bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental experiences of the impacts of COVID-19 on the care of young children; qualitative interview findings from the Nairobi Early Childcare in Slums (NECS) Project
Authors: Hughes Robert C , Muendo Ruth , Bhopal Sunil S , Onyango Silas , Kimani-Murage Elizabeth , Kirkwood Betty R , Hill Zelee , Kitsao-Wekulo Patricia 
Published: September 2022

AbstractIntroductionThe Covid-19 pandemic, and societal attempts to control it, have touched almost every aspect of people’s lives around the world, albeit in unequal ways. In particular, there is considerable concern about the way that stringent ‘lockdowns’, as implemented in Kenya and many other countries, affected young children, especially those living in informal settlements. However, to date, there has been little research attempting to unpack and understand how the pandemic has impacted on the care of young children.MethodsIn-depth telephone interviews were conducted with 21 parents/carers of children aged under five years living in three Nairobi slums between May and September 2021 exploring the ways in which covid-19, and policies to control the pandemic, impacted on their household and the care of their child/children.ResultsThe impacts of covid-19 control measures on the care of children have been widely felt, deep and multiple. The impact of economic hardship has been significant, reportedly undermining food security and access to services including healthcare and childcare. Respondents reported an associated increase in domestic and community violence. Many people relied on help from others; this was most commonly reported to be in the form of variable levels of flexibility from landlords and help from other community members. No direct harms from covid-19 disease were reported by respondents.ConclusionThe impacts of covid-19 control measures on the care of young children in informal settlements have been indirect but dramatic. Given the breadth and depth of these reported impacts, and the particular vulnerability of young children, deeper consideration ought to inform decisions about approaches to implementation of stringent disease control measures in future. In addition, these findings imply a need for both short- and long-term policy responses to ameliorate the impacts described.Key messagesYoung children living in slums, while at low direct risk from Covid-19, are highly vulnerable to early childhood adversity, so may be at great risk from economic and other hardships that are a likely ‘side effect’ of blunt pandemic control measures like stringent ‘lockdowns’.Parent/carers described a set of indirect impacts of covid-19 control efforts that were broad, deep and protracted. Core to these impacts was widespread economic hardship, with knock on effects on household food security, wellbeing and community safety.Considering the particular risks and vulnerability that blunt pandemic control measures present to young children, especially those in slums, needs to be central to policy discussions about if and how to implement stringent disease-control measures. In addition, more research is required to quantify the issues identified in this qualitative inquiry.
A dynamic template complex mediates Munc18-chaperoned SNARE assembly
Authors: Yang Jie , Jin Huaizhou , Liu Yihao , Guo Yaya , Zhang Yongli 
Published: September 2022

