bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of antiviral activity of nordihydroguaiaretic acid against Fort Sherman-like virus (Orthobunyavirus)
Authors: Martinez Florencia , Mugas María Laura , Aguilar Juan Javier , Marioni Juliana , Contigiani Marta Silvia , Núñez Montoya Susana C. , Konigheim Brenda S. 
Published: August 2020

AbstractThe genus Orthobunyavirus are a group of viruses within arbovirus, with a zoonotic cycle, some of which could lead to human infection. A characteristic of these viruses is their lack of antiviral treatment or vaccine for its prevention. The objective of this work was to study thein vitroantiviral activity of nordihydroguaiaretic acid (NDGA), the most important active compound ofLarrea divaricataCav. (Zigophyllaceae), against Fort Sherman-like virus (FSV-like) as a model of Orthobunyavirus genus. At the same time, the effect of NDGA as a lipolytic agent on the cell cycle of this viral model was assessed. The method of reducing plaque forming units on LLC-MK2 cells was used to detect the action of NDGA on CbaAr426 and SFCrEq231 isolates of FSV-like. NDGA did not show virucidal effect, but it had antiviral activity with a similar inhibition in both isolates, which was dose dependent. It was established that the NDGA has a better inhibition one-hour post infection (p.i.), showing a different behavior in each isolate, which was dependent upon the time p.i. Since virus multiplication is dependent on host cell lipid metabolism, the antiviral effect of NDGA has been previously related to its ability to disturb the lipid metabolism, probably by interfering with the sterol regulatory element-binding proteins (SREBP) pathway and the 5-lipoxigenase (5-LOX). We determined by using caffeic acid, a 5-LOX inhibitor, that the inhibition of this enzyme negatively affected the FSV-like replication; and by the use of resveratrol, a SREBP1 inhibitor, it was showed that the negative regulation of this pathway only had action on the SFCrEq231 reduction. In addition, it was proved that the NDGA acts intracellularly, since it showed the ability to incorporate into LLC-MK2 cells. The information provided in this work converts the NDGA in a good antiviral candidate, especially for Orthobunyavirus infections, and a useful tool for the biochemical study of FSV-like that causes an infection poorly studied and potentially dangerous.
The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS-mTOR signaling and vascular function
Authors: Alghanem Ahmad F. , Ta Chau , Maurer Joshua M. , Gunasekar Susheel K. , Kumar Ashutosh , Fatima Urooj , Kang Chen , Xie Litao , Adeola Oluwaseun , Abello Javier , Riker Megan , Elliot-Hudson Macaulay , Minerath Rachel A. , Stratman Amber , Grueter Chad E. , Mullins Robert F. , Sah Rajan 
Published: August 2020

AbstractThe endothelium responds to a multitude of chemical and mechanical factors in regulating vascular tone, angiogenesis, blood pressure and blood flow. The endothelial volume regulatory anion channel (VRAC) has been proposed to be mechano-sensitive, to activate in response to fluid flow/hydrostatic pressure and putatively regulate vascular reactivity and angiogenesis. Here, we show that the Leucine Rich Repeat Containing Protein 8a, LRRC8a (SWELL1) functionally encodes VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial SWELL1 (SWELL1) expression positively regulates AKT-eNOS signaling while negatively regulating mTOR signaling, via a SWELL1-GRB2-Cav1-eNOS signaling complex. Endothelium-restricted SWELL1 KO (SWELL1 KO) mice exhibit enhanced tube formation from ex-vivo aortic ring explants in matrigel angiogenesis assays, develop hypertension in response to chronic angiotensin II infusion and have impaired retinal blood flow with both diffuse and focal blood vessel narrowing in the setting of Type 2 diabetes (T2D). These data demonstrate that SWELL1 antithetically regulates AKT-eNOS and mTOR signaling in endothelium and is required for maintaining vascular function, particularly in the setting of T2D.
A distinct innate immune signature marks progression from mild to severe COVID-19
Authors: Chevrier Stéphane , Zurbuchen Yves , Cervia Carlo , Adamo Sarah , Raeber Miro E. , de Souza Natalie , Sivapatham Sujana , Jacobs Andrea , Bächli Esther , Rudiger Alain , Stüssi-Helbling Melina , Huber Lars C. , Schaer Dominik J. , Nilsson Jakob , Boyman Onur , Bodenmiller Bernd 
Published: August 2020

AbstractCoronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Excessive inflammation has been postulated to be a major factor in the pathogenesis of severe COVID-19 and innate immune mechanisms are likely to be central in the inflammatory response. We used 40-plex mass cytometry and targeted serum proteomics to profile innate immune cell populations from peripheral blood of patients with mild or severe COVID-19 and healthy controls. Sampling at different stages of COVID-19 allowed us to reconstruct a pseudo-temporal trajectory of the innate immune response. Despite the expected patient heterogeneity, we identified consistent changes during the course of the infection. A rapid and early surge of CD169+monocytes associated with an IFNγ+MCP-2+signature quickly followed symptom onset; at symptom onset, patients with mild and severe COVID-19 had a similar signature, but over the course of the disease, the differences between patients with mild and severe disease increased. Later in the disease course, we observed a more pronounced re-appearance of intermediate/non-classical monocytes and mounting systemic CCL3 and CCL4 levels in patients with severe disease. Our data provide new insights into the dynamic nature of the early inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identifies sustained pathological innate immune responses as a likely key mechanism in severe COVID-19, further supporting investigation of targeted anti-inflammatory interventions in severe COVID-19.
FDR control in GWAS with population structure
Authors: Sesia Matteo , Bates Stephen , Candès Emmanuel , Marchini Jonathan , Sabatti Chiara 
Published: August 2020

AbstractWe present a comprehensive statistical framework to analyze data from genome-wide association studies of polygenic traits, producing distinct and interpretable discoveries while controlling the false discovery rate. This approach leverages sophisticated multivariate models, correcting for linkage disequilibrium, and accounts for population structure and relatedness, adapting to the characteristics of the samples at hand. A key element is the recognition that the observed genotypes can be considered as a random sample from an appropriate model, encapsulating our knowledge of genetic inheritance and human populations. This allows us to generate imperfect copies (knockoffs) of these variables which serve as ideal negative controls; knockoffs are indistinguishable from the original genotypes in distribution, and independent from the phenotype. In sharp contrast with state-of-the-art methods, the validity of our inference in no way depends on assumptions about the unknown relation between genotypes and phenotype. We develop and leverage a model for the genotypes that accounts for arbitrary and unknown population structure, which may be due to diverse ancestries or familial relatedness. We build a pipeline that is robust to the most prominent possible confounders, facilitating the discovery of causal variants. Validity and effectiveness are demonstrated by extensive simulations with real data, as well as by the analysis of several phenotypes in the UK Biobank. Finally, fast software is made available for researchers to apply the proposed methodology to Biobank-scale data sets.
What p53 sees: ATM and ATR activation through crosstalk between DNA damage response pathways
Authors: Fedak Elizabeth A. , Adler Frederick R. , Abegglen Lisa M. , Schiffman Joshua D. 
Published: August 2020

1AbstractCells losing the ability to self-regulate in response to damage is a hallmark of cancer. When a cell encounters damage, regulatory pathways estimate the severity of damage and promote repair, cell cycle arrest, or apoptosis. This decision-making process would be remarkable if it were based on the total amount of damage in the cell, but because damage detection pathways vary in the rate and intensity with which they promote pro-apoptotic factors, the cell’s real challenge is to reconcile dissimilar signals. Crosstalk between repair pathways, crosstalk between pro-apoptotic signaling kinases, and signals induced by damage byproducts complicate the process further. The cell’s response toγand UV radiation neatly illustrates this concept. While these forms of radiation produce lesions associated with two different pro-apoptotic signaling kinases, ATM and ATR, recent experiments show that ATM and ATR react to both forms of radiation. To simulate the pro-apoptotic signal induced byγand UV radiation, we construct a mathematical model that includes three modes of crosstalk between ATM and ATR signaling pathways: positive feedback between ATM/ATR and repair proteins, ATM and ATR mutual upregulation, and changes in lesion topology induced by replication stress or repair. We calibrate the model to agree with 21 experimental claims about ATM and ATR crosstalk. We alter the model by adding or removing specific processes, then examine the effects of each process on ATM/ATR crosstalk by recording which claims the altered model violates. Not only is this the first mathematical model of ATM/ATR crosstalk, its implications provide a strong argument for treating pro-apoptotic signaling as a holistic effort rather than attributing it to a single dominant kinase.
Consumer cross-channel behaviour: is it always planned?
Authors: Maggioni Isabella , Sands Sean James , Ferraro Carla Renee , Pallant Jason Ian , Pallant Jessica Leigh , Shedd Lois , Tojib Dewi 
Published: August 2020

