bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNATE IMMUNE INTERFERENCE ATTENUATES INFLAMMATION INBACILLUSENDOPHTHALMITIS
Authors: Mursalin Md Huzzatul , Coburn Phillip S. , Miller Frederick C. , Livingston Erin , Astley Roger , Callegan Michelle C. 
Published: June 2020

ABSTRACTPURPOSEBacillusendophthalmitis is a sight-threatening bacterial infection that sometimes requires enucleation. Inflammation in this disease is driven by activation of innate Toll-like receptor (TLR) pathways. Here, we explored the consequences of innate immune interference on intraocular inflammatory responses duringBacillusendophthalmitis.METHODSEndophthalmitis was induced in mice by injecting 100 CFUBacillus thuringiensisin to the mid-vitreous. We interfered with activation of the TLR2 and TLR4 pathways by 1) injecting a group of mice with S layer protein-deficient (ΔslpA)B. thuringiensisor 2) injecting a group of wild type (WT)-infected mice with a TLR2/4 inhibitor, oxidized phospholipid (OxPAPC). At 10 hours postinfection, infected eyes were removed and total RNA was purified. mRNA expression was then analyzed by NanoString using a murine inflammation panel. We compared findings with expression data from eyes infected with eyes injected with WTB. thuringiensis, eyes injected with OxPAPC alone, and uninfected eyes.RESULTSInterference of TLR2 and TLR4 pathways resulted in differential expression of mouse inflammatory genes compared to expression in WT-infected eyes. In WT-infected eyes, 56% of genes were significantly upregulated compared to that of uninfected controls. However, compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and ΔslpA-infected eyes, respectively. The expression of 61 genes which were significantly upregulated in WT-infected eyes was decreased in WT+OxPAPC or ΔslpA-infected eyes. Interference with activation of the TLR2 and TLR4 pathways resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate genes such as TLR2, TLR4, TLR6, TLR8, MyD88, Nod2, Nlrp3, NF-κB, STAT3, RelA, RelB, and Ptgs2. Interference with activation of the TLR2 and TLR4 pathways also reduced the expression of several inflammatory cytokines such as CSF3, IL-6, IL-1β, CSF2, IL-1α, TNFα, IL-23α, TGFβ1, and IL-12β and chemokines CCL2, CCl3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL9, and CXCL10. All of the aforementioned genes were significantly upregulated in WT-infected eyes.CONCLUSIONSThese results suggest that interfering with the activation of innate immune pathways duringBacillusendophthalmitis significantly reduced the intraocular inflammatory response. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment.
Corticocortical Connections of the Rostral Forelimb Area in Rats: A Quantitative Tract-Tracing Study
Authors: Urban Edward T , Nishibe Mariko , Barbay Scott , Guggenmos David J , Nudo Randolph J 
Published: June 2020

AbstractThe rostral forelimb area (RFA) in the rat is considered to be a premotor cortical region based primarily on its efferent projections to the primary motor cortex. The purpose of the present study was to identify corticocortical connections of RFA, and to describe the relative strength of connections with other cortical areas. This will allow us to better understand the broader cortical network in which RFA participates, and thus, determine its function in motor behavior. In the present study, the RFA of adult male Long-Evans rats (n=6) was identified using intracortical microstimulation techniques and injected with the tract tracer, biotinylated dextran amine (BDA). In post-mortem tissue, location of BDA-labeled terminal boutons and neuronal somata were plotted and superimposed on cortical field boundaries. The results demonstrated that the RFA has dense to moderate reciprocal connections with primary motor cortex, the frontal cortex medial and lateral to RFA, primary somatosensory cortex (S1), and lateral somatosensory areas. Importantly, S1 connections were dense to moderate in dysgranular zones, but sparse to negligible in granular zones. Cortical connections of RFA in rat are strikingly similar to cortical connections of the ventral premotor cortex in non-human primates, suggesting that these areas share similar functions.
Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
Authors: Coleman Andrew K. , Joca Humberto C. , Shi Guoli , Lederer W. Jonathan , Ward Christopher W. 
Published: June 2020

AbstractMicrotubules tune cytoskeletal stiffness to regulate the mechanics and mechanotransduction of striated muscle. While recent evidence suggests that microtubules enriched in detyrosinated α-tubulin are responsible for these effects in healthy muscle, and for their excess in disease, the possible contribution from several other α-tubulin modifications has not been investigated. Here we used genetic or pharmacologic strategies in isolated cardiomyocytes or skeletal myofibers to increase the level of acetylated α-tubulin without altering the level of detyrosinated α-tubulin. We show that microtubules enriched in acetylated α-tubulin contribute to the cytoskeletal stiffness and viscoelastic resistance, showing slowed rates of contraction and relaxation during unloaded contraction, and increased activation of NADPH Oxidase 2 (Nox2) by mechanotransduction. Together these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle in health and disease.
CD11c+CD88+CD317+myeloid cells are critical mediators of persistent CNS autoimmunity
Authors: Manouchehri Navid , Hussain Rehana Z. , Cravens Petra D. , Edelson Brian T. , Wu Gregory F. , Cross Anne H. , Doelger Richard , Loof Nicolas , Eagar Todd N. , Forsthuber Thomas G. , Calvier Laurent , Herz Joachim , Stüve Olaf 
Published: June 2020

