bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and property of short tungsten fibre/Zr-based metallic glass composite
Authors: Zhang Bo , Fu Huameng , Zhang Haifeng , Mu Juan , Wang Mingna
Published: June 2019

The short tungsten fibre reinforced Zr41.2Ti13.8Ni10.0Cu12.5Be22.5 bulk metallic glass composites with macroscopic isotropic mechanical properties were prepared by infiltration and rapid solidification. The diameters of the tungsten fibres are 300, 500 and 700 µm with a length of 1000 µm and the fibre volume fraction in three kinds of composites is between 60 and 65%. The room temperature compressive deformation behaviours of these composites were investigated systematically. The results show that the strength and plasticity of the composites increase with the decrease in the tungsten fibre diameter. The maximum compressive strength and plastic strain of the composite with 300 µm fibre, respectively, reach 3079 MPa and 37%. The fracture modes of all the composites are shear fracture. The superior compressive property of the composites with short tungsten fibre is due to the competition among different fracture modes and the inhibition effect of the interface on the shear band extension.
A specific isoform of Pyd/ZO-1 mediates junctional remodeling and formation of slit diaphragms
Authors: Carrasco-Rando Marta , Prieto-Sánchez Silvia , Culi Joaquim , Tutor Antonio S. , Ruiz-Gómez Mar
Published: June 2019

The podocyte slit diaphragm (SD), responsible for blood filtration in vertebrates, is a major target of injury in chronic kidney disease. The damage includes severe morphological changes with destabilization of SDs and their replacement by junctional complexes between abnormally broadened foot processes. In Drosophila melanogaster, SDs are present in nephrocytes, which filter the fly's hemolymph. Here, we show that a specific isoform of Polychaetoid/ZO-1, Pyd-P, is essential for Drosophila SDs, since, in pyd mutants devoid of Pyd-P, SDs do not form and the SD component Dumbfounded accumulates at ectopic septate-like junctions between abnormally aggregated nephrocytes. Reintroduction of Pyd-P leads to junctional remodeling and their progressive normalization toward SDs. This transition requires the coiled-coil domain of Pyd-P and implies formation of nonclathrin vesicles containing SD components and their trafficking to the nephrocyte external membrane, where SDs assemble. Analyses in zebrafish suggest a conserved role for Tjp1a/ZO-1 in promoting junctional remodeling in podocytes.
Reply to “Phosphorylation of G3BP1-S149 does not influence stress granule assembly”
Authors: Tourrière Hélène , Tazi Jamal
Published: June 2019

In this issue, Panas et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201801214) challenge the data published in the Tourrière et al. (2003. J. Cell Biol. https://doi.org/10.1083/jcb.200212128) paper on the role of G3BP phosphorylation in stress granule (SG) assembly. This reply addresses that letter and suggests that more work is needed to understand the role of this modification in SG formation.
Otoplasty Using the Combined Mustardé-Furnas Technique: Satisfaction and Objective Results
Authors: García-Purriños Francisco , Raposo Alberto , Guilllén Alberto , Calero Juan , Giribet Ana , Barrios Andrés
Published: June 2019

Background

To understand the level of satisfaction among patients undergoing otoplasty using the combined Mustardé-Furnas technique. To evaluate surgery outcomes using McDowell/Wright (MW) criteria.

Objectives

The authors sought to analyze any possible correlation between satisfaction level and surgery outcome.

Methods

The authors conducted a retrospective study on patients who underwent combined Mustardé and Furnas otoplasty between 1996 and 2016. All patients were assessed 12 months after surgery employing MW goals and satisfaction surveys.

Results

The study includes 172 patients who underwent 343 otoplasty procedures. There were 134 patients (77.9%) who had all 6 of the criteria for surgical success as defined by MW 12 months after surgery, reporting satisfaction levels of 9 to 10. Fifteen patients (9.3%) had 5 of the 6 MW criteria, reporting satisfaction levels of 9 to 10, and 22 patients (12.79%) had only 4 MW objectives and reported satisfaction levels of 7 to 10. The Spearman rho coefficient was 0.545 and the Kendall coefficient was 0.375, with a statistically significant association (P < 0.001).

Conclusions

Patient satisfaction increases as the number of MW goals are met, although the correlation is moderate to low. Patients perceive the results of the surgery as satisfactory or very satisfactory, even when ENT surgeons consider outcomes to be poor according to MW criteria.

Level of Evidence: 4
RERconverge: an R package for associating evolutionary rates with convergent traits
Authors: Kowalczyk Amanda , Meyer Wynn K , Partha Raghavendran , Mao Weiguang , Clark Nathan L , Chikina Maria
Published: June 2019

Motivation

When different lineages of organisms independently adapt to similar environments, selection often acts repeatedly upon the same genes, leading to signatures of convergent evolutionary rate shifts at these genes. With the increasing availability of genome sequences for organisms displaying a variety of convergent traits, the ability to identify genes with such convergent rate signatures would enable new insights into the molecular basis of these traits.

Results

Here we present the R package RERconverge, which tests for association between relative evolutionary rates of genes and the evolution of traits across a phylogeny. RERconverge can perform associations with binary and continuous traits, and it contains tools for visualization and enrichment analyses of association results.

