bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy and Safety in Screw Placement in the High Cervical Spine
Authors: Hur Jung-Woo , Kim Jin-Sung , Ryu Kyeong-Sik , Shin Myeong-Hoon
Published: March 2019

Study Design:

This study was a retrospective analysis.

Objective:

The purpose of present study was to evaluate accuracy, efficiency, and safety of intraoperative O-arm–based navigation system for the placement of C1 lateral mass screw (C1LMS) and C2 pedicle screws (C2PSs) in high cervical spine operations.

Summary of Background Data:

High screw misplacement rates, various pedicle morphometry and vertebral body size variations have led to a search of image-guided systems to improve the surgical accuracy of screw insertion in high cervical spine. The use of O-arm has been proposed for more accurate and efficient spinal instrumentation.

Materials and Methods:

Between June 2009 and August 2016, a total of 48 patients with atlantoaxial instability were surgically treated using the image-guidance system. To reconstruct atlantoaxial instability, we have been using Harm’s technique of C1LMS and C2PS fixations. A frameless, stereotactic O-arm–based image-guidance system was used for correct screw placement. Postoperative computed tomographic scan with multiplanar reconstructions were used to determine the accuracy of the screw placement.

Results:

A total of 182 screws, including 90 C1LMS and 92 C2PSs were inserted using image-guidance system. In total, 4.4% (4/90) of C1LMS and 7.6% (10/92) of C2PS had cortex violation over 2 mm and considered as “significant.” Among the significant cortex violations, “unexpected breech” was 3.3% of all the screws inserted. Two (2.1%) screws inserted had perforated the vertebral artery canal and iatrogenic vertebral artery stenosis was proved with postoperative computed tomography angiography. When divided into time periods, 60% of significant breech occurred during the beginning stage, 40% during adaptation stage and none during expert stage.

Conclusions:

In this study, the authors demonstrated that use of image-guidance system seems to be beneficial for high cervical instrumentation which requires much experience and steep learning curves. However, incidence of cortex violation does not disappear completely due to the close proximity to spinal canal and surrounding vessels.
Heritability of Corneal Curvature and Pentacam Topometric Indices: A Population-Based Study
Authors: Heydarian Samira , Hashemi Hassan , Yekta Abbasali , Ostadimoghaddam Hadi , Derakhshan Akbar , Aghamirsalim Mohammadreza , Khabazkhoob Mehdi
Published: March 2019

Purpose:

To investigate familial aggregation of anterior and posterior corneal curvature, corneal astigmatism, and some corneal topometric indices using the Pentacam.

Methods:

Of 3,851 eligible individuals who resided in the selected areas, 2,779 met the conditions for analysis. However, analysis was limited to families whose Pentacam measures were available for at least 2 family members (father or mother and a child), resulting in 1,383 individuals in 382 families. All selected subjects underwent a set of examinations, including refraction, uncorrected and corrected visual acuity measurement, slitlamp biomicroscopy, and Pentacam imaging. Heritability estimation was used to calculate familial aggregation.

Results:

The results of our study showed a fairly high corneal curvature heritability. The heritability of K2 and K1 in the anterior surface was 58.61% (95% confidence interval [CI], 54.99–62.23) and 55.82% (95% CI, 52.66–58.98), respectively. The heritability of posterior corneal curvature was slightly higher than that of the anterior corneal curvature. The heritability of K2 and K1 in the posterior surface was 63.42% (95% CI, 60.07–66.77) and 59.67% (95% CI, 55.85–63.49), respectively. Investigation of the quantitative topographic corneal indices showed that index of surface variance (ISV), central keratoconus index, and index of vertical asymmetry (IVA) had the highest levels of heritability (81.2% [95% CI, 73.64–88.76], 75.21% [95% CI, 67.19–82.28], and 66.46% [95% CI, 61.99–70.93], respectively). However, keratometric power deviation and index of height asymmetry had the lowest heritability levels (7.48% 95% CI, [4.94–10.02] and 18.31% [95% CI, 16.07–20.55], respectively).

