bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: September 2021

AbstractSevere acute respiratory syndrome corona virus 2 (SARS-CoV-2)/ coronavirus disease 2019 (COVID-19) infection is the leading cause of respiratory tract infection associated mortality worldwide. The aim of the current investigation was to identify the differentially expressed genes (DEGs) and enriched pathways in COVID-19 infection and its associated complications by bioinformatics analysis, and to provide potential targets for diagnosis and treatment. Valid next-generation sequencing (NGS) data of 93 COVID 19 samples and 100 non COVID 19 samples (GSE156063) were obtained from the Gene Expression Omnibus database. Gene ontology (GO) and REACTOME pathway enrichment analysis was conducted to identify the biological role of DEGs. In addition, a protein-protein interaction network, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network and receiver operating characteristic curve (ROC) analysis were used to identify the key genes. A total of 738 DEGs were identified, including 415 up regulated genes and 323 down regulated genes. Most of the DEGs were significantly enriched in immune system process, cell communication, immune system and signaling by NTRK1 (TRKA). Through PPI, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network analysis, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were selected as hub genes, which were expressed in COVID-19 samples relative to those in non COVID-19 samples, respectively. Among them, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were suggested to be diagonstic factors for COVID-19. The findings from this bioinformatics analysis study identified molecular mechanisms and the key hub genes that might contribute to COVID-19 infection and its associated complications.
Effects of arm swing amplitude and lower limb asymmetry on motor variability patterns during treadmill gait
Authors: Bailey Christopher A. , Hill Allen , Graham Ryan , Nantel Julie 
Published: September 2021

AbstractMotor variability is a fundamental feature of gait. Altered arm swing and lower limb asymmetry (LLA) may be contributing factors having been shown to affect the magnitude and dynamics of variability in spatiotemporal and trunk motion. However, the effects on lower limb joints remain unclear.Full-body kinematics of 15 healthy young adults were recorded during treadmill walking using the Computer-Assisted Rehabilitation Environment system. Participants completed six trials, combining three arm swing (AS) amplitude (normal, active, held) and two LLA (symmetrical, asymmetrical) conditions. The mean standard deviation (meanSD), maximum Lyapunov exponent (λmax), detrended fluctuation analysis scaling exponent of range of motion (DFAα), and sample entropy (SaEn) were computed for tridimensional trunk, pelvis, and lower limb joint angles, and compared using repeated-measures ANOVAs.Relative to normal AS, active AS increased meanSD of all joint angles, λmax of frontal plane hip and ankle angles, and SaEn of sagittal plane ankle angles. Active AS, however, did not affect λmax or SaEn of trunk or pelvis angles. LLA increased meanSD of sagittal plane joint angles, λmax of Euclidean norm trunk angle and of lower limb joint angles, and SaEn of ankle dorsiflexion/ plantarflexion, but decreased SaEn of tridimensional trunk angles and hip rotation in the slower moving leg.Alterations in lower limb variability with active AS and LLA suggest that young adults actively exploit their lower limb redundancies to maintain gait. This appears to preserve trunk stability and regularity during active AS but not during LLA.
Neutron crystallography reveals novel mechanisms used by Pseudomonas aeruginosa for host-cell binding
Authors: Gajdos Lukas , Blakeley Matthew P. , Haertlein Michael , Forsyth V. Trevor , Devos Juliette M. , Imberty Anne 
Published: September 2021

SummaryThe opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.
Deep-learning based retinal fluid segmentation in optical coherence tomography images using a cascade of ENets
Authors: Loizillon Sophie , Meurée Cédric , Breuil Camille , Faucon Timothée , Lambert Arnaud 
Published: September 2021

AbstractOptical coherence tomography (OCT) is a non-invasive, painless and reproducible examination which allows ophthalmologists to visualize retinal layers. This imaging modality is useful to detect diseases such as diabetic macular edema (DME) or age related macular degeneration (AMD), which are associated with fluid accumulations. In this paper, a cascade of deep convolutional neural networks is proposed using ENets for the segmentation of fluid accumulations in OCT B-Scans. After denoising the B-Scans, a first ENet extracts the region of interest (ROI) between the inner limiting membrane (ILM) and the Bruch’s membrane (BM), whereas the second ENet segments the fluid in the ROI. A random forest classifier was applied on the segmented fluid regions to reject false positive. Our framework was trained on three different datasets with several diseases such as diabetic retinopathy (DR) and AMD. Our method achieves an average Dice Score for fluid segmentation of 0.80, 0.83 and 0.83 on the UMN DME, UMN AMD and Kermany datasets respectively.
Regulation of membrane homeostasis by TMC1 mechanoelectrical transduction channels is essential for hearing
Authors: Ballesteros Angela , Swartz Kenton J. 
Published: September 2021

