bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective mitochondrial-lysosomal axis promotes extracellular vesicles release of mitochondrial components in Huntington’s Disease
Authors: Beatriz Margarida , Vilaça Rita , Anjo Sandra I. , Manadas Bruno , Januário Cristina , Rego A. Cristina , Lopes Carla 
Published: February 2022

ABSTRACTMitochondrial and autophagy dysfunction are mechanisms proposed to be involved in the pathogenesis of several neurodegenerative diseases. Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with mutant Huntingtin-induced abnormalities in neuronal mitochondrial dynamics and quality control. Former studies suggest that the removal of defective mitochondria may be compromised in HD. The mitochondrial quality control is a complex, well-orchestrated pathway that can be compromised through mitophagy dysregulation or impairment in the mitochondrial-lysosomal axis. Another mitochondrial stress response is the generation of mitochondrial-derived vesicles that fuse with the endolysosomal system and form multivesicular bodies that are extruded from cells as extracellular vesicles (EVs).In this study, we comprehensively characterized the mitochondrial and autophagy alterations in premanifest and manifest HD patients and performed a proteomic and genomic EVs profile. We observed that manifest HD patients exhibit mitochondrial and autophagy impairment associated with enhanced EVs release. Further, we detected mitochondrial components in EVs released by HD cells and in neuron-derived EVs. The EV-associated mtDNA copies were elevated in manifest HD patients suggesting to be an alternative pathway for secretion of reactive mitochondrial components. This study provides a novel framework connecting EVs enhanced release of mitochondrial components to mitochondrial and lysosomal dysfunction in HD.
RNA triplex structures revealed by WAXS-driven MD simulations
Authors: Chen Yen-Lin , He Weiwei , Kirmizialtin Serdal , Pollack Lois 
Published: February 2022

AbstractRNA triple helices are commonly observed tertiary motifs that are increasingly associated with critical biological functions, including signal transduction. Because the recognition of their biological importance is relatively recent, their full range of structures and function has not yet been elucidated. The integration of solution wide-angle X-ray scattering (WAXS) with data-driven molecular dynamics (MD) simulations, described here, provides a new way to capture the structures of major-groove RNA triplexes that evade crystallographic characterization. This method yields excellent agreement between measured and computed WAXS profiles, and allows for an atomically detailed visualization of these motifs. Using correlation maps, the relationship between well-defined features in the scattering profiles and real space characteristics of RNA molecules is easily defined, including the subtle conformational variations in the double-stranded RNA upon the incorporation of a third strand by base-triples. This readily applicable approach provides unique insight into some of the interactions that stabilize RNA tertiary structure and enable function.
A novel Bayesian factor analysis method improves detection of genes and biological processes affected by perturbations in single-cell CRISPR screening
Authors: Zhou Yifan , Luo Kaixuan , Chen Mengjie , He Xin 
Published: February 2022

AbstractCRISPR screening coupled with single-cell RNA-sequencing has emerged as a powerful tool to characterize the effects of genetic perturbations on the whole transcriptome at a single-cell level. However, due to the sparsity and complex structure of data, analysis of single-cell CRISPR screening data remains challenging. In particular, standard differential expression analysis methods are often under-powered to detect genes affected by CRISPR perturbations. We developed a novel method for such data, called Guided Sparse Factor Analysis (GSFA). GSFA infers latent factors that represent co-regulated genes or gene modules, and by borrowing information from these factors, infers the effects of genetic perturbations on individual genes. We demonstrated through extensive simulation studies that GSFA detects perturbation effects with much higher power than state-of-the-art methods. Using single-cell CRISPR data from human CD8+ T cells and neural progenitor cells, we showed that GSFA identified biologically relevant gene modules and specific genes affected by CRISPR perturbations, many of which were missed by existing methods, providing new insights into the functions of genes involved in T cell activation and neurodevelopment.
Solution structure of the phosphatidylinositol 3-phosphate binding domain from theLegionellaeffector SetA
Authors: Beck Wendy H.J. , Enoki Thais A. , Wu Xiaochun , Zhang Qing , Nicholson Linda K. , Oswald Robert E. , Mao Yuxin 
Published: February 2022

