bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent changes in COVID-19 Vaccine Hesitancy among Healthcare Workers
Authors: O’Brien Emily C. , Xu Haolin , Cohen Lauren W. , Shenkman Elizabeth A. , Rothman Russell L. , Forrest Christopher B. , Hernandez Adrian F.
Published: March 2021

Introduction

Early COVID-19 vaccine acceptance rates suggest that up to one-third of HCWs may be vaccine-hesitant. However, it is unclear whether hesitancy among HCWs has improved with time and if there are temporal changes whether these differ by healthcare worker role.

Methods

In October 2020, a brief survey was sent to all participants in the Healthcare Worker Exposure Response and Outcomes (HERO) Registry with a yes/no question regarding vaccination under emergency use authorization (EUA): “If an FDA emergency use-approved vaccine to prevent coronavirus/COVID-19 was available right now at no cost, would you agree to be vaccinated?” The poll was repeated in December 2020, with the same question sent to all registry participants. Willingness was defined as a “Yes” response, and hesitancy was defined as a “No” response. Participants were stratified into clinical care roles. Baseline demographics of survey respondents at each timepoint were compared using appropriate univariate statistics (chi-squared and t-tests). Analyses were descriptive, with frequencies and percentages reported for each category.

Results

Of 4882 HERO active registry participants during September 1 – October 31, 2020, 2070 (42.4%) completed the October survey, and n=1541 (31.6%) completed the December survey. 70.2% and 67.7% who were in clinical care roles, respectively. In October, 54.2% of HCWs in clinical roles said they would take an EUA-approved vaccine, which increased to 76.2% in December. The largest gain in vaccine willingness was observed among physicians, 64.0% of whom said they would take a vaccine in October, compared with 90.5% in December. Nurses were the least likely to report that they would take a vaccine in both October (46.6%) and December (66.9%). We saw no statistically significant differences in age, race/ethnicity, gender, or medical role between time points. When restricting to the 998 participants who participated at both time points, 69% were vaccine-willing at both time points; 15% were hesitant at both time points, 13% who were hesitant in October were willing in December; and 2.9% who were willing in October were hesitant in December.

Conclusions

In a set of cross-sectional surveys of vaccine acceptance among healthcare workers, willingness improved substantially over 2 calendar months during which the US had a presidential election and two vaccine manufacturers released top-line Phase 3 trial results. While improved willingness was observed in all role categories, nurses reported the most vaccine hesitancy at both time points.
Preparation of large-scale digitization samples for automated electron microscopy of tissue and cell ultrastructure
Authors: Dittmayer Carsten , Goebel Hans-Hilmar , Heppner Frank L. , Stenzel Werner , Bachmann Sebastian
Published: March 2021

Manual selection of targets in experimental or diagnostic samples by transmission electron microscopy (TEM), based on single overview and detail micrographs, has been time- consuming and susceptible to bias. Substantial information and throughput gain may now be achieved by automated acquisition of virtually all structures in a given EM section. Resulting datasets allow convenient pan-and-zoom examination of tissue ultrastructure with preserved microanatomical orientation. The technique is, however, critically sensitive to artifacts in sample preparation. We therefore established a methodology to prepare large-scale digitization samples (LDS) designed to acquire entire sections free of obscuring flaws. For evaluation, we highlight the supreme performance of scanning EM in transmission mode compared to other EM technology. The use of LDS will substantially facilitate access to EM data for a broad range of applications.
The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation
Authors: Chavkin Nicholas W. , Sano Soichi , Wang Ying , Oshima Kosei , Ogawa Hayato , Horitani Keita , Sano Miho , MacLauchlan Susan , Nelson Anders , Setia Karishma , Vippa Tanvi , Watanabe Yosuke , Saucerman Jeffrey J. , Hirschi Karen K. , Gokce Noyan , Walsh Kenneth
Published: March 2021

Background

A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early pro-inflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation.

Methods and Results

The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction (TAC) surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after TAC surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2-KO mice displayed a pro-inflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, TAC surgery led to the death of all mice by day 6 that was associated with myocardial hyper-inflammation and vascular leakage.

