectures within either the PFAM + Clan, SCOP/Superfamily or CATH/Gene3D domain definition schemes. From each dataset, homologous and non-homologous protein pairs were aligned using each tool, and standard performance metrics calculated. We further measured congruence of domain architecture assignments in the three domain databases.
Results: CSBLAST and PHMMER had overall highest accuracy. FASTA, UBLAST and USEARCH showed large trade-offs of accuracy for speed optimization.
Conclusion: Profile methods are superior at inferring remote homologs but the difference in accuracy between methods is relatively small. PHMMER and CSBLAST stand out with the highest accuracy, yet still at a reasonable computational cost. Additionally, we show that less than 0.1% of Swiss-Prot protein pairs considered homologous by one database are considered non-homologous by another, implying that these classifications represent equivalent underlying biological phenomena, differing mostly in coverage and granularity.
Availability and Implementation: Benchmark datasets and all scripts are placed at ( http://sonnhammer.org/download/Homology_benchmark ).
Contact: forslund@embl.de
Supplementary information : Supplementary data are available at Bioinformatics online.
A novel role for poly(C) binding proteins in programmed ribosomal frameshifting
Authors: Napthine Sawsan , Treffers Emmely E. , Bell Susanne , Goodfellow Ian , Fang Ying , Firth Andrew E. , Snijder Eric J. , Brierley Ian 
Published: June 2016

Abstract
Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.
Normal Percentile Reference Curves and Correlation of Acetabular Index and Acetabular Depth Ratio in Children
Authors: Novais Eduardo N. , Pan Zhaoxing , Autruong Patrick T. , Meyers Mariana L. , Chang Frank M. 
Published: June 2016

Background:
Radiographic surveillance of the hip is vital in the diagnosis and treatment of developmental dysplasia of the hip (DDH) in children. The acetabular index (AI) and the acetabular depth ratio (ADR) are radiographic parameters for evaluation of acetabular morphology. Normal reference curves for these parameters that allow for serial evaluation of acetabular development in a manner that is independent of age are necessary and clinically useful. The purpose of this study was (1) to establish normal values of AI and ADR in the normally developing pediatric hip up to age 14, (2) to generate percentile reference curves of both parameters, (3) to determine the extent of correlation between AI and ADR, and (4) to assess intrarater and interrater reliability of AI measurement.

Methods:
We identified 1734 patients who underwent anterior-posterior pelvic radiography between 2004 and 2014. A total of 1152 patients (age range, 0.15 to 13.97 y; 2304 hips) were identified as radiographically normal in the radiology report, signed by the attending pediatric radiologist on the basis of the absence of structural deformity of the hip and previously established reference values for DDH assessment. A review of the medical records confirmed that patients had no diagnosis of DDH or any other orthopaedic hip pathology. The AI and ADR were measured in all radiographs. Normal values and fully parametric percentile curves were generated from birth to skeletal maturity. Correlation between AI and ADR was assessed using linear regression analysis.

Results:
Normal AI decreased, and ADR increased, with age. Percentile curves were generated for AI and ADR. Using the provided equations, measured values can be converted to age-appropriate percentile and Z-score. The 2 parameters exhibited strong correlation (Pearson correlation=−0.789, P<0.001). For every unit increase in ADR, AI decreased by 0.94 degrees.

Conclusions:
We present updated normative values of AI that expand up to age 14, and novel reference values for ADR. The reference curves allow for the easy conversion of measured values to percentile and Z-score. Using the presented method during surveillance of the pathologic hip, change in acetabular development can now be assessed in a manner that is independent of age and the natural development of the acetabulum.

Level of Evidence:
Level IV—case series.
Performing a Definitive Fusion in Juvenile CP Patients is a Good Surgical Option
Authors: Yaszay Burt , Sponseller Paul D. , Shah Suken A. , Asghar Jahangir , Miyanji Firoz , Samdani Amer F. , Bartley Carrie , Newton Peter O. 
Published: June 2016

Background:
In juveniles with progressive curves, there is debate regarding the use of growth friendly implants versus definitive fusion. This study presents outcomes of juvenile cerebral palsy (CP) scoliosis patients who underwent definitive fusion before age 11.

Methods:
A review of a prospective, multicenter registry identified patients 10 years and younger who had a definitive posterior fusion for their CP scoliosis. Preoperative and postoperative demographic and radiographic changes were evaluated with descriptive statistics. Repeated measures analysis of variance were utilized to compare outcome scores.

