bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Association Study Meta-Analysis for Parkinson’s Disease Motor Subtypes
Authors: Alfradique-Dunham Isabel , Al-Ouran Rami , von Coelln Rainer , Blauwendraat Cornelis , Hill Emily , Luo Lan , Stillwell Amanda , Young Emily , Tan Manuela , Liao Calwing , Hernandez Dena G. , Pihlstrom Lasse , Grosset Donald , Shulman Lisa M. , Liu Zhandong , Rouleau Guy A. ,   International Parkinson’s Disease Genomics Consortium (IPDGC), Nalls Mike A. , Singleton Andrew B. , Morris Huw , Jankovic Joseph , Shulman Joshua M. 
Published: June 2020

AbstractOBJECTIVETo discover genetic determinants of Parkinson disease (PD) motor subtypes, including Tremor Dominant (TD) and Postural Instability/Gait Difficulty (PIGD) forms.METHODSIn 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining two complementary outcome traits derived from the Unified Parkinson’s Disease Rating Scale (UPDRS), including dichotomous motor subtype (TD vs. PIGD) or a continuous tremor / PIGD score ratio. Logistic or linear regression models were adjusted for sex, age of onset, disease duration, and 5 ancestry principal components, followed by meta-analysis.RESULTSAmong 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, includingGPNMB(rs199347, psubtype= 0.01, pratio= 0.03),SH3GL2(rs10756907, psubtype= 0.02, pratio= 0.01),HIP1R(rs10847864, psubtype= 0.02),RIT2(rs12456492, psubtype= 0.02), andFBRSL1(rs11610045, psubtype= 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (p = 0.026, ß = −0.04, 95% CI = −0.07, 0). Based on top results of our GWAS, we identify a novel suggestive association at theSTK32Blocus (rs2301857, pratio= 6.6×10−7), which harbors an independent risk allele for essential tremor.CONCLUSIONSMultiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant atSTK32Bsuggests a possible overlap between genetic risk for essential tremor and tremor-dominant PD.
Structure of the Bacterial Ribosome at 2 Å Resolution
Authors: Watson Zoe L. , Ward Fred R. , Méheust Raphaël , Ad Omer , Schepartz Alanna , Banfield Jillian F. , Cate Jamie H.D. 
Published: June 2020

AbstractContinuing advances in cryo-electron microscopy (cryo-EM) demonstrate the promise it holds for revealing biological structures at chemical resolution, in which noncovalent interactions, RNA and protein modifications, and solvation can be modeled accurately. At present, the best cryo-EM-derived models of the bacterial ribosome are of the large (50S) ribosomal subunit with effective global resolutions of 2.4-2.5 Å, based on map-to-model Fourier shell correlation (FSC). Here we present a model of theE. coli70S ribosome with an effective global resolution of 2.0 Å, based on maps showcasing unambiguous positioning of residues, their detailed chemical interactions, and chemical modifications. These modifications include the first examples of isopeptide and thioamide backbone substitutions in ribosomal proteins, the former of which is likely conserved in all domains of life. The model also defines extensive solvation of the small (30S) ribosomal subunit for the first time, as well as interactions with A-site and P-site tRNAs, mRNA, and the antibiotic paromomycin. The high quality of the maps now allows a deeper phylogenetic analysis of ribosomal components, and identification of structural conservation to the level of solvation. The maps and models of the bacterial ribosome presented here should enable future structural analysis of the chemical basis for translation, and the development of robust tools for cryo-EM structure modeling and refinement.
bioPROTACs establish RAS as a degradable target and provide novel RAS biology insights
Authors: Lim Shuhui , Khoo Regina , Juang Yu-Chi , Gopal Pooja , Zhang Huibin , Yeo Constance , Peh Khong Ming , Teo Jinkai , Ng Simon , Henry Brian , Partridge Anthony W. 
Published: June 2020