Conclusion:

The familial aggregation and relatively high heritability of the corneal curvature and some keratoconus-related indices, such as ISV and IVA, confirm a high correlation between these phenotypes and genetic factors and warrant further investigation of the genetic mechanisms in keratoconus.
Hybrid Neurofibroma/Schwannoma of the Orbit
Authors: Stevenson Louis J. , McElnea Elizabeth M. , McKelvie Penelope A. , Hardy Thomas G.
Published: March 2019

A 68-year-old female presented for assessment of a space occupying lesion of her right orbit, demonstrated on MRI. An upper lid crease anterior orbitotomy was performed and the lesion excised completely. Postoperatively, she had reduced sensation in the distribution of the supraorbital nerve. Histopathologic examination of the excised lesion revealed a hybrid neurofibroma/schwannoma. This represents the fourth reported case of such a lesion arising within the orbit.
Using Nontraditional Curricular Tools to Address Death and Dying in Nurse Education
Authors: Schreiner Lynnette , Wolf Bordonaro Gaelynn P.
Published: March 2019

Nurse educators have a unique role to prepare nursing students for all aspects of patient and family care, from birth through death. Knowing that death is inevitable is not the challenge. Preparing nursing students to cope with death and address personal and community myths about death and dying are the challenges. Opportunities for students to examine personal and community associations with death are essential for nursing students preparing to enter the field. Biophysiological processes and treatment protocols are an essential part of each course; however, one course in a Department of Nursing in a small university in the Midwestern United States provides students the opportunity to reflect on death and dying and includes the experience of creating a tangible symbol to “hold on to” as they professionally and thoughtfully work with dying patients and their families, as well as cope with their own experiences of loss and grief in their careers.
Cultural Insensitivity Pervasive in Spanish Online Cosmetic Surgery Resources
Authors: Johnson Anna Rose , Bravo Miguel G. , Granoff Melisa D. , Lee Bernard T.
Published: March 2019

Background

Hispanics are the second largest demographic that underwent cosmetic surgery in 2017. The popularity of cosmetic surgeries among this group has increased significantly within the past decade and is projected to continue rising. Patient-directed websites that provide educational materials addressing these procedures should include information that is accurate, comprehensible, and sensitive to the demographic's diverse cultural and ethnic needs. Online health resources have been shown to vary significantly in their quality and reliability. This can be inimical for patients, as misinformation has been associated with poor health outcomes. The aim of this study is to evaluate online Spanish patient-directed materials for the top 5 cosmetic surgeries performed in 2017 using validated metrics.

Methods

The top 5 cosmetic surgeries performed in 2017 according to the American Society of Plastic Surgeons were identified, and a Google search was performed using the following terms: “breast augmentation,” “liposuction,” “rhinoplasty,” “blepharoplasty,” and “abdominoplasty.” The top 10 websites providing relevant information in Spanish were identified for each procedure. Fifty unique web links were analyzed by 2 independent bilingual raters using the Cultural Sensitivity Assessment Tool, and mean reading grade level was determined. Interrater reliability was computed using a Cohen κ.

Results

Online information in Spanish was difficult to encounter, with an average of 130 websites evaluated to identify 10 websites for each surgery. The mean reading grade level of all evaluated pages was 10.19, appropriate for a high school sophomore. There were no statistically significant differences between cosmetic surgery procedures (P = 0.69). The mean cultural sensitivity score was 2.20 (2.08–2.38). No subgroup met the threshold score for acceptable cultural sensitivity of >2.5.

Conclusion

This study demonstrates that US websites do not offer appropriate-level Spanish materials for patients seeking information on cosmetic surgeries. Websites providing information in Spanish were often inaccurate automatic translations and further compromised reader understanding. In our search, we frequently encountered organizational statements expressing a commitment to diversity. Increased awareness and development of more culturally appropriate materials is paramount to effectively communicate with patients and begin to close the gap in cultural disparities in health literacy.
Clinical spectrum of central nervous system myelin oligodendrocyte glycoprotein autoimmunity in adults
Authors: Cobo-Calvo Alvaro , Vukusic Sandra , Marignier Romain
Published: March 2019

Purpose of review

The clinical interest for auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) has recently reemerged, with the use of more specific detection methods. Large national cohorts have allowed characterizing a more precise clinical spectrum delineated by the presence of human MOG-antibodies.

Recent findings

In adults with MOG-antibodies, optic neuritis is the most frequent clinical presentation, with features different from multiple sclerosis (MS), including bilateral involvement and predilection for the anterior part of the optic nerve. Myelitis and brainstem syndrome are also frequent, and may clinically mimic neuromyelitis optica spectrum disorders (NMOSD). Despite the frequently severe clinical presentation, most of patients recover quickly after steroids initiation. Other less typical presentations include encephalitis with seizures, cranial nerve involvement, and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids-like. Although the majority of adult patients follow a relapsing course, long-term prognosis differs from aquaporin-4-antibodies NMOSD, with only a small proportion of patients with a poor outcome.

