bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Energy, Lateral Ankle Injuries in Pediatric and Adolescent Patients: A Systematic Review of Ankle Sprains and Nondisplaced Distal Fibula Fractures
Authors: Beck Jennifer J. , VandenBerg Curtis , Cruz Aristides I. , Ellis Henry B. 
Published: August 2019

Background:
Lateral ankle injuries are one of the most common musculoskeletal injuries sustained by pediatric and adolescent athletes. These injuries can result in significant time lost from competition, affect performance when returning to play, and represent a significant burden on the health care system as a whole. The purpose of this study was to systematically review the literature on the diagnosis, treatment, and prevention of acute lateral ankle injuries and their chronic effects in pediatric and adolescent athletes (younger than 19 y).

Methods:
This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines between September and December 2018. PubMed and Google Scholar were systematically searched using the search terms: (“distal fibula fracture” OR “ankle sprain”) AND (“youth” OR “pediatric” OR “adolescent”). All authors participated in article review (N=172) for relevance and age restrictions in which 30 met the inclusion criteria.

Results:
Thirty articles met inclusion criteria [Levels of Evidence I to IV (I: n=4, II: n=16, III: n=9, and IV: n=1)] including distal fibula fracture diagnosis and treatment, and risk factors, prevention, and chronic sequela of lateral ankle injuries in pediatric and adolescent patients.

Conclusions:
Low-energy, lateral ankle injuries are common in pediatric and adolescent patients, yet underrepresented in the medical literature. There is a lack of high-quality literature on diagnosis, treatment, and outcomes after Salter-Harris I distal fibula fractures. Available literature, however, suggests that there remains over diagnosis and over treatment of presumed Salter-Harris I distal fibula fractures. Adolescent ankle sprains dominate the available literature likely due to the high recurrence rate. Youth athletes and coaches should address risk factors and engage in injury prevention programs to prevent and minimize the effect of acute lateral ankle injuries.

Levels of Evidence:
Level III—Systematic review.
Nurse Practitioners and Physician Assistants in Acute and Critical Care: A Concise Review of the Literature and Data 2008–2018
Authors: Kleinpell Ruth M. , Grabenkort W. Robert , Kapu April N. , Constantine Roy , Sicoutris Corinna 
Published: August 2019

Objectives:
To provide a concise review of the literature and data pertaining to the use of nurse practitioners and physician assistants, collectively called advanced practice providers, in ICU and acute care settings.

Data Sources:
Detailed search strategy using the databases PubMed, Ovid MEDLINE, and the Cumulative Index of Nursing and Allied Health Literature for the time period from January 2008 to December 2018.

Study Selection:
Studies addressing nurse practitioner, physician assistant, or advanced practice provider care in the ICU or acute care setting.

Data Extraction:
Relevant studies were reviewed, and the following aspects of each study were identified, abstracted, and analyzed: study population, study design, study aims, methods, results, and relevant implications for critical care practice.

Data Synthesis:
Five systematic reviews, four literature reviews, and 44 individual studies were identified, reviewed, and critiqued. Of the research studies, the majority were retrospective with others being observational, quasi-experimental, or quality improvement, along with two randomized control trials. Overall, the studies assessed a variety of effects of advanced practice provider care, including on length of stay, mortality, and quality-related metrics, with a majority demonstrating similar or improved patient care outcomes.

Conclusions:
Over the past 10 years, the number of studies assessing the impact of advanced practice providers in acute and critical care settings continue to increase. Collectively, these studies identify the value of advanced practice providers in patient care management, continuity of care, improved quality and safety metrics, patient and staff satisfaction, and on new areas of focus including enhanced educational experience of residents and fellows.
Keeping Time: Implementing Appointment-based Family-centered Rounds
Authors: Bekmezian Arpi , Fiore Darren M. , Long Michele , Monash Bradley J. , Padrez Ryan , Rosenbluth Glenn , Sun Karen I. 
Published: August 2019

Background:
Family-centered rounds (FCRs) provide many benefits over traditional rounds, including higher patient satisfaction, and shared mental models among staff. These benefits can only be achieved when key members of the care team are present and engaged. We aimed to improve patient engagement and satisfaction with our existing bedside rounds by designing a new FCR process.

Methods:
We conducted a needs assessment and formed a multidisciplinary FCR committee that identified appointment-based family-centered rounds (aFCRs) as a primary intervention. We designed, implemented, and iteratively refined an aFCR process. We tracked process metrics (rounds attendance by key participants), a balancing metric (time per patient), and outcome metrics (patient satisfaction domains) during the intervention and follow-up periods.

