bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
Authors: Pita-Thomas Wolfgang , Gonçalves Tassia Mangetti , Zhao Guoyan , Cavalli Valeria 
Published: March 2021

ABSTRACTRetinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote RGC axon regeneration, we identified transcription factors (TF) and chromatin accessible sites enriched in embryonic RGCs (high axon growth capacity) compared to postnatal RGC (low axon growth capacity). Developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the differentially opened regions of the chromatin in embryonic RGCs and proteomic analysis confirmed their expression in RGC nuclei. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon growth. Consistently, overexpression of CREB fused to the VP64 transactivation domain in RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.
The localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York State
Authors: Lasek-Nesselquist Erica , Lapierre Pascal , Schneider Erasmus , George Kirsten St. , Pata Janice 
Published: March 2021

AbstractThe E484K mutation in the spike protein of SARS CoV-2 contributes to immune escape from monoclonal antibodies as well as neutralizing antibodies in COVID-19 convalescent plasma. It appears in two variants of concern – B.1.351 and P.1 - but has evolved multiple times in different SARS-CoV-2 lineages, suggesting an adaptive advantage. Here we report on the emergence of a 484K variant in the B.1.526 lineage that has recently become prevalent in New York State, particularly in the New York City metropolitan area. In addition to the E484K mutation, these variants also harbor a D235G substitution in spike that might help to reduce the efficacy of neutralizing antibodies.
Long-Term SARS-CoV-2-Specific Immune and Inflammatory Responses Across a Clinically Diverse Cohort of Individuals Recovering from COVID-19
Authors: Peluso Michael J. , Deitchman Amelia N. , Torres Leonel , Iyer Nikita S. , Nixon Christopher C. , Munter Sadie E. , Donatelli Joanna , Thanh Cassandra , Takahashi Saki , Hakim Jill , Turcios Keirstinne , Janson Owen , Hoh Rebecca , Tai Viva , Hernandez Yanel , Fehrman Emily , Spinelli Matthew A. , Gandhi Monica , Trinh Lan , Wrin Terri , Petropoulos Christos J. , Aweeka Francesca T. , Rodriguez-Barraquer Isabel , Kelly J. Daniel , Martin Jeffrey N. , Deeks Steven G. , Greenhouse Bryan , Rutishauser Rachel L. , Henrich Timothy J. 
Published: March 2021

ABSTRACTA detailed understanding of long-term SARS-CoV-2-specific T cell responses and their relationship to humoral immunity and markers of inflammation in diverse groups of individuals representing the spectrum of COVID-19 illness and recovery is urgently needed. Data are also lacking as to whether and how adaptive immune and inflammatory responses differ in individuals that experience persistent symptomatic sequelae months following acute infection compared to those with complete, rapid recovery. We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally up to 9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection. The participants had varying degrees of initial disease severity and were enrolled in the northern California Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort. Adaptive T cell responses remained remarkably stable in all participants across disease severity during the entire study interval. Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated with higher long-term SARS-CoV2-specific CD8+ T cell responses, independent of initial disease severity or age. Neutralizing antibody levels were strongly correlated with SARS-CoV-2-specific CD4+ T but not CD8+ T cell responses. Importantly, we did not identify substantial differences in long-term virus-specific T cell or antibody responses between participants with and without COVID-19-related symptoms that persist months after initial infection.
Mathematical modeling to inform vaccination strategies and testing approaches for COVID-19 in nursing homes
Authors: Kahn Rebecca , Holmdahl Inga , Reddy Sujan , Jernigan John , Mina Michael J. , Slayton Rachel B. 
Published: March 2021

AbstractBackgroundNursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies.MethodsWe use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario.ResultsIncreasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms.ConclusionsEncouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness.SummaryThe extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents.
Prioritizing the first doses of SARS-CoV-2 vaccine to save the elderly: the case study of Italy
Authors: Pontrelli Giuseppe , Cimini Giulio , Roversi Marco , Gabrielli Andrea , Salina Gaetano , Bernardi Stefania , Rocchi Francesca , Simonetti Alessandra , Giaquinto Carlo , Rossi Paolo , Labini Francesco Sylos 
Published: March 2021

AbstractMany countries are currently facing high mortality caused by the circulation of SARS-CoV-2 among the elderly not yet vaccinated. Vaccine shortage poses relevant challenges to health authorities, called to act in a timely manner, and with scarcity of vaccine, and data. We have developed a model for estimating the impact of vaccination on the mortality of the elderly following a schedule of mRNA SARS-CoV-2 vaccine that prioritize first dose administration, as alternative to the standard schedule of two doses administered 3 to 4 weeks apart. We studied the Italian scenario, considering it representative of other Countries facing similar conditions in terms of virus circulation, mortality, and vaccine shortage, in the period from February, 10 to April, 14 2021. Under different conditions of quantity of vaccine administration, the schedule prioritizing first doses showed always significant increase of protected individuals, and a decrease of deaths, up to 19.8% less than the standard schedule. These findings support the vaccination option of prioritizing first dose in the elderly until vaccine supplies are adequate.
Covid-19 lockdown: Ethnic differences in children’s self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional study from the Born in Bradford birth cohort study
Authors: Bingham Daniel D , Daly-Smith Andy , Hall Jennifer , Seims Amanda , Dogra Sufyan A. , Fairclough Stuart J , Ajebon Mildred , Kelly Brian , Hou Bo , Shire Katy A , Crossley Kirsty L , Mon-Williams Mark , Wright John , Pickett Kate , McEachan Rosemary , Dickerson Josie , Barber Sally E 
Published: March 2021

BackgroundIn England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report childrens self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of childrens self-reported PA prior to and during the first UK lockdown.MethodsThis study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9-13 years). A sub-sample (n=634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with children’s PA. Differences in children’s levels of being sufficiently active were examined using the McNemar test examined change in PA prior to and during the lockdown, and multivariable logistic regression to identify factors explaining change.ResultsDuring the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or ‘Other’ ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%).ConclusionsPromoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Children’s PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon children’s PA which is a key and vital behaviour for health and development.
The Charitable Feeding System helps Food Insecure Participants maintain Fruit and Vegetable intake during COVID-19
Authors: Bertmann Farryl , Rogomentich Katherine , Belarmino Emily H. , Niles Meredith T. 
Published: March 2021

AbstractCharitable food services, including food banks and pantries, support individual and households’ food access, potentially maintaining food security and diet quality during emergencies. During the COVID-19 pandemic, the use of food banks and pantries has increased in the US. Here we examine perceptions of the charitable food system and its relationship to food security and dietary quality, specifically fruit and vegetable (FV) intake during the first six months of the COVID-19 pandemic, using a statewide representative survey (n=600) of residents of Vermont. We find that demand for charitable food services increased by 68%. The utilization of food pantries was more common among food insecure households and households with children. Among food insecure respondents, those who used the charitable food system were less likely to reduce their FV intake during the pandemic than those who did not use the charitable food system. Further, we find significant interactions between food pantry use and food insecure households, suggesting that, for food, insecure households, utilizing a food pantry since the onset of the COVID-19 pandemic was associated with higher fruit consumption. These results indicate that these services may support food access and diet quality for at-risk populations during emergencies.
Enhancing oscillations in intracranial electrophysiological recordings with data-driven spatial filters
Authors: Schaworonkow Natalie , Voytek Bradley 
Published: March 2021

