bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intercellular viral spread and intracellular transposition ofDrosophilagypsy
Authors: Keegan Richard M. , Chang Yung-Heng , Metzger Michael J. , Dubnau Josh 
Published: May 2020

AbstractIt has become increasingly clear that retrotransposons (RTEs) are more widely expressed in somatic tissues than previously appreciated. RTE expression has been implicated in a myriad of biological processes ranging from normal development and aging, to age related diseases such as cancer and neurodegeneration. Long Terminal Repeat (LTR)-retrotransposons are evolutionary ancestors to, and share many features with, exogenous retroviruses. In fact, many organisms contain endogenous retroviruses (ERVs) that derive from an exogenous retrovirus that have integrated into the germ line. These ERVs are inherited in Mendelian fashion like RTEs, and some retain the ability to transmit between cells like viruses, while others develop the ability to act as RTEs. The process of evolutionary transition between LTR-RTE and retroviruses is thought to involve multiple steps by which the element loses or gains the ability to transmit copies between cells versus the ability to replicate intracellularly. But, typically, these two modes of transmission are incompatible because they require assembly in different sub-cellular compartments. Like murine IAP/IAP-E elements, the gypsy family of retroelements in arthropods appear to sit along this evolutionary transition. The fact that gypsy elements have been found to actively mobilize in neurons and glial cells during normal aging and in models of neurodegeneration raises the question of whether their replication in somatic cells occurs via intracellular retrotransposition, intercellular viral spread, or some combination of the two. These modes of replication in somatic tissues would have quite different biological implications. Here, we demonstrate that Drosophila gypsy is capable of both cell-associated and cell-free viral transmission between cultured S2 cells of somatic origin. Further, we demonstrate that the ability of gypsy to move between cells is dependent upon a functional copy of its viral envelope protein. This argues that the gypsy element has transitioned from an RTE into a functional endogenous retrovirus with the acquisition of its envelope gene. On the other hand, we also find that intracellular retrotransposition of the same genomic copy of gypsy can occur in the absence of the Env protein. Thus, gypsy exhibits both intracellular retrotransposition and intercellular viral transmission as modes of replicating its genome.
Lung cancer models reveal SARS-CoV-2-induced EMT contributes to COVID-19 pathophysiology
Authors: Stewart C. Allison , Gay Carl M. , Ramkumar Kavya , Cargill Kasey R. , Cardnell Robert J. , Nilsson Monique B. , Heeke Simon , Park Elizabeth M. , Kundu Samrat T. , Diao Lixia , Wang Qi , Shen Li , Xi Yuanxin , Zhang Bingnan , Della Corte Carminia Maria , Fan Youhong , Kundu Kiran , Gao Boning , Avila Kimberley , Pickering Curtis R. , Johnson Faye M. , Zhang Jianjun , Kadara Humam , Minna John D. , Gibbons Don L. , Wang Jing , Heymach John V. , Byers Lauren Averett 
Published: May 2020

AbstractCOVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation ofACE2andTMPRSS2. We find thatACE2expression is restricted to a select population of highly epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium, induces metabolic and transcriptional changes consistent with epithelial to mesenchymal transition (EMT), including upregulation ofZEB1andAXL, resulting in an increased EMT score. Additionally, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT via TGFbeta, ZEB1 overexpression and onset of EGFR TKI inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect. These observations highlight the utility of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses, and offer important insights into the potential mechanisms underlying the morbidity and mortality of COVID-19 in healthy patients and cancer patients alike.
Restarting after COVID-19: A Data-driven Evaluation of Opening Scenarios
Authors: Aravindakshan Ashwin , Boehnke Jörn , Gholami Ehsan , Nayak Ashutosh 
Published: May 2020