Results:
Fourteen children with a mean age of 9.7 years (8.3 to 10.8 y) and a minimum of 2 years follow-up (range 2 to 3 y) were identified. The mean preoperative curve magnitude and pelvic obliquity was 84±25 degrees (range 63 to 144 degrees) and 25±14 degrees, respectively. All patients were skeletally immature with open triradiate cartilage. Three patients had unit rods with wires while the rest incorporated pedicle screws. Immediately postoperation, the average major curve was 25±17 degrees (P≤0.001, 71% correction rate). At most recent follow-up, the average major curve increased to 30±18 degrees (P≤0.001) for a 65% correction rate. Pelvic obliquity improved to 4±4 degrees (84% correction, P≤0.001) immediately postoperation and to 6±5 degrees (P=0.002) at latest follow-up for a 76% correction rate. None of the patients required revision surgery for progression. From pre to most recent follow-up, the CPchild Health outcome scores improved from 47 to 58 (P=0.019). One patient had a deep infection, and 1 patient had a broken rod that did not require any further treatment.

Conclusions:
Progressive scoliosis in juvenile CP patients requires the surgeon to balance the need for further growth with the risks of progression or repeated surgical procedures. Our study demonstrates that definitive fusion once the curves approach 90 degrees results in significant radiographic and quality of life improvements, but further follow-up is needed to determine whether those results remain after skeletal maturity.

Level of Evidence:
Level IV—therapeutic.
Value of General Medical Knowledge Examinations in Performance Assessment of Practicing Physicians With Potential Competence and Performance Deficiencies
Authors: Wenghofer Elizabeth F. , Henzel Thomas R. , Miller Stephen H. , Norcross William , Boal Peter 
Published: June 2016

Introduction:
Problems with a physician's performance may arise at any point during their career. As such, there is a need for effective, valid tools and processes to accurately assess and identify deficiencies in competence or performance. Although scores on multiple-choice questions have been shown to be predictive of some aspects of physician performance in practicing physicians, their relationship to overall clinical competence is somewhat uncertain particularly after the first 10 years of practice. As such, the purpose of this study was to examine how a general medical knowledge multiple-choice question examination is associated with a comprehensive assessment of competence and performance in experienced practicing physicians with potential competence and performance deficiencies.

Methods:
The study included 233 physicians, of varying specialties, assessed by the University of California, San Diego Physician Assessment and Clinical Education Program (PACE), between 2008 and 2012, who completed the Post-Licensure Assessment System Mechanisms of Disease (MoD) examination. Logistic regression determined if the examination score significantly predicted passing assessment outcome after correcting for gender, international medical graduate status, certification status, and age.

Results:
Most physicians (89.7%) received an overall passing assessment outcome on the PACE assessment. The mean MoD score was 66.9% correct, with a median of 68.0%. Logistic regression (P = .038) was significant in indicating that physicians with higher MoD examination scores had an increased likelihood of achieving a passing assessment outcome (odds ratio = 1.057).

Discussion:
Physician MoD scores are significant predictors of overall physician competence and performance as evaluated by PACE assessment.
Locally Advanced Cervical Cancer
Authors: Manders Dustin B. , Morón Abel , McIntire Donald , Miller David S. , Richardson Debra L. , Kehoe Siobhan M. , Albuquerque Kevin V. , Lea Jayanthi S. 
Published: June 2016

Objective:
Adherence to treatment regimen and schedule is recommended to improve control of disease and overall survival (OS) in locally advanced cervical cancer. However, treatment-related toxicities and patient and physician factors all impact timely completion of treatment. We sought to correlate adherence to treatment plan with survival and toxicities of patients treated for locally advanced cervical cancer.

Materials and Methods:
A retrospective review of patients treated for advanced cervical cancer at our institution between 2003 and 2011 was performed. Demographics, clinicopathologic variables, treatment, and disease outcomes were collected. Endpoints of disease outcome were disease-free survival and OS. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis.

Results:
A total of 162 patients met the inclusion criteria and were included in study analysis. A total of 95% of patients were treated with both radiation and concurrent chemotherapy. Mean radiation dose to point A was 72 Gy. In total, 77% had complete response to primary therapy. Severe (grade 3/4) late radiation toxicities were seen in 10.5% of patients. Stage and total radiation dose to point A were significant predictors of survival for the entire cohort. Among patients receiving at least 72 Gy and brachytherapy, duration of treatment was significantly associated with both disease-free survival and OS.

Conclusions:
Adherence to both optimal treatment time and radiation dose is significantly associated with improved survival. Total radiation dose is an independent predictor of survival among patients with locally advanced cervical cancer.
Prevalence and Correlates of HIV Disclosure Among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review
Authors: Britto Carl , Mehta Kayur , Thomas Rwituja , Shet Anita 
Published: June 2016

ABSTRACT:

Objective:
Disclosure of HIV status among children and adolescents living with HIV has both beneficial and challenging aspects. To address existing knowledge gaps and update the literature on childhood disclosure, we conducted a systematic review on caregivers' perceptions and practices of HIV disclosure in low- and middle-income countries (LMICs).

