bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal transport practices and effectiveness of the use of low-cost interventions on the morbidity and mortality of transported neonates in Sub-Saharan Africa: A systematic review protocol
Authors: Okai Emmanuel , Soltani Hora , Fair Frankie J 
Published: August 2022

AbstractObjectivesPoor pre-transport and intra-transport care are associated with early neonatal morbidity and mortality. The objective of this study is to produce a critical overview of research on neonatal transport practices, the use of any low-cost interventions, including Kangaroo mother care (KMC) employed in neonatal transport on the outcomes of neonates transported for specialized care in Sub-Saharan Africa, through a systematic review and narrative synthesis.Study designThe study design is a protocol for systematic reviewMethodsA comprehensive literature search will be conducted using the electronic databases of CINAHL, EMBASE, MEDLINE, Web of Science, as well as Google Scholar. A manual search will be carried out of the reference lists of eligible studies for relevant papers. The search strategy will include combining three key blocks of terms, namely: ‘neonates’, ‘transport’ and ‘Sub Saharan Africa,’ using database-specific subject headings and text words. Two independent reviewers will screen and assess data quality and extraction for synthesis. Any disagreements during the data extraction and quality assessment stages will be determined by consensus with the involvement of a third reviewer. Study quality will be assessed using the Mixed-Methods Appraisal Tool (MMAT); a narrative synthesis will be undertaken to integrate and summarise findings. Subgroup analysis will be done where data is available within countries with different groups of neonates and modes of transportation.Ethics and disseminationApproval by a research ethics committee is not required for this study since the review only includes published and publicly accessible data. Findings from this review will inform research into the use of Kangaroo Mother Care (KMC) in neonatal transport in Ghana. We will publish our findings in a peer-reviewed journal as per Preferred Reporting for Systematic Review and Meta-analysis (PRISMA) 2020 GuidanceRegistrationPROSPERO registration CRD42022352401
Programmable enveloped delivery vehicles for human genome engineeringin vivo
Authors: Hamilton Jennifer R. , Chen Evelyn , Perez Barbara S. , Sandoval Espinoza Cindy R. , Kang Min Hyung , Trinidad Marena , Doudna Jennifer A. 
Published: August 2022

AbstractViruses and virally-derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR-Cas9 protein and guide RNA can target genome editing tools to specific cells. These Cas9-packaging enveloped delivery vehicles (Cas9-EDVs), programmed with different displayed antibody fragments, confer genome editing in target cells over bystander cells in mixed cell populations bothex vivoandin vivo.This strategy enabled the generation of genome-edited chimeric antigen receptor (CAR) T cells in humanized mice, establishing a new programmable delivery modality with widespread therapeutic utility.One-Sentence SummaryCell-specific molecular delivery with enveloped delivery vehicles (EDVs) enables genome editingex vivoandin vivo.
FBXW7 triggers degradation of WDR5 to prevent mitotic slippage
Authors: Hänle-Kreidler Simon , Richter Kai T. , Hoffmann Ingrid 
Published: August 2022

AbstractDuring prolonged mitotic arrest induced by anti-microtubule drugs, cell fate decision is determined by two alternative pathways, one leading to cell death, the other inducing premature escape from mitosis by mitotic slippage. FBWX7, a member of the F-box family of proteins and substrate-targeting subunit of the SCF (SKP1-CUL1-F-Box) E3 ubiquitin ligase complex promotes mitotic cell death and prevents mitotic slippage. In this study, we report that WDR5, a component of the mixed lineage leukemia (MLL) complex of Histone 3 Lysine 4 (H3K4) methyltransferases is a substrate of FBXW7. WDR5 binds to FBXW7 in vivo and in vitro and its ubiquitin-mediated proteasomal degradation is mediated by FBXW7. Furthermore, we find that WDR5 depletion counteracts FBXW7 loss-of-function by reducing mitotic slippage and polyploidization. Our data elucidate a new mechanism in mitotic cell fate regulation which might contribute to prevent chemotherapy resistance in patients after anti-microtubule drug treatment.
Leptospiral lipopolysaccharide dampens inflammation through upregulation of autophagy adaptor p62 and NRF2 signaling in macrophages
Authors: Bonhomme Delphine , Santecchia Ignacio , Escoll Pedro , Papadopoulos Stylianos , Vernel-Pauillac Frédérique , Boneca Ivo G. , Werts Catherine 
Published: August 2022

