bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic validation of the use of tocilizumab, statins and dexamethasone in COVID-19
Authors: Schooling CM , Yeung SL Au , Kwok MK , Zhao JV 
Published: July 2020

AbstractBackgroundNew means of treating COVID-19 are urgently needed. Genetic validation of drugs can foreshadow trial results, and help prioritize investigations. We assessed whether common drugs, suggested as possible treatments for COVID-19 (tocilizumab, anakinra and statins) with established genetic proxies, are effective in COVID-19. We also included dexamethasone as a positive control exposure because the RECOVERY trial suggested benefit in severe COVID-19.MethodsWe assessed, using Mendelian randomization, whether genetic proxies of tocilizumab, anakinra, statins and dexamethasone use affected risk of very severe (cases=536, non-cases=329391) or hospitalized (cases=3199, non-cases=897488) COVID-19 using a recent genome-wide association study.ResultsUsing rs2228145 (IL6R) to proxy effects of tocilizumab use, no association with very severe COVID-19 was found, but possibly an inverse association with hospitalized COVID-19 (odds ratio (OR) 0.83 per standardized effect of higher soluble interleukin-6r, 95% confidence interval 0.67 to 1.02). Using rs12916 (HMGCR) to proxy effects of statins use, an inverse association with very severe COVID-19 was found (OR 0.30 per standardized effect, 95% CI 0.10 to 0.89). Using rs6743376 and rs1542176 to proxy effects of anakinra use, no associations with COVID-19 were found. Dexamethasone, instrumented by cortisol, was possibly inversely associated with very severe COVID-19 (OR 0.20 per standardized effect 95% CI 0.04 to 1.04).ConclusionOur study provides some genetic validation for the use of both tocilizumab and statins in COVID-19, but not anakinra, whilst being consistent with the findings from the RECOVERY trial about dexamethasone. Investigation of the underlying mechanisms might facilitate re-purposing and development of effective treatments.
Individuals with and without Normal Tension Glaucoma Exhibit Comparable Performance on Tests of Cognitive Function
Authors: Cui Qi N. , Green David , Jethi Mohit , Porco Travis C. , Kuo Jane , Driver Todd , Ward Michael , Possin Katherine , Ou Yvonne 
Published: July 2020

AbstractAimGlaucoma and dementia are both age-related neurodegenerative diseases with significant societal impact. Despite evidence suggesting an association between normal tension glaucoma (NTG) and dementia, lack of consensus remains due to conflicting reports. This cross-sectional cohort study administered a battery of neurocognitive tests targeting executive function, learning, and memory in subjects with NTG and unaffected controls to evaluate aspects of cognition impacted by dementia.MethodsFifty NTG and 50 control patients ≥ 50 years of age were recruited from the UCSF Department of Ophthalmology. Demographic data and glaucoma parameters were extracted from electronic medical records for both groups. Tests of executive function (Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [EXAMINER]) and learning and memory (California Verbal Learning Test–Second Edition [CVLT-II]) were administered to both NTG and Controls. Race, handedness, best-corrected visual acuity, maximum intraocular pressure, optic nerve cup-to-disc ratio, visual field and optic nerve optical coherence tomography parameters, and a measure of general health (Charlson Comorbidity Index) were compared between NTG and Controls as well as within NTG subgroups. Multivariate linear regression was used to compare group performances on the EXAMINER battery and CVLT-II while controlling for age, sex, and years of education.ResultsNTG and Controls were comparable with respect to age, sex, race, education, handedness, and the Charlson Comorbidity Index (p>0.05 for all). Performance on the EXAMINER composite score and the CVLT-II did not differ between NTG and Controls (p>0.05 for both).ConclusionsThis is the first prospective study in which the cognitive function of subject with NTG were evaluated using a comprehensive, computerized neurocognitive battery. Subjects with NTG subjects did not perform worse than unaffected controls on tests of executive function, learning, and memory. Results do not support the hypothesis that individuals with NTG are at higher risk for cognitive dysfunction and/or dementia.
The structure and spontaneous curvature of clathrin lattices at the plasma membrane
Authors: Sochacki Kem A. , Heine Bridgette L. , Haber Gideon J. , Jimah John R. , Prasai Bijeta , Alfonzo-Mendez Marco A. , Roberts Aleah D. , Somasundaram Agila , Hinshaw Jenny E. , Taraska Justin W. 
Published: July 2020

