bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain predictors of fatigue in Rheumatoid Arthritis: a machine learning study
Authors: Goñi María , Basu Neil , Murray Alison D. , Waiter Gordon D. 
Published: October 2021

AbstractBackgroundFatigue is a common and burdensome symptom in Rheumatoid Arthritis (RA), yet is poorly understood. Currently, clinicians rely solely on fatigue questionnaires, which are inherently subjective measures. For the effective development of future therapies and stratification, it is of vital importance to identify biomarkers of fatigue. In this study, we identify brain differences between RA patients who improved and did not improve their levels of fatigue, and we compared the performance of different classifiers to distinguish between these samples at baseline.MethodsFifty-four fatigued RA patients underwent a magnetic resonance (MR) scan at baseline and 6 months later. At 6 months we identified those whose fatigue levels improved and those for whom it did not. More than 900 brain features across three data sets were assessed as potential predictors of fatigue improvement. These data sets included clinical, structural MRI (sMRI) and diffusion tensor imaging (DTI) data. A genetic algorithm was used for feature selection. Three classifiers were employed in the discrimination of improvers and non-improvers of fatigue: a Least Square Linear Discriminant (LSLD), a linear Support Vector Machine (SVM) and a SVM with Radial Basis Function kernel. Results: The highest accuracy (67.9%) was achieved with the sMRI set, followed by the DTI set (63.8%), whereas classification performance using clinical features was at the chance level. The mean curvature of the left superior temporal sulcus was most strongly selected during the feature selection step, followed by the surface are of the right frontal pole and the surface area of the left banks of the superior temporal sulcus. Conclusions: The results presented in this study evidence a superiority of brain metrics over clinical metrics in predicting fatigue changes. Further exploration of these methods may enable clinicians to triage patients towards the most appropriate fatigue alleviating therapies.
A scoping review of the research integrity architecture and how it is addressed in legal frameworks, institutional policies, and the scholarly literature: Research protocol
Authors: Pérez Juan Guillermo , Torres-Sarmiento Carolina , Castro Andrés Felipe Duarte , Gómez Luis Eduardo , Bachelet Vivienne C. 
Published: October 2021

AbstractBackgroundResearch integrity is a dynamic area within the ethical research ecosystem. Several efforts have been made to incorporate this topic in scientific governance frameworks. However, the efforts generally result in non-binding declarations and policies. Due to differences in legal systems, research cultures, and institutional approaches worldwide, there is a need to identify and map existent strategies on sound scientific practices.ObjectiveThis scoping review aims to systematically search, map, and evaluate the best available evidence on strategies and recommendations regarding research integrity. The goal is to identify international, national, regional, and local legal frameworks, institutional policies and guidelines, research integrity policies, interventions, strategies, and recommendations for:The design and conduct of research projects,The publication of research results,The monitoring of scientific practices,The implementation of corrective actions, andMentoring and education on research integrity.MethodsThe search will follow the PRISMA Extension for Scoping Reviews (PRISMA-ScR) and the methodological approach designed by Arksey and O’Malley. It will include legal frameworks, national and international governmental and non-governmental documentation, and scholarly articles published in peer-reviewed journals on research integrity. The search will be conducted in PubMed/MEDLINE, Web of Science, JSTOR, Latin American & Caribbean Health Sciences Literature (Lilacs), Scopus, OECD Library. It will be complemented with hand searching and scanning, covering other databases and grey literature sources. We will extract and synthesize the data using two macro-genres: legal documents (soft law and hard law) and non-legal documents.
A Thermostable Cas12b fromBrevibacillusLeverages One-pot Detection of SARS-CoV-2 Variants of Concern
Authors: Nguyen Long T. , Macaluso Nicolas C. , Pizzano Brianna L.M. , Cash Melanie N. , Spacek Jan , Karasek Jan , Dinglasan Rhoel R. , Salemi Marco , Jain Piyush K. 
Published: October 2021