Availability and implementation

RERconverge source code, documentation and a detailed usage walk-through are freely available at https://github.com/nclark-lab/RERconverge. Datasets for mammals, Drosophila and yeast are available at https://bit.ly/2J2QBnj.

Supplementary information

Supplementary data are available at Bioinformatics online.
Hepatitis B virus X protein enhances the development of liver fibrosis and the expression of genes associated with epithelial-mesenchymal transitions and tumor progenitor cells
Authors: Ahodantin James , Lekbaby Bouchra , Bou Nader Myriam , Soussan Patrick , Kremsdorf Dina
Published: June 2019

The hepatitis B virus X protein (HBx) has pleiotropic biological effects, which underlies its potential role in cell transformation. However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic for the full-length HBx (FL-HBx) were used. To create liver fibrosis, FL-HBx transgenic and control mice were chronically exposed to carbon tetrachloride (CCl4). Modulation of the expression of proteins involved in matrix remodeling, hepatic metabolism and epithelial-mesenchymal transition (EMT) were investigated. In transgenic mice, FL-HBx expression potentiates CCl4-induced liver fibrosis with increased expression of proteins involved in matrix remodeling (Collagen1a, α-Sma, PdgfR-β, MMP-13). In FL-HBx transgenic mice, an increase in EMT was observed with a higher transcription of two inflammatory cytokines (TNF-α and TGF-β) and a decrease of glutamine synthetase expression level. This was associated with a sustained cell cycle and hepatocyte polyploidy alteration consistent with p38 and ERK1/2 overactivation, increase of PLK1 transcription, accumulation of SQSTM1/p62 protein and increase expression of Beclin-1. This correlates with a higher expression of tumor progenitor cell markers (AFP, Ly6D and EpCam), indicating a higher risk of progression from fibrosis to hepatocellular carcinoma (HCC) in the presence of FL-HBx protein. In conclusion, our results show that FL-HBx protein enhances the development of liver fibrosis and contributes to the progression of liver disease from chronic hepatitis to HCC.
Liquid chromatography tandem mass spectrometry for the quantification of steroid hormone profiles in blubber from stranded humpback whales (Megaptera novaeangliae)
Authors: Dalle Luche Greta , Bengtson Nash Susan , Kucklick John R , Mingramm Fletcher M J , Boggs Ashley S P
Published: June 2019

Marine mammal blubber is known to have quantifiable concentrations of steroid hormones and is increasingly chosen as a matrix for the detection of these reproductive and stress biomarkers. Steroid hormones act through complex cascades, often in concert, yet studies conducted on cetaceans have rarely measured more than two steroids simultaneously. Due to the role of steroid hormones in multiple physiological processes, and variability in concentration among individuals, data on single compounds are often difficult to interpret. Here a liquid chromatography tandem mass spectrometry method for the simultaneous analyses of multiple steroid hormones in cetacean blubber was validated and applied to samples from 10 stranded humpback whales (Megaptera novaeangliae). Progesterone, 17α-hydroxyprogesterone, testosterone, androstenedione, oestrone, oestradiol, cortisone, cortisol, corticosterone and 11-deoxycorticosterone were reliably (relative standard deviation on six replicates <15%) and accurately (recovery of an amended sample between 70% and 120%) quantified, but not 11-deoxycortisol. With the exception of progesterone, testosterone, oestradiol and cortisol, these compounds were quantified for the first time in humpback whales. Given that blubber is frequently collected from free-swimming cetaceans in ongoing research programs, the technique developed here could substantially strengthen understanding and monitoring of the physiological condition of these species.
Self-reported Vision Impairment and Subjective Well-being in Older Adults: A Longitudinal Mediation Analysis
Authors: Xiang Xiaoling , Freedman Vicki A , Shah Khushali , Hu Rita X , Stagg Brian C , Ehrlich Joshua R
Published: June 2019

Background

Vision impairment (VI) in older adults is associated with declines in well-being. However, the pathways through which poor vision leads to declines in well-being have not been well-described. The purpose of this study was to determine whether activity limitations and social participation restrictions mediate the impact of self-reported VI on subjective well-being.

Methods

The National Health and Aging Trends Study (NHATS) is a nationally representative longitudinal study of Medicare beneficiaries 65 and older that includes detailed measures of the disablement process. A longitudinal mediation model was conceptualized linking self-reported VI and subjective well-being. Structural equation modeling was used to test the mediating effects of activity limitations and social participation restrictions while adjusting for relevant covariates.

Results

The final sample included 5,431 respondents. At baseline, 8.0% of Medicare beneficiaries had self-reported VI. Subjective well-being scores were significantly lower among respondents with self-reported VI (15.7; 95% confidence interval [CI]: 15.2, 16.2) compared with those without VI (17.6; 95% CI: 17.5, 17.7). Self-reported VI had a significant indirect effect on subjective well-being through limiting mobility (β = −0.04; 95% CI: −0.07, −0.03) and household activities (β = −0.05; 95% CI: −0.08, −0.03), but not self-care limitations (β = 0.0; 95% CI = 0.0, 0.0) or participation restrictions (β = 0.0; 95% CI = −0.01, 0.00). Total indirect effects from all mediation paths accounted for 42% of the effect of VI on well-being.