Results:
After implementing aFCR, 65% of patients reported positive experience with rounds and communication. Rounds duration per patient was similar (9 versus 9.4 min). Nurse, subspecialist, and interpreter attendance on rounds was 72%, 60%, and 90%, respectively. We employed a Rounding Coordinator to complete the scheduling and communication required for successful aFCR.

Discussion:
We successfully improved our rounding processes through the introduction of aFCR with the addition of a rounding coordinator. Our experience demonstrates one method to increase multidisciplinary team member attendance on rounds and patient satisfaction with physician communication in the inpatient setting.
Don't Have a Doubt, Get the Catheter Out: A Nurse-Driven CAUTI Prevention Protocol
Authors: Schiessler Melissa M. , Darwin Lisa M. , Phipps Amber R. , Hegemann Lindsay R. , Heybrock Brenda S. , Macfadyen Andrew J. 
Published: August 2019

Background:
Despite the use of sterile technique for indwelling urinary catheter insertion, as well as use of the defined catheter-associated urinary tract infection (CAUTI) bundle elements per Children’s Hospitals’ Solutions for Patient Safety, the CAUTI rate in the pediatric intensive care unit (PICU) at a free-standing pediatric hospital was increasing. In 2017, the PICU accounted for 87% of the organization’s CAUTIs and 65% of the total indwelling catheter device days. With an important risk factor for CAUTIs being the duration of catheterization, the indication for catheters became an organizational executive priority.

Methods:
An early 2017 review of the bundle elements identified that the indication for catheterization was not consistently addressed in daily patient rounds. A multidisciplinary project team applying the Plan, Do, Check, Act methodology developed an evidenced-based, nurse-driven indwelling urinary catheter removal protocol. This protocol allows nursing autonomy when removing a catheter by providing clinical indications for catheter use and promoting prompt removal when no longer indicated.

Results:
Indwelling urinary catheter device days in the PICU decreased by 28% within 6 months of protocol implementation. The PICU CAUTI rate declined from 4.8 (per 1,000 device days) in 2017 to 0.8 in 2018, 1 year after protocol implementation.

Conclusions:
Providing the bedside nurse with an evidence-based protocol that is driven by specific patient indications and diagnoses allows them to practice autonomously in catheter removal. Prompt removal of indwelling urinary catheters results in decreased device days and decreased incidence of CAUTIs.
Disclosure of Adverse Events: A Guide for Clinicians
Authors: Peterson Kimberly A. , Rutherford Mary , Drvol Denise , Barkman Darlene , Phipps Amber R. , Hales Roberta , Dawson Aaron , Stevens Laurie , Teman Susan , Teets Jeanette 
Published: August 2019

Introduction:
Children’s Hospitals’ Solutions for Patient Safety (SPS) acknowledged a recommendation from the American Academy of Pediatrics to develop education programs on the communication of adverse events with patients and families. SPS set out to create a guide that would outline a standardized disclosure process and provide a training curriculum and tools so that providers would feel better prepared to have effective disclosure conversations.

Methods:
SPS disclosure work began with the development of a project team made up of 9 network hospitals. The team utilized key driver diagrams and process maps to show the relationship between the project aims, key drivers, and specific interventions. The team developed a training curriculum, guide, and tools for each area of improvement. To ensure these were effective, they were tested using case studies and plan-do-study-act cycles.

Results:
One of the cohort hospitals piloted the curriculum and tools, training 48 physicians, nurses, executives, and other allied health professionals. Pretest to posttest scores improved from an average of 82.7% to 90.2%. Survey feedback was favorable with 100% of respondents noting that they strongly agree or agree that attending this educational activity increased or improved their competency, performance, and patient outcomes.

Conclusions:
Initial testing suggests that the developed curriculum is empowering for frontline clinicians. Materials are available in an electronic format on the SPS external website. As member hospitals implement these materials, they will be evaluating learner satisfaction and provider usage. SPS will seek out feedback from these hospitals to further develop the materials and support clinicians.
Tacrolimus Intrapatient Variability, Time in Therapeutic Range, and Risk of De Novo Donor–Specific Antibodies
Authors: Davis Scott , Gralla Jane , Klem Patrick , Stites Erik , Wiseman Alexander , Cooper James E. 
Published: August 2019

Background.
Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor–specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself.

Methods.
We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non–dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years.

Results.
Patients with CV >44.2% and TTR <40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P < 0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV >44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV <44.2% (lower intrapatient variability).

Conclusions.
These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non–dose-corrected TAC levels irrespective of reason or indication.
The TOMATO Study (Tacrolimus Metabolization in Kidney Transplantation): Impact of the Concentration–Dose Ratio on Death-censored Graft Survival
Authors: Jouve Thomas , Fonrose Xavier , Noble Johan , Janbon Benedicte , Fiard Gaelle , Malvezzi Paolo , Stanke-Labesque Françoise , Rostaing Lionel 
Published: August 2019

Background.
Tacrolimus trough concentrations (mean/variability), as well as concentration-to-dose ratio (C/D ratio), affect kidney allograft outcomes. We investigated the link between the C/D ratio and death-censored kidney graft survival (DCGS).