MOG-antibodies-associated disease is a new entity in the spectrum of inflammatory demyelinating diseases, distinct from both MS and NMOSD. There is a crucial need to identify factors associated to the risk of relapse or poor outcome, to seek patient subgroups in which immunoactive treatments could be beneficial.
Report on the spatial spread of defective interfering particles and its role in suppressing infectious particles
Authors: Ali Qasim , Ke Ruian
Published: March 2019

Defective interfering particles (DIPs) are categorized as non-infectious viruses with large deletions in their genomic material. A cell infected by a DIP require co-infection by a wild-type virus to complete its replicative lifecycle. There is an increasing interest in developing DIP based therapies in the form of molecular parasites that steal genetic resources of infectious particles. This parasitic behavior is enhanced by constructing engineering designs of DIPs to optimize their role in suppressing the virus infection within-host. Recent experimental studies characterize viral infection as a spatial process and emphasize on its spread rate and the area populated by the infectious particles (IPs). We developed a spatio-temporal model in the framework of reaction-diffusion equations to depict the functional organization of virus particles distributed over a tissue surface. Our model investigates the scenarios and figures out the aspects that can play a vital role to suppress the infection within-host. We studied the impact of initial dose of DIPs, the efficiency of DIP production and the role of cell maturation. Our results show that an engineered DIP can substantially decrease the concentration of IPs. We assert that the decrease in the rate of spatial spread of IPs requires non-deterministic settings.
Interaction Effects of Apolipoprotein E ε 4 and Cognitive Status on the Functional Connectivity within Default Mode Network in Individuals at Risk of Cognitive Impairments
Authors: Lu Hanna , Ma Suk Ling , Chiu Wing Winnie Chu , Ho Wong Savio Wai , Lam Linda C. W.
Published: March 2019

Background

Disturbance of intrinsic brain networks is often associated with APOE ε 4 allele and cognitive dysfunction. However, little is known about the functional connectivity strength (FCS) within default mode network (DMN).

Objective

We aimed to examine the independent effects APOE ε 4 and cognitive status and the interaction effect on the functional connectivity within DMN.

Methods

Resting-state functional MRI was conducted for sixty-five senior adults who had normal cognition or cognitive decline with or without APOE ε 4. Regions within DMN include mPFC, IPL, LTC, hippocampus and PCC. The absolute values of correlation coefficient between DMN regions were employed as the measures of FCS for quantifying the functional connectivity.

Results

Main effect of APOE ε 4 was found on the FCS of bilateral PCC (F = 6.133, p = 0.016), while the main effect of cognitive status was found on the FCS of left IPL and right mPFC (F = 4.585, p = 0.036). Interaction effect was found in the FCS of right mPFC and left LTC (F = 4.698, p = 0.034), right hippocampus and left LTC (F = 7.673, p = 0.008), left PCC and left LTC (F = 6.719, p = 0.012), right IPL and right LTC (F = 4.516, p = 0.038).

Conclusions

APOE ε 4 carriers with cognitive impairment denote a preclinical status characterized by aberrant inter-hemispheric FC within DMN. The network-level connectivity may be useful in the evaluation of the individuals at risk for developing AD and affiliate network-guided brain stimulation.
Genomic profiling of childhood tumor patient-derived xenograft models to enable rational clinical trial design
Authors: Rokita Jo Lynne , Rathi Komal S. , Cardenas Maria F. , Upton Kristen A. , Jayaseelan Joy , Cross Katherine L. , Pfeil Jacob , Ritenour Laura E. , Modi Apexa , Farrel Alvin , Way Gregory P. , Kendsersky Nathan M. , Patel Khushbu , Lopez Gonzalo , Vaksman Zalman , Mayoh Chelsea , Nance Jonas , McCoy Kristyn , Haber Michelle , Evans Kathryn , McCalmont Hannah , Bendak Katerina , Böhm Julia W. , Marshall Glenn M. , Tyrrell Vanessa , Kalletla Karthik , Braun Frank K. , Qi Lin , Du Yunchen , Zhang Huiyuan , Lindsay Holly B. , Zhao Sibo , Shu Jack , Baxter Patricia , Morton Christopher , Kurmashev Dias , Zheng Siyuan , Chen Yidong , Bowen Jay , Bryan Anthony C. , Leraas Kristen M. , Coppens Sara E. , Doddapaneni HarshaVardhan , Momin Zeineen , Zhang Wendong , Sacks Gregory I. , Hart Lori S. , Krytska Kateryna , Mosse Yael P. , Gatto Gregory J. , Sanchez Yolanda , Greene Casey S. , Diskin Sharon J. , Vaske Olena Morozova , Haussler David , Gastier-Foster Julie M. , Kolb E. Anders , Gorlick Richard , Li Xiao-Nan , Reynolds C. Patrick , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A. , Lock Richard B. , Raman Pichai , Wheeler David A. , Maris John M.
Published: March 2019

Accelerating cures for children with cancer remains an immediate challenge due to extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs) from high-risk childhood cancers, many refractory to current standard-of-care treatments. Here, we genomically characterize 261 PDX models from 29 unique pediatric cancer malignancies and demonstrate faithful recapitulation of histologies, subtypes, and refine our understanding of relapsed disease. Expression and mutational signatures are used to classify tumors forTP53andNF1inactivation, as well as impaired DNA repair. We anticipate that these data will serve as a resource for pediatric oncology drug development and guide rational clinical trial design for children with cancer.

