bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hearing Damage Induced by Blast Overpressure at Mild TBI Level in a Chinchilla Model
Authors: Smith Kyle D , Chen Tao , Gan Rong Z 
Published: February 2020

Abstract

Introduction
The peripheral auditory system and various structures within the central auditory system are vulnerable to blast injuries, and even blast overpressure is at relatively mild traumatic brain injury (TBI) level. However, the extent of hearing loss in relation to blast number and time course of post-blast is not well understood. This study reports the progressive hearing damage measured in chinchillas after multiple blast exposures at mild TBI levels (103–138 kPa or 15–20 psi).

Materials and Methods
Sixteen animals (two controls) were exposed to two blasts and three blasts, respectively, in two groups with both ears plugged with foam earplugs to prevent the eardrum from rupturing. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were measured in pre- and post-blasts. Immunohistochemical study of chinchilla brains were performed at the end of experiment.

Results
Results show that the ABR threshold and DPOAE level shifts in 2-blast animals were recovered after 7 days. In 3-blast animals, the ABR and DPOAE shifts remained at 26 and 23 dB, respectively after 14 days. Variation of auditory cortex damage between 2-blast and 3-blast was also observed in immunofluorescence images.

Conclusions
This study demonstrates that the number of blasts causing mild TBI critically affects hearing damage.
Ex-Vivo Normothermic Limb Perfusion With a Hemoglobin-Based Oxygen Carrier Perfusate
Authors: Said Sayf A , Ordeñana Carlos X , Rezaei Majid , Figueroa Brian A , Dasarathy Srinivasan , Brunengraber Henri , Rampazzo Antonio , Gharb Bahar Bassiri 
Published: February 2020

Abstract

Introduction
Ex-vivo normothermic limb perfusion (EVNLP) has been proven to preserve limb viability better than standard cold storage. Perfusates containing packed red blood cells (pRBC) improve outcomes when compared to acellular perfusates. Limitations of pRBC-based perfusion include limited availability, need for cross match, mechanical hemolysis, and activation of pro-inflammatory proteins. Hemoglobin-based oxygen carrier (HBOC)-201 (Hemopure) is a solution of polymerized bovine hemoglobin, characterized by low immunogenicity, no risk of hemolytic reaction, and enhanced convective and diffusive oxygen delivery. This is a preliminary study on the feasibility of EVNLP using HBOC-201 as an oxygen carrier.

Materials and Methods
Three porcine forelimb perfusions were performed using an established EVNLP model and an HBOC-201-based perfusate. The perfusion circuit included a roller pump, oxygenator, heat exchanger, and reservoir. Electrolytes, limb temperature, weight, compartment pressure, nerve conduction, and perfusion indicated by indocyanine green angiography and infra-red thermography were monitored. Histological evaluation was performed with hematoxylin and eosin and electron microscopy.

Results
Three limbs were perfused for 21.3 ± 2.1 hours. Muscle contractility was preserved for 10.6 ± 2.4 hours. Better preservation of the mitochondrial ultrastructure was evident at 12 hours in contrast to crystallization and destruction features in the cold-storage controls.

Conclusions
An HBOC-201-EVNLP produced outcomes similar to RBC-EVNLP with preservation of muscle contractility and mitochondrial structure.
Chemokine Receptor Antagonists in Combination with Morphine as a Novel Strategy for Opioid Dose Reduction in Pain Management
Authors: Eisenstein Toby K , Chen Xiaohong , Inan Saadet , Meissler Joseph J , Tallarida Christopher S , Geller Ellen B , Rawls Scott M , Cowan Alan , Adler Martin W 
Published: February 2020

Abstract

Introduction
Although opioids are widely prescribed for pain, in many circumstances, they have only modest efficacy. Preclinical studies have shown that chemokines, immune mediators released during tissue injury and inflammation, can desensitize opioid receptors and block opioid analgesia by a process termed “heterologous desensitization.” The present studies tested the hypothesis that in evoked pain, certain chemokine receptor antagonists (CRAs), given with a submaximal dose of morphine, would result in enhanced morphine potency.

Methods
Three rodent pain assays were used: incisional pain in rats, the cold-water tail flick test in rats, and the formalin test in mice. The FDA-approved, commercially available CRAs, maraviroc and AMD3100, were used. They block the chemokine receptors and ligands, CCR5/CCL5 (RANTES) and CXCR4/CXCL4 (SDF-1α), respectively.