Conclusions

Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.
Positive supercoiling favors transcription elongation through lac repressor-mediated DNA loops
Authors: Xu Wenxuan , Yan Yan , Artsimovitch Irina , Dunlap David , Finzi Laura
Published: March 2021

Some proteins, like thelacrepressor (LacI), mediate long-range loops that alter DNA topology and create torsional barriers. During transcription, RNA polymerase generates supercoiling that may facilitate passage through such barriers. We monitoredE. coliRNA polymerase progress along templates in conditions that prevented, or favored, LacI-mediated DNA looping. Tethered particle motion measurements revealed that RNA polymerase paused longer at unlooped LacI obstacles or those barring entry to a loop than those barring exit from the loop. Enhanced dissociation of a LacI roadblock by the positive supercoiling generated ahead of a transcribing RNA polymerase within a torsion-constrained DNA loop may be responsible. In support of this, RNA polymerase transcribed a looped segment more slowly than an unlooped segment and paused more briefly at LacI obstacles on positively supercoiled templates, especially under increased tension (torque). Positive supercoiling propagating ahead of polymerase appears to facilitate elongation along topologically-complex, protein-coated templates.
Widespread translational control regulates retinal development in mouse
Authors: Chen Kaining , Chen Congying , Li Huihui , Yang Jiaqi , Xiang Mengqing , Wang Hongwei , Xie Zhi
Published: March 2021

Retinal development is tightly regulated to ensure the generation of appropriate cell types and the assembly of functional neuronal circuitry. Despite remarkable advances that have been made in understanding the regulation of gene expression during retinal development, how translational regulation guides retinogenesis is less understood. Here, we conduct a comprehensive translatome and transcriptome survey to the mouse retinogenesis from the embryonic to the adult stages. We discover thousands of genes that have dynamic changes at the translational level and pervasive translational regulation in a developmental stage-specific manner with specific biological functions. We further identify genes whose translational efficiencies are frequently controlled by changing usage in the upstream open reading frames during retinal development. These genes are enriched for biological functions highly important to neurons, such as neuron projection organization and microtubule-based protein transport. Surprisingly, we discover hundreds of previously uncharacterized micropeptides, translated from putative long non-coding RNAs and circular RNAs. We validate their protein productsin vitroandin vivoand demonstrate their potentials in regulating retinal development. Together, our study presents a rich and complex landscape of translational regulation and provides novel insights into their roles during retinogenesis.
Vibration analysis of an aviation engine turbine shaft shield
Authors: Noga Stanisław , Maciejowska Kaja , Rogalski Tomasz
Published: March 2021

Purpose

This paper aims to deal with the problem of vibration in an aircraft engine turbine shaft shield. The physical model of the system under study is inspired by the PZL-10W aviation jet engine shaft shield and is a structure of the profile circular arc. The main goal of the presented research is to develop a modal model of the discussed object. Another task is to determine the impact of the shaft shield damage on the change of dynamic parameters (the values of the natural frequencies and changing of the shape of the corresponding natural forms) of the discussed object. Finally, the task is connected with the calculation of the excitation speeds of the discussed shaft shield’s respective natural frequencies.

Design/methodology/approach

To realize the main goal finite element method simulation and experimental investigation were conducted. The quality of the achieved models is determined based on the relative error of natural frequencies and the similarity to normal modes established on the basis of the modal assurance criterion (MAC) indicator. The Campbell diagram was used to calculate the excitation speeds of the discussed shaft shield’s respective natural frequencies.

Findings

The obtained results indicate the changes in the dynamic properties of the shaft shield as a result of its cracking. On the basis of the adopted measurement (MAC indicator), the level of similarity was established between the numerical simulation results and the measurement results for the undamaged shield. Verification of the different mode shapes using the CrossMAC tool is an effective method, which allows comparing of the shape of the natural form and may be helpful in the process of adjusting modal models to the results of experimental tests.

Practical implications

It is important to note that as a result of using commercial software (ANSYS program) and a commercial measuring system (Bruel and Kjaer), the presented analysis can be attractive for design engineers dealing with the dynamics of aviation systems.

Originality/value

The paper presents the authors’ original approach to the dynamic analysis of the aviation engine turbine shaft shield, which can be useful for engineers dealing with the issue of vibration in shaft shield systems.
Towards crisis protection(ism)? COVID-19 and selective de-globalization
Authors: Branicki Layla , Sullivan-Taylor Bridgette , Brammer Stephen
Published: March 2021

Purpose

Drawing on Wendt’s (1995, 1999) thin constructivist approach to international relations this paper aims to critically examine how the measures taken by the Australian Government to protect the country from coronavirus (COVID-19) have prompted politicians and opinion-makers to mobilize globalizing and de-globalizing discourses towards divergent conceptualizations of national resilience.

Design/methodology/approach

The paper examines 172 Australian political and media articles, which focus on both COVID-19 and globalization/de-globalization published between February and June 2020. The data were imported to NVivo to enable in-depth thematic analysis.

Findings

The paper develops the concept of crisis protectionism to explain how COVID-19 has been mobilized in discourses aimed at accelerating selective de-globalization in Australia. Selective de-globalization is inductively theorized as involving material structures (i.e. border closures), ideational structures (i.e. national identity) and intersubjectivities (i.e. pre-existing inter-country antagonisms).

