bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Hydrocodone/Acetaminophen for Pediatric Laceration Repair: A Randomized Trial
Authors: Chumpitazi Corrie E. , Caviness A. Chantal , Grawe Glenda H. , Camp Elizabeth A. , Shah Manish I. 
Published: December 2019

Background:
Laceration repair is a common procedure, and causes pain and distress in children. The purpose of this study was to measure the effect of hydrocodone/acetaminophen elixir in reducing both pain and anxiety in children undergoing sutured laceration repair in the emergency department.

Methods:
The authors conducted a randomized, double-blinded, placebo-controlled trial in children aged 2 to 17 years, stratified by age younger than 8 years, with topical lidocaine-treated lacerations requiring sutured repair in the emergency department. The primary outcome was pain score at 5 minutes of laceration repair. Secondary outcomes included progression to procedural sedation and anxiety scores in older children.

Results:
Eighty-five children were randomized, 43 to the hydrocodone/acetaminophen group and 42 to the placebo group. Median 5-minute pain scores in children aged 2 to 7 years were significantly lower in the medication group (5.0; interquartile range, 4.0 to 6.50) compared with the placebo group (7.0; interquartile range, 5.25 to 10.0; p = 0.01). Three patients (12 percent) in the placebo group proceeded to procedural sedation. For children aged 8 to 17 years, there was no significant difference in pain scores between the treatment (0.5; interquartile range, 0.0 to 0.1; p = 0.81) and placebo groups (0.1; interquartile range, 0.01 to 0.4) or in anxiety scores using the State-Trait Anxiety Inventory for Children.

Conclusion:
Adjuvant oral hydrocodone/acetaminophen is more effective than placebo in reducing pain in children younger than 8 years undergoing topical lidocaine–treated laceration repair, but it does not decrease pain or anxiety in older children.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Snapshot Multispectral Imaging Is Not Inferior to SPY Laser Fluorescence Imaging When Predicting Murine Flap Necrosis
Authors: Jones Glyn E. , Yoo Aran , King Victor A. , Sowa Michael , Pinson David M. 
Published: December 2019

Background:
Objective assessment of tissue viability is critical to improve outcomes of cosmetic and reconstructive procedures. A widely used method to predict tissue viability is indocyanine green angiography. The authors present an alternative method that determines the relative proportions of oxyhemoglobin to deoxyhemoglobin through multispectral reflectance imaging. This affordable, hand-held device is noninvasive and may be used in clinic settings. The authors hypothesize that multispectral reflectance imaging is not inferior to indocyanine green angiography in predicting flap necrosis in the murine model.

Methods:
Reverse McFarlane skin flaps measuring 10 × 3 cm were raised on 300- to 400-g male Sprague-Dawley rats. Indocyanine green angiography and multispectral reflectance imaging was performed before surgery, immediately after surgery, and 30 minutes after surgery. Clinical outcome images acquired 72 hours after surgery were evaluated by three independent plastic surgeons. Objective data obtained immediately after surgery were compared to postsurgical clinical outcomes to determine which method more accurately predicted flap necrosis.

Results:
Nine reverse McFarlane skin flaps were evaluated 72 hours after flap elevation. Data analysis demonstrated that the 95 percent confidence intervals for the sensitivity of postoperative multispectral reflectance imaging and indocyanine green angiography imaging to predict 72-hour tissue viability at a fixed specificity of 90 percent for predicting tissue necrosis were 86.3 to 91.0 and 79.1 to 86.9, respectively.

Conclusions:
In this experimental animal model, multispectral reflectance imaging does not appear to be inferior to indocyanine green angiography in detecting compromised tissue viability. With the advantages of noninvasiveness, portability, affordability, and lack of disposables, multispectral reflectance imaging has an exciting potential for widespread use in cosmetic and reconstructive procedures.
Quality and Safety in Healthcare, Part LXII
Authors: Harolds Jay A. 
Published: December 2019

Abstract
Multiple national organizations promote resident wellness. The Accreditation Council for Graduate Medical Education limits work hours and sleep deprivation for residents. The Accreditation Council for Graduate Medical Education requires that residency programs take into consideration the intensity of the work, how residents are scheduled, and that residents be given reasonable time off to go to medical and dental care appointments. The Action Collaborative on Clinician Well-Being and Resilience, the National Wellness Institute, the American Medical Association, and the American College of Radiology are some of the other national organizations fighting burnout and promoting wellness.
Quantification of Perinodular Emphysema in High-risk Patients Offers No Benefit in Lung Nodule Risk-Stratification of Malignancy Potential
Authors: Amundson William H. , Swanson Eric J. , Petersen Ashley , Bell Brian J. , Hatt Charles , Wendt Chris H. 
Published: December 2019

Purpose:
Pulmonary nodules, found either incidentally or on lung cancer screening, are common. Evaluating the benign or malignant nature of these nodules is costly in terms of patient risk and expense. The presence of both global and regional emphysema has been linked to increased lung cancer risk. We sought to determine whether the measurement of emphysema directly adjacent to a lung nodule could inform the likelihood of a nodule being malignant.

