bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain Assessment in Pediatric Emergency Departments
Authors: Haupt Joshua , Shah Nipam , Fifolt Matthew , Jorge Eric , Glaeser Peter , Zisette Jacob , Pruitt Christopher 
Published: December 2019

ObjectiveAccurate and consistent assessment of pain is essential in the pediatric emergency setting. Despite recommendations for formal assessment protocols, current data are lacking on pain assessment in pediatric emergency departments (EDs) and, specifically, whether appropriate tools are being used for different age groups. Our aim was to determine the status of pain assessment in US pediatric EDs.MethodsWe disseminated an online cross-sectional survey (after piloting) to pediatric EDs within the Children's Hospital Association. Responses were analyzed for each question owing to incomplete responders. We report descriptive statistics, with categorical variables compared with χ2(P< 0.05 considered statistically significant).ResultsFrom 120 pediatric EDs, we received 57 responses (48%). Most respondents (28/49, 57%) were from freestanding pediatric centers. All 57 EDs (100%) performed formal pain assessments, with 31 (63%) of 49 using an ED-specific protocol. Freestanding children's hospitals were more likely to have ED-specific protocols (21/31, 68%) than nonfreestanding (10/31, 32%) (P= 0.04). Among 56 responders, 100% stated that nurses are tasked with assessing pain. For children 0 to 2 years, 29 (54%) of 54 used the Face, Legs, Activity, Cry, Consolability scale. Numerical scales were increasingly used with older ages: 3 to 4 years, 40 (80%) of 50; 5 to 10 years, 49 (98%) of 50; and 11 to 21 years, 50 (100%) of 50.ConclusionsIn contrast to prior research, US pediatric EDs are routinely assessing pain with scales that are mostly appropriate for their respective age groups. Further research is needed to explore barriers to implementing appropriate pain ratings for all children and, ultimately, how these assessments impact the care of children in the emergency setting.
Longitudinal Change in Common Impairments in Children With Cerebral Palsy From Age 1.5 to 11 Years
Authors: Jeffries Lynn M. , Fiss Alyssa LaForme , Westcott McCoy Sarah , Avery Lisa 
Published: December 2019

Purpose:This project aimed to determine whether change occurs over time for impairments of balance, range of motion, endurance, and strength of children with cerebral palsy, by Gross Motor Function Classification System (GMFCS) levels.Methods:Measurements were completed in 77 children at 2 sessions (T1,T2) on average 5.8 years apart. Mean ages were 2.9 years (SD = 0.9) and 8.7 years (SD = 1.1) atT1andT2, respectively.Results:There were significant differences fromT1toT2for some children (GMFCS levels I, II, and III/IV: balance increased; GMFCS levels I and II: strength increased; and GMFCS levels III/IV and V: range of motion decreased). Endurance scores were not different and did not change.Conclusions:Longitudinal changes in most impairments occurred in children with cerebral palsy. Monitoring and targeted interventions should support each child's development.
Addressing Critiques of the Proposed CMS Metric of Organ Procurement Organ Performance: More Data Isn’t Better
Authors: Goldberg David S. , Doby Brianna , Lynch Raymond 
Published: December 2019

Background.
Centers for Medicare and Medicaid Services (CMS) has proposed a rule change to redefine the metric by which organ procurement organizations (OPOs) are evaluated. The metric relies on Centers for Disease Control and Prevention (CDC) data on inpatient deaths from causes consistent with donation among patients <75 years of age. Concerns have been raised that this metric does not account for rates of ventilation, and prevalence of cancer and severe sepsis, without objective data to substantiate or refute such concerns.

Methods.
We estimated OPO-level donation rates using CDC data, and used Agency for Healthcare Research and Quality/Healthcare Cost and Utilization Project data from 43 State Inpatient Databases to calculate “adjusted” donation rates.