Highlights

Multiplatform genomic analysis defines landscape of 261 pediatric cancer patient derived xenograft (PDX) models

Pediatric patient derived xenografts faithfully recapitulate relapsed disease

InferredTP53pathway inactivation correlates with pediatric cancer copy number burden

Somatic mutational signatures predict impaired DNA repair across multiple histologies
Neonatal morphometric similarity mapping for predicting brain age and characterizing neuroanatomic variation associated with preterm birth
Authors: Galdi Paola , Blesa Manuel , Stoye David Q. , Sullivan Gemma , Lamb Gillian J. , Quigley Alan J. , Thrippleton Michael J. , Bastin Mark E. , Boardman James P.
Published: March 2019

Multi-contrast MRI captures information about brain macro- and micro-structure which can be combined in an integrated model to obtain a detailed “fingerprint” of the anatomical properties of an individual’s brain. Inter-regional similarities between features derived from structural and diffusion MRI, including regional volumes, diffusion tensor metrics, neurite orientation dispersion and density imaging measures, can be modelled as morphometric similarity networks (MSNs). Here, individual MSNs were derived from 105 neonates (59 preterm and 46 term) who were scanned between 38 and 45 weeks postmenstrual age (PMA). Inter-regional similarities were used as predictors in a regression model of age at the time of scanning and in a classification model to discriminate between preterm and term infant brains. When tested on unseen data, the regression model predicted PMA at scan with a mean absolute error of 0.70±0.56 weeks, and the classification model achieved 92% accuracy. We conclude that MSNs predict chronological brain age accurately; and they provide a data-driven approach to identify networks that characterise typical maturation and those that contribute most to neuroanatomic variation associated with preterm birth.

Highlights

Multiple MRI features are integrated in a single model to study brain maturation in newborns.

Morphometric similarity networks (MSNs) provide a whole-brain description of the structural properties of neonatal brain.

The information encoded in MSNs is predictive of chronological brain age in the perinatal period.

MSNs provide a novel data-driven method for investigating neuroanatomic variation associated with preterm birth.
DUX is a non-essential synchronizer of zygotic genome activation
Authors: Iaco Alberto De , Verp Sonia , Offner Sandra , Trono Didier
Published: March 2019

Some of the earliest transcripts produced in fertilized human and mouse oocytes code for DUX, a double homeodomain protein that promotes embryonic genome activation (EGA). Deleting Dux by genome editing at the 1- to 2-cell stage in the mouse impairs EGA and blastocyst maturation. Here, we demonstrate that mice carrying homozygous Dux deletions display markedly reduced expression of DUX target genes and defects in both pre- and post-implantation development, with notably a disruption of the pace of the first few cell divisions and significant rates of late embryonic mortality. However, some Dux-/- embryos give raise to viable pups, indicating that DUX is important but not strictly essential for embryogenesis.

Summary statement

Murine DUX regulates transcription in the first embryonic cell divisions but it’s not necessary for embryogenesis
β-Caryophyllene Enhances the Transcriptional Upregulation of Cholesterol Biosynthesis in Breast Cancer Cells
Authors: Mboge Mam Y. , Ramirez-Mata Andrea , Bullock Adam , O’Donnell Riley , Mathias John V. , Davila Julie , Frost Christopher J. , Frost Susan C.
Published: March 2019

β-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells. Here, we examine the hypothesis that BCP induces membrane remodeling. Our data show that high concentrations of BCP increase membrane permeability of human breast cells (hBrC) causing detachment and cell death. At a sub-lethal concentration of BCP, we show that BCP induces a striking upregulation of genes involved in cholesterol biosynthesis, including the gene that encodes for HMGCoA reductase (HMGCR), the rate-determining step in cholesterol biosynthesis. In addition, stearoyl-CoA desaturase (SCD) is also upregulated which would lead to the enhanced formation of monounsaturated fatty acids, specifically oleate and palmitoleate from stearoyl CoA and palmitoyl CoA, respectively. These fatty acids are major components of membrane phospholipids and cholesterol esters. Together, these data suggest that cells respond to BCP by increasing the synthesis of components found in membranes. These responses could be viewed as a repair mechanism and/or as a mechanism to mount resistance to the cytotoxic effect of BCP. Blocking HMGCR activity enhances the cytotoxicity of BCP, suggesting that BCP may provide an additional therapeutic tool in controlling breast cancer cell growth.
Single-cell RNA-seq reveals spatially restricted multicellular fibrotic niches during lung fibrosis
Authors: Joshi Nikita , Watanabe Satoshi , Verma Rohan , Jablonski Renea P. , Chen Ching-I , Cheresh Paul , Reyfman Paul A. , McQuattie-Pimentel Alexandra C. , Sichizya Lango , Flozak Annette S. , Gottardi Cara J. , Cuda Carla M. , Perlman Harris , Jain Manu , Kamp David W. , Budinger GR Scott , Misharin Alexander V.
Published: March 2019

Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms. We applied lineage tracing, spatial methods and single-cell RNA-seq to a spatially-restricted model of asbestos-induced pulmonary fibrosis. We demonstrate that while tissue-resident interstitial macrophages, tissue-resident alveolar macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche, only monocyte-derived alveolar macrophages are causally related to fibrosis. Monocyte-derived alveolar macrophages were specifically localized to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including PDGFA. Moreover, we identified autocrine M-CSF/M-CSFR signaling in monocyte-derived alveolar macrophages as a novel mechanism promoting their self-maintenance and persistence in the fibrotic niche. Pharmacological blockade of M-CSF signaling led to disappearance of the established population of monocyte-derived alveolar macrophages. Thus, our data indicate that monocyte-derived alveolar macrophages are specifically recruited to the fibrotic niche where they are maintained by autocrine signaling and drive fibrosis by stimulating fibroblast proliferation.
FAIM opposes stress-induced loss of viability and blocks the formation of protein aggregates
Authors: Kaku Hiroaki , Rothstein Thomas L.
Published: March 2019

A number of proteinopathies are associated with accumulation of misfolded proteins, which form pathological insoluble deposits. It is hypothesized that molecules capable of blocking formation of such protein aggregates might avert disease onset or delay disease progression. Here we report that Fas Apoptosis Inhibitory Molecule (FAIM) counteracts stress-induced loss of viability. We found that levels of ubiquitinated protein aggregates produced by cellular stress are much greater in FAIM-deficient cells and tissues. Moreover, in an in vitro cell-free system, FAIM specifically and directly prevents pathological protein aggregates without participation by other cellular elements, in particular the proteasomal and autophagic systems. Although this activity is similar to the function of heat shock proteins (HSPs), FAIM, which is highly conserved throughout evolution, bears no homology to any other protein, including HSPs. These results identify a new actor that protects cells against stress-induced loss of viability by preventing protein aggregates.
Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines
Authors: Asquith Christopher R. M. , Fleck Neil , Torrice Chad D. , Crona Daniel J. , Grundner Christoph , Zuercher William J.
Published: March 2019

We screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis (Mtb). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy-N-(4-((4-methylbenzyl)oxy)phenyl)quinolin-4-amine (34) with an MIC90 value of 0.63-1.25 μM. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry.
A unified method for rare variant analysis of gene-environment interactions
Authors: Lim Elise , Chen Han , Dupuis Josée , Liu Ching-Ti
Published: March 2019

Advanced technology in whole-genome sequencing has offered the opportunity to comprehensively investigate the genetic contribution, particularly rare variants, to complex traits. Many rare variants analysis methods have been developed to jointly model the marginal effect but methods to detect gene-environment (GE) interactions are underdeveloped. Identifying the modification effects of environmental factors on genetic risk poses a considerable challenge. To tackle this challenge, we develop a unified method to detect GE interactions of a set of rare variants using generalized linear mixed effect model. The proposed method can accommodate both binary and continuous traits in related or unrelated samples. Under this model, genetic main effects, sample relatedness and GE interactions are modeled as random effects. We adopt a kernel-based method to leverage the joint information across rare variants and implement variance component score tests to reduce the computational burden. Our simulation study shows that the proposed method maintains correct type I error rates and high power under various scenarios, such as differing the direction of main genotype and GE interaction effects and the proportion of causal variants in the model for both continuous and binary traits. We illustrate our method to test gene-based interaction with smoking on body mass index or overweight status in the Framingham Heart Study and replicate theCHRNB4gene association reported in previous large consortium meta-analysis of single nucleotide polymorphism (SNP)-smoking interaction. Our proposed set-based GE test is computationally efficient and is applicable to both binary and continuous phenotypes, while appropriately accounting for familial or cryptic relatedness.
Extracellular vesicle-mediated RNA release inHistoplasma capsulatum
Authors: Alves Lysangela R. , da Silva Roberta Peres , Sanchez David A. , Zamith-Miranda Daniel , Rodrigues Marcio L. , Goldenberg Samuel , Puccia Rosana , Nosanchuk Joshua D.
Published: March 2019