AbstractLegionella pneumophilais a facultative intracellular pathogen that causes Legionnaires’ disease or Pontiac fever in humans upon accidental inhalation ofLegionella-contaminated aerosols. During infection,L. pneumophilasecretes more than 300 effectors into the host for the biogenesis of a replication-permissive niche, known as theLegionella containingvacuole (LCV). Among these, a large number of effectors harbor protein domains that recognize specific phosphoinositide (PI) lipids and mediate the anchoring of these effectors to the surface of LCV or other host membrane-bound organelles. TheLegionellaeffector SetA contains a unique C-terminal domain (SetA-CTD) that has been shown to specifically bind with phosphatidylinositol-3-phosphate (PI(3)P) and target SetA to endosomes and LCVs. Here, we report the NMR solution structure of SetA-CTD, which mainly comprises a four α-helix bundle. The structure reveals a basic pocket at one end of the α-helix bundle for PI(3)P binding and two hydrophobic loops for membrane insertion. Mutations of key residues involved in lipid binding result in the loss of SetA in membrane association and endosomal localization. Structural comparison with other PI(3)P-binding domains highlights a general theme applied by multiple families of phosphoinositide-binding domains across species.
Ultrahigh-throughput directed evolution of a metal-free α/β-hydrolase with a Cys-His-Asp triad into an efficient phosphotriesterase
Authors: Schnettler Fernández David , Klein Oskar James , Kaminski Tomasz S. , Colin Pierre-Yves , Hollfelder Florian 
Published: February 2022

ABSTRACTThe recent massive release of new, man-made substances into the environment requires bioremediation, but a very limited number of enzymes evolved in response are available. When environments have not encountered the potentially hazardous materials in their evolutionary history, existing enzymes have to be repurposed. The recruitment of accidental, typically low-level promiscuous activities provides a head start that, after gene duplication, can adapt and provide a selectable advantage. This evolutionary scenario raises the question whether it is possible to adaptively improve the low-level activity of enzymes recruited from non- (or only recently) contaminated environments quickly to the level of evolved bioremediators.Here we address the evolution of phosphotriesterases (enzymes for hydrolysis of organophosphate pesticides or chemical warfare agents) in such a scenario: In a previous functional metagenomics screening we had identified a promiscuous phosphotriesterase activity of the α/β-hydrolase P91, with an unexpected Cys-His-Asp catalytic triad as the active site motif. We now probe evolvability of P91 using ultrahigh-throughput screening in microfluidic droplets, and test for the first time whether the unique catalytic motif of a cysteine-containing triad can adapt to achieve rates that rival existing phosphotriesterases. These mechanistically distinct enzymes achieve their high rates based on catalysis involving a metal-ion cofactor. A focussed, combinatorial library of P91 (> 105 members) was screened on-chip in microfluidic droplets by quantification of the reaction product, fluorescein. Within only two rounds of evolution P91’s phosphotriesterase activity was increased ≈ 400-fold to a kcat/KM of ≈ 106 M−1s−1, matching the catalytic efficiencies of naturally evolved metal-dependent phosphotriesterases. In contrast to its homologue acetylcholinesterase that suffers suicide inhibition, P91 shows fast de-phosphorylation rates and is rate-limited by the formation of the covalent adduct rather than by its hydrolysis. Our analysis highlights how the combination of focussed, combinatorial libraries with the ultrahigh throughput of droplet microfluidics can be leveraged to identify and enhance mechanistic strategies that have not reached high efficiency in Nature, resulting in alternative reagents with a novel catalytic machinery.GRAPHICAL ABSTRACT
A pili-driven bacterial turbine
Authors: Pönisch Wolfram , Zaburdaev Vasily 
Published: February 2022