Research limitations/implications

The paper relies upon publicly available data about Australian discourses that relate to a unique globally disrupting extreme event.

Practical implications

Crisis protectionism and selective de-globalization are important to multinational enterprises (MNE) that operate in essential industry sectors (e.g. medical supply firms), rely upon open borders (e.g. the university sector) and for MNEs entering/operating in a host country experiencing antagonistic relationships with their home country.

Originality/value

The paper extends Witt’s (2019) political theorization of de-globalization towards a socialized theory of de-globalization. By rejecting liberal and realist explanations of the relationship between COVID-19 and de-globalization, this study highlights the importance and endogeneity of non-market risks and non-economic logic to international business and MNE strategy.
Understanding the intention to revisit a destination by expanding the theory of planned behaviour (TPB)
Authors: Abbasi Ghazanfar Ali , Kumaravelu Janani , Goh Yen-Nee , Dara Singh Karpal Singh
Published: March 2021

Purpose

The purpose of this study is to unearth the factors that influence tourists’ revisit intention. The proposed model of the study is grounded on using the theory of planned behaviour (TPB) and extending it with additional variables, i.e. satisfaction, destination image, perceived risk, service quality and perceived value.

Design/methodology/approach

This study adopted a cross-sectional approach to collect data. The data were collected by conducting a field survey questionnaire on 330 respondents and were analysed using partial least squares version 3.2.9.

Findings

The results show that perceived behavioural control, perceived value, destination image and satisfaction significantly affect visitors’ revisit intention. The influence of perceived value, perceived service quality and destination image on satisfaction is also confirmed. On the other hand, satisfaction is found to be a significant mediator between perceived service quality, destination image and perceived value.

Originality/value

The extended TPB model that includes perceived service quality, perceived value, perceived risk and satisfaction provided a model with a theoretical basis to explain tourist revisit intentions to a tourist destination.
Providing, Performing and Protecting: The Importance of Work Identities in Negotiating Conflicting Work–Family Ideals as a Single Mother
Authors: Radcliffe Laura , Cassell Catherine , Malik Fatima
Published: March 2021

The aims of this paper are twofold. First, we aim to expand understanding of work–family experiences beyond the prevalent emphasis on traditional couple‐headed families within organization and management literatures by focusing on the experiences of employed single mothers. Second, we aim to gain insight into how work and family meanings may be negotiated in the context of heightened conflicting ideals and demands. Drawing on rich qualitative data from in‐depth interviews and diaries, our findings make three important contributions to the existing work–family literature. First, we show that conflicting work and family ideals are not only exacerbated for single mothers, but viable narrative strategies with which to negotiate this conflict are also restricted. Second, we highlight how narratives constructed around the meaning of work are key to single mothers’ negotiation of conflicting work and family ideals and identify three work narratives drawn upon by single mothers focused on providing, performing and protecting. Finally, we demonstrate how shifts between single mothers’ work narratives are particularly influenced by progression opportunities and a supportive work environment. We conclude by making suggestions for future work–family research.
Early‐ and late‐onset postpartum depression exhibit distinct associated factors: the IGEDEPP prospective cohort study
Authors: Tebeka S , Le Strat Y , Mandelbrot L , Benachi A , Dommergues M , Kayem G , Lepercq J , Luton D , Ville Y , Ramoz N , Mullaert J , Dubertret C ,   IGEDEPP Groups
Published: March 2021

Objective

To identify risk factors for early‐ and late‐onset postpartum depression (PPD) among a wide range of variables, including sociodemographic characteristics, childhood trauma, stressful life events during pregnancy and history of personal and family psychiatric disorders, and to assess the contribution of each risk factor.

Design

Nested case–control study in a prospective longitudinal cohort study.

Setting

Eight maternity departments in the Paris metropolitan area, France.

Sample

A cohort of 3310 women with deliveries between November 2011 and June 2016.

Methods

Cases were women with early‐ or late‐onset PPD. Controls were women without depression during pregnancy or the postpartum period. Logistic regression adjusted on sociodemographic variables was performed for each outcome and a multivariable model was proposed based on a stepwise selection procedure.

Main outcome measures

Early‐ and late‐onset PPD assessed at 2 months and 1 year postpartum, respectively.

Results

Stressful life events during pregnancy have a dose–response relationship with both early‐ and late‐onset PPD.

Conclusions

Early‐ and late‐onset PPD presented distinct patterns of determinants. These results have important consequences in terms of prevention and specific care.