Eukaryotic cells, including fungi, release extracellular vesicles (EVs). These lipid bilayered compartments play essential roles in cellular communication and pathogenesis. EV composition is complex and includes proteins, glycans, pigments, and RNA. RNA classes with putative roles in pathogenesis have been described in EVs produced by fungi. Here we describe the RNA content in EVs produced by the G186AR and G217B strains ofHistoplasma capsulatum, an important human fungal pathogen. A total of 124 mRNA were identified in both strains. In this set of RNA classes, 93 transcripts were enriched in EVs from the G217B strain, while 31 enriched in EVs produced by the G186AR strain. This result suggests that there are important strain-specific properties in the mRNA composition of fungal EVs. We also identified short fragments (25-40 long) that were strain-specific, with a greater number of them identified in EVs produced by the G217B strain. Remarkably, the most enriched processes were stress responses and translation. Half of these fragments aligned to the reverse strand of the transcript, suggesting the occurrence of miRNA-like molecules in fungal EVs. We also compared the transcriptome profiles ofH. capsulatumwith the RNA composition of EVs and no correlation was observed. Altogether, our study provided information about the RNA molecules present inH. capsulatumEVs, and the differences in composition between the G186AR and G217B strains. In addition, we showed that the correlation between the most expressed transcripts in the cell and their presence in the EVs, reinforcing the idea that the RNAs were directed to the EVs by a regulated mechanism.

Importance

Extracellular vesicles (EVs) play important roles in cellular communication and pathogenesis. The RNA molecules in EVs have been implicated in a variety of processes. In pathogenic fungi, EV-associated RNA classes have recently been described; however, only a few studies describing the RNA in fungal EVs are available. An improved knowledge on EV-associated RNA will contribute to the understanding of their role during infection. In this study, we described the RNA content in EVs produced by two isolates ofHistoplasma capsulatum. Our results add this important pathogen to the current short list of fungal species with the ability to use EVs for the extracellular release of RNA.
In vitro analysis of RNA polymerase II elongation complex dynamics
Authors: Joo Yoo Jin , Ficarro Scott B. , Chun Yujin , Marto Jarrod A. , Buratowski Stephen
Published: March 2019

RNA polymerase II elongation complexes (ECs) were assembled from nuclear extract on immobilized DNA templates and analyzed by quantitative mass spectrometry. Time-course experiments showed that initiation factor TFIIF can remain bound to early ECs, while levels of core elongation factors Spt4–Spt5, Paf1C, Spt6–Spn1, and Elf1 remain steady. Importantly, the dynamic phosphorylation patterns of the Rpb1 C-terminal domain (CTD) and the factors that recognize them change as a function of postinitiation time rather than distance elongated. Chemical inhibition of Kin28/Cdk7 in vitro blocks both Ser5 and Ser2 phosphorylation, affects initiation site choice, and inhibits elongation efficiency. EC components dependent on CTD phosphorylation include capping enzyme, cap-binding complex, Set2, and the polymerase-associated factor (PAF1) complex. By recapitulating many known features of in vivo elongation, this system reveals new details that clarify how EC-associated factors change at each step of transcription.
Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans
Authors: Zhivagui Maria , Ng Alvin W.T. , Ardin Maude , Churchwell Mona I. , Pandey Manuraj , Renard Claire , Villar Stephanie , Cahais Vincent , Robitaille Alexis , Bouaoun Liacine , Heguy Adriana , Guyton Kathryn Z. , Stampfer Martha R. , McKay James , Hollstein Monica , Olivier Magali , Rozen Steven G. , Beland Frederick A. , Korenjak Michael , Zavadil Jiri
Published: March 2019

Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide. We next show that the glycidamide mutational signature is found in a full one-third of approximately 1600 tumor genomes corresponding to 19 human tumor types from 14 organs. The highest enrichment of the glycidamide signature was observed in the cancers of the lung (88% of the interrogated tumors), liver (73%), kidney (>70%), bile duct (57%), cervix (50%), and, to a lesser extent, additional cancer types. Overall, our study reveals an unexpectedly extensive contribution of acrylamide-associated mutagenesis to human cancers.
Measurement error correlation within blocks of indicators in consistent partial least squares
Authors: Rademaker Manuel E. , Schuberth Florian , Dijkstra Theo K.
Published: March 2019

Purpose

The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors.

Design/methodology/approach

Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted.

Findings

In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators.

Originality/value

Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.
Identifying the resource integration processes of green service
Authors: Guyader Hugo , Ottosson Mikael , Frankelius Per , Witell Lars
Published: March 2019

Purpose

The purpose of this paper is to improve the understanding of green service. In particular, the focus is on identifying homopathic and heteropathic resource integration processes that preserve or increase the resourceness of the natural ecosystem.

Design/methodology/approach

Through an extensive multiple case study involving ten service providers from diverse sectors based on a substantial number of interviews, detailed accounts of green service are provided.

Findings

Six resource integration processes were identified: reducing, recirculating, recycling, redistributing, reframing and renewing. While four of these processes are based on homopathic resource integration, both reframing and renewing are based on heteropathic resource integration. While homopathic processes historically constitute a green service by mitigating the impact of consumption on the environment, heteropathic resource integration increases the resourceness of the natural ecosystem through emergent processes and the (re)creation of natural resources.

Research limitations/implications

The present study breaks away from the paradigm that “green service” is about reducing the negative environmental impact of existing services, toward providing a green service that expands biological diversity and other natural resources.

Originality/value

Transformative service research on environmental sustainability is still in its infancy. The present study contributes through conceptualizing green service, redefining existing resource integration processes (reducing, recirculating, recycling) and identifying new resource integration processes (redistributing, reframing, renewing).
I hate what you love: brand polarization and negativity towards brands as an opportunity for brand management
Authors: Osuna Ramírez Sergio Andrés , Veloutsou Cleopatra , Morgan-Thomas Anna
Published: March 2019

Purpose

Negativity towards a brand is typically conceived as a significant problem for brand managers. This paper aims to show that negativity towards a brand can represent an opportunity for companies when brand polarization occurs. To this end, the paper offers a new conception of the brand polarization phenomenon and reports exploratory findings on the benefits of consumers’ negativity towards brands in the context of brand polarization.

Design/methodology/approach

To develop a conception of brand polarization, the paper builds on research on polarizing brands and extends it by integrating insights from systematic literature reviews in three bodies of literature: scholarship on brand rivalry and, separately, polarization in political science and social psychology. Using qualitative data from 22 semi-structured interviews, the paper explores possible advantages of brand polarization.

Findings

This paper defines the brand polarization phenomenon and identifies multiple perspectives on brand polarization. Specifically, the findings highlight three distinct parties that can benefit from brand polarization: the polarizing brand as an independent entity; the brand team behind the polarizing brand; and the passionate consumers involved with the polarizing brand. The data reveal specific advantages of brand polarization associated with the three parties involved.

Practical implications

Managers of brands with a polarizing nature could benefit from having identified a group of lovers and a group of haters, as this could allow them to improve their focus when developing and implementing the brands’ strategies.

Originality/value

This exploratory study is the first explicitly focusing on the brand polarization phenomenon and approaches negativity towards brands as a potential opportunity.
Analysing mobile advergaming effectiveness: the role of flow, game repetition and brand familiarity
Authors: Catalán Sara , Martínez Eva , Wallace Elaine
Published: March 2019

Purpose

This paper aims to explain the effect of flow, game repetition and brand familiarity on players’ brand attitude and purchase intention in the context of mobile advergaming.

Design/methodology/approach

Data from 227 participants who played a mobile advergame were analysed. Structural equation modelling with partial least squares was used to test the research model.

Findings

The results reveal that the independent variables (i.e. game repetition and brand familiarity) significantly influence the dependent variables explored in this study (i.e. brand attitude and purchase intentions of players). Results also show that brand familiarity influences players’ flow experience, which in turn significantly affects players’ purchase intentions.

Research limitations/implications

The findings of this study are important for advertising practitioners and advergames’ developers as understanding the determinants of mobile advergaming effectiveness is crucial for designing successful advergames that persuade players the most.

Originality/value

This study contributes to the literature in two ways. First, it provides new insights into the effectiveness of mobile advergames, which is an under-researched area. Second, it offers empirical evidence of the effects of game repetition, flow and brand familiarity on mobile advergaming effectiveness.
The instrumental time of memory: local politics and urban aesthetics in a tourism context
Authors: Nogués-Pedregal Antonio-Miguel
Published: March 2019

Purpose

This paper aims to show that tourism is one of the most perfect creations of the capitalist mode of production insofar as not only does it consume places and territories and perpetuate dependency relations, but in the expressive dimension, it also produces feelings and meanings and generates a new relationship of the past with the present and future (chronotope).

Design/methodology/approach

The study was carried out using a socio-anthropological approach with participant observation over several decades.

Findings

The modes of time are described and how the tourism chronotope shapes the historic centre of a consolidated tourist destination. The case study, analysed with the model of the “conversion of place through the mediation of tourism space”, illustrates the prevalence of instrumental and commercial values over one’s own aesthetic-expressive values in tourism contexts. This fact encourages the emergence of local political projects and the incorporation of uniformities outside the local place. These processes end up uprooting the anchors from collective memory. The definition of territories according to visitors’ imaginaries and expectations encourages the abusive occupation of public space and the adoption of new aesthetic attributes of urban space.