ABSTRACTMutations to RAS proteins (H-, N-, and K-RAS) are amongst the most common oncogenic drivers and tumors harboring these lesions are some of the most difficult to treat. Although the recently discovered covalent small molecules against the KRASG12Cmutant have shown promising efficacy against lung cancers, traditional barriers remain for drugging the more prevalent KRASG12Dand KRASG12Vmutants. Targeted degradation has emerged as an attractive alternative approach but for KRAS, identification of the required high-affinity ligands continues to be a challenge. Another significant hurdle is the discovery of a hybrid molecule that appends an E3 ligase-recruiting moiety in a manner that satisfies the precise geometries required for productive polyubiquitin transfer while maintaining favorable drug-like properties. As a tool to gain insights into the advantages and feasibility of KRAS targeted-degradation, we applied the bioPROTAC approach. This workflow centers on the intracellular expression of a chimeric protein consisting of a high-affinity target-binding domain fused to an engineered E3 ligase adapter. We generated a series of anti-RAS bioPROTACs that span different RAS isoform/nucleotide-state specificities and leverage different E3 ligases. Overall, our results provide definitive evidence for the degradability of RAS proteins. We further elucidate the functional consequences of RAS degradation, the susceptibility and degradation kinetics of various mutant KRAS, and the prevalence of different nucleotide-states in WT and mutant KRAS. Finally, if delivery challenges can be addressed, anti-RAS bioPROTACs will be exciting candidates for clinical development.
Factors impacting e-learning in health sciences education: a protocol for systematic review and meta-analysis
Authors: Regmi Krishna , Jones Linda 
Published: June 2020

AbstractE-learning has been widely used in higher education as it provides better access to learning resources online, utilising technology – regardless of learners’ geographical locations and timescale – to enhance learning. Despite growing evidence claiming that e-learning is as effective as traditional means of learning, there is very limited evidence. This protocol aims to assess the effects of e-learning factors that impact on health sciences education (HSE). We will conduct a systematic review meta-analysis research of both randomised controlled trials and non-randomised controlled trials. Seven databases – MEDLINE, EMBASE, Allied & Complementary Medicine, DH-DATA, PsycINFO, CINAHL, and Global Health – will be searched, from 1980 through 2020. The PRISMA-P checklist will be used while preparing this protocol. Two reviewers will independently screen the papers and extract data. We will utilise the JBI quality appraisal tools for quantitative and qualitative studies, and Mixed Methods Appraisal Tool appraisal tools to assess the quality. A narrative synthesis, using thematic analysis, will be conducted for the included studies. If sufficient data are available, the random-effects model for meta-analysis will be performed to measure the effect size of e-learning on health sciences education or the strengths of relationships. The outcome of this review will provide a useful checklist of potential factors to develop an e-learning approach in HSE. This might provide a basis for developing the best methods of e-learning in education so that e-learning policy in education and learning settings in the HSE context could be administered effectively, efficiently and equitably.
A Metapopulation Network Model for the Spreading of SARS-CoV-2: Case Study for Ireland⋆
Authors: Humphries Rory , Spillane Mary , Mulchrone Kieran , Wieczorek Sebastian , O’Riordain Micheal , Hövel Philipp 
Published: June 2020

ABSTRACTWe present preliminary results on an all-Ireland network modelling approach to simulate the spreading the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), commonly known as the coronavirus. In the model, nodes correspond to locations or communities that are connected by links indicating travel and commuting between different locations. While this proposed modelling framework can be applied on all levels of spatial granularity and different countries, we consider Ireland as a case study. The network comprises 3440 electoral divisions (EDs) of the Republic of Ireland and 890 superoutput areas (SOAs) for Northern Ireland, which corresponds to local administrative units below the NUTS 3 regions. The local dynamics within each node follows a phenomenological SIRX compartmental model including classes of Susceptibles, Infected, Recovered and Quarantined (X) inspired from Science 368, 742 (2020). For better comparison to empirical data, we extended that model by a class of Deaths. We consider various scenarios including the 5-phase roadmap for Ireland. In addition, as proof of concept, we investigate the effect of dynamic interventions that aim to keep the number of infected below a given threshold. This is achieved by dynamically adjusting containment measures on a national scale, which could also be implemented at a regional (county) or local (ED/SOA) level. We find that – in principle – dynamic interventions are capable to limit the impact of future waves of outbreaks, but on the downside, in the absence of a vaccine, such a strategy can last several years until herd immunity is reached.
Deducing the Dose-response Relation for Coronaviruses from COVID-19, SARS and MERS Meta-analysis Results
Authors: Zhang Xiaole , Wang Jing 
Published: June 2020

