bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase
Authors: Shannon A. , Selisko B. , Le NTT , Huchting J. , Touret F. , Piorkowski G. , Fattorini V. , Ferron F. , Decroly E. , Meier C , Coutard B. , Peersen O. , Canard B. 
Published: May 2020

AbstractThe ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.
Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex
Authors: Prakash Rohit , Sandoval Thomas , Morati Florian , Zagelbaum Jennifer A , Taylor Brett , Wang Raymond , Desclos Emilie C B , Sullivan Meghan R , Rein Hayley L , Bernstein Kara A , Krawczyk Przemek M , Gautier Jean , Modesti Mauro , Vanoli Fabio , Jasin Maria 
Published: May 2020

AbstractHomology-directed repair (HDR), a critical DNA repair pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these different outcomes are often not well understood. Here we show that SWS1-SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly of RAD51 recombinase at DNA damage sites, these proteins are not essential for intra-chromosomal HDR, providing insight into why patients and mice with mutations are viable. However, SWS1-SWSAP1-SPIDR is critical for inter-homolog HDR, the first mitotic factor identified specifically for this function. Furthermore, SWS1-SWSAP1-SPIDR drives the high level of sister-chromatid exchange, promotes long-range loss of heterozygosity often involved with cancer initiation, and impels the poor growth of BLM helicase-deficient cells. The relevance of these genetic interactions is evident as SWSAP1 loss prolongsBlm-mutant embryo survival, suggesting a possible druggable target for the treatment of Bloom syndrome.
RADX condenses single-stranded DNA to antagonize RAD51 loading
Authors: Zhang Hongshan , Schaub Jeffrey M. , Finkelstein Ilya J. 
Published: May 2020

AbstractRADX is a mammalian single-stranded DNA-binding protein that stabilizes telomeres and stalled replication forks. Cellular biology studies have shown that the balance between RADX and Replication Protein A (RPA) activities is critical for DNA replication integrity. RADX is also a negative regulator of RAD51-mediated homologous recombination at stalled forks. However, the mechanism of RADX acting on DNA and its interactions with RPA and RAD51 are enigmatic. Using singlemolecule imaging of the key proteinsin vitro, we reveal that RADX condenses ssDNA filaments, even when the ssDNA is coated with RPA at physiological protein ratios. RADX compacts RPA-coated ssDNA filaments via higher-order assemblies that can capture ssDNAin trans. Furthermore, RADX blocks RPA displacement by RAD51 and prevents RAD51 loading on ssDNA. Our results indicate that RADX is an ssDNA condensation protein that inhibits RAD51 filament formation and may antagonize other ssDNA-binding proteins on RPA-coated ssDNA.
‘Readiness to lead’: a tentative tool for analysis
Authors: Johnston Jenny , Shipway Bradley 
Published: May 2020

PurposeThis paper reports on research into Australian school principals' leadership. It explores an emerging construct – that of ‘readiness to lead’ – and showcases the development of a tentative tool for determining school principals' readiness to lead.Design/methodology/approachSeven principals from Australian and International Schools were interviewed about their leadership strategies, intentions and expectations for impending school reform. Qualitative analyses using grounded theory and an interpretivist constructivist paradigm were applied.FindingsThe construct of ‘readiness to lead’ emerged during initial analysis and a tool was developed from a compilation of literature on leadership. Findings revealed that five principals were well-aligned with the strategies, intentions and expectations the research literature indicates are characteristic of good leadership. These principals could be regarded as ‘ready to lead’ their schools in significant school reform. An unexpected finding was that the concepts of ‘hope’ and ‘trust’ also played a significant role in leadership. ‘Hope’ appeared important as a major strategy for the less-well aligned principals, whereas mutual ‘trust’ appeared to be evident in the principals with stronger leadership readiness.Research limitations/implicationsThe tool warrants peer review and validation; data revealed an emerging construct and review is welcomed. The authors are continuing to research and investigate in this field, and invite further academic dialogue.Originality/valueThe study has explored the fecundity of the tool for analysis, and evaluated the principals' preparedness to lead reform. Having a tool to determine whether and to what degree school principals are ready to lead would be advantageous for the profession.
Cost-risk contingency framework for managing cost overrun in metropolitan projects: using fuzzy-AHP and simulation
Authors: Afzal Farman , Yunfei Shao , Junaid Danish , Hanif Muhammad Shehzad 
Published: May 2020