Conclusions

Mobility and household activity limitations are significant mediators that explain a considerable portion of the impact of poor vision on well-being. Interventions to promote successful accommodation may result in greater overall well-being for older adults with poor vision.
A Coordinated Multi-study Analysis of the Longitudinal Association Between Handgrip Strength and Cognitive Function in Older Adults
Authors: Zammit Andrea R , Piccinin Andrea M , Duggan Emily C , Koval Andriy , Clouston Sean , Robitaille Annie , Brown Cassandra L , Handschuh Philipp , Wu Chenkai , Jarry Valérie , Finkel Deborah , Graham Raquel B , Muniz-Terrera Graciela , Praetorius Björk Marcus , Bennett David , Deeg Dorly J , Johansson Boo , Katz Mindy J , Kaye Jeffrey , Lipton Richard B , Martin Mike , Pederson Nancy L , Spiro Avron , Zimprich Daniel , Hofer Scott M
Published: June 2019

Objective

Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis.

Methods

We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis.

Results

After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44–0.56). We also found a high level of heterogeneity in this association across studies.

Discussion

Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers.
An anti-RANKL treatment reduces muscle inflammation and dysfunction and strengthens bone in dystrophic mice
Authors: Hamoudi Dounia , Marcadet Laetitia , Piette Boulanger Antoine , Yagita Hideo , Bouredji Zineb , Argaw Anteneh , Frenette Jérôme
Published: June 2019

Duchenne muscular dystrophy (DMD) is the most severe form of muscular dystrophy which leads to progressive muscle degeneration and inflammation. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK), which are expressed in bone and skeletal and cardiac muscles, form a signaling network upstream from nuclear factor-kappa B (NF-κB). We thus hypothesized that prolonged silencing RANKL/RANK signaling would significantly improve DMD. We showed that RANK and RANKL protein levels were increased in the microenvironment of myofibers of 5-month-old utrophin haploinsufficient mdx (mdx/utrn+/−) mice and that a 4 mg/kg dose of anti-RANKL antibody every 3 d for 28 days is optimal and more effective than 1 mg/kg every 3 d for improving the ex vivo maximum specific force (sP0) of dystrophic EDL muscles from mdx/utrn+/− mice. This functional improvement was associated with a reduction in muscle edema, damage, and fibrosis and a marked reduction in serum CK levels. The anti-RANKL treatment inhibited the NF-κB pathway, increased the proportion of anti-inflammatory and non-cytotoxic M2 macrophages, and reduced the number of centrally-nucleated myofibers and the frequency of small myofibers, suggesting that anti-RANKL inhibits the cycle of degeneration/regeneration in dystrophic mice. A three-point bending test showed that a 28-d anti-RANKL treatment increases the mechanical properties of bone in mdx/utrn+/− dystrophic mice. In conclusion, the anti-RANKL treatment protected against skeletal muscle dysfunctions while enhancing bone mechanical properties, filling two needs with one deed in the context of muscular dystrophy.
Low ivermectin use among 5- to 6-year-old children: observations from door-to-door surveys in onchocerciasis-endemic regions in Africa
Authors: Siewe Fodjo J N , Mubiru F , Ukaga C , Logora M Y , Mmbando B P , Mandro M , Njamnshi A K , Colebunders R
Published: June 2019

During door-to-door surveys in onchocerciasis-endemic regions in Africa, the age-specific ivermectin coverage in 29 722 individuals was assessed. Children 5–6 y of age had significantly lower coverage compared with older participants. Insufficient ivermectin intake among young children could prolong onchocerciasis elimination prospects, as they may serve as human reservoirs of Onchocerca volvulus; moreover, it increases the risk of developing onchocerciasis-associated epilepsy (OAE). The causes of the low ivermectin coverage observed among children 5–6 y of age need to be explored. Integrating ivermectin distribution into chemoprophylaxis strategies for other neglected diseases could increase coverage in a cost-effective manner.
The association between specific sports activities and sport performance following hip arthroscopy for femoroacetabular impingement syndrome: A secondary analysis of a cross-sectional cohort study including 184 athletes
Authors: Ishøi Lasse , Thorborg Kristian , Kraemer Otto , Hölmich Per
Published: June 2019

The main purpose of this secondary analysis was to compare the proportion of athletes with moderate-to-extreme difficulties in eight specific sport activities in athletes with optimal versus impaired sport performance after a hip arthroscopy for femoroacetabular impingement syndrome. Subjects were identified in a nationwide registry and invited to answer a return to sport and performance questionnaire, and the Copenhagen Hip and Groin Outcome Score Sport subscale investigating difficulties in eight specific sports activities (HAGOS sport items) as; none, mild, moderate, severe or extreme. Subjects were divided into two groups based on sport performance (optimal or impaired). The proportion of athletes with none-to-mild versus moderate-to-extreme difficulties in the eight specific sport activities was compared between groups. The association between difficulties in sport activities and sport performance were investigated using logistic regression analysis. One hundred and eighty-four athletes (31 athletes with optimal and 153 athletes with impaired sport performance) were included at a mean follow-up of 33.1 ± 16.3 months. Up to six athletes (<20%) with optimal sport performance had moderate-to-extreme difficulties in sport activities. Contrary, 43–108 athletes (28.1–70.6%) with impaired performance had moderate-to-extreme difficulties in sport activities. Furthermore, moderate-to-extreme difficulties in HAGOS sport items: ‘running as fast as you can’ and ‘kicking, skating etc.’ increased the odds (14.7 and 6.1 times, respectively) of having impaired sport performance. Many athletes with impaired sport performance reported moderate-to-extreme difficulties in sport activities, specifically moderate-to-extreme difficulties in ‘running as fast as you can’ and ‘kicking, skating etc.’ were associated with patients having impaired sport performance.
In search for drought-tolerant soybean: is the slow-wilting phenotype more than just a curiosity?
Authors: Kunert Karl , Vorster Barend J
Published: June 2019