Research limitations/implications

Because of the chosen research approach and methodologies, the research results may lack generalisability. Therefore, researchers are encouraged to test both the model and the propositions further.

Originality/value

This study approaches the relationship of the idea Tourism with the idea Development based on the anchors of memory.
Dietary coconut oil ameliorates skin contact hypersensitivity through mead acid production in mice
Authors: Tiwari Prabha , Nagatake Takahiro , Hirata So‐ichiro , Sawane Kento , Saika Azusa , Shibata Yuki , Morimoto Sakiko , Honda Tetsuya , Adachi Jun , Abe Yuichi , Isoyama Junko , Tomonaga Takeshi , Kiyono Hiroshi , Kabashima Kenji , Kunisawa Jun
Published: March 2019

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis‐5, 8, 11‐eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B4 production required for secondary recruitment of neutrophils. Our findings provide valuable insights into the preventive roles of coconut oil and mead acid against skin inflammation, thereby offering attractive therapeutic possibilities.
Macular vascular circulation and retinal oxygen saturation changes for idiopathic macular epiretinal membrane after vitrectomy
Authors: Li Zhixi , Zhang Jie , Lin Tao , Peng Wenyan , Lu Lin , Hu Jie
Published: March 2019

Purpose

To investigate the postoperative changes in retinal‐choroidal blood flow area and retinal vascular oxygen saturation among patients with idiopathic macular epiretinal membranes (iERMs).

Methods

This study prospectively included 24 eyes of 24 consecutive patients who underwent vitrectomy for iERMs. The flow area of choriocapillary layer, retinal superficial capillary plexuses (SCPs) and retinal deep capillary plexuses (DCPs) were performed using optical coherence tomography angiography with angiovue prototype software, and retinal vascular oxygen saturation was measured using retinal oximeter with the built‐in software. The flow area of choriocapillary layers and mean retinal vessel oxygen saturation before and after surgery were compared.

Results

Three months after vitrectomy, the foveal flow area of choriocapillary layer increased clinically significantly from 1.5 ± 0.2 to 1.6 ± 0.2 mm2 (p = 0.02). The retinal vascular changes of SCPs and DCPs were not statistically significant. The mean retinal arterial oxygen saturation was 89.9 ± 11.3% preoperatively and increased to 94.5 ± 9.7% postoperatively (p = 0.04). Foveal retinal thickness revealed a clinically significant decrease from 547.8 ± 88.2 μm to 403.0 ± 47.5 μm after surgery (p < 0.05). Postoperative best corrected visual acuity had no statistically significant correlation with foveal flow area of the choriocapillary layer and retinal vascular oxygen saturation.

Conclusions

There was a decrease of retinal thickness, an improved flow area of choriocapillary layer in macular region, and an increase of retinal arterial vascular oxygen among iERMs patients after vitrectomy.
Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure‐lowering
Authors: Floyd Christopher N. , Lidder Satnam , Hunt Joanne , Omar Sami A. , McNeill Karen , Webb Andrew J.
Published: March 2019

Aims

Dietary inorganic nitrate (NO3−) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type 2 diabetes mellitus (T2DM). Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesized that acute physiological elevations in plasma [glucose]/[insulin] blunt the haemodynamic responses to NO3−, a pertinent question for carbohydrate‐rich Western diets.

Methods

We conducted an acute, randomized, placebo‐controlled, double‐blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO3) vs. potassium chloride (KCl; placebo) administered 1 hour prior to an oral glucose tolerance test in 33 healthy volunteers.

Results

Compared to placebo, there were no significant differences in systolic or diastolic BP (P = 0.27 and P = 0.30 on ANOVA, respectively) with KNO3, nor in pulse wave velocity or central systolic BP (P = 0.99 and P = 0.54 on ANOVA, respectively). Whilst there were significant elevations from baseline for plasma [glucose] and [C‐peptide], no differences between interventions were observed. A significant increase in plasma [insulin] was observed with KNO3 vs. KCl (n = 33; P = 0.014 on ANOVA) with the effect driven by the high‐dose cohort (24 mmol, n = 13; P < 0.001 on ANOVA; at T = 0.75 h mean difference 210.4 pmol/L (95% CI 28.5 to 392.3), P = 0.012).

Conclusions

In healthy adults, acute physiological elevations of plasma [glucose] and [insulin] result in a lack of BP‐lowering with dietary nitrate. The increase in plasma [insulin] without a corresponding change in [C‐peptide] or [glucose] suggests that high‐dose NO3− decreases insulin clearance. A likely mechanism is via NO‐dependent inhibition of insulin‐degrading enzyme.