Results.
The CMS metric and the ventilation-adjusted CMS metric were highly concordant in absolute terms (Spearman and Pearson correlation coefficients ≥0.95). In the Bland-Altman plot, 100% (48/48) of paired values (standard deviations [SDs] of the CMS and “ventilation adjusted” metrics) were within 1.96 SDs of the mean difference, with near-perfect correlation in Passing and Bablok regression (Lin’s concordance correlation coefficient: 0.97). The CMS metric and the ventilation/cancer/sepsis-adjusted metric were highly concordant in absolute terms (Spearman and Pearson correlation coefficients ≥0.94). In the Bland-Altman plot, 97.9% (47/48) of paired values (SDs of the CMS and “ventilation/cancer/sepsis adjusted” metrics) were within 1.96 SDs of the mean difference, with near-perfect correlation in the Passing and Bablok regression (Lin’s concordance correlation coefficient: 0.97).

Conclusions.
These conclusions should provide CMS, and the transplant community, with comfort that the proposed CMS metric using CDC inpatient death data as a tool to compare OPO is not compromised by its lack of inclusion of ventilation or other comorbidity data.
Focal cerebral arteriopathy and childhood stroke
Authors: Fearn Nicola D. , Mackay Mark T. 
Published: December 2019

Purpose of review
Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischaemic stroke in a previously healthy child. Distinguishing between different subtypes of arteriopathy is challenging and has significant management implications.

Recent findings
Recent studies have helped to define the subtypes of focal cerebral arteriopathies and improved understanding of their clinical and radiological features. In addition, they have reported new evidence for the association between viral infection and inflammation in the pathogenesis of FCA and proposed new radiological, serum and cerebrospinal fluid biomarkers to guide diagnosis and management. There is limited evidence to guide treatment of FCA but a role for steroids and antiviral therapies have been reported.

Summary
Despite the recent advances there is a limited knowledge of the pathophysiology and outcomes following FCA. Research priorities include the identification of biomarkers to improve accuracy of initial diagnosis and predict progression, and interventional trials to determine best treatments to reduce stroke recurrence risk.
A preliminary report on alcohol-associated DNA methylation and suicidal behavior: evidence using Mendelian randomization
Authors: Adams Charleen D. 
Published: December 2019

AbstractAlcohol consumption, a risk factor for suicide, is associated with changes in DNA methylation, which may play a role in the pathophysiology of suicidality. Here, Mendelian randomization probes whether alcohol-associated changes in DNA methylation mediate risk for suicidal behavior. The results suggest that higher alcohol-associated DNA methylation levels at cg18120259 confer a weak causal effect. cg18120259 is instrumented by a cis-methylation quantitative trait locus (rs9472155) that is upstream of VEGFA and associated with circulating VEFG levels. To ascertain whether the cg18120259 finding is confounded by VEGF levels, a Mendelian randomization of VEGF levels on suicidality was performed, revealing a null effect. This implies circulating VEGF levels (observed among suicide attempters) may mark but not cause suicide. Both mechanisms should be re-examined in large replication studies, as the information might be harnessed for early detection of at-risk individuals and possibly save lives.
Prevalence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis
Authors: Sherrard Laura J. , Wee Bryan A. , Duplancic Christine , Ramsay Kay A. , Dave Keyur A. , Ballard Emma , Wainwright Claire E. , Grimwood Keith , Sidjabat Hanna E. , Whiley David M. , Beatson Scott A. , Kidd Timothy J. , Bell Scott C. 
Published: December 2019

ABSTRACTDefective OprD porins contribute to carbapenem resistance and may be important in Pseudomonas aeruginosa adaptation to cystic fibrosis airways. It is unclear whether oprD mutations are fixed in populations of shared strains that are transmitted between patients or whether novel variants arise during infection. We investigated oprD sequences and antimicrobial resistance of two common Australian shared strains, constructed P. aeruginosa mutants with the most common oprD allelic variants and compared characteristics between patients with or without evidence of infection with strains harbouring these variants. Our data show that three independently acquired nonsense mutations arising from a 1-base pair substitution are fixed in strain sub-lineages. These nonsense mutations are likely to contribute to reduced carbapenem susceptibility in the sub-lineages without compromising in vitro fitness. Not only was lung function worse among patients infected with strains harbouring the nonsense mutations than those without, but they also had an increased hazard rate of lung transplantation/death. Our findings further highlight that understanding adaptive changes may help to distinguish patients with greater adverse outcomes despite infection with the same strain.
Using Paired Agent-Based Simulations To Test Strategies For Limiting The Effects Of Epidemics
Authors: Armstrong Margaret , Coelho Flávio Codeço 
Published: December 2019