Methods.
We performed a retrospective study on 1029 kidney transplant patients (2004–2016) with the following criteria: tacrolimus-based immunosuppression, >1-year graft survival, no initial use of everolimus, and available anti–human leukocyte antigen antibody data. We analyzed the impact of the time-varying C/D ratio on DCGS. Fast metabolizers were defined by a C/D ratio < 1.05. We also investigated the effect of an early (mo 3 to mo 6 post transplantation) C/D ratio below 1.05. Cox survival analyses were performed, adjusting for potential confounders (tacrolimus trough, variability of tacrolimus trough, de novo donor-specific antibody development, cytochrome P450 3A5 genotype, pregraft sensitization, mo 3 glomerular filtration rate).

Results.
Time-varying C/D ratio was significantly associated with DCGS (hazard ratio [HR], 2.35; P < 0.001) in a univariate model, on the full analysis set comprising 1029 patients. In the multivariate time-varying model, based on 666 patients with available cytochrome P450 3A5 genotypes, the effect of the C/D ratio remained significant (HR, 2.26; P = 0.015); even when glomerular filtration rate at month 3 < 30 mL/min/1.73 m2 (HR, 2.61; P = 0.011), de novo donor-specific antibody development (HR, 4.09; P < 0.001) and continued steroid prescription (HR=2.08, P = 0.014) were taken into account (other covariates, including tacrolimus trough concentrations, were nonsignificant). In the same multivariate model, the effect of early C/D ratio (median at mo 3 and mo 6) remained significantly associated with DCGS (HR, 2.25; P = 0.041).

Conclusions.
C/D ratio is an independent and early predictor of DCGS. Identification of fast metabolizers could be a strategy to improve graft survival, for example, by optimizing tacrolimus formulation. Mechanistic studies to understand the C/D ratio effect are required.
IgEvolution: clonal analysis of antibody repertoires
Authors: Safonova Yana , Pevzner Pavel A. 
Published: August 2019

AbstractConstructing antibody repertoires is an important error-correcting step in analyzing immunosequencing datasets that is important for reconstructing evolutionary (clonal) development of antibodies. However, the state-of-the-art repertoire construction tools typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction. Thus, although repertoire construction is a prerequisite for follow up clonal tree reconstruction, the existing repertoire reconstruction algorithms are not well suited for this task. Since clonal analysis has the potential to reveal errors in the constructed repertoires and contribute to constructing more accurate repertoires, we advocate a tree-guided construction of antibody repertoires that combines error correction and clonal reconstruction as interconnected (rather than independent) tasks. We developed the IgEvolution algorithm for simultaneous repertoire and clonal tree reconstruction and applied it for analyzing multiple immunosequencing datasets representing antigen-specific immune responses. We demonstrate that analysis of clonal trees reveals highly mutable positions that correlate with antigen-binding sites and light-chain contacts in crystallized antibody-antigen complexes. We further demonstrate that this analysis leads to a new approach for identifying complementarity determining regions (CDRs) in antibodies.
A report on the detection and management of a finding of PSTVd (Potato Spindle Tuber Viroid) in potato breeding material in Northern Ireland, UK
Authors: O’Hanlon Richard , Watts Paul , Martin Rodney , Young Gillian , Fleming Colin 
Published: August 2019

AbstractPotato Spindle Tuber Viroid (PSTVd) is an infectious unencapsidated, small, circular, single-stranded RNA, that causes serious losses in infected potato plants. The pathogen has been detected in several European countries, including in England in the UK. In August 2016, the National Plant Protection Organisation of the Netherlands reported a finding of PSTVd in breeding material that originated in Northern Ireland, UK. A scheme of testing was carried out in Northern Ireland to identify the source of the infected breeding material. Trace-forward and trace-back tests identified 21 infected samples, of which 16 were from true seed samples, out of a total of 591 tested up to November 2016. The number of positive findings in true seed was further reduced to 4 after the samples were surface sterilized. Tests indicated that the infection probably entered the breeding station in Northern Ireland in the mid 1980’s, with limited spread in the collection via contaminated breeding equipment. The instance of spread in the field could not be ruled out. Eradication efforts included removal and destruction of infected field stocks and neighbouring stocks, destruction of stored museum material by deep burial, and destruction of other field material by ploughing and exposing tubers to frost. The risk of potato genitor material for spreading PSTVd is discussed. The situation of PSTVd in Northern Ireland, UK is Transient, actionable, under eradication.
Identifying and removing haplotypic duplication in primary genome assemblies
Authors: Guan Dengfeng , McCarthy Shane A. , Wood Jonathan , Howe Kerstin , Wang Yadong , Durbin Richard 
Published: August 2019

