bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of clinical characteristics and laboratory findings of COVID-19 in children-Systematic review and Meta-analysis
Authors: Kharoud Harmeet Kaur , Asim Rizwana , Siegel Lianne , Chahal Lovepreet , Singh Gagan Deep 
Published: September 2020

ABSTRACTOBJECTIVETo conduct a systematic review and meta-analysis to assess the prevalence of various clinical symptoms and laboratory findings of COVID-19 in children.METHODSPubMed, MEDLINE, and SCOPUS databases were searched to include studies conducted between January 1, 2020, and July 15, 2020 which reported data about clinical characteristics and laboratory findings in laboratory-confirmed diagnosis of COVID-19 in pediatric patients. Random effects meta-analysis using generalized linear mixed models was used to estimate the pooled prevalence.RESULTSThe most prevalent symptom of COVID-19 in children was 46.17% (95%CI 39.18-53.33%), followed by cough (40.15%, 95%CI 34.56-46.02%). Less common symptoms were found to be dyspnea, vomiting, nasal congestion/rhinorrhea, diarrhea, sore throat/pharyngeal congestion, headache, and fatigue. The prevalence of asymptomatic children was 17.19% (95%CI 11.02-25.82%).The most prevalent laboratory findings in COVID-19 children were elevated Creatinine Kinase (26.86%, 95%CI 16.15-41.19%) and neutropenia (25.76%, 95%CI 13.96-42.58%). These were followed by elevated LDH, thrombocytosis, lymphocytosis, neutrophilia, elevated D Dimer, Elevated CRP, elevated ESR, leukocytosis, elevated AST and leukopenia. There was a low prevalence of elevated ALT and lymphopenia in children with COVID-19.CONCLUSIONS AND RELEVANCEThis study provides estimates of the pooled prevalence of various symptoms and laboratory findings of COVID-19 in the pediatric population.
Tailoring the assembly of collagen fibers in alginate microspheres
Authors: Lehnert Sarah , Sikorski Pawel 
Published: September 2020

AbstractThe application of microspheres instead of bulk hydrogels in cell-laden biomaterials offers multiple advantages such as a high surface-to-volume-ratio and, consequently, a better nutrition and oxygen transfer to and from cells. The preparation of inert alginate microspheres is facile, quick, and well-established and the fabrication of alginate-collagen microspheres has been previously reported. However, no detailed characterization of the collagen fibrillogenesis in the alginate matrix is available. We use second-harmonic imaging microscopy reflection microscopy and turbidity assay to study assembly of collagen in alginate microspheres. We show that the assembly of collagen fibers in a gelled alginate matrix is a complex process that can be aided by addition of small polar molecules, such as glycine and by a careful selection of the gelling buffer used to prepare alginate hydrogels.HighlightsIn situcharacterization of collagen fiber assembly in a gelled alginate matrix using collagen-specific second harmonic generated microscopyCollagen fibrillogenesis is positively influenced by the presence of small molecules in the solution prior microsphere preparationThe ratio and amount of calcium, sodium and chloride ions used for the alginate gelling has also a crucial impact on the development of a collagen fiber network
Exploring the Landscape of Ectodomain Shedding by Quantitative Protein Terminomics
Authors: Tsumagari Kazuya , Chang Chih-Hsiang , Ishihama Yasushi 
Published: September 2020

AbstractEctodomain shedding is a proteolytic process that regulates the levels and functions of membrane proteins. Dysregulated shedding is linked to severe diseases, including cancer and Alzheimer’s disease. However, the exact cleavage sites of shedding substrates remain largely unknown. Here, we explore the landscape of ectodomain shedding by generating large-scale, cell-type-specific maps of shedding cleavage sites. By means of N- and C-terminal peptide enrichment and quantitative mass spectrometry, we quantified protein termini in the culture media of 10 human cell lines and identified 411 cleavage sites on the ectodomain of 132 membrane proteins whose proteolytic terminal fragments are downregulated in the presence of a broad-spectrum metalloprotease inhibitor. A major fraction of the presented cleavage sites was identified in a cell-type-specific manner, and mapped onto receptors, cell adhesion molecules, and protein kinases and phosphatases. We confidently identified 86 cleavage sites as metalloprotease substrates by means of knowledge-based scoring.
Samplot: A Platform for Structural Variant Visual Validation and Automated Filtering
Authors: Belyeu Jonathan R. , Chowdhury Murad , Brown Joseph , Pedersen Brent S. , Cormier Michael J. , Quinlan Aaron R. , Layer Ryan M. 
Published: September 2020