AbstractAgent-based simulations are widely used nowadays in public health research for comparing different strategies for mitigating epidemics and for planning appropriate responses in the aftermath of crises in large urban areas because they can capture fine scale heterogeneities that may have important non-linear effects on the results. Given the costs of implementing strategies, decision-makers have to be convinced that the proposed treatment/procedure leads to a statistically significant improvement.This paper presents an innovative method for constructing paired agent-based simulations where exactly the same set of random effects is applied to simulations with and without the treatment/procedure. Statistical Analysis of Variance distinguishes the sum of squares between groups (BSS) from the sum of squares within groups (WSS). Our aim was to filter out the within sum of squares (WSS) leaving only the sum of squares between the control group and the treatment group (BSS). We propose to filter out the WSS by constructing paired simulations because as is well known, when paired t-tests can be used, they are much more powerful than ordinary t-tests. Pearson’s Chi-squared goodness of fit, the Kolmogorov-Smirnov statistic and the Kullback-Leibler Divergence are then used to test whether the effect is statistically significant. This procedure has been tested on a case-study on the propagation of the Zika epidemic in Rio de Janeiro in 2015.Author summaryAgent-based simulations are emerging as a powerful tool in computational biology because they can capture fine scale heterogeneities that can have important effects on the propagation of epidemics.In silicoexperiments can be used to test different strategies for mitigating epidemics quickly and inexpensively. Given the inherent variability from one simulation to another, it is difficult to statistically prove their effectiveness. We have developed a powerful method rather like paired t-tests, for testing whether a given treatment is statistically better than the control. We do this by generating paired simulations with exactly the same random variables in the control simulation and the one with a treatment. Using the terminology of analysis of variance, we want to filter out the sum of squares within the group, leaving only the sum of squares between the control and the treatment. This procedure has been applied to a case-study to see whether enclosing and air-conditioning the transport hub in Rio de Janeiro would have slowed down the propagation of Zika.
Neutrophil extracellular trap formation correlates with improved overall survival in ovarian cancer
Authors: Muqaku Besnik , Pils Dietmar , Mader Johanna C. , Aust Stefanie , Mangold Andreas , Muqaku Liridon , Slany Astrid , Del Favero Giorgia , Gerner Christopher 
Published: December 2019

AbstractIt is still a question of debate whether neutrophils, often found in the tumor microenvironment, mediate tumor-promoting or rather tumor-inhibiting activities. The present study focusses on the involvement of neutrophils in high grade serous ovarian cancer (HGSOC). Multi-omics data comprising proteomics, eicosadomics, metabolomics, Luminex-based cytokinomics, and FACS data were generated from ascites samples. Integrated data analysis demonstrates a significant increase of neutrophil extracellular trap-(NET) associated molecules in non-miliary ascites samples. A co-association network analysis performed with the ascites data further revealed a striking co-correlation between NETosis-associated metabolites with several eicosanoids. Investigating primary neutrophils from healthy domors, NET formation was induced using ionomycin or phorbol ester. Data congruence with ascites analyses indicated the predominance of NOX-independent NETosis. NETosis is associated with S100A8/A9 release. An increase of the S100A8/CRP abundance ratio was found to correlate with improved survival of HGSOC patients. The analysis of additional five independent proteome studies with regard to S100A8/CRP ratios confirmed this observation. In conclusion, here we present evidence that increased NET formation relates to improved outcomes in cancer patients.Graphical abstractNETs releasing neutrophils through detaching of small tumor nods dictate the building of bigger in size and fewer in number of tumors in the non-miliary spreading tumor. Increased angiogenesis associated with increased blood circulation may contribute to less suppressive effects on NETs formation in the non-miliary tumor type. Tumor origin,i.e. fallopian tube for the miliary or ovary for the non-miliary tumors, may influence the angiogenesis and therewith – through facilitating of neutrophils activation – (co)determine the type of tumor spread.
A naturally segregating polymorphism balancing semelparous reproduction versus reproductive diapause revealed via microfluidic assessment of starvation stress inCaenorhabditis elegans
Authors: Archer Heather , Banse Stephen , Blue Ben , Phillips Patrick C. 
Published: December 2019