ABSTRACTWork generated by self-propelled bacteria can be harnessed with the help of microdevices. Such nanofabricated microdevices, immersed in a bacterial bath, may exhibit unidirectional rotational or translational motion. Swimming bacteria that propel with the help of actively rotating flagella are a prototypical example of active agents that can power such microdevices.In this work, we propose a computational model of a micron-sized turbine powered by bacteria that rely on active type IV pili appendages for surface-associated motility. We find that the turbine can rotate persistently over a time scale that significantly exceeds the characteristic times of the single cell motility. The persistent rotation is explained by the collective dynamics of multiple pili of groups of cells attaching to and pulling on turbine. Furthermore, we show that the turbine can rotate permanently in the same direction by altering the pili binding to the turbine surface in an asymmetric fashion. We thus can show that by changing the adhesive properties of the turbine while keeping its symmetric geometry, we can still break the symmetry of its rotation.Altogether, this study widely expands the range of bacteria that can be used to power nanofabricated microdevices, and, due to high pili forces generated by pili retraction, promises to push the harnessed work by several orders of magnitude.
Feminine traits improve transformational leadership advantage: investigation of leaders’ gender traits, sex and their joint impacts on employee contextual performance
Authors: Chen Shu-Chen , Shao Jieqi 
Published: February 2022

Purpose
This research aims to examine the indirect relationship between feminine traits and employee contextual performance through transformational leadership. Additionally, it explored the role of leaders’ sex in moderating the relationship between feminine traits and transformational leadership through a moderated mediation model that subsequently influences employee contextual performance.

Design/methodology/approach
This study tested and validated the moderated mediation model using a two-wave survey with 295 samples. Bootstrapping was adopted for model testing.

Findings
The results indicated that leaders’ sex moderated the relationship between feminine traits and employee contextual performance through transformational leadership, such that the indirect effect was stronger for female leaders than for male leaders.

Practical implications
Female leaders can improve employee contextual performance by demonstrating transformational leadership with feminine traits. Organizations must implement measures (i.e. training) to promote the acceptance and application of leader gender and gender-role trait diversity, reduce the prevalence of gender stereotypes and help leaders benefit from learning and implementing the effective combination of leadership and feminine traits.

Originality/value
The study demonstrated the joint effects of leaders’ sex (difference) and gender-role traits on employee contextual performance through transformational leadership. These results provide female leaders with feminine traits to gain a leadership advantage and an in-depth understanding of role congruity theory from the perspective of leadership effectiveness.
Self-efficacy and academic programme satisfaction: mediating effect of meaningfulness of study
Authors: Azila-Gbettor Edem M. , Mensah Christopher , Abiemo Martin Kwasi 
Published: February 2022

PurposeThe paper examined the mediating effect of meaningfulness of study on the relation between self-efficacy and academic programme satisfaction within higher education setup.Design/methodology/approachA total of 376 randomly selected students took part in the study by completing a self-reported survey. Data were analysed using PLS-SEM.FindingsResults suggest self-efficacy and meaningfulness of studies positively predict student's satisfaction with academic programme. Besides, meaningfulness of study mediates the relation between self-efficacy and student's satisfaction of academic programme.Originality/valueThis study is one of the first to provide empirical evidence of the influence of meaningfulness of studies on self-efficacy and student academic programme satisfaction in the higher education context.
Community engagement in development projects: government versus private funded projects in Ghana
Authors: Arkorful Helen , Hilton Sam Kris , Awaah Fred 
Published: February 2022

Purpose
The abandonment of governmental development projects either after completion or midway completion at the taxpayer’s expense in Ghana could be attributed to lack of effective community engagement (CE). Thus, this study aims to assess CE in development projects by comparing government-sponsored projects to private-sponsored projects.

