bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of mobility restrictions on the SARS-CoV-2 diffusion during the first wave: what are the impacts in Sweden, USA, France and Colombia
Authors: Olivier Telle , Benkimoun Samuel , Paul Richard 
Published: February 2021

ResuméCombined with sanitation and social distancing measures, control of human mobility has quickly been targeted as a major leverage to contain the spread of SARS-CoV-2 in a great majority of countries worldwide. The extent to which such measures were successful, however, is uncertain (Gibbs et al. 2020; Kraemer et al. 2020). Very few studies are quantifying the relation between mobility, lockdown strategies and the diffusion of the virus in different countries. Using the anonymised data collected by one of the major social media platforms (Facebook) combined with spatial and temporal Covid-19 data, the objective of this research is to understand how mobility patterns and SARS-CoV-2 diffusion during the first wave are connected in four different countries: the west coast of the USA, Colombia, Sweden and France. Our analyses suggest a relatively modest impact of lockdown on the spread of the virus at the national scale. Despite a varying impact of lockdown on mobility reduction in these countries (83% in France and Colombia, 55% in USA, 10% in Sweden), no country successfully implemented control measures to stem the spread of the virus. As observed in Hubei (Chinazzi et al. 2020), it is likely that the virus had already spread very widely prior to lockdown; the number of affected administrative units in all countries was already very high at the time of lockdown despite the low testing levels. The second conclusion is that the integration of mobility data considerably improved the epidemiological model (as revealed by the QAIC). If inter-individual contact is a fundamental element in the study of the spread of infectious diseases, it is also the case at the level of administrative units. However, this relational dimension is little understood beyond the individual scale mostly due to the lack of mobility data at this scale. Fortunately, these types of data are getting increasingly provided by social media or mobile operators, and they can be used to help administrations to observe changes in movement patterns and/or to better locate where to implement disease control measures such as vaccination (Pollina & Busvine 2020; Pullano et al. 2020; Romm et al. 2020).
Wastewater surveillance for SARS-CoV-2 on college campuses: Initial efforts, lessons learned and research needs
Authors: Harris-Lovett Sasha , Nelson Kara , Beamer Paloma , Bischel Heather N. , Bivins Aaron , Bruder Andrea , Butler Caitlyn , Camenisch Todd D. , Long Susan K. De , Karthikeyan Smruthi , Larsen David A. , Meierdiercks Katherine , Mouser Paula , Pagsuyoin Sheree , Prasek Sarah , Radniecki Tyler S. , Ram Jeffrey L. , Roper D. Keith , Safford Hannah , Sherchan Samendra P. , Shuster William , Stalder Thibault , Wheeler Robert T. , Korfmacher Katrina Smith 
Published: February 2021

AbstractBackgroundWastewater surveillance for SARS-CoV-2 is an emerging approach to help identify the risk of a COVID-19 outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, nursing homes) scales.ObjectivesThis research aims to understand the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation.MethodsThis paper presents the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resource needs, and lessons learned from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions.DiscussionOur analysis suggests that wastewater monitoring at colleges requires consideration of information needs, local sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members.
cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment
Authors: Breitenbach Tim , Englert Nils , Osmanoglu Özge , Rukoyatkina Natalia , Wangorsch Gaby , Friebe Andreas , Butt Elke , Feil Robert , Dittrich Marcus , Gambaryan Stepan , Dandekar Thomas 
Published: February 2021

AbstractBackgroundThe cyclic nucleotides cAMP and cGMP inhibit platelet activation.ResultsWe extended an older model and systematically integrated drugs as external stimuli. Data driven modeling allowed us to design models that provide a quantitative output for quantitative input information. This relies on condensed information about involved regulation and modeling of pharmacological interventions by systematic optimization methods. By multi-experiment fitting, we validated our model optimizing the parameters of the model. In addition, we show how the output of the developed cGMP model can be used as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets.ConclusionsWe present a model for cGMP signaling and VASP phosphorylation, that allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and has been validated by experimental data.
Ecological interactions in breast cancer: Cell facilitation promotes growth and survival under drug pressure
Authors: Emond Rena , Griffiths Jason I. , Grolmusz Vince Kornél , Nath Aritro , Chen Jinfeng , Medina Eric F. , Sousa Rachel S. , Adler Frederick R. , Bild Andrea H. 
Published: February 2021

