bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo
Authors: Yoo Ji Young , Swanner Jessica , Otani Yoshihiro , Nair Mitra , Park Flora , Banasavadi-Siddegowda Yeshavanth , Liu Joseph , Jaime-Ramirez Alena Cristina , Hong Bangxing , Geng Feng , Guo Deliang , Bystry Darlene , Phelphs Mitch , Quadri Haroon , Lee Tae Jin , Kaur Balveen 
Published: April 2019

AbstractBackgroundHyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation. Here we investigated the effect of blocking MEK signaling in conjunction with oncolytic HSV-1 (oHSV) for brain tumors.MethodsInfected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. Enzyme-linked immunosorbent assay, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. Pharmacokinetic (PK) analysis of mouse plasma and brain tissue was used to evaluate trametinib delivery to the CNS. Intracranial human and mouse glioma-bearing immune deficient and immune competent mice were used to evaluate the antitumor efficacy.ResultOncolytic HSV treatment rescued trametinib-mediated feedback reactivation of the mitogen-activated protein kinase signaling pathway in glioma. In vivo, PK analysis revealed enhanced blood–brain barrier penetration of trametinib after oHSV treatment. Treatment by trametinib, a MEK kinase inhibitor, led to a significant reduction in microglia- and macrophage-derived tumor necrosis factor alpha (TNFα) secretion in response to oHSV treatment and increased survival of glioma-bearing mice. Despite the reduced TNFα production observed in vivo, the combination treatment activated CD8+ T-cell mediated immunity and increased survival in a glioma-bearing immune-competent mouse model.ConclusionThis study provides a rationale for combining oHSV with trametinib for the treatment of brain tumors.
Model Choice, Missing Data, and Taxon Sampling Impact Phylogenomic Inference of Deep Basidiomycota Relationships
Authors: Prasanna Arun N , Gerber Daniel , Kijpornyongpan Teeratas , Aime M Catherine , Doyle Vinson P , Nagy Laszlo G 
Published: April 2019

AbstractResolving deep divergences in the tree of life is challenging even for analyses of genome-scale phylogenetic data sets. Relationships between Basidiomycota subphyla, the rusts and allies (Pucciniomycotina), smuts and allies (Ustilaginomycotina), and mushroom-forming fungi and allies (Agaricomycotina) were found particularly recalcitrant both to traditional multigene and genome-scale phylogenetics. Here, we address basal Basidiomycota relationships using concatenated and gene tree-based analyses of various phylogenomic data sets to examine the contribution of several potential sources of bias. We evaluate the contribution of biological causes (hard polytomy, incomplete lineage sorting) versus unmodeled evolutionary processes and factors that exacerbate their effects (e.g., fast-evolving sites and long-branch taxa) to inferences of basal Basidiomycota relationships. Bayesian Markov Chain Monte Carlo and likelihood mapping analyses reject the hard polytomy with confidence. In concatenated analyses, fast-evolving sites and oversimplified models of amino acid substitution favored the grouping of smuts with mushroom-forming fungi, often leading to maximal bootstrap support in both concatenation and coalescent analyses. On the contrary, the most conserved data subsets grouped rusts and allies with mushroom-forming fungi, although this relationship proved labile, sensitive to model choice, to different data subsets and to missing data. Excluding putative long-branch taxa, genes with high proportions of missing data and/or with strong signal failed to reveal a consistent trend toward one or the other topology, suggesting that additional sources of conflict are at play. While concatenated analyses yielded strong but conflicting support, individual gene trees mostly provided poor support for any resolution of rusts, smuts, and mushroom-forming fungi, suggesting that the true Basidiomycota tree might be in a part of tree space that is difficult to access using both concatenation and gene tree-based approaches. Inference-based assessments of absolute model fit strongly reject best-fit models for the vast majority of genes, indicating a poor fit of even the most commonly used models. While this is consistent with previous assessments of site-homogenous models of amino acid evolution, this does not appear to be the sole source of confounding signal. Our analyses suggest that topologies uniting smuts with mushroom-forming fungi can arise as a result of inappropriate modeling of amino acid sites that might be prone to systematic bias. We speculate that improved models of sequence evolution could shed more light on basal splits in the Basidiomycota, which, for now, remain unresolved despite the use of whole genome data.
I English Language
Authors: Kostadinova Viktorija , Yáñez-Bouza Nuria , Dreschler Gea , Gregersen Sune , Gyuris Beáta , Allan Kathryn , Scott Maggie , Anderwald Lieselotte , Leuckert Sven , Kraš Tihana , Cogo Alessia , Gan Tian , Parise Ida , Ting Shawnea Sum Pok , Souza Da Silva Juliana , Hansen Beke , Norledge Jessica 
Published: April 2019

