bluuebunny/crossref_metadata_2025_split huggingface dataset:
BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus
Authors: Moyon Quentin , Sterlin Delphine , Miyara Makoto , Anna François , Mathian Alexis , Lhote Raphael , Ghillani-Dalbin Pascale , Breillat Paul , Mudumba Sasi , de Alba Sophia , Cohen-Aubart Fleur , Haroche Julien , Pha Micheline , Du Boutin Thi Huong , Chaieb Hedi , Pedro Flores , Charneau Pierre , Gorochov Guy , Amoura Zahir 
Published: July 2021

ABSTRACTObjectivesOur aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination.MethodsIn this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose.ResultsBNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naïve B cell frequencies (β=2; p=0.018, β=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.ConclusionMMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.KEY MESSAGESWhat is already known about this subject?BNT162b2 efficacy and safety has been described in studies mixing different RMDsWhat does this study add?No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients.Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody responseAlbeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders.How might this impact on clinical practice or future developments?These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.
“What do you mean I can’t have a doctor? This is Canada!” – A Qualitative Study of the Myriad Consequences for Unattached Patients Awaiting Primary Care Attachment
Authors: Marshall Emily Gard , Wuite Sara , Lawson Beverley , Andrew Melissa K. , Edwards Lynn , MacKenzie Adrian , Woodrow Ana Correa , Peddle Sarah 
Published: July 2021

AbstractBackgroundPatient access to primary healthcare (PHC) is the foundation of a strong healthcare system and healthy populations. Attachment to a regular PHC provider, a key to healthcare access, has seen a decline in some jurisdictions. This study explored the consequences of unattachment from a patient perspective, an under-studied phenomenon to date.MethodsA realist-informed qualitative study was conducted with unattached patients in Nova Scotia, Canada. Semi-structured interviews with nine participants were conducted and transcribed for analysis. The framework method was used to carry out analysis, which was guided by Donabedian’s model of assessing healthcare access and quality.ResultsFive key findings were noted in this study: 1) Participants experienced a range of consequences from not having a regular PHC provider. Participants used creative strategies to 2) attempt to gain attachment to a regular PHC provider, and, to 3) address their health needs in the absence of a regular PHC provider. 4) Participants experienced negative feelings about themselves and the healthcare system, and 5) stress related to the consequences and added work of being unattached and lost care.ConclusionsUnattached patients experienced a burden of care related to lost care and managing their own health and related information, due to the download of medical record management and system navigation to them. These findings may underestimate the consequences for further at-risk populations who would not have been included in our recruitment. This may result in poorer health outcomes, which could be mitigated by interventions at the structural level, such as enhanced centralized waitlists to promote attachment. Such waitlists may benefit from a triage approach to appropriately attach patients based on need.
The Impact of Sampling Type, Frequency and Scale of Collection System on SARS-CoV-2 Quantification Fidelity
Authors: George Andrea D. , Kaya Devrim , Layton Blythe A. , Bailey Kestrel , Kelly Christine , Williamson Kenneth J. , Radniecki Tyler S. 
Published: July 2021

AbstractWith the rapid onset of the COVID-19 pandemic, wastewater-based epidemiology (WBE) sampling methodologies for SARS-CoV-2 were often implemented quickly and may not have taken the unique drainage catchment characteristics into account. One question of debate is the relevance of grab versus composite samples when surveying for SARS-CoV-2 at various catchment scales. This study assessed the impact of grab versus composite sampling on the detection and quantification of SARS-CoV-2 in catchment basins with flow rates ranging from high-flow (wastewater treatment plant influent), to medium-flow (neighborhood-scale micro-sewershed), to low-flow (city block-scale micro-sewershed) and down to ultra-low flow (building scale). At the high-flow site, grab samples were reasonably comparable to 24-h composite samples with the same non-detect rate (0%) and SARS-CoV-2 concentrations that differed by 32% on the Log10 scale. However, as the flow rates decreased, the percentage of false-negative grab samples increased up to 44% and the SARS-CoV-2 concentrations of grab samples varied by up to 1-2 orders of magnitude compared to their respective composite sample concentrations. At the ultra-low-flow site, increased sampling frequencies down to every 5 min led to composite samples with higher fidelity to the SARS-CoV-2 load. Thus, composite sampling is superior to grab sampling, especially as flow decreases.SynopsisThe need for composite sampling to generate reliable SARS-CoV-2 wastewater based epidemiology results increases as the collection basin scale decreases.Table of Content Art
Twins in Guinea-Bissau have a ‘thin-fat’ body composition compared to singletons
Authors: Wagh Rucha , Bjerregaard-Andersen Morten , Bandyopadhyay Souvik , Yajnik Pranav , Prasad Rashmi B , Otiv Suhas , Byberg Stine , Hennild Ditte Egegaard , Gomes Gabriel Marciano , Christensen Kaare , Sodemann Morten , Jensen Dorte Møller , Yajnik Chittaranjan 
Published: July 2021