AbstractTo contain the COVID-19 pandemic, several governments introduced strict Non-Pharmaceutical Interventions (NPI) that restricted movement, public gatherings, national and international travel, and shut down large parts of the economy. Yet, the impact of the enforcement and subsequent loosening of these policies on the spread of COVID-19 is not well understood. Accordingly, we measure the impact of NPI on mitigating disease spread by exploiting the spatio-temporal variations in policy measures across the 16 states of Germany. This quasi-experiment identifies each policy’s effect on reducing disease spread. We adapt the SEIR (Susceptible-Exposed-Infected-Recovered) model for disease propagation to include data on daily confirmed cases, intra- and inter-state movement, and social distancing. By combining the model with measures of policy contributions on mobility reduction, we forecast scenarios for relaxing various types of NPIs. Our model finds that, in Germany, policies that mandated contact restrictions (e.g., movement in public space limited to two persons or people co-living), initial business closures (e.g., restaurant closures), stay-at-home orders (e.g., prohibition of non-essential trips), non-essential services (e.g., florists, museums) and retail outlet closures led to the sharpest drops in movement within and across states. Contact restrictions were the most effective at lowering infection rates, while border closures had only minimal effects at mitigating the spread of the disease, even though cross-border travel might have played a role in seeding the disease in the population. We believe that a deeper understanding of the policy effects on mitigating the spread of COVID-19 allows a more accurate forecast of the disease spread when NPIs are (partially) loosened, and thus also better informs policymakers towards making appropriate decisions.
The effectiveness of eight nonpharmaceutical interventions against COVID-19 in 41 countries
Authors: Brauner Jan M. , Mindermann Sören , Sharma Mrinank , Stephenson Anna B. , Gavenčiak Tomáš , Johnston David , Leech Gavin , Salvatier John , Altman George , Norman Alexander John , Monrad Joshua Teperowski , Besiroglu Tamay , Ge Hong , Mikulik Vladimir , Hartwick Meghan A. , Teh Yee Whye , Chindelevitch Leonid , Gal Yarin , Kulveit Jan 
Published: May 2020

AbstractBackgroundGovernments are attempting to control the COVID-19 pandemic with nonpharmaceutical interventions (NPIs). However, it is still largely unknown how effective different NPIs are at reducing transmission. Data-driven studies can estimate the effectiveness of NPIs while minimizing assumptions, but existing analyses lack sufficient data and validation to robustly distinguish the effects of individual NPIs.MethodsWe collect chronological data on NPIs in 41 countries between January and May 2020, using independent double entry by researchers to ensure high data quality. We estimate NPI effectiveness with a Bayesian hierarchical model, by linking NPI implementation dates to national case and death counts. To our knowledge, this is the largest and most thoroughly validated data-driven study of NPI effectiveness to date.ResultsWe model each NPI’s effect as a multiplicative (percentage) reduction in the reproduction number R. We estimate the mean reduction in R across the countries in our data for eight NPIs: mandating mask-wearing in (some) public spaces (2%; 95% CI: −14%–16%), limiting gatherings to 1000 people or less (2%; −20%–22%), to 100 people or less (21%; 1%–39%), to 10 people or less (36%; 16%–53%), closing some high-risk businesses (31%; 13%–46%), closing most nonessential businesses (40%; 22%–55%), closing schools and universities (39%; 21%–55%), and issuing stay-at-home orders (18%; 4%–31%). These results are supported by extensive empirical validation, including 15 sensitivity analyses.ConclusionsOur results suggest that, by implementing effective NPIs, many countries can reduce R below 1 without issuing a stay-at-home order. We find a surprisingly large role for school and university closures in reducing COVID-19 transmission, a contribution to the ongoing debate about the relevance of asymptomatic carriers in disease spread. Banning gatherings and closing high-risk businesses can be highly effective in reducing transmission, but closing most businesses only has limited additional benefit.
The binding mechanism ofStreptococcus suisaccessory virulence factor and adhesin SadP to globotetraosylceramide
Authors: Johansson Miralda Madar , Bélurier Eva , Papageorgiou Anastassios C. , Sundin Anders P. , Rahkila Jani , Kallonen Teemu , Nilsson Ulf J. , Maatsola Santeri , Nyholm Thomas K.M. , Käpylä Jarmo , Corander Jukka , Leino Reko , Finne Jukka , Teneberg Susann , Haataja Sauli 
Published: May 2020