AbstractVisual validation is an essential step to minimize false positive predictions resulting from structural variant (SV) detection. We present Samplot, a tool for quickly creating images that display the read depth and sequence alignments necessary to adjudicate purported SVs across multiple samples and sequencing technologies, including short, long, and phased reads. These simple images can be rapidly reviewed to curate large SV call sets. Samplot is easily applicable to many biological problems such as prioritization of potentially causal variants in disease studies, family-based analysis of inherited variation, orde novoSV review. Samplot also includes a trained machine learning package that dramatically decreases the number of false positives without human review. Samplot is available via the conda package manager or athttps://github.com/ryanlayer/samplot.ContactRyan Layer, Ph.D., Assistant Professor, University of Colorado Boulder,ryan.layer@colorado.edu.
Functionalized bead assay to measure 3-dimensional traction forces during T-cell activation
Authors: Aramesh Morteza , Mergenthal Simon , Issler Marcel , Plochberger Birgit , Weber Florian , Qin Xiao-Hua , Liska Robert , Duda Georg N. , Huppa Johannes B. , Ries Jonas , Schütz Gerhard J. , Klotzsch Enrico 
Published: September 2020

AbstractWhen T-cells probe their environment for antigens, the bond between the T-cell receptor (TCR) and the peptide-loaded major histocompatibility complex (MHC) is put under tension, thereby influencing the antigen discrimination process. Yet, the quantification of such forces in the context of T-cell signaling is technically challenging. Common approaches such as traction force microscopy (TFM) employ a global readout of the force fields, e.g. by measuring the displacements of hydrogel-embedded marker beads. Recent data, however, indicated that T-cells exert tensile forces locally via TCR-enriched microvilli while scanning the surface of antigen-presenting cells. Here, we developed a traction force microscopy platform, which allows for quantifying the pulls exerted via T-cell microvilli, in both tangential and normal directions, during T-cell activation. For this, we immobilized specific T-cell activating antibodies directly on the marker beads used to read out the hydrogel deformation. Microvilli targeted the functionalized beads, as confirmed by superresolution microscopy of the local actin organization. Moreover, we found that cellular components, such as actin, TCR and CD45 reorganize upon interaction with the beads, such that actin forms a vortex-like ring structure around the beads and TCR is enriched at the bead surface, whereas, CD45 is excluded from bead-microvilli contacts.Significance statementDuring the antigen recognition process, T-cells explore and probe their environment via microvilli, which exert local pushes and pulls at the surface of the antigen presenting cell. It is currently believed that these forces influence or even enable the antigen recognition process. Here, we describe the development of a platform, which allows us to quantify the magnitude and direction of traction forces exerted locally by T cell microvilli. Simultaneous Ca2+imaging was used to link the measured forces to the overall T cell activation status. Superresolution microscopy resolved the contact sites of bead-microvilli contact at the nanoscale: cells contacted beads via actin vortex-like structures, which excluded the phosphatase CD45 from the contacts.
NIAGADS Alzheimer’s GenomicsDB: A resource for exploring Alzheimer’s Disease genetic and genomic knowledge
Authors: Greenfest-Allen Emily , Valladares Otto , Kuksa Pavel P. , Gangadharan Prabhakaran , Lee Wan-Ping , Cifello Jeffrey , Katanic Zivadin , Kuzma Amanda B. , Wheeler Nicholas , Bush William S. , Leung Yuk Yee , Schellenberg Gerard , Stoeckert Christian J. , Wang Li-San 
Published: September 2020

