bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational identification of micro-structural variations and their proteogenomic consequences in cancer
Authors: Lin Yen-Yi , Gawronski Alexander , Hach Faraz , Li Sujun , Numanagić Ibrahim , Sarrafi Iman , Mishra Swati , McPherson Andrew , Collins Colin C , Radovich Milan , Tang Haixu , Sahinalp S Cenk 
Published: December 2017

Abstract

Motivation
Rapid advancement in high throughput genome and transcriptome sequencing (HTS) and mass spectrometry (MS) technologies has enabled the acquisition of the genomic, transcriptomic and proteomic data from the same tissue sample. We introduce a computational framework, ProTIE, to integratively analyze all three types of omics data for a complete molecular profile of a tissue sample. Our framework features MiStrVar, a novel algorithmic method to identify micro structural variants (microSVs) on genomic HTS data. Coupled with deFuse, a popular gene fusion detection method we developed earlier, MiStrVar can accurately profile structurally aberrant transcripts in tumors. Given the breakpoints obtained by MiStrVar and deFuse, our framework can then identify all relevant peptides that span the breakpoint junctions and match them with unique proteomic signatures. Observing structural aberrations in all three types of omics data validates their presence in the tumor samples.

Results
We have applied our framework to all The Cancer Genome Atlas (TCGA) breast cancer Whole Genome Sequencing (WGS) and/or RNA-Seq datasets, spanning all four major subtypes, for which proteomics data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) have been released. A recent study on this dataset focusing on SNVs has reported many that lead to novel peptides. Complementing and significantly broadening this study, we detected 244 novel peptides from 432 candidate genomic or transcriptomic sequence aberrations. Many of the fusions and microSVs we discovered have not been reported in the literature. Interestingly, the vast majority of these translated aberrations, fusions in particular, were private, demonstrating the extensive inter-genomic heterogeneity present in breast cancer. Many of these aberrations also have matching out-of-frame downstream peptides, potentially indicating novel protein sequence and structure.

Availability and implementation
MiStrVar is available for download at https://bitbucket.org/compbio/mistrvar, and ProTIE is available at https://bitbucket.org/compbio/protie.

Supplementary information
Supplementary data are available at Bioinformatics online.
Effect of the BASIC Examination on Knowledge Acquisition during Anesthesiology Residency
Authors: Zhou Yan , Sun Huaping , Lien Cynthia A. , Keegan Mark T. , Wang Ting , Harman Ann E. , Warner David O. 
Published: December 2017

Abstract

Background
The American Board of Anesthesiology recently introduced the BASIC Examination, a component of its new staged examinations for primary certification, typically offered to residents at the end of their first year of clinical anesthesiology training. This analysis tested the hypothesis that the introduction of the BASIC Examination was associated with an acceleration of knowledge acquisition during the residency training period, as measured by increments in annual In-Training Examination scores.

Methods
In-Training Examination performance was compared longitudinally among four resident cohorts (n = 6,488) before and after the introduction of the staged system using mixed-effects models that accounted for possible covariates.

Results
Compared with previous cohorts in the traditional examination system, the first resident cohort in the staged system had a greater improvement in In-Training Examination scores between the first and second years of clinical anesthesiology training (by an estimated 2.0 points in scaled score on a scale of 1 to 50 [95% CI, 1.7 to 2.3]). By their second year, they had achieved a score similar to that of third-year clinical anesthesiology residents in previous cohorts. The second cohort to enter the staged system had a greater improvement of the scores between the clinical base year and the first clinical anesthesiology year, compared with the previous cohorts.

Conclusions
These results support the hypothesis that the introduction of the BASIC Examination is associated with accelerated knowledge acquisition in residency training and provides evidence for the value of the new staged system in promoting desired educational outcomes of anesthesiology training.
Rhythmic Auditory Music Stimulation Enhances Walking Distance in Patients With Claudication
Authors: Bronas Ulf G. , Everett Steve , Steffen Alana , Briller Joan , Hannan Mary , Hernandez Alison , Collins Eileen 
Published: December 2017

Purpose:
Patients with claudication have altered gait, characterized by slower pace and shorter stride length, compared with matched controls. Rhythmic auditory music stimulation has been used successfully to reduce symptoms of pain and improve walking ability in patients with neurological gait alterations. The purpose of this study was to test the hypothesis that rhythmic auditory music stimulation via increased tempo and bass would immediately increase total walking distance in patients with claudication compared with music-without rhythm-enhancement condition or a no-music condition (standard).