PurposeRisk analysis plays a vital role in controlling and managing cost overruns in complex construction projects, particularly where uncertainty is high. This study attempts to address an important issue of cost overrun that encountered by metropolitan rapid transit projects in relation to the significance of risk involved under high uncertainty.Design/methodology/approachIn order to solve cost overrun problems in metropolitan transit projects and facilitate the decision-makers for effective future budgeting, a cost-risk contingency framework has been designed using fuzzy logic, analytical hierarchy process and Monte Carlo simulation.FindingsInitially, a hierarchical breakdown structure of important complexity-driven risk factors has been conceptualized herein using relative importance index. Later, a proposed cost-risk contingency framework has investigated the expected total construction cost in order to consider the additional budgeted cost required to mitigate the risk consequences for particular project activity. The results of cost-risk analysis imply that poor design issues, an increase in material prices and delays in relocating facilities show higher dependency and increase the risk of cost overrun in metropolitan transit projects.Practical implicationsThe findings and implication for project managers could possibly be achieved by assuming the proposed cost-risk contingency framework under high uncertainty of cost found in this research. Furthermore, this procedure may be used by experts from other engineering domains by replacing and considering the complex relationship between complexity-risk factors.Originality/valueThis study contributes to the body of knowledge by providing a practical contingency model to identify and evaluate the additional risk cost required to compute total construction cost for getting stability in future budgeting.
Reliability evaluation of repairable weighted system using interval valued universal generating function
Authors: Bisht Soni , Singh S. B. , Tamta Renu 
Published: May 2020

PurposeTo find the reliability characteristics of repairable weighted (u,v)- out-of-(x,y) system using the interval valued universal generating function (IUGF).Design/methodology/approachIn this paper (u,v)-out-of-(x,y) system is an extension of thek-out-of-nsystem. Here, the interval valued universal generating function (UGF) is present and the corresponding operators are defined.FindingsThe present paper proposes a interval valued universal generating function (IUGF) to compute the reliability indices of the considered system. The current study investigates the reliability and sensitivity of the proposed system with respect to system parameters by applying Markov process with the help of the interval valued UGF approach.Originality/valueIn this work, the considered system, i.e. repairable weighted (u,v)-of-the- (x,y) is the extension ofk-out-of-nsystem for the assessment of reliability characteristics using the interval valued UGF.
Anatomy of an effective workplace health intervention: a comprehensive new model
Authors: Hennessey Sean Peter , Rehman Laurene 
Published: May 2020

PurposeThis study proposes a new model, called the Integrated Human Health Model (IHHM), to improve the design and effectiveness of Workplace Health Promotion (WHP) interventions.Design/methodology/approachEighteen participants were purposefully selected from 44 participants in a 2.5-day WHP intervention targeting multiple health behaviours (MHB). The intervention has shown to improve quality of life and health-related behaviours in rigorous studies. Qualitative data collection methods were observations, repeat semi-structured interviews and weekly e-journals collected over three months. Template analysis was used to develop the IHHM describing participants' experiences.FindingsThe IHHM describes the health behaviour change process using eight themes: facilitation, assessment, desired life, barriers, knowledge and skills, insights, action planning, and monitor and support.Practical implicationsWith the paucity of evidence informing WHP intervention effectiveness, this study provides a preliminary model serving practitioners to design more effective interventions and scholars to improve evidence.Originality/valueThis study proposes a practical comprehensive model for practitioners and leaders to more effectively design and evaluate successful MHB WHP interventions compared to existing models.
Promoting firm innovativeness through servant leadership and corporate social responsibility to employees
Authors: Mallén Broch Francisco Fermín , Domínguez Escrig Emilio , Chiva Gómez Ricardo , Lapiedra Alcamí Rafael 
Published: May 2020

PurposeBased on the upper echelons and organisational identification theories, this paper focuses on the relationship between servant leadership and firm innovativeness, as well as the underlying mechanisms that explain this relationship. More specifically, we analyse the relationship between servant leadership, firm innovativeness and corporate social responsibility to employees (CSRE).Design/methodology/approachA total of 285 Spanish firms took part in the study, and 570 questionnaires were gathered. Structural equation modelling was used to validate the proposed hypotheses.FindingsResults suggest that servant leadership has a positive relationship with firm innovativeness, and this relationship is fully mediated by CSRE.Research limitations/implicationsHR managers have an overall view of their company and of the behaviour of other leaders. However, future research should also consider employees perceptions. The present study is cross-sectional, and it would be interesting to study the development of the interaction between leaders and followers, which calls for longitudinal and multilevel studies.Practical implicationsAccording to our results, managers could foster firm innovativeness if they select and promote leaders who display the different leadership behaviours related to servant leadership: empowerment, servitude, accountability, courage, authenticity, humility and stewardship. Moreover, training programmes should also foster these behaviours.Originality/valueFew empirical studies analyse the relationship between servant leadership and innovation. The main contribution of the present research is to further the current knowledge of this relationship by disentangling the mediating role of corporate social responsibility to employees.
Dermoscopic features and differential diagnosis of sebaceous carcinoma
Authors: Cheng Chun‐Yu , Su Hsing‐Jou , Kuo Tseng‐Tong 
Published: May 2020