AbstractINTRODUCTIONThe NIAGADS Alzheimer’s Genomics Database (GenomicsDB) is a public knowledgebase of Alzheimer’s disease (AD) genetic datasets and genomic annotations.METHODSIt uses a custom systems architecture to adopt and enforce rigorous standards that facilitate harmonization of AD-relevant GWAS summary statistics datasets with functional annotations, including a database of >230 million annotated variants from the AD Sequencing Project’s joint-calling efforts.RESULTSThe knowledgebase generates genome browser tracks and interactive compiled from harmonized datasets and annotations in the underlying database. These facilitate data sharing and discovery, by contextualizing AD-risk associations in a broader functional genomic context or summarizing them in the context of functionally annotated genes and variants.DISCUSSIONCreated to make AD-genetics knowledge more accessible to AD-researchers, the GenomicsDB shares annotated AD-relevant summary statistics datasets via a web interface designed to guide users unfamiliar with genetic data in not only exploring, but also interpreting this ever-growing volume of data.
Transcriptomic Analysis of Early Stages of Intestinal Regeneration inHolothuria glaberrima
Authors: Quispe-Parra David J. , Medina-Feliciano Joshua G. , Cruz-González Sebastián , Ortiz-Zuazaga Humberto , García-Arrarás José E. 
Published: September 2020

AbstractEchinoderms comprise a group of animals with impressive regenerative capabilities. They can replace complex internal organs following injury or autotomy. In holothurians or sea cucumbers, cellular processes of intestinal regeneration have been extensively studied. The molecular machinery behind this faculty, however, remains to be understood. Here we assembled and annotated a de novo transcriptome using RNA-seq data consisting of regenerating and non-regenerating intestinal tissues from the sea cucumberHolothuria glaberrima. Comparisons of differential expression were made using the mesentery as a reference against 24 hour and 3 days regenerating intestine, revealing a large number of differentially expressed transcripts. Gene ontology and pathway enrichment analysis showed evidence of increasing transcriptional activity. Further analysis of transcripts associated with transcription factors revealed diverse expression patterns with mechanisms involving developmental and cancer-related activity that could be related to the regenerative process. Our study demonstrates the broad and diversified gene expression profile during the early stages of the process using the mesentery as the focal point of intestinal regeneration. It also establishes the genes that are the most important candidates in the cellular processes that underlie regenerative responses.
Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington’s Like Disorder in Preclinical Model
Authors: Adhikari Aniruddha , Mondal Susmita , Das Monojit , Biswas Pritam , Pal Uttam , Darbar Soumendra , Bhattacharya Siddhartha Sankar , Pal Debasis , Saha-Dasgupta Tanusri , Das Anjan Kumar , Mallick Asim Kumar , Pal Samir Kumar 
Published: September 2020

ABSTRACTThe potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiologicalmilieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4NP) efficiently mimics glutathione peroxidase enzyme in the physiologicalmilieuand easily incorporates into the cellular multienzyme cascade for H2O2scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established thein vivotherapeutic efficacy of C-Mn3O4nanozyme in a preclinical animal model of Huntington’s disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date.SUMMARYAlthough, nano-enzymes have shown lots of promises in the management of several diseases, two major concerns limit their clinical translation. Apart from the inherent toxicity of the constituent materials (e.g., cerium, vanadium, gold, etc.), activities of contemporary nanozymes are often inhibited in physiologicalmilieu. Furthermore, most of them are incapable of incorporation into the cellular metabolic networks for functioning in tandem and parallel with natural enzymes, a major criteria for potential therapeutics.Here, we have shown that citrate-functionalized spherical Mn3O4nanoparticles can efficiently mimic glutathione peroxidase (GPX) enzyme without the limitations of contemporary nanozymes, and effectively manage neurodegenerative Huntington’s disease in preclinical animal model. The choice of the material in the nanozyme lies on the fact that Mn is an essential micronutrient for mammals, and the stabilizing ligand citrate helps the nanoparticles to cross the blood-brain-barrier to reach brain. We have shown that the nanozyme can easily be incorporated in cellular antioxidant enzyme cascade. The specificity and efficacy of the nanozyme in the cascade was significantly higher compared to other reported nanozymes. We have justified our experimental findings with a detailed computational study. Understanding the mode of operation and management of Huntington’s disease in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.
Visceral Leishmaniasis-HIV coinfection as a predictor of increased leishmania transmission at the village level in Bihar, India
Authors: Cloots Kristien , Marino Pia , Burza Sakib , Gill Naresh , Boelaert Marleen , Hasker Epco 
Published: September 2020

