bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Multidisciplinary Care Coordination Program for Frequent Users of the Emergency Department
Authors: Flowers Angela , Shade Kate 
Published: August 2019

Purpose of Study:
The purpose of this study was to evaluate the impact of a quality improvement multidisciplinary care coordination program designed to reduce frequent emergency department (ED) utilization and hospital admissions.

Primary Practice Setting:
The single hospital ED is part of a large, integrated, managed care delivery system in Northern California serving the city of Oakland, California.

Methodology and Sample:
A retrospective cohort study design was used to analyze a multidisciplinary care coordination program on 58 patients during January 2015 and August 2018. Patients were identified from a high-utilization report when they had 10 or more ED visits in a 6-month period, were 18 years of age or older, and members of the integrated delivery system's health plan. Data were collected at initiation and 6 months postintervention. The pre-/postanalysis consisted of descriptive statistics, Wilcoxon signed ranks test, and binary logistic regression.

Results:
There was a statistically significant pre-/postdifference of 7.7 ED visits (95% confidence interval [CI] = 4.44–10.97, p < .001). The program did not result in statistically significant reduced hospital admissions (95% CI =−1.24 to 1.45, p = .875). Prior frequent use, number of pre-ED visits, age, sex, complex medical history, and mental health disorder had a significant effect on frequent ED use (χ2[6] =17.62, p = .007, McFadden R
2 = .32]. Sex (odds ratio [OR] = 5.13, p = .070), prior frequent use (OR = 2.87, p = .252), and complex medical history (OR = 2.52, p = .412) had the greatest odds of ongoing frequent ED use.

Implications for Case Management Practice:
We demonstrated reductions in ED use among frequent users with a low-cost care management intervention. Our multidisciplinary care coordination program confirms the positive impact case management has on utilization and health outcomes. We established that a care coordination program can optimize the overall quality of care and control hospital costs incurred by this vulnerable population. The effectiveness of this program contributes to the advancement of case management efforts in undertaking the challenging health care issue of reducing repeated visits by frequent users, a practice that strains emergency medical services.
Delayed Admissions to the Pediatric Intensive Care Unit
Authors: Czolgosz Thomas , Cashen Katherine , Farooqi Ahmad , Kannikeswaran Nirupama 
Published: August 2019

Objectives
Few studies have evaluated impact of emergency department (ED) management on delayed transfers to the pediatric intensive care unit (PICU). Our study objectives were to describe patient characteristics of PICU transfers less than or equal to 12 hours of admission and determine the reason for transfer.

Methods
We conducted a retrospective chart review of patients transferred to PICU less than or equal to 12 hours of admission. We extracted patient demographics, emergency severity index category, ED, floor and PICU length of stay (LOS), and PICU “significant” interventions. Charts were reviewed independently by the study principal investigator and a PICU attending who classified transfers as secondary to progression of disease or error in ED management. Furthermore, errors were classified as diagnostic, management, or disposition errors.

Results
A total of 164 patients met inclusion criteria. Most were male (86/164, 52.4%), with emergency severity index category 2 (116/164, 70.7%) and respiratory diagnosis (98/164, 59.8%). Most transfers (136/164, 82.9%) resulted from progression of illness. No significant interventions were performed in 48.8% (80/164) of patients. Of 164 transfers, 28 (17.1%) resulted from ED error, and half of these were management errors. Compared with disease progression, the ED error group had a significantly shorter median floor LOS {3.45 [interquartile range (IQR): 2.15, 7.56] vs 6.58 (IQR: 3.70, 9.20); P = 0.005}, more PICU interventions [1.5 (IQR: 0, 4) vs 0 (IQR: 0, 2); P = 0.006], and longer PICU LOS [2.50 (IQR: 1.09, 4.25) vs 1.36 (IQR: 0.80, 2.50); P = 0.013].

Conclusions
Most PICU transfers less than or equal to 12 hours after admission result from illness progression. Half of these do not require significant interventions. The PICU transfers after ED management error had significantly shorter floor LOS, longer PICU LOS, and more interventions.
Management of Pediatric Condyle Fractures
Authors: McGoldrick David M. , Parmar Paras , Williams Rhodri , Monaghan Andrew , McMillan Kevin 
Published: August 2019

Introduction:
Mandibular condyle fractures are a common type of facial fracture in children. The authors aimed to examine the demographics, etiology, treatment, and outcomes of these fractures managed in a single pediatric trauma unit.

Materials and Methods:
A retrospective review was performed of patients presenting to a pediatric hospital between 2003 and 2016 with mandibular condyle fractures. Initial data was extracted from a dedicated trauma database. Included patient's medical records and imaging were then reviewed. Data on demographics, etiology, fracture type, and treatment were recorded. Univariate statistical analysis was performed.

