bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential of SARS-CoV-2 antigen-detection tests in the screening of asymptomatic persons
Authors: Wachinger Jonas , Olaru Ioana Diana , Horner Susanne , Schnitzler Paul , Heeg Klaus , Denkinger Claudia M. 
Published: June 2021

AbstractObjectivesTo assess the performance of antigen-based rapid diagnostic tests (Ag-RDTs) for SARS CoV-2 when implemented for large-scale universal screening of asymptomatic individuals.MethodsThis study presents data from a pragmatic implementation study for universal Ag-RDT-based screening at a tertiary care hospital in Germany where all incoming patients without symptoms suggestive of SARS-CoV-2 were screened with an Ag-RDT prior to admission since October 2020.ResultIn total, 49,542 RDTs were performed in 27,199 asymptomatic individuals over a duration of five months. Out of 222 positive results, 196 underwent in-house confirmatory testing with PCR, out of which 170 were confirmed positive, indicating a positive predictive value (PPV) of 86.7%. Negative Ag-RDTs were not routinely tested with PCR, but a total of 94 cases of false negative Ag-RDTs were detected due to PCR tests being performed within the following five days with a median CT-value of 33.ConclusionsThis study provides evidence that Ag-RDTs can have a high diagnostic yield for transmission relevant infections with limited false-positives when utilized at the point of care on asymptomatic patients and thus can be a suitable public-health test for universal screening.
BNT162b2 mRNA vaccinations in Israel: understanding the impact and improving the vaccination policies by redefining the immunized population
Authors: Ross Chana , Spector Oren , Tsadok Meytal Avgil , Weiss Yossi , Barnea Royi 
Published: June 2021

AbstractBy the end of February 2021, when 48% of the Israeli population was immune, the number of new positive COVID-19 cases significantly dropped across all ages. Understanding which parameters influenced this drop and how to minimize the number of hospitalizations and overall positive cases is urgently needed.In this study we conducted an observational analysis which included COVID-19 data with over 12,000,000 PCR tests from 250 cities in Israel. In addition, we performed a simulation of different vaccination campaigns to find the optimal policy.Our analysis revealed that cities with younger populations reached a decrease in new cases when a lower percentage of their residents were immunized, showing that median age is a crucial parameter effecting overall immunity, while other parameters appeared to be insignificant. This variance between cities is explained by recalculating the immunized population and multiplying each individual by a factor symbolizing the impact of their age on the spread on the virus. This factor is easily calculated from historical data of positive cases per age.The simulation proves that prioritizing different age groups or changing the rate of vaccinations drastically effects the overall hospitalizations and positive cases.One-Sentence Summaryunderstanding what influences reaching covid-19 overall immunity and how to maximize the effect of the vaccination campaign.
Pulsation changes link to impaired glymphatic function in a mouse model of vascular cognitive impairment
Authors: Li Mosi , Kitamura Akihiro , Beverley Joshua , Koudelka Juraj , Duncombe Jessica , Platt Bettina , Wiegand Ulrich K. , Carare Roxana O. , Kalaria Rajesh N. , Iliff Jeffrey J. , Horsburgh Karen 
Published: June 2021

AbstractLarge vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild- type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning and memory. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Since our findings show that BCAS may influence VCI by impaired glymphatic drainage and reduced vascular pulsation we propose that these additional targets need to be considered when treating VCI.
An Unsupervised Graph Embeddings Approach to Multiplex Immunofluorescence Image Exploration
Authors: Innocenti Christopher , Zhang Zhenning , Selvaraj Balaji , Gaffney Isabelle , Frangos Michalis , Cohen-Setton Jake , Dillon Laura A L , Surace Michael J , Pedrinaci Carlos , Hipp Jason , Baykaner Khan 
Published: June 2021

ABSTRACTUnderstanding the complex biology of the tumor microenvironment (TME) is necessary to understand the mechanisms of action of immuno-oncology therapies and to match the right therapies to the right patients. Multiplex immunofluorescence (mIF) is a useful technology that has tremendous potential to further our understanding of cancer patho-biology; however, tools that fully leverage the high dimensionality of this data are still in their infancy. We describe here a novel deep learning pipeline aimed to allow Graph-based Inspection of Tissues via Embeddings, GraphITE. GraphITE transforms mIF data into a graph representation, where unsupervised learning algorithms can be utilised to generate embeddings representing cellular ‘neighbourhoods’. The embeddings can be downprojected and explored for clustering analysis, and patterns can be mapped back to the image as well as interrogated for phenotypical, morphological, or structural distinctiveness. GraphITE supports the extraction of information not only on the phenotypes of individual cells or the relationships between specific cell types, but is able to characterize cell neighborhoods to look for more complex interactions, thereby allowing pathologists and data scientists to explore mIF data sets, uncovering patterns that are otherwise obscured by the high-dimensionality of the data. In this work, we showcase the current setup of the system, going from raw input data all the way to a user friendly exploration tool. Using this tool, we show how the data can be navigated in a way previously not possible.
Draft genome assembly data of Anoxybacillus sp. strain MB8 isolated from Tattapani hot springs, India
Authors: Vishnu Prasoodanan P K , Menon Shruti S. , Saxena Rituja , Waiker Prashant , Sharma Vineet K. 
Published: June 2021