Results
In the incisional pain assay, it was found that the combination of a single CRA, or of both CRAs, with morphine significantly shifted the morphine dose-response curve to the left, as much as 3.3-fold. In the cold-water tail flick and formalin tests, significant increases of the antinociceptive effects of morphine were also observed when combined with CRAs.

Conclusions
These results support the potential of a new “opioid-sparing” approach for pain treatment, which combines CRAs with reduced doses of morphine.
The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction
Authors: Himes Benjamin T , Peterson Timothy E , de Mooij Tristan , Garcia Luz M Cumba , Jung Mi-Yeon , Uhm Sarah , Yan David , Tyson Jasmine , Jin-Lee Helen J , Parney Daniel , Abukhadra Yasmina , Gustafson Michael P , Dietz Allan B , Johnson Aaron J , Dong Haidong , Maus Rachel L , Markovic Svetomir , Lucien Fabrice , Parney Ian F 
Published: February 2020

Abstract

Background
Immunosuppression in glioblastoma (GBM) is an obstacle to effective immunotherapy. GBM-derived immunosuppressive monocytes are central to this. Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule, expressed by GBM cells and GBM extracellular vesicles (EVs). We sought to determine the role of EV-associated PD-L1 in the formation of immunosuppressive monocytes.

Methods
Monocytes collected from healthy donors were conditioned with GBM-derived EVs to induce the formation of immunosuppressive monocytes, which were quantified via flow cytometry. Donor-matched T cells were subsequently co-cultured with EV-conditioned monocytes in order to assess effects on T-cell proliferation. PD-L1 constitutive overexpression or short hairpin RNA–mediated knockdown was used to determined the role of altered PD-L1 expression.

Results
GBM EVs interact with both T cells and monocytes but do not directly inhibit T-cell activation. However, GBM EVs induce immunosuppressive monocytes, including myeloid-derived suppressor cells (MDSCs) and nonclassical monocytes (NCMs). MDSCs and NCMs inhibit T-cell proliferation in vitro and are found within GBM in situ. EV PD-L1 expression induces NCMs but not MDSCs, and does not affect EV-conditioned monocytes T-cell inhibition.

Conclusion
These findings indicate that GBM EV-mediated immunosuppression occurs through induction of immunosuppressive monocytes rather than direct T-cell inhibition and that, while PD-L1 expression is important for the induction of specific immunosuppressive monocyte populations, immunosuppressive signaling mechanisms through EVs are complex and not limited to PD-L1.
Neurosurgical Randomized Trials in Low- and Middle-Income Countries
Authors: Griswold Dylan P , Khan Ahsan A , Chao Tiffany E , Clark David J , Budohoski Karol , Devi B Indira , Azad Tej D , Grant Gerald A , Trivedi Rikin A , Rubiano Andres M , Johnson Walter D , Park Kee B , Broekman Marike , Servadei Franco , Hutchinson Peter J , Kolias Angelos G 
Published: February 2020

Abstract

BACKGROUND
The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before.

OBJECTIVE
To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs.

METHODS
From January 2003 to July 2016, English-language trials with >5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method.

RESULTS
A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively.

CONCLUSION
We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated.
Eosinophilic gastroenteritis: epidemiology, diagnosis, and treatment
Authors: Kinoshita Yoshikazu , Ishihara Shunji 
Published: February 2020

Purpose of review
Although several reviews concerning diagnosis and treatment of eosinophilic esophagitis (EoE) have been presented, there are few in regard to eosinophilic gastroenteritis (EGE). Fortunately, findings related to epidemiology, as well as diagnosis and treatment of this disease have recently been increasing.

Recent findings
The rates of incidence of both EoE and EGE have been reported to be increasing. For accurate diagnosis, plasma concentrations of thymic stromal lymphopoietin and IL-33 may be useful as biomarkers, though consensus has not been reached, while increased eosinophil infiltration in gastrointestinal tissue remains a critical factor. Topical glucocorticoid administration, an elimination diet, and molecular target therapy with neutralizing antibodies are potentially effective therapies that have recently been evaluated.