Results:
Forty-four patients with 49 condyle fractures were included. The average age of patients was 11.4 years (range 3–15 years). A fall from a bicycle/scooter was the most common mechanism. Twenty-six fractures were isolated and 23 involved a further fracture of the mandibular arch. The condylar neck was the most common site of fracture (55%). There was no statistical significance between age (0–10 years, 10–16 years) and site of fracture or the presence of an associated arch fracture. The majority of isolated fractures (73%) were treated conservatively without inter-maxillary fixation. Thirty-nine patients attended the follow-up and the median follow-up period was 196 days (interquartile range 21–165 days). Two patients had a malocclusion at follow-up that required intervention.

Conclusion:
There was a broad range of presentations in our cohort. Conservative management in isolated fractures resulted in stable outcomes and this large case series supports the consensus that management of pediatric condyle fractures should be as conservative as possible.
Unexpected Total Zygomatic Arch Bone Resorption Induced by Reduction Malarplasty
Authors: Zhou Jing , Zheng Houbing , Qi Zuoliang , Jin Xiaolei 
Published: August 2019

Abstract
In this report, the authors introduce a rare complication after reduction malarplasty in 2 patients. One patient underwent temporal rhytidectomy and malar osteotomy. The other patient underwent zygoma grinding without osteotomy. Both patients presented malar depression and cheek ptosis after surgery and visited the clinic. Physical examination, cephalometric radiographs, and facial 3-dimensional computed tomography were conducted, which indicated total zygomatic arch bone resorption. After examining the possible causes of the complication, the authors concluded that preserving enough blood supply and performing adequate rigid fixation of the separated zygoma bone are key prevention for bone resorption. This is the first report of total zygomatic arch bone resorption after reduction malarplasty.
The development of competency frameworks in healthcare professions: a scoping review
Authors: Batt Alan M. , Tavares Walter , Williams Brett 
Published: August 2019

BackgroundCompetency frameworks serve various roles including outlining characteristics of a competent workforce, facilitating mobility, and analysing or assessing expertise. Given these roles and their relevance in the health professions, we sought to understand the methods and strategies used in the development of existing competency frameworks.MethodsWe applied the Arksey and O’Malley framework to undertake this scoping review. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, and ERIC) and three grey literature sources (greylit.org, Trove and Google Scholar) using keywords related to competency frameworks. We screened studies for inclusion by title and abstract, and we included studies of any type that described the development of a competency framework in a healthcare profession. Two reviewers independently extracted data including study characteristics. Data synthesis was both quantitative and qualitative.ResultsAmong 5,710 citations, we selected 190 for analysis. The majority of studies were conducted in medicine and nursing professions. Literature reviews and group techniques were conducted in 116 studies each (61%), and 85 (45%) outlined some form of stakeholder deliberation. We observed a significant degree of diversity in methodological strategies, inconsistent adherence to existing guidance on the selection of methods, who was involved, and based on the variation we observed in timeframes, combination, function, application and reporting of methods and strategies, there is no apparent gold standard or standardised approach to competency framework development.ConclusionsWe observed significant variation within the conduct and reporting of the competency framework development process. While some variation can be expected given the differences across and within professions, our results suggest there is some difficulty in determining whether methods were fit-for-purpose, and therefore in making determinations regarding the appropriateness of the development process. This uncertainty may unwillingly create and legitimise uncertain or artificial outcomes. There is a need for improved guidance in the process for developing and reporting competency frameworks.
An integrated analysis of myeloid cells identifies gaps in in vitro models of in vivo biology
Authors: Rajab Nadia , Angel Paul W , Deng Yidi , Gu Jennifer , Jameson Vanta , Kurowska-Stolarska Mariola , Milling Simon , Pacheco Chris M , Rutar Matt , Laslett Andrew L , Lê Cao Kim Anh , Choi Jarny , Wells Christine A 
Published: August 2019

SummaryThe Stemformatics myeloid atlas is an integrated transcriptome atlas of human macrophages and dendritic cells that systematically compares freshly isolated tissue-resident, cultured, and stem-cell derived myeloid cell types. We identified two broad classes of tissue-resident macrophages with lung, gut and tumour-associated macrophages most similar to monocytes. Microglia, Kupffer cells and synovial macrophages shared similar profiles with each other, and with cultured macrophages. Pluripotent stem cell-derived macrophages were not reminiscent of fetal-derived cells. Instead, they were characterized by atypical expression of collagen and a highly efferocytotic phenotype. Likewise, Flt3L-derived cord blood dendritic cells were distinct from conventional dendritic cell subsets isolated from primary tissues and lacked expression of key pattern recognition receptors. Myeloid subsets were reproducible across different experimental series, showing the resource is a robust reference for new data. External users can annotate and benchmark their own samples, including annotation of myeloid single cell data at www.stemformatics.org/atlas/myeloid/.
JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis
Authors: Zhou Jun , Boutros Michael 
Published: August 2019