ABSTRACTThe mechanoelectrical transduction (MET) channel complex of auditory hair cells converts sound into electrical signals, allowing us to hear. After decades of research, the transmembrane-like channel 1 and 2 (TMC1 and TMC2) have been recently identified as pore-forming subunits of the MET channels, but the molecular peculiarity that differentiates these two proteins and makes TMC1 essential for hearing remains elusive. Here, we show that TMC1, but not TMC2, is essential for membrane remodeling triggered by a decrease in intracellular calcium concentration. We demonstrate that inhibition of MET channels or buffering of intracellular calcium lead to pronounced phosphatidylserine externalization, membrane blebbing and ectosome release at the hair cell sensory organelle, culminating in the loss of TMC1 protein. Moreover, three TMC1 deafness-causing mutations cause constitutive phosphatidylserine externalization that correlates with the deafness phenotype, suggesting that the mechanisms of hearing loss involve alterations in membrane homeostasis.
Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1
Authors: To Albert , Wong Teri Ann S. , Lieberman Michael M. , Thompson Karen , Pessaint Laurent , Greenhouse Jack , Daham Nisrine , Cook Anthony , Narvaez Brandon , Flinchbaugh Zack , Ry Alex Van , Yalley-Ogunro Jake , Elyard Hanne Andersen , Lai Chih-Yun , Donini Oreola , Lehrer Axel T. 
Published: September 2021

AbstractFDA-approved and Emergency Use Authorized (EUA) vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease, however, information on their long-term efficacy and protective breadth against SARS-CoV-2 Variants of Concern (VOCs) is currently scarce. Here we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT™ in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], B.1.617 [Delta]) for at least 3 months after the final boost. Protective efficacy and post-exposure immunity were evaluated using a heterologous P.1 challenge nearly 3 months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Post-challenge IgG concentrations were restored to peak immunity levels and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (non-vaccinated but challenged) macaques suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide long-lasting and protective immunity against circulating VOCs.One Sentence SummaryA recombinant subunit protein formulated with CoVaccine HT™ adjuvant induces superior immunity than natural infection and reduces viral load while protecting cynomolgus macaques from COVID-19-like disease caused by late SARS-CoV-2 P.1 (Gamma) challenge.
SARS-CoV-2 Transmission Potential and Policy Changes in South Carolina, February 2020 – January 2021
Authors: Davies Margaret R. , Hua Xinyi , Jacobs Terrence D. , Wiggill Gabi I. , Lai Po-Ying , Du Zhanwei , DebRoy Swati , Robb Sara Wagner , Chowell Gerardo , Hai Fung Isaac Chun 
Published: September 2021

AbstractIntroductionWe aimed to examine how public health policies influenced the dynamics of COVID-19 time-varying reproductive number (Rt) in South Carolina from February 26, 2020 to January 1, 2021.MethodsCOVID-19 case series (March 6, 2020 - January 10, 2021) were shifted by 9 days to approximate the infection date. We analyzed the effects of state and county policies on Rt using EpiEstim. We performed linear regression to evaluate if per-capita cumulative case count varies across counties with different population size.ResultsRt shifted from 2-3 in March to <1 during April and May. Rt rose over the summer and stayed between 1.4 and 0.7. The introduction of statewide mask mandates was associated with a decline in Rt (−15.3%; 95% CrI, -13.6%, -16.8%), and school re-opening, an increase by 12.3% (95% CrI, 10.1%, 14.4%). Less densely populated counties had higher attack rate (p<0.0001).ConclusionThe Rt dynamics over time indicated that public health interventions substantially slowed COVID-19 transmission in South Carolina, while their relaxation may have promoted further transmission. Policies encouraging people to stay home, such as closing non-essential businesses, were associated with Rt reduction, while policies that encouraged more movement, such as re-opening schools, were associated with Rt increase.
Induction of robust neutralizing antibodies against the COVID-19 Delta variant with ChAdOx1 nCoV-19 or BNT162b2 as a booster following a primary vaccination series with CoronaVac
Authors: Patamatamkul Samadhi , Thammawat Sutthiwan , Buranrat Benjaporn 
Published: September 2021