Design/methodology/approach
A qualitative approach was adopted where a multiple case study design was used as a research strategy. Data was collected from selected districts in the Central Region of Ghana by using a semi-structured interview guide and analyzed using the thematic and comparative analysis techniques.

Findings
The results reveal that CE in government-funded projects was low, while CE in projects funded by private organizations was high. Three levels of engagement (consultation, participation in decision-making and consent) were also identified. Furthermore, the roles of public participation, including knowledge sharing, collective sense of ownership, among others, were ascertained. Finally, resources constraints, competing interests, lack of information flow, public attitudes toward change and central government/political interference are challenges of CE in development projects.

Originality/value
This study has provided an empirical basis for government and other development agents to draft a policy on CE to serve as a guide, spell out the role of CE, mitigate the challenges of CE and ensure strict compliance to the three levels of engagement.
The association of dietary inflammatory index, functional foods and some antioxidants intake with COVID-19 vaccine side effects in Iranian adults
Authors: Mohajeri Mahsa 
Published: February 2022

Purpose
This study aims to assess the association of dietary inflammatory index (DII), consumption of functional food and some antioxidants with COVID-19 vaccine side effects in Iranian adults.

Design/methodology/approach
This was a case–control study conducted among the 1,067 Iranian adults who were invited to participate through WhatsApp software. The dietary intake was assessed using the food frequency questionnaire.

Findings
There was a significant difference (p = 0.04) in vitamin D consumption between healthy people and persons with a vaccine side effect. Vitamin E intake in healthy participants was significantly (p = 0.04) more than case group. There was a significant difference in the consumption of zinc (p = 0.01), selenium (p = 0.02) and vitamin C (p = 0.02), between persons without vaccine side effects and the case group. Consumption of onion (82.5 ± 9.5 g/day vs 32.2 ± 6.3; p = 0.0001), garlic (6 ± 0.3 g/day vs 0.2 ± 0.08; p = 0.0001) and oat (2.2 ± 0.05 g/day vs 0.5 ± 0.01; p = 0.001) in the control group was significantly more than persons with vaccine side effects. With the increase in each unit in the score of the DII, the risk of COVID-19 vaccine side effect incidence increased 1.7 times (OR = 1.7; 95% CI: 1.3–1.8).

Originality/value
To the best of the authors’ knowledge, this study is the first that investigated the association between functional food intake and side effects of the COVID-19 vaccine.
Outcomes during delivery hospitalisations with inflammatory bowel disease
Authors: Yu K. , Faye A. S. , Wen T , Guglielminotti J. R. , Huang Y. , Wright J. D. , D’Alton M. E.  , Friedman A. M. 
Published: February 2022

AbstractObjectiveTo characterise inflammatory bowel disease (IBD) trends and associated risk during delivery hospitalisations.DesignCross‐sectional.SettingUS delivery hospitalisations.PopulationDelivery hospitalisations in the 2000–2018 National Inpatient Sample.MethodsThis study analysed a nationally representative hospital discharge database based on the presence of IBD. Temporal trends in IBD were analysed using joinpoint regression to estimate the average annual percent change (AAPC). IBD severity was characterised by the presence of diagnoses such as penetrating and stricturing disease and history of bowel resection. Risks for adverse outcomes were analysed based on presence of IBD. Poisson regression models were performed with unadjusted and adjusted risk ratios (aRR) as measures of effect.Main Outcome MeasurePrevalence of IBD and associated adverse outcomes.ResultsOf 73 109 790 delivery hospitalisations, 89 965 had a diagnosis of IBD. IBD rose from 0.06% in 2000 to 0.21% in 2018 (AAPC 7.3%, 95% CI 6.7–7.9%). Among deliveries with IBD, IBD severity diagnoses increased from 4.1% to 8.1% from 2000 to 2018. In adjusted analysis, IBD was associated with increased risk for preterm delivery (aRR 1.50, 95% CI 1.47–1.53), severe maternal morbidity (aRR 1.93, 95% CI 1.83–2.04), venous thrombo‐embolism (aRR 2.76, 95% CI 2.39–3.18) and surgical injury during caesarean delivery hospitalisation (aRR 5.03, 95% CI 4.76–5.31). In the presence of a severe IBD diagnosis, risk was further increased for all adverse outcomes.ConclusionIBD is increasing in the obstetric population and is associated with adverse outcomes. Risk is increased in the presence of a severe IBD diagnosis.Tweetable AbstractDeliveries among women with inflammatory bowel disease are increasing. Disease severity is associated with adverse outcomes.
Second and third trimester estimation of gestational age using ultrasound or maternal symphysis‐fundal height measurements: A systematic review
Authors: Self Alice , Daher Lama , Schlussel Michael , Roberts Nia , Ioannou Christos , Papageorghiou Aris T. 
Published: February 2022