ABSTRACTIn all animals, the intestinal epithelium forms a tight barrier to the environment. The epithelium regulates the absorption of nutrients, mounts immune responses and prevents systemic infections. Here, we investigate the consequences of tumorigenesis on the microbiome using a Drosophila intestinal tumor model. We show that upon loss-of BMP signaling, tumors lead to aberrant activation of JNK signaling, followed by intestinal barrier dysfunction and commensal imbalance. In turn, the dysbiotic microbiome triggers a regenerative response and stimulates tumor growth. We find that inhibiting JNK signaling or depletion of the microbiome restores barrier function of the intestinal epithelium, leading to a reestablishment of host-microbe homeostasis, and organismic lifespan extension. Our experiments identify a JNK-dependent feedback amplification loop between intestinal tumors and the microbiome. They also highlight the importance of controlling the activity level of JNK signaling to maintain epithelial barrier function and host-microbe homeostasis.
TALE and NF-Y co-occupancy marks enhancers of developmental control genes during zygotic genome activation in zebrafish
Authors: Stanney William , Ladam Franck , Donaldson Ian J. , Parsons Teagan J. , Maehr René , Bobola Nicoletta , Sagerström Charles G 
Published: August 2019

SUMMARYAnimal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts control to the embryo at early blastula stages. ZGA is thought to be mediated by specialized maternally deposited transcription factors (TFs), but here we demonstrate that NF-Y and TALE – TFs with known later roles in embryogenesis – co-occupy unique genomic elements at zebrafish ZGA. We show that these elements are selectively associated with early-expressed genes involved in transcriptional regulation and possess enhancer activity in vivo. In contrast, we find that elements individually occupied by either NF-Y or TALE are associated with genes acting later in development – such that NF-Y controls a cilia gene expression program while TALE TFs control expression ofhoxgenes. We conclude that NF-Y and TALE have a shared role at ZGA, but separate roles later during development, demonstrating that combinations of known TFs can regulate subsets of key developmental genes at vertebrate ZGA.
Perinatal Inflammation Influences but Does Not Arrest Rapid Immune Development in Preterm Babies
Authors: Kamdar S. , Hutchinson R. , Laing A. , Stacey F. , Ansbro K. , Millar M.R. , Costeloe K. , Wade W.G. , Fleming P. , Gibbons D. L. 
Published: August 2019

AbstractInfection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this, there is limited understanding of the development of the immune system in those born prematurely and how it is influenced by perinatal factors. To investigate this, we prospectively and longitudinally followed a cohort of babies born before 32 weeks of gestation. We demonstrated that preterm babies, including those born extremely prematurely, were capable of rapidly acquiring adult levels of immune functionality; that immune maturation appeared to occur independently of the developing microbiome, which was highly heterogeneous across different infants; and that the biggest drivers of change in the trajectory of perinatal immune development was exposure to infection in utero or post-natally. Conspicuously, a unifying factor among infants who developed infection despite their growing immune potentials was an inability to mount adequate T cell CXCL8 responses. Because this defect was present at birth, it may predict those babies likely to have poor clinical outcomes.
A new twist on bacterial motility – two distinct type IV pili revealed by cryoEM
Authors: Neuhaus Alexander , Selvaraj Muniyandi , Salzer Ralf , Langer Julian D. , Kruse Kerstin , Sanders Kelly , Daum Bertram , Averhoff Beate , Gold Vicki A. M. 
Published: August 2019

SummaryMany bacteria express flexible protein filaments on their surface that enable a variety of important cellular functions. Type IV pili are examples of such filaments and are comprised of a helical assembly of repeating pilin subunits. Type IV pili are involved in motility (twitching), surface adhesion, biofilm formation and DNA uptake (natural transformation). They are therefore powerful structures that enable bacterial proliferation and genetic adaptation, potentially leading to the development of pathogenicity and antibiotic resistance. They are also targets for drug development.By a complement of experimental approaches, we show that the bacteriumThermus thermophilusproduces two different forms of type IV pilus. We have determined the structures of both and built atomic models. The structures answer key unresolved questions regarding the molecular architecture of type IV pili and identify a new type of pilin. We also delineate the roles of the two filaments in promoting twitching and natural transformation.
Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks
Authors: Exelby Katherine , Herrera-Delgado Edgar , Perez Lorena Garcia , Perez-Carrasco Ruben , Sagner Andreas , Metzis Vicki , Sollich Peter , Briscoe James 
Published: August 2019

AbstractDuring development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.
scribble abrogation induces tumor growth through JNK-Wnt pathways depending on cellular-microenvironment in Drosophila wing imaginal tissue
Authors: Yadav Amarish Kumar , Fatima Roshan , Srikrishna Saripella 
Published: August 2019