This article comments on:

Ye H, Song L, Schapaugh WT, Ali MDL, Sinclair TR, Riar MK, Raymond RN, Li Y, Vuong T, Valliyodan B, Neto PA, Klepadlo M, Song Q, Shannon JG, Chen P, Nguyen HT. 2019. The importance of slow canopy wilting in drought tolerance in soybean, Journal of Experimental Botany 71, 642–652.
Cooling of hypernuclear compact stars: Hartree–Fock models and high-density pairing
Authors: Raduta Adriana R , Li Jia Jie , Sedrakian Armen , Weber Fridolin
Published: June 2019

The thermal evolution of hypernuclear compact stars is studied for stellar models constructed on the basis of covariant density functional theory in Hartree and Hartree–Fock approximation. Parametrizations of both types are consistent with the astrophysical mass constraints on compact stars and available hypernuclear data. We discuss the differences of these density functionals and highlight the effects they have on the composition and on the cooling of hypernuclear stars. It is shown that hypernuclear stars computed with density functional models that have a low symmetry energy slope, L, are fairly consistent with the cooling data of observed compact stars. The class of stellar models based on larger L values gives rise to the direct Urca process at low densities, which leads to significantly faster cooling. We conjecture high-density pairing for protons and Λ’s in the P-wave channel and provide simple scaling arguments to obtain these gaps. As a consequence the most massive stellar models with masses 1.8 ≤ M/M⊙ ≤ 2 experience slower cooling by hyperonic dUrca processes which involve Λ’s and protons.
Prospective Observational Study Comparing Sepsis-2 and Sepsis-3 Definitions in Predicting Mortality in Critically Ill Patients
Authors: Poutsiaka Debra D , Porto Maura C , Perry Whitney A , Hudcova Jana , Tybor David J , Hadley Susan , Doron Shira , Reich John A , Snydman David R , Nasraway Stanley A
Published: June 2019

Background

Sepsis definitions have evolved, but there is a lack of consensus over adoption of the most recent definition, Sepsis-3. We sought to compare Sepsis-2 and Sepsis-3 in the classification of patients with sepsis and mortality risk at 30 days.

Methods

We used the following definitions: Sepsis-2 (≥2 systemic inflammatory response syndrome criteria + infection), Sepsis-3 (prescreening by quick Sequential Organ Failure Assessment [qSOFA] of ≥2 of 3 criteria followed by the complete score change ≥2 + infection), and an amended Sepsis-3 definition, iqSOFA (qSOFA ≥2 + infection). We used χ 2 or Wilcoxon rank-sum tests, receiver-operator characteristic curves, and survival analysis.

Results

We enrolled 176 patients (95% in an intensive care unit, 38.6% female, median age 61.4 years). Of 105 patients classified by Sepsis-2 as having sepsis, 80 had sepsis per Sepsis-3 or iqSOFA (kappa = 0.72; 95% confidence interval [CI], 0.62–0.82). Twenty-five (14.8%) died (20 of 100 with sepsis per Sepsis-2 [20%], and 20 of 77 [26.0%] with sepsis per Sepsis-3 or iqSOFA). Results for Sepsis-3 and iqSOFA were identical. The area under the curve of receiver-operator characteristic (ROC) curves for identifying those who died were 0.54 (95% CI, 0.41–0.68) for Sepsis-2, 0.84 (95% CI, 0.74–0.93) for Sepsis-3, and 0.69 (95% CI, 0.60–0.79) for iqSOFA (P < .01). Hazard ratios for death associated with sepsis were greatest for sepsis or septic shock per Sepsis-3.

Conclusions

Sepsis-3 and iqSOFA were better at predicting death than Sepsis-2. Using the SOFA score might add little advantage compared with the simpler iqSOFA score.
XMM-Newton spectrum of the magnetar CXOU J171405.7–381031
Authors: Watanabe Haruka , Bamba Aya , Shibata Shinpei , Watanabe Eri
Published: June 2019