AbstractMunc18 chaperones assembly of three membrane-anchored soluble N-ethylmaleimide- sensitive factor attachment protein receptors (SNAREs) into a four-helix bundle to mediate membrane fusion between vesicles and plasma membranes, leading to neurotransmitter or insulin release, GLUT4 translocation, or other exocytotic processes. Yet, the molecular mechanism underlying chaperoned SNARE assembly is not well understood. Recent evidence suggests that Munc18-1 and Munc18-3 simultaneously bind their cognate SNAREs to form ternary template complexes - Munc18-1:Syntaxin-1:VAMP2 for synaptic vesicle fusion and Munc18-3:Syntaxin-4:VAMP2 for GLUT4 translocation and insulin release, which facilitate binding of SNAP-25 or SNAP-23 to conclude SNARE assembly. Here, we further investigate the structure, dynamics, and function of the template complexes using optical tweezers. Our results suggest that the synaptic template complex transitions to an activated state with a rate of ∼0.05 s−1 and ∼6.8 kBT higher energy for efficient SNAP-25 binding. The transition depends upon the linker region of syntaxin-1 upstream of its helical bundle-forming SNARE motif. In addition, the template complex is stabilized by a poorly characterized disordered loop region in Munc18-1. While the synaptic template complex efficiently binds both SNAP-25 and SNAP-23, the GLUT4 template complex strongly favors SNAP-23 over SNAP-25, despite similar stabilities of their assembled SNARE bundles. Together, our data demonstrate that a highly dynamic template complex mediates efficient and specific SNARE assembly.SignificanceMunc18-1 chaperones coupled folding and assembly of three synaptic SNAREs, syntaxin-1, VAMP2, and SNAP-25, into a four-helix bundle to mediate membrane fusion and neurotransmitter release. Recent evidence suggests that Munc18-1, syntaxin-1, and VAMP2 first form a weak template complex and then bind to SNAP-25 to complete SNARE assembly. However, the dynamics and function of the template complex are not well understood. Using optical tweezers, we found that the template complex undergoes a conformational change to bind SNAP-25 in a way dependent upon the syntaxin linker region and that Munc18 kinetically proofreads SNARE pairing not governed by its thermodynamic stability. Our study reveals a more dynamic template complex than that seen in its cryo-EM structure.
Mistle: bringing spectral library predictions to metaproteomics with an efficient search index
Authors: Nowatzky Yannek , Benner Philipp , Reinert Knut , Muth Thilo 
Published: September 2022

AbstractMotivationDeep learning has moved to the forefront of tandem mass spectrometry-driven proteomics and authentic prediction for peptide fragmentation is more feasible than ever. Still, at this point spectral prediction is mainly used to validate database search results or used for confined search spaces. Fully predicted spectral libraries have not yet been efficiently adapted to large search space problems that often occur in metaproteomics or proteogenomics.ResultsIn this study, we showcase a workflow that uses Prosit for spectral library predictions on two common metaproteomes and implement an indexing and search algorithm, Mistle, to efficiently identify experimental mass spectra within the library. Hence, the workflow emulates a classic protein sequence database search with protein digestion but builds a searchable index from spectral predictions as an in-between step. We compare Mistle to popular search engines, both on a spectral and database search level, and provide evidence that this approach is more accurate than a database search using MSFragger. Mistle outperforms other spectral library search engines in terms of run time and proves to be extremely memory efficient with an 8 to 22-fold decrease in RAM usage. This makes Mistle universally applicable to large search spaces, e.g. covering comprehensive sequence databases of diverse microbiomes.AvailabilityMistle is freely available on GitHub at https://github.com/BAMeScience/Mistle.Contactthilo.muth@bam.de
Apelin Stimulation of the Perivascular MuSC Niche Enhances Endogenous Repair in Muscular Dystrophy
Authors: Le Moal Emmeran , Liu Yuguo , Collerette-Tremblay Jasmin , Dumontier Simon , Boutin Joël , Dort Junio , Orfi Zakaria , Michaud Joris , Giguère Hugo , Desroches Alexandre , Trân Kien , Vézina François , Bedard Sonia , Raynaud Catherine , Balg Frederic , Sarret Philippe , Scott Michelle S. , Feige Jerome N. , Denault Jean-Bernard , Dumont Nicolas A. , Marsault Eric , Auger-Messier Mannix , Bentzinger C. Florian 
Published: September 2022

AbstractImpaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here we describe that defects in the endothelial cell (EC) compartment of the perivascular stem cell niche in three different types of MD are associated with inefficient mobilization of MuSCs following tissue damage. Using chemoinformatic analysis, we identified the 13 amino acid form of the peptidic hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. In dystrophic mice, administration of AP-13 generates a pro-myogenic EC-rich niche that supports MuSC function and markedly improves tissue regeneration, muscle strength, and physical performance. Moreover, we demonstrate that EC specific knockout of the AP-13 receptor leads to regenerative defects that phenocopy major pathological features of MD. Altogether, we provide in vivo proof-of-concept that enhancing endogenous repair by targeting the perivascular niche is a viable therapeutic avenue for MD and characterize AP-13 as a novel drug candidate for systemic treatment of stem cell dysfunction.
G-quadruplexes rescuing protein folding
Authors: Son Ahyun , Huizar Cabral Veronica , Litberg Theodore J , Horowitz Scott 
Published: September 2022

SummaryMaintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of E. coli. However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in E. coli further demonstrate that these G4s primarily improve protein folding quality in E. coli as opposed to preventing protein aggregation. The ability for a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins.
Regulatory annotation identifies KAN1, MYB44 and PIF4 as regulators of Arabidopsis lincRNAs expressed in root
Authors: Liu Li , Heidecker Michel , Depuydt Thomas , Perez Nicolas Manosalva , Crespi Martin , Blein Thomas , Vandepoele Klaas 
Published: September 2022

ABSTRACTThousands of long intergenic noncoding RNAs (lincRNAs) have been identified in plant genomes. While some lincRNAs have been characterized as important regulators in different biological processes, little is known about the transcriptional regulation for most plant lincRNAs. Through the integration of eight annotation resources, we defined 6,599 high-confidence lincRNA loci inArabidopsis thaliana. For lincRNAs belonging to different evolutionary age categories, we identified major differences in sequence and chromatin features, as well as in the level of conservation and purifying selection acting during evolution. Spatiotemporal gene expression profiles combined with transcription factor (TF) chromatin immunoprecipitation data were used to construct a TF- lincRNA regulatory network containing 2,659 lincRNAs and 15,686 interactions. We found that properties characterizing lincRNA expression, conservation and regulation differ between plants and animals. Experimental validation confirmed the role of three TFs, KAN1, MYB44, and PIF4, as key regulators controlling root- specific lincRNA expression, demonstrating the predictive power of our network. Furthermore, we identified 58 lincRNAs, regulated by these TFs, showing strong root cell-type specific expression or chromatin accessibility, which are linked with GWAS genetic associations related to root system development and growth. The multi-level genome-wide characterization covering chromatin state information, promoter conservation, and ChIP-based TF binding, for all detectable lincRNAs across 769 expression samples, permits to rapidly define the biological context and relevance of lincRNAs in Arabidopsis regulatory networks.One-line sentenceA multi-level Arabidopsis gene regulatory network identifies novel regulators controlling root-specific lincRNA expression, offering a promising strategy to identify lincRNAs involved in plant biology.
Disability in Multiple Sclerosis is Associated with Vascular Factors: An Ultrasound study
Authors: Kemp Merlisa , Johannes Clint , van Rensburg Susan J , Kidd Martin , Isaacs Ferial , Kotze Maritha J , Engel-Hills Penelope 
Published: September 2022