AbstractClathrin mediated endocytosis is the primary pathway for receptor and cargo internalization in eukaryotic cells. It is characterized by a polyhedral clathrin lattice that coats budding membranes. The mechanism and control of lattice assembly, curvature, and vesicle formation at the plasma membrane has been a matter of longstanding debate. Here, we use platinum replica and cryo electron microscopy and tomography to present a global structural framework of the pathway. We determine the shape and size parameters common to clathrin-mediated endocytosis. We show that clathrin sites maintain a constant surface area during curvature across multiple cell lines. Flat clathrin is present in all cells and spontaneously curves into coated pits without additional energy sources or recruited factors. Finally, we attribute curvature generation to loosely connected and pentagon-containing flat lattices that can rapidly curve when a flattening force is released. Together, these data present a new universal mechanistic model of clathrin-mediated endocytosis.
Strategic HRM and organisational performance: does turnover intention matter?
Authors: Haque Amlan 
Published: July 2020

PurposeApplying the job-demand resources model and the psychological contract theory, this paper aims to examine the mediating influence of employee turnover intentions (ETI) on the relationship between strategic human resource management (SHRM) and perceived organisational performance (POP).Design/methodology/approachWith a two-phase data-collection method, 200 complete responses were collected through an online questionnaire survey. This study applied a structural equation modelling to examine the multivariate associations and provided comprehensive outcomes for the proposed hypothesised model.FindingsThis study suggests that SHRM has direct significant effects on both ETI and POP; partial mediational effect on POP via ETI; and ETI has negative effect on POP.Practical implicationsThis paper suggests that organisations aiming higher POP should encourage SHRM and improve their strategic approaches of HRM. The implications of the study results can help organisations to recognise the adverse effects of ETI and effective SHRM outcomes.Originality/valueDespite the significant relationship between HRM and organisational performance, limited empirical research has been conducted on the mediational influence of ETI. This paper examines the unique meditational role of ETI on the relationship between SHRM and POP, which has not been utterly observed from employee perspective.
Knowledge sharing and absorptive capacity: interdependency and complementarity
Authors: Balle Andrea Raymundo , Oliveira Mírian , Curado Carla Maria Marques 
Published: July 2020

Purpose
This study aims to resolve contradictions in the literature regarding the relationship between knowledge sharing (KS) and absorptive capacity (AC). The authors analyze the reasons for which KS has been interpreted as an antecedent and those for which it has been seen as a consequent of AC.

Design/methodology/approach
The study uses a systematic review of the literature to identify the arguments supporting the relationships between the constructs and propose a model. Additionally, the hypotheses were tested using SEM to assess the proposed model.

Findings
The findings reveal the nature of the relationship between KS and AC. Suggesting AC is bi-dimensional, consisting of potential AC and realized AC, while the relationship between these two dimensions depends on KS.

Research limitations/implications
This study provides consistent theoretical grounds for future empirical research. The study findings demonstrate KS provides a real contribution towards AC, validating the previous literature on the impact of KS antecedents on realized AC. Additionally, the authors provide evidence to suggest knowledge donation is an output of the AC process, thus generating a debate on the nature of knowledge donation (requested vs unrequested), which raises interesting research questions to be addressed in the future. As a limitation, empirical data was only collected in the context of software development in two countries.

Practical implications
The results elucidate the central role of knowledge collection within AC. For managers, the importance of the role of knowledge collection to fully benefit from AC and exploit knowledge is highlighted.

