bluuebunny/crossref_metadata_2025 huggingface dataset:
A cautionary note on recall vaccination in ex-COVID-19 subjects
Authors: Levi Riccardo , Azzolini Elena , Pozzi Chiara , Ubaldi Leonardo , Lagioia Michele , Mantovani Alberto , Rescigno Maria
Published: February 2021

Currently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naïve subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. This poses caution for ExCOVID subjects to receive a second jab both because they may have a overreaction of the inflammatory response and also in light of the current vaccine shortage.
A claims-based score for the prediction of bleeding in a contemporary cohort of patients receiving oral anticoagulation for venous thromboembolism
Authors: Alonso Alvaro , Norby Faye L. , MacLehose Richard F. , Zakai Neil A. , Walker Rob F. , Adam Terrence J. , Lutsey Pamela L.
Published: February 2021

Background

Current scores for bleeding risk assessment in patients with venous thromboembolism (VTE) undergoing oral anticoagulation (OAC) have limited predictive capacity. We developed and internally validated a bleeding prediction model using healthcare claims data.

Methods and Results

We selected patients with incident VTE in the 2011-2017 MarketScan databases initiating OAC. Hospitalized bleeding events were identified using validated algorithms in the 180 days after VTE diagnosis. We evaluated demographic factors, comorbidities, and medication use prior to OAC initiation as potential predictors of bleeding using stepwise selection of variables in Cox models ran on 1000 bootstrap samples of the patient population. Variables included in >60% of all models were selected for the final analysis. We internally validated the model using bootstrapping and correcting for optimism. We included 165,434 VTE patients initiating OAC, of which 2,294 had a bleeding event. After undergoing the variable selection process, the final model included 20 terms (15 main effects and 5 interactions). The c-statistic for the final model was 0.68 (95% confidence interval [CI] 0.67-0.69). The internally validated c-statistic corrected for optimism was 0.68 (95%CI 0.67-0.69). For comparison, the c-statistic of the HAS-BLED score in this population was 0.62 (95%CI 0.61-0.63).

Conclusion

We have developed a novel model for bleeding prediction in VTE using large healthcare claims databases. Performance of the model was moderately good, highlighting the urgent need to identify better predictors of bleeding to inform treatment decisions.
One Year of Evidence on Mental Health Disorders in China during the COVID-19 Crisis - A Systematic Review and Meta-Analysis
Authors: Chen Xi , Chen Jiyao , Zhang Meimei , Chen Richard Z. , Dong Rebecca Kechen , Dong Zhe , Ye Yingying , Tong Lingyao , Chen Bryan Z. , Zhao Ruiying , Cao Wenrui , Li Peikai , Zhang Stephen X.
Published: February 2021

This paper provides a systematic review and meta-analysis on the prevalence rate of mental health issues of general population, general and frontline healthcare workers (HCWs) in China over one year of the COVID-19 crisis. We systematically searched PubMed, Embase, Web of Science, and Medrxiv at November 16th, 2020, pooled data using random-effects meta-analyses to estimate the prevalence rates, and ran meta-regression to tease out the heterogeneity. The meta-regression results uncovered several predictors of the prevalence rates, including severity, type of mental issues, population, sampling location, and study quality. Pooled prevalence rates are significantly different from, yet largely between, the findings of previous meta-analyses, suggesting the results of our larger study are consistent with yet more accurate than the findings of the smaller, previous meta-analyses. The prevalence rates of distress and insomnia and those of frontline HCWs are higher suggest future research and interventions should pay more attention to those mental outcomes and populations. Our findings suggest a need to examine the prevalence rates at varying levels of severity. The one-year cumulative evidence on sampling locations (Wuhan vs. non-Wuhan) corroborates the typhoon eye effect theory.

Trial registration

CRD4202022059
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

Resumé

Combined 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

Background

Wastewater 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.

Objectives

This 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.

Methods

This 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.

Discussion

Our 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

Background

The cyclic nucleotides cAMP and cGMP inhibit platelet activation.

Results

We 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.

Conclusions

We 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

The 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

Background

The 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.

Objective

Herein, 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.

Methods

We 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.

Results

DLPC 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.

Conclusion

C12:0 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

The 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

Objectives

The 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 & Methods

From 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.

Results

We 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.

Conclusions

The 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

Introduction

Faecal 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.

Methods

Killed 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.

Results

In 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.

Conclusions

RT-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

The 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 Summary

Country 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

Blooms 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

A 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

Cell 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.