AbstractBackgroundAlthough multiple sclerosis (MS) is an immune-related disorder, pharmaceutical interventions targeting the immune system do not stop or reverse disability progression; the major challenge for this condition. Studies show that disability progression in MS is associated with vascular comorbidity and brain volume loss, indicating that a multi-targeted approach is required to prevent debilitation. The aim of the present study was to examine the associations between vascular ultrasound, disability, biochemistry and lifestyle data in people with MS (pwMS).MethodsExtracranial vascular ultrasound was performed on 51 pwMS and 25 age-matched controls. Sonographic interrogation determined carotid intima-media thickness (cIMT) and abnormal blood flow patterns. Disability was assessed using the Expanded Disability Status Scale (EDSS). Biochemical and lifestyle data were obtained for all participants.ResultsThe EDSS had a highly significant positive association with the cIMT of the right (r = 0.63; p = 0.001) and left (r = 0.49; p = 0.001) common carotid arteries and negative associations with the peak systolic blood flow velocity of the right vertebral artery (r = -0.42; p = 0.01) as well as end-diastolic velocity of the left internal carotid artery (r = -0.47; p = 0.01). These associations were significantly influenced by biochemical and lifestyle factors. Both cIMT and age showed significant associations with the EDSS. When cIMT was adjusted for age in a regression analysis, the association between the EDSS and the cIMT remained significant (p < 0.01), while the age association was reduced to being significant only at 10% (p = 0.06). There was no association between the use of MS medication and the EDSS (p = 0.56).ConclusionPwMS who had increased cIMT, a surrogate marker for atherosclerosis, and reduced carotid artery blood flow velocities were at risk for greater disability over and above the effect of aging. These findings provide important information for disease management and disability prevention in pwMS. Modification of diet and lifestyle may promote the unhindered flow of essential nutritional factors into the brain in pwMS.
Multicentre diagnostic evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among symptomatic individuals in Brazil and The United Kingdom
Authors: Thompson Caitlin R , Torres Pablo Muñoz , Kontogianni Konstantina , Byrne Rachel L ,   LSTM Diagnostic group, Noguera Saidy Vásconez , Luna-Muschi Alessandra , Marchi Ana Paula , Andrade Pâmela S , Santos Barboza Antonio dos , Nishikawara Marli ,   CONDOR steering group, Body Richard , de Vos Margaretha , Escadafal Camille , Adams Emily , Costa Silvia Figueiredo , Cubas Atienzar Ana I 
Published: September 2022

ABSTRACTThe COVID-19 pandemic has given rise to numerous commercially available antigen rapid diagnostic tests (Ag-RDTs). To generate and share accurate and independent data with the global community, multi-site prospective diagnostic evaluations of Ag-RDTs are required. This report describes the clinical evaluation of OnSite COVID-19 Rapid Test (CTK Biotech, California, USA) in Brazil and The United Kingdom.A total of 496 paired nasopharyngeal (NP) swabs were collected from symptomatic healthcare workers at Hospital das Clínicas in São Paulo, and 211 NP swabs were collected from symptomatic participants at a COVID-19 drive-through testing site in Liverpool, England. These swabs were analysed by Ag-RDT and results were compared to RT-qPCR.The clinical sensitivity of the OnSite COVID-19 Rapid test in Brazil was 90.3% [95% Cl 75.1 – 96.7%] and in the United Kingdom was 75.3% [95% Cl 64.6 – 83.6%]. The clinical specificity in Brazil was 99.4% [95% Cl 98.1 – 99.8%] and in the United Kingdom was 95.5% [95% Cl 90.6 – 97.9%]. Analytical evaluation of the Ag-RDT was assessed using direct culture supernatant of SARS-CoV-2 strains from Wild-Type (WT), Alpha, Delta, Gamma and Omicron lineages. Analytical limit of detection was 1.0×103pfu/mL, 1.0×103pfu/mL, 1.0×102pfu/mL, 5.0×103pfu/mL and 1.0×103pfu/mL, giving a viral copy equivalent of approximately 2.1×105copies/mL, 2.1×104copies/mL, 1.6×104copies/mL, 3.5×106copies/mL and 8.7 × 104for the Ag-RDT, when tested on the WT, Alpha, Delta, Gamma and Omicron lineages, respectively.This study provides comparative performance of an Ag-RDT across two different settings, geographical areas, and population. Overall, the OnSite Ag-RDT demonstrated a lower clinical sensitivity than claimed by the manufacturer… Sensitivity and specificity from the Brazil study fulfilled the performance criteria determined by the World Health Organisation but the performance obtained from the UK study failed to. Further evaluation of the use of Ag-RDTs should include harmonised protocols between laboratories to facilitate comparison between settings.
Drivers for agility in times of crisis
Authors: Solheim Marte C.W. , Aadland Torgeir , Eide Ann Elida , Haneberg Dag Håkon 
Published: September 2022

Purpose
Agile organisations do not arise from a single characteristic but comprise a combination of various aspects. Thus, this study aims to examine the combined effects on organisational agility regarding firms’ utilisation of digital technology to create value during the COVID-19 pandemic, how firms perceive uncertainty related to their own organisational response and the degree to which they have an entrepreneurial mindset.