AbstractThe interplay of positive and negative interactions between drug sensitive and resistant cells influences the effectiveness of treatment in heterogeneous cancer cell populations. In a study of isogenic estrogen receptor positive (ER+) breast cancer cell lineages sensitive and resistant to ribociclib-induced CDK4/6 inhibition in mono- and co-culture, we find that sensitive cells grow and compete more effectively in the absence of treatment. During treatment with ribociclib, sensitive cells survive and proliferate better when grown together with resistant cells than when grown in monoculture, termed facilitation in ecology. Both liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays and single cell RNA-sequencing (scRNAseq) indicate that resistant cell production of estradiol, a highly active estrogen metabolite, is the mechanism of facilitation. Higher estradiol production by resistant cells drives a shift in sensitive cell phenotype to a resistant cell state in coculture. Adding estradiol in monoculture provides sensitive cells with increased resistance to therapy, and cancels facilitation in coculture. Mathematical modeling quantifies the strength of competition and facilitation and predicts that blocking facilitation has the potential to control both resistant and sensitive cell populations and inhibit the emergence of a refractory population.
LRH-1 NUTRIGENOMICS: The Provision of Lauric Acid Results in the Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and LRH-1 Transactivation
Authors: Klatt KC , Zhang S. , Malysheva OV , Sun Z. , Dong B. , Brenna JT. , Moore DD. , Roberson MS. , Caudill MA 
Published: February 2021

ABSTRACTBackgroundThe unusual phosphatidylcholine species, dilauroylphosphatidylcholine (DLPC), has been reported to bind and activate the orphan nuclear receptor, liver receptor homolog-1 (LRH-1). To date, DLPC has not been reported endogenously in metabolomic databases.ObjectiveHerein, we test the hypothesis that the provision of the acyl constituent of DLPC, lauric acid (C12:0), a saturated fatty acid rich in tropical oils such as coconut oil, will 1) result in endogenous DLPC production and 2) enhance LRH-1 transcriptional activity.MethodsWe measured DLPC following provision of C12:0 to HepG2 cells, C57/BL6J mice, and to healthy human participants in an acute, randomized, controlled cross-over trial. LRH-1fl/fland LRH-1fl/flAlbumin-Cre mice were used inex vivoandin vivoapproaches. to assess the impact of C12:0 on LRH-1 target gene expression. 1-13C-lauric acid and methyl-d9-choline were used to assess DLPC production dynamics.ResultsDLPC was not observed in any C12:0-free approach. Provision of C12:0 in the culture media or to C57/BL6J mice resulted in the rapid production of DLPC, including DLPC’s presence in multiple LRH-1 expressing tissues. Coconut oil-fed human participants exhibited DLPC in postprandial serum samples.Ex vivoand in vivoC12:0 provision resulted in increased mRNA expression of LRH-1 target genes, an effect that was not observed in hepatic knockout mice. Methyl-d9-choline administration revealed a complex reliance on CDP-choline-derived DLPC.ConclusionC12:0 provision results in endogenous production of the LRH-1 ligand, DLPC, and LRH-1 transcriptional activation phenotypes. Our findings highlight pleiotropic effects of lauric acid, a common hypercholesterolemic dietary saturated fatty acid, secondary to LRH-1 agonism.
Improved accuracy for automated counting of a fish in baited underwater videos for stock assessment
Authors: Connolly RM , Fairclough DV , Jinks EL , Ditria EM , Jackson G , Lopez-Marcano S , Olds AD , Jinks KI 
Published: February 2021