AbstractThe fundamental dose-response relation is still missing for better evaluating and controlling the transmission risk of COVID-19. A recent study by Chu et al. has indicated that the anticipated probability of viral infection is about 12.8% within 1 m and about 2.6% at further distance through a systematic review and meta-analysis. This important information provides us a unique opportunity to assess the dose-response relation of the viruses, if reasonable exposure dose could be estimated. Here we developed a simple framework to integrate the a priori dose-response relation for SARS-CoV based on mice experiments, and the recent data on infection risk and viral shedding, to shed light on the dose-response relation for human. The developed dose-response relation is an exponential function with a constant k in the range of 6.19×104 to 7.28×105 virus copies. The result mean that the infection risk caused by one virus copy in viral shedding is about 1.5×10−6 to 1.6×10−5. The developed dose-response relation provides a tool to quantify the magnitude of the infection risk.
Non-work-related rejection of temporary members
Authors: Kristensen Anette Kaagaard , Kristensen Martin Lund 
Published: June 2020

PurposeThis paper aims to highlight the social dynamics associated with the interaction between temporary and permanent organizational members in non-work-related situations. This view contrasts with previous studies which predominantly focus on work-related situations. Inspired by Goffman's dramaturgical metaphor, a perspective which emphasizes the influence of social regions on group membership as well as the ritual foundation of everyday social interactions is developed.Design/methodology/approachThis paper’s methodological foundation is a constructivist grounded theory study of 15 undergraduate nursing students' experiences as temporary members during their clinical placements.FindingsTemporary members arrive at their new organization with an expectation of attending non-work-related situations on similar terms as permanent members. However, they do not expect to be treated as new colleagues. They experience being excluded and ignored, which makes them feel humiliated, denied recognition and deprived of their dignity.Originality/valueIlluminating social dynamics related to backstage access provides valuable insights to studies of the relationship between temporary and permanent organizational members. Furthermore, redirecting the analytical focus from social dynamics associated with work-related situations to non-work-related ones provides new perspectives on moral exclusion by emphasizing the ritual foundation and its close connection to moral concepts such as dignity and recognition.
Classification of malicious insiders and the association of the forms of attacks
Authors: Glancy Fletcher , Biros David P. , Liang Nan , Luse Andy 
Published: June 2020

Purpose
The authors argue that the current studies about malicious insiders confuse the fact that malicious attacks belong to two different categories, namely, those that launch instrumental attacks and expressive attacks. The authors collect malicious insider data from publicly available sources and use text-mining techniques to analyze the association between malicious insiders’ characteristics and the different types of attack.

Design/methodology/approach
The authors investigated the relationship between personality characteristics and different types of malicious attacks. For the personality characteristics, the authors use the same method as Liang et al. (2016), which extracted these characteristics based on a keyword-characteristic dictionary. For different types of malicious attacks, two raters rated each case based on criteria modified from criminology research to determine the degree of expressiveness and instrumentality.

Findings
The results show that malicious insiders who are manipulative or seeking personal gain tend to carry out instrumental attacks. Malicious insiders who are arrogant tend to conduct expressive attacks.

Research limitations/implications
This study uses third party articles to identify the personality characteristics of known malicious insiders. As such, not all personality characteristics may have been reported. Data availability was an issue.

Practical implications
Understanding if different personality characteristics lead different types of attacks can help managers identify employees who exhibit them and mitigate an attack before it occurs.

Social implications
Malicious insider attacks can have devastating results on businesses and employees. Help to identify potential malicious insiders before they act, may prevent undue harm.