AbstractCaenorhabditis eleganstypically feeds on rotting fruit and plant material in a fluctuating natural habitat, a boom-and-bust lifestyle. Moreover, stage specific developmental responses to low food concentration suggest that starvation-like conditions are a regular occurrence. In order to assess variation in theC. elegansstarvation response under precisely controlled conditions and simultaneously phenotype a large number of individuals with high precision, we have developed a microfluidic device that, when combined with image scanning technology, allows for high-throughput assessment at a temporal resolution not previously feasible and applied this to a large mapping panel of fully sequenced intercross lines. Under these conditions worms exhibit a markedly reduced adult lifespan with strain-dependent variation in starvation resistance, ranging from <24 hours to ∼120 hours. Genome-wide mapping of the responses of more than 7,855 individuals identified four quantitative trait loci (QTL) of large effects. Three of these loci are associated with single genes (ash-2, exc-6,anddpy-28) and the fourth is a ∼26 KB region on Chromosome V encompassing several genes. Backcross with selection confirmed the effect of the Chromosome V locus. Segregating natural variation for starvation response in this species suggests that different isolates may use different strategies (facultative vivipary versus reproductive diapause) for dealing with extreme food deprivation.
Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics
Authors: Pedrera Lohans , Espiritu Rafael A. , Ros Uris , Schmitt Anja , Hailfinger Stephan , García-Sáez Ana J. 
Published: December 2019

SummaryFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis correlate with the activation of ESCRT-III-mediated membrane repair, which counterbalances the kinetics of cell death and modulates the inflammatory signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained high levels of cytosolic Ca2+ prior to plasma membrane disruption are a common feature of regulated necrosis and position ESCRT-III as a general protective mechanism in these inflammatory cell death pathways.
Compact attractors of an antithetic integral feedback system have a simple structure
Authors: Margaliot Michael , Sontag Eduardo D. 
Published: December 2019

AbstractSince its introduction by Briat, Gupta and Khammash, the antithetic feedback controller design has attracted considerable attention in both theoretical and experimental systems biology. The case in which the plant is a two-dimensional linear system (making the closed-loop system a nonlinear four-dimensional system) has been analyzed in much detail. This system has a unique equilibrium but, depending on parameters, it may exhibit periodic orbits. An interesting open question is whether other dynamical behaviors, such as chaotic attractors, might be possible for some parameter choices. This note shows that, for any parameter choices, every bounded trajectory satisfies a Poincaré-Bendixson property. The analysis is based on the recently introduced notion of k-cooperative dynamical systems. It is shown that the model is a strongly 2-cooperative system, implying that the dynamics in the omega-limit set of any precompact solution is conjugate to the dynamics in a compact invariant subset of a two-dimensional Lipschitz dynamical system, thus precluding chaotic and other strange attractors.
Energy Shortage in Human and Mouse Models ofSLC4A11-Associated Corneal Endothelial Dystrophies
Authors: Zhang Wenlin , Frausto Ricardo , Chung Doug D. , Griffis Christopher G. , Kao Liyo , Chen Angela , Azimov Rustam , Sampath Alapakkam P. , Kurtz Ira , Aldave Anthony J. 
Published: December 2019