Tweetable abstract

Early‐ and late‐onset postpartum depression are associated with stressful life events and psychiatric history.
Non‐destructive DNA recovery from handwritten documents using a dry vacuum technique
Authors: McLaughlin Patrick , Hopkins Christian , Springer Eliot , Prinz Mechthild
Published: March 2021

Investigations of many crimes such as robberies, kidnappings, and terrorism are often associated with the recovery of a paper document which has been written by the perpetrator. Paper can provide a variety of forensic evidence such as DNA, latent fingermarks, and indented writing. The focus of this study was DNA recovery from handwritten notes through a vacuum suction device while preserving the other evidence types and the integrity of the document. Copy paper was used to create handwritten documents and sheets with deliberate fingerprints, and indentations. The homemade vacuum device consists of a glass pipette blocked with a moistened swab and attached to a vacuum source. The method collected sufficient DNA amounts for DNA typing analysis with 80% of the 11 copy paper samples tested giving probative DNA profiles with five being eligible for DNA database entry. DNA recovery was also tested on other commonly encountered paper types. DNA quantities would have been sufficient for STR typing for approximately 50% of manila envelopes and notebook paper samples, but not for magazine pages and bank deposit slips. Deliberate sebaceous and eccrine latent fingermarks placed onto copy paper and developed with magnetic fingerprint developer or 1,2 indanedione were not affected by the vacuum swabbing technique. Simulated robbery notes with indented writing and processed using an Electrostatic Detection Apparatus (ESDA) demonstrated no interference through the DNA collection. This vacuum‐based collection method enables laboratories to reverse the current questioned document workflow and start with DNA collection.
Purification and characterization of a novel cypermethrin‐hydrolyzing esterase from Bacillus licheniformis B‐1
Authors: Zhang Mengmei , Lai Wen , Zhu Yuanting , Chen Shujuan , Zhou Kang , Ao Xiaolin , He Li , Yang Yong , Zou Likou , Liu Aiping , Yao Kai , Liu Shuliang
Published: March 2021

Cypermethrin (CY) is a synthetic pyrethroid widely used to control insect pests and it elicits a toxic effect on the human body. In this study, Bacillus licheniformis B‐1 isolated from tea garden soil was used to degrade CY effectively. A specific enzyme was mainly localized in the extracellular compartments of B‐1. This enzyme was identified as an esterase that could be produced without CY. The enzyme was purified 23.03‐fold to apparent homogeneity with 8.38% overall recovery by ammonium sulfate precipitation, anion exchange chromatography, and gel filtration chromatography. The molecular mass of the CY‐degrading enzyme was 66.4 kDa, and its optimal pH and temperature were 8.5 and 40 °C, respectively. Appropriate Zn2+, Mn2+, Mg2+, Tween 80, SDS, Triton X‐100, and BSA concentrations could greatly increase the activity of this enzyme. By contrast, EDTA, 1,10‐phenanthroline, NaF, and PMSF strongly inhibited its activity. The purified enzyme showed Km and Vmax values were 5.532 nmol/mL and 33.445 nmol/min. The CY residue in lettuce and cherry tomatoes could be removed more than 50% under the conditions of the treatment concentration for 500 mg/L and the enzyme preparation dilution of 100 times. These results suggested that the CY‐degrading enzyme, a constitutive enzyme that mainly exists in the extracellular space, was a novel esterase that might be used to detoxify CY, and could remove CY in vegetables effectively.

Practical Application

Our research found a novel cypermethrin‐hydrolyzing esterase from Bacillus licheniformis B‐1 and proved that the enzyme could remove cypermethrin in vegetables effectively.
Improving the reliability of eDNA data interpretation
Authors: Burian Alfred , Mauvisseau Quentin , Bulling Mark , Domisch Sami , Qian Song , Sweet Michael
Published: March 2021

Global declines in biodiversity highlight the need to effectively monitor the density and distribution of threatened species. In recent years, molecular survey methods detecting DNA released by target‐species into their environment (eDNA) have been rapidly on the rise. Despite providing new, cost‐effective tools for conservation, eDNA‐based methods are prone to errors. Best field and laboratory practices can mitigate some, but the risks of errors cannot be eliminated and need to be accounted for. Here, we synthesize recent advances in data processing tools that increase the reliability of interpretations drawn from eDNA data. We review advances in occupancy models to consider spatial data‐structures and simultaneously assess rates of false positive and negative results. Further, we introduce process‐based models and the integration of metabarcoding data as complementing approaches to increase the reliability of target‐species assessments. These tools will be most effective when capitalizing on multi‐source data sets collating eDNA with classical survey and citizen‐science approaches, paving the way for more robust decision‐making processes in conservation planning.
Competitive differential pricing
Authors: Chen Yongmin , Li Jianpei , Schwartz Marius
Published: March 2021