Methods:
Fourteen patients with claudication (mean age = 66.1 ± 7.7 y; ankle-brachial index = 0.63 ± 17) underwent three 6-min walk tests on the same day in random order. One with music-without rhythm enhancement with the tempo set at the usual walking cadence of the patient, one without music, and one with rhythmically enhanced music with the tempo increased 10 to 15 beats/min above the usual walking cadence of the patient. This increase in tempo is considered imperceptible to the untrained ear.

Results:
The paired t test indicated an increase in total walking distance by 22.1 ± 25.4 m (P = .006) during the rhythmic auditory stimulation condition compared with the no-music condition and by 20.7 ± 24.4 m compared with the music-without enhancement condition (P = .007). Functional claudication distance increased by 40.0 ± 49.0 m during the rhythmically enhanced music condition (P = .009) compared with the no-music condition.

Conclusions:
These results suggest that rhythmic auditory stimulation immediately increases total walking distance in patients with claudication due to peripheral artery disease. This technology may provide a tool for clinicians to use when prescribing exercise, improve motivation, and increase adherence to exercise rehabilitation programs.
SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF THE MACULA AND VITREOMACULAR INTERFACE IN PERSISTENT FETAL VASCULATURE SYNDROME WITH POSTERIOR INVOLVEMENT
Authors: De la Huerta Irina , Mesi Oltion , Murphy Breanne , Drenser Kimberly A. , Capone Antonio , Trese Michael T. 
Published: December 2017

Purpose:
To describe the microstructural features of the macula and vitreomacular interface in persistent fetal vasculature syndrome (PFVS) with posterior involvement managed with early vitrectomy or with observation, with functional correlation.

Methods:
We retrospectively identified 45 consecutive pediatric patients with PFVS with posterior involvement treated from 2005 to 2016. The eyes that could be imaged with spectral domain optical coherence tomography were included, and images were correlated with best-corrected visual acuity.

Results:
Thirty-eight imaging sessions were performed on 10 eyes from 9 patients, including 7 that had been managed with vitrectomy for PFVS-related tractional retinal detachment, and 3 that had been observed. Mean age of the patients who were imaged was 9.1 years and their average length of follow-up was 5.9 years. Best-corrected visual acuities of the eyes imaged ranged from 20/30 to count fingers, with mean best-corrected visual acuity 20/163. All eyes imaged had microstructural anomalies identified. The main anomalous features included posterior hyaloidal organization, vitreoretinal traction, vitreopapillary traction, diminished foveal contour, foveal displacement, and disruption of the ellipsoid zone. Posterior hyaloidal organization (P = 0.043), diminished foveal contour (P = 0.019), and disruption of the ellipsoid zone (P = 0.014) were associated with worse best-corrected visual acuity.

Conclusion:
Macular and vitreomacular interface anomalies were identified in all pediatric patients with posterior PFVS imaged with spectral domain optical coherence tomography. These microstructural findings, together with functional measures, may inform the diagnosis and management of PFVS with posterior involvement.
A Standardized Clinical Pathway to Decrease Hospital Admissions Among Febrile Children With Sickle Cell Disease
Authors: Ellison Angela M. , Smith Whitley Kim , Kittick Marlena , Schast Aileen , Norris Cynthia , Hartung Helge , McKnight Therese , Coyne Erin , Lavelle Jane 
Published: December 2017

Background and Objective:
Recurrent hospital admissions for patients with sickle cell disease (SCD) are costly and contribute to a low quality of life for patients. We implemented a clinical pathway to safely discharge SCD patients with fever who are evaluated in the emergency department (ED) of a large tertiary care center.

Methods:
An interdisciplinary team of ED and hematology physicians, nurses, and an improvement advisor developed a clinical pathway that identified febrile SCD patients at low risk of serious bacterial infection based on historical, clinical, and laboratory criteria who could be discharged from the ED. Phone follow-up was planned through the use of an automated electronic notification that was sent to an established hematology follow-up pool at the time of ED discharge. We conducted two “fake front end” trials in the ED to receive feedback on our process before full implementation. A postpathway implementation quality improvement team monitored discharge rates, phone follow-up rates and adverse events.

Results:
In the first 9 weeks postpathway implementation, 100 SCD patients were evaluated for fever; 84 (24%) met low-risk criteria and were discharged home. This reduction in admission rate has been maintained throughout the 3 years postimplementation. Successful phone follow-up was achieved in all discharged patients within 24 hours and no adverse events were identified.