AbstractWe determined the antibody response among CoronaVac vaccinees who were boosted with either BNT162b2 or ChAdOx1 nCoV-19. Increase in anti-S-RBD antibodies and surrogate neutralizing antibodies against the Delta variant was higher in BNT162b2 recipients than in ChAdOx1 nCoV-19 recipients. High proportions of reactogenicity were seen for both booster regimens.
Functional Data Analysis: Transition from Daily Observation of COVID-19 Prevalence in France to Functional Curves
Authors: Oshinubi Kayode , Ibrahim Firas , Rachdi Mustapha , Demongeot Jacques 
Published: September 2021

AbstractIn this paper we use the technique of functional data analysis to model daily hospitalized, deceased, ICU cases and return home patient numbers along the COVID-19 outbreak, considered as functional data across different departments in France while our response variables are numbers of vaccinations, deaths, infected, recovered and tests in France. These sets of data were considered before and after vaccination started in France. We used some smoothing techniques to smooth our data set, then analysis based on functional principal components method was performed, clustering using k-means techniques was done to understand the dynamics of the pandemic in different French departments according to their geographical location on France map and we also performed canonical correlations analysis between variables. Finally, we made some predictions to assess the accuracy of the method using functional linear regression models.
Modeling of COVID-19 Transmission Dynamics on US Population: Inter-transfer Infection in Age Groups, Mutant Variants and Vaccination Strategies
Authors: Roy Jyotirmoy , Heath Samuel , Ramkrishna Doraiswami , Wang Shiyan 
Published: September 2021

AbstractThe in-depth understanding of the dynamics of COVID-19 transmission among different age groups is of great interest for governments and health authorities so that strategies can be devised to reduce the pandemic’s detrimental effects. We developed the SIRDV-Virulence epidemiological model based on a population balance equation to study the effect of mutants of the virus and the effect of vaccination strategies on mitigating the transmission among the population in the United States. Based on the available data from the Centers for Disease Control and Prevention (CDC), we obtain the key parameters governing the dynamic evolution of the spread of the COVID-19 pandemic. In the context studied, the results show that a large fraction of infected cases comes from the adult and children populations in the presence of a mutant variant of COVID-19 with high infection rates. We further investigate the optimum vaccine distribution strategy among different age groups. Given the current situation in the United States, the results show that prioritizing children and adult vaccinations over that of seniors can contain the spread of the active cases, thereby preventing the healthcare system from being overwhelmed and minimizing subsequent deaths. The model suggests that the only option to curb the effects of this pandemic is to reduce the population of unvaccinated individuals. A higher fraction of ‘Anti/Non-vaxxers’ can lead to the resurgence of the pandemic.Author summaryThe changing dynamics of the COVID-19 pandemic are primarily due to the mutations of the SARS-CoV-2 virus. It is often seen that these mutants not only have a higher infection rate but also evade the presently administered vaccines. To consider the fact that different age population groups are affected to varied extent by these mutants, we build a mathematical model to account for the inter-transfer infection among age groups, which can predict the overall COVID-19 transmission in the United States. The parameter quantification of our mathematical model is based on the public data for infected cases, deaths and vaccinated from the Centers for Disease Control and Prevention (CDC). Additionally, our study shows that the vaccine distribution strategies should be developed with a priority given to the most infected age groups in order to curb the total infected and death cases. We also show how the ‘Anti/Non-vaxxers’ can be a potential reason for resurgence of the pandemic. These results are of immediate practical application in determining future vaccine distribution regarding to the pandemic and ensuring the health care system is ready to deal with the worst-case scenario with a very high infection rate.
Control of subunit stoichiometry in single-chain MspA nanopores
Authors: Pavlenok Mikhail , Yu Luning , Herrmann Dominik , Wanunu Meni , Niederweis Michael 
Published: September 2021