AbstractThe ongoing need to sustainably manage fishery resources necessitates fishery-independent monitoring of the status of fish stocks. Camera systems, particularly baited remote underwater video stations (BRUVS), are a widely-used and repeatable method for monitoring relative abundance, required for building stock assessment models. The potential for BRUVS-based monitoring is restricted, however, by the substantial costs of manual data extraction from videos. Computer vision, in particular deep learning models, are increasingly being used to automatically detect and count fish at low abundances in videos. One of the advantages of BRUVS is that bait attractants help to reliably detect species in relatively short deployments (e.g. 1 hr). The high abundances of fish attracted to BRUVS, however, make computer vision more difficult, because fish often occlude other fish. We build upon existing deep learning methods for identifying and counting a target fisheries species across a wide range of fish abundances. Using BRUVS imagery targeting a recovering fishery species, Australian snapper (Chrysophrys auratus), we tested combinations of three further mathematical steps likely to generate accurate, efficient automation: 1) varying confidence thresholds (CTs), 2) on/off use of sequential non-maximum suppression (Seq-NMS), and 3) statistical correction equations. Output from the deep learning model was accurate at very low abundances of snapper; at higher abundances, however, the model over-predicted counts by as much as 50%. The procedure providing the most accurate counts across all fish abundances, with counts either correct or within 1 to 2 of manual counts (R2= 93.4%), used Seq-NMS, a 55% confidence threshold, and a cubic polynomial corrective equation. The optimised modelling provides an automated procedure offering an effective and efficient method for accurately identifying and counting snapper in BRUV footage. Further testing is required to ensure that automated counts of snapper remain accurate in the survey region over time, and to determine the applicability to other regions within the distributional range of this species. For monitoring stocks of fishery species more generally, the specific equations will differ but the procedure demonstrated here would help to increase the usefulness of BRUVS, while decreasing costs.
Correlates of patient-reported cognitive performance with regard to disability
Authors: Van Laethem Delphine , De Cock Alexander , Van Schependom Jeroen , Benedict Ralph HB , Nagels Guy , D’hooghe Marie 
Published: February 2021

AbstractObjectivesThe patient-reported Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is inconsistently related to objective cognitive tests in multiple sclerosis (MS), while being strongly correlated with depression. In this study we test whether the relation between subjective and objective cognitive performance is moderated by physical disability, assessed by the Expanded Disability Status Scale (EDSS).Materials & MethodsFrom 275 MS patients who completed the patient-report MSNQ and the two-question screening tool for depression, we collected Symbol Digit Modalities Test (SDMT) and EDSS scores, indicators of respectively objective cognitive performance and physical disability. We analysed correlations between these variables in the total group and in three EDSS subgroups: Low 0.0 – 3.0, Medium 3.5 – 6.0 and High 6.5 – 9.0. We also investigated the use of a composite measure of cognitive impairment and depression.ResultsWe found no significant correlations between patient-reported MSNQ and SDMT scores in the total group or the EDSS subgroups. MSNQ scores correlated significantly with depression in all subgroups. After correcting for several variables, MSNQ scores contributed adversely to SDMT scores in the total group, not in any subgroup. MSNQ scores contributed significantly to the prediction of the composite measure of impairment in the total group and in all EDSS subgroups.ConclusionsThe relationship between measures of subjective and objective cognitive performance is not influenced by the patient’s level of physical disability. MSNQ scores are substantially influenced by depression, and reflect cognitive function to some degree. The patient-report MSNQ can be useful to identify patients requiring further (neuro)psychological assessment.
Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions
Authors: Manzoor Susan E , Zaman Shafquat , Whalley Celina , Inglis David , Bosworth Andrew , Kidd Michael , Shabir Sahida , Quraishi Nabil , Green Christopher A , Iqbal Tariq , Beggs Andrew D 
Published: February 2021

ABSTRACTIntroductionFaecal transplantation is an evidence based treatment forClostridiodes difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for FMT, spiked samples and asymptomatic inpatients in an acute surgical unit.MethodsKilled SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool & FMT and a linear dilution series from 10−1to 10−5and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested.ResultsIn a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10−2dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10−1with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR.ConclusionsRT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool.
Association Between Preparedness and Response Measures and COVID-19 Incidence and Mortality
Authors: Lee Christopher T. , Buissonnière Marine , McClelland Amanda , Frieden Thomas R. 
Published: February 2021