Methods:
Standard databases were searched for studies conducted in LMICs, published in English between 2004 and 2015. Excluded articles were reviews or case reports, and those not reporting childhood disclosure. Data regarding prevalence, correlates and impact of disclosure, were presented as frequencies.

Results:
Two authors independently screened 982 articles. After applying eligibility criteria, 22 articles representing 12 countries and 2,843 children were reviewed. The proportion of fully disclosed children ranged from 1.7% to 41.0%. Up to 49.5% children were provided “deflected” information (use of a non-HIV-related reason for explaining illness and health care visits). Factors associated with full disclosure included antiretroviral treatment initiation and caregivers' felt need for maintaining optimal adherence. Barriers to disclosure included fear of negative psychological reactions and inadvertent disclosure to others. Caregivers perceived a strong need for active participation from health care providers to aid the process of disclosure.

Conclusions:
Full disclosure of HIV status was not common among children and adolescents in LMICs, while the practice of deflected disclosure was prominent. Caregivers perceived the need for support from health care providers during the disclosure process. Evidence-based guidelines incorporating the developmental status of the child, locally prevalent cultures, and caregiver perceptions are prerequisite to enhancing disclosure in these settings.
Advances in eyelid reconstruction
Authors: Dhar Shumon I. , Kopp Robert , Tatum Sherard A. 
Published: June 2016

Purpose of review
To describe the principles of eyelid reconstruction that must balance aesthetic and functional concerns of one of the most important areas of physical beauty on the human body. Our review seeks to give an overview of how to utilize a variety of techniques along the reconstructive ladder from direct closure to complex grafts and local flaps.

Recent findings
We describe novel modifications of existing flaps that have been traditionally used in eyelid reconstruction along with analysis of many time honored techniques and current research in improving our understanding of the factors which allow a successful reconstruction.

Summary
A familiarity with the variety of options for reconstruction will give the surgeon the fluidity to analyze a defect and choose the best possible method.
Attention deficit hyperactivity disorder medications in children with heart disease
Authors: Berger Stuart 
Published: June 2016

Purpose of review
Attention deficit hyperactivity disorder (ADHD) is quite common in the general pediatric population, Its incidence is thought to be even higher in the population of patients with congenital heart disease, especially in those patients with complex disease and who have had cardiac surgical interventions early in life. There has been controversy as to the safety of ADHD medications, especially in the latter population of patients. This compendium is meant to review the effects of the ADHD medications and the safety of these medications in patients with either known or undiagnosed congenital heart disease.

Recent findings
The concern with regard to the use of ADHD medications has been as a result of the reports of sudden unexpected deaths among patients taking stimulant drugs for ADHD. Therefore, the question of whether or not stimulant drugs increase the risk of adverse cardiovascular events has led to a discussion of the appropriate use of these drugs in patients with known cardiovascular disease, as well as a discussion as to the appropriate evaluation in order to identify undiagnosed ‘at-risk’ patients with congenital heart disease or arrhythmias. This article will review and amplify these discussions, as well as the conclusions that have come forth as a result of these discussions.

Summary
Currently available data suggest that there is no evidence for serious adverse cardiovascular complications in children with known cardiovascular diseases including patients of congenital heart disease who are treated with stimulant medications. Despite this, if the patient does have known cardiac disease, or if the history and physical examination is suggestive of cardiac disease, it is suggested that consultation/evaluation with a pediatric cardiologist occur. It is extremely unlikely that stimulant medications would be contraindicated in almost any condition that falls under this category. However, a few specific cardiac conditions might tailor the choice of the specific ADHD medication. Therefore the coordination of care between the primary care physician, the ADHD medication-prescribing physician, and the pediatric cardiologist may be very important in this circumstance.
Burkholderia cepacia pseudobacteremia traced to contaminated antiseptic used for skin antisepsis prior to blood collection
Authors: Tandel Kundan , Bhatt Puneet , Sen Sourav , Gupta Rajiv Mohan , Hazra Nandita , Praharaj A.K. , Kumar Satish , Sahni A.K. 
Published: June 2016

Background:

Burkholderia (previously Pseudomonas) cepacia is a Gram-negative bacillus commonly found in soil and moist environments and capable of surviving and growing in nutrient-poor surroundings. It is a problematic pulmonary pathogen in patients with cystic fibrosis and is associated with a poor prognosis. Small hospital outbreaks are frequent, usually because of a single contaminated source such as disinfectant.

Aim:
To identify the source and route of infection of B. cepacia grown from 12 patients from a surgical ICU.

Methods:
We carried out an environmental and epidemiological investigation to identify the source and route of infection. Environmental samples previously reported to be potential reservoirs of B. cepacia were collected and processed.

