bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers for predicting response to long‐term high dose aspirin therapy in aspirin‐exacerbated respiratory disease
Authors: Mastalerz Lucyna , Tyrak Katarzyna E. 
Published: August 2021

AbstractIntroductionAspirin‐exacerbated respiratory disease (AERD) is a phenotype of asthma characterized by eosinophilic inflammation in the airways, mast cell activation, cysteinyl leukotriene overproduction, and acute respiratory reactions on exposure to cyclooxygenase‐1 inhibitors. Aspirin desensitization followed by daily high‐dose aspirin therapy is a safe and effective treatment option for the majority of patients with AERD. However, there is still some percentage of the population who do not derive benefits from daily aspirin use.MethodsBased on the current literature, the biomarkers, which might predict aspirin treatment outcomes in AERD patients, were evaluated.Results and conclusionsPatients with severe symptoms of chronic rhinosinusitis, type 2 asthma based on blood eosinophilia, non‐neutrophilic inflammatory phenotype based on sputum cells, as well as high plasma level of 15‐hydroxyeicosatetraenoic acid (15‐HETE) are potentially good responders to long term high‐dose aspirin therapy. Additionally, high expression of the hydroxyprostaglandin dehydrogenase gene, HPGD encoding prostaglandin‐degrading enzyme 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) and low expression of the proteoglycan 2 gene, PRG2 encoding constituent of the eosinophil granule in sputum cells might serve as a predictor of good response to aspirin therapy. Variations in the expression of cysteinyl leukotriene receptor 1 in the airways could additionally influence the response to long‐term aspirin therapy. Arachidonic acid metabolites levels via the 5‐lipoxygenase as well as via the cyclooxygenase pathways in induced sputum supernatant do not change during high dose long‐term aspirin therapy and do not influence outcomes of aspirin treatment.
The effects of orexin‐A and orexin receptors on anxiety‐ and depression‐related behaviors in a male rat model of post‐traumatic stress disorder
Authors: Han Dan , Shi Yuxiu , Han Fang 
Published: August 2021

AbstractOrexin neurons play an important role in stress‐related mental disorders including post‐traumatic stress disorder (PTSD). Anxiety‐ and depression‐related symptoms commonly occur in combination with PTSD. However, the role of the orexin system in mediating alterations in these affective symptoms remains unclear. The medial prefrontal cortex (mPFC) is implicated in both cognitive and emotional processing. In the present study, we investigated anxiety‐ and depression‐related behavioral changes using the elevated plus maze, the sucrose preference test, and the open field test in male rats with single prolonged stress (SPS) induced‐PTSD. The expression of orexin‐A in the hypothalamus and orexin receptors (OX1R and OX2R) in the mPFC was detected and quantified by immunohistochemistry, western blotting, and real‐time polymerase chain reaction. We found that the SPS rats exhibited enhanced levels of anxiety, reduced exploratory activities, and anhedonia. Furthermore, SPS resulted in reductions in the expression of orexin‐A in the hypothalamus and the increased the expression of OX1R in the mPFC. The intracerebroventricular administration of orexin‐A alleviated behavioral changes in SPS rats and partly restored the increased levels of OX1R in the mPFC. These results suggest that the orexin system plays a role in the anxiety‐ and depression‐related symptoms observed in PTSD.
Enhanced Multiplexing of Immunofluorescence Microscopy Using a Long‐Stokes‐Shift Fluorophore
Authors: Reitz Sydney J. , Sauerbeck Andrew D. , Kummer Terrance T. 
Published: August 2021