Materials and Methods:
Within a population of Veterans at high risk for lung cancer, 58 subjects with malignant nodules found on computerized tomographic chest scans were matched by lobe and nodule size to 58 controls. Lung densitometry was measured via determination of the low attenuation area percentage at −950 Hounsfield units (LAA950) and the Hounsfield unit (HU) value at which 15% of lung voxels have a lower lung density (Perc15), at predefined lung volumes that encompassed the nodule to evaluate both perinodular and regional lung fields. The association between measured lung density and malignancy was investigated using conditional logistic regression models, with densitometry measurements used as the primary predictor, adjusting for age alone, or age and computerized tomographic scan characteristics.

Results:
No significant differences in emphysema measurements between malignant and benign nodules were identified at lung volumes encompassing both perinodular and regional emphysema. Furthermore, emphysema quantification remained stable across lung volumes within individuals.

Conclusions:
In this study, quantifying the degree of perinodular or regional emphysema did not offer any benefit in the risk stratification of lung nodules.
Association of Perioperative Variables and the Acute Respiratory Distress Syndrome in Liver Transplant Recipients
Authors: Ripoll Juan G. , Wanta Brendan T. , Wetzel David R. , Frank Ryan D. , Findlay James Y. , Vogt Matthew N.P. 
Published: December 2019

Background.
The assessment of perioperative risk factors for the development of acute respiratory distress syndrome (ARDS) has been described in various surgical populations. However, there are only limited data among patients undergoing liver transplantation (LT), particularly regarding the influence of intraoperative ventilation parameters. We sought to identify the perioperative risk factors associated with the development of ARDS in LT recipients.

Methods.
This is a single-center, retrospective cohort study of adult patients who underwent LT at a tertiary academic medical center between January 1, 2006, and January 31, 2016. Postoperative ARDS was identified using the Berlin definition. Multivariable logistic regression analysis was used to identify perioperative risk factors for ARDS.

Results.
Of 817 eligible patients who underwent an LT during the study period, 20 (2.45%) developed postoperative ARDS. In the preoperative model, ongoing dialysis (odds ratio, 6.41; P < 0.01) was identified as an independent risk factor of ARDS post-LT. A higher mean peak inspiratory pressure per increase of 1 cm H2O (odds ratio, 1.31; P < 0.01) was the only independent risk factor in the intraoperative model. Patients who developed ARDS postoperatively had significantly greater intensive care unit and hospital stay compared to non-ARDS patients (P < 0.001). There were no significant differences in the 30-day (P = 0.16) and 1-year (P = 0.51) mortality between the groups.

Conclusions.
Dialysis at the time of transplant and elevated intraoperative mean peak inspiratory pressure were associated with the development of ARDS. ARDS post LT was associated with increased intensive care unit and hospital length of stay, but not increased mortality.
Neutrophil: Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during RSV Infection
Authors: Deng Yu , Herbert Jenny A. , Robinson Elisabeth , Ren Luo , Smyth Rosalind L. , Smith Claire M. 
Published: December 2019

ABSTRACTRespiratory syncytial virus (RSV) is a major cause of paediatric respiratory disease. Large numbers of neutrophils are recruited into the airways of children with severe RSV disease. It is not clear whether or how neutrophils enhance recovery from disease or contribute to its pathology.Using anin vitromodel of the differentiated airway epithelium, we found that addition of physiological concentrations of neutrophils to RSV infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilia loss, less tight junction expression (ZO-1) and more detachment of epithelial cells than seen with RSV infection alone. This was also associated with a decrease in infectious virus and fewer RSV positive cells in cultures after neutrophil exposure compared to pre-exposure. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1h), and neutrophil degranulation with significantly greater cellular expression of CD11b, MPO and higher neutrophil elastase and myeloperoxidase activity in apical surface medias compared to that from mock-infected AECs. We also recovered more apoptotic neutrophils from RSV infected cultures (>40%), compared to <5% in mock infected cultures after 4h.The results of this study could provide important insights into the role of neutrophils in host response in the airway.
Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons
Authors: Fontaine Arjun K. , Ramirez David G. , Littich Samuel F. , Piscopio Robert A. , Kravets Vira , Caldwell John H. , Weir Richard F. , Benninger Richard K.P. 
Published: December 2019

