bluuebunny/crossref_metadata_2025_split huggingface dataset:
Will the Large-scale Vaccination Succeed in Containing the COVID-19 Epidemic and How Soon?
Authors: Zhao Shilei , Sha Tong , Xue Yongbiao , Wu Chung-I , Chen Hua 
Published: April 2021

The availability of vaccines provides a promising solution to containing the COVID-19 pandemic. Here, we develop an epidemiological model to quantitatively analyze and predict the epidemic dynamics of COVID-19 under vaccination. The model is applied to the daily released numbers of confirmed cases of Israel and United States of America to explore and predict the trend under vaccination based on their current epidemic status and intervention measures.For Israel, of which 53.83% of the population was fully vaccinated, under the current intensity of NPIs and vaccination scheme, the pandemic is predicted to end between May 14, 2021 to May 16, 2021 depending on an immunity duration between 180 days and 365 days; Assuming no NPIs after March 24, 2021, the pandemic will ends later, between July 4, 2021 to August 26, 2021. For USA, if we assume the current vaccination rate (0.268% per day) and intensity of NPIs, the pandemic will end between February 3, 2022 and August 17, 2029 depending on an immunity duration between 180 days and 365 days. However, assuming an immunity duration of 180 days and with no NPIs, the pandemic will not end, and instead reach an equilibrium state with a proportion of the population remaining actively infected.Overall the daily vaccination rate should be chosen according to the vaccine efficacy and the immunity duration to achieve herd immunity. In some situations, vaccination alone cannot stop the pandemic, and NPIs are necessary both to supplement vaccination and accelerate the end of the pandemic. Considering that vaccine efficacy and duration of immunity may be reduced for new mutant strains, it is necessary to remain cautiously optimistic about the prospect of the pandemic under vaccination.
Role of hyper-reflective spots in predicting outcomes of intravitreal therapy in diabetic macular edema: A systematic review and meta-analysis
Authors: Ganne Pratyusha , Krishnappa Nagesha C , Chaitanya Ganne , Karthikeyan Siddharth K 
Published: April 2021

AbstractPurposePredicting response to intravitreal therapy in DME has become a challenging task. Individual studies have shown that HRS could be a reliable biomarker. This systematic review aimed to determine if there was a quantitative reduction in hyperreflective spots (HRS) following intravitreal therapy in diabetic macular edema (DME), if the type of intravitreal therapy (anti-VEGF versus steroid) had differential effects on quantitative HRS change and finally, if HRS at the start of therapy was associated with improvement in visual acuity (VA) or reduction in central macular thickness (CMT). We also aimed at bringing out the lacunae in the existing literature on HRS in DME and propose goals for future studies.MethodsPubMed/MEDLINE, Scopus, ProQuest, CINAHL, Wiley online and Web of Science were searched based on MOOSE guidelines for non-randomized studies evaluating HRS as a biomarker in DME (between 1st January 2011 and 1st July 2020). Publication bias was analyzed using Begg and Mazumdar rank correlation test and funnel plots. Heterogeneity was assessed using the I2 statistic. Meta-analysis was done using a random-effects model.ResultsA total of 1168 eyes from 19 studies were eligible for inclusion. Pooled standardized mean differences showed that intravitreal therapy was associated with a reduction in quantitative HRS (z=-6.3, CI95%=-1.09 to −0.55, p<0.0001). Extreme between-study heterogeneity was observed (I2=93.2%) with significant publication bias. There was no difference in outcomes between anti-VEGF and steroid therapies (p=0.23). No definite conclusions could be drawn regarding the predictive value of HRS in determining the final VA and CMT.ConclusionThis review could conclude that there is a definite reduction in quantitative HRS following either form of intravitreal therapy. Our conclusion about the role of HRS in predicting visual outcome and CMT change was limited by the number of analyzable studies owing to the wide variation in the study designs, methods and reporting.
Healthy longevity from incidence-based models: More kinds of health than stars in the sky
Authors: Caswell Hal , van Daalen Silke F. 
Published: April 2021