ABSTRACTLeptospira interrogansare pathogenic bacteria responsible for leptospirosis, a worldwide zoonosis. All vertebrates can be infected, and some species like humans are susceptible to the disease whereas rodents such as mice are resistant and become asymptomatic renal carriers. Leptospires are stealth bacteria that are known to escape several immune recognition pathways and resist killing mechanisms. We recently published that leptospires may survive intracellularly and exit macrophages, in part by escaping xenophagy, a pathogen-targeting form of autophagy. Interestingly, autophagy is one of the antimicrobial mechanisms often highjacked by bacteria to evade the host immune response. In this study we therefore explored whether leptospires subvert the key molecular players of autophagy to facilitate the infection. We showed in macrophages that leptospires triggered a specific accumulation of autophagy-adaptor p62 in puncta-like structures, without major alteration of autophagy flux. Unlike active bacterial mechanisms described to date, we demonstrated that leptospires trigger p62 accumulation using a passive mechanism of LPS signaling via TLR4/TLR2. p62 is a central pleiotropic protein, not only involved in autophagy, but also mediating cell stress and death,viathe translocation of transcription factors. We demonstrated thatLeptospira-driven accumulation of p62 induced the translocation of transcription factor NRF2. However, NRF2 translocation uponLeptospirainfection did not result as expected in antioxydant response, but dampened the production of inflammatory mediators such as iNOS/NO, TNF and IL6. Overall, these findings highlight a novel passive bacterial mechanism linked to p62/NRF2 signaling that decreases inflammation and contributes to the stealthiness of leptospires.
Conformational change of the Plasmodium TRAP I domain is essential for sporozoite migration and transmission of malaria
Authors: Braumann Friedrich , Klug Dennis , Kehrer Jessica , Lu Chafen , Springer Timothy A. , Frischknecht Friedrich 
Published: August 2022

AbstractEukaryotic cell adhesion and migration relies on surface adhesins connecting extracellular ligands to the intracellular actin cytoskeleton.Plasmodiumsporozoites are transmitted by mosquitoes and rely on adhesion and gliding motility to colonize the salivary glands and to reach the liver after transmission. During gliding the essential sporozoite adhesin TRAP engages actin filaments in the cytoplasm of the parasite., while binding ligands on the substrate through its inserted (I)-domain. Crystal structures of TRAP from differentPlasmodiumspecies revealed the I-domain in closed and open conformations. Here, we probe the importance of these two conformational states by generating parasites expressing versions of TRAP with the I-domain stabilized in either the open or closed state with disulfide bonds. Strikingly, both mutations impact sporozoite gliding, mosquito salivary gland entry and transmission. Absence of gliding in sporozoites expressing the open TRAP I-domain could be partly rescued by adding a reducing agent. This suggests that dynamic conformational change is required for ligand binding, gliding motility and organ invasion and hence sporozoite transmission from mosquito to mammal.
The use of Statin-class compounds to suppress methanogenesis in lake sediment inoculated microbial fuel cells
Authors: Jayathilake Chamindu , Dilangani Gayani P. , Bandara Sampath , Nazeer Zumaira , Thilini Nirath , Bandara Wijendra , Herath Ajith C. , Kyazze Godfrey , Fernando Eustace Y. 
Published: August 2022