AbstractImmunofluorescence labeling and microscopy offer a highly specific means to visualize proteins or other molecular species in a sample by labeling target antigens with fluorescent probes. These fluorescent probes can then be visualized using a fluorescence microscope, allowing their relative spatial relationships to be determined. Due to spectral overlap of common fluorophores, however, it can be challenging to analyze more than three antigens in a single sample with standard imaging approaches. This article describes multiplexed labeling and imaging of four target antigens through the use of a long‐Stokes‐shift fluorophore—a fluorophore with an unusually large gap between its excitation and emission maxima—in tandem with three conventional fluorophores. This combination allows for multiplexed imaging of four antigens in a single sample with excellent spectral discrimination suitable for sensitive analyses using standard imaging hardware. Particular advantages of this approach are its flexibility in terms of target antigens and the lack of any specialized procedures, reagents, or equipment beyond the commercially available labeling reagent coupled to the long‐Stokes‐shift fluorophore. © 2021 Wiley Periodicals LLC.Basic Protocol 1: Four‐probe immunofluorescence labelingBasic Protocol 2: Four‐probe immunofluorescence imaging
Species distribution models for invasive Eurasian watermilfoil highlight the importance of data quality and limitations of discrimination accuracy metrics
Authors: Thomas Shyam M. , Verhoeven Michael R. , Walsh Jake R. , Larkin Daniel J. , Hansen Gretchen J. A. 
Published: August 2021

AbstractAimAvailability of uniformly collected presence, absence, and abundance data remains a key challenge in species distribution modeling (SDM). For invasive species, abundance and impacts are highly variable across landscapes, and quality occurrence and abundance data are critical for predicting locations at high risk for invasion and impacts, respectively. We leverage a large aquatic vegetation dataset comprising point‐level survey data that includes information on the invasive plant Myriophyllum spicatum (Eurasian watermilfoil) to: (a) develop SDMs to predict invasion and impact from environmental variables based on presence–absence, presence‐only, and abundance data, and (b) compare evaluation metrics based on functional and discrimination accuracy for presence–absence and presence‐only SDMs.LocationMinnesota, USA.MethodsEurasian watermilfoil presence–absence and abundance information were gathered from 468 surveyed lakes, and 801 unsurveyed lakes were leveraged as pseudoabsences for presence‐only models. A Random Forest algorithm was used to model the distribution and abundance of Eurasian watermilfoil as a function of lake‐specific predictors, both with and without a spatial autocovariate. Occurrence‐based SDMs were evaluated using conventional discrimination accuracy metrics and functional accuracy metrics assessing correlation between predicted suitability and observed abundance.ResultsWater temperature degree days and maximum lake depth were two leading predictors influencing both invasion risk and abundance, but they were relatively less important for predicting abundance than other water quality measures. Road density was a strong predictor of Eurasian watermilfoil invasion risk but not abundance. Model evaluations highlighted significant differences: Presence–absence models had high functional accuracy despite low discrimination accuracy, whereas presence‐only models showed the opposite pattern.Main conclusionComplementing presence–absence data with abundance information offers a richer understanding of invasive Eurasian watermilfoil's ecological niche and enables evaluation of the model's functional accuracy. Conventional discrimination accuracy measures were misleading when models were developed using pseudoabsences. We thus caution against the overuse of presence‐only models and suggest directing more effort toward systematic monitoring programs that yield high‐quality data.
Large-scale evolution of body temperatures in land vertebrates
Authors: Moreira Matthew O. , Qu Yan-Fu , Wiens John J. 
Published: August 2021

AbstractBody temperature is a crucial variable in animals that affects nearly every aspect of their lives. Here we analyze for the first time largescale patterns in the evolution of body temperatures across terrestrial vertebrates (tetrapods: including amphibians, mammals, birds and other reptiles). Despite the traditional view that endotherms (birds and mammals) have higher body temperatures than ectotherms, we find they are not significantly different. However, rates of body-temperature evolution are significantly different, with lower rates in endotherms than ectotherms, and the highest rates in amphibians. We find that body temperatures show strong phylogenetic signal and conservatism over 350 million years of evolutionary history in tetrapods, and some lineages appear to have retained similar body temperatures over time for hundreds of millions of years. Although body temperatures are often unrelated to climate in tetrapods, we find that body temperatures are significantly related to day-night activity patterns. Specifically, body temperatures are generally higher in diurnal species than nocturnal species, both across ectotherms and, surprisingly, across endotherms also. Overall, our results suggest that body temperatures are significantly linked to phylogeny and diel-activity patterns within and among tetrapod groups, rather than just climate and the endotherm-ectotherm divide.
Blood glucose lowering and effect of oyster (Pleurotus ostreatus)‐ and shiitake (Lentinus subnudus)‐supplemented diet on key enzymes linked diabetes and hypertension in streptozotocin‐induced diabetic in rats
Authors: Agunloye Odunayo Michael , Oboh Ganiyu 
Published: August 2021