PurposeFor consumers, cross-channel behaviour is increasingly prevalent. Such behaviour involves consumers actively engaging in (and deriving benefit) from one channel during a product search but switching to another channel when making a purchase. Drawing on multi-attribute utility theory, this study proposes a cross-channel behaviour typology consisting of three key aspects: channel choice behaviour, functional and economic outcomes and consumer-specific psychographic and demographic variables.Design/methodology/approachSegmentation analysis conducted via latent class analysis (LCA) was performed on a sample of 400 US consumers collected via an online survey.FindingsCross-channel behaviour is not always intentional. We identify a specific segment of consumers that most often engage in unplanned, rather than intentional, cross-channel switching. We find that of all shoppers that engage in cross-channel behaviour, a fifth (20%) are forced to switch channels at the point of purchase.Practical implicationsCross-channel behaviour can be mitigated by retailers via a deep understanding of the driving factors of different configurations of showrooming and webrooming.Originality/valueIn contrast with existing conceptualisations, this study suggests that cross-channel behaviour often stems from consumers being “forced” by factors outside of their control, but within the retailers' control. This research presents a nuanced approach to decompose consumer cross-channel behaviour from the consumer perspective as planned, forced or opportunistic.
Coping with COVID-19. Dugnad: a case of the moral premise of the Norwegian welfare state
Authors: Nilsen Ann Christin Eklund , Skarpenes Ove 
Published: August 2020

PurposeThis paper provides an analysis of the notion of dugnad (collective effort) in the context of the first weeks of the outbreak of COVID-19 in Norway. By appealing to people's sense of collective effort (dugnadsånd) Norwegian leaders successfully managed to coordinate the actions of the population and beat the outbreak.Design/methodology/approachThe argument builds on the pragmatic sociology associated with Boltanski and Thévenot and their “orders of worth”. Building on qualitative interview studies of the Norwegian middle and working classes a moral ideal type labelled “the socially responsible citizen” is identified.FindingsThe authors argue that dugnad is embedded in a moral repertoire of the socially responsible citizen that is indicative of a specific Norwegian welfare mentality and that is imperative for the sustainability and resilience of the Norwegian welfare model. This repertoire is found across social classes and has to be understood in light of the Norwegian welfare model and the role of civil society.Social implicationsThe analysis explains the societal impact of the appeal and endorsement of the notion of dugnad in the context of the outbreak of COVID-19.Originality/valueThe paper explores the roots and impact of a social phenomenon that has not been a matter for much sociological analysis.
Journey of a concept: span of control – the rise, the decline, and what is next?
Authors: Zoller Yaron J. , Muldoon Jeff 
Published: August 2020

Purpose
Although the topic of span of control (SOC) has been discussed in detail in management literature and education, less focus has been placed on the decline research since the 1970s and, thus, the future relevance of the concept. By providing a historical overview of the literature on SOC through the work of key management scholars, this paper aims to explain why the literatures’ coverage of the topic has been significantly diminished in recent decades and offers suggestions as to why further research on the topic is needed.

Design/methodology/approach
The authors provide a historical literature review and analysis on the decline of SOC as a construct of interest.

Findings
The findings of the paper include a brief analysis of SOC. The concept was a very strong concept that declined as management became more scientific, rejecting classical management theory. This rejection occurred because SOC was impacted by multiple factors making it impossible to effectively study, making it imprecise. Likewise, SOC is too applied and lacked theoretical relevance. However, SOC still has value, especially when paired with a theory such as leader-member-exchange (LMX).