PurposeTo elucidate the molecular events in solute carrier family 4 member 11 (SLC4A11)-deficient corneal endothelium that lead to the endothelial dysfunction that characterizes the dystrophies associated withSLC4A11mutations, congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy 4.MethodsComparative transcriptomic analysis (CTA) was performed in primary human corneal endothelial cells (pHCEnC) and murine corneal endothelial cells (MCEnC) with normal and reduced levels of SLC4A11 (SLC4A11KD pHCEnC) and Slc4a11 (Slc4a11−/−MCEnC), respectively. Validation of differentially expressed genes was performed using immunofluorescence staining of CHED corneal endothelium, as well as western blot and quantitative PCR analysis ofSLC4A11KD pHCEnC andSlc4a11−/−MCEnC. Functional analyses were performed to investigate potential functional changes associated with the observed transcriptomic alterations.ResultsCTA revealed inhibition of cell metabolism and ion transport function as well as mitochondrial dysfunction, leading to reduced adenosine triphosphate (ATP) production, inSLC4A11KD pHCEnC andSlc4a11−/−MCEnC. Co-localization of SNARE protein STX17 with mitochondria marker COX4 was observed in CHED corneal endothelium, as was activation of AMPK–p53/ULK1 in bothSLC4A11KD pHCEnC andSlc4a11−/−MCEnC, providing additional evidence of mitochondrial dysfunction and mitophagy. Reduced Na+-dependent HCO3−transport activity and altered NH4Cl-induced membrane potential changes were observed inSlc4a11−/−MCEnC.ConclusionsReduced steady-state ATP levels and subsequent activation of the AMPK–p53 pathway provide a link between the metabolic functional deficit and transcriptome alterations, as well as evidence of insufficient ATP to maintain the Na+/K+-ATPase corneal endothelial pump as the cause of the edema that characterizesSLC4A11-associated corneal endothelial dystrophies.
The ClpX and ClpP2 Orthologs of Chlamydia trachomatis Perform Discrete and Essential Functions in Organism Growth and Development
Authors: Wood Nicholas A. , Blocker Amanda M. , Seleem Mohamed A. , Conda-Sheridan Martin , Fisher Derek J. , Ouellette Scot P. 
Published: December 2019

Abstract:Chlamydia trachomatis (Ctr) is an obligate intracellular bacterium that undergoes a complex developmental cycle in which the bacterium differentiates between two functionally and morphologically distinct forms, the EB and RB, each of which expresses its own specialized repertoire of proteins. Both primary (EB to RB) and secondary (RB to EB) differentiation require protein turnover, and we hypothesize that proteases are critical for mediating differentiation. The Clp protease system is well conserved in bacteria and important for protein turnover. Minimally, the system relies on a serine protease subunit, ClpP, and a AAA+ ATPase, such as ClpX, that recognizes and unfolds substrates for ClpP degradation. In Chlamydia, ClpX is encoded within an operon 3’ to clpP2. We present evidence that the chlamydial ClpX and ClpP2 orthologs are essential to organism viability and development. We demonstrate here that chlamydial ClpX is a functional ATPase and forms the expected homohexamer in vitro. Overexpression of a ClpX mutant lacking ATPase activity had a limited impact on DNA replication or secondary differentiation but, nonetheless, reduced EB viability with observable defects in EB morphology noted. Conversely, the overexpression of a catalytically inactive ClpP2 mutant significantly impacted developmental cycle progression by reducing the overall number of organisms. Blocking clpP2X transcription using CRISPR interference led to a decrease in bacterial growth, and this effect was complemented in trans by a plasmid copy of clpP2. Taken together, our data indicate that ClpX and the associated ClpP2 serve distinct functions in chlamydial developmental cycle progression and differentiation.ImportanceChlamydia trachomatis is the leading cause of infectious blindness globally and the most reported bacterial sexually transmitted infection both domestically and internationally. Given the economic burden, the lack of an approved vaccine, and the use of broad-spectrum antibiotics for treatment of infections, an understanding of chlamydial growth and development is critical for the advancement of novel, targeted antibiotics. The Clp proteins comprise an important and conserved protease system in bacteria. Our work highlights the importance of the chlamydial Clp proteins to this clinically important bacterium. Additionally, our study implicates the Clp system playing an integral role in chlamydial developmental cycle progression, which may help establish models of how Chlamydia spp. and other bacteria progress through their respective developmental cycles. Our work also contributes to a growing body of Clp-specific research that underscores the importance and versatility of this system throughout bacterial evolution and further validates Clp proteins as drug targets.