ABSTRACTCurrent SARS-CoV-2 detection platforms lack the ability to differentiate among variants of concern (VOCs) in an efficient manner. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has the potential to transform diagnostics due to its programmability. However, many of the CRISPR-based detection methods are reliant on either a multi-step process involving amplification or elaborate guide RNA designs. A complete one-pot detection reaction using alternative Cas effector endonucleases has been proposed to overcome these challenges. Yet, current approaches usingAlicyclobacillus acidiphilusCas12b (AapCas12b) are limited by its thermal instability at optimum reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction temperatures. Herein, we demonstrate that a novel Cas12b fromBrevibacillussp. SYP-B805 (referred to as BrCas12b) has robust trans-cleavage activity at ideal RT-LAMP conditions. A competitive profiling study of BrCas12b against Cas12b homologs from other bacteria genera underscores the potential of BrCas12b in the development of new diagnostics. As a proof-of-concept, we incorporated BrCas12b into an RT-LAMP-mediated one-pot reaction system, coined CRISPR-SPADE (CRISPR Single Pot Assay for Detecting Emerging VOCs) to enable rapid, differential detection of SARS-CoV-2 VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) in 205 clinical samples. Notably, a BrCas12b detection signal was observed within 1-3 minutes of amplification, achieving an overall 98.1% specificity, 91.2% accuracy, and 88.1% sensitivity within 30 minutes. Significantly, for samples with high viral load (Ctvalue ≤ 30), 100% accuracy and sensitivity were attained. To facilitate dissemination and global implementation of the assay, we combined the lyophilized one-pot reagents with a portable multiplexing device capable of interpreting fluorescence signals at a fraction of the cost of a qPCR system. With relaxed design requirements, one-pot detection, and simple instrumentation, this assay has the capability to advance future diagnostics.
Effects of a multimedia campaign on HIV self-testing and PrEP outcomes among young people in South Africa: A mixed-methods impact evaluation of ‘MTV Shuga Down South’
Authors: Birdthistle Isolde , Mulwa Sarah , Sarrassat Sophie , Baker Venetia , Khanyile David , O’Donnell Dominique , Cawood Cherie , Cousens Simon 
Published: October 2021

ABSTRACTIntroductionInnovative HIV technologies can help to reduce HIV incidence, yet uptake of such tools is relatively low among young people. To create awareness and demand among adolescents and young adults, a new campaign of the pan-African MTV Shuga series (“Down South 2”; DS2), featured storylines and messages about HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) through television, radio and accompanying multimedia activities in 2019-2020.MethodsWe conducted a mixed-methods evaluation of the new MTV Shuga series among 15-24 year-olds in Eastern Cape, South Africa, in 2020. A web-based survey, promoted via social media platforms of schools, universities, and communities, assessed exposure to MTV Shuga and knowledge of HIV status; secondary outcomes included awareness and uptake of HIVST and PrEP. An embedded qualitative evaluation explored mechanisms of MTV Shuga’s impact through in-depth individual and group interviews.ResultsAmong 3,431 online survey participants, 43% had engaged with MTV Shuga and 24% with DS2 specifically. Knowledge of HIV status was higher among those exposed to DS2 (58%) versus those who were not (35%; adjusted OR=2.06 [95% CI:1.64-2.58]). Exposure was also associated with increased awareness of HIVST (60% vs 28%; aOR=1.99[1.61-2.47]) and use of HIVST (29% vs 10%; aOR=2.49[1.95-3.19]). One-third of respondents were aware of PrEP, with higher proportions among those exposed versus non-exposed to DS2 (52% vs 27%; aOR=1.90[1.53-2.35]). Qualitative insights identified mechanisms by which DS2 increased awareness, confidence and motivation to use HIVST and PrEP, but had less influence on service access.ConclusionsWe found evidence consistent with a positive causal impact of the MTV Shuga DS2 campaign on HIV prevention outcomes among young people in a high-prevalence setting. As diverse testing and PrEP technologies become accessible, an immersive edutainment campaign can help to expand HIV prevention choices and close age and gender gaps in HIV testing and prevention goals.
Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution
Authors: Castro Inês Gomes , Shortill Shawn P. , Dziurdzik Samantha K. , Cadou Angela , Ganesan Suriakarthiga , Fenech Emma Joanne , Meyer Hadar , Fadel Amir , David Yotam , Davey Michael , Mattes Carsten , Valenti Rosario , Ernst Robert , Zaremberg Vanina , Levine Tim P. , Stefan Christopher J. , Conibear Elizabeth , Schuldiner Maya 
Published: October 2021