Originality/value
The authors argue that SOC is still relevant today and management scholars should align its study with its practice in modern organizational structures. However, its focus needs to change and be added to other theories such as LMX.
Will robo-advisors continue? Roles of task-technology fit, network externalities, gratifications and flow experience in facilitating continuance intention
Authors: Cheng Yung-Ming 
Published: August 2020

PurposeThe purpose of this study is to propose a synthetic post-adoption model based on the expectation-confirmation model (ECM) and flow theory to examine whether the fit factor, network factors and psychological factors as antecedents to end-users’ beliefs can affect their continuance intention of the robo-advisor.Design/methodology/approachThis study used the research model based on ECM and flow theory to examine the effects of the fit factor, network factors and psychological factors on end-users’ beliefs and continuance intention of the robo-advisor. Sample data were collected from end-users at three financial services companies in Taiwan. A total of 450 questionnaires were distributed and 360 (80.0%) usable questionnaires were analyzed using structural equation modeling.FindingsThis study proposes a solid research model that based on ECM and flow theory, three types of factors, namely, fit factor, network factors and psychological factors, as antecedents to end-users’ continuance intention of the robo-advisor have been examined and this study’s results strongly support the research model with all hypothesized links being significant.Originality/valueIt is particularly worth mentioning that a synthetic post-adoption model can be proposed in this study by introducing the fit factor extracted from task-technology fit model, network factors originated from the theory of network externalities and psychological factors derived from uses and gratifications theory as antecedents to perceived usefulness, confirmation, satisfaction and continuance intention referred in ECM and flow experience derived from flow theory. Thus, this study’s research model and findings can reveal deep insights into the evaluation of determinants in the field of end-users’ continuance intention of the robo-advisor.
Port service quality (PSQ) and customer satisfaction: an exploratory study of container ports in Vietnam
Authors: Phan Tien Minh , Thai Vinh V. , Vu Thao Phuong 
Published: August 2020

Purpose
This study aims to investigate the concept of port service quality (PSQ) and examine its influence on customer satisfaction in the container port sector in Vietnam. Despite the importance of the maritime industry in which port is a critical sector in the national economy, there has been no research so far which examines what PSQ entails and how it affects customer satisfaction in the context of Vietnam.

Design/methodology/approach
Following a literature review, a conceptual model of PSQ and its influence on customer satisfaction was proposed. A survey questionnaire was then developed and piloted with senior executives who are working in various container shipping lines and logistics companies in Vietnam. The questionnaire was first designed in English and then refined through the process of translation and back-translation to ensure language non-discrepancies. The survey was administered to 200 members of Vietnam Shipowners’ Association, Vietnam Logistics Associations and Vietnam Shippers’ Council. By the cut-off date, 108 questionnaires were received, in which 99 valid replies were used for further analysis.

Findings
Results from this study reveal that PSQ is a construct of 4 factors and 16 items, and that enhanced PSQ will positively influence customer satisfaction, in which the outcomes of port service performance and its image would have the greatest impact. Interestingly, most items relating to social and environmental responsibility were dropped, and this result is expected in the context of a developing country like Vietnam.

Originality/value
Findings from this research may enhance port managers’ understanding on areas of PSQ to improve so as to meet and exceed their customers’ satisfaction.
Prefiguring a feminist academia: a multi-vocal autoethnography on the creation of a feminist space in a neoliberal university
Authors: Deschner Claire Jin , Dorion Léa , Salvatori Lidia 
Published: August 2020

PurposeThis paper is a reflective piece on a PhD workshop on “feminist organising” organised in November 2017 by the three authors of this paper. Calls to resist the neoliberalisation of academia through academic activism are gaining momentum. The authors’ take on academic activism builds on feminist thought and practice, a tradition that remains overlooked in contributions on resisting neoliberalisation in academia. Feminism has been long committed to highlighting the epistemic inequalities endured by women and marginalised people in academia. This study aims to draw on radical feminist perspectives and on the notion of prefigurative organising to rethink the topic of academic activism. How can feminist academic activism resist the neoliberal academia?Design/methodology/approachThis study explores this question through a multi-vocal autoethnographic account of the event-organising process.FindingsThe production of feminist space within academia was shaped through material and epistemic tensions. The study critically reflects on the extent to which the event can be read as prefigurative feminist self-organising and as neoliberal academic career-focused self-organising. The study concludes that by creating a space for sisterhood and learning, the empowering potential of feminist organising is experienced.Originality/valueThe study shows both the difficulties and potentials for feminist organising within the university. The concept of “prefiguration” provides a theoretical framework enabling us to grasp the ongoing efforts on which feminist organising relies. It escapes a dichotomy between success and failure that fosters radical pessimism or optimism potentially hindering political action.
DNA methylation of Hugl‐2 is a prognostic biomarker in kidney renal clear cell carcinoma
Authors: Miao Yi , Cao Fang , Li Pingping , Liu Peijun 
Published: August 2020