We observe the magnetar CXOU J171405.7−381031 with XMM-Newton and obtain the most reliable X-ray spectral parameters for this magnetar. After removing the flux from the surrounding supernova remnant CTB 37B, the radiation of CXOU J171405.7−381031 is best described by a two-component model, consisting of a blackbody and power law. We obtain a blackbody temperature of $0.58^{+0.03}_{-0.03}$ keV, a photon index of $2.15^{+0.62}_{-0.68}$, and an unabsorbed 2–10 keV band flux of $2.33^{+0.02}_{-0.02} \times 10^{-12}$ erg cm−2 s−1. These new parameters enable us to compare CXOU J171405.7−381031 with other magnetars, and it is found that the luminosity, temperature, and photon index of CXOU J171405.7−381031 are aligned with the known trend among the magnetar population with a slightly higher temperature, which could be caused by its young age. All magnetars with a spin-down age of less than 1000 yr show time variation or bursts except for CXOU J171405.7−381031. We explore the time variability for six observations between 2006 and 2015, but there is no variation larger than ∼10%.
Why is the mission impossible? Decoupling the mirror Ginsparg–Wilson fermions in the lattice models for two-dimensional Abelian chiral gauge theories
Authors: Kikukawa Y
Published: June 2019

It is known that the four-dimensional Abelian chiral gauge theories of an anomaly-free set of Wely fermions can be formulated on the lattice preserving the exact gauge invariance and the required locality property in the framework of the Ginsparg–Wilson relation. This holds true in two dimensions. However, in the related formulation including the mirror Ginsparg–Wilson fermions, and therefore having a simpler fermion path-integral measure, it has been argued that the mirror fermions do not decouple: in the 345 model with Dirac– and Majorana–Yukawa couplings to the XY-spin field, the two-point vertex function of the (external) gauge field in the mirror sector shows a singular non-local behavior in the paramagnetic strong-coupling phase. We re-examine why the attempt seems to be a “Mission: Impossible” in the 345 model. We point out that the effective operators to break the fermion number symmetries (‘t Hooft operators plus others) in the mirror sector do not have sufficiently strong couplings even in the limit of large Majorana–Yukawa couplings. We also observe that the type of Majorana–Yukawa term considered is singular in the large limit due to the nature of the chiral projection of the Ginsparg–Wilson fermions, but a slight modification without such a singularity is allowed by virtue of their very nature. We then consider a simpler four-flavor axial gauge model, the $1^4(-1)^4$ model, in which the U(1)$_A$ gauge and Spin(6)(SU(4)) global symmetries prohibit the bilinear terms but allow the quartic terms to break all the other continuous mirror fermion symmetries. We formulate the model so that it is well behaved and simplified in the strong-coupling limit of the quartic operators. Through Monte Carlo simulations in the weak gauge-coupling limit, we show numerical evidence that the two-point vertex function of the gauge field in the mirror sector shows regular local behavior, and we argue that all you need is to kill the continuous mirror fermion symmetries with would-be gauge anomalies non-matched, as originally claimed by Eichten and Preskill. Finally, by gauging a U(1) subgroup of the U(1)$_A$$\times$ Spin(6)(SU(4)) of the previous model, we formulate the $2 1 (-1)^3$ chiral gauge model, and argue that the induced fermion measure term satisfies the required locality property and provides a solution to the reconstruction theorem formulated by Lüscher. This gives us “A New Hope” for the mission to be accomplished.
PIR-B expressing CD8+ T cells exhibit features of Tc1 and Tc17 in SKG mice
Authors: Rothe Kathrin , Quandt Dagmar , Köhler Gabriele , Jasinski-Bergner Simon , Seliger Barbara , Pierer Matthias , Wagner Ulf
Published: June 2019

Objective

In autoimmune arthritis, TCR signalling is attenuated by peripheral tolerance mechanisms. We have described previously a population of inhibitory receptor LIR-1 expressing autoreactive CD8+ T cells in rheumatoid arthritis. Here, we investigated the role of CD8+ T cells in murine autoimmune arthritis by analysing their expression of the mouse orthologue of LIR-1, PIR-B.

Methods

Frequencies of PIR-B+CD8+ T cells were determined in the SKG arthritis model. The phenotype of those cells was determined ex vivo by FACS and functionality was investigated by means of cytokine production and cytolytic potential upon activation in vitro.

Results

SKG mice, under non-SPF (specific pathogen-free) conditions with clinical symptoms of arthritis, were found to harbour significantly increased frequencies of PIR-B+CD8+ T cells. Those cells showed a pro-inflammatory phenotype with preferential production of IL-17 and IFN-γ. The frequency of those cells correlated inversely with the arthritis score, indicating that they might represent autoreactive, but functionally inhibited, CD8+ T cells.

Conclusion

PIR-B+CD8+ T cells from SKG mice show a cytotoxic and pro-inflammatory phenotype. Inhibition of CD8+ T cell autoreactivity by PIR-B/LIR-1 receptor signalling might be a counter-regulatory mechanism to curb autoreactivity and arthritis.
Evolutionary persistence of insect bunyavirus infection despite host acquisition and expression of the viral nucleoprotein gene
Authors: Ballinger Matthew J , Taylor Derek J
Published: June 2019