AbstractDiabetes is a global pandemic typified by impaired carbohydrate metabolism. In folklore, mushrooms consumption has been linked to diabetes management. However, this study aims to unravel the blood‐glucose‐lowering mechanisms of oyster mushroom (Pleurotus ostreatus) and shiitake mushroom (Lentinus subnudus) in streptozotocin induced‐diabetic rats. Forty two adult Wistar rats were randomly divided into seven groups: the control (C), untreated diabetic rats (group 2), diabetic rats treated with acarbose (25 mg/bodyweight) (group 3), and diabetic rats placed on diet supplemented with 10% and 20% oyster mushroom and shiitake mushroom designated as groups 4–7, respectively. The experiment lasted for 14 days. However, the fasting blood glucose (FBG), activity of α‐amylase, α‐glucosidase, angiotensin‐1 converting enzyme (ACE), arginase, lipid peroxidation, and antioxidant status in rat's pancreas and heart were evaluated. The FBG level, activity of α‐amylase, α‐glucosidase, ACE, and arginase were all reduced significantly (p < .05) in normal rats and in diabetic rat placed on oyster mushroom and shiitake mushroom inclusion diets when compared with untreated diabetic rats. Similarly, activity of superoxide dismutase and catalase was significantly (p < .05) elevated in diets‐treated diabetic rats when compared with an untreated diabetic rat. Also, elevated malondialdehyde equivalent compounds in untreated diabetic rats were significantly reduced in diabetic rats fed with the supplemented diets. Nevertheless, oyster‐mushroom‐ and shiitake‐mushroom‐supplemented diets exhibited FBG lowering ability, reduced activity of α‐amylase, α‐glucosidase, ACE, and improved diabetic rats antioxidant status. Nevertheless, shiitake‐mushroom‐supplemented diets exhibited better effects than oyster‐mushroom‐supplemented diets in treated diabetic rats.
Improving the efficacy and reliability of rTMS language mapping by increasing the stimulation frequency
Authors: Nettekoven Charlotte , Pieczewski Julia , Neuschmelting Volker , Jonas Kristina , Goldbrunner Roland , Grefkes Christian , Weiss Lucas Carolin 
Published: August 2021

AbstractRepetitive TMS (rTMS) with a frequency of 5–10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right‐handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2–5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC = .315) and 30 Hz (ICC = .427), whereas 50 Hz showed a moderate reliability (ICC = .597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS‐protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest.
Hepatitis E virus RNA‐dependent RNA polymerase is involved in RNA replication and infectious particle production
Authors: Oechslin Noémie , Da Silva Nathalie , Szkolnicka Dagmara , Cantrelle François‐Xavier , Hanoulle Xavier , Moradpour Darius , Gouttenoire Jérôme 
Published: August 2021

Abstract

Background and Aims
Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis worldwide. Its positive‐strand RNA genome encodes three open reading frames (ORF). ORF1 is translated into a large protein composed of multiple domains and is known as the viral replicase. The RNA‐dependent RNA polymerase (RDRP) domain is responsible for the synthesis of viral RNA.

Approach and Results
Here, we identified a highly conserved α‐helix located in the RDRP thumb subdomain. Nuclear magnetic resonance demonstrated an amphipathic α‐helix extending from amino acids 1628 to 1644 of the ORF1 protein. Functional analyses revealed a dual role of this helix in HEV RNA replication and virus production, including assembly and release. Mutations on the hydrophobic side of the amphipathic α‐helix impaired RNA replication and resulted in the selection of a second‐site compensatory change in the RDRP palm subdomain. Other mutations enhanced RNA replication but impaired virus assembly and/or release.