AbstractIt has been reported that loss of Hugl‐2 contributes to tumour formation and progression in vitro and in vivo. However, whether Hugl‐2 levels decrease during kidney renal clear cell carcinoma (KIRC) and the mechanism involved remain unknown. This study aimed to investigate whether DNA methylation of Hugl‐2 reduces its expression, leading to the progression and poor prognosis of KIRC. Hugl‐2 methylation and mRNA expression and KIRC clinicopathological data were extracted from The Cancer Genome Atlas (TCGA), and relationships among these factors were analyzed using UALCAN, MethHC, Wanderer and LinkedOmics web tools. We found that Hugl‐2 mRNA and protein levels were reduced in KIRC tissues. Moreover, Hugl‐2 mRNA levels were related to tumour grade and overall survival, and Hugl‐2 methylation was increased in KIRC. According to the results of methylation‐specific PCR, KIRC cells had higher Hugl‐2 DNA methylation levels than HKC cells. Moreover, Hugl‐2 DNA methylation correlated negatively with Hugl‐2 mRNA and was also related to the pathology and T stage of KIRC patients. KIRC patients with high Hugl‐2 DNA methylation also had shorter overall survival. Additionally, methylation of cg08827674, a Hugl‐2 probe, was related to pathologic stage, T stage, neoplasm histologic grade, serum calcium level without laterality, M stage, N stage, and ethnicity. Furthermore, treatment with the DNA methylation inhibitor decitabine resulted in upregulation of Hugl‐2 mRNA and protein levels in KIRC cell lines. These results indicate that Hugl‐2 DNA methylation may be both a prognostic marker and a therapeutic target in KIRC.
Liraglutide improves obesity‐induced renal injury by alleviating uncoupling of the glomerular VEGF–NO axis in obese mice
Authors: Li Kai , Sun Jinhong , Huang Na , Ma Yuting , Han Fang , Liu Yongping , Hou Ningning , Sun Xiaodong 
Published: August 2020

AbstractObesity‐related kidney disease is associated with generalized endothelial dysfunction. Liraglutide, a glucagon‐like peptide‐1 agonist, has cardiovascular–renal protective effects in patients with diabetes. In this study, the ability of liraglutide to reduce urinary albumin excretion by alleviating glomerular vascular endothelial growth factor‐nitric oxide (VEGF–NO) axis uncoupling was assessed in high fat diet‐induced obese mice. C57BL/6J mice were divided into control and obesity groups, treated with or without liraglutide (200 μg/kg/day). Blood biochemistry and urinary albumin excretion were measured. Glomerular VEGF and the AMPK–endothelial nitric oxide synthase (eNOS) pathway were assayed by western blotting. Glomerular NO, renal haeme oxygenase‐1 activity, and malondialdehyde levels were also measured. Treatment of obese mice with liraglutide led to significant reductions in body weight gain (46 ± 1 g vs 55 ± 1 g, P < .0001), visceral fat (8.9 ± 0.6 g vs 14.5 ± 0.6 g, P < .0001), perirenal fat (2.9 ± 0.2 g vs 5.4 ± 0.3 g, P < .0001), and free fatty acid (1.71 ± 0.12 mmol/L vs 1.02 ± 0.08 mmol/L, P < .0001). Liraglutide significantly improved glucose homeostasis, which was impaired in obese mice. Liraglutide reduced urinary albumin excretion and glomerular hypertrophy in obese mice. Additionally, liraglutide significantly decreased VEGF and increased glomerular NO production in glomeruli, indicating restoration of the glomerular VEGF–NO axis. Furthermore, liraglutide activated the glomerular AMPK–eNOS pathway in obese mice, upregulated renal haeme oxygenase‐1 activity, and reduced the renal malondialdehyde levels in obese mice. In conclusion, liraglutide reduced microalbuminuria and ameliorated renal injury by alleviating the uncoupling of the glomerular VEGF–NO axis.