AbstractMotivationRapid development in long read sequencing and scaffolding technologies is accelerating the production of reference-quality assemblies for large eukaryotic genomes. However, haplotype divergence in regions of high heterozygosity often results in assemblers creating two copies rather than one copy of a region, leading to breaks in contiguity and compromising downstream steps such as gene annotation. Several tools have been developed to resolve this problem. However, they either only focus on removing contained duplicate regions, also known as haplotigs, or fail to use all the relevant information and hence make errors.ResultsHere we present a novel tool “purge_dups” that uses sequence similarity and read depth to automatically identify and remove both haplotigs and heterozygous overlaps. In comparison with the current standard, purge_haplotigs, we demonstrate that purge_dups can reduce heterozygous duplication and increase assembly continuity while maintaining completeness of the primary assembly. Moreover, purge_dups is fully automatic and can be easy integrated into assembly pipelines.AvailabilityThe source code is written in C and is available at https://github.com/dfguan/purge_dups.Contactydwang@hit.edu.cn, rd109@cam.ac.uk
Properties of decision-making tasks govern the tradeoff between model-based and model-free learning
Authors: Abzug Zachary M , Sommer Marc A , Beck Jeffrey M 
Published: August 2019

AbstractWhen decisions must be made between uncertain options, optimal behavior depends on accurate estimations of the likelihoods of different outcomes. The contextual factors that govern whether these estimations depend on model-free learning (tracking outcomes) vs. model-based learning (learning generative stimulus distributions) are poorly understood. We studied model-free and model-based learning using serial decision-making tasks in which subjects selected a rule and then used it to flexibly act on visual stimuli. A factorial approach defined a family of behavioral models that could integrate model-free and model-based strategies to predict rule selection trial-by-trial. Bayesian model selection demonstrated that the subjects strategies varied depending on lower-level task characteristics such as the identities of the rule options. In certain conditions, subjects integrated learned stimulus distributions and tracked reward rates to guide their behavior. The results thus identify tradeoffs between model-based and model-free decision strategies, and in some cases parallel utilization, depending on task context.
Rough substrates constrain walking speed in ants through modulation of stride frequency and not stride length
Authors: Clifton G.T. , Holway D. , Gravish N. 
Published: August 2019

AbstractNatural terrain is rarely flat. Substrate irregularities challenge walking animals to maintain stability, yet we lack quantitative assessments of walking performance and limb kinematics on naturally rough ground. We measured how continually rough 3D-printed substrates influence walking performance of Argentine ants by measuring walking speeds of workers from lab colonies and by testing colony-wide substrate preference in field experiments. Tracking limb motion in over 8,000 videos, we used statistical models that associate walking speed with limb kinematic parameters to compare movement over flat versus rough ground. We found that rough substrates reduced preferred and peak walking speeds by up to 42% and that ants actively avoided rough terrain in the field. Observed speed reductions were modulated primarily by shifts in stride frequency and not stride length, a pattern consistent across flat and rough substrates. Modeling revealed that walking speeds on rough substrates were accurately predicted based on flat walking data for over 89% of strides. Those strides that were not well modeled primarily involved limb perturbations, including missteps, active foot repositioning, and slipping. Together these findings relate kinematic mechanisms underlying walking performance on rough terrain to ecologically-relevant measures under field conditions.
Th22 cells are a major contributor to the mycobacterial CD4+ T cell response and are depleted during HIV infection
Authors: Bunjun Rubina , Omondi Fidilia M.A. , Makatsa Mohau S. , Müller Tracey L. , Prentice Caryn S.L. , Wilkinson Robert J. , Riou Catherine , Burgers Wendy A. 
Published: August 2019

ABSTRACTHIV-1 infection substantially increases the risk of developing tuberculosis (TB). Some mechanisms, such as defects in the Th1 response to Mycobacterium tuberculosis (M.tb) in HIV-infected individuals have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17 and IL-22 production in response to mycobacterial antigens in individuals with latent TB infection (LTBI) and HIV co-infection. Upon stimulating with mycobacterial antigens, we observed a distinct CD4+ T helper lineage producing IL-22 in the absence of IL-17 and IFN-γ. Th22 cells were present at high frequencies in response to mycobacterial antigens in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-γ Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M.tb-specific Th1 cells (i.e. predominantly early-differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, while their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were three-fold lower in HIV-infected individuals compared to uninfected individuals, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific T helper subsets and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity.