bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway
Authors: Tang Chao-Zhi , Yang Jun‐Tang , Liu Qing-Hui , Wang Ya-Ru , Wang Wen-Sheng 
Published: August 2018

ABSTRACTDepression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR‐192‐5p and its target gene fibulin (Fbln)‐2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)–induced depression through regulation of the TGF‐β1 signal transduction pathway. Verification of the targeting relationship between miR‐192‐5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual‐luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR‐192‐5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS‐induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF‐βl signaling pathway, and decreased expression of miR‐192‐5p, synaptophysin, brain‐derived neurotrophic factor, N‐methyl‐d‐aspartate receptor subunit 2B, and calmodulin‐dependent protein kinase II were noted. Up‐regulated miR‐192‐5p targeting Fbln2 acts to alleviate CUMS‐induced depression by inhibiting the TGF‐β1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up‐regulated levels of miR‐192‐5p expression act to suppress activation of the TGF‐β1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.—Tang, C.‐Z., Yang, J.‐T., Liu, Q.‐H., Wang, Y.‐R., Wang, W.‐S., Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway. FASEB J. 33, 606–618 (2019). www.fasebj.org
Reconstructive considerations in low and middle-income countries
Authors: Cervenka Brian , Trudeau Stephen , Fagan Johan , Zender Chad 
Published: August 2018

Purpose of reviewSurgical mission trips in head and neck surgery are common. There are an increasing number of surgical groups performing complex reconstructions in low and middle-income countries (LMIC). Consideration of reconstructive options that are location and patient specific are critical for optimum patient care and local physician education.Recent findingsThe pectoralis muscle regional flap is a versatile and reliable option and has been shown to reconstruct defects in nearly every head and neck subsite. Additional regional flap options described are the supraclavicular island flap and submental island flap. There are 15 published case series describing experience with performing microvascular reconstructions in LMIC. The average success rate was 87.1%. Both loupe and microscope magnification are used.SummaryComplex reconstructions are successfully being performed in LMIC. Although microvascular reconstruction is being utilized by some groups, local and patient-specific factors should be carefully considered, as many regional and local flap options available provide the same reconstruction benefit while minimizing operating room time, resources, and postoperative care needs.
Cardiovascular disease in survivors of childhood cancer
Authors: Bansal Neha , Amdani Shahnawaz M. , Hutchins Kelley K. , Lipshultz Steven E. 
Published: August 2018

Purpose of review
We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the subsequent cardiovascular disease in survivors of childhood cancer. We discuss various preventive measures, especially the cardioprotectant, dexrazoxane, whose use with anthracycline chemotherapy, including doxorubicin, is based on strong evidence. Most treatment recommendations for this unique population are based on expert opinion, not on empirical evidence.

Recent findings
As patients with childhood cancers live longer, morbidity from the cardiac side effects of chemotherapy is increasing. Treatment-related cardiac damage is irreversible and often progressive. It is imperative that such damage be prevented with strategies such as limiting the cumulative anthracycline dose, the use of anthracycline structural analogues and the use of cardioprotective agents.

Summary
A deeper understanding of the mechanisms of their cardiotoxicity reveals that there is no ‘safe’ dose of anthracyclines. However, certain risk factors, such as higher lifetime anthracycline cumulative doses, higher anthracycline dose rates, female sex, longer follow-up, younger age at anthracycline treatment and cardiac irradiation, are associated with more severe cardiotoxicity. We advocate the use of dexrazoxane to limit the cardiotoxic effects of anthracycline chemotherapy.
Complete Restoration of Respiratory Muscle Function in Three Subjects With Spinal Cord Injury
Authors: DiMarco Anthony F. , Geertman Robert T. , Tabbaa Kutaiba , Kowalski Krzysztof E. 
Published: August 2018

Objectives
The aim of this study was to assess the safety and efficacy of complete restoration of respiratory muscle function in subjects with spinal cord injury.

Methods
This was an interventional study investigating three subjects maintained on a diaphragm pacing system who were implanted with the spinal cord stimulation system to restore cough. Peak expiratory airflow and airway pressure generation were the primary physiologic outcome measures; an assessment of the degree of difficulty in raising secretions was the primary clinical outcome measure.

Results
Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH2O, respectively. When spinal cord stimulation was applied after pacing volume associated with the subject's maximum inspiratory effort and synchronized with the subject's maximum expiratory effort, peak expiratory airflow and airway pressure generation were 9.0 ± 1.9 L/s and 90 ± 6 cmH2O, respectively (P < 0.05). Moreover, each subject experienced much greater ease in raising secretions and marked improvement in the ease in raising secretions compared with other methods.

Conclusions
Complete restoration of respiratory muscle function can be safely and effectively achieved in the same individuals with spinal cord injury. Spinal cord stimulation results in peak expiratory airflow and airway pressure generation characteristic of a normal cough, whereas diaphragm pacing was successful in maintaining patients off mechanical ventilation.
Impact of Chronic Steroid Use on Plastic Surgery Outcomes: Analysis of 94,140 Cases
Authors: Barcha Carolina P. , Ranzer Matthew J. 
Published: August 2018

Background:
Chronic steroid use suppresses inflammation, edema, and autoimmunity, and delays wound healing. Using data from the American College of Surgeons National Surgical Quality Improvement Program, this study characterizes the risk of perioperative chronic steroid use for complications in plastic surgery cases.

Methods:
A retrospective study was performed on 94,140 plastic surgery cases from the American College of Surgeons National Surgical Quality Improvement Program database for the years 2006 to 2015. CPT codes were used to categorize operations. Patients were separated into two cohorts based on chronic steroid use status. Univariate analysis was performed using chi-square, Fisher’s exact, or Wilcoxon rank sum test. Logistic regression models were fitted to evaluate the association between chronic steroid use and postoperative complications. Total hospital length of stay was compared. Odds ratios were computed at the 95 percent confidence interval.

Results:
Chronic steroid users were more likely to develop surgical complications (OR, 1.3; p = 0.0452) and medical complications (OR, 1.8; p = 0.0002) compared with nonusers. Among the 10 most frequent procedures performed on chronic steroid users, steroid use was a significant risk factor for postoperative complications after reduction mammaplasty (OR, 2.2; p = 0.001); delayed insertion of breast prosthesis following mastopexy or mastectomy or during reconstruction (OR, 2.2; p = 0.049); and in trunk muscle, myocutaneous, or fasciocutaneous flap surgery (OR, 7.2; p = 0.0029).

Conclusion:
With this information in hand, plastic surgeons will be better equipped to counsel patients and adequately design perioperative protocols for chronic steroid users.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Introducing Knowledge Translation to Plastic Surgery: Turning Evidence into Practice
Authors: Moltaji Syena , Alkhatib Ahmad H. , Liu Henry , Murphy Jessica , Gallo Lucas , Karpinski Marta , Mowakket Sadek , Thoma Achilleas 
Published: August 2018

Summary:
Best evidence has no bearing on quality of life if it is not implemented in clinical practice. The authors introduce knowledge translation as a theoretical framework for closing the gap between evidence and practice in plastic surgery. The current state of published evidence in plastic surgery is reviewed and evaluated, with the recommendation to use the EQUATOR Network’s guidelines for reporting clinical research findings. Tools and strategies are offered for the reader to understand and integrate evidence at the bedside. Systemic solutions are also proposed for the dissemination of best evidence to facilitate its translation into practice.
Comparison of Navigator Triggering Reduced Field of View and Large Field of View Diffusion-Weighted Imaging of the Pancreas
Authors: Mannelli Lorenzo , Monti Serena , Corrias Giuseppe , Fung Maggie M. , Nyman Charles , Golia Pernicka Jennifer S. , Do Richard K.G. 
Published: August 2018

Rationale and Objectives
The purpose of this study is to compare image quality, presence and grade of artifacts, signal-to-noise ratio, and apparent diffusion coefficient (ADC) values in pancreatic tissue between high-resolution navigator-triggered (NT) restricted field of view (rFOV) FOCUS single-shot (SS) echo-planar imaging (EPI) diffusion-weighted imaging (DWI) and NT large FOV SS-EPI DWI.