AbstractPrevious studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.
Long reads from Nanopore sequencing as a tool for animal microbiome studies
Authors: Delgado Beatriz , Serrano Magdalena , González Carmen , Bach Alex , González-Recio Oscar 
Published: December 2019

AbstractIn the era of bioinformatics and metagenomics, the study of the ruminal microbiome has gained considerable relevance in the field of animal breeding, since the composition of the rumen microbiota significantly impacts production and the environment. Illumina sequencing is considered the gold standard for the analysis of microbiomes, but it is limited by obtaining only short DNA sequences to analyze. As an alternative, Oxford Nanopore Technologies (ONT) has developed a new sequencing technique based on nanopores that can be carried out in the MinION, a portable device with a low initial cost which long DNA readings can be obtained with. The aim of this study was to compare the performance of both types of sequencing applied to samples of ruminal content using a similar pipeline. The ONT sequencing provided similar results to the Illumina sequencing, although it was able to classify a greater number of readings at the species level, possibly due to the increase in the read size. The results also suggest that, due to the size of the reads, it would be possible to obtain the same amount of information in a smaller number of hours. However, detection of archaeal and eukaryotic species is still difficult to accomplish due to their low abundance in the rumen compared to bacteria, suggesting different pipelines and strategies are needed to obtain a whole representation of the less abundant species in the rumen microbiota.
A novel G protein-biased and subtype selective agonist for a G protein-coupled receptor discovered from screening herbal extracts
Authors: Zhang Bingjie , Zhao Simeng , Yang Dehua , Wu Yiran , Xin Ye , Cao Haijie , Huang Xi-Ping , Cai Xiaoqing , Sun Wen , Ye Na , Xu Yueming , Peng Yao , Zhao Suwen , Liu Zhi-Jie , Zhong Guisheng , Wang Ming-Wei , Shui Wenqing 
Published: December 2019

AbstractSubtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2Creceptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2Cwithout activating the 5-HT2Aor 5-HT2Breceptors. Remarkably, this novel ligand exhibited exclusive bias towards G protein signaling for which key residues were identified, and it showed comparablein vivoefficacy for food intake suppression and weight loss as the anti-obesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.
TNF deficiency dysregulates inflammatory cytokine production leading to lung pathology and death during respiratory poxvirus infection
Authors: Kels Ma. Junaliah Tuazon , Ng Esther , Al Rumaih Zahrah , Pandey Pratikshya , Ruuls Sigrid R. , Korner Heinrich , Newsome Timothy P. , Chaudhri Geeta , Karupiah Gunasegaran 
Published: December 2019

AbstractExcessive tumor necrosis factor (TNF) is known to cause significant pathology. Paradoxically, deficiency in TNF (TNF-/-) also caused significant pathology during respiratory ectromelia virus (ECTV) infection, a surrogate mouse model for smallpox. TNF-/-mice succumbed to fulminant disease whereas wild-type mice, and those expressing only transmembrane TNF, recovered. TNF deficiency did not affect viral load or leukocyte recruitment but caused severe lung pathology and excessive production of the cytokines IL-6, IL-10, TGF-β, and IFN-γ. Blockade of these cytokines reduced lung pathology concomitant with induction of protein inhibitor of activated STAT3 (PIAS3) and/or suppressor of cytokine signaling 3 (SOCS3), factors that inhibit STAT3 activation. Short-term inhibition of STAT3 activation in ECTV-infected TNF-/-mice with an inhibitor reduced lung pathology. TNF is essential for regulating inflammation and its deficiency exacerbates ECTV infection as a consequence of significant lung pathology caused by dysregulation of inflammatory cytokine production, in part via overactivation of STAT3.
Cryo-EM Structures and Regulation of Arabinofuranosyltransferase AftD from Mycobacteria
Authors: Tan Yong Zi , Zhang Lei , Rodrigues José , Zheng Ruixiang Blake , Giacometti Sabrina I. , Rosário Ana L. , Kloss Brian , Dandey Venkata P. , Wei Hui , Brunton Richard , Raczkowski Ashleigh M. , Athayde Diogo , Catalão Maria João , Pimentel Madalena , Clarke Oliver B. , Lowary Todd L. , Archer Margarida , Niederweis Michael , Potter Clinton S. , Carragher Bridget , Mancia Filippo 
Published: December 2019