AbstractActively maintained close appositions, or contact sites, between organelle membranes, enable the efficient transfer of biomolecules between the various cellular compartments. Several such sites have been described together with their tethering machinery. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize the proteome of contact sites and support the discovery of new tethers and functional molecules, we established a high throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, two of which have never been studied before, on the background of 1165 strains expressing a mCherry-tagged yeast protein that have a cellular punctate distribution (a hallmark of contact sites). By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified one set of hits as previously unrecognized homologs to Vps13 and Atg2. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell.
Mapping Molecular Gene Signatures Among Respiratory Viruses Based on Large-Scale and Genome-wide Transcriptomics Analysis
Authors: Smith Thomas , Rohaim Mohammed A. , Munir Muhammad 
Published: October 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging RNA virus causing COVID-19 disease across the globe. SARS-CoV-2 infected patients exhibit acute respiratory distress syndrome which can be compounded by endemic respiratory viruses and thus highlighting the need to understand the genetic bases of clinical outcome under multiple respiratory infections. In this study, 42 individual datasets and a multi-parametric based selected list of over 12,000 genes against five medically important respiratory viruses (SARS-CoV-2, SARS-CoV-1, influenza A, respiratory syncytial virus (RSV) and rhinovirus were collected and analysed in an attempt to understand differentially regulated gene patterns and to cast genetic markers of individual and multiple co-infections. While a certain cohort of virus-specific genes were regulated (negatively and positively), notably results revealed a greatest correlation among gene regulation by SARS-CoV-2 and RSV. Furthermore, out of analysed genes, the MAP2K5 and NFKBIL1 were specifically and highly upregulated in SARS-CoV-2 infection in vivo or in vitro. In contrast, several genes including GPBAR1 and SC5DL were specifically downregulated in SARS-CoV-2 datasets. Additionally, we catalogued a set of genes that were conserved or differentially regulated across all the respiratory viruses. These finding provide foundational and genome-wide data to gauge the markers of respiratory viral infections individually and under co-infection.
The genetic architecture of language functional connectivity
Authors: Mekki Yasmina , Guillemot Vincent , Lemaitre Hervé , Carrion-Castillo Amaia , Forkel Stephanie , Frouin Vincent , Philippe Cathy 
Published: October 2021

AbstractLanguage is a unique trait of the human species, of which the genetic architecture remains largely unknown. Through language disorders studies, many candidate genes were identified. However, such complex and multifactorial trait is unlikely to be driven by only few genes and case-control studies, suffering from a lack of power, struggle to uncover significant variants. In parallel, neuroimaging has significantly contributed to the understanding of structural and functional aspects of language in the human brain and the recent availability of large scale cohorts like UK Biobank have made possible to study language via image-derived endophenotypes in the general population. Because of its strong relationship with task-based fMRI activations and its easiness of acquisition, resting-state functional MRI have been more popularised, making it a good surrogate of functional neuronal processes. Taking advantage of such a synergistic system by aggregating effects across spatially distributed traits, we performed a multivariate genome-wide association study (mvGWAS) between genetic variations and resting-state functional connectivity (FC) of classical brain language areas in the inferior frontal (pars opercularis, triangularis and orbitalis), temporal and inferior parietal lobes (angular and supramarginal gyri), in 32,186 participants from UK Biobank. Twenty genomic loci were found associated with language FCs, out of which three were replicated in an independent replication sample. A locus in 3p11.1, regulatingEPHA3gene expression, is found associated with FCs of the semantic component of the language network, while a locus in 15q14, regulatingTHBS1gene expression is found associated with FCs of the perceptualmotor language processing, bringing novel insights into the neurobiology of language.
The protein-binding pocket of Botulinum neurotoxin B accommodates a preassembled synaptotagmin / ganglioside complex
Authors: Ramirez-Franco Jorge , Azzaz Fodil , Sangiardi Marion , Ferracci Géraldine , Youssouf Fahamoe , Popoff Michel R. , Seagar Michael , Lévêque Christian , Fantini Jacques , Far Oussama EL 
Published: October 2021