AbstractSebaceous carcinoma is a rare malignant skin neoplasm arising from sebaceous glands. Its clinical diagnosis is difficult and reports of dermoscopic findings have been limited. This study aims to analyze its dermoscopic features and differential diagnosis in dermoscopic examination. The study included patients diagnosed with histologically proven sebaceous carcinomas as well as diagnosed cases of sebaceous hyperplasia, sebaceoma, squamous cell carcinoma and basal cell carcinoma for comparison of dermoscopic findings. The dermoscopic criterion of presence of sebaceous carcinoma was scored only if the two evaluators reached a consensus. Fifteen cases of histologically diagnosed sebaceous carcinoma were included in our study. All cases were extraocular sebaceous carcinoma. A total of 60 (15 basal cell carcinomas, 15 squamous cell carcinomas, 15 sebaceous hyperplasias and 15 sebaceomas) cases were collected for comparing dermoscopic features with sebaceous carcinoma. In dermoscopic analysis of sebaceous carcinoma, the majority of tumors (66.67%) presented polymorphic vessel pattern. Other features included whitish‐pink areas (80%), yellowish structures (73.33%) and yellowish structureless areas (60%). Yellowish structures in sebaceous carcinomas are the main dermoscopic findings to differentiate squamous cell and basal cell carcinomas (P < 0.001), whereas purplish globules, shiny white blotches and strands and whitish‐pink area distinguish sebaceous carcinomas from other sebaceous tumors (P < 0.05).
Kampo medicines suppress the production of exfoliative toxins causing impetigo in Staphylococcus aureus
Authors: Katayama Ibu , Nakaminami Hidemasa , Yamada Tetsuya , Ikoshi Hideaki , Noguchi Norihisa 
Published: May 2020

AbstractAn alternative approach, such as antivirulence therapy that modulates the production of bacterial toxins or virulence factors, is necessary to tackle the emergence of antimicrobial‐resistant strains. Here, we investigated the potential antivirulence effects of seven Kampo medicines (Jumihaidokuto, Eppikajutsuto, Jizusoippo, Shomakakkonto, Sammotsuogonto, Hainosankyuto and Inchinkoto) against exfoliative toxin (ET)‐positive Staphylococcus aureus, which is the major causative agent of impetigo. A growth inhibition assay showed that all of the selected Kampo medicines inhibited the growth of S. aureus at 1/5 (2.5 mg/mL) or less of the conventionally used concentrations. Among these, Jizusoippo and Inchinkoto (0.25–1 mg/mL) suppressed the production of ET without inhibiting the bacterial growth. Furthermore, Jizusoippo and Inchinkoto significantly suppressed the expression of ET genes in a concentration‐dependent manner. Our findings strongly suggest, for the first time, that Kampo medicines, especially Jizusoippo and Inchinkoto, have the potential to serve as antivirulence agents against skin infections caused by S. aureus by suppressing the production of ET.
The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK
Authors: Elsaid Fahmy G. , Alshehri Mohamed A. , Shati Ali A. , Al‐Kahtani Mohamed A. , Alsheri Ali S. , Massoud Ehab E. , El‐kott Attalla F. , El‐Mekkawy Haitham I. , Al‐Ramlawy Amira M. , Abdraboh Mohamed E. 
Published: May 2020

AbstractThis study investigated the effect of ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr389) and 4EBP‐1 (Thr37/46), two downstream targets of mTORC1, and p‐Akt (Thr308) but increased levels of AMPK (Thr172) and p‐raptor (Ser792), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
Biochemical investigation of rs1801282 variations in PPAR‐γ gene and its correlation with risk factors of diabetes mellitus in coronary artery disease
Authors: Rehman Kanwal , Jabeen Komal , Awan Fazli Rabbi , Hussain Misbah , Saddique Muhammad Asim , Akash Muhammad Sajid Hamid 
Published: May 2020

AbstractWe aimed to investigate the association of single nucleotide polymorphism of Pro/Ala (rs1801282) in peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) gene with risk factors of diabetes mellitus (DM) in cardiovascular disease (CVD) patients. We recruited 244 participants from Faisalabad Institute of Cardiology and Department of Cardiology, Sargodha District Head Quarter Teaching Hospital, Pakistan. Out of 244 participants, 144 cases were CVD patients and 100 were healthy controls. CVD patients were further divided into 111 coronary artery disease (CAD) and 33 cardiomyopathy (CMP) patients. Assessment of variant specific polymorphism/mutation of Pro/Pro and Pro/Ala genotypes was done through amplification refractory mutation system polymerase chain reaction (ARMS‐PCR). Further, serum biomarkers were measured to investigate the association among risk factors of DM and Pro/Ala polymorphism in PPAR‐γ gene. About 31.5% Pro/Ala genotype was found in CVD patients out of which 22.5% were CAD patients and 9% were CMP patients. As a result, obesity, hypertension and smoking (35%, 23%, 21%, respectively) were observed to be the most critical risk factors accompanying Pro/Ala mutation in PPAR‐γ particularly in CAD patients as compared to that in CMP patients. A similar pattern of association was observed among the elevated levels of glucose, cholesterol, triglyceride and ALT with Pro/Ala mutation in CAD patients. Further, CAD patients using ACE inhibitors (18%) and β‐blockers (13%) were found to be the carriers of Pro/Ala genotype and also showed significant increase in glucose level. This study suggests that hyperglycaemia in CAD patients particularly obese, smokers and hypertensives having Pro/Ala polymorphism in PPAR‐γ gene are at high risk of developing DM as clearly observed by hyperglycaemia in CAD patients.
Commodity or Propriety? Unauthorised Transfer of Intangible Entitlements in the EU Emissions Trading System
Authors: Holligan Bonnie 
Published: May 2020