We analyze welfare under differential versus uniform pricing across oligopoly markets that differ in costs of service, and establish general demand conditions for differential pricing by symmetric firms to increase consumer surplus, profit, and total welfare. The analysis reveals why competitive differential pricing is generally beneficial—more than price discrimination—but not always, including why profit may fall, unlike for monopoly. The presence of more competitors tends to enlarge consumers' share of the gain from differential pricing, though profits often still rise. When firms have asymmetric costs, however, profit or consumer surplus can fall even with ‘simple’ linear demands.
Detecting Financial Misreporting with Real Production Activity: Evidence from an Electricity Consumption Analysis*
Authors: Allee Kristian D. , Baik Bok , Roh Yongoh
Published: March 2021

This study examines whether a real production activity measure, firm‐level electricity consumption growth, is useful in detecting firm financial misreporting. Identifying proxies for a firm's underlying financial performance that are not a function of the firm's accounting system is essential for detection of misreporting. We propose that the difference between revenue growth and electricity consumption growth (i.e., growth wedge (GW)) is a useful signal of financial misreporting. Using electricity consumption data for Korean firms from 2006 to 2014, we find that the GW is positively associated with discretionary revenues and accruals and the likelihood of financial misreporting as proxied by accounting restatements, qualified audit opinions, and regulatory enforcement actions. The GW provides incremental information over firm characteristics and earnings management signals examined by prior research. Our findings are robust to a battery of additional tests, including within‐firm and industry comparisons that do not require access to cross‐sectional firm‐level electricity data. Overall, our study documents new evidence on the role of a real production activity measure from an independent reporting entity in detecting financial misreporting. Our evidence speaks to the potential usefulness of real activity metrics in forensic economics.
Animal‐related facial fractures in South Australia
Authors: Diab Jason , H. Moore Mark
Published: March 2021

Background

Animal‐related facial fractures can affect livelihoods impacting the hard and soft tissues of the face. Animal husbandry and recreational sports have close relationships with animals, which can lead to injuries equivalent to those of road traffic accidents and assaults. Our aim is to describe epidemiological trends of animal‐related facial fractures in the paediatric and adult age group across South Australia.

Methods

A retrospective review from January 2012 to January 2017 at the Women and Children's Hospital and Royal Adelaide Hospital in Adelaide. All animal‐related injuries that attended or were referred to the unit were included in this study.

Results

There were 50 patients who presented with an animal‐related facial fracture. There was an equal distribution of males to females with horses as the most common animal to cause injury from kicking. The orbit and orbitozygomatic fracture equally represented the most common type of facial fracture with 38% of all cases having an associated injury. The operative rate was 56% with four post‐operative complications. There were differences between males and females for season, post‐operative complications and length of stay (P < 0.05). Females, multiple fractures and associated injuries were independently associated with increased length of stay (P = 0.001).

Conclusions

Female adolescents and young women involved with horses were more likely to have facial fractures with associated injuries, post‐operative complications and an extended length of stay compared to males. Educational awareness for trainees about interdisciplinary care and prevention strategies for patients are key to better understanding and managing facial trauma.
Yokoyama procedure for esotropia associated with high myopia: real‐world data from a large‐scale multicentre analysis
Authors: Wabbels Bettina , Fricke Julia , Schittkowski Michael , Gräf Michael , Lorenz Birgit , Bau Viktoria , Nentwich Martin M. , Atili Abed , Eckstein Anja , Sturm Veit , Beisse Christina , Sterker Ina , Neppert Birte , Mauschitz Matthias M.
Published: March 2021

Purpose

High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far.

Methods

We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models.

Results

We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia.

Conclusion

Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large‐scale real‐world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.
Activation of thyroid hormone receptor‐β improved disease activity and metabolism independent of body weight in a mouse model of non‐alcoholic steatohepatitis and fibrosis
Authors: Kannt Aimo , Wohlfart Paulus , Madsen Andreas Nygaard , Veidal Sanne Skovgård , Feigh Michael , Schmoll Dieter
Published: March 2021

Background and Purpose

Activation of hepatic thyroid hormone receptor β (THR‐β) is associated with systemic lipid lowering, increased bile acid synthesis, and fat oxidation. In patients with non‐alcoholic steatohepatitis (NASH), treatment with THR‐β agonists decreased hepatic steatosis and circulating lipids, and induced resolution of NASH. We chose resmetirom (MGL‐3196), a liver‐directed, selective THR‐β agonist, as a prototype to investigate the effects of THR‐β activation in mice with diet‐induced obesity (DIO) and biopsy‐confirmed advanced NASH with fibrosis.

Experimental Approach

C57Bl/6J mice were fed a diet high in fat, fructose, and cholesterol for 34 weeks, and only biopsy‐confirmed DIO‐NASH mice with fibrosis were included. Resmetirom was administered at a daily dose of 3 mg·kg−1 p.o., for 8 weeks. Systemic and hepatic metabolic parameters, histological non‐alcoholic fatty liver disease (NAFLD) activity and fibrosis scores, and liver RNA expression profiles were determined to assess the effect of THR‐β activation.