AbstractBackgroundNatalizumab, a humanized monoclonal antibody (mAb) against α4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4-integrin in CD11c+cells should curtail their migration to the CNS and ameliorate experimental autoimmune encephalomyelitis (EAE).MethodsWe generated CD11c.Cre+/-ITGA4fl/flC57/Bl6 mice to selectively delete α4-integrin in CD11c+cells. Active immunization and adoptive transfer EAE models were employed. Multi-parameter flow cytometry was utilized to immunophenotype leukocytes. Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells.Resultsα4-integrin expression by CD11c+cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre+/-ITGA4fl/flmice. In active EAE, a delayed disease onset was observed in CD11c.Cre+/-ITGA4fl/flmice, during which CD11c+CD88+cells were sequestered in the blood. Upon EAE onset, CD11c+CD88+cells accumulated in the CNS and expressed CD317+. In adoptive transfer experiments, CD11c.Cre+/-ITGA4fl/flmice had ameliorated clinical disease associated with diminished numbers of CNS CD11c+CD88+CD317+cells. The transcription profile of CD11c+CD88+CD317+cells placed them within previously defined microglia-like cells in human CSF. We show that activated, but not naïve microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery.ConclusionCD11c+CD88+CD317+cells in the CNS promote inflammatory damage. Transcriptional analysis identifies CD11c+CD88+CD317+cells as a unique myeloid subset in human CSF. The disease-propagating effects of these cells can be antagonized using anti-CD317 mAb.
Adaptive time-dependent priors and Bayesian inference to evaluate SARS-CoV-2 public health measures validated on 31 countries
Authors: Turbé Hugues , Bjelogrlic Mina , Robert Arnaud , Gaudet-Blavignac Christophe , Goldman Jean-Philippe , Lovis Christian 
Published: June 2020

AbstractWith the rapid spread of the SARS-CoV-2 virus since Fall 2019, public health confinement measures to contain the propagation of the pandemic are taken. Our method to estimate the reproductive number using Bayesian inference with time-dependent priors enhances previous approaches by considering a dynamic prior continuously updated as restrictive measures and comportments within the society evolve. In addition, to allow direct comparison between reproductive number and introduction of public health measures in a specific country, the infection dates are inferred from daily confirmed cases and death with the mean time between a case being declared as positive and its death estimated on 1430 cases at 10.7 days. The evolution of the reproductive rate in combination with the stringency index is analyzed on 31 European countries. We show that most countries required tough state interventions with a stringency index equal to 83.6 out of 100 to reduce the reproductive number below one and control the progression of the epidemic. In addition, we show a direct correlation between the time taken to introduce restrictive measures and the time required to contain the spread of the epidemic with a median time of 8 days. Our analysis reinforces the importance of having a fast response with a coherent and comprehensive set of confinement measures to control the epidemic. Only combinations of non-pharmaceutical interventions (NPIs) have shown to be effective.
Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic
Authors: Banerjee Amitava , Chen Suliang , Pasea Laura , Lai Alvina G. , Katsoulis Michail , Denaxas Spiros , Nafilyan Vahe , Williams Bryan , Wong Wai Keong , Bakhai Ameet , Khunti Kamlesh , Pillay Deenan , Noursadeghi Mahdad , Wu Honghan , Pareek Nilesh , Bromage Daniel , McDonagh Theresa A. , Byrne Jonathan , Teo James T.H. , Shah Ajay M , Humberstone Ben , Tang Liang V. , Shah Anoop S. V. , Rubboli Andrea , Guo Yutao , Hu Yu , Sudlow Cathie L. M. , Lip Gregory Y. H. , Hemingway Harry 
Published: June 2020