Materials and Methods
Magnetic resonance imaging examinations were performed with GE 3-T systems using a 32-channel body array coil. Seventeen consecutive patients were imaged. A 5-point scale semiquantitative grading system was used to evaluate image quality and general artifacts. Signal-to-noise ratio and ADC were measured in the head, body, and tail of the pancreas. Statistical analysis was performed using Student t test and Wilcoxon signed rank test, with differences considered significant for P value less than 0.05.

Results
More artifacts were present on large FOV compared with rFOV FOCUS SS-EPI DW images (P < 0.01). Restricted field of view image quality was subjectively better (P < 0.01). No difference in the signal-to-noise ratio was demonstrated between the 2 image datasets. Apparent diffusion coefficient values were significantly lower (P < 0.01) when calculated from rFOV images than large FOV images.

Conclusions
Our results demonstrate better image quality and reduced artifacts in rFOV images compared with large FOV DWI. Measurements from ADC maps derived from rFOV DWI show significantly lower ADC values when compared with ADC maps derived from large FOV DWI.
Deciphering regulatory DNA sequences and noncoding genetic variants using neural network models of massively parallel reporter assays
Authors: Movva Rajiv , Greenside Peyton , Marinov Georgi K. , Nair Surag , Shrikumar Avanti , Kundaje Anshul 
Published: August 2018

AbstractThe relationship between noncoding DNA sequence and gene expression is not well-understood. Massively parallel reporter assays (MPRAs), which quantify the regulatory activity of large libraries of DNA sequences in parallel, are a powerful approach to characterize this relationship. We present MPRA-DragoNN, a convolutional neural network (CNN)-based framework to predict and interpret the regulatory activity of DNA sequences as measured by MPRAs. While our method is generally applicable to a variety of MPRA designs, here we trained our model on the Sharpr-MPRA dataset that measures the activity of ~500,000 constructs tiling 15,720 regulatory regions in human K562 and HepG2 cell lines. MPRA-DragoNN predictions were moderately correlated (Spearmanρ= 0.28) with measured activity and were within range of replicate concordance of the assay. State-of-the-art model interpretation methods revealed high-resolution predictive regulatory sequence features that overlapped transcription factor (TF) binding motifs. We used the model to investigate the cell type and chromatin state preferences of predictive TF motifs. We explored the ability of our model to predict the allelic effects of regulatory variants in an independent MPRA experiment and fine map putative functional SNPs in loci associated with lipid traits. Our results suggest that interpretable deep learning models trained on MPRA data have the potential to reveal meaningful patterns in regulatory DNA sequences and prioritize regulatory genetic variants, especially as larger, higher-quality datasets are produced.
Mechanism of Microbicidal Action of E-101 Solution, a Myeloperoxidase-Mediated Antimicrobial, and its Oxidative Products
Authors: Denys G. A. , Devoe Neil C. , Gudis P. , May M. , Allen R.C. , Stephens J. T. 
Published: August 2018

ABSTRACTE-101 Solution is a first in class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous vehicle. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastucture changes and microbicidal activity against methicillin-resistantStaphylococcus aureus(MRSA) andEscherichia coli. Time kill and transmission electron microscopy studies were performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and MBC determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA andE. colicells. When pMPO was omitted, high levels of H2O2generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest the primary site that E-101solution exerts microbicidal action is the cell membrane by inactivation of essential cell membrane components.
SiCloneFit: Bayesian inference of population structure, genotype,and phylogeny of tumor clones from single-cell genome sequencing data
Authors: Zafar Hamim , Navin Nicholas , Chen Ken , Nakhleh Luay 
Published: August 2018