Abstract
This chapter has fourteen sections: 1. General; 2. History of English Linguistics; 3. Phonetics and Phonology (not covered this year); 4. Morphology; 5. Syntax; 6. Semantics; 7. Lexicography, Lexicology, and Lexical Semantics; 8. Onomastics; 9. Dialectology and Sociolinguistics; 10. New Englishes and Creolistics; 11. Second Language Acquisition. 12. English as a Lingua Franca; 13. Pragmatics and Discourse. 14. Stylistics. Section 1 is by Viktorija Kostadinova; section 2 is by Nuria Yáñez-Bouza; sections 4 and 5 are by Gea Dreschler and Sune Gregersen; section 6 is by Beáta Gyuris; section 7 is by Kathryn Allan; section 8 is by Maggie Scott; section 9 is by Lieselotte Anderwald; section 10 is by Sven Leuckert; section 11 is by Tihana Kraš; section 12 is by Tian Gan, Ida Parise, Sum Pok Ting, Juliana Souza da Silva and Alessia Cogo; section 13 is by Beke Hansen; section 14 is by Jessica Norledge.
Exploring Validity Evidence Associated With Questionnaire-Based Tools for Assessing the Professional Performance of Physicians: A Systematic Review
Authors: van der Meulen Mirja W. , Smirnova Alina , Heeneman Sylvia , oude Egbrink Mirjam G.A. , van der Vleuten Cees P.M. , Lombarts Kiki M.J.M.H. 
Published: April 2019

Purpose
To collect and examine—using an argument-based validity approach—validity evidence of questionnaire-based tools used to assess physicians’ clinical, teaching, and research performance.

Method
In October 2016, the authors conducted a systematic search of the literature seeking articles about questionnaire-based tools for assessing physicians’ professional performance published from inception to October 2016. They included studies reporting on the validity evidence of tools used to assess physicians’ clinical, teaching, and research performance. Using Kane’s validity framework, they conducted data extraction based on four inferences in the validity argument: scoring, generalization, extrapolation, and implications.

Results
They included 46 articles on 15 tools assessing clinical performance and 72 articles on 38 tools assessing teaching performance. They found no studies on research performance tools. Only 12 of the tools (23%) gathered evidence on all four components of Kane’s validity argument. Validity evidence focused mostly on generalization and extrapolation inferences. Scoring evidence showed mixed results. Evidence on implications was generally missing.

Conclusions
Based on the argument-based approach to validity, not all questionnaire-based tools seem to support their intended use. Evidence concerning implications of questionnaire-based tools is mostly lacking, thus weakening the argument to use these tools for formative and, especially, for summative assessments of physicians’ clinical and teaching performance. More research on implications is needed to strengthen the argument and to provide support for decisions based on these tools, particularly for high-stakes, summative decisions. To meaningfully assess academic physicians in their tripartite role as doctor, teacher, and researcher, additional assessment tools are needed.
Preliminary Evidence of a Dose-Response for Continuing to Play on Recovery Time After Concussion
Authors: Charek Daniel B. , Elbin R. J. , Sufrinko Alicia , Schatz Philip , D'Amico Nathan R. , Collins Michael W. , Kontos Anthony P. 
Published: April 2019

Objective:
To investigate a dose-response relationship between continuing to play following concussion and outcomes.

Participants:
A total of 130 athletes (age 11-19 years).

Design:
Repeated-measures design comparing symptoms, neurocognitive performance, and recovery time between 52 athletes immediately removed from play (Removed), 24 who continued to play for 15 minutes or less (Short-Play), and 32 who continued to play for more than 15 minutes (Long-Play).

Main Measures:
Recovery was the number of days from injury to clearance. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) measured neurocognitive outcomes and the Post-Concussion Symptom Scale (PCSS) measured symptom severity.