Summary
As seen with other allergic diseases, EGE seems to be increasing. Several research projects regarding diagnosis and treatment of the disease are currently in progress.
Limitations of the UNAIDS 90-90-90 metrics: a simulation-based comparison of cross-sectional and longitudinal metrics for the HIV care continuum
Authors: Haber Noah A. , Lesko Catherine R. , Fox Matthew P. , Powers Kimberly A. , Harling Guy , Edwards Jessie K. , Salomon Joshua A. , Lippman Sheri A. , Bor Jacob , Chang Angela Y. , Anglemyer Andrew , Pettifor Audrey 
Published: February 2020

Objectives:
The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 and other cross-sectional metrics can lead to potentially counterintuitive conclusions when used to evaluate health systems’ performance. This study demonstrates how time and population dynamics impact UNAIDS 90–90–90 metrics in comparison with a longitudinal analogue.

Design:
A simplified simulation representing a hypothetical population was used to estimate and compare inference from UNAIDS 90–90–90 metrics and longitudinal metrics based on Kaplan–Meier-estimated 2-year probability of transition between stages.

Methods:
We simulated a large cohort over 15 years. Everyone started out at risk for HIV, and then transitioned through the HIV care continuum based on fixed daily probabilities of acquiring HIV, learning status, entering care, initiating antiretroviral therapy (ART), and becoming virally suppressed, or dying. We varied the probability of ART initiation over three five-year periods (low, high, and low). We repeated the simulation with an increased probability of death.

Results:
The cross-sectional probability of being on ART among persons who were diagnosed responded relatively slowly to changes in the rate of ART initiation. Increases in ART initiation rates caused apparent declines in the cross-sectional probability of being virally suppressed among persons who had initiated ART, despite no changes in the rate of viral suppression. In some cases, higher mortality resulted in the cross-sectional metrics implying improved healthcare system performance. The longitudinal continuum was robust to these issues.

Conclusion:
The UNAIDS 90–90–90 care continuum may lead to incorrect inference when used to evaluate health systems performance. We recommend that evaluation of HIV care delivery include longitudinal care continuum metrics wherever possible.
HIV influences microtubule associated protein-2: potential marker of HIV-associated neurocognitive disorders
Authors: Avdoshina Valeria , Mahoney Matthew , Gilmore Sean F. , Wenzel Erin D. , Anderson Albert , Letendre Scott L. , Imamichi Tomozumi , Fischer Nicholas O. , Mocchetti Italo 
Published: February 2020

Objective:
Postmortem brains of patients diagnosed with HIV-1-associated neurocognitive disorders (HAND) exhibit loss of dendrites. However, the mechanisms by which synapses are damaged are not fully understood.

Design:
Dendrite length and remodeling occurs via microtubules, the dynamics of which are regulated by microtubule-binding proteins, including microtubule-associated protein 2 (MAP2). The HIV protein gp120 is neurotoxic and interferes with neuronal microtubules. We measured MAP2 concentrations in human cerebrospinal fluid (CSF) and MAP2 immunoreactivity in rat cortical neurons exposed to HIV and gp120.

Methods:
First, we examined whether HIV affects MAP2 levels by analyzing the CSF of 27 persons living with HIV (PLH) whose neurocognitive performance had been characterized. We then used rat cortical neurons to study the mechanisms of HIV-mediated dendritic loss.

Results:
PLH who had HAND had greater MAP2 concentrations within the CSF than cognitive normal PLH. In cortical neurons, the deleterious effect of HIV on MAP2-positive dendrites occurred through a gp120-mediated mechanism. The neurotoxic effect of HIV was blocked by a CCR5 antagonist and prevented by Helix-A, a peptide that displaces gp120 from binding to microtubules, conjugated to a nanolipoprotein particle delivery platform.

Conclusion:
Our findings support that HIV at least partially effects its neurotoxicity via neuronal cytoskeleton modifications and provide evidence of a new therapeutic compound that could be used to prevent the HIV-associated neuropathology.
Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses
Authors: Jaimes Javier A. , André Nicole M. , Millet Jean K. , Whittaker Gary R. 
Published: February 2020

AbstractThe 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.
Model Reduction Tools For Phenomenological Modeling of Input-Controlled Biological Circuits
Authors: Pandey Ayush , Murray Richard M. 
Published: February 2020