Conclusions
Structure‐function analyses identified a conserved amphipathic α‐helix in the thumb subdomain of the HEV RDRP with a dual role in viral RNA replication and infectious particle production. This study provides structural insights into a key segment of the ORF1 protein and describes the successful use of reverse genetics in HEV, revealing functional interactions between the RDRP thumb and palm subdomains. On a broader scale, it demonstrates that the HEV replicase, similar to those of other positive‐strand RNA viruses, is also involved in virus production.
Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance
Authors: Hlady Ryan A. , Zhao Xia , El Khoury Louis Y. , Luna Aesis , Pham Kien , Wu Qunfeng , Lee Jeong‐Heon , Pyrsopoulos Nikolaos T. , Liu Chen , Robertson Keith D. 
Published: August 2021

Abstract

Background and Aims
Chronic HCV infection is a leading etiologic driver of cirrhosis and ultimately HCC. Of the approximately 71 million individuals chronically infected with HCV, 10%‐20% are expected to develop severe liver complications in their lifetime. Epigenetic mechanisms including DNA methylation and histone modifications become profoundly disrupted in disease processes including liver disease.

Approach and Results
To understand how HCV infection influences the epigenome and whether these events remain as “scars” following cure of chronic HCV infection, we mapped genome‐wide DNA methylation, four key regulatory histone modifications (H3K4me3, H3K4me1, H3K27ac, and H3K27me3), and open chromatin in parental and HCV‐infected immortalized hepatocytes and the Huh7.5 HCC cell line, along with DNA methylation and gene‐expression analyses following elimination of HCV in these models through treatment with interferon‐α (IFN‐α) or a direct‐acting antiviral (DAA). Our data demonstrate that HCV infection profoundly affects the epigenome (particularly enhancers); HCV shares epigenetic targets with interferon‐α targets; and an overwhelming majority of epigenetic changes induced by HCV remain as “scars” on the epigenome following viral cure. Similar findings are observed in primary human patient samples cured of chronic HCV infection. Supplementation of IFN‐α/DAA antiviral regimens with DNA methyltransferase inhibitor 5‐aza‐2’‐deoxycytidine synergizes in reverting aberrant DNA methylation induced by HCV. Finally, both HCV‐infected and cured cells displayed a blunted immune response, demonstrating a functional effect of epigenetic scarring.

Conclusions
Integration of epigenetic and transcriptional data elucidate key gene deregulation events driven by HCV infection and how this may underpin the long‐term elevated risk for HCC in patients cured of HCV due to epigenome scarring.
Hepatocyte‐specific deletion of adipose triglyceride lipase (adipose triglyceride lipase/patatin‐like phospholipase domain containing 2) ameliorates dietary induced steatohepatitis in mice
Authors: Fuchs Claudia D. , Radun Richard , Dixon Emmanuel D. , Mlitz Veronika , Timelthaler Gerald , Halilbasic Emina , Herac Merima , Jonker Johan W. , Ronda Onne A. H. O. , Tardelli Matteo , Haemmerle Guenter , Zimmermann Robert , Scharnagl Hubert , Stojakovic Tatjana , Verkade Henkjan J. , Trauner Michael 
Published: August 2021

Abstract

Background and Aims
Increased fatty acid (FA) flux from adipose tissue to the liver contributes to the development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting adipose triglyceride lipase (ATGL)/patatin‐like phospholipase domain containing 2 (PNPLA2), the main enzyme driving lipolysis, may attenuate steatohepatitis.