BackgroundCardiovascular diseases(CVD) increase mortality risk from coronavirus infection(COVID-19), but there are concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both “direct”, through infection, and “indirect”, through changes in healthcare.MethodsWe used population-based electronic health records from 3,862,012 individuals in England to estimate pre- and post-COVID-19 mortality risk(“direct” effect) for people with incident and prevalent CVD. We incorporated: (i)pre-COVID-19 risk by age, sex and comorbidities, (ii)estimated population COVID-19 prevalence, and (iii)estimated relative impact of COVID-19 on mortality(relative risk, RR: 1.5, 2.0 and 3.0). For “indirect” effects, we analysed weekly mortality and emergency department data for England/Wales and monthly hospital data from England(n=2), China(n=5) and Italy(n=1) for CVD referral, diagnosis and treatment until 1 May 2020.FindingsCVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy and England during the pandemic. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown, and is still reduced in Italy and England. Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous(peak RR 1.4). For total CVD(incident and prevalent), at 10% population COVID-19 rate, we estimated direct impact of 31,205 and 62,410 excess deaths in England at RR 1.5 and 2.0 respectively, and indirect effect of 49932 to 99865 excess deaths.InterpretationSupply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the COVID-19 pandemic.FundingNIHR, HDR UK, Astra Zeneca
Gender differences in mental health prevalence in autism
Authors: Sedgewick Felicity , Leppanen Jenni , Tchanturia Kate 
Published: June 2020

PurposeMental health conditions are known to be more common amongst autistic than non-autistic people. To date, there is little work exploring gender differences in mental health amongst autistic people and no work including non-binary/trans people. This paper aims to address this gap.Design/methodology/approachThis was a large-scale online study, with 948 participants between 18 and 81 years old. Participants self-reported autism, anxiety, depression and eating disorder status. Analyses were run examining gender differences in the rates of these conditions in each group.FindingsAutistic people are more likely to have anxiety and depression than non-autistic people of all genders. Autistic women and non-binary people experienced mental health issues at higher rates than men and at similar rates to each other. Autistic people were twice as likely as non-autistic people to have all eating disorders. Further, gendered patterns of eating disorders seen in the non-autistic population are also present in the autistic population.Research limitations/implicationsThere are inherent issues with self-report of diagnoses online, but this study showed that using screening questionnaires is effective.Originality/valueThis is the first paper to look at gender differences in common mental health issues amongst autistic and non-autistic adults. It highlights that there are significant gendered patterns in the prevalence of mental health issues in both the autistic and non-autistic population and that these have an impact for how treatment should be approached to be effective.
Capturing differences in conservatism following earnings restatements: further evidence from Tehran Stock Exchange
Authors: Farhangdoust Shayan , Sayadi Lida 
Published: June 2020

PurposeThe present study seeks to shed further light on the effectiveness of Basu (1997) and Khan and Watts' (2009) differential timeliness metrics in detecting predictable differences in conservatism following corrections of restated earnings.Design/methodology/approachUsing cross-sectional and time-series analyses for companies listed on the Tehran Stock Exchange during 2009–2013, the results indicate lower conservatism for restating firms as compared to their counterparts during prerestatement period.FindingsUsing cross-sectional and time-series analyses for companies listed on the Tehran Stock Exchange during 2009–2013, the results indicate lower conservatism for restating firms as compared to their counterparts during prerestatement period. In contrast, our findings are indicative of higher conservatism among these restating firms during the years of restatements. Moreover, the time-series approach captures a higher conservatism for the restating firms during restatement years than prerestatement periods. Overall, these results provide insight into the usefulness of the metrics used in the restatement setting.Originality/valueSimilar to recent papers, the present study seeks to shed further light on the ability of Basu-based coupled with Khan–Watts-based measures of conservatism to detect situations in which companies' earnings are known to be significantly restated.
Does entrepreneurial leadership encourage innovation work behavior? The mediating role of creative self-efficacy and support for innovation
Authors: Akbari Morteza , Bagheri Afsaneh , Imani Saheb , Asadnezhad Mohammad 
Published: June 2020

PurposeThe crucial importance of innovation leadership for high technology small and medium-size enterprises (SMEs) has been suggested in the literature. However, few studies empirically examined the impact of leadership style on innovation work behavior (IWB) of employees in the context of SMEs. Furthermore, our knowledge is limited about how leaders of high technology SMEs influence the IWB of their employees. The present study explores the effect of entrepreneurial leadership on IWB of employees and introduces creative self-efficacy and support for innovation as the mechanisms through which the leaders encourage their employees' IWB in information and communications technology (ICT) SMEs in Iran.Design/methodology/approachThe sample was selected from high technology ICT SMEs using the simple random sampling method and included 175 CEOs and owner-managers of the businesses. We used validated questionnaires to test the hypothesized relationships between entrepreneurial leadership, IWB, creative self-efficacy and support for innovation.FindingsThe findings show that entrepreneurial leadership has a significant and positive impact on IWB of employees in ICT SMEs. Furthermore, employees’ creative self-efficacy and leaders’ support for innovation mediate the relationship between entrepreneurial leadership and IWB. Implications of the results and suggestions for developing IWB among the employees of high technology SMEs are suggested.Originality/valueThe study makes important contributions to both entrepreneurial leadership and the innovation behavior literature and theory development specifically in high technology SMEs in the transitioning economy of Iran. The findings also contribute to the existing empirical studies on how entrepreneurial leadership affects IWB of employees by examining the mediating role of creative self-efficacy and support for innovation and in the settings of ICT high technology SMEs.
Mandatory integrated reporting disclosure and corporate misreporting
Authors: Hoang Thinh Gia , Vu Trang Kieu , Nguyen Ha Tuyet , Luu Hiep Ngoc 
Published: June 2020