Results:
Out of 67 blood samples received in a 2-month period from the ICU (surgical) of a tertiary care centre, B. cepacia was isolated from blood specimens of 12 patients, whereas 34 samples grew organisms other than B. Cepacia, 20 specimens were culture negative. There were no cases of B. Cepacia in the last 1 year before this outbreak. We isolated B. cepacia from the cetrimide + chlorhexidine solution used for skin antisepsis prior to blood collection.

Conclusion:

B. cepacia has the potential to cause fatal infections and its multidrug resistance makes its presence dangerous in hospital settings. The surveillance of B. cepacia infections should not be neglected, especially in the ICUs. Given the high transmissibility of the microorganism and previous epidemic reports, strict infection control measures should be applied in the case of diagnosis of B. cepacia infection.
Streptococcus constellatus Tubo-ovarian Abscess in a Non–Sexually Active Adolescent Female
Authors: Mills David , Sharon Bazak , Schneider Kari 
Published: June 2016

Abstract
Tubo-ovarian abscess (TOA) in non–sexually active female adolescents is a rare presentation to the pediatric emergency department. In the following case, bilateral TOA secondary to Streptococcus constellatus was diagnosed in a 13-year-old virginal female. The patient was seen 4 months before presentation for interventional radiology-guided drainage and antibiotic treatment for an intra-abdominal abscess due to suspected appendiceal rupture. Exploratory laparotomy on the most recent presentation demonstrated an appendix with inflammation and serositis on pathology report, a concern for chronic appendicitis with microperforation and subsequent bacterial translocation of the bilateral ovaries. This case report identifies a rare cause, pathogen, and the patient's demographics presenting with bilateral TOA. Most importantly, this case demonstrates the need for emergency medicine physicians to have a high index of suspicion for TOA in patients with a significant medical history of intra-abdominal pathology to promptly diagnose and treat high-morbidity pathology.
Pre–Trauma Center Management of Intracranial Pressure in Severe Pediatric Traumatic Brain Injury
Authors: Hansen Gregory , McDonald Patrick J. , Martin Doug , Vallance Jeff K. 
Published: June 2016

Objectives
Pre–trauma center care is a critical component in severe pediatric traumatic brain injury (TBI). For geographically large trauma catchment areas, optimizing increased intracranial pressure (ICP) management may potentially improve outcomes. This retrospective study examined ICP management in nontrauma centers and during interfacility transport to the trauma center.

Methods
Charts from a pediatric level I trauma center were reviewed for admissions between 2008 and 2013. Patients with a Glasgow Coma Scale score of 8 or less, head Abbreviated Injury Scale score of 3 or higher, and requiring intubation at a nontrauma center were included. Exclusion criteria included head injury secondary to drowning, stroke, obstetrical complications, asphyxia, and afflicted head trauma (younger than 5 years). Trauma center charts contained coalesced data from first responders, nontrauma centers, and transport.

Results
Twenty-five patients (74%) had increased ICP upon admission at trauma center, 48% experienced ICPs greater than 20 cm H2O within 12 hours of admission, 12% required an urgent craniotomy, and 16% had herniation syndromes on neuroimaging. Pre–trauma center ICP management included osmotherapy and head-of-bed elevation. Sixty-four percent of patients with increased ICP at trauma center admission received pre–trauma center ICP management.

Conclusions
Early increased ICP is a common presentation of severe pediatric TBI during pre–trauma center management. However, what constitutes optimal care remains unknown. Given the difficulties of diagnosing early increased ICP in this setting, prophylactic raising ICP-lowering strategies may be considered.
Antagonistic roles of Polycomb repression and Notch signaling in the maintenance of somatic cell fate inC. elegans.
Authors: Pueschel Ringo , Coraggio Francesca , Marti Alisha , Meister Peter 
Published: June 2016

AbstractReprogramming of somatic cells in intact nematodes allows characterization of cell plasticity determinants, which knowledge is crucial for regenerative cell therapies. By inducing muscle or endoderm transdifferentiation by the ectopic expression of selector transcription factors, we show that cell fate is remarkably robust in fully differentiated larvae. This stability depends on the presence of the Polycomb-associated histone H3K27 methylation, but not H3K9 methylation: in the absence of this epigenetic mark, many cells can be transdifferentiated which correlates with definitive developmental arrest. A candidate RNAi screen unexpectedly uncovered that knock-down of somatic NotchLIN-12signaling rescues this larval arrest. Similarly in a wild-type context, genetically increasing NotchLIN-12signaling renders a fraction of the animals sensitive to induced transdifferentiation. This reveals an antagonistic role of the Polycomb repressive complex 2 stabilizing cell fate and Notch signaling enhancing cell plasticity.