AbstractStreptococcus suisis part of the pig commensal microbiome and a major pathogen causing pneumonia and meningitis in pigs and occasionally also zoonotic meningitis. According to genomic analysis,S. suisis divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. The virulence factorS. suisadhesin P (SadP) recognizes the galabiose Galα1–4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes PNand PO. We show here that subtype PNis distributed in the systemic strains that cause meningitis, whereas type POis found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype PNstrain also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type PNSadP adhesin showed that the amino acid asparagine-285, which is replaced by an aspartate residue in type Po SadP, was required for binding to Gb4 and, strikingly, it was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided further insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and urea-group. Thus, the Asn-285-mediated molecular mechanism of type PNSadP binding to Gb4 could be used as a candidate to selectively targetS. suisin invasive systemic disease without interfering with commensal strains, which may open up new venues for developing intervention strategies against this pathogen.
Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
Authors: Nief Corrine A. , Morhard Robert , Chelales Erika , Alvarez Daniel Adrianzen , Bourla Ioanna , Lam Christopher T. , Sag Alan A. , Crouch Brian T. , Mueller Jenna L. , Katz David , Dewhirst Mark W. , Everitt Jeffrey I. , Ramanujam Nirmala 
Published: May 2020

AbstractFocal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution within vivoimaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 µL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 µL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.Graphical AbstractThe inclusion of ethylcellulose limits extra-tumoral leakage of ethanol and increases the target-tissue ablation.
SARS-CoV-2 transmission chains from genetic data: a Danish case study
Authors: Bluhm Andreas , Christandl Matthias , Gesmundo Fulvio , Klausen Frederik Ravn , Mančinska Laura , Steffan Vincent , França Daniel Stilck , Werner Albert H. 
Published: May 2020

AbstractBackgroundThe COVID-19 pandemic caused by the SARS-CoV-2 virus started in China in December 2019 and has since spread globally. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Denmark is currently opening up after a lockdown in mid-March.MethodsWe perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries.ResultOur findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark and in at least one case find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes is stable after lockdown.ConclusionOur work shows how genetic data can be used to identify routes of introduction of a virus into a region and provide alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission chains suggesting that Denmark was part of a network of countries among which the virus was being transmitted; thus challenging the common narrative that Denmark only got infected from abroad. Our analysis does not indicate that the major haplotypes appearing in Denmark have a different degree of virality. Our methods can be applied to other countries, regions or even highly localised outbreaks. When used in real-time, we believe they can serve to identify transmission events and supplement traditional methods such as contact tracing.
TowardsMycobacterium tuberculosisdetection at the point-of-care: a brighter solvatochromic probe permits the detection of mycobacteria within minutes
Authors: Kamariza Mireille , Keyser Samantha G. L. , Utz Ashley , Knapp Benjamin D. , Ahn Green , Cambier C. J. , Chen Teresia , Huang Kerwyn Casey , Bertozzi Carolyn R. 
Published: May 2020

ABSTRACTThere is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate that specifically detectsMycobacterium tuberculosis(Mtb) in minutes. 3-hydroxychromone (3HC) dyes, known to yield high fluorescence quantum yields, exhibit shifts in fluorescence intensity in response to changes in environmental polarity. We synthesized two analogs of 3HC-trehalose conjugates (3HC-2-Tre and 3HC-3-Tre) and determined that 3HC-3-Tre has exceptionally favorable properties for Mtb detection. 3HC-3-Tre-labeled mycobacterial cells displayed a 10-fold increase in fluorescence intensity compared to our previously reports on the dye 4,4-N,N-dimethylaminonapthalimide (DMN-Tre). Excitingly, we detected fluorescent Mtb cells within 10 minutes of probe treatment. Thus, 3HC-3-Tre permits rapid visualization of mycobacteria that ultimately could empower improved Mtb detection at the point-of-care in low-resource settings.
GeneBreaker - Variant simulation to improve the diagnosis of Mendelian rare genetic diseases
Authors: Richmond Phillip A. , Av-Shalom Tamar V. , Fornes Oriol , Modi Bhavi , Elliott Alison M. , Wasserman Wyeth W. 
Published: May 2020

AbstractMendelian rare genetic diseases affect 5-10% of the population, and with over 5,300 genes responsible for ~7,000 different diseases, they are challenging to diagnose. The use of whole genome sequencing (WGS) has bolstered the diagnosis rate significantly. Effective use of WGS relies upon the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant calling and prioritization, and is the beneficiary of improvements to sequencing technology, variant calling approaches, and increased capacity to prioritize genomic variants with potential pathogenicity. As analysis pipelines continue to improve, careful testing of their efficacy is paramount. However, real-life cases typically emerge anecdotally, and utilization of clinically sensitive and identifiable data for testing pipeline improvements is regulated and limiting. We identified the need for a gene-based variant simulation framework which can create mock rare disease scenarios, utilizing known pathogenic variants or through the creation of novel gene-disrupting variants. To fill this need, we present GeneBreaker, a tool which creates synthetic rare disease cases with utility for benchmarking variant calling approaches, testing the efficacy of variant prioritization, and as an educational mechanism for training diagnostic practitioners in the expanding field of genomic medicine. GeneBreaker is freely available athttp://GeneBreaker.cmmt.ubc.ca.
Objective dystonia prediction with MRI after neonatal hypoxic-ischemic encephalopathy
Authors: Chintalapati Keerthana , Miao Hanyang , Mathur Amit , Neil Jeff , Aravamuthan Bhooma R. 
Published: May 2020