ABSTRACTTransmembrane protein channels enable fast and highly sensitive electrical detection of single molecules. Nanopore sequencing of DNA was achieved using an engineered Mycobacterium smegmatis porin A (MspA) in combination with a motor enzyme. Due to its favorable channel geometry, the octameric MspA pore exhibits the highest current level as compared to other pore proteins. To date, MspA is the only protein nanopore with a published record of DNA sequencing. While widely used in commercial devices, nanopore sequencing of DNA suffers from significant base-calling errors due to stochastic events of the complex DNA-motor-pore combination and the contribution of up to five nucleotides to the signal at each position. Asymmetric mutations within subunits of the channel protein offer an enormous potential to improve nucleotide resolution and sequencing accuracy. However, random subunit assembly does not allow control of the channel composition of MspA and other oligomeric protein pores. In this study, we showed that it is feasible to convert octameric MspA into a single-chain pore by connecting eight subunits using peptide linkers. We constructed single-chain MspA trimers, pentamers, hexamers and heptamers to demonstrate that it is feasible to alter the subunit stoichiometry and the MspA pore diameter. All single-chain MspA proteins formed functional channels in lipid bilayer experiments. Importantly, we demonstrated that single-chain MspA discriminated all four nucleotides identical to MspA produced from monomers. Thus, single-chain MspA constitutes a new milestone in its development and adaptation as a biosensor for DNA sequencing and many other applications.STATEMENT OF SIGNFICANCENanopore sequencing of DNA is a fast and cheap technology that uniquely delivers multi-kilobase reads. It is currently used world-wide in many applications such as genome sequencing, epigenetics, and surveillance of viral and bacterial pathogens and has started to revolutionize human lives in medicine, agriculture and environmental studies. However, the high base-calling error rates prevent nanopore DNA sequencing from reaching its full potential. In this study, we converted octameric MspA into a single-chain pore enabling asymmetric mutations to fine-tune the pore geometry and chemistry and address the shortcomings of nanopores. Thus, single-chain MspA constitutes a new milestone in its development and adaptation as a biosensor for DNA sequencing and many other applications.
In-silico analysis: common biomarkers of NDs
Authors: Sarkar Deepanjan , Chakraborty Souvik , Bhowmick Sushmita , Maiti Tarasankar 
Published: September 2021

AbstractNeurodegenerative disorders (NDs) are a class of rapidly rising devastating diseases and the reason behind are might be an improper function of related genes or a mutation in a particular gene or even could be autoimmune also. Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington’s disease (HD) are some of the NDs, and still, incurable fully. Apart from the similarities in symptoms, there are common genes that express somehow a differential manner in patients of PDs, MSs, and HDs. A total of 1197 differentially expressed genes (DEGs) are obtained by analyzing the chosen datasets. The protein interactions by STRING online tool and degree sorted hubs obtained through a plug-in in Cytoscape; Cyto-Hubba. Among the sorted hubs KRAS, CREB1, PIK3CA, JAK2 are the ones that are not only common to all the studied datasets of NDs but also in other neurological disorders like Alzheimer’s. The enriched pathways with biological process, molecular function, cellular component, and KEGG pathway details are obtained and analyzed using Enricher. This paper frames that the obtained hub genes could be potential biomarkers also and a need for further drug design for finding a possible cure.
In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
Authors: Maes Michael , Del Tedesco Junior Walton Luiz , Lozovoy Marcell Alysson Batisti , Mori Mayara Tiemi Enokida , Danellii Tiago , Delicato de Almeida Elaine Regina , Tejo Alexandre Mestre , Tano Zuleica Naomi , Reiche Edna Maria Vissoci , Simão Andréa Name Colado 
Published: September 2021

AbstractBackgroundIn COVID-19, the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection. Acute infections are accompanied by a sickness symptom complex (SSC) which is a highly conserved symptom complex that protects against infections and hyperinflammation. Aims: To examine the associations of COVID-19, SSC and the NLPR3 rs10157379 T>C and NLPR3 rs10754558 C>G SNV variants; and the protective role of SSC in severe acute respiratory syndrome (SARS)-CoV-2 infection.MethodsWe recruited COVID-19 patients, 308 with critical, 63 with moderate and 157 with mild disease.ResultsIncreased SSC protects against SARS, critical disease, and death due to COVID-19. Increasing age, male sex and rs10754558 CG significantly predict reduced SSC protection. The rs10157379 CT and rs10754558 GG genotypes are positively associated with SARS. Partial Least Squares analysis shows a) that 41.8% of the variance in critical COVID-19 symptoms could be explained by SSC and oxygen saturation (inversely associated), and inflammation, chest computed tomography abnormalities, increased body mass index, SARS and age (positively associated); and b) the effects of the NLRP3 rs10157379 and rs10754558 variants on critical COVID-19 are mediated via SSC (protective) and SARS (detrimental). SSC includes anosmia, dysgeusia and gastrointestinal symptoms.ConclusionsIntersections among the rs10754558 variant, age, and sex increase risk towards critical COVID-19 by attenuating SSC. NLRP3 variants play an important role in SARS, and severe and critical COVID-19 especially in individuals with reduced SSC, elderly people, and those with increased BMI, hypertension, and diabetes type 2. SSC is a new drug target to combat acute COVID-19.