AbstractMethanogenesis conducted by archaea acts as a competing metabolic pathway that diverts available carbon and electrons away from exo-electrogenic metabolism in mixed culture inoculated microbial fuel cells (MFCs). Statin-class compounds are known to selectively inhibit eukaryotic and archaeal versions of HMG Co-A reductase (class-I) enzyme and the bacterial version of the same enzyme (class-II) is known to be unresponsive to statins. The results of this study demonstrated that the two model statin compounds Simvastatin and Atorvastatin were effective in suppressing methanogenesis in MFCs when applied in moderate concentrations (5 mg/L and 40 mg/L respectively) in MFC anodes. Power densities increased 2 fold compared to control (to 63 ± 1.8 mW/m2) and 2.5 fold (to 69.5 ± 1.8 mW/m2) with Simvastatin and Atorvastatin addition respectively. There was an almost complete suppression of CH4 production with the addition of both statins into MFC anodes as shown by gas composition analysis. Quantitative FISH (qFISH) analysis showed that methanogens Methanosarcina, Metanobacteria and Methanomicrobiales together with all archaea were almost completely suppressed when statins were supplemented into MFC anodes. This study demonstrated that the statins addition can be used to boost power densities in MFCs.
A genome-wide atlas of recurrent repeat expansions in human cancer
Authors: Erwin Graham S. , Gürsoy Gamze , Al-Abri Rashid , Suriyaprakash Ashwini , Dolzhenko Egor , Zhu Kevin , Hoerner Christian R. , White Shannon M. , Ramirez Lucia , Vadlakonda Ananya , Vadlakonda Alekhya , von Kraut Konor , Park Julia , Brannon Charlotte M. , Sumano Daniel A. , Kirtikar Raushun A. , Erwin Alicia A. , Metzner Thomas J. , Yuen Ryan K. C. , Fan Alice C. , Leppert John T. , Eberle Michael A. , Gerstein Mark , Snyder Michael P. 
Published: August 2022

AbstractExpansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs (STRs), a phenomenon termed microsatellite instability (MSI); however larger repeat expansions have not been systematically analyzed in cancer. Here, we identified TR expansions in 2,622 cancer genomes, spanning 29 cancer types. In 7 cancer types, we found 160 recurrent repeat expansions (rREs); most of these (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with an enrichment near candidate cis-regulatory elements, suggesting a role in gene regulation. One rRE located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, targeting cells harboring this rRE with a rationally designed, sequence-specific DNA binder led to a dose-dependent decrease in cell proliferation. Overall, our results demonstrate that rREs are an important but unexplored source of genetic variation in human cancers, and we provide a comprehensive catalog for further study.
Antibiotic heteroresistance generated by multi-copy plasmids
Authors: Hernandez-Beltran JCR , Rodríguez-Beltrán J , Aguilar-Luviano B , Velez-Santiago J , Mondragón-Palomino O , MacLean RC , Fuentes-Hernández A , Millán A San , Peña-Miller R 
Published: August 2022

ABSTRACTHeteroresistance – in which a clonal bacterial population contains a cell subpopulation with higher resistance to antibiotics than the main population – is a growing clinical problem that complicates susceptibility determination and threatens therapeutic success. Despite the high prevalence of heteroresistance in clinical settings, the underlying genetic mechanisms that stably maintain heterogeneous bacterial populations are poorly understood. Using fluorescence microscopy, single-cell microfluidics, and quantitative image analysis, we show that random replication and segregation of multicopy plasmids produce populations of bacterium Escherichia coli MG1655 in which cells with low-and high-plasmid copy numbers stably co-exist. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression, we show that copy number variability confers the bacterial population with transient resistance to a lethal concentration of a β -lactam antibiotic. Moreover, this surviving, high plasmid copy minority is capable of regenerating a heterogeneous bacterial population with low and high plasmid copy numbers through segregational instability, rapidly alleviating the fitness burden of carrying large numbers of plasmids. Our results provide further support for the tenet that plasmids are more than simple vehicles for horizontal transmission of genetic information between cells, as they can also drive bacterial adaptation in dynamic environments by providing a platform for rapid amplification and attenuation of gene copy number that can accelerate the rate of resistance adaptation and can lead to treatment failure.
Intentions to get vaccinated against Monkeypox in Healthcare workers in France and Belgium correlates with attitudes toward COVID-19 vaccination
Authors: Gagneux-Brunon Amandine , Dauby Nicolas , Launay Odile , Botelho-Nevers Elisabeth 
Published: August 2022