AbstractThe COVID-19 pandemic is the most disruptive global health threat in a century. We analyzed publicly available data on preparedness capacity, COVID-19 incidence and mortality, governance, and testing. Although other analyses have suggested that preparedness assessments do not correlate with effective pandemic response, we found that testing rates correlate with both COVID-19 incidence and mortality and strongly correlated with country preparedness capacity as measured by the Joint External Evaluation (JEE). There is a statistically significant association between preparedness capacities and COVID-19 case incidence and an independent association between governance and COVID-19 case and mortality rates. Legislation, surveillance, and risk communication capacities were associated with lower COVID-19 case incidence and mortality. Preparedness and governance are independently associated with COVID-19 pandemic severity. Preparedness capacities are not sufficient — capacity and governance are both critical to pandemic control. Countries must improve public health systems and implement strong government leadership.Article SummaryCountry preparedness capacities and country leadership policy response (governance) are both critically important to control pandemics. Without appropriate policy action, public health preparedness is insufficient for effective pandemic response.
Die hard in Lake Bourget! The case of Planktothrix rubescens
Authors: Moiron Marthe , Rimet Frédéric , Girel Cyrille , Jacquet Stéphan 
Published: February 2021

AbstractBlooms of Planktothrix rubescens have been recorded for 15 years in Lake Bourget (France), from 1995 to 2009. Then, the presence of this filamentous and toxic cyanobacterium became anecdotic between 2010 and 2015 and it was clearly thought that such a proliferation was over. However, against all odds, blooms occurred again in 2016 and 2017 despite apparent very low phosphorus concentrations in surface waters of the lake. Aims of this study were thus to explain the reasons of this come back in order to propose scenarios likely to be helpful to stakeholders who need to know if such proliferations may occur again in the future. We show that phosphorus input, both from the main tributaries to the lake and possibly from the sediments, were likely the triggers of the new development of the cyanobacterium since a minimum autumn/winter inoculum of P. rubescens was detected the year before. Then, the bloom, that was observed deeper than previous years, was associated to a conjunction of factors already well-known to favour the development of this very competitive species (i.e. mild winter temperature, water column stability, available light at depth, surface water transparency, low predation, etc…). Although many factors and processes could account for the occurrence and bloom of the cyanobacterium, not observed, measured or taken into account here, a plausible scenario could be proposed and may be useful to deciders. One thing remains unclear: where do the cyanobacterium hides when it is not observed during the routine monitoring survey and thus from which place it could initiate its development (nearshore, in the pelagic zone, from the sediment?), unless it is simply not sampled and observed due to methodological bias.
Identification of APOE4 modulators, targeted therapeutic candidates in Coronary Artery Disease, using Molecular Docking studies
Authors: Hazarika Lima , Sen Supriyo , Zawar Akshaykumar , Doshi Jitesh 
Published: February 2021

AbstractA significant genetic suspect for coronary artery disease is the pathological adaptation of apolipoprotein E4 (APOE4) through intramolecular interaction. With the prevailing evidences on APOE4 genotype and its prevalence in coronary artery disease, the present study has investigated the protein–ligand binding affinity and unveil the receptor binding abilities of different classes of ligands for APOE4 through molecular docking studies. Structural basis of APOE4 involvement in CAD suggests that the intramolecular domain interactions to be a suitable target for therapeutic intervention. Various classes of ligands including known drugs used in the treatment of CAD, fragment-based stabilizers and their similar structures and molecules with known bioactivity against APOE4 were screened for their binding affinity and further investigated for their interactions with APOE4. Computational studies show the benzyl amide derived structures to be useful candidates in modulation of APOE4. The dynamics of the binding analysis can be further achieved with an in-depth understanding of drug-receptor interactions performing molecular dynamic simulation studies.
Potent in vitro Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain
Authors: Ma Huan , Zeng Weihong , Meng Xiangzhi , Huang Xiaoxue , Yang Yunru , Zhao Dan , Zhou Peigen , Wang Xiaofang , Zhao Changcheng , Sun Yong , Wang Peihui , Ou Huichao , Hu Xiaowen , Xiang Yan , Jin Tengchuan 
Published: February 2021

AbstractCell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KDranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KDranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KDof 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL (∼0.043 nM) and 3.18 ng/mL (∼0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnosis reagents for COVID-19.ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics including SARS-CoV-2 targeting antibodies remains critical. Due to their small size (13-15 kDa), highly solubility and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multi-valent formats, compared to the conventional antibody. Here, we report a serial of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.