How insects combat RNA virus infection is a subject of intensive research owing to its importance in insect health, virus evolution, and disease transmission. In recent years, a pair of potentially linked phenomena have come to light as a result of this work—first, the pervasive production of viral DNA from exogenous nonretroviral RNA in infected individuals, and second, the widespread distribution of nonretroviral integrated RNA virus sequences (NIRVs) in the genomes of diverse eukaryotes. The evolutionary consequences of NIRVs for viruses are unclear and the field would benefit from studies of natural virus infections co-occurring with recent integrations, an exceedingly rare circumstance in the literature. Here, we provide evidence that a novel insect-infecting phasmavirus (Order Bunyavirales) has been persisting in a phantom midge host, Chaoborus americanus, for millions of years. Interestingly, the infection persists despite the host’s acquisition (during the Pliocene), fixation, and expression of the viral nucleoprotein gene. We show that virus prevalence and geographic distribution are high and broad, comparable to the host-specific infections reported in other phantom midges. Short-read mapping analyses identified a lower abundance of the nucleoprotein-encoding genome segment in this virus relative to related viruses. Finally, the novel virus has facilitated the first substitution rate estimation for insect-infecting phasmaviruses. Over a period of approximately 16 million years, we find rates of (0.6 − 1.6) × 10−7 substitutions per site per year in protein coding genes, extraordinarily low for negative-sense RNA viruses, but consistent with the few estimates produced over comparable evolutionary timescales.
III Middle English
Authors: Ash-Irisarri Kate , Black Daisy , Brazil Sarah , Dow Anna , Grossman Joel , Kobayashi Yoshiko , Pattwell Niamh , Perry R D , Sawyer Daniel , Wu Xiaoling
Published: June 2019

Due to the resignation of its former editor, and a turnover of contributors, this chapter has fewer contributors than previously. It is hoped to catch up subsequently with missing areas and to include them retrospectively. The chapter has nine sections: 1. Theory; 2. Manuscript and Textual Studies; 3. Religious Prose; 4. Piers Plowman; 5. Romance: Metrical, Alliterative, Prose; 6. Gower; 7. Hoccleve and Lydgate; 8. Older Scots; 9. Drama. Section 1 is by R.D. Perry; section 2 is by Daniel Sawyer; section 3 is by Niamh Pattwell; section 4 is by Joel Grossman; section 5 is by Anna Dow; section 6 is by Yoshiko Kobayashi; section 7 is by Xiaoling Wu; section 8 is by Kate Ash-Irisarri; section 9 is by Daisy Black and Sarah Brazil.
Topical tacrolimus for allergic eye diseases
Authors: Erdinest Nir , Ben-Eli Hadas , Solomon Abraham
Published: June 2019

Purpose of review

The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies.

Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs.

The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases.

Recent findings

Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC.

Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency.

Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.
Clinician–Educator Tracks for Trainees in Graduate Medical Education: A Scoping Review
Authors: Friedman Karen , Lester Janice , Young John Q.
Published: June 2019

Purpose

Clinician–educator tracks (CETs) appear to be increasing in prevalence in graduate medical education (GME) and may play an important role in medical education workforce development. The authors conducted a scoping review to characterize the current state of knowledge about CETs’ structure, content, and outcomes.

Method

Six databases were searched in January 2018 for English-language peer-reviewed articles published through 2017 to identify articles describing CETs in GME. To be included, the CET had to target GME learners (residents/fellows), be longitudinal, have the primary aim of developing trainees into clinician–educators (CEs), and address at least one CE core competency (direct teaching, curriculum development, mentorship/advising, leadership, assessment, educational scholarship). The authors extracted and analyzed data from included articles.

Results

Of 1,434 articles identified, 19 were included in the review, representing 18 separate CETs. All but 2 CETs (11%) were specialty-specific. Most included a core curriculum with classroom-based sessions (18; 100%), workplace-based opportunities to practice skills (17; 94%), and a required scholarly project (16; 89%). Seventeen (94%) focused on skills related to direct teaching. Four (22%) identified mentoring/advising as a core curriculum focus. Five (28%) required project dissemination. Time spent in CETs varied widely (median: 166 hours; range: 8 hours/4-month period to 1,288 hours/2-year period). The most common reported outcomes were learner reactions (7; 39%) and career tracking (11; 61%).

Conclusions

This review yields a composite picture of the current state of CETs in GME. The results highlight the paucity of outcomes data and areas for potential standardization and future research.
A Mixed-Methods Exploration of the Educational Climate and Safety Climate During the First Year of Clinical Practice in Ireland
Authors: Lydon Sinéad , Byrne Dara , Vellinga Akke , Walsh Chloe , Madden Caoimhe , Connolly Fergal , O’Connor Paul
Published: June 2019

Purpose

Educational climate (EC) and safety climate (SC) are key determinants of residents’ professional development. The goal of this study was to gather longitudinal EC data and data on perceptions of SC in residency, and provide data on practices related to perceptions of EC and SC, by identifying factors associated with and changes in perceptions of EC and SC across the first year of practice, and elucidating good and poor practice relating to key elements of EC and SC.

Method

A mixed-methods design was adopted. First, 131 first-year residents in Ireland were surveyed at the end of each of their first 3 rotations (August 2016–March 2017). The survey measured EC and SC using established measures. Next, 69 semistructured interviews were conducted with a representative sample of residents (March–May 2017). An interview schedule was developed to aid in-depth probing of EC and SC perceptions. A deductive content analysis approach was adopted.

Results

Perceptions of EC worsened over time. The EC and SC of surgical rotations were significantly poorer than those of medical rotations. Residents were more likely to describe team practices, rather than organizational practices, that contributed positively to their perceptions of EC and SC.