AbstractBotulinum neurotoxin serotype B (BoNT/B) uses two separate protein and polysialoglycolipid-binding pockets to interact with synaptotagmin 1/2 and gangliosides. However, an integrated model of BoNT/B bound to its neuronal receptors in a native membrane topology is still lacking. Using a panel of in silico and experimental approaches, we present here a new model for BoNT/B binding to neuronal membranes, in which the toxin binds to a preassembled synaptotagmin-ganglioside GT1b complex and a free ganglioside. This interaction allows a lipid-binding loop of BoNT/B to engage in a series of concomitant interactions with the glycone part of GT1b and the transmembrane domain of synaptotagmin. Furthermore, our data provide molecular support for the decrease in BoNT/B sensitivity in Felidae that harbor the natural variant synaptotagmin2-N59Q. These results reveal multiple interactions of BoNT/B with gangliosides and support a novel paradigm in which a toxin recognizes a protein/ganglioside complex.TeaserA new molecular mechanism for botulinum neurotoxin type B binding
M1 dynamics share similar inputs for initiating and correcting movement
Authors: Malonis Peter J. , Hatsopoulos Nicholas G. , MacLean Jason N. , Kaufman Matthew T. 
Published: October 2021

AbstractMotor cortex is integral to generating voluntary movement commands. However, as a dynamical system, it is unclear how motor cortical movement commands are informed by either new or sensory-driven corrective instructions. Here, we examine population activity in the primary motor cortex of macaques during a continuous, sequential arm movement task in which the movement instruction is updated several times over the course of a trial. We use Latent Factor Analysis via Dynamical Systems (LFADS) to decompose population activity into a portion explainable via dynamics, and a stream of inferred inputs required to instruct that dynamical system. The time series of inferred inputs had several surprising properties. First, input timing was more strongly locked to target appearance than to movement onset, suggesting that variable reaction times may be a function of how inputs interact with ongoing dynamics rather than variability in instruction timing. Second, inferred inputs were tuned nearly identically for both initial and corrective movements, suggesting a commonality in the structure of inputs across visually-instructed and corrective movements that was previously obscured by the complexity of the dynamical system that is M1.
Increase in nutrient availability promotes success of invasive plants through increasing growth and decreasing anti-herbivory defenses
Authors: Shan Liping , Oduor Ayub M.O. , Huang Wei , Liu Yanjie 
Published: October 2021

SummaryInvasive plant species often exhibit greater growth and lower anti-herbivory defense than native plant species. However, it remains unclear how nutrient enrichment of invaded habitats may interact with competition from resident native plants to affect growth and defense of invasive plants.In a greenhouse experiment, we grew five congeneric pairs of invasive and native plant species under two levels of nutrient availability (low vs. high) that were fully crossed with simulated herbivory (clipping vs. no-clipping) and competition (alone vs. competition).Invasive plants produced more gibberellic acid, and grew larger than native species. Nutrient enrichment caused a greater increase in total biomass of invasive plants than of native plants, especially in the absence of competition or without simulated herbivory treatment. Nutrient enrichment decreased leaf flavonoid contents of invasive plants under both simulated herbivory conditions, but increased flavonoid of native plants under simulated herbivory condition. Nutrient enrichment only decreased tannins production of invasive species under competition. For native species, it enhanced their tannins production under competition, but decreased the chemicals when growing alone.The results indicate that the higher biomass production and lower flavonoids production in response to nutrient addition may lead to competitive advantage of invasive species than native species.
Linking photoacclimation responses and microbiome shifts between depth-segregated sibling species of reef corals
Authors: Prada Carlos , López-Londoño Tomás , Pollock F. Joseph , Roitman Sofia , Ritchie Kim B. , Levitan Don R. , Knowlton Nancy , Woodley Cheryl , Iglesias-Prieto Roberto , Medina Mónica 
Published: October 2021