Results:
Long-Play (44.09 ± 27.01 days) took longer to recover than Short-Play (28.42±12.74 days) and Removed (18.98 ± 13.76 days). Short-Play was 5.43 times more likely, and Long-Play 11.76 times more likely, to experience protracted recovery relative to Removed. Both Play groups had worse neurocognitive performance and higher symptom scores than Removed at days 1 to 7, with Long-Play demonstrating worse reaction time than Short-Play. At days 8 to 30, both Play groups performed worse than Removed on visual memory and visual motor speed, while only Long-Play performed worse on verbal memory and reaction time.

Conclusions:
Results provide initial evidence of a dose-response effect for continuing to play on recovery from concussion, highlighting the importance of removal from play.
Elevated Tau in Military Personnel Relates to Chronic Symptoms Following Traumatic Brain Injury
Authors: Pattinson Cassandra L. , Shahim Pashtun , Taylor Patricia , Dunbar Kerri , Guedes Vivian A. , Motamedi Vida , Lai Chen , Devoto Christina , Peyer Jordan , Roy Michael J. , Gill Jessica M. 
Published: April 2019

Objective:To understand the relationships between traumatic brain injury (TBI), blood biomarkers, and symptoms of posttraumatic stress disorder (PTSD), depression, and postconcussive syndrome symptoms.Design:Cross-sectional cohort study using multivariate analyses.Participants:One hundred nine military personnel and veterans, both with and without a history of TBI.Main Measures:PTSD Checklist–Civilian Version (PCL-C); Neurobehavioral Symptom Inventory (NSI); Ohio State University TBI Identification Method; Patient Health Questionnaire-9 (PHQ-9); Simoa-measured concentrations of tau, amyloid-beta (Aβ) 40, Aβ42, and neurofilament light (NFL).Results:Controlling for age, sex, time since last injury (TSLI), and antianxiety/depression medication use, NFL was trending toward being significantly elevated in participants who had sustained 3 or more TBIs compared with those who had sustained 1 or 2 TBIs. Within the TBI group, partial correlations that controlled for age, sex, TSLI, and antianxiety/depression medication use showed that tau concentrations were significantly correlated with greater symptom severity, as measured with the NSI, PCL, and PHQ-9.Conclusions:Elevations in tau are associated with symptom severity after TBI, while NFL levels are elevated in those with a history of repetitive TBIs and in military personnel and veterans. This study shows the utility of measuring biomarkers chronically postinjury. Furthermore, there is a critical need for studies of biomarkers longitudinally following TBI.
Lifetime History of Traumatic Brain Injury and Behavioral Health Problems in a Population-Based Sample
Authors: Bogner Jennifer , Corrigan John D. , Yi Honggang , Singichetti Bhavna , Manchester Kara , Huang Lihong , Yang Jingzhen 
Published: April 2019

Objective:
To investigate the relationships between indices of lifetime history of traumatic brain injury (TBI) exposure and measures of behavioral health status among Ohioans.

Participants:
A random sample (n = 6996) of Ohioans contacted to complete the 2014 Ohio Behavioral Risk Factors Surveillance System (BRFSS).

Design:
A cross-sectional survey.

Main measures:
The Ohio State University TBI Identification Method adapted for BRFSS module and BRFSS behavioral indicators.

Results:
After demographic adjustment, lifetime history of TBI was found to be associated with increased odds of binge drinking, heavy drinking, smoking, a depressive disorder, or mental health not being good (≥2 days and ≥14 days in last 30 days). Mixed findings across behavioral indicators were observed in regard to number and severity of injury. Age at first injury showed no remarkable associations with the behavioral health indicators.

Conclusions:
Ohioans who have sustained at least one TBI with loss of consciousness in their lifetime are at increased risk for poor behavioral health, including alcohol misuse, smoking, and depression. The findings underscore the need for community-based mental health treatment programs to screen for TBI history in their intake evaluations, and to train clinicians on the provisions of accommodations for cognitive and behavioral deficits.
Characteristics of Corneal Biomechanics in Chinese Preschool Children With Different Refractive Status
Authors: Long Wen , Zhao Yiming , Hu Yin , Li Zhouyue , Zhang Xiaoxiao , Zhao Wenchen , Yang Xiao , Cui Dongmei , Trier Klaus 
Published: April 2019

Purpose:
To investigate the characteristics of corneal biomechanics in Chinese preschool children with different refractive status.