AbstractBackgroundHealthy longevity (HL) is an important measure of the prospects for quality of life in ageing societies. Incidence-based (cf. prevalence-based) models describe transitions among age classes and health stages. Despite the probabilistic nature of those transitions, analyses of healthy longevity have focused persistently on means (“health expectancy”), neglecting variances and higher moments.ObjectivesOur goal is a comprehensive methodology to analyse HL in terms of any combination of health stages and age classes, or of transitions among health stages, or of values (e.g., quality of life) associated with health stages or transitions.MethodsWe construct multistate Markov chains for individuals classified by age and health stage and use Markov chains with rewards to compute all moments of HL.ResultsWe present a new and straightforward algorithm to create the multistate reward matrices for occupancy, transitions, or values associated with occupancy or transitions. As an example, we analyse a published model for colorectal cancer. The possible definitions of HL in this simple model outnumber the stars in the visible universe. Our method can analyse any of them; we show four examples: longevity without abnormal cells, cancer-free longevity, and longevity with cancer before or after a critical age.ContributionOur methods make it possible to analyse any incidence-based model, with any number of health stages, any pattern of transitions, and any kind of values assigned to stages. It is easily computable, requires no simulations, provides all the moments of healthy longevity, and solves the inhomogeneity problem.
Prospective predictive performance comparison between Clinical Gestalt and validated COVID-19 mortality scores
Authors: Soto-Mota Adrian , Marfil-Garza Braulio A. , de Obeso Santiago Castiello , Martínez Erick , Carrillo-Vázquez Daniel Alberto , Tadeo-Espinoza Hiram , Guerrero-Cabrera Jessica Paola , Dardón-Fierro Francisco Eduardo , Escobar Valderrama Juan Manuel , Alanis-Mendizabal Jorge , Gutiérrez Juan 
Published: April 2021

ABSTRACTBackgroundMost COVID-19 mortality scores were developed in the early months of the pandemic and now available evidence-based interventions have helped reduce its lethality. It has not been evaluated if the original predictive performance of these scores holds true nor compared it against Clinical Gestalt predictions. We tested the current predictive accuracy of six COVID-19 scores and compared it with Clinical Gestalt predictions.Methods200 COVID-19 patients were enrolled in a tertiary hospital in Mexico City between September and December 2020. Clinical Gestalt predictions of death (as a percentage) and LOW-HARM, qSOFA, MSL-COVID-19, NUTRI-CoV and NEWS2 were obtained at admission. We calculated the AUC of each score and compared it against Clinical Gestalt predictions and against their respective originally reported value.Results106 men and 60 women aged 56+/-9 and with confirmed COVID-19 were included in the analysis. The observed AUC of all scores was significantly lower than originally reported; LOW-HARM 0.96 (0.94-0.98) vs 0.76 (0.69-0.84), qSOFA 0.74 (0.65-0.81) vs 0.61 (0.53-0.69), MSL-COVID-19 0.72 (0.69-0.75) vs 0.64 (0.55-0.73) NUTRI-CoV 0.79 (0.76-0.82) vs 0.60 (0.51-0.69), NEWS2 0.84 (0.79-0.90) vs 0.65 (0.56-0.75), Neutrophil-Lymphocyte ratio 0.74 (0.62-0.85) vs 0.65 (0.57-0.73). Clinical Gestalt predictions were non-inferior to mortality scores (AUC=0.68 (0.59-0.77)). Adjusting the LOW-HARM score with locally derived likelihood ratios did not improve its performance. However, some scores performed better than Clinical Gestalt predictions when clinician’s confidence of prediction was <80%.ConclusionNo score was significantly better than Clinical Gestalt predictions. Despite its subjective nature, Clinical Gestalt has relevant advantages for predicting COVID-19 clinical outcomes.
CCL2/CCR2 inhibition in atherosclerosis: a meta-analysis of preclinical studies
Authors: Živković Luka , Asare Yaw , Bernhagen Jürgen , Dichgans Martin , Georgakis Marios K. 
Published: April 2021