AbstractWe present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits from descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assumptions of time-scale separation, conservation laws, and species’ abundance to obtain the reduced models that can be used for design of synthetic biological circuits. We consider an example of a simple gene expression circuit and another example of a layered genetic feedback control circuit to demonstrate the use of the model reduction procedure.
The effects of microcystin-LR inOryza sativaroot cells: F-actin as a new target of cyanobacterial toxicity
Authors: Pappas D. , Gkelis S. , Panteris E. 
Published: February 2020

ABSTRACTMicrocystins are toxins produced by cyanobacteria, notorious for negatively affecting a wide range of living organisms, among which several plant species. Although microtubules are a well-established target of microcystin toxicity, its effect on filamentous actin (F-actin) in plant cells has not been studied yet.The effects of microcystin-LR (MC-LR) and the extract of a microcystin-producing freshwater cyanobacterial strain (Microcystis flos-aquaeTAU-MAC 1510) on the cytoskeleton (F-actin and microtubules) ofOryza sativa(rice) root cells, were studied by light, confocal, and transmission electron microscopy. Considering the role of F-actin in endomembrane system distribution, the endoplasmic reticulum and the Golgi apparatus in extract-treated cells were also examined.F-actin in both MC-LR- and extract-treated meristematic and differentiating root cells exhibited time-dependent alterations, ranging from disorientation and bundling to the formation of ring-like structures, eventually resulting to a collapse of the F-actin network at longer treatments. Disorganization and eventual depolymerization of microtubules, as well as abnormal chromatin condensation were observed following treatment with the extract, effects which could be attributed to microcystins and other bioactive compounds. Moreover, cell cycle progression was inhibited in extract-treated roots, specifically affecting the mitotic events. As a consequence of F-actin network disorganization, endoplasmic reticulum elements appeared stacked and diminished, while Golgi dictyosomes appeared aggregated.These results support that F-actin is a prominent target of MC-LR, both in pure form and as an extract ingredient. Endomembrane system alterations can also be attributed to the effects of cyanobacterial bioactive compounds (including microcystins) on F-actin cytoskeleton.
Learning polygenic scores for human blood cell traits
Authors: Xu Yu , Vuckovic Dragana , Ritchie Scott C , Akbari Parsa , Jiang Tao , Grealey Jason , Butterworth Adam S. , Ouwehand Willem H , Roberts David J , Di Angelantonio Emanuele , Danesh John , Soranzo Nicole , Inouye Michael 
Published: February 2020

AbstractPolygenic scores (PGSs) for blood cell traits can be constructed using summary statistics from genome-wide association studies. As the selection of variants and the modelling of their interactions in PGSs may be limited by univariate analysis, therefore, such a conventional method may yield sub-optional performance. This study evaluated the relative effectiveness of four machine learning and deep learning methods, as well as a univariate method, in the construction of PGSs for 26 blood cell traits, using data from UK Biobank (n=~400,000) and INTERVAL (n=~40,000). Our results showed that learning methods can improve PGSs construction for nearly every blood cell trait considered, with this superiority explained by the ability of machine learning methods to capture interactions among variants. This study also demonstrated that populations can be well stratified by the PGSs of these blood cell traits, even for traits that exhibit large differences between ages and sexes, suggesting potential for disease prevention. As our study found genetic correlations between the PGSs for blood cell traits and PGSs for several common human diseases (recapitulating well-known associations between the blood cell traits themselves and certain diseases), it suggests that blood cell traits may be indicators or/and mediators for a variety of common disorders via shared genetic variants and functional pathways.
When foreign brands appear local, and local brands appear foreign
Authors: Chen Bo 
Published: February 2020

PurposeBoth foreign and local companies frequently name their brands in foreign language on the market of developing countries, and some of them choose to disclose the brands' country of origin to consumers. The purpose of this research is to investigate the joint effects between the practices of disclosing the actual country of origin of the brands and the language of the brand names on consumers' purchase intention for foreign brands and local brands in developing countries.Design/methodology/approachThe proposed hypotheses were tested in two studies, namely an experiment and a field experimental survey, with stimuli from two product categories.FindingsThe results of the two empirical studies with Chinese participants consistently demonstrate that revealing the actual country of origin of the brands undermines consumers' purchase intention for local brands that use foreign brand names, but does not impact consumers' purchase intention for foreign brands that use local brand names.Originality/valueThis research first investigates the effects of adapting the brand names into local language of developing countries for brands from developed countries on consumers' purchase intention, which provides new insight into the literature on foreign branding and country of origin effects as well as practical implications for brand managers.