Abstract textBackgroundFront-line healthcare workers (HCWs) could be at-risk for Monkeypox infections. Vaccine hesitancy also affects HCWs and has an impact on their own attitudes toward vaccination. In the context of the exhaustion due to COVID-19 pandemic, we aimed to evaluate intentions to get vaccinated against Monkeypox in HCWs in France and Belgium.MethodsWe performed a cross-sectional study (snowball sampling) using a self-administered online questionnaire to evaluate intentions to get vaccinated against Monkeypox in HCWs if a recommendation for HCWs vaccination was made. We compared demographics characteristics, vaccine readiness, eagerness for COVID-19 vaccine, and confidence in HCW with Chi-square tests, student-t and performed a binary regression.ResultsAmon the 397 respondents, if a specific recommendation was made for HCWs vaccination against Monkeypox was made, 55.4 % will probably get the vaccine, while 79 % would accept the vaccine if recommended to the general population. COVID-19 vaccine eagerness and having concerns about Monkeypox epidemics were associated with favorable attitude toward Monkeypox vaccination in HCWs with respective adjusted odds ratio and 95 % Confidence Interval 2.5 (1.03-6.1), 2.6 (1.3-5.3). Forty-four HCWs (11 %) self-identified as at-risk for Monkeypox infections.ConclusionAcceptance of Monkeypox vaccination in HCWs is probably moderate, HCWs are probably complacent and did not perceive the risk of Monkeypox infections in the context of professional exposure.
Deciphering the alphabet of disorder — Glu and Asp act differently on local but not global properties
Authors: Roesgaard Mette Ahrensback , Lundsgaard Jeppe E. , Newcombe Estella A. , Jacobsen Nina L. , Pesce Francesco , Tranchant Emil E. , Lindemose Søren , Prestel Andreas , Hartmann-Petersen Rasmus , Lindorff-Larsen Kresten , Kragelund Birthe B. 
Published: August 2022

AbstractCompared to folded proteins, the sequences of intrinsically disordered proteins (IDPs) are enriched in polar and charged amino acids. Glutamate is one of the most enriched amino acids in IDPs, while the chemically similar amino acid aspartate is less enriched. So far, the underlying functional differences of glutamates and aspartates in IDPs remain poorly understood. In this study, we examine the differential effects of aspartate and glutamates in IDPs by comparing the function and conformational ensemble of glutamate and aspartate variants of the disordered protein Dss1, using a range of assays, including interaction studies, nuclear magnetic resonance spectroscopy, small angle X-ray scattering and molecular dynamics simulation. First, we analyze the sequences of the rapidly growing data base of experimentally verified IDPs (DisProt) and show that the glutamate enrichment is not caused by a taxonomy bias in IDPs. From analyses of local and global structural properties as well as cell growth and protein-protein interactions using a model acidic IDP from yeast and three Glu/Asp variants, we find that while Glu/Asp support similar function and global dimensions, the variants differ in their binding affinities and population of local transient structural elements. We speculate that these local structural differences may play roles in functional diversity where glutamates can support increased helicity important for folding and binding, while aspartates support extended structures and form helical caps, as well as playing more relevant roles in e.g., transactivation domains and ion-binding.
Family involvement and proactive tax management behaviour in private family SMEs
Authors: Clemente-Almendros José Antonio , González-Cruz Tomás 
Published: August 2022