Conclusions

Further research is necessary to facilitate improvement of EC and SC for residents, particularly within surgical training. Future research exploring the contribution of organizational practices to EC and SC, the impact of targeted improvement activities, and best practices for involving residents in quality and safety initiatives is recommended.
Understanding the Broker Role of Clinician–Scientists: A Realist Review on How They Link Research and Practice
Authors: Barry Margot , de Groot Esther , Baggen Yvette , Smalbrugge Martin , Moolenaar Nienke , Bartelink Marie-Louise E.L. , Damoiseaux Roger A.M.J. , Scherpbier Nynke , Kluijtmans Manon
Published: June 2019

Purpose

Clinician–scientists are said to be well placed to connect research and practice, but their broker role has been underexplored. This review sought to gain an understanding of the broker role of clinician–scientists.

Method

The authors conducted a realist review to describe context–mechanism–outcome (CMO) configurations associated with the broker role of clinician–scientists. CINAHL, PubMed, PsycINFO, Web of Science, and Embase were searched between May and August 2017. Data were analyzed qualitatively; data synthesis focused on assembling CMO configurations.

Results

Of an initial 2,241 articles, 9 were included in the final review. Included papers show that clinician–scientists, in their broker role, achieve 2 organizational-level outcomes: an increased volume of clinically relevant, research, and increased evidence application to improve care. They also achieve the individual-level outcome of professional development as a researcher, clinician, and broker. Multidimensional skills and management support are necessary context factors. Mechanisms that contribute to outcomes include balancing economic and scientific interests and performing boundary-crossing activities. Four CMO configurations by which clinician–scientists achieve outcomes in brokering a connection between research and practice were identified. Useful program theories for explaining these are boundary crossing, social network, communities of practice, and diffusion of innovation theory.

Conclusions

The mechanisms found may provide insight for interventions aiming to support clinician–scientists in their broker role. The authors expect that if more attention is paid to learning multidimensional skills and management support for the broker role is strengthened, stronger links between research and practice could be forged.
Treatment of juvenile idiopathic arthritis: what's new?
Authors: Giancane Gabriella , Ruperto Nicolino
Published: June 2019

Purpose of review

The present review highlights the advances in disease outcome achieved with currently available biologic medications and future perspectives for JIA management.

Recent findings

In the last two decades, the management of juvenile idiopathic arthritis (JIA) has been revolutionized by appropriate legislative initiatives, the existence of very large collaborative networks and the increased availability of the novel biologic medications.

A more rational approach to the management of JIA is being fostered by the recent publication of therapeutic recommendations, consensus treatment plans and for a treat-to-target strategy.
Factors Influencing Interbody Cage Subsidence Following Anterior Cervical Discectomy and Fusion
Authors: Igarashi Hidetoshi , Hoshino Masahiro , Omori Keita , Matsuzaki Hiromi , Nemoto Yasuhiro , Tsuruta Takashi , Yamasaki Koji
Published: June 2019

Study Design:

This is a prospective study.

Objective:

The purpose of this study was to analyze the factors influencing subsidence following anterior cervical discectomy and fusion (ACDF) using a stand-alone cage.

Summary of Background Data:

The relationship between cage subsidence and cage height and material has been reported in previous studies.

Methods:

Clinical and radiologic data from 78 patients, 105 levels, undergoing single-level and 2-level ACDF without plates from 2007 to 2015 were collected prospectively. Patients were followed for at least 12 months after surgery. Radiographs were obtained preoperatively, at 1 week, and at 1, 3, 6, and 12 months postoperatively to determine the presence of fusion and cage subsidence.

Results:

There was a correlation in cage height and subsidence (Spearman P<0.05). Cage subsidence was significantly shorter in the polyetheretherketone cages than in titanium cages (P<0.05). However, when cage height was <5 mm, the difference between the 2 groups was not significant. Large subsidence (>3 mm) was observed in 17 patients, 20 levels, many of whom exhibited sinking in the first month after surgery.

Conclusions:

The greater the cage height, the greater the risk of cage subsidence in ACDF. Polyetheretherketone cages are superior to titanium cages for the maintenance of intervertebral height in cases where cage height is >5.5 mm.

Level of Evidence:

Level 3.
Tranexamic Acid in Thoracic and Lumbar Fusions and Perioperative Blood Loss
Authors: Wanderman Nathan , Robinson William , Carlson Bayard , Bydon Mohamad , Currier Brad , Huddleston Paul , Nassr Ahmad , Freedman Brett
Published: June 2019

Study Design:

This study was a retrospective cohort design.

Objective:

The objective of this study was to examine the impact of tranexamic acid (TXA) on total perioperative wound output following thoracic and lumbar spinal fusions.

Summary of Background Data:

TXA has been extensively studied with regard to intraoperative blood loss and transfusion rates. Few studies have looked specifically at the effect of TXA on postoperative drain output.

Materials and Methods:

We examined blood loss patterns in 617 consecutive adult patients undergoing lumbar and/or thoracic fusions at a single institution from January 2009 to 2016. These patients were divided into TXA and non-TXA, as well as high-dose and low-dose TXA, groups and analyzed using a propensity score to account for differences between cohorts.