AbstractDiscovery of novel thermophiles has shown promising applications in the field of biotechnology. Due to their thermal stability, they can survive the harsh processes in the industries, which make them important to be characterized and studied. Members of Anoxybacillus are alkaline tolerant thermophiles and have been extensively isolated from manure, dairy-processed plants, and geothermal hot springs. This article reports the assembled data of an aerobic bacterium Anoxybacillus sp. strain MB8, isolated from the Tattapani hot springs in Central India, where the 16S rRNA gene shares an identity of 97% (99% coverage) with Anoxybacillus kamchatkensis strain G10. The de novo assembly and annotation performed on the genome of Anoxybacillus sp. strain MB8 comprises of 2,898,780 bp (in 190 contigs) with a GC content of 41.8% and includes 2,976 protein-coding genes,1 rRNA operon, 73 tRNAs, 1 tm-RNA and 10 CRISPR arrays. The predicted protein-coding genes have been classified into 21 eggNOG categories. The KEGG Automated Annotation Server (KAAS) analysis indicated the presence of assimilatory sulfate reduction pathway, nitrate reducing pathway, and genes for glycoside hydrolases (GHs) and glycoside transferase (GTs). GHs and GTs hold widespread applications, in the baking and food industry for bread manufacturing, and in the paper, detergent and cosmetic industry. Hence, Anoxybacillus sp. strain MB8 holds the potential to be screened and characterized for such commercially relevant enzymes.Specifications TableValues of DataThe Anoxybacillus sp. strain MB8 genome assembly data provides insights into functional potential of thermophilic enzymes of this thermotolerant microbe.The presence of genes for Glycoside Hydrolase (GHs) like alpha-amylase, pullulanase, neopullulanase, alpha-glucosidase, beta-fructofuranosidase etc. and genes for Glycosyl Transferase (GTs) like sucrose synthase, maltodextrin phosphorylase, starch synthase, and glycogen phosphorylase were identified, which hold strong industrial values.The taxonomic annotation of Anoxybacillus sp. strain MB8 using different approaches indicates that the closest relatives were Anoxybacillus gonensis NZ CP012152T (96.86% ANI) and Anoxybacillus kamchatkensis G10 NZ CP025535 (96.83% ANI) obtained from. The strain MB8 most likely belongs to the same subspecies of Anoxybacillus gonensis NZ CP012152T.
A rat model of pregnancy in the male parabiont
Authors: Zhang Rongjia , Liu Yuhuan 
Published: June 2021

AbstractMale pregnancy is a unique phenomenon in syngnathidae which refers to embryo or fetus incubation by males. However, whether male mammalian animals have the potential to conceive and maintain pregnancy remains unclear. Here, we constructed a rat model of pregnancy in the male parabiont using a four-step strategy. First, a heterosexual parabiotic pair was produced by surgically joining a castrated male rat and a female rat. After 8 weeks, uterus transplantation was performed on the male parabiont. After recovery, blastocyst-stage embryos were transplanted to the grafted uterus of the male parabiont and the native uterus of the female parabiont. Caesarean section was performed at embryonic day 21.5. The success rate of the model was 3.68%, and pups were only delivered from the male parabiont under pregnant blood exposure. Our results reveal the potential for rat embryonic development in male parabionts, which may have a profound impact on reproductive biology.One-sentence summaryA rat model of pregnancy was constructed in the male parabiont using a four-step strategy.
The hedgehog signaling pathway is expressed in the adult mouse hypothalamus and modulated by fasting
Authors: Antonellis Patrick J. , Engle Staci E. , Brewer Kathryn M. , Berbari Nicolas F. 
Published: June 2021