Design/methodology/approach
Using a fuzzy-set qualitative comparative analysis, this study investigates 355 established firms and start-ups in Norway.

Findings
This study finds digitalisation is required for agility to develop, but that it needs to be combined with having an entrepreneurial mindset or being a start-up and lower levels of perceived uncertainty. Hence, entrepreneurial mindset and low uncertainty are important factors for digitalisation, and in turn, for agility to be developed.

Originality/value
Agility is recognised as being pivotal for firms’ competitiveness and innovation and argued to be significant in overcoming sudden economic shocks. However, lacking empirical scrutiny are investigations into the relationship between digitalisation and agility, and how digitalisation might act as a driver for building agility, which the authors tackle herein.
Charting value creation strategies B2B salespeople use throughout the sales process: learning from social media influencers
Authors: Cheng Zixuan , Plangger Kirk , Cai Feng , Campbell Colin L. , Pitt Leyland 
Published: September 2022

Purpose
This paper aims to explore how business-to-business (B2B) salespeople use social media and emulate value creation strategies used by social media influencers.

Design/methodology/approach
Using 28 interviews with salespeople, this paper develops six propositions and a conceptual framework that outlines when and how B2B salespeople use social media in value-creating sales.

Findings
This study’s findings provide a critical analysis of when social media are most effective and beneficial in supporting salespeople’s value-creating sales in various stages in the sales process (e.g. prospecting, opening relationships, qualifying prospects and serving accounts) and when they are less effective (e.g. presenting sales messages and closing sales).

Research limitations/implications
This research yields a substantive understanding of the evolving role that social media play in B2B sales by examining B2B salespeople’s value creation strategies through the lens of social media influencers’ practice and outlines ideas for future research on B2B salespeople’s social media strategies.

Practical implications
The findings of this research can be used by B2B organizations to structure the training of B2B salespeople to use social media to the fullest extent by aligning specific strategies with different parts of the sales process.

Originality/value
This paper contributes by summarizing the B2B sales literature on social media and integrating recent insights from the social media influencer literature; empirically identifying how B2B salespeople use social media to create value, thus validating previous findings and extending understanding by offering a set of six theoretical propositions; and delineating B2B salespeople’s social media practice into 11 value creation strategies that are critically explored for their place in the sales process.
Implementing data analysis based on the mixed clustering technique for sustainable participatory waste management in a low-budget area
Authors: Warintarawej Pattaraporn , Nillaor Pichetwut 
Published: September 2022

Purpose
The research objectives are as follows: to understand the situation of solid waste management in the Makham Tia Subdistrict Administrative Organization, Surat Thani Province, Thailand; identify the patterns in household waste generation and 3Rs behavior (recycle, reuse and reduce waste); and formulate sustainable municipal solid waste management guidelines.

Design/methodology/approach
This study aimed to propose the solution by using data analysis and a participatory research approach to set the guidelines for sustainable community waste management in a low-budget area. A survey of household behavior was done with questionnaires. Mixed clustering using the Gower coefficient was performed to assess the categorical socio-demographic variables along with the numeric variables related to the 3Rs behavior. The guidelines for waste management were generated based on the characteristics of the household groups.

Findings
The guidelines for waste management were generated based on the characteristics of the household groups. An appropriate practical plan for municipal solid waste management in Makham Tia Subdistrict was proposed in this work. The study showed that the guidelines were implemented and revised by members of the community, and this led to the development of sustainable community solid waste management for the future.

Originality/value
The goal of this study was to provide a solution for sustainable community waste management in a low-budget location by using data mining techniques and a participatory research approach. The study showed that the guidelines were implemented and revised by members of the community, and this led to the development of sustainable community solid waste management for the future.