AbstractIn invasive electrophysiological recordings, a variety of neuronal oscillations can be detected across the cortex, with overlap in space and time. This overlap complicates measurement of neuronal oscillations using standard referencing schemes, like common average or bipolar referencing. Here, we illustrate the effects of spatial mixing on measuring neuronal oscillations in invasive electrophysiological recordings and demonstrate the benefits of using data-driven referencing schemes in order to improve measurement of neuronal oscillations. We discuss referencing as the application of a spatial filter. Spatio-spectral decomposition is used to estimate data-driven spatial filters, a computationally fast method which specifically enhances signal-to-noise ratio for oscillations in a frequency band of interest. We show that application of these data-driven spatial filters has benefits for data exploration, investigation of temporal dynamics and assessment of peak frequencies of neuronal oscillations. We demonstrate multiple use cases, exploring between-participant variability in presence of oscillations, spatial spread and waveform shape of different rhythms as well as narrowband noise removal with the aid of spatial filters. We find high between-participant variability in the presence of neural oscillations, a large variation in spatial spread of individual rhythms and many non-sinusoidal rhythms across the cortex. Improved measurement of cortical rhythms will yield better conditions for establishing links between cortical activity and behavior, as well as bridging scales between the invasive intracranial measurements and noninvasive macroscale scalp measurements.
Photochromic fluorophores enable imaging of lowly-expressed proteins in the autofluorescent fungusCandida albicans
Authors: Van Genechten Wouter , Demuyser Liesbeth , Duwé Sam , Vandenberg Wim , Van Dijck Patrick , Dedecker Peter 
Published: March 2021

AbstractFluorescence microscopy is a standard research tool in many fields, though collecting reliable images can be difficult in systems characterized by low expressions levels and/or high background fluorescence. We present the combination of a photochromic fluorescent protein and stochastic optical fluctuation imaging (SOFI) to deliver suppression of the background fluorescence. This strategy makes it possible to resolve lowly- or endogenously-expressed proteins, as we demonstrate for Gcn5, a histone acetyltransferase required for complete virulence, and Erg11, the target of the azole antifungals agents in the fungal pathogenC. albicans. We expect that our method can be readily used for sensitive fluorescence measurements in systems characterized by a high background fluorescence.ImportanceUnderstanding the spatial and temporal organization of proteins-of-interest is key to unravel cellular processes and identify novel possible antifungal targets. Only a few therapeutic targets have been discovered inCandida albicansand resistance mechanisms against these therapeutic agents is rapidly acquired. Fluorescence microscopy is a valuable tool to investigate molecular processes and assess the localization of possible antifungal targets. Unfortunately, fluorescence microscopy ofC. albicanssuffers from extensive autofluorescence. In this work we present the use of a photochromic fluorescent protein and stochastic optical fluctuation imaging to enable imaging of lowly-expressed proteins inC. albicansthrough the suppression of autofluorescence. This method can be applied inC. albicansresearch or adapted for other fungal systems allowing the visualization of intricate processes.
The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Māori and Pacific ancestry
Authors: Burden Hannah J. , Adams Shannon , Kulatea Braydon , Wright-McNaughton Morag , Sword Danielle , Ormsbee Jennifer J. , Watene-O’Sullivan Conor , Merriman Tony R. , Knopp Jennifer L. , Chase J. Geoffrey , Krebs Jeremy D. , Hall Rosemary M. , Plank Lindsay D. , Murphy Rinki , Shepherd Peter R. , Merry Troy L. 
Published: March 2021

AbstractAimThe minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased body mass index (BMI), but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Māori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes.MethodsA mixed meal tolerance test was completed by 172 men (56 with the A allele) of Māori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation.ResultsThe A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins GLP-1 or GIP. Consistent with this point, following an intravenous infusion of a glucose bolus, participants with an A allele had higher early (p<0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p>0.05) in insulin sensitivity index or glucose disposal during hyperinsulinemic-euglycemic clamp.Conclusion/interpretationrs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase maximal ability for β-cells to release insulin to reduce the risk of type 2 diabetes.
Evaluating the trade-off between transmissibility and virulence of SARS-CoV-2 by mathematical modeling
Authors: Yang Hyun Mo , Lombardi Junior Luis Pedro , Yang Ariana Campos 
Published: March 2021