AbstractThe importance of the primary cilium was initially highlighted by the class of human genetic disorders known as ciliopathies. Patients with ciliopathies such as Bardet-Biedl and Alström syndrome exhibit hyperphagia-associated obesity as a core clinical phenotype. How primary cilia contribute to energy homeostasis and feeding behavior is complex and unclear, but cilia appear important in both developmental and homeostatic processes. Primary cilia are important signaling centers, required for hedgehog signaling and localization of specific G protein-coupled receptors (GPCRs) with known roles in feeding behavior in mammals. The hedgehog pathway is best known for its role in developmental patterning, but now has recognized roles in adult tissues as well. In the postnatal brain, cilia and hedgehog signaling are important for growth and maintenance of neural progenitors, however, the role of hedgehog signaling in the differentiated adult brain is less clear. Here, we provide a detailed analysis of the expression of core components of the hedgehog signaling pathway in the adult mouse hypothalamus with an emphasis on feeding centers. We show that hedgehog pathway genes continue to be expressed in differentiated neurons important for regulation of feeding behavior. Furthermore, we demonstrate for the first time that pathway activity is regulated at the transcriptional level by fasting. These data suggest that hedgehog signaling is involved in the proper functioning of brain regions which regulate feeding behavior and that hedgehog pathway dysfunction may play a role in the obesity observed in certain ciliopathies.Significance StatementHere we investigate the expression of hedgehog pathway components in the adult mouse hypothalamus. Using dual labeling in situ hybridization we show that core components of the signaling pathway are expressed in multiple neuronal cell types within the hypothalamic feeding centers. Our findings also support previous findings that astrocytes are responsive to hedgehog signaling, as determined byGli1andPtch1expression. Using qPCR analysis, we show that hypothalamic hedgehog pathway activity is upregulated in response to fasting and this response is nuclei specific. These data not only provide a more detailed understanding of hedgehog pathway expression in the adult mouse hypothalamus but also provide direct evidence of a novel role for hedgehog signaling in the physiological response to fasting.
Incorporation of unnatural amino acid for the tagging of cannabinoid receptors 1 and 2 reveals receptor roles in regulating cAMP levels
Authors: Thomas Alix , Schultz Carsten , Laguerre Aurélien 
Published: June 2021

AbstractThe role of CB1/CB2 co-expression in cell signaling remains elusive. We established a simplified mammalian cell model system in which expression of CB1 or CB2 can be easily monitored under a confocal microscope. For this, we applied amber codon suppression in live cells to incorporate a single trans-cyclooctene (TCO) bearing amino acid in one of the extracellular loops of CB1 or CB2, followed by fluorescent labeling via click chemistry. We employed genetically encoded biosensors to measure the roles of CB1 and/or CB2 in regulating intracellular calcium ([Ca2+]i) and cAMP ([cAMP]i) levels. We show that the agonist-mediated activation of tagged-CB1 or -CB2 can transiently elevate [Ca2+]i levels. However, when the two receptors were co-expressed in the same cell, CB2 no longer signaled through calcium although CB1-mediated transient elevation of [Ca2+]i levels was unaffected. Because of the existence of crosstalk between calcium and cAMP signaling, we measured the effects of CB1 and/or CB2 in regulating adenylate cyclase activity. We found that the expression of CB1 increased forskolin-induced [cAMP]i levels compared to non-transfected cells. Conversely, CB2 expression decreased stimulated [cAMP]i levels under the same conditions. Finally, co-expressed CB1 and CB2 receptors showed additive yet opposing effects on stimulated [cAMP]i levels. These observations suggest that co-expressed CB1/CB2 act locally as a pair in regulating cell excitability by modulating stimulated [cAMP]i levels.
Mutational bias in spermatogonia impacts the anatomy of regulatory sites in the human genome
Authors: Kaiser Vera B. , Talmane Lana , Kumar Yatendra , Semple Fiona , MacLennan Marie ,   Deciphering Developmental Disorders Study, FitzPatrick David R. , Taylor Martin S. , Semple Colin A. 
Published: June 2021

AbstractMutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (>=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.
A mixed-method approach to tailor the implementation of a participatory Total Worker Health® program
Authors: Nobrega Suzanne , Morocho Cesar , Robertson Michelle M. , Kurowski Alicia , Rice Serena , Henning Robert A. , Punnett Laura 
Published: June 2021

PurposeTotal Worker Health® (TWH) programs, which represent a holistic approach for advancing worker safety, health and well-being, require an employer to adapt programmatic coordination and employee involvement in program design and delivery. Organizational readiness for such measures requires competencies in leadership, communication, subject expertise and worker participation. In the absence of documented methods for TWH readiness assessment, the authors developed a process to prospectively identify implementation facilitators and barriers that may be used to strengthen organizational competencies and optimize the organizational “fit” in advance.Design/methodology/approachThe mixed-method baseline assessment instruments comprised an online organizational readiness survey and a key leader interview; these were administered with key organizational and labor leaders in five US healthcare facilities. Findings about organizational resources, skills available and potential implementation barriers were summarized in a stakeholder feedback report and used to strengthen readiness and tailor implementation to the organizational context.FindingsThe research team was able to leverage organizational strengths such as leaders' commitment and willingness to address nontraditional safety topics to establish new worker-led design teams. Information about program barriers (staff time and communication) enabled the research team to respond with proactive tailoring strategies such as training on participant roles, extending team recruitment time and providing program communication tools and coaching.Originality/valueA new method has been developed for prospective organizational readiness assessment to implement a participatory TWH program. The authors illustrate its ability to identify relevant organizational features to guide institutional preparation and tailor program implementation.
Ancient saltern metagenomics: tracking changes in microbes and their viruses from the underground to the surface
Authors: Ramos‐Barbero Mª Dolores , Viver Tomeu , Zabaleta Ane , Senel Ece , Gomariz María , Antigüedad Iñaki , Santos Fernando , Martínez‐García Manuel , Rosselló‐Móra Ramon , Antón Josefa 
Published: June 2021

SummaryMicrobial communities in hypersaline underground waters derive from ancient organisms trapped within the evaporitic salt crystals and are part of the poorly known subterranean biosphere. Here, we characterized the viral and prokaryotic assemblages present in the hypersaline springs that dissolve Triassic‐Keuper evaporite rocks and feed the Añana Salt Valley (Araba/Alava, Basque Country, Spain). Four underground water samples (around 23% total salinity) with different levels of exposure to the open air were analysed by means of microscopy and metagenomics. Cells and viruses in the spring water had lower concentrations than what are normally found in hypersaline environments and seemed to be mostly inactive. Upon exposure to the open air, there was an increase in activity of both cells and viruses as well as a selection of phylotypes. The underground water was inhabited by a rich community harbouring a diverse set of genes coding for retinal binding proteins. A total of 35 viral contigs from 15 to 104 kb, representing partial or total viral genomes, were assembled and their evolutionary changes through the spring system were followed by SNP analysis and metagenomic island tracking. Overall, both the viral and the prokaryotic assemblages changed quickly upon exposure to the open air conditions.
Can Fiat‐backed Stablecoins Be Considered Cash or Cash Equivalents Under International Financial Reporting Standards Rules?
Authors: Hampl Filip , Gyönyörová Lucie 
Published: June 2021

AbstractStablecoins are a rapidly evolving subcategory of cryptocurrency that aim to reduce the price fluctuations of traditional cryptocurrencies and thus become a common digital payment instrument. This paper aims to assess the material substance of fiat‐backed stablecoins to determine whether fiat‐backed stablecoins could be considered, in accordance with IFRS, as cash or cash equivalents. We chose 11 fiat‐backed stablecoins representing 99.97% of the total market capitalisation of all fiat‐backed stablecoins. Using a three‐step approach, we performed an analysis of the legal and general terms and conditions of the selected stablecoins and of cryptocurrency exchanges, and quantitatively analysed their risk characteristics in comparison with fiat currency pairs, money market indexes and instruments, and traditional cryptocurrencies. The results show that nine of the 11 stablecoins met the objective requirements of cash equivalents according to their material substance and, using an extensive interpretation of IAS 7, could be reported as cash equivalents. This study enhances understanding of the material substance of fiat‐backed stablecoins for their financial reporting and can be used by entities when creating accounting policies under existing IFRS rules and by accounting standard setters as evidence when formulating new rules or officially interpreting existing ones to provide guidance on the financial reporting of fiat‐backed stablecoins.
CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia
Authors: Liu Xiao‐Rong , Ye Ting‐Ting , Zhang Wen‐Jun , Guo Xuan , Wang Jie , Huang Shao‐Ping , Xie Long‐Shan , Song Xing‐Wang , Deng Wei‐Wen , Li Bing‐Mei , He Na , Wu Qian‐Yi , Zhuang Min‐Zhi , Xu Meng , Shi Yi‐Wu , Su Tao , Yi Yong‐Hong , Liao Wei‐Ping ,   For the China Epilepsy Gene 1.0 Project
Published: June 2021

AbstractAimsCHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy.MethodsTrios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy.ResultsFour novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy.ConclusionsCHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.