AbstractThis article argues that the law governing transfer of allowances within the EU Emissions Trading System (EU ETS) should place greater weight upon transactional (and environmental) integrity, even over market liquidity. More broadly, it reflects on the role played by registries in sharing or concealing information about the material world. Although property rules enable market activity through the creation of an abstract carbon commodity, they must also link past to future entitlements in a just way. In emissions trading markets, justice in private transactions is intimately connected to public questions of environmental justice. The relevant EU Regulation prioritises facility of transfer over protection of existing holders, insulating registered entitlements from prior proprietary claims. This approach ignores the important connections between history, integrity and responsibility in both public and private spheres. A preferable response would be to distinguish between transactional and register error, protecting against register mistakes, but not transactional defects.
Impact of different prenatal management strategies in short‐ and long‐term outcomes in monochorionic twin pregnancies with selective intrauterine growth restriction and abnormal flow velocity waveforms in the umbilical artery Doppler: a retrospective observational study of 108 cases
Authors: Colmant C , Lapillonne A , Stirnemann J , Belaroussi I , Leroy‐Terquem E , Kermovant‐Duchemin E , Bussieres L , Ville Y 
Published: May 2020

ObjectivesTo review perinatal and neurodevelopmental outcome (NDO) following selective fetoscopic laser coagulation (SFLC), cord coagulation (CC) or expectant management of monochorionic diamniotic twin pregnancies complicated with selective intrauterine growth restriction (sIUGR) and absent or reverse end‐diastolic flow (AREDF) in the umbilical arteries (UA).Design and settingSingle‐centre retrospective observational study.Population108 cases of sIUGR diagnosed before 26+6 weeks’ gestation with AREDF in the UA.MethodsSurvival rate and potential risk factors were analysed. NDO was assessed using parental questionnaires.Main outcomes measuresSurvival, gestational age at delivery and NDO.ResultsSFLC, CC and EM were performed in 13, 50 and 45 cases, respectively, with an overall survival of 23.1, 40 and 77.8% and intrauterine demise of the co‐twin of 30.8, 10 and 6.7% respectively. Intrauterine demise of the sIUGR twin occurred in 76.9 and 17.8% following SFLC and EM, respectively. The discordance in EFW at diagnosis was higher and absent/negative a‐wave in the ductus venosus (DV) was more prevalent in the surgical groups. NDO in survivors at follow up was abnormal in 0 and 18% in the smaller twin following SFLC and EM, respectively, and in 25, 24 and 21% in the larger twin following SFLC, CC and EM, respectively.ConclusionSFLC yielded a poor result. EM seems a valid option when EFW discordance is <30% and a‐wave in DV is positive. Otherwise, CC should be considered to protect the AGA co‐twin. The long‐term outcome of both small and large twins seems unaffected by the choice in primary prenatal management strategy.Tweetable abstractIn type II sIUGR in MC twins, long‐term neurodevelopment is normal in over 80% of the survivors.
Integrating genomics into conservation management
Authors: Latch Emily K. 
Published: May 2020

Captive populations play a vital role in conservation, supporting both in situ and ex situ conservation projects. A healthy, self‐sustaining captive population serves as valuable insurance against extinctions and a source of individuals for reintroduction into the wild. Genetic and genomic data can advance conservation and management across a range of scenarios. Although expanding, genomic data do not exist for most captive populations and there remain few examples of how these data can be integrated directly into conservation efforts. In this issue of Molecular Ecology Resources, Humble et al. (2020) present a chromosomal‐level genome assembly for the extinct‐in‐the‐wild scimitar‐horned oryx (Oryx dammah), and resequencing data to survey genetic variation across captive populations. These data are exciting for reintroduction planning by offering guidance for selecting source populations to maximize global genetic variation and valuable resources for effective post‐release monitoring. The genomic resources generated also are valuable tools with the power to yield novel and important insights into the evolution of scimitar‐horned oryx and other antelope species.