Conclusions:
Low-risk febrile patients with SCD can be safely discharged from the ED. An automated notification system within the electronic medical record system can facilitate patient follow-up after ED discharge. Future quality improvement efforts aimed to further reduce admissions in this population should target patients with modifiable risk factors for serious bacterial infection.
Contextualizing library assessment within a broader ecosystem
Authors: Madsen Christine , Hurst Megan 
Published: December 2017

Purpose
The purpose of this paper is to draw a picture of the current landscape of library assessment based on the data gathered in interviews. The authors will focus specifically on the continuum between micro and strategic assessment and share the lessons learned from diverse institutions and geographies about how to build a culture of assessment.

Design/methodology/approach
Between 2015 and 2017, the researchers have interviewed more than 75 library directors and leaders, library assessment practitioners, and academic experts on four continents about library assessment and its current state in their institutions.

Findings
The results reveal a varied landscape, with libraries in widely varying stages of assessment performance and readiness.

Originality/value
This paper presents the results of a large-scale study over more than two years. More than 75 people have been interviewed in five countries. The scale and scope of the work is both significant and unique.
Rehabilitating prisoners: the place of basic life skills programmes
Authors: Jolley Michelle 
Published: December 2017

Purpose
Tackling high reoffending rates in England and Wales is of significant political interest, with education and training being viewed as an important mechanism to achieve change. The purpose of this paper is to present the findings of a small empirical study examining a life skills programme delivered in a Category C prison in the West Midlands.

Design/methodology/approach
The study used a multi-method approach incorporating observations of two modules, four focus groups with prisoners enrolled on the programme, questionnaires with programme completers, and semi-structured interviews with staff.

Findings
The findings indicate that life skills are an important component in rehabilitation. More specifically, developing the necessary tools to assist prisoners in everyday life, such as recognition, interpretation, reflection, response, and planning is fundamental to rehabilitation.

Research limitations/implications
A limitation of this study was that only prisoners currently at this Category C prison were included. This could be complemented by the inclusion of more participants who had completed the programme; however, access and data protection considerations limited the study to one location.

Practical implications
The key message of this study is that without addressing basic life skills, education and vocational rehabilitation is severely limited.

Social implications
To reduce reoffending rates, it is important to conceive rehabilitation in broader terms, not simply in relation to education and vocational training.

Originality/value
This paper offers insight into an unreported area of good practice in prison rehabilitation provision.
Genome Sequencing Links Persistent Outbreak of Legionellosis in Sydney (New South Wales, Australia) to an Emerging Clone of Legionella pneumophila Sequence Type 211
Authors: Timms Verlaine J. , Rockett Rebecca , Bachmann Nathan L. , Martinez Elena , Wang Qinning , Chen Sharon C.-A. , Jeoffreys Neisha , Howard Peter J. , Smith Anna , Adamson Sheena , Gilmour Robin , Sheppeard Vicky , Sintchenko Vitali 
Published: December 2017

ABSTRACT

The city of Sydney, Australia, experienced a persistent outbreak of
Legionella pneumophila
serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and guide public health actions, the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks were examined. A total of 48 isolates from human cases and cooling towers were sequenced and compared using single-nucleotide polymorphism (SNP)-based core-genome multilocus sequencing typing (MLST) and pangenome approaches. All three methods confirmed phylogenetic relatedness between isolates associated with outbreaks in the Central Business District (CBD) in March and May and those in suburb 1. These isolates were designated the “main cluster” and consisted of isolates from two patients from the CBD March outbreak, one patient and one tower isolate from suburb 1, and isolates from two cooling towers and three patients from the CBD May outbreak. All main cluster isolates were sequence type 211 (ST211), which previously has only been reported in Canada. Significantly, pangenome analysis identified mobile genetic elements containing a unique type IV A F-type secretion system (T4ASS), which was specific to the main cluster, and cocirculating clinical strains, suggesting a potential mechanism for increased fitness and persistence of the outbreak clone. Genome sequencing enabled linking of the geographically dispersed environmental sources of infection among the spatially and temporally coinciding cases of legionellosis in a highly populated urban setting. The discovery of a unique T4ASS emphasizes the role of genome recombination in the emergence of successful Lp1 clones.