Importance

To 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.
Assigning Secondary Structure in Proteins using AI
Authors: Antony Jisna Vellara , Madhu Prayagh , Balakrishnan Jayaraj Pottekkattuvalappil
Published: February 2021

Knowledge about protein structure assignment enriches the structural and functional understanding of proteins. Accurate and reliable structure assignment data is crucial for secondary structure prediction systems. Since the ’80s various methods based on hydrogen bond analysis and atomic coordinate geometry, followed by Machine Learning, have been employed in protein structure assignment. However, the assignment process becomes challenging when missing atoms are present in protein files. Our model develops a multi-class classifier program named DLFSA for assigning protein Secondary Structure Elements(SSE) using Convolutional Neural Networks(CNN). A fast and efficient GPU based parallel procedure extracts fragments from protein files. The model implemented in this work is trained with a subset of protein fragments and achieves 88.1% and 82.5% train and test accuracy, respectively. Our model uses only Cαcoordinates for secondary structure assignments. The model is successfully tested on a few full-length proteins also. Results from the fragment-based studies demonstrate the feasibility of applying deep learning solutions for structure assignment problems.
System Analysis of the Sequencing Quality of Human Whole Exome Samples on Bgi Ngs Platform
Authors: Belova Vera , Pavlova Anna , Afasizhev Robert , Moskalenko Viktoria , Korzhanova Margarita , Cheranev Valery , Krivoy Andrey , Nikashin Boris , Bulusheva Irina , Rebrikov Denis , Korostin Dmitriy
Published: February 2021

Human whole exome sequencing (WES) is now the standard for most medical genetics applications worldwide. The leaders are manufacturers of enrichment kits that base their protocols on a hybridization approach using cRNA or cDNA biotinylated samples specific to regions of interest in the genome. Recently, platforms from the Chinese company MGI Tech have been successfully promoted in the markets of many countries in Europe and Asia. There is no longer any question about their reliability and the quality of the data obtained. However, very few task-specific kits for WES, in particular, are presented for these sequencers. We have developed our solution for library pre-capture pooling and exome enrichment using Agilent probes. In this work, we demonstrate on a set of standard benchmark samples from the Platinum Genome Collection that our protocol, called “RSMU_exome”, is superior to the kit from MGI Tech in qualitative and quantitative terms. It allows detecting more SNVs and CNVs with superior sensitivity and specificity values, generates fewer PCR duplicates, allows more samples to be pooled in a single enrichment, and requires less raw data to produce results comparable to the MGI Tech solution. Also, our protocol is significantly cheaper than the kit from the Chinese manufacturer.
INCORPORATING A DYNAMIC GENE-BASED PROCESS MODULE INTO A CROP SIMULATION MODEL
Authors: Oliveira Fabio A.A. , Jones James W. , Pavan Willingthon , Bhakta Mehul , Vallejos C. Eduardo , Correll Melanie J. , Boote Kenneth J. , Fernandes José M.C. , Hölbig Carlos A. , Hoogenboom Gerrit
Published: February 2021

Dynamic crop simulation models are tools that predict plant phenotype grown in specific environments for genotypes using genotype-specific parameters (GSPs), often referred to as “genetic coefficients.” These GSPs are estimated using phenotypic observations and may not represent “true” genetic information. Instead, estimating GSPs requires experiments to measure phenotypic responses when new cultivars are released. The goal of this study was to evaluate a new approach that incorporates a dynamic gene-based module for simulating time-to-flowering for common bean (Phaseolus vulgarisL.) into an existing dynamic crop model. A multi-environment study conducted in 2011 and 2012 included 187 recombinant inbred lines (RILs) from a bi-parental bean family to measure the effects of quantitative trait loci (QTL), environment (E), and QTL×E interactions across five sites. The dynamic mixed linear model from Vallejos et al. (2020) was modified in this study to create a dynamic module that was then integrated into the CSM-CROPGRO-Drybean model. This new hybrid crop model, with the gene-based flowering module replacing the original flowering component, requires allelic makeup of each genotype being simulated and daily E data. The hybrid model was compared to the original CSM model using the same E data and previously estimated GSPs to simulate time-to-flower. The integrated gene-based module simulated days of first flower agreed closely with observed values (root mean square error of 2.73 days and model efficiency of 0.90) across the five locations and 187 genotypes. The hybrid model with its gene-based module also described most of the G, E and G×E effects on time-to-flower and was able to predict final yield and other outputs simulated by the original CSM. These results provide the first evidence that dynamic crop simulation models can be transformed into gene-based models by replacing an existing process module with a gene-based module for simulating the same process.
Identification of the SHREK family of proteins as broad-spectrum host antiviral factors
Authors: Dabbagh Deemah , He Sijia , Hetrick Brian , Chilin Linda , Andalibi Ali , Wu Yuntao
Published: February 2021

Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123), that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 virus-like particle. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.
Structure of plant PSI-plastocyanin complex reveals strong hydrophobic interactions
Authors: Caspy Ido , Fadeeva Mariia , Kuhlgert Sebastian , Borovikova-Sheinker Anna , Klaiman Daniel , Masrati Gal , Drepper Friedel , Ben-Tal Nir , Hippler Michael , Nelson Nathan
Published: February 2021

Photosystem I is defined as plastocyanin-ferredoxin oxidoreductase. Taking advantage of genetic engineering, kinetic analyses and cryo-EM, our data provide novel mechanistic insights into binding and electron transfer between PSI and Pc. Structural data at 2.74 Å resolution reveals strong hydrophobic interactions in the plant PSI-Pc ternary complex, leading to exclusion of water molecules from PsaA-PsaB / Pc interface once the PSI-Pc complex forms. Upon oxidation of Pc, a slight tilt of bound oxidized Pc allows water molecules to accommodate the space between Pc and PSI to drive Pc dissociation. Such a scenario is consistent with the six times larger dissociation constant of oxidized as compared to reduced Pc and mechanistically explains how this molecular machine optimized electron transfer for fast turnover.

One Sentence Summary

Genetic engineering, kinetics and cryo-EM structural data reveal a mechanism in a major step of oxygenic photosynthesis
Bacterial expression and purification of functional recombinant SARS-CoV-2 spike receptor binding domain
Authors: Prahlad Janani , Struble Lucas R. , Lutz William E. , Wallin Savanna A. , Khurana Surender , Schnaubelt Andy , Broadhurst Mara J. , Bayles Kenneth W. , Borgstahl Gloria E. O.
Published: February 2021

The COVID-19 pandemic caused by SARS-CoV-2 has applied significant pressure on overtaxed healthcare around the world, underscoring the urgent need for rapid diagnosis and treatment. We have developed a bacterial strategy for the expression and purification of the SARS-CoV-2 spike protein receptor binding domain using the CyDisCo system to create and maintain the correct disulfide bonds for protein integrity and functionality. We show that it is possible to quickly and inexpensively produce functional, active antigen in bacteria capable of recognizing and binding to the ACE2 (angiotensin-converting enzyme) receptor as well as antibodies in COVID-19 patient sera.
Low-pass sequencing increases the power of GWAS and decreases measurement error of polygenic risk scores compared to genotyping arrays
Authors: Li Jeremiah H. , Mazur Chase A. , Berisa Tomaz , Pickrell Joseph K.
Published: February 2021

Low-pass sequencing (sequencing a genome to an average depth less than 1× coverage) combined with genotype imputation has been proposed as an alternative to genotyping arrays for trait mapping and calculation of polygenic scores. To empirically assess the relative performance of these technologies for different applications, we performed low-pass sequencing (targeting coverage levels of 0.5× and 1×) and array genotyping (using the Illumina Global Screening Array [GSA]) on 120 DNA samples derived from African- and European-ancestry individuals that are part of the 1000 Genomes Project. We then imputed both the sequencing data and the genotyping array data to the 1000 Genomes Phase 3 haplotype reference panel using a leave-one-out design. We evaluated overall imputation accuracy from these different assays as well as overall power for GWAS from imputed data and computed polygenic risk scores for coronary artery disease and breast cancer using previously derived weights. We conclude that low-pass sequencing plus imputation, in addition to providing a substantial increase in statistical power for genome-wide association studies, provides increased accuracy for polygenic risk prediction at effective coverages of ∼0.5× and higher compared to the Illumina GSA.
Unpacking the effects of star architecture projects
Authors: Alaily-Mattar Nadia , Bartmanski Dominik , Dreher Johannes , Koch Michael , Löw Martina , Pape Timothy , Thierstein Alain
Published: February 2021

Purpose

To explain the process of how star architecture projects generate impact, one must first describe the outputs of such projects and then unpack the wide array of potential effects, which are generated by these outputs. This requires the application of multi-disciplinary research perspectives. Only then can one begin to systematically analyse the long-term impacts. The purpose of this paper is to illustrate how the complexity of such multi-disciplinary research exercise can be managed through the application of a methodological strategy aided by a conceptual impact model.

Design/methodology/approach

A conceptual impact model is presented, which describes the process of the development of star architecture projects, the various outputs of these projects and the possible effects generated by these outputs. The effects of three case study star architecture projects are discussed.