Originality/value
This study used 132 cases of none malicious insiders to examine their attack objectives. No other study that the authors know of used that many cases.
Trickle-down effect of benevolent leadership on unethical employee behavior: a cross-level moderated mediation model
Authors: Rui Jiang , Xinqi Lin 
Published: June 2020

PurposeConducting research on the relationship between benevolent leadership and unethical employee behavior can help us find solutions to reduce unethical employee behavior. This paper also discusses how the benevolent manager leadership can be transmitted to the employee's unethical behavior through the benevolent supervisor leadership and the moderating effect of LMX and ethical climate.Design/methodology/approachThrough a questionnaire survey of 406 pairs of leaders, supervisor and employees, the authors use data aggregation test, confirmatory factor analysis, descriptive statistics and multilevel model (HLM) to test our hypothesis.Findings(1) Manager supervisor leadership is negatively related to unethical employee behavior, (2) benevolent supervisor leadership mediates the relationship between benevolent manager leadership and unethical employee behavior, (3) LMX positively moderates the relationship between benevolent manager leadership and benevolent supervisor leadership and moderates the mediating effect of benevolent supervisor leadership, and (4) ethical climate positively moderates the relationship between benevolent supervisor leadership and unethical employee behavior and moderates the mediating effect of benevolent supervisor leadership.Originality/valueFirst, based on previous studies, this study further proves that benevolent leadership is a popular positive leadership among the three dimensions of paternalistic leadership that extends its influence to unethical employee behavior. Second, the study traces the source of the benevolent leadership of employees' supervisors and reveals the action mechanism of how benevolent manager leadership affects unethical employee behavior (trickle-down effect). LMX and the ethical climate provide the organizational context of the trickle-down effect and the occurrence of unethical employee behavior.
Chronic traffic noise increases food intake and alters gene expression associated with metabolism and disease in bats
Authors: Song Shengjing , Chang Yang , Wang Daiping , Jiang Tinglei , Feng Jiang , Lin Aiqing 
Published: June 2020

Abstract

Anthropogenic noise exposure has deleterious effects on the foraging ecology of many animals. However, the effects of chronic anthropogenic noise on food intake and health condition in wildlife remain largely unknown.

We tested whether traffic noise exposure over multiple days would change food intake and would have effects on the health of Asian particoloured bats. We broadcast traffic noise to the bats of two noise‐exposure groups (group A, five bats; group C, six bats) and broadcast silence files to the bats of two control groups (group B, five bats; group D, six bats) for 12 days. We measured the changes in food intake, body weight and concentration of faecal triiodothyronine (T3) and thyroxine (T4) in groups A and B. We compared the transcriptional profiles in brain, kidney and liver tissues between bats in groups C and D.

The bats exposed to traffic noise had a significantly higher daily food intake and a significantly greater body weight than bats in control group during the period of playback. Faecal T3 and T4 were higher in the noise‐exposure group after playback had been on for more than 1 day.

We found a total of 169 differentially expressed genes (DEGs) between noise‐exposure and control groups. Some DEGs related to stress response were upregulated in the bats exposed to noise. The 169 DEGs were mainly enriched in Gene Ontology (GO) terms associated with metabolism, fundamental cellular processes, stress response and immune response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways affected by noise exposure were linked with metabolism, disease, apoptosis, autophagy, phagosome and ribosome.

Synthesis and applications. Our results suggest that bats exposed to chronic traffic noise while roosting may need more energetic intake and have a greater motivation to forage than others not exposed to noise, probably as a result of a stress response. Furthermore, chronic traffic noise may increase the risk of metabolic dysregulation, immune disorders and other diseases. Management measures for reducing noise disturbance, for example, implementing sound barriers, are essential.
Expression of ribosomal protection protein RppA is regulated by a ribosome‐dependent ribo‐regulator and two mistranslation products
Authors: Cai Xia , Zhan Yunda , Cao Zhanglei , Yan Bing , Cai Jun 
Published: June 2020