ABSTRACTBackgroundVisceral leishmaniasis (VL) is on the verge of being eliminated as a public health problem in the Indian subcontinent. Although Post-kala-azar dermal leishmaniasis (PKDL) is recognized as an important reservoir of transmission, we hypothesized that patients with VL co-infected with Human Immunodeficiency Virus (HIV) may also be important reservoirs of sustained leishmania transmission. We therefore investigated to what extent cases of PKDL or VL-HIV are associated with VL incidence at the village level in Bihar, India.MethodsVL, VL-HIV, and PKDL case data from six districts within the highly VL-endemic state of Bihar, India were collected through the Kala-Azar Management Information System for the years 2014 – 2019. Multivariate analysis was done using negative binomial regression controlling for year as a fixed effect and block (subdistrict) as a random effect.FindingsPresence of VL-HIV and PKDL cases were both associated with a more than twofold increase in VL incidence at village level, with Incidence Rate Ratios (IRR) of 2.16 (95% CI 1.81 – 2.58) and 2.37 (95% CI 2.01 – 2.81) for VL-HIV and PKDL cases respectively. A sensitivity analysis showed the strength of the association to be similar in each of the six included subdistricts.ConclusionsThese findings indicate the importance of VL-HIV patients as infectious reservoirs, and suggest that they represent a threat equivalent to PKDL patients towards the VL elimination initiative on the Indian subcontinent, therefore warranting a similar focus.CONTRIBUTION TO THE FIELDVisceral leishmaniasis (VL) – also called kala azar on the Indian subcontinent - is a parasitic disease which is fatal if not treated timely. Since the elimination initiative was launched in 2005 in the Indian subcontinent, the number of cases has come down drastically in this region. However, with the regional incidence of VL decreasing, understanding the role of potentially highly infectious subgroups in maintaining refractory Leishmania transmission is becoming increasingly important. Patients with Post-Kala-Azar Dermal Leishmaniasis (PKDL) are recognized as an important reservoir of transmission. We hypothesized that VL patients co-infected with Human Immunodeficiency Virus (HIV) may also be important reservoirs of sustained leishmania transmission. In this study, we found that the presence of VL-HIV and PKDL patients are both associated with a twofold increase incidence of VL at village level, suggesting they are equally important reservoirs for leishmania transmission. Our paper suggests that VL-HIV patients pose a threat equivalent to PKDL patients towards the VL elimination initiative and that therefore they should receive a similar focus.
The 4R Genome Duplication In Salmonine Fishes: Insights From Conserved Non-Coding Elements
Authors: Castillo Anibal H. 
Published: September 2020

ABSTRACTGene and genome duplications are essential processes in evolution. Salmonids are ideal animal model systems to study these processes, as they originated from a tetraploid ancestor. Conserved non-coding elements (CNEs) are of interest because of their highly conserved DNA consensus motifs spanning lineages as diverse and divergent as humans and fish. The main goal of this study is to test CNEs as a tool to study genome duplications and to revisit the “4R” hypothesis and phylogeny of Salmonine fishes (Salmonidae)Salmo salar,Salvelinus alpinusandOncorhynchus mykissthrough the study of copy number and nucleotide variation in six pairs of CNEs. Allele numbers for most CNE sequence pairs are consistent with the 4R hypothesis, as is the symmetric phylogenetic topology shown by some CNE pairs; the estimated date of CNE duplication is consistent with the only reported range of 25-100Mya. However, the phylogenetic relationships within Salmoninae remain unresolved.
Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models
Authors: Brunaugh Ashlee D. , Seo Hyojong , Warnken Zachary , Ding Li , Seo Sang Heui , Smyth Hugh D.C. 
Published: September 2020

ABSTRACTNiclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and may protect against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to CoV infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization
Reappraisal of Spinach-based RNA Visualization in Plants
Authors: Yu Zhiming , Mei Fengling , Yan Haiting , Chen Qiyuan , Yao Mengqin , Liu Shuyue , Wang Yue , Zhang Xian , Zhang Pengcheng , Jackson Stephen , Shi Nongnong , Liu Yule , Hong Yiguo 
Published: September 2020

ABSTRACTRNAs can be imaged in living cells using molecular beacons, RNA-binding labeled proteins and RNA aptamer-based approaches. However, Spinach RNA-mimicking GFP (RMG) has not been successfully used to monitor cellular RNAs in plants. In this study, we re-evaluated Spinach-based RNA visualization in different plants via transient, transgenic, and virus-based expression strategies. We found that like bacterial, yeast and human cellular tRNAs, plant tRNAs such as tRNALys(K) can protect and/or stabilize the spinach RNA aptamer interaction with the fluorophore DFHBI enabling detectable levels of green fluorescence to be emitted. The tRNALys-spinach-tRNALys(KSK), once delivered into “chloroplast-free” onion epidermal cells can emit strong green fluorescence in the presence of DFHBI. Transgenic or virus-based expression of monomer KSK, in either stably transformed or virus-infectedNicotinana benthamianaplants, failed to show RMG fluorescence. However, incorporating tandem repeats of KSK into recombinant viral RNAs, enabled qualitative and quantitative detection, both in vitro and ex vivo (ex planta), of KSK-specific green fluorescence, though RMG was less obvious in vivo (in planta). These findings demonstrate Spinach-based RNA visualization has the potential forex vivoandin vivomonitoring RNAs in plant cells.One sentence summarySpinach-based RMG technology was reevaluated to have potential for ex vivo and in vivo monitoring RNAs in plant cells.
Phosphorylated paxillin and FAK constitute subregions within focal adhesions
Authors: Bachmann Michael , Skripka Artiom , Wehrle-Haller Bernhard , Bastmeyer Martin 
Published: September 2020

AbstractIntegrin-mediated adhesions are convergence points of multiple signaling pathways. Their inner structure and their diverse functions can be studied with super-resolution microscopy. We used structured illumination microscopy (SIM) to analyze spatial organization of paxillin phosphorylation (pPax) within adhesions. We found that pPax and focal adhesion kinase (FAK) form spot-like, spatially defined clusters within adhesions in several cell lines. In contrast, other adhesion proteins showed no consistent organization in such clusters. Live-cell super-resolution imaging revealed that pPax-FAK clusters persist over time but modify distance to each other dynamically. Moreover, we show that the distance between separate clusters of pPax is mechanosensitive. Thus, in this work we introduce a new structural organization within focal adhesions and demonstrate its regulation and dynamics.
Histone modifications at the transcription start site of non-coding RNA revealed regulatory patterns of activation inCaenorhabditis elegansembryo
Authors: Bandeira Megan A. , Boeck Max E. 
Published: September 2020

AbstractHistone modifications play an essential role in regulating recruitment of RNA polymerase II and through this regulation of transcription itself. Which modifications are essential for regulating the transcription of non-coding RNA (ncRNA) species and how these patterns differ between the different types of ncRNA remains less studied compared to mRNA. We performed a principal component analysis (PCA) of histone modifications patterns surrounding the transcription start site (TSS) of ncRNA in an attempt to understand how histone modifications predict polymerase recruitment and transcription of ncRNA in earlyC. elegansdevelopment We found that our first PCA axis was a better predictor of polymerase recruitment and expression than any single histone modification for ncRNA and miRNA. This indicates an integrated analysis of many histone modifications is essential for predicting expression based on histone modifications and that each ncRNA species have unique regulation of RNA polymerase recruitment through histone modifications.