Findings

Empirical research findings indicate that while the isolation of effects serves the operationalisation of research, the investigation of the impact of star architecture projects on their respective cities must draw on the intertwinement of the fields of urban economy, society and morphology. The paper concludes by arguing for the application of the described methodological strategy as the basis for understanding in which dimensions a star architecture project generates impacts.

Practical implications

The potential of the proposed impact model for urban analysis when considered as a field of intertwined relations is demonstrated in this article. It helps to reveal how particular local developments change the city significantly in socio-cultural and spatial terms.

Originality/value

The transformative impact of star architecture projects and the role of economic and other effects in this process has hardly been studied, particularly in small and medium-sized cities. This article presents a unique multi-disciplinary research project approached consecutively in the aforementioned fields.
Developing a methodology to create nutritionally balanced meals
Authors: Giazitzi Katerina , Boskou George
Published: February 2021

Purpose

The purpose of the present study was to develop a methodology for the creation of nutritionally balanced (NB) recipes and meals.

Design/methodology/approach

Nutritional criteria were set for energy, fats, saturated fats, carbohydrates, sugars and salt. A sample of 50 main courses and 29 salads was evaluated and nutritionally reformulated to meet the criteria. One sample t-test, paired sample t-test, Pearson correlation coefficient and linear regression analysis were performed.

Findings

The original main courses and salads did not meet the nutritional criteria for fats and energy. Both original and NB main courses had high mean protein content. The reformulation of recipes caused a significant change on the provided energy (−50.2%), fats (−57.6%), saturated fats (−58.8%), carbohydrates (−24.2%), proteins (−35.6%) and salt (−53.8%) for the salads (p = 0.001). Accordingly, reformulation of recipes caused a significant change on provided energy (−38.4%), fats (−55.2%), saturated fats (−58.3%), proteins (−25.9%) and salt (−50%) for the main courses (p < 0.001). Predictive models (linear regression analysis) for fats (R2 = 0.345), proteins (R2 = 0.876) and carbohydrates (R2 = 0.797) on the NB recipes were performed.

Originality/value

This is the first attempt to improve the nutritional value of cooking recipes, based on specific nutritional criteria. A methodological procedure for the creation of NB meals is proposed. This methodology could be a useful tool for the nutritionists and chefs, which, in a context of cooperation, could create databases and cooking books with NB recipes easily accessed to public and caterers. The recipes that constitute NB meals could guarantee the standardization of the recipes' reformulation, within a certification standard for restaurants.
Digital divide in the major regions of the world and the possibility of convergence
Authors: Inegbedion Henry Egbezien
Published: February 2021

Purpose

The purpose of this paper is to investigate the nature of the inequalities in the usage of the internet and inequalities in the growth rate in the usage of the internet, and thus ascertain the possibility of convergence of the digital divide between the major regions of the world.

Design/methodology/approach

The design was a longitudinal study of the usage of internet and growth rate in the usage of the internet in the different regions of the world for the period 2009–2019. The quantitative research method was used. Simple percentages and F-test were used in data analysis.

Findings

The usage of internet in Asia and Europe is higher than all the other regions in the world but there is no significant difference in usage between the other regions. The results further showed that some of the digitally disadvantaged regions had higher growth rates in the usage of the internet and these digitally disadvantage states are not disadvantaged in access to smartphones and the emerging 5G technology, thus suggesting the possibility of imminent convergence in access to the internet given the increasing usage of smartphones for the internet subscription.

Research limitations/implications

The focus on internet usage in the major regions of the world without recourse to the variability of the usage and growth rate of internet usage within the regions. The dearth of the empirical literature on quantitative research on the research problem was another constraint. Finally, restriction in available statistics on digital divide constrained the use of 2009–2019 as the periodic scope of the study.

Practical implications

Inclusion of ICT in the school curricula of the component states to acquaint them with information and communication technology (ICT) usage at an early stage, as well as provision of the enabling environment for business to thrive and through a national culture that will encourage businesses to be vibrant, and thus lay a foundation for future convergence.

Social implications

Enhancement in employment opportunities through the increased investment in the ICT facilities and the subsequent reduction in social vices.

Originality/value

Use of secondary data through a longitudinal design to categorically indicate the differences between the different regions of the world in terms of internet usage, as well as the empirical determination of the discrepancies between the growth rates in the access to internet and usage of internet by different regions of the world, especially as regard some of the digitally disadvantaged regions having higher growth rates in the usage of the internet than the perceived digitally advantaged regions.