Approach and Results
Hepatocyte‐specific ATGL knockout (ATGL LKO) mice were challenged with methionine‐choline–deficient (MCD) or high‐fat high‐carbohydrate (HFHC) diet. Serum biochemistry, hepatic lipid content and liver histology were assessed. Mechanistically, hepatic gene and protein expression of lipid metabolism, inflammation, fibrosis, apoptosis, and endoplasmic reticulum (ER) stress markers were investigated. DNA binding activity for peroxisome proliferator‐activated receptor (PPAR) α and PPARδ was measured. After short hairpin RNA–mediated ATGL knockdown, HepG2 cells were treated with lipopolysaccharide (LPS) or oleic acid:palmitic acid 2:1 (OP21) to explore the direct role of ATGL in inflammation in vitro. On MCD and HFHC challenge, ATGL LKO mice showed reduced PPARα and increased PPARδ DNA binding activity when compared with challenged wild‐type (WT) mice. Despite histologically and biochemically pronounced hepatic steatosis, dietary‐challenged ATGL LKO mice showed lower hepatic inflammation, reflected by the reduced number of Galectin3/MAC‐2 and myeloperoxidase‐positive cells and low mRNA expression levels of inflammatory markers (such as IL‐1β and F4/80) when compared with WT mice. In line with this, protein levels of the ER stress markers protein kinase R–like endoplasmic reticulum kinase and inositol‐requiring enzyme 1α were reduced in ATGL LKO mice fed with MCD diet. Accordingly, pretreatment of LPS‐treated HepG2 cells with the PPARδ agonist GW0742 suppressed mRNA expression of inflammatory markers. Additionally, ATGL knockdown in HepG2 cells attenuated LPS/OP21‐induced expression of proinflammatory cytokines and chemokines such as chemokine (C‐X‐C motif) ligand 5, chemokine (C‐C motif) ligand (Ccl) 2, and Ccl5.

Conclusions
Low hepatic lipolysis and increased PPARδ activity in ATGL/PNPLA2 deficiency may counteract hepatic inflammation and ER stress despite increased steatosis. Therefore, lowering hepatocyte lipolysis through ATGL inhibition represents a promising therapeutic strategy for the treatment of steatohepatitis.
Assessing job crafting competencies to predict tradeoffs between competing outcomes
Authors: Bruning Patrick F. , Campion Michael A. 
Published: August 2021

AbstractWe introduce the job crafting competency construct and apply it to predict tradeoffs between competing outcomes that are inherent in job crafting, like performance and well‐being or engagement and withdrawal. Job crafting competencies are the clusters of individual knowledge, skills, and abilities that are necessary to achieve personal objectives through effective job crafting problem‐solving. We create a framework of job crafting competencies consisting of comprehensive/simplistic heuristic information use and approach/avoidance problem‐solving skills. In Study 1, we operationalize competencies as profiles demonstrated through an aptitude‐oriented assessment that predicts differences in outcomes. Five distinct profiles emerged in a sample of 174 workers. The high‐volume analytic problem‐solving profile was associated with higher performance and strain, while the ambivalent acquiescence profile was associated with lower performance and strain. The practical problem‐solving profile minimized tradeoffs between performance and strain. Rapid problem‐solving and low‐volume analytic problem‐solving profiles were variants in between these other patterns. Study 2 used a survey of 323 workers to support the uniqueness of the five competencies, and their relationships with approach/avoidance job crafting, engagement, and withdrawal. The research identifies a new job crafting individual difference (job crafting competencies) to delineate outcomes and tradeoffs according to unique competency profiles.
Heat and mass transfer characteristics of double‐diffusive natural convection in a porous annulus: A higher‐order compact approach
Authors: Dutta Sailen , Kalita Jiten C. 
Published: August 2021

AbstractIn this paper, we apply a reconstructed higher‐order compact scheme on nonuniform grids to the problem of double‐diffusive natural convection in a vertical porous annulus. The Darcy model is adopted for the fluid flow coupled with energy and mass equations. Computations are carried out in the regime , , , , and , where is the aspect ratio, is the radius ratio, is the Lewis number, is the buoyancy ratio, and is the thermal Rayleigh number. Extensive computations are carried out to investigate the influence of these parameters on the flow and a general pattern of heat and mass transfer characteristics emerges from the study. Particular attention has been paid to the transient flow behavior while investigating the influence of on the buoyancy ratio configuration.