ABSTRACT‘Thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example ofin uterogrowth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data was available on 7–34 year-old twins (n=209, 97 males) and singletons (n=182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birth weight (2420 vs 3100 g, p<0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p=0.055), weight (WAZ -0.73, p=0.024) and BMI (BAZ -0.22, p=0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p=0.001). Twins also had higher fasting (+0.38 SD, p<0.001) and 2-hr OGTT glucose concentrations (+0.29 SD, p<0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socioeconomic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
The potential for mobile demersal fishing to reduce carbon storage and sequestration in seabed sediments
Authors: Epstein Graham , Hawkins Julie P. , Norris Catrin R. , Roberts Callum M. 
Published: July 2021

AbstractSubtidal marine sediments are one of the planet’s primary carbon stores and strongly influence the oceanic sink for atmospheric CO2. By far the most pervasive human activity occurring on the seabed is bottom trawling and dredging for fish and shellfish. A global first-order estimate suggested mobile demersal fishing activities may cause 160-400 Mt of organic carbon (OC) to be remineralised annually from seabed sediment carbon stores. There are, however, many uncertainties in this calculation. Here, we discuss the potential drivers of change in seabed OC stores due to mobile demersal fishing activities and conduct a systematic review, synthesising studies where this interaction has been directly investigated. Mobile demersal fishing would be expected to reduce OC in seabed stores, albeit with site-specific variability. Reductions would occur due to lower production of flora and fauna, the loss of fine flocculent material, increased sediment resuspension, mixing and transport, and increased oxygen exposure. This would be offset to some extent by reduced faunal bioturbation and respiration, increased off-shelf transport and increases in primary production from the resuspension of nutrients. Studies which directly investigated the impact of demersal fishing on OC stocks had mixed results. A finding of no significant effect was reported in 51% of 59 experimental contrasts; 41% reported lower OC due to fishing activities, with 8% reporting higher OC. In relation to remineralisation rates within the seabed, 14 experimental contrasts reported that demersal fishing activities decreased remineralisation, with four reporting higher remineralisation rates. The direction of effects was related to sediment type, impact duration, study design and local hydrography. More evidence is urgently needed to accurately quantify the impact of anthropogenic physical disturbance on seabed carbon in different environmental settings, and incorporate full evidence-based carbon considerations into global seabed management.
MPA_Pathway_Tool: User-friendly, automatic assignment of microbial community data on metabolic pathways
Authors: Walke Daniel , Schallert Kay , Ramesh Prasanna , Benndorf Dirk , Lange Emanuel , Reichl Udo , Heyer Robert 
Published: July 2021

AbstractMotivationTaxonomic and functional characterization of microbial communities from diverse environments such as the human gut or biogas plants by multi-omics methods plays an ever more important role. Researchers assign all identified genes, transcripts, or proteins to biological pathways to better understand the function of single species and microbial communities. However, due to the versatility of microbial metabolism and a still increasing number of new biological pathways, linkage to standard pathway maps such as the KEGG (Kyoto Encyclopedia of Genes and Genomes) central carbon metabolism is often problematic.ResultsWe successfully implemented and validated a new user-friendly, stand-alone web application, the MPA_Pathway_Tool. It consists of two parts, called ‘Pathway-Creator’ and ‘Pathway-Calculator’. The ‘Pathway-Creator’ enables an easy setup of user-defined pathways with specific taxonomic constraints. The ‘Pathway-Calculator’ automatically maps microbial community data from multiple measurements on selected pathways and visualizes the results.Availability and ImplementationThe MPA_Pathway_Tool is implemented in Java and ReactJS. It is freely available onhttp://mpa-pathwaymapper.ovgu.de/. Further documentation and the complete source code are available on GitHub (https://github.com/danielwalke/MPA_Pathway_Tool).Contactdaniel.walke@ovgu.de, mailto:heyer@mpi-magdeburg.mpg.deheyer@mpi-magdeburg.mpg.deSupplementary InformationAdditional files and images are available atMDPIonline.Highlightsuser-friendly generation of pathways, re-using of existent metabolic pathways, automated mapping of data
Identifying Protein Complexes in Protein-protein Interaction Data using Graph Convolution Network
Authors: Zaki Nazar , Singh Harsh 
Published: July 2021