Abstractscribble (scrib) is a cell-polarity determinant in Drosophila and human. Cell polarity plays a crucial role in the maintenance of tissue homeostasis and its disruption leads to neoplastic cancer progression. However, the underlying mechanisms by which loss of cell-polarity regulators drives cancer progression are poorly known. In this study, we have explored the tumor progression mechanisms upon scrib knockdown in Drosophila wing imaginal disc using UASRNAi-GAL4 approach. We have found that scrib knockdown in wing disc leads to tumor growth with disrupted actin cytoskeleton, loss of cell-polarity and elevated JNK signalling, resulting in absolute early pupal lethality. Further, scrib abrogated cells in a large area of the disc are capable of invading the surrounding wild type cells and inducing apoptosis along with compensatory proliferation through JNK-Wnt pathways. Moreover, JNK pathway upstream candidate hep (JNKK) knockdown in scrib abrogated cells rescues the cell polarity defects, actin cytoskeleton disruption and tumor growth, while constitutive hep activation further aggravates the tumor phenotype. Interestingly, generation of undead cells by apoptosis inhibition in these hep knockdown cells by p35 expression further leads to tumor development. Hence, we conclude that scrib knockdown in a large area of wing disc might have a ‘group-protection’ and ‘undead-cells’ microenvironment that modulates the action of JNK signalling resulting in tumor formation. Furthermore, JNK dependent activation of Wnt/Ca2+ signalling also supports the tumor growth and actin cytoskeleton disruption. Thus, our results importantly highlight the role of JNK signalling in tumor progression upon scrib loss of function depending on cellular-microenvironment.
Regenerative neurogenic response from glia requires insulin driven neuron-glia communication
Authors: Harrison Neale , Connolly Elizabeth , Gubieda Alicia Gascón , Yang Zidan , Altenhein Benjamin , Losada-Perez Maria , Moreira Marta , Hidalgo Alicia 
Published: August 2019

ABSTRACTSome animals can regenerate their central nervous system (CNS) after injury by inducing de novo neurogenesis: discovering the underlying mechanisms would help promote regeneration in the damaged human CNS. Glial cells could be the source of regenerative neurogenesis, but this is debated. The glia transmembrane protein Neuron-Glia antigen-2 (NG2) may have a key role in sensing injury-induced neuronal signals, however these have not been identified. Here, we used Drosophila genetics to search for functional neuronal partners of the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Alterations in Ia-2 function induced neural stem cell fate, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic epistasis analysis and lineage tracing, we demonstrate that Ia-2 functions with Kon to regulate Drosophila insulin-like peptide 6 (Dilp-6) which in turn generates both more glial cells and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia, and reprograms glia into neural stem cells for CNS regeneration.
Co-translational folding allows misfolding-prone proteins to circumvent deep kinetic traps
Authors: Bitran Amir , Jacobs William M. , Zhai Xiadi , Shakhnovich Eugene 
Published: August 2019

Many large proteins suffer from slow or inefficient foldingin vitro. Here, we provide evidence that this problem can be alleviatedin vivoif proteins start folding co-translationally. Using an all-atom simulation-based algorithm, we compute the folding properties of various large protein domains as a function of nascent chain length, and find that for certain proteins, there exists a narrow window of lengths that confers both thermodynamic stability and fast folding kinetics. Beyond these lengths, folding is drastically slowed by non-native interactions involving C-terminal residues. Thus, co-translational folding is predicted to be beneficial because it allows proteins to take advantage of this optimal window of lengths and thus avoid kinetic traps. Interestingly, many of these proteins’ sequences contain conserved rare codons that may slow down synthesis at this optimal window, suggesting that synthesis rates may be evolutionarily tuned to optimize folding. Using kinetic modelling, we show that under certain conditions, such a slowdown indeed improves co-translational folding efficiency by giving these nascent chains more time to fold. In contrast, other proteins are predicted not to benefit from co-translational folding due to a lack of significant non-native interactions, and indeed these proteins’ sequences lack conserved C-terminal rare codons. Together, these results shed light on the factors that promote proper protein folding in the cell, and how biomolecular self-assembly may be optimized evolutionarily.Significance StatementMany proteins must adopt a specific structure in order to perform their functions, and failure to do so has been linked to disease. Although small proteins often fold rapidly and spontaneously to their native conformations, larger proteins are less likely to fold correctly due to the myriad incorrect arrangements they can adopt. Here, we show that this problem can be alleviated if proteins start folding while they are being translated, namely, built one amino acid at a time on the ribosome. This process of co-translational folding biases certain proteins away from misfolded states that tend to hinder spontaneous refolding. Signatures of unusually slow translation suggest that some of these proteins have evolved to fold co-translationally.