Results:

The TXA and non-TXA groups were demographically similar. The mean number of levels fused was higher in the TXA group (4.8 vs. 3.1 levels,P<0.01). There was a significant reduction in both intraoperative blood loss (77.7 mL per level,P=0.020) and postoperative drain output (83.3 mL per level,P=0.002) in the TXA group when examined on a per level fused basis, but no significant difference without controlling for a number of levels. Postoperative blood loss tended to be higher in the TXA group for surgeries involving >5 levels fused. There was a significantly less blood loss in the high-dose TKA group both intraoperatively (296.4 mL per level fused,P<0.001) and postoperatively (133.4 mL per level fused,P<0.001).

Conclusions:

TXA significantly reduced both intraoperative and postoperative blood loss in lumbar and thoracic fusions when examined on a per level basis. However, with surgeries involving fusions >5 levels, TXA may increase postoperative drain output, with those losses offset by reduced intraoperative blood loss. High-dose TXA further reduced both intraoperative and postoperative blood loss as compared with low-dose TXA.
Gluteal Augmentation with Polymethyl Methacrylate: A 10-year Cohort Study
Authors: Chacur Roberto , Sampaio Menezes Honório , Maria Bordin da Silva Chacur Nívea , Dias Alves Danuza , Cadore Mafaldo Rodrigo , Dias Gomes Leandro , dos Santos Barreto Gisele
Published: June 2019

Background:

Many techniques for buttocks augmentation have been developed and published, for a more natural, satisfactory, and safe result for the patient. It has been a challenge to find a technique that presented not only volume gain but also gluteal remodeling.

Methods:

A total of 1,681 patients who underwent gluteal augmentation with Polymethyl methacrylate (PMMA) between 2009 and 2018 were selected for this retrospective cohort study. Data collected included demographics, procedures data, and postoperative outcomes. Side effects were calculated and compared using the Student’s t test.

Results:

A total of 1,681 patients (1,583 women and 98 men) who underwent 2,770 gluteal fillings had their cases retrospectively analyzed. They were injected with 540,751.00 mL of PMMA injected. The patients’ mean age was 39 years, and the mean volume injected in each section was 237 mL during the first procedure and 147 mL during the second procedure. The authors observed 52 cases presenting side effects, representing a rate of 1.88% of 2,770 procedures carried out. The statistically significant (P = 0.02) presence of side effects was detected in relation to the total filling volume.

Conclusions:

This study has demonstrated that gluteal augmentation with PMMA is one of the best options for this type of procedure. In addition, the findings suggest that the guidelines concerning gluteal augmentation must include PMMA filler as an option because PMMA proved to cause few side effects, as demonstrated by this patient cohort.
Long-Term Stability With the Athens Protocol (Topography-Guided Partial PRK Combined With Cross-Linking) in Pediatric Patients With Keratoconus
Authors: Kanellopoulos Anastasios John , Vingopoulos Filippos , Sideri Anna Maria
Published: June 2019

Purpose:

To evaluate the safety, efficacy, and stability of topography-guided partial PRK combined with corneal cross-linking (CXL) (the Athens Protocol [AP]) in pediatric patients with keratoconus over a 4-year follow-up period.

Methods:

This prospective study included 39 keratoconic eyes of 21 patients younger than 18 years with clinical and imaging evidence of keratoconus progression. Partial topography-guided excimer laser ablation in conjunction with high-fluence CXL was performed in all patients according to the AP. Uncorrected distance visual acuity, corrected distance visual acuity, refraction, keratometry, endothelial cell density, topography, and tomography using both Scheimpflug and optical coherence tomography (OCT) were evaluated for 4 years postoperatively.

Results:

At 4 years postoperative, there was significant improvement in mean uncorrected distance visual acuity from 0.51 ± 0.31 (decimal) to 0.65 ± 0.26 (decimal; P < 0.05). Mean corrected distance visual acuity improved from 0.71 ± 0.22 (decimal) preoperatively to 0.81 ± 0.19 (decimal; P < 0.05), respectively. Mean flat keratometry (K1) and mean steep keratometry (K2) readings reduced from 44.95 ± 3.71 D and 49.32 ± 5.05 D, respectively, preoperatively to 43.14 ± 2.95 D and 46.28 ± 4.87 D, respectively, (P < 0.05) at 4 years. The mean anterior maximum keratometry (Kmax) reading reduced from 56.81 ± 2.94 D preoperatively to 48.11 ± 3.17 D at 48 months. The mean index of height decentration was 0.105 ± 0.054 μm preoperatively and 0.049 ± 0.024 (P < 0.05) at 4 years postoperative. Mean preoperative corneal thickness at the thinnest point was 436.7 ± 42.6 μm preoperatively, 392.50 ± 45.68 μm at 12 months postoperative, and 418.42 ± 17.01 μm at 4-year follow-up. Late-onset deep corneal haze, a potential intrinsic complication of this technique in pediatric patients, was encountered in 2 cases at least 1 year after the procedure.

Conclusions:

Long-term results of the AP seem to be safe and effective in pediatric patients, with marked improvement in visual function and keratometric symmetry indices.