AbstractBackgroundAccurate assessment of gestational age (GA) is important for managing pregnancies at an individual level and monitoring preterm birth rates at a population level.ObjectivesAs many women first seek antenatal care in late pregnancy, our aim was to assess the methodology of studies reporting equations for estimating GA after 20 weeks’ gestation using ultrasound or symphysis‐fundal height (SFH) measurements.Search strategySix electronic databases were searched for studies published from January 1970 to April 2021.Selection criteriaStudies were included if they contained a formula using SFH or ultrasound‐measured biometry to estimate GA after 20 weeks in healthy singleton pregnancies.Data collection and analysisTwo reviewers and a statistician reviewed study design, statistical methods, and reporting methods using 29 criteria. Each article was awarded an overall quality score, predefined as the percentage of the 29 criteria scored at low risk of bias. 95% prediction intervals were calculated for studies that used recommended first trimester dating to confirm true GA.Main resultsThe search yielded 4209 results. Ninety‐seven full‐text articles were included in the analysis. The mean quality score was 32% (range 7%–97%). Only 10 articles scored low risk in 18 or more criteria. Their formulas estimated GA using one or more ultrasound‐measured biometry parameters and SFH measurements. Twenty‐three articles used recommended first trimester dating. A single‐parameter formula using transcerebellar diameter (TCD) gave the lowest 95% prediction interval.ConclusionsThere is considerable methodological heterogeneity in studies developing equations for estimating GA. Formulas using ultrasound‐based measurements more accurately estimated GA after 20 weeks than formulas using SFH measurement. While the clinical priority remains promotion of early engagement with antenatal care, we suggest unified standards for GA and growth assessment.Tweetable abstractMany vulnerable women seek antenatal care late in pregnancy. How should gestational age be determined? We examine all available studies estimating GA >20 weeks. Ultrasound is much better than fundal height, and using cerebellar measurement appears to be the most accurate.
What are the perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays? A systematic review of the literature
Authors: Grant Claire , Jones Anne , Land Helen 
Published: February 2022

AbstractObjectiveTo identify the attitudes and perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays.DesignSystematic Literature Review.MethodAn electronic search of databases Scopus, CINAHL, MEDLINE, PEDro, Speechbite, OTseeker and ScienceDirect was undertaken in October 2020. Articles were compared with eligibility criteria by 2 authors. All articles were appraised for quality and level of evidence.FindingsFourteen studies were deemed to be eligible. Results were synthesised using a narrative analysis. The themes identified were technology, self‐efficacy, replacement of face‐to‐face services, time management, relationships, access and family‐centred care. Each of these themes was seen as both a potential barrier and a facilitator when trying to provide services via telehealth.ConclusionsThe results in this review cannot be generalised due to small sampling size, low response rates, lack of maximum variation sampling and under‐representation of occupational therapists and physiotherapists. Study design was either mixed‐methods survey or interview or only survey or interview. Risk of bias in studies was high. Further research is required including comparison studies and cost‐benefit analysis.