AbstractBackgroundAt the beginning of 2020, SARS-CoV-2 spread to all continents, and since then, mutations have appeared in different regions of the world. The appearance of more virulent mutations leads to asseverate that they are also more transmissible. We analyzed the lower and higher virulent SARS-CoV-2 epidemics to establish a relationship between transmissibility and virulence based on a mathematical model.MethodsA compartmental mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality was applied to evaluate the SARS-CoV-2 transmissibility and virulence. The transmissibility was measured by the basic reproduction numberR0and the virulence by the proportion of asymptomatic individuals. The model parameters were fitted considering the observed data from São Paulo State.ResultsThe numbers of severe CoViD-19 and deaths are three times higher, butR0is 25% lower in more virulent SARS-CoV-2 transmission than in a less virulent one. However, the number of more virulent SARS-CoV-2 transmitting individuals is 25% lower, mainly due to symptomatic individuals’ isolation, explaining the increased transmission in lower virulence.ConclusionsThe quarantine study in São Paulo State showed that the more virulent SARS-CoV-2 resulted in a higher number of fatalities but less transmissible than the less virulent one. One possible explanation for the number of deaths surpassing that predicted by the low virulent SARS-CoV-2 infection could be the transmission of more virulent variant(s).
Brain simulation augments machine-learning-based classification of dementia
Authors: Triebkorn Paul , Stefanovski Leon , Dhindsa Kiret , Diaz-Cortes Margarita-Arimatea , Bey Patrik , Bülau Konstantin , Pai Roopa , Spiegler Andreas , Solodkin Ana , Jirsa Viktor , McIntosh Anthony Randal ,   for the Alzheimer’s Disease Neuroimaging Initiative, Ritter Petra 
Published: March 2021

ABSTRACTINTRODUCTIONComputational brain network modeling using The Virtual Brain (TVB) simulation platform acts synergistically with machine learning and multi-modal neuroimaging to reveal mechanisms and improve diagnostics in Alzheimer’s disease.METHODSWe enhance large-scale whole-brain simulation in TVB with a cause-and-effect model linking local Amyloid β PET with altered excitability. We use PET and MRI data from 33 participants of Alzheimer’s Disease Neuroimaging Initiative (ADNI3) combined with frequency compositions of TVB-simulated local field potentials (LFP) for machine-learning classification.RESULTSThe combination of empirical neuroimaging features and simulated LFPs significantly outperformed the classification accuracy of empirical data alone by about 10% (weighted F1-score empirical 64.34% vs. combined 74.28%). Informative features showed high biological plausibility regarding the Alzheimer’s-typical spatial distribution.DISCUSSIONThe cause-and-effect implementation of local hyperexcitation caused by Amyloid β can improve the machine-learning-driven classification of Alzheimer’s and demonstrates TVB’s ability to decode information in empirical data employing connectivity-based brain simulation.RESEARCH IN CONTEXTSYSTEMATIC REVIEW. Machine-learning has been proven to augment diagnostics of dementia in several ways. Imaging-based approaches enable early diagnostic predictions. However, individual projections of long-term outcome as well as differential diagnosis remain difficult, as the mechanisms behind the used classifying features often remain unclear. Mechanistic whole-brain models in synergy with powerful machine learning aim to close this gap.INTERPRETATION. Our work demonstrates that multi-scale brain simulations considering Amyloid β distributions and cause-and-effect regulatory cascades reveal hidden electrophysiological processes that are not readily accessible through measurements in humans. We demonstrate that these simulation-inferred features hold the potential to improve diagnostic classification of Alzheimer’s disease.FUTURE DIRECTIONS. The simulation-based classification model needs to be tested for clinical usability in a larger cohort with an independent test set, either with another imaging database or a prospective study to assess its capability for long-term disease trajectories.