Methods:
Study participants were 108 Chinese children (216 eyes) aged 4 to 6 years with a spherical equivalent refraction between −9.00 and +9.00 diopters (D). Cycloplegic refraction was measured using an autorefractor, axial length using an IOL Master (Zeiss, Oberkochen, Germany), and corneal biomechanical metrics and corneal power using an ultra-high-speed camera (Corvis ST; Oculus, Wetzlar, Germany) and Pentacam (Oculus; Menlo Park, CA). Differences in corneal biometry and biomechanical characteristics among myopia, emmetropia, and hyperopia eyes were analyzed by SPSS 17.0.

Results:
The spherical equivalent refraction was significantly positively correlated with the stiffness parameter at the first applanation (SP-A1, r = 0.22, P < 0.01) and corneal velocity at the second applanation (A2 velocity, r = 0.25, P < 0.001), whereas it was negatively correlated with the peak distance (r = −0.32, P < 0.001) and deformation amplitude ratio (DA ratio, r = −0.34, P < 0.001). In the hyperopia, emmetropia, and myopia groups, the SP-A1 successively decreased (108.70 ± 22.93 vs. 100.50 ± 18.98 vs. 97.97 ± 18.91, P < 0.01), whereas the peak distance progressively increased (4.39 ± 0.32 vs. 4.56 ± 0.30 vs. 4.63 ± 0.34 mm, P < 0.001). In the same order of groups, an increasing trend was found for the axial length (21.11 ± 0.76 vs. 22.39 ± 0.72 vs. 24.09 ± 1.37 mm, P < 0.001), central anterior chamber depth (CACD, 3.04 ± 0.41 vs. 3.21 ± 0.33 vs. 3.37 ± 0.40 mm, P < 0.001) and flat meridian keratometry (K1, 41.92 ± 1.59 vs. 42.73 ± 1.39 vs. 42.98 ± 1.60 D, P < 0.001). Central corneal thickness significantly decreased in the same order of groups (565.46 ± 33.22 vs. 551.97 ± 24.66 vs. 543.36 ± 37.74 µm, P < 0.001).

Conclusions:
Corneal stiffness is reduced in myopia and increased in hyperopia compared with emmetropia in children aged 4 to 6 years. Corneal biometry and biomechanical characteristics in preschool children seem to depend on refractive status.
Perioperative Corneal Abrasions After Nonocular Surgery: A Systematic Review
Authors: Papp Alexandra M. , Justin Grant A. , Vernau Christian T. , Aden James K. , Fitzgerald Brian M. , Kraus Gregory P. , Legault Gary L. 
Published: April 2019

Purpose:
To perform a systematic review of the international literature evaluating the risk factors, preventative steps, and treatments for perioperative corneal injuries for nonocular surgery.

Methods:
PubMed, Embase, and Evidence-Based Medicine Reviews databases were searched on April 13, 2018. Two hundred four articles were identified with 16 meeting the inclusion criteria. All studies were evaluated for quality and level of evidence. Two types of studies were included. The first were primary epidemiological studies that looked at the rates of perioperative corneal injuries after nonocular surgery and the second were trials that either studied preventative steps or treatments.

Results:
A statistical analysis was completed to reveal trends in perioperative corneal abrasions. Rates ranged from 0.01% to 59% with a cumulative rate of 0.64% (95% confidence interval 0.36%–1.35%). Primary risk factors were identified as longer procedures, general anesthesia, and advanced age. The most commonly associated ocular injuries were found to include chemical injury, conjunctivitis, blurred vision, and conjunctival congestion. Treatment strategies for corneal abrasion in the literature recommended erythromycin ointment and ample ocular lubrication for the fastest recovery. Education interventions alone, as studied in 2 of the 16 articles, demonstrated a significant decrease in the rate of corneal abrasions.

Conclusions:
Standardized ocular protection, reporting, and education initiatives were found to maximally decrease rates of perioperative corneal abrasions after nonocular surgery. However, no gold standard currently exists for intraoperative ocular protection. More research needs to be conducted on specific prevention strategies and content of educational initiatives in hopes of standard development across facilities nationwide.
Trends in Research Related to Keratoconus From 2009 to 2018: A Bibliometric and Knowledge Mapping Analysis
Authors: Zhao Fangkun , Du Fengkun , Zhang Jinsong , Xu Jun 
Published: April 2019

Purpose:
To map the publication trends in and explore hotspots of keratoconus research.

Methods:
A bibliometric analysis based on the Web of Science Core Collection was conducted to investigate the publication trends in research related to keratoconus. The records extracted were analyzed, and a knowledge map was constructed using VOSviewer v.1.6.10 to visualize the annual publication number, distribution of countries, international collaborations, author productivity, source journals, intellectual base, and research hotspots in the field of keratoconus.