SUMMARYMycobacterium tuberculosiscauses tuberculosis, a disease that kills over one million people each year. Its cell envelope is a common antibiotic target and has a unique structure due, in part, to two lipidated polysaccharides – arabinogalactan and lipoarabinomannan. Arabinofuranosyltransferase D (AftD) is an essential enzyme involved in assembling these glycolipids. We present the 2.9 Å resolution structure ofM. abscessusAftD determined by single particle cryo-electron microscopy. AftD has a conserved GT-C glycosyltransferase fold and three carbohydrate binding modules. Glycan array analysis shows that AftD binds complex arabinose glycans. Additionally, AftD is non-covalently complexed with an acyl carrier protein (ACP). 3.4 and 3.5 Å structures of a mutant with impaired ACP binding reveal a conformational change that suggests the ACP may regulate AftD function. Using a conditional knock-out constructed inM. smegmatis, mutagenesis experiments confirm the essentiality of the putative active site and the ACP binding for AftD function.
Estimating allele-specific expression of SNVs from 10x Genomics Single-Cell RNA-Sequencing Data
Authors: Prashant N M , Liu Hongyu , Bousounis Pavlos , Spurr Liam , Alomran Nawaf , Ibeawuchi Helen , Sein Justin , Reece-Stremtan Dacian , Horvath Anelia 
Published: December 2019

AbstractWith the recent advances in single-cell RNA-sequencing (scRNA-seq) technologies, estimation of allele expression from single cells is becoming increasingly reliable. Allele expression is both quantitative and dynamic and is an essential component of the genomic interactome. Here, we systematically estimate allele expression from heterozygous single nucleotide variant (SNV) loci using scRNA-seq data generated on the 10x Genomics platform. We include in the analysis 26,640 human adipose-derived mesenchymal stem cells (from three healthy donors), with an average sequencing reads over 120K/cell (more than 4 billion scRNA-seq reads total). High quality SNV calls assessed in our study contained approximately 15% exonic and >50% intronic loci. To analyze the allele expression, we estimate the expressed Variant Allele Fraction (VAFRNA) from SNV-aware alignments and analyze its variance and distribution (mono- and bi-allelic) at different cutoffs for required minimal number of sequencing reads. Our analysis shows that when assessing SNV loci covered by a minimum of 3 unique sequencing reads, over 50% of the heterozygous SNVs show bi-allelic expression, while at minimum of 10 reads, nearly 90% of the SNVs are bi-allelic. Consistent with single cell studies on RNA velocity and models of transcriptional burst kinetics, we observe a substantially higher rate of monoallelic expression among intronic SNVs, signifying the usefulness of scVAFRNAto assess dynamic cellular processes. Our analysis demonstrates the feasibility of scVAFRNAestimation from current scRNA-seq datasets and shows that the 3’-based library generation protocol of 10x Genomics scRNA-seq data can be highly informative in SNV-based analyses.
Adenosine receptor and its downstream targets, mod(mdg4) and Hsp70, work as a signaling pathway modulating cytotoxic damage inDrosophila
Authors: Lin Yu-Hsien , Maaroufi Houda Ouns , Kucerova Lucie , Rouhova Lenka , Filip Tomas , Zurovec Michal 
Published: December 2019

SummaryAdenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in ‘danger-sensing’ and tissue-protection. Yet, little is known about the role of Ado signaling inDrosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which carry out its function. Finally, we showed that a decrease in Ado signaling affect otherDrosophilastress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses inDrosophila.
Plasticity ofMedicago truncatulaseed dormancy relates to large-scale environment variation
Authors: Renzi Juan Pablo , Duchoslav Martin , Brus Jan , Hradilová Iveta , Pechanec Vilém , Václavek Tadeáš , Machalová Jitka , Hron Karel , Verdier Jerome , Smýkal Petr 
Published: December 2019

AbstractSeed dormancy and timing of its release is important developmental transition determining the survival of individual as well as population and species. We usedMedicago truncatulaas model to study legume seed dormancy in ecological and genomics context. The effect of oscillating temperatures as one of the dormancy release factor was tested over the period of 88 days on the set of 178 accessions originating from variable environmental conditions of Mediterranean basin. Phenotypic plasticity of final dormancy was significantly correlated with increased aridity, suggesting that plastic responses to external stimuli provide seeds with strong bet-hedging capacity and the potential to cope with high levels of environmental heterogeneity. Genome-wide association analysis identified candidate genes associated with dormancy release related to secondary metabolites synthesis, hormone regulation and modification of the cell wall likely mediating seed coat permeability and ultimately imbibition and germination.HighlightMedicago seed dormancy was correlated with increased aridity of the environment, suggesting that plastic responses provide seeds with a bet-hedging capacity. Genome-wide association analysis identified candidate genes associated with release from dormancy.