AbstractProtein complexes are groups of two or more polypeptide chains that join together to build noncovalent networks of protein interactions. A number of means of computing the ways in which protein complexes and their members can be identified from these interaction networks have been created. While most of the existing methods identify protein complexes from the protein-protein interaction networks (PPIs) at a fairly decent level, the applicability of advanced graph network methods has not yet been adequately investigated. In this paper, we proposed various graph convolutional networks (GCNs) methods to improve the detection of the protein functional complexes. We first formulated the protein complex detection problem as a node classification problem. Second, the Neural Overlapping Community Detection (NOCD) model was applied to cluster the nodes (proteins) using a complex affiliation matrix. A representation learning approach, which combines the multi-class GCN feature extractor (to obtain the features of the nodes) and the mean shift clustering algorithm (to perform clustering), is also presented. We have also improved the efficiency of the multi-class GCN network to reduce space and time complexities by converting the dense-dense matrix operations into dense-spares or sparse-sparse matrix operations. This proposed solution significantly improves the scalability of the existing GCN network. Finally, we apply clustering aggregation to find the best protein complexes. A grid search was performed on various detected complexes obtained by applying three well-known protein detection methods namely ClusterONE, CMC, and PEWCC with the help of the Meta-Clustering Algorithm (MCLA) and Hybrid Bipartite Graph Formulation (HBGF) algorithm. The proposed GCN-based methods were tested on various publicly available datasets and provided significantly better performance than the previous state-of-the-art methods. The code and data used in this study are available fromhttps://github.com/Analystharsh/GCN_complex_detection
Gene co-expression reveals the modularity and integration of C4and CAM inPortulaca
Authors: Gilman Ian S. , Moreno-Villena Jose J. , Lewis Zachary R. , Goolsby Eric W. , Edwards Erika J. 
Published: July 2021

AbstractC4photosynthesis and Crassulacean acid metabolism (CAM) have been considered as largely independent adaptations in spite of sharing key biochemical modules.Portulacais a geographically widespread clade of over 100 annual and perennial angiosperm species that primarily use C4, but facultatively exhibit CAM when drought stressed, a photosynthetic system known as C4+CAM. It has been hypothesized that C4+CAM is rare because of pleiotropic constraints, but these have not been deeply explored. We generated a chromosome-level genome assembly ofP. amilisand sampled mRNA fromP. amilisandP. oleraceaduring CAM induction. Gene co-expression network analyses identified C4and CAM gene modules shared and unique to bothPortulacaspecies. A conserved CAM module linked phosphoenolpyruvate carboxylase (PEPC) to starch turnover during the day-night transition and was enriched in circadian clock regulatory motifs in theP. amilisgenome. Preservation of this co-expression module regardless of water status suggests thatPortulacaconstitutively operate a weak CAM cycle that is transcriptionally and post-transcriptionally upregulated during drought. C4and CAM mostly used mutually exclusive genes for primary carbon fixation and it is likely that nocturnal CAM malate stores are shuttled into diurnal C4decarboxylation pathways, but we find evidence that metabolite cycling may occur at low levels. C4likely evolved inPortulacathrough co-option of redundant genes and integration of the diurnal portion of CAM. Thus, the ancestral CAM system did not strongly constrain C4evolution because photosynthetic gene networks are not co-regulated for both daytime and nighttime functions.
metaboprep: an R package for pre-analysis data description and processing
Authors: Hughes David A , Taylor Kurt , McBride Nancy , Lee Matthew A , Mason Dan , Lawlor Deborah A , Timpson Nicholas J , Corbin Laura J 
Published: July 2021