Originality/value
The research design is original in that it combines a systematic and integrative literature review to the ground and propose hypotheses with empirically testing of the emerging model. The study clarifies the relationship between KS and AC, providing evidence to show knowledge donation is an output of the AC process. The benefits of this study can be seen at the team and firm-level.
Negotiating conflicts of interest: working with multiple stakeholders
Authors: Kristensen Catharina Juul 
Published: July 2020

PurposeThe purpose of this article is to examine conflicts of interest (COI) in qualitative social research with multiple and often powerful stakeholders such as organisations and funders.Design/methodology/approachThe article offers an explorative qualitative analysis of a selected group of Danish doctoral students' experiences and negotiations of COI in their qualitative, multiple stakeholder research. The point of departure is that while potential and readily identifiable sources of COI, such as funding institutions, are important to disclose this may provide inadequate insight into stakeholders' actual – and potentially undue – influence on the research during the research process. This calls for a focus on research practice. Finally, the current neoliberal policy changes affecting universities provide the backdrop for the study.FindingsFocusing on negotiations around COI in practice, the analysis illuminates the complex reality of negotiating different – and sometimes conflicting – expectations and interests when conducting long-term qualitative studies. It also shows examples of stakeholders' attempts to potentially, and unduly, influence doctoral students' research. Finally, it suggests that stakeholders and researchers alike can be both powerful and potentially vulnerable when engaging in qualitative research.Originality/valueThe article contributes to the existing literature by explicitly focusing on COI in qualitative social research, and by exploring experiences and negotiations of COI in practice.
Sequential co‐infections drive parasite competition and the outcome of infection
Authors: Zilio Giacomo , Koella Jacob C. 
Published: July 2020

Abstract

Co‐infections by multiple parasites are common in natural populations. Some of these are likely to be the result of sequential rather than simultaneous infections. The timing of the co‐infections may affect their competitive interactions, thereby influencing the success of the parasites and their impact on the host. This may have important consequence for epidemiological and eco‐evolutionary dynamics.

We examined in two ecological conditions the effect of sequential co‐infection on the outcome of infection by two microsporidians, Vavraia culicis and Edhazardia aedis, that infect the mosquito Aedes aegypti. The two parasites have different transmission strategies: V. culicis is transmitted horizontally either among larvae or from adults to larvae, while E. aedis can be transmitted horizontally among larvae or vertically from females to their eggs.

We investigated how the timing and order of the co‐infection and how the host's food availability affected the parasite's transmission potential (the percentage of individuals that harboured transmissible spores) and the host's juvenile survival, its age at emergence and its longevity.

The outcome of co‐infection was strongly affected by the order at which the parasites arrived. In co‐infections, V. culicis had greater horizontal transmission if it arrived early, whereas the transmission potential of E. aedis, either vertical or horizontal, was not affected by the competitor V. culicis. The availability of food determined the duration of infection leading to variation in mortality and in the transmission potential. For both parasites low food decreased juvenile survival, delayed emergence to adulthood and increased horizontal transmission potential. High food increased juvenile survival and the probability of emergence with higher vertical transmission for E. aedis. Overall, our results suggest that early infection favours transmission and that (a) V. culicis plastically responded to co‐infection, (b) E. aedis was not affected by co‐infection but it was more susceptible to factors extending or decreasing the time it spent in the host (time of infection and food).

Our results emphasize the complexity of the impact of co‐infection on host–parasite interactions. In particular, the timing and order of sequential co‐infections can result in different within‐host dynamics and modify infection outcomes.
Characterization of NMCR‐2, a new non‐mobile colistin resistance enzyme: implications for an MCR‐8 ancestor
Authors: Ullah Saif , Ji Kai , Li Jun , Xu Yongchang , Jiang Chengjian , Zhang Huimin , Huang Man , Feng Youjun 
Published: July 2020