AbstractAimTo determine an objective and clinically-feasible method to predict dystonia in cerebral palsy (CP) using magnetic resonance imaging (MRI) following neonatal hypoxic-ischemic encephalopathy (HIE).MethodsIn this retrospective case-control study, we examined brain MRIs in neonates at age 4–5 days who underwent therapeutic hypothermia for HIE at a single tertiary care center. The lower average apparent diffusion coefficient (ADC) values between the left and right striatum and thalamus were determined using clinically-integrated software (IBM iConnect Access). Neonatal neurology, movement disorder, and cerebral palsy specialist notes were screened through age 5 years for motor abnormality documentation.ResultsIn 50 subjects, ADC values significantly predicted dystonia in CP with receiver operator characteristic areas under the curve of 0.862 (p = 0.0004) in the striatum and 0.838 (p = 0.001) in the thalamus. Striatal ADC values less than 1.014×10−3 mm2/s provided 100% specificity and 70% sensitivity for dystonia. Thalamic ADC values less than 0.973×10−3 mm2/s provided 100% specificity and 80% sensitivity for dystonia.InterpretationIn this small retrospective study, analysis of clinically-acquired MRIs predicted dystonia with high specificity following neonatal HIE. This could be a useful prognostication adjunct guiding when to establish appropriate vigilance for dystonia in CP.
Predicting Growth of COVID-19 Confirmed Cases in Each U.S. County with a Population of 50,000 or More, Revised July 8, 2020
Authors: Robertson Leon S. 
Published: May 2020

ABSTRACTA simple model of local spread of COVID-19 is needed to assist local governments and health care providers prepare for surges of clinical cases in their communities. National and state based models are inadequate because the virus is introduced and spreads at different rates in local areas. In the U.S. as of July 3, 2020, 73 percent of cases and 84 percent of deaths occurred in the 200 counties with the most cases and deaths. Each county has its own function of cases in time that can be used to predict increases in reported cases two weeks in advance for each of 988 counties in the U.S. with populations of 50,000 or more inhabitants. A logarithmic model based on growth in cases during the past 30 days is substantially predictive of increase in cases during the subsequent 14 days. Predicted increase in cases for the 988 U.S. counties will be published online daily.
Financial reporting quality, audit fees and risk committees
Authors: Bhuiyan Md. Borhan Uddin , Salma Ummya , Roudaki Jamal , Tavite Siata 
Published: May 2020

PurposeThe purpose of this paper is to examine the association between the existence of a risk committee (RC) in a firm and financial reporting quality. We also investigate whether having an RC has an effect on audit pricing. We argue that the existence of an RC in a firm contributes to higher financial reporting quality and this, eventually, affects audit pricing.Design/methodology/approachThis study uses two different proxies for RC measures and investigates the impact on financial reporting quality and audit pricing. Multivariate regression analysis and propensity score matching techniques are both applied to data from the Australian Stock Exchange's listed companies for the years 2001–2013.FindingsThe results indicate that the existence of an RC reduces the discretionary accruals; this means the financial reporting quality improves when RCs are in operation. Our findings also indicate that the existence of an RC increases audit fees.Practical implicationsThe findings from this study will be beneficial to the regulatory authorities responsible for improving the compliance of corporate governance (CG). An RC can serve as a risk-mitigating tool in the investment decision-making process. Finally, the results are beneficial for the development of best practices in CG by promoting the existence of an RC.Originality/valueThis study goes beyond the traditional focus on CG as we use the existence of an RC as an indicator of better governance practices to mitigate financial and non-financial risk factors. To the best of our knowledge, this paper is among the first to investigate the consequences for firms operating with RCs. This issue has implications for investors, auditors, directors and regulators.