PurposeThis paper aims to enrich our understanding of whether mandatory IR adoption lures firm into misreporting or forces them to reduce it.Design/methodology/approachThe empirical analysis is carried out based on the sample containing all publicly listed firms in South Africa. Many different rigorous econometric techniques are adopted to thoroughly evaluate whether corporate misreporting practices increase or decrease following the mandatory adoption of IR.FindingsThe empirical results reveal that mandatory IR disclosure results in a decline in the misreporting practices of firms. The authors further find that as firms increasingly comply with the IR guidelines, especially with the “Content Elements” and “Guiding Principles,” their misreporting levels decrease.Research limitations/implicationsThis study has implications for a wide range of stakeholders, especially for regulatory authorities, international policymakers and regulators, as well as users of integrated reports of listed firms on the Johannesburg Stock Exchange (JSE).Practical implicationsRegulatory authorities should be aware of misreporting determinants to set adequate and fitting corporate reporting standards that restrict the opportunistic behaviour of managers and amend IR guidelines to make them more comprehensible for integrated report preparers, therefore improves the implementation of IR.Social implicationsThis study sheds light on the current state and consequences of IR adoption in South Africa before and after the mandatory IR disclosure requirement, thus, international policymakers and regulators can refer to the critical aspects in our findings when considering whether to support IR mandatory adoption in their markets.Originality/valueThis paper sheds light on the emerging debate over the usefulness of IR and the necessity of mandatorily adopting this new reporting framework. In addition, by showing that the mandatory adoption of IR significantly reduces corporate misreporting practices, we also contribute to the literature on corporate misreporting behaviour.
The relationship between the audit committee, internal audit and firm performance
Authors: Alzeban Abdulaziz 
Published: June 2020

PurposeThis study explores the role played by audit committees (ACs) in illuminating the effectiveness of internal audit (IA) as a facilitator of the achievement of organisational goals, specifically examining whether the AC mediates the relationship between IA and firm performance (FP).Design/methodology/approachData are gathered from survey questionnaires directed to chief internal auditors (CIAs) and from the annual reports of 119 listed companies in Saudi Arabia (SA) and the United Arab Emirates (UAE). Ordinary least squares (OLS) regression and mediation tests are used to assess the study’s hypotheses.FindingsThe findings indicate that the independence of the AC and having members with accounting and auditing expertise mediate the effects of IA independence and size on FP. However, no such mediation is found with respect to IA competence and FP. Further, AC meetings do not mediate the effects of IA characteristics on FP. Additional measures of the tested variables determine the robustness of the obtained findings.Originality/valueWhile much research examines the relationship between FP and corporate governance (CG) mechanisms, this study considers IA, as a key element of CG, and its impact on FP, which has received more limited attention. Hence, the findings contribute to the literature by providing new understandings regarding IA as a component of CG and its relationship with FP. Furthermore, they bring additional evidence of the influence of IA upon FP, which is mediated by AC independence and expertise.
Adherence to expense report approval control: an application of the theory of planned behavior
Authors: Héroux Sylvie , Fortin Anne , Goupil Céline 
Published: June 2020

PurposeThis study aims to identify sociocognitive determinants of managers' adherence to the expense report approval control. A behavioral view of control was adopted, drawing on the theory of planned behavior.Design/methodology/approachManagers authorized to approve subordinates' expense reports in three large organizations were surveyed.FindingsResults indicate that managers' perception of overall consequences (for the organization or for themselves) resulting from their adherence to the expense report approval control (attitude) and their perception of control over the approval (perceived behavioral control) are positively related to their intention to adhere to the expense report approval control, while their perceived pressures from important referents in that matter (subjective norm) are not.Research limitations/implicationsBy adopting a behavioral view of control to examine individual-level adherence, this study contributes to the accounting literature. By focusing on a positive response to control (adherence), it contributes specifically to the literature on control effectiveness and acts as a counterpoint to the abundant literature on negative control responses such as fraud.Practical implicationsResults could help organizations identify motivations and barriers to managers' adherence to expense report approval control. This could help reduce losses, improve asset safeguarding and provide insights into the understanding of behavioral/individual factors that can influence the application of other control policies and procedures.Originality/valueThe study defines and measures the “adherence” construct in a control context.