AbstractAccumulation and selection of somatic mutations in a Darwinian framework result in intra-tumor heterogeneity (ITH) that poses significant challenges to the diagnosis and clinical therapy of cancer. Identification of the tumor cell populations (clones) and reconstruction of their evolutionary relationship can elucidate this heterogeneity. Recently developed single-cell DNA sequencing (SCS) technologies promise to resolve ITH to a single-cell level. However, technical errors in SCS datasets, including false-positives (FP), false-negatives (FN) due to allelic dropout and cell doublets, significantly complicate these tasks. Here, we propose a non-parametric Bayesian method that reconstructs the clonal populations as clusters of single cells, genotypes of each clone and the evolutionary relationships between the clones. It employs a tree-structured Chinese restaurant process as the prior on the number and composition of clonal populations. The evolution of the clonal populations is modeled by a clonal phylogeny and a finite-site model of evolution to account for potential mutation recurrence and losses. We probabilistically account for FP and FN errors, and cell doublets are modeled by employing a Beta-binomial distribution. We develop a Gibbs sampling algorithm comprising of partial reversible-jump and partial Metropolis-Hastings updates to explore the joint posterior space of all parameters. The performance of our method on synthetic and experimental datasets suggests that joint reconstruction of tumor clones and clonal phylogeny under a finite-site model of evolution leads to more accurate inferences. Our method is the first to enable this joint reconstruction in a fully Bayesian framework, thus providing measures of support of the inferences it makes.
Geography, not food availability, reflects compositional differences in the bacterial communities associated with larval sea urchins
Authors: Carrier Tyler J. , Dupont Sam , Reitzel Adam M. 
Published: August 2018

AbstractDetermining the principles underlying the assembly, structure, and diversity of symbiont communities remains a focal point of animal-microbiome research. Much of these efforts focus on taxonomic variation within or between animal populations, but rarely test the proportional impacts of ecological components that may affect animal-associated microbiota. Using larvae from the sea urchinStrongylocentrotus droebachiensisfrom the Atlantic and Pacific Oceans, we test the hypothesis that inter-population differences in the composition of animal-associated bacterial communities are more pronounced than intra-population variation due to a heterogeneous feeding environment. Despite significant differences in bacterial community structure within eachS. droebachiensislarval population (based on food availability, time, development, and phenotype), variation in OTU membership and community composition correlated more strongly with geography. Moreover, across these three locations, 20-30% of OTUs were specific to a single population while less than 10% were shared. Taken together, these results suggest that inter-populational variation in symbiont communities is more pronounced than intra-populational variation. This difference may suggest that ecological variables over broad geographic scales may mask smaller scale ecological variables; however, explicit testing of this potential principle requires common garden experiments as well as molecular and functional manipulations.
NaPi- II b as a potential diagnostic and prognostic biomarker in ovarian cancers
Authors: Zhao Shoufeng , Wang Zhipeng 
Published: August 2018

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.
Business volatility and employee performance
Authors: Chiang Wen-Chyuan , Sun Li , Walkup Brian R. 
Published: August 2018

Purpose
The purpose of this paper is to examine the impact of business volatility on employee performance.

Design/methodology/approach
The authors use regression analysis to examine the authors’ research question.

Findings
The results suggest that business volatility has a significant and positive impact on employee performance. Furthermore, the authors find that the relationship between business volatility and employee performance is stronger for larger firms and firms with higher labor intensity.

Originality/value
The study links and contributes to two streams of literature: employee/labor cost management from the accounting literature and business volatility from the management literature. Whether business volatility affects employee performance remains an interesting question that has not been definitively answered empirically. To the best of the authors’ knowledge, this is the first empirical study that directly examines the relationship between business volatility and employee performance at the firm level.
Stakeholder management in PPP projects: external stakeholders’ perspective
Authors: Amadi Chika , Carrillo Patricia , Tuuli Martin 
Published: August 2018

Purpose
This paper focusses on external stakeholders’ perspective of stakeholder management in public–private partnerships (PPP) projects within the context of developing countries where public opposition to PPP projects is prevalent. The purpose of this paper is to identify the key enablers to PPP projects’ success from the perspective of external stakeholders.

Design/methodology/approach
Data were collected from two case studies via semi-structured interviews in two PPP project locations in Nigeria. In total, 14 external stakeholders comprising community leaders, trade unionists and human right activist participated in the research.

Findings
Five key enablers of external stakeholder management were identified. These are as follows: the choice of project location; transparency of the internal stakeholders; timing of stakeholder engagement; knowledge of PPP; and relationship with internal stakeholders.

Originality/value
External stakeholders’ perspective of stakeholder management in PPP projects within the context of developing countries new to PPP has been established. The practical implications of the five enablers can be used by policy makers and industry professionals to ensure effective stakeholder management of PPP projects.