SummaryGene expression is tightly controlled by transcription factors and RNA regulatory elements, including trans‐acting small RNAs, cis‐regulatory riboswitches and ribosome‐dependent ribo‐regulators. In the present study, we demonstrated that a ribosome‐dependent ribo‐regulator and two mistranslation products co‐regulate rppA (encoding a ribosomal protection protein) expression in Bacillus thuringiensis BMB171. The leader RNA of the rppA gene controls rppA expression via translation of leader ORF1 resident in its sequence. In the presence of chloramphenicol, a +1 frameshift product (ORF2) and a stop codon readthrough product (ORF3) of ORF1 emerged. ORF3 exerted a negative effect on rppA expression. By contrast, the ORF2 promoted rppA expression. The regulation mode identified in the present study will lead to a deeper understanding of bacterial gene expression.
Understanding the Role of Profession in Multidisciplinary Team Innovation: Professional Identity, Minority Dissent and Team Innovation
Authors: Mitchell Rebecca , Boyle Brendan 
Published: June 2020

AbstractOrganizational teams are capable of addressing complex and multifaceted problems through innovative solutions, but their capacity to innovate is far from guaranteed. The quest to address this dilemma has yet to explore the interactive roles of professional and team identification; a surprising omission as both professional and team identification have been separately shown to play an important role in determining team innovation. Responding to this research gap, we explore the potential for professional identity salience to enhance or undermine healthcare team innovation through minority dissent, and argue that team identification is capable of differentiating between these two contrasting effects. Our survey‐based study of 63 US healthcare teams supports our moderated mediation model, which provides evidence of the potential complementarity of different forms of identification and opens an opportunity for teams to reap the benefits, as well as avoid the detriments, typically associated with each form.
Lively Lands: The Spatial Reproduction Squeeze and the Failure of the Urban Imaginary
Authors: Ghertner D. Asher 
Published: June 2020

AbstractThis article argues that the theoretical invisibility of non‐privatized land tenures constitutes a failure of the urban imaginary, which restricts the ability to forge less commodified urban futures. The article explicates two attributes of non‐privatized land—fungibilityandcombinatoriality—that produce an urban land nexus capable of fostering pro‐poor agglomeration economies and generating socialities that exceed the model of the separative self that is hegemonic in more propertied settings. Fungibility, it shows, externalizes supportive economies of production and reproduction into surrounding neighborhoods by shifting the boundaries and terms of usufruct without cadastral oversight or regulation. Combinatoriality—a hybrid formulation of combined territories and combined territorialities—describes overlapping forms of access to land or demarcations of legitimate land use, either competitive or reciprocal. Together, these two attributes of non‐privatized land systems produce a propinquity requirement for economic production, or a social density and liveliness more limited in privatized land markets. Through a diagnostic analogy with the simple reproduction squeeze characteristic of subsistence agrarian settings, it charts how anurbanspatial reproduction squeeze—felt globally in dense, rising‐rent environments across the global North and South—generates subsistence needs that mixed‐tenure environments are uniquely capable of fulfilling and that can provide inspiration for radical housing struggles elsewhere.
The contextual effect of trust on perceived support: Evidence from Roma and non‐Roma in East‐Central Europe
Authors: Sendroiu Ioana , Upenieks Laura 
Published: June 2020

AbstractIn recent years, trust has been conceptualized as an important source of social capital, setting off cross‐disciplinary research on both the benefits and predictors of trust at the individual and contextual level. In this paper, we turn to the individual outcomes of living in a trustful context, and explore the relationship between trust, itself one of the main components of social capital, and social support, seen as one of the most important effects of social capital. In particular, we ask how social capital—and the relationship between trust and social support—functions in the context of unequal societies. We model perceived support as an outcome across three levels, from no support to proximate to distal support, and using a cross‐national study of Roma and non‐Roma across 12 European countries, we track the relationship between trust and support across both mainstream and marginalized populations. Our findings suggest that living in contexts with more trust has protective effects particularly for members of marginalized groups: the Roma are more likely to have distal support in contexts with higher trust. We conclude that contextual trust helps to broaden the circle of support beyond family and friends; thus, trust can indeed be a synthetic force that binds individuals together in broadened structures of support.