ABSTRACTMetazoans host complex communities of microorganisms that include dinoflagellates, fungi, bacteria, archaea, and viruses. Interactions among members of these complex assemblages allow hosts to adjust their physiology and metabolism to cope with environmental variation and occupy different habitats. Here, using reciprocal transplantation across depths, we studied adaptive divergence in the Caribbean corals Orbicella annularis and O. franksi. When transplanted from deep to shallow, O. franksi experienced fast photoacclimation, low mortality, and maintained a consistent bacterial community. In contrast, O. annularis experienced higher mortality, and limited photoacclimation when transplanted from shallow to deep. The photophysiological collapse of O. annularis in the deep environment was associated with an increased microbiome variability and reduction of some bacterial taxa. Differences in the symbiotic algal community were more pronounced between coral species than between depths. Our study suggests that these sibling species are adapted to distinctive light environments partially driven by the algae photoacclimation capacity and the microbiome robustness, highlighting the importance of niche specialization in symbiotic corals for the maintenance of species diversity. Our findings have implications for the management of these threatened Caribbean corals and the effectiveness of coral reef restoration efforts.
Differential nuclear import sets the timing of protein access to the embryonic genome
Authors: Nguyen Thao , Costa Eli , Deibert Tim , Reyes Jose , Keber Felix , Stadlmeier Michael , Gupta Meera , Kumar Chirag K. , Amodeo Amanda , Gatlin Jesse C. , Wühr Martin 
Published: October 2021

SummaryThe development of a fertilized egg to an embryo requires the proper temporal control of gene expression1-6. During cell differentiation, timing is often controlled via cascades of transcription factors (TFs)7,8. However, in early development, transcription is often inactive, and many TF levels are constant, suggesting that unknown mechanisms govern the observed rapid and ordered onset of gene expression9. Here, we find that in early embryonic development, access of maternally deposited nuclear proteins to the genome is temporally ordered via importin affinities, thereby timing the expression of downstream targets. We quantify changes in the nuclear proteome during early development and find that nuclear proteins, such as TFs and RNA polymerases, enter nuclei sequentially. Moreover, we find that the timing of the access of nuclear proteins to the genome corresponds to the timing of downstream gene activation. We show that the affinity of proteins to importin is a major determinant in the timing of protein entry into embryonic nuclei. Thus, we propose a mechanism by which embryos encode the timing of gene expression in early development via biochemical affinities. This process could be critical for embryos to organize themselves before deploying the regulatory cascades that control cell identities.Graphical abstract
Pathogen-derived mechanical cues regulate the spatio-temporal implementation of plant defense
Authors: Léger Ophélie , Garcia Frédérick , Khafif Mehdi , Leblanc-Fournier Nathalie , Duclos Aroune , Tournat Vincent , Badel Eric , Didelon Marie , Le Ru Aurélie , Raffaele Sylvain , Barbacci Adelin 
Published: October 2021

AbstractHow immune responses are activated and regulated is a central question in immunology. In addition to molecular signaling, recent work has shown that physical forces regulate the immune response of vertebrates by modifying transmembrane protein conformation and cell contact. Mechanical stress and strain produced by forces constitute physical cues perceived by cells instructing gene expression. Whether mechanical cues generated by pathogens during host colonization can trigger adaptive responses in plant cells remains elusive. We found that local and progressive variations of plant cell wall tension caused by fungal pathogen attacks are transmitted to neighboring healthy tissue around the infection site and trigger immunity in distal cells. This ‘thigmoimmunity’ process requires the reorganization of cortical microtubules and contributes strongly to Arabidopsis disease resistance.One-Sentence SummaryActivation of plants immunity depends on fluctuations of mechanical tension caused by a fungal pathogen.