PurposeThis paper investigates whether board composition, a family chief executive officer (CEO) and the firm's managerial capabilities affect proactive tax management in family small and medium-sized enterprises (SMEs). The main statement is that the professionalisation of corporate government and management practices explains the difference in tax avoidance behaviour in closely held family SMEs.Design/methodology/approachUsing the 2012 Spanish thin-capitalisation rule as a quasi-experiment, the authors estimate panel regressions with firm fixed effects and robust standard errors. This model represents a triple difference-in-differences combined with propensity score matching (PSM-DID).FindingsAnalysis shows that having a high proportion of non-family board members and a high endowment of managerial capabilities lead to tax liability optimisation in family SMEs. Conversely, familial boards and family SMEs with low managerial capabilities lack enough expertise to weigh the costs of tax avoidance over the benefits, resulting in a reluctance to engage in tax optimisation behaviours. Alike, results show no significant relation between CEO's family affiliation and tax management behaviour.Practical implicationsWhen implementing fiscal policies, the specific needs of family SMEs should be considered, and how these needs interact with corporate governance and managerial mechanisms. Moreover, policymakers need a deeper understanding of family SMEs in order to develop policies appropriate to their characteristics. A more comprehensive knowledge of how family firm heterogeneity affects corporate decisions, such as indebtedness and fiscal decisions, may improve public policies.Originality/valueThis study addresses the issue of tax behaviour in family SMEs in a particular event that implies a specific logic to weigh the pros and cons of each alternative: reducing debt or paying more taxes. This study’s conclusions are based on a model that deals with potential endogeneity problems, which avoids bias in the findings.
Market integration and volatility spillover across major East Asian stock and Bitcoin markets: an empirical assessment
Authors: Zeng Hongjun , Ahmed Abdullahi D. 
Published: August 2022

PurposeThis paper aims to provide new perspectives on the integration of East Asian stock markets and the dynamic volatility transmission to the Bitcoin market utilising daily data from 2014 to 2020.Design/methodology/approachThe authors undertake comprehensive analyses of the dependency dynamics, systemic risk and volatility spillover between major East Asian stock and Bitcoin markets. The authors employ a vine-copula-CoVaR framework and a VAR-BEKK-GARCH method with a Wald test.Findings(a) With exception of KS11 and N225; HSI and SSE; HSI and KS11, which have moderate dependence, dependencies among other markets are low. In terms of tail risk, the upper tail risk is more significant in capturing strong common variation. (b) Two-way and asymmetric risk spillover effects exist in all markets. The Hong Kong and Japanese stock markets have significant risk spillovers to other markets, and quite notably, the Chinese stock market is the largest recipient of systemic risk. However, the authors observe a more significant risk spillover from the Chinese stock market to the Bitcoin market. (c) The VAR-BEKK-GARCH results confirm that the Korean market is a significant emitter of volatility spillovers. The Bitcoin market does provide diversification benefits. Interestingly, the Chinese stock market has an intriguing relationship with Bitcoin. (d) An increase in spillovers in East Asia boosts spillovers to Bitcoin, but there is no intuitive effect of Bitcoin spillovers on East Asian spillovers.Originality/valueFor the first time, the authors examine the dynamic linkage between Bitcoin and the major East Asian stock markets.
Key drivers, challenges and strategies towards successful low-carbon campus: the case of UiTM Shah Alam campus
Authors: Mustaffa N.K. , Kudus S.A. , Aziz M.F.H.A. 
Published: August 2022

Purpose
There is a growing awareness of the dangers of climate change and global warming due to increasing energy consumption and associated greenhouse gas emissions. Campus universities are critical for implementing low-carbon development efficiently, given the large population and socio-economic activities concentrated on campus. This paper aims to explore the existing campus management initiatives and recommends holistic driving elements towards successful low-carbon campus development.

Design/methodology/approach
This study’s triangulation of information was supplemented by contributions from 116 respondents on the UiTM Shah Alam campus and eight professional interviews with stakeholders involved in low-carbon campus projects.

Findings
The study reported that low-carbon strategies had been implemented on the UiTM Shah Alam campus, with most existing programmes and activities focusing on low-hanging fruit initiatives. Moreover, the findings indicate that financial, cultural, behavioural, organisational and physical constraints are critical challenges to effectively implementing low-carbon approaches. The proposed techniques suggest that generating green funding, defining clear targets, developing standard procedures for carbon assessment and monitoring, also boosting education and outreach programmes lead to the improvement of low-carbon campus efforts.

Practical implications
The outcomes of this paper offer perspective to campus administration and community into an evaluation of current approaches and strategies for merging low-carbon systems. The effectiveness of low-carbon implementation was ensured by addressing issues concerning low-carbon uptake and fostering low-carbon improvement.

Originality/value
Besides providing a better understanding of techniques to implementing low-carbon development in Malaysia, the critical hurdles and driving factors, the output from this study adds to the existing knowledge available concerning the campus community’s existing comprehension.