Key Results

Treatment with resmetirom did not influence body weight but led to significant reduction in liver weight, hepatic steatosis, plasma alanine aminotransferase activity, liver and plasma cholesterol, and blood glucose. These metabolic effects translated into significant improvement in NAFLD activity score. Moreover, a lower content of α‐smooth muscle actin and down‐regulation of genes involved in fibrogenesis indicated a decrease in hepatic fibrosis.

Conclusion and Implications

Our model robustly reflected clinical observations of body weight‐independent improvements in systemic and hepatic metabolism including anti‐steatotic activity.
The role of statins in the differentiation and function of bone cells
Authors: Chamani Sajad , Liberale Luca , Mobasheri Leila , Montecucco Fabrizio , Al‐Rasadi Khalid , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: March 2021

Background

Statins are 3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low‐density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL‐cholesterol (LDL‐C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL‐C‐lowering impact, statins also have other so‐called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation.

Design

The most relevant papers on the bone‐related ‘pleiotropic’ effects of statins were selected following literature search in databases and were reveiwed.

Results

Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein‐2 (BMP‐2), glucocorticoids, transforming growth factor‐beta (TGF‐β), alkaline phosphatase (ALP), type I collagen and collagenase‐1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation.

Conclusion

This review summarizes the literature exploring bone‐related ‘pleiotropic’ effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis.
CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma
Authors: He Min , Han Ying , Cai Changjing , Liu Ping , Chen Yihong , Shen Hong , Xu Xingyuan , Zeng Shan
Published: March 2021

CLEC10A, (C‐type lectin domain family 10, member A), as the member of C‐type lectin receptors (CLRs), plays a vital role in modulating innate immunity and adaptive immunity and has shown great potential as an immunotherapy target for cancers. However, there is no functional research of CLEC10A in prognostic risk, immunotherapy or any other treatment of lung adenocarcinoma (LUAD). We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analysed with online databases such as HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB. We found that lower expression of CLEC10A was accompanied with worse outcomes of LUAD patients. Moreover, CLEC10A expression was significantly correlated with a variety of the tumour‐infiltrating immune cells (TIICs). As a promising prognosis predictor and potential immunotherapy target, the potential influence and mechanisms of CLEC10A in LUAD deserve further exploring.
CIDEC silencing attenuates diabetic nephropathy via inhibiting apoptosis and promoting autophagy
Authors: Zheng Gao‐shu , Tan Yan‐min , Shang Yuan‐yuan , Liu Ya‐peng , Hu Bo‐ang , Wang Di , Han Lu , Wang Zhi‐hao , Zhang Wei , Ti Yun , Zhong Ming
Published: March 2021

Objective

The role of cell death‐inducing DFF45‐like effector C (CIDEC) in insulin resistance has been established, and it is considered to be an important trigger factor for the progression of diabetic nephropathy (DN). We intend to explore whether CIDEC plays an important role in the regulation of DN and its potential mechanism.

Methods

High‐fat diet and low dose streptozotocin were used to establish type 2 diabetic rat model. We investigate the role of CIDEC in the pathogenesis and process of DN through histopathological analysis, western blot and gene silencing. Meanwhile, the effect of CIDEC on renal tubular epithelial cells stimulated by high glucose was also verified.

Results

DM group exhibited glucose and lipid metabolic disturbance, with hypertrophy of kidneys, damaged renal function, increased apoptosis, decreased autophagy, glomerulosclerosis and interstitial fibrosis. CIDEC gene silencing improved metabolic disorder and insulin resistance, alleviated renal hypertrophy and renal function damage, decreased glomerular and tubular apoptosis, increased autophagy and inhibited renal fibrosis. At the cellular level, high glucose stimulation increased CIDEC expression in renal tubular epithelial cells, accompanied by increased apoptosis and decreased autophagy. CIDEC gene silencing can improve autophagy and reduce apoptosis. At the molecular level, CIDEC gene silencing also decreased the expression of early growth response factor (EGR)1 and increased the expression of adipose triglyceride lipase (ATGL).

Conclusion

CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.
Global publication productivity in dermatology: a bibliometric description of the past and estimation of the future
Authors: Gantenbein L. , Arora P. , Navarini A. , Brandt O. , Mueller S.M.
Published: March 2021

Background

In the past two centuries, generations of dermatologists around the world have created an enormous number of publications. To our knowledge, no bibliometric analysis of these publications has been performed so far, nor have registered trials been analysed to anticipate future publication trends.

Objectives

To determine the global distribution of national publication productivity, most published topics, institutions and funding sources contributing most to publications and to anticipate future trends based on registered clinical trials.