SummaryMCR‐4 and MCR‐8 are two recently identified members of an ongoing MCR family of colistin resistance. Although that aquatic reservoir for MCR‐4 is proposed, the origin and mechanism of MCR‐8 is poorly understood. Here we report a previously unrecognized non‐mobile colistin resistance enzyme, termed NMCR‐2, originating from the plant pathogen Kosakonia pseudosacchari. NMCR‐2 (551aa) gives 67.3% identity to MCR‐8 (565aa). NMCR‐2 is placed as a progenitor/ancestor for MCR‐8 in phylogeny of MCR members. Genetic study reveals that nmcr‐2 is comparable to mcr‐8 in the ability of producing phenotypic colistin resistance. Biochemical analyses determine that these two enzymes catalyse the transfer of PEA from the donor PE lipid substrate to the recipient lipid A molecule by a putative ‘ping‐pong’ trade‐off. Further experiment of protein engineering demonstrates that the two motifs (TM region and catalytic domain) of NMCR‐2 are functionally exchangeable with that of MCR‐8, rather than MCR‐1. Physiological impacts of nmcr‐2 and/or mcr‐8 are detected in Escherichia coli, featuring with fitness cost. Evidently, the action and mechanism of NMCR‐2 is analogous to that of MCR‐8. Therefore, our finding underlines that NMCR‐2 might be a possible progenitor of MCR‐8.
Transboundary crisis management under the volcano: The case of the Icelandic ash cloud
Authors: Bravo‐Laguna Carlos 
Published: July 2020

AbstractThis paper discusses the intricacies of external transboundary crises, namely those cross‐border threats whose management requires coordination among EU and non‐EU countries. Specifically, it explores the extent to which European integration theories shed light on the coordination of external transboundary crisis responses by assessing the weight and role of the actor constellations involved in the civil aviation response to the 2010 Icelandic ash cloud crisis. The use of social network analysis as a methodological tool generates novel empirical evidence on the configuration of crisis management structures. The analysis shows that many EU Member States led decision‐making, whereas supranational organizations were instrumental in the coordination of the ash cloud crisis response. The centrality of these bodies contrasts with the peripheral position of most interest groups. This paper also suggests that external transboundary crises present complex management dynamics that distinguish them from generic transboundary threats. For example, the response to the ash cloud crisis was not commanded by the European Economic Area/European Free Trade Association countries where its epicentre was located. The empirical analysis was based on information extracted from a survey to experts involved in the management of this episode, as well as from ten semi‐structured elite interviews.
Tick‐borne viruses: Current trends in large‐scale viral surveillance
Authors: Park Ki Beom , Jo Yong Hun , Kim Nam‐Yeon , Lee Wook‐Gyo , Lee Hee‐Il , Cho Shin‐Hyeong , Patnaik Bharat Bhusan , Han Yeon Soo 
Published: July 2020

AbstractTicks are ectoparasites that transmit pathogens, such as tick‐borne viruses, to their hosts. Tick‐borne viruses are diverse: they can be categorized into two orders, nine families, and at least 12 genera. Almost 25% of these viruses are infectious to humans and some are a serious threat to public health. The global rise in tick‐borne virus diseases has been linked to climate change which has reduced tick mortality in the winter and extended their active period. The spread of tick‐borne viral diseases to humans has received significant interest due to the increased threat to human life; epidemiological monitoring of tick‐borne viruses using molecular, immunological, and environmental methods is now a priority. Nevertheless, many tick‐borne diseases remain undiagnosed, which poses a challenge to public administration and health care officials. This review discusses three major tick‐borne RNA viruses that cause serious infection in humans: severe fever with thrombocytopenia syndrome (SFTS) virus, tick‐borne encephalitis (TBE), and Crimean–Congo hemorrhagic fever (CCHF) virus. Specifically, we discuss the epidemiological monitoring, vector control measures, molecular diagnostics, vaccines, and environmental determinants related to these viruses. Furthermore, we review the current surveillance of these tick‐borne viruses with a specific focus on diagnostic approaches that employ molecular interventions such as viral nucleic acid isolation, PCR‐based diagnostics, and high‐throughput sequencing technologies.
Effects of Groundwater‐Surface Water Exchange Mechanism in the National Water Model over the Northern High Plains Aquifer, USA
Authors: Jachens Elizabeth R. , Hutcheson Holly , Thomas Matthew B. , Steward David R. 
Published: July 2020