IMPORTANCE
A new emerging clone has been responsible for a prolonged legionellosis outbreak in Sydney, Australia. The use of whole-genome sequencing linked two outbreaks thought to be unrelated and confirmed the outliers. These findings led to the resampling and subsequent identification of the source, guiding public health actions and bringing the outbreak to a close. Significantly, the outbreak clone was identified as sequence type 211 (ST211). Our study reports this ST in the Southern Hemisphere and presents a description of ST211 genomes from both clinical and environmental isolates. A unique mobile genetic element containing a type IV secretion system was identified in Lp1 ST211 isolates linked to the main cluster and Lp1 ST42 isolates that were cocirculating at the time of the outbreak.
Cohort profile: the Healthy Life in an Urban Setting (HELIUS) study in Amsterdam, The Netherlands
Authors: Snijder Marieke B , Galenkamp Henrike , Prins Maria , Derks Eske M , Peters Ron J G , Zwinderman Aeilko H , Stronks Karien 
Published: December 2017

PurposeEthnic minority groups usually have a more unfavourable disease risk profile than the host population. In Europe, ethnic inequalities in health have been observed in relatively small studies, with limited possibilities to explore underlying causes. The aim of the Healthy Life in an Urban Setting (HELIUS) study is to investigate the causes of (the unequal burden of) diseases across ethnic groups, focusing on three disease categories: cardiovascular diseases, mental health and infectious diseases.ParticipantsThe HELIUS study is a prospective cohort study among six large ethnic groups living in Amsterdam, the Netherlands. Between 2011 and 2015, a total 24 789 participants (aged 18–70 years) were included at baseline. Similar-sized samples of individuals of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan origin were included. Participants filled in an extensive questionnaire and underwent a physical examination that included the collection of biological samples (biobank).Findings to dateData on physical, behavioural, psychosocial and biological risk factors, and also ethnicity-specific characteristics (eg, culture, migration history, ethnic identity, socioeconomic factors and discrimination) were collected, as were measures of health outcomes (cardiovascular, mental health and infections). The first results have confirmed large inequalities in health between ethnic groups, such as diabetes and depressive symptoms, and also early markers of disease such as arterial wave reflection and chronic kidney disease, which can only just partially be explained by inequalities in traditional risk factors, such as obesity and socioeconomic status. In addition, the first results provided important clues for targeting prevention and healthcare.Future plansHELIUS will be used for further research on the underlying causes of ethnic differences in health. Follow-up data will be obtained by repeated measurements and by linkages with existing registries (eg, hospital data, pharmacy data and insurance data).
Feasibility of a hyper-acute stroke unit model of care across England: a modelling analysis
Authors: Allen Michael , Pearn Kerry , Villeneuve Emma , Monks Thomas , Stein Ken , James Martin 
Published: December 2017

ObjectivesThe policy of centralising hyperacute stroke units (HASUs) in England aims to provide stroke care in units that are both large enough to sustain expertise (>600 admissions/year) and dispersed enough to rapidly deliver time-critical treatments (<30 min maximum travel time). Currently, just over half (56%) of patients with stroke access care in such a unit. We sought to model national configurations of HASUs that would optimise both institutional size and geographical access to stroke care, to maximise the population benefit from the centralisation of stroke care.DesignModelling of the effect of the national reconfiguration of stroke services. Optimal solutions were identified using a heuristic genetic algorithm.Setting127 acute stroke services in England, serving a population of 54 million people.Participants238 887 emergency admissions with acute stroke over a 3-year period (2013–2015).InterventionModelled reconfigurations of HASUs optimised for institutional size and geographical access.Main outcome measureTravel distances and times to HASUs, proportion of patients attending a HASU with at least 600 admissions per year, and minimum and maximum HASU admissions.ResultsSolutions were identified with 75–85 HASUs with annual stroke admissions in the range of 600–2000, which achieve up to 82% of patients attending a stroke unit within 30 min estimated travel time (with at least 95% and 98% of the patients being within 45 and 60 min travel time, respectively).ConclusionsThe reconfiguration of hyperacute stroke services in England could lead to all patients being treated in a HASU with between 600 and 2000 admissions per year. However, the proportion of patients within 30 min of a HASU would fall from over 90% to 80%–82%.
Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis
Authors: Leber Werner , Beresford Lee , Nightingale Claire , Barbosa Estela Capelas , Morris Stephen , El-Shogri Farah , McMullen Heather , Boomla Kambiz , Delpech Valerie , Brown Alison , Hutchinson Jane , Apea Vanessa , Symonds Merle , Gilliham Samantha , Creighton Sarah , Shahmanesh Maryam , Fulop Naomi , Estcourt Claudia , Anderson Jane , Figueroa Jose , Griffiths Chris 
Published: December 2017

IntroductionHIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets).Methods and analysisService evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses.Ethics and disseminationThe chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners.