bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saliva Sample as a Non-Invasive Specimen for the Diagnosis of Coronavirus Disease-2019 (COVID-19): a Cross-Sectional Study
Authors: Pasomsub Ekawat , Watcharananan Siriorn P. , Boonyawat Kochawan , Janchompoo Pareena , Wongtabtim Garanyuta , Suksuwan Worramin , Sungkanuparph Somnuek , Phuphuakrat Angsana 
Published: April 2020

AbstractObjectivesAmid the increasing number of global pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus 2019 (SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19.MethodsFrom 27 March to 4 April, 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared.ResultsTwo-hundred pairs of the samples were collected. Sixty-nine (34.5%) patients were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% [95% confidence interval (CI) 79.2%-89.3%], and 98.9% (95% CI 97.5-100.3%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (kappa coefficient 0.851, 95% CI 0.723-0.979; p <0.001).ConclusionsSaliva specimens can be used for the diagnosis of COVID-19. The collection method is non-invasive, and non-aerosol generating. Using a saliva sample as a specimen for the detection of SARS-CoV-2 could facilitate the diagnosis of the disease, which is one of the strategies that helps in controlling the epidemic.
COVID-19: An Update on the Epidemiological, Genomic Origin, Phylogenetic study, India centric to Worldwide current status
Authors: Nandagopal Murugan , Jansi R. Sagaya 
Published: April 2020

AbstractThe pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study.
Revealing COVID-19 Transmission by SARS-CoV-2 Genome Sequencing and Agent Based Modelling
Authors: Rockett Rebecca J , Arnott Alicia , Lam Connie , Sadsad Rosemarie , Timms Verlaine , Gray Karen-Ann , Eden John-Sebastian , Chang Sheryl , Gall Mailie , Draper Jenny , Sim Eby , Bachmann Nathan L , Carter Ian , Basile Kerri , Byun Roy , O’Sullivan Matthew V , Chen Sharon C-A , Maddocks Susan , Sorrell Tania C. , Dwyer Dominic E , Holmes Edward C , Kok Jen , Prokopenko Mikhail , Sintchenko Vitali 
Published: April 2020

ABSTRACTCommunity transmission of the new coronavirus SARS-CoV-2 is a major public health concern that remains difficult to assess. We present a genomic survey of SARS-CoV-2 from a during the first 10 weeks of COVID-19 activity in New South Wales, Australia. Transmission events were monitored prospectively during the critical period of implementation of national control measures. SARS-CoV-2 genomes were sequenced from 209 patients diagnosed with COVID-19 infection between January and March 2020. Only a quarter of cases appeared to be locally acquired and genomic-based estimates of local transmission rates were concordant with predictions from a computational agent-based model. This convergent assessment indicates that genome sequencing provides key information to inform public health action and has improved our understanding of the COVID-19 evolution from outbreak to epidemic.
Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy
Authors: Carsana Luca , Sonzogni Aurelio , Nasr Ahmed , Rossi Roberta Simona , Pellegrinelli Alessandro , Zerbi Pietro , Rech Roberto , Colombo Riccardo , Antinori Spinello , Corbellino Mario , Galli Massimo , Catena Emanuele , Tosoni Antonella , Gianatti Andrea , Nebuloni Manuela 
Published: April 2020

ABSTRACTImportanceThe analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness.ObjectiveTo determine the histological patterns in lung tissue of patients with severe COVID-19.Design and participantsLungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed.ResultsThe features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstice. Electron microscopy revealed viral particles in the cytoplasm of pneumocytes.Conclusions and relevanceThe predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.
Osteocyte Transcriptome Mapping Identifies a Molecular Landscape Controlling Skeletal Homeostasis and Susceptibility to Skeletal Disease
Authors: Youlten Scott E. , Kemp John P. , Logan John G. , Ghirardello Elena J. , Sergio Claudio M. , Dack Michael R. G. , Guilfoyle Siobhan E. , Leitch Victoria D. , Butterfield Natalie C. , Komla-Ebri Davide , Chai Ryan C. , Corr Alexander P. , Smith James T. , Mohanty Sindhu , Morris John A. , McDonald Michelle M. , Quinn Julian M. W. , McGlade Amelia R. , Bartonicek Nenad , Jansson Matt , Hatzikotoulas Konstantinos , Irving Melita D. , Beleza-Meireles Ana , Rivadeneira Fernando , Duncan Emma , Richards J. Brent , Adams David J. , Lelliott Christopher J. , Brink Robert , Phan Tri Giang , Eisman John A. , Evans David M. , Zeggini Eleftheria , Baldock Paul A. , Bassett J. H. Duncan , Williams Graham R. , Croucher Peter I. 
Published: April 2020

AbstractOsteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define anosteocyte transcriptome signatureof 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this program is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26osteocyte transcriptome signaturegenes that control bone structure and function. We showedosteocyte transcriptome signaturegenes are enriched for human orthologs that cause monogenic skeletal disorders (P=2.4×10-22) and are associated with the polygenic diseases osteoporosis (P=1.8×10-13) and osteoarthritis (P=1.6×10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance ofosteocytesin human skeletal disease.
SARS-CoV-2 Encodes a PPxY Late Domain Motif Known to Enhance Budding and Spread in Enveloped RNA Viruses
Authors: Maaroufi Halim 
Published: April 2020

ABSTRACTThe current COVID-19 (CoronavirusDisease-2019) pandemic is affecting the health and/or socioeconomic welfare of almost everyone in the world. Finding vaccines and therapeutics is therefore urgent, but elucidation of the molecular mechanisms that allow some viruses to cross host species boundaries, becoming a threat to human health, must also be given close attention. Here, analysis of all proteins of SARS-CoV-2 revealed a unique PPxY Late (L) domain motif,25PPAY28, in a spike (S) protein inside a predicted hot disordered loop subject to phosphorylation and binding. PPxY motifs in enveloped RNA viruses are known to recruit Nedd4 E3 ubiquitin ligases and ultimately the ESCRT complex to enhance virus budding and release, resulting in higher viral loads, hence facilitating new infections. Interestingly, proteins of SARS-CoV-1 do not feature PPxY motifs, which could explain why SARS-CoV-2 is more contagious than SARS-CoV-1. Should an experimental assessment of this hypothesis show that the PPxY motif plays the same role in SARS-CoV-2 as it does in other enveloped RNA viruses, this motif will become a promising target for the development of novel host-oriented antiviral therapeutics for preventing S proteins from recruiting Nedd4 E3 ubiquitin ligase partners.
Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples
Authors: Tan Xiaotian , Lin Cory , Zhang Jie , Khaing Oo Maung Kyaw , Fan Xudong 
Published: April 2020

AbstractCOVID-19 pandemic has caused tens of thousands of deaths and is now a severe threat to global health. Clinical practice has demonstrated that the SARS-CoV-2 S1 specific antibodies and viral antigens can be used as diagnostic and prognostic markers of COVID-19. However, the popular point-of-care biomarker detection technologies, such as the lateral-flow test strips, provide only yes/no information and have very limited sensitivities. Thus, it has a high false negative rate and cannot be used for the quantitative evaluation of patient’s immune response. Conventional ELISA (enzyme-linked immunosorbent assay), on the other hand, can provide quantitative, accurate, and sensitive results, but it involves complicated and expensive instruments and long assay time. In addition, samples need to be sent to centralized labs, which significantly increases the turn-around time. Here, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen – S protein in serum. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. Furthermore, we demonstrated that our microfluidic ELISA platform can be used for rapid affinity evaluation of monoclonal anti-S1 antibodies. The microfluidic ELISA device is highly portable and requires less than 10 μL of samples for each channel. Therefore, our technology will greatly facilitate rapid and quantitative analysis of COVID-19 patients and vaccine recipients at point-of-care.
Transcranial Direct Current Stimulation (tDCS) Augments the Effects of Gamified, Mobile Attention Bias Modification
Authors: Myruski Sarah , Cho Hyein , Bikson Marom , Dennis-Tiwary Tracy A. 
Published: April 2020

AbstractAnxiety-related attentional bias (AB) is the preferential processing of threat observed in clinical and sub-clinical anxiety. Attention bias modification training (ABMT) is a computerized cognitive training technique designed to systematically direct attention away from threat and ameliorate AB, but mixed and null findings have highlighted gaps in our understanding of mechanisms underlying ABMT and how to design the most effective delivery systems. One neuromodulation technique, transcranial direct current stimulation (tDCS) across the prefrontal cortex (PFC) may augment the effects of ABMT by strengthening top-down cognitive control processes, but the evidence base is limited and has not been generalized to current approaches in digital therapeutics, such as mobile applications. The present study tested whether tDCS across the PFC, versus sham stimulation, effectively augments the beneficial effects of a gamified ABMT mobile app. Thirty-eight adults (Mage = 23.92, SD = 4.75; 18 females) evidencing low-to-moderate anxiety symptoms were randomly assigned to active or sham tDCS for 30-minutes while receiving ABMT via a mobile app. Participants reported on potential moderators of ABMT, including life stress and trait anxiety. ECG was recorded during a subsequent stressor to generate respiratory sinus arrhythmia (RSA) suppression as a metric of stress resilience. The app overall reduced subjective anxiety, whereas adding tDCS (compared to sham) reduced AB and boosted stress resilience measured via RSA suppression, particularly for those reporting low life stress. Our results integrating tDCS with ABMT provide insight into the mechanisms of AB modulation and support ongoing evaluations of enhanced ABMT reliability and effectiveness via tDCS.
In vivo high-content screening in zebrafish for developmental nephrotoxicity of approved drugs
Authors: Westhoff JH , Steenbergen PJ , Thomas LSV , Heigwer J , Bruckner T , Cooper L , Tönshoff B , Hoffmann GF , Gehrig J 
Published: April 2020

AbstractDespite widespread drug exposure, for example during gestation or in prematurely born children, organ-specific developmental toxicity of most drugs is poorly understood. Developmental and functional abnormalities are a major cause of kidney diseases during childhood; however, the potential causal relationship to exposure with nephrotoxic drugs during nephrogenesis is widely unknown. To identify developmental nephrotoxic drugs in a large scale, we established and performed an automated high-content screen to score for phenotypic renal alterations in theTg(wt1b:EGFP)zebrafish line. During early nephrogenesis, embryos were exposed to a compound library of approved drugs. After treatment, embryos were aligned within microtiter plates using 3D-printed orientation tools enabling the robust acquisition of consistent dorsal views of pronephric kidneys by automated microscopy. To qualitatively and quantitatively score and visualize phenotypes, we developed software tools for the semi-automated analysis, processing and visualization of this large image-based dataset. Using this scoring scheme, we were able to categorize compounds based on their potential developmental nephrotoxic effects. About 10% of tested drugs induced pronephric phenotypes including glomerular and tubular malformations, or overall changes in kidney morphology. Major chemical compound groups identified to cause glomerular and tubular alterations included dihydropyridine derivatives, HMG CoA reductase inhibitors, fibrates, imidazole, benzimidazole and triazole derivatives, corticosteroids, glucocorticoids, acetic acid derivatives and propionic acid derivatives. In conclusion, the presented study demonstrates the large-scale screening of kidney-specific toxicity of approved drugs in a live vertebrate embryo. The associated technology and tool-sets can be easily adapted for other organ systems providing a unique platform forin vivolarge-scale assessment of organ-specific developmental toxicity or other biomedical applications. Ultimately, the presented data and associated visualization and browsing tools provide a resource for potentially nephrotoxic drugs and for further investigations.
Synchronization of human retinal pigment ephitilial-1 (RPE-1) cells in mitosis
Authors: Scott Stacey J. , Suvarna Kethan , D’Avino Pier Paolo 
Published: April 2020

ABSTRACTHuman retinal pigment ephitilial-1 (RPE-1) cells are increasingly being used as a model to study mitosis because they represent a non-transformed alternative to cancer cell lines, such as HeLa cervical adenocarcinoma cells. However, the lack of an efficient method to synchronize RPE-1 cells in mitosis precludes their application for large-scale biochemical and proteomics assays. Here we report a protocol to synchronize RPE-1 cells based on sequential treatments with the Cdk4/6 inhibitor PD 0332991 (palbociclib) and the microtubule depolymerizing drug nocodazole. With this method, the vast majority (80-90%) of RPE-1 cells arrested at prometaphase and exited mitosis synchronously after release from nocodazole. Furthermore, we show that this protocol could be successfully employed for the characterization of the protein-protein interaction network of the kinetochore protein Ndc80 by immunoprecipitation coupled with mass spectrometry. This synchronization method significantly expands the versatility and applicability of RPE-1 cells to the study of cell division and might be applied to other cell lines that do not respond to treatments with DNA synthesis inhibitors.
Identification ofTrypanosoma brucei gambienseandT. b. rhodesiensein vectors using multiplexed high-resolution melt analysis
Authors: Garrod Gala , Adams Emily R. , Lingley Jessica K. , Saldanha Isabel , Torr Stephen J. , Cunningham Lucas J. 
Published: April 2020

AbstractBackgroundHuman African Trypanosomiasis (HAT) is a potentially fatal parasitic infection caused by the trypanosome sub-speciesTrypanosoma brucei gambienseandT. b. rhodesiensetransmitted by tsetse flies. Currently, global HAT case numbers are reaching less than 1 case per 10,000 people in many disease foci. As such, there is a need for simple screening tools and strategies to replace active screening of the human population which can be maintained post-elimination for Gambian HAT and long-term Rhodesian HAT. Here we describe the development of a novel high-resolution melt assay for the xenomonitoring ofTrypanosoma brucei gambienseandT. b. rhodesiensein tsetse.MethodsPrimers forT. b. rhodesienseandT. b. gambiensewere designed to target species-specific single copy genes. An additional primer set was included in the multiplex to determine if samples have sufficient genomic material for detecting low copy number targets. The assay was evaluated on 96 wild-caught tsetse previously identified to be positive forT. brucei s. l.of which two were infected withT. b. rhodesiense.ResultsThe assay was found to be highly specific with no cross-reactivity with non-target trypanosome species and the assay limit of detection was 104tryps/mL. HRM successfully identified threeT. b. rhodesiensepositive flies and was in agreement with the reference sub-species-specific PCRs. This assay provides an alternative to running multiple PCRs when screening for pathogenic sub-species ofT. bruceis. l and produces results in ~2 hours, avoiding gel electrophoresis.ConclusionsThis method could provide a component of a simple and efficient method of screening large numbers of tsetse flies in known HAT foci or in areas at risk of recrudescence or threatened by the changing distribution of both forms of HAT.
Minimising severity of dengue serotype 1 infection by transmissible interfering particles
Authors: Shausan A. , Aaskov J. , Drovandi C. , Mengersen K. 
Published: April 2020

AbstractTransmissible interfering dengue particles (DENV–TIPs) are engineered dengue virus mutants which are defective and can replicate only with the help of dengue wild–type virus (DENV).In vitrostudies have found that when DENV–TIPs and DENV coinfect a cell, they compete for viral genomes and cell proteins for replication and packaging, and DENV–TIPs outperform DENV in this process. Thus, it is hypothesised that DENV–TIPs may be used as a novel therapeutic agent. However, the effectiveness of DENV–TIPs as an antiviral agent is yet to be explored at an epidemiological scale. We present a mathematical model for the replication of DENV and DENV–TIPs as they interact with human host cells, accounting for the effectiveness of DENV–TIPs in blocking DENV from coinfected cells. We fit the model to sequentially measured plasma viral titre data from primary and secondary dengue serotype 1 infected patients in Vietnam. We show that variation in initial DENV load is sufficient to recreate the observed variation between patients. Parameter estimates, differing in primary and secondary infections, do not confirm a significant difference between these two types of infection. We use our model to investigate the potential impact of DENV–TIPs as an antiviral agent. We conclude that, when the effectiveness of DENV–TIPs in inhibiting DENV from coinfected cells is at least 80%, a dose as high as 1012copies per millilitre of blood is required to reduce duration of infection and peak DENV serotype 1 infection level at any time point of infection. This work provides a quantitative understanding of the relationship between DENV–TIPs levels and their efficiency in clearing dengue viral infection. It will guide future development of mechanistic models of how DENV–TIPs might contribute as an antiviral agent in limiting natural dengue infection.Author summaryInhibition of dengue wild–type virus (DENV) by transmissible interfering dengue particles (DENV–TIPs) is seen in somein vitrostudies, and it is hypothesised that DENV–TIPs may be used as a therapeutic agent. However, the efficiency of DENV–TIPs in limiting DENV infection in patients is yet to be explored at an epidemiological scale. Using data collected from dengue serotype 1 infected patients, we model how DENV replicates in an infected patient and how effective DENV–TIPs are in controlling that replication. Our results are of use in the evaluation of DENV–TIPs as a potential antiviral agent.
β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes
Authors: Hattori Kazuki , Wakatsuki Hiroaki , Sakauchi Chihiro , Furutani Shotaro , Hatta Tomohisa , Natsume Tohru , Ichijo Hidenori 
Published: April 2020

AbstractBoosting energy expenditure by harnessing the activity of brown adipocytes is a promising strategy for combatting the global epidemic of obesity. Many studies have revealed that the β3-adrenergic receptor agonist is a potent activator of brown adipocytes, even in humans, and PKA and p38 MAPK have been demonstrated for regulating the transcription of a wide range of critical genes such as Ucp1. We previously revealed that the PKA-ASK1-p38 axis is activated in immature brown adipocytes and contributes to functional maturation. However, the downstream mechanisms of PKA that initiate the p38 MAPK cascade are still mostly unknown in mature brown adipocytes. Here, we identified the ASK family as a crucial signaling molecule bridging PKA and MAPK in mature brown adipocytes. Mechanistically, the phosphorylation of ASK1 at threonine 99 and serine 993 is critical in PKA-dependent ASK1 activation. Additionally, PKA also activates ASK2, which contributes to MAPK regulation. These lines of evidence provide new details for tailoring a βAR-dependent brown adipocyte activation strategy.