Methods

Following pre‐assessment on PubMed, Embase, Web of Science and Scopus, the number of publications for ‘dermatology’ was determined for each of 195 countries, normalized per 1 Mio inhabitants and bibliometrically analysed. Dermatology‐related trials registered at clinicaltrials.gov were specified by the top‐10 diagnoses for the top‐10 countries.

Results

The search yielded 1 071 518 publications between 1832 and 2019 with the top‐5 diagnoses being melanoma, basal cell carcinoma, psoriasis, pruritus/itch and atopic dermatitis. The top‐3 countries with highest absolute numbers of publications were the USA (30.6%), Germany (8.1%) and the UK (8.1%), whereas Switzerland, Denmark and Sweden had the highest publication rates when normalized by inhabitants. The most productive affiliation was the Harvard Medical School, the leading funding source the National Institutes of Health. Currently, maximum number of trials are registered in the USA (8111), France (1543) and Canada (1368). The highest percentage of all dermatology‐related trials in a specific country were as follows: Melanoma in the Netherlands (24.8%), psoriasis in Germany (21.7%) and atopic dermatitis in Japan (15.9%).

Conclusion

The top‐10 countries including the USA, Canada, a few European and Asian countries contributed more than 3/4 of all publications. The USA hold the dominant leader position both in past publication productivity and currently registered trials. While most Western countries continue to focus their research on the top‐10 topics, China and India appear to prioritize their scope towards other topics.
Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell‐to‐cell viral transfer
Authors: Valdebenito Silvana , Castellano Paul , Ajasin David , Eugenin Eliseo A.
Published: March 2021

The major barrier to eradicating Human immunodeficiency virus‐1 (HIV) infection is the generation of tissue‐associated quiescent long‐lasting viral reservoirs refractory to therapy. Upon interruption of anti‐retroviral therapy (ART), HIV replication can be reactivated. Within the brain, microglia/macrophages and a small population of astrocytes are infected with HIV. However, the role of astrocytes as a potential viral reservoir is becoming more recognized because of the improved detection and quantification of HIV viral reservoirs. In this report, we examined the infectivity of human primary astrocytes in vivo and in vitro, and their capacity to maintain HIV infection, become latently infected, be reactivated, and transfer new HIV virions into neighboring cells. Analysis of human brain tissue sections obtained from HIV‐infected individuals under effective and prolonged ART indicates that a small population of astrocytes has integrated HIV‐DNA. In vitro experiments using HIV‐infected human primary astrocyte cultures confirmed a low percentage of astrocytes had integrated HIV‐DNA, with poor to undetectable replication. Even in the absence of ART, long‐term culture results in latency that could be transiently reactivated with histone deacetylase inhibitor, tumor necrosis factor‐alpha (TNF‐α), or methamphetamine. Reactivation resulted in poor viral production but efficient cell‐to‐cell viral transfer into cells that support high viral replication. Together, our data provide a new understanding of astrocytes' role as viral reservoirs within the central nervous system (CNS).

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The impact of ultraviolet radiation on skin photoaging — review of in vitro studies
Authors: Gromkowska‐Kępka Krystyna Joanna , Puścion‐Jakubik Anna , Markiewicz‐Żukowska Renata , Socha Katarzyna
Published: March 2021

Background

Photoaging, ultra violet (UV) induced skin aging is a gradual process that depends on the time and intensity of solar radiation.

Aim

The aim of this paper was to review of the literature focused on in vitro studies explaining the mechanisms of photoaging.

Methods

Electronic databases, including PubMed and MEDLINE, were searched for in vitro studies on the importance of UV radiation in the skin photoaging process of peer‐reviewed scientific journals. Only articles available in English and full version publications were considered for this review.

Results

Three main modes of UV radiation action on skin cells which lead to photoaging, there are changes in cell metabolism, induction of oxidative stress due to the change in enzyme activity.

Conclusion

The information gathered in this publication will help to better understand the complex and multidirectional mechanism of skin photoaging, which will contribute to the development of research on potential cosmetic products that provide effective and safe sun protection or repair damage caused by UV radiation.
Mining oomycete proteomes for metalloproteases leads to identification of candidate virulence factors in Phytophthorainfestans
Authors: Schoina Charikleia , Rodenburg Sander Y. A. , Meijer Harold J. G. , Seidl Michael F. , Lacambra Lysette T. , Bouwmeester Klaas , Govers Francine
Published: March 2021