AbstractSurface water and groundwater are intimately connected by a two‐way flux between the stream and underlying aquifers. The National Water Model (NWM) currently only considers a one‐way flux, where groundwater can enter a stream but cannot return to the aquifer. The Northern High Plains Aquifer, USA is used as a case study to investigate the consequences of omitting two‐way stream–aquifer fluxes on streamflow prediction capabilities of the NWM during hydrologic extremes. Instead of traditional field techniques to identify stream–aquifer fluxes, this study presents an integrated approach to classify likely stream regimes using three identification methods: United States Geological Survey (USGS) gage data, simulated stream–aquifer fluxes from an existing USGS Groundwater Availability Model, and the normalized difference vegetation index from remote sensing. For flood events, the modeled flood response for losing streams is characterized by statistically significant earlier peak discharges and an overestimate of the observed flood volume when compared to gaining streams. For drought events, our study found no statistical difference between losing and gaining streams, however, modeled streamflow from the NWM overestimated the observed USGS hydrograph. The systematic overestimate of streamflow by the NWM could be, in part, due to the lack of a losing stream mechanism which was on average 0.1% streamflow loss per streamwise km along the river.
Bayesian compositional regression with structured priors for microbiome feature selection
Authors: Zhang Liangliang , Shi Yushu , Jenq Robert R. , Do Kim‐Anh , Peterson Christine B. 
Published: July 2020

AbstractThe microbiome plays a critical role in human health and disease, and there is a strong scientific interest in linking specific features of the microbiome to clinical outcomes. There are key aspects of microbiome data, however, that limit the applicability of standard variable selection methods. In particular, the observed data are compositional, as the counts within each sample have a fixed‐sum constraint. In addition, microbiome features, typically quantified as operational taxonomic units, often reflect microorganisms that are similar in function, and may therefore have a similar influence on the response variable. To address the challenges posed by these aspects of the data structure, we propose a variable selection technique with the following novel features: a generalized transformation and z‐prior to handle the compositional constraint, and an Ising prior that encourages the joint selection of microbiome features that are closely related in terms of their genetic sequence similarity. We demonstrate that our proposed method outperforms existing penalized approaches for microbiome variable selection in both simulation and the analysis of real data exploring the relationship of the gut microbiome to body mass index.
Resampling‐based confidence intervals for model‐free robust inference on optimal treatment regimes
Authors: Wu Yunan , Wang Lan 
Published: July 2020

AbstractWe propose a new procedure for inference on optimal treatment regimes in the model‐free setting, which does not require to specify an outcome regression model. Existing model‐free estimators for optimal treatment regimes are usually not suitable for the purpose of inference, because they either have nonstandard asymptotic distributions or do not necessarily guarantee consistent estimation of the parameter indexing the Bayes rule due to the use of surrogate loss. We first study a smoothed robust estimator that directly targets the parameter corresponding to the Bayes decision rule for optimal treatment regimes estimation. This estimator is shown to have an asymptotic normal distribution. Furthermore, we verify that a resampling procedure provides asymptotically accurate inference for both the parameter indexing the optimal treatment regime and the optimal value function. A new algorithm is developed to calculate the proposed estimator with substantially improved speed and stability. Numerical results demonstrate the satisfactory performance of the new methods.
Fostering students’ creativity via educational robotics: An investigation of teachers’ pedagogical practices based on teacher interviews
Authors: Yang Yuqin , Long Yanwen , Sun Daner , Van Aalst Jan , Cheng Sanyin 
Published: July 2020

AbstractThis study explored how educational robotics (ER) was implemented in classrooms to foster creativity among elementary school students and identified challenges associated with its implementation. Twenty‐six teachers at different elementary schools were interviewed. In‐depth teacher interviews and grounded theory were used to collect and analyze the interviews. We found that the intended creative learning outcome for students was mastery of the developmental process of creativity. The teachers generally reported using a four‐phase instructional framework consisting of eight sub‐phases and targeted teaching strategies to support students’ learning outcomes. Challenges included insufficient appropriate learning materials, a lack of expansive learning activities and tasks and limited opportunities to engage students in the process of design thinking and developing metacognitive abilities. The findings have practical implications for teachers and researchers who are interested in developing pedagogical practices (PP) incorporating ER to support students’ creativity. The study also has theoretical value, offering insights into teachers’ PP in implementing ER.