AbstractMotivationMetabolomics is an increasingly common part of health research and there is need for pre-analytical data processing. Researchers typically need to characterize the data and to exclude errors within the context of the intended analysis. While some pre-processing steps are common, there is currently a lack of standardization and reporting transparency for these procedures.ResultsHere we introduce metaboprep, a standardized data processing workflow to extract and characterize high quality metabolomics data sets. The package extracts data from pre-formed worksheets, provides summary statistics and enables the user to select samples and metabolites for their analysis based on a set of quality metrics. A report summarizing quality metrics and the influence of available batch variables on the data is generated for the purpose of open disclosure. Where possible, we provide users flexibility in defining their own selection thresholds.Availability and implementationmetaboprep is an open-source R package available at https://github.com/MRCIEU/metaboprepContactd.a.hughes@bristol.ac.uk or laura.corbin@bristol.ac.uk
A single cell transcriptome atlas reveals the heterogeneity of the healthy human cornea and identifies novel markers of the corneal limbus and stroma
Authors: Català Pere , Groen Nathalie , Dehnen Jasmin A. , Soares Eduardo , van Velthoven Arianne J.H. , Nuijts Rudy M.M.A. , Dickman Mor M. , LaPointe Vanessa L.S. 
Published: July 2021

ABSTRACTThe cornea is the clear window that lets light into the eye. It is composed of five layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium. The maintenance of its structure and transparency are determined by the functions of the different cell types populating each layer. Attempts to regenerate corneal tissue and understand disease conditions requires knowledge of how cell profiles vary across this heterogeneous tissue. We performed a single cell transcriptomic profiling of 19,472 cells isolated from eight healthy donor corneas. Our analysis delineates the heterogeneity of the corneal layers by identifying cell populations and revealing cell states that contribute in preserving corneal homeostasis. We identified that the expression of CAV1, CXCL14, HOMER3 and CPVL were exclusive to the corneal epithelial limbal stem cell niche, CKS2, STMN1 and UBE2C were exclusively expressed in highly proliferative transit amplifying cells, and NNMT was exclusively expressed by stromal keratocytes. Overall, this research provides a basis to improve current primary cell expansion protocols, for future profiling of corneal disease states, to help guide pluripotent stem cells into different corneal lineages, and to understand how engineered substrates affect corneal cells to improve regenerative therapies.
Establishment of 3D chromatin structure after fertilization and the metabolic switch at the morula-to-blastocyst transition require CTCF
Authors: Andreu Maria Jose , Alvarez-Franco Alba , Portela Marta , Gimenez-Llorente Daniel , Cuadrado Ana , Badia-Careaga Claudio , Tiana Maria , Losada Ana , Manzanares Miguel 
Published: July 2021

AbstractThe eukaryotic genome is tightly packed inside the nucleus, where it is organized in 3D at different scales. This structure is driven and maintained by different chromatin states and by architectural factors that bind DNA, such as the multi-zinc finger protein CTCF. Zygotic genome structure is established de novo after fertilization, but the impact of such structure on genome function during the first stages of mammalian development is still unclear. Here, we show that deletion of the Ctcf gene in mouse embryos impairs the correct establishment of chromatin structure, but initial lineage decisions take place and embryos are viable until the late blastocyst stage. Furthermore, we observe that maternal CTCF is not necessary for development. Transcriptomic analyses of mutant embryos show that the changes in metabolic and protein homeostasis programs that occur during the progression from the morula to the blastocyst depend on CTCF. Yet, these changes in gene expression do not correlate with disruption of chromatin structure, but mainly with proximal binding of CTCF to the promoter region of genes downregulated in mutants. Our results show that CTCF regulates both 3D genome organization and transcription during mouse preimplantation development, but mostly as independent processes.
Directional Cell Migration Guided by a Strain Gradient
Authors: Yang Feiyu , Chen Pengcheng , Xie Tianfa , Shao Yue , Li Bo , Sun Yubing 
Published: July 2021

ABSTRACTStrain gradients, a graded change in the percentage of the deformation across a continuous field by applying forces, widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, and density and topography of extracellular matrices have been well-established. However, it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, we develop a programmable uniaxial cell stretch device coupled with geometrical constraints to create controllable strain gradients on cells. We demonstrate that single rat embryonic fibroblasts respond to very small strain gradients. In a gradient level of ∼4% per mm, over 60% of the REFs prefer to migrate towards the lower strain side in both the static and the 0.1 Hz cyclic stretch conditions. We confirm that such responses to strain gradient are distinct from durotaxis or haptotaxis. Moreover, we discover that the directional migration of the cells is initiated by increased focal adhesion contact areas and higher rate of protrusion formation on the lower strain side of the cell. We further establish a 2D extended motor-clutch model to explain the molecular mechanism. Through our model, we find that the strain-introduced traction force determines integrin fibronectin pairs’ catch-release dynamics, which drives such directional migration. Together, our results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights into development and tissue repairs.