Pathogens deploy a wide range of pathogenicity factors, including a plethora of proteases, to modify host tissue or manipulate host defences. Metalloproteases (MPs) have been implicated in virulence in several animal and plant pathogens. Here we investigated the repertoire of MPs in 46 stramenopile species including 37 oomycetes, 5 diatoms, and 4 brown algae. Screening their complete proteomes using hidden Markov models (HMMs) trained for MP detection resulted in over 4,000 MPs, with most species having between 65 and 100 putative MPs. Classification in clans and families according to the MEROPS database showed a highly diverse MP repertoire in each species. Analyses of domain composition, orthologous groups, distribution, and abundance within the stramenopile lineage revealed a few oomycete‐specific MPs and MPs potentially related to lifestyle. In‐depth analyses of MPs in the plant pathogen Phytophthora infestans revealed 91 MPs, divided over 21 protein families, including 25 MPs with a predicted signal peptide or signal anchor. Expression profiling showed different patterns of MP gene expression during pre‐infection and infection stages. When expressed in leaves of Nicotiana benthamiana, 12 MPs changed the sizes of lesions caused by inoculation with P. infestans; with 9 MPs the lesions were larger, suggesting a positive effect on the virulence of P. infestans, while 3 MPs had a negative effect, resulting in smaller lesions. To the best of our knowledge, this is the first systematic inventory of MPs in oomycetes and the first study pinpointing MPs as potential pathogenicity factors in Phytophthora.
The α isoform of cGMP‐dependent protein kinase 1 (PKG1α) is expressed and functionally important in intrinsic primary afferent neurons of the guinea pig enteric nervous system
Authors: Li Zhi S. , Hung Lin Y. , Margolis Kara G. , Ambron Richard T. , Sung Ying J. , Gershon Michael D.
Published: March 2021

Background

Intrinsic primary afferent neurons (IPANs) enable the gut to manifest reflexes in the absence of CNS input. PKG1α is selectively expressed in a subset of neurons in dorsal root ganglia (DRG) and has been linked to nociception and long‐term hyperexcitability.

Methods

We used immunoblotting, immunocytochemistry, and in vitro assays of IPAN‐dependent enteric functions to test hypotheses that subsets of primary neurons of the ENS and DRG share a reliance on PKG1α expression.

Key Results

PKG1α immunoreactivity was demonstrated in immunoblots from isolated myenteric ganglia. PKG1α, but not PKG1β, immunoreactivity, was coincident with that of neuronal markers (HuC/D; β3‐tubulin) in both enteric plexuses. PKG1α immunoreactivity also co‐localized with the immunoreactivities of the IPAN markers, calbindin (100%; myenteric plexus) and cytoplasmic NeuN (98 ± 1% submucosal plexus). CGRP‐immunoreactive DRG neurons, identified as visceral afferents by retrograde transport, were PKG1α–immunoreactive. We used intraluminal cholera toxin to determine whether PKG1α was necessary to enable stimulation of the mucosa to activate Fos in enteric neurons. Tetrodotoxin (1.0 µM), low Ca2+/high Mg2+ media, and the PKG inhibitor, N46 (100 µM), all inhibited Fos activation in myenteric neurons. N46 also concentration dependently inhibited peristaltic reflexes in isolated preparations of distal colon (IC50 = 83.3 ± 1.3 µM).

Conclusions & Inferences

These data suggest that PKG1α is present and functionally important in IPANs and visceral afferent nociceptive neurons.
Investigating new serological and tissue markers for the follow‐up of patients operated for alveolar echinococcosis
Authors: Bellanger Anne‐Pauline , Wang Junhua , Gbaguidi‐Haore Houssein , Barrera Coralie , Bresson‐Hadni Solange , Zlobec Inti , Lachenmayer Anja , Richou Carine , Turco Celia , Gottstein Bruno , Millon Laurence , Beldi Guido
Published: March 2021

Aims

Alveolar echinococcosis (AE) is characterized by a chronically progressing hepatic injury caused by Echinococcus multilocularis. Surgery presently remains the best curative option. Currently, biological predictive features derived from the resected specimens are not suitable to assess surgery efficacy. The present study was designed to investigate whether a selection of markers measured on the resected specimens exhibits predictive features related to parasite viability, or to a total elimination of the parasite, in addition to serological markers.

Methods and Results

In a collaboration between two centres, one in France (Besançon), and one in Switzerland (Bern), samples from 40 AE patients were analysed by microarray and serology techniques, individually. Paired serum samples before and after surgery were obtained for 26 patients. In the sera, a significant decrease in PD‐L1 levels was observed after surgery, in addition to anti‐Em18 levels. In the liver tissue, low levels of Cluster of Differentiation (CD)‐3 were correlated with the absence of serum anti‐Em18 after surgery.

Conclusion

This study showed PD‐L1 is promising as a potential serological marker and further confirmed the performance of anti‐Em18 serology. Further studies on a larger cohort are needed to confirm the utility of performing systematically microarray on resected liver tissue.