Results:
In total, 3194 peer-reviewed publications on keratoconus published between 2009 and 2018 were retrieved, and the annual research output increased with time. The United States ranked the highest among the countries with the most publications, and Tehran University of Medical Sciences was the most active institution. JL Alio contributed to the most number of publications on keratoconus, and Cornea was the most prolific journal publishing keratoconus research. The top cited references mainly focused on corneal collagen cross-linking. The keywords formed 6 clusters: 1) pathogenesis of keratoconus, 2) corneal collagen cross-linking, 3) management for early-stage keratoconus, 4) corneal parameter measurement, 5) surgical treatment of keratoconus, and 6) corneal biomechanics-related research.

Conclusions:
On the basis of the data extracted from the Web of Science Core Collection, the quantity and quality of publications on keratoconus were assessed using bibliometric techniques. The cited references and research hotspots could provide insights into keratoconus research as well as valuable information to cornea specialists for performing research in this field and discovering potential collaborators.
Lack of Efficacy of Lactobacillus reuteri DSM 17938 for the Treatment of Acute Gastroenteritis: A Randomized Controlled Trial
Authors: Szymański Henryk , Szajewska Hania 
Published: April 2019

Objective:
To assess the efficacy of Lactobacillus reuteri DSM 17938 (L. reuteri) for the treatment of acute gastroenteritis in children.

Study design:
Children younger than 5 years with acute diarrhea, defined as a change in stool consistency to a loose or liquid form and/or an increase in the frequency of evacuations (≥3 in 24 hours), lasting for no longer than 5 days, were eligible for inclusion. Participants (n = 100) were recruited from the pediatrics department of a Polish hospital and randomly assigned to receive L. reuteri in a dose 2 × 108 colony-forming units or placebo, for 5 days, in addition to standard rehydration therapy. The primary outcome measure was duration of diarrhea.

Results:
Ninety-one of the 100 children randomized were included in the intention-to-treat analysis (L. reuteri n = 44; placebo n = 47). The duration of diarrhea after randomization in both groups was similar (P = 0.6). The groups were also similar with respect to all secondary outcome measures, with one exception. Compared with the placebo group, patients in the L. reuteri group had a shorter duration of hospitalization (P = 0.048). Adverse events were similar in both groups.

Conclusions:
Among children with acute gastroenteritis who were younger than 5 years of age, L. reuteri compared with placebo, as an adjunct to rehydration therapy, did not reduce the duration of diarrhea; however, it reduced the duration of hospitalization.
Sex differences in the temporal development of pronociceptive immune responses in the tibia fracture mouse model
Authors: Guo Tian-Zhi , Shi Xiaoyou , Li Wen-Wu , Wei Tzuping , Clark J. David , Kingery Wade S. 
Published: April 2019

Abstract
Previously, distinct sex differences were observed in the pronociceptive role of spinal immune cells in neuropathic and inflammatory mouse pain models. Both peripheral and central innate and adaptive immune changes contribute to sensitization in the tibia fracture rodent model of complex regional pain syndrome, and the current study evaluated sex differences in the development of pronociceptive immune responses after fracture. At 4 and 7 weeks after fracture, the analgesic effects of a microglia inhibitor were tested in male and female mice, and polymerase chain reaction was used to measure inflammatory mediator expression in skin and spinal cord. The temporal progression of complex regional pain syndrome–like changes in male and female wild-type and muMT fracture mice lacking B cells and antibodies were evaluated, and IgM antibody deposition measured. Pronociceptive effects of injecting wild-type fracture mouse serum into muMT fracture mice were also tested in both sexes, and the role of sex hormones was evaluated in the postfracture development of pronociceptive immune responses. Long-lasting immune changes developed in the fracture limb and corresponding spinal cord of both male and female mice, including upregulated neuropeptide and cytokine signaling, microglial activation, and pronociceptive autoimmunity. These complex postfracture immune responses were sexually dichotomous and interacted in temporally evolving patterns that generated post-traumatic nociceptive sensitization in both sexes lasting for up to 5 months. Unfortunately, the redundancy and plasticity of these chronic post-traumatic immune responses suggest that clinical interventions focusing on any single specific pronociceptive immune change are likely to be ineffectual.