AbstractRationaleThe CC-chemokine ligand-2 (CCL2)/ CC-chemokine receptor-2 (CCR2) axis governs monocyte recruitment to atherosclerotic lesions. Coherent evidence from experimental studies employing genetic deletion of CCL2 or CCR2 and human epidemiological studies support a causal involvement of the CCL2/CCR2 axis in atherosclerosis. Still, preclinical studies testing pharmacological inhibition of CCL2 or CCR2 in atheroprone mice apply widely different approaches and report inconsistent results, thus halting clinical translation.ObjectiveTo systematically review and meta-analyze preclinical studies pharmacologically targeting the CCL2/CCR2 axis in atherosclerosis in an effort to inform the design of future trials.Methods and ResultsWe identified 14 studies testing CCL2/CCR2 inhibition using 11 different pharmacological agents in mouse models of atherosclerosis. In meta-analyses, blockade of CCL2 or CCR2 attenuated atherosclerotic lesion size in the aortic root or arch (g=-0.75 [-1.17 to -0.32], p=6×10−4; N=171/171 mice in experimental/control group), the carotid (g=-2.39 [-4.23 to -0.55], p=0.01; N=24/25) and the femoral artery (g=-2.38 [-3.50 to -1.26], p=3×10−5; N=10/10). Furthermore, CCL2/CCR2 inhibition reduced intralesional macrophage accumulation and increased smooth muscle cell content and collagen deposition, consistent with a plaque-stabilizing effect. While there was heterogeneity across studies, the effects of CCL2/CCR2 inhibition on lesion size correlated with reductions in plaque macrophage accumulation, in accord with a prominent role of CCL2/CCR2 signaling in monocyte recruitment. Subgroup analyses revealed similar efficacy of both CCL2- and CCR2-inhibiting approaches across different atherosclerosis models in reducing lesion size and intralesional macrophage accumulation, but stronger atheroprotective effects in carotid and femoral arteries, as compared to the aorta.ConclusionsPharmacological targeting of CCL2 or CCR2 lowers atherosclerotic lesion burden and confers plaque stability in mice across different vascular territories, drug candidates, and models of atherosclerosis. Our findings in conjunction with recent human data highlight the translational potential of targeting the CCL2/CCR2 axis in atherosclerosis and can inform future clinical trials.Subject codesatherosclerosis, inflammation, vascular biology, translational studies
Hybridisation boosts dispersal of two contrasted ecotypes in a grass species
Authors: Curran Emma V. , Scott Matilda S. , Olofsson Jill K. , Nyirenda Florence , Sotelo Graciela , Bianconi Matheus E. , Manzi Sophie , Besnard Guillaume , Christin Pascal-Antoine 
Published: April 2021

SummaryIn the absence of strong reproductive barriers, genetic exchanges between closely related groups of organisms with different adaptations have well-documented beneficial and detrimental consequences. In plants, pollen-mediated exchanges affect the sorting of alleles across physical landscapes, and influence rates of hybridisation. How these dynamics affect the emergence and spread of novel ecological strategies remains only partially understood.We use phylogenomics and population genomics to retrace the origin of two geographically overlapping ecotypes of the African grassAlloteropsis angusta.We report the existence of a previously undescribed ecotype inhabiting miombo woodlands and grasslands. The two ecotypes have divergent nuclear genomes. However, the seed-transported chloroplast genomes are consistently shared by distinct ecotypes inhabiting the same region. These patterns suggest that the nuclear genome of one ecotype can reach the seeds of the other via pollen movements, with strong selection subsequently sorting nuclear alleles by habitat.The contrasting ecotypes ofA. angustacan use each other as a gateway to new locations across a large part of Africa. Coupled with newly discovered hybridisation with the sister speciesA. semialata, our results show that hybridisation can facilitate the geographical dispersal of distinct ecotypes of the same grass species.
Genome of the estuarine oyster provides insights into climate impact and adaptive plasticity
Authors: Li Ao , Dai He , Guo Ximing , Zhang Ziyan , Zhang Kexin , Wang Chaogang , Wang Wei , Chen Hongju , Li Xumin , Zheng Hongkun , Zhang Guofan , Li Li 
Published: April 2021

AbstractUnderstanding the roles of genetic divergence and phenotypic plasticity in adaptation is central to evolutionary biology and important for assessing adaptive potential of species under climate change. Analysis of a chromosome-level assembly and resequencing of individuals across wide latitude distribution in the estuarine oyster (Crassostrea ariakensis) revealed unexpectedly low genomic diversity and population structures shaped by historical glaciation, geological events and oceanographic forces. Strong selection signals were detected in genes responding to temperature and salinity stress, especially of the expandedsolute carrierfamilies, highlighting the significance of gene expansion in environmental adaptation. Genes exhibiting high plasticity showed strong selection in upstream regulatory regions that modulate transcription, indicating selection favoring plasticity. Our findings suggest that genomic variation and population structure in marine bivalves are heavily influenced by climate history and physical forces, and gene expansion and selection may enhance phenotypic plasticity that is critical for the adaptation to rapidly changing environments.
Sonicated fibrils of huntingtin exon-1 preferentially seed neurons and produce toxic assemblies
Authors: Chongtham Anjalika , Isas J Mario , Pandey Nitin K , Rawat Anoop , Yoo Jung Hyun , Mastro Tara , Kennedy Marry , Langen Ralf , Khoshnan Ali 
Published: April 2021

AbstractHuntington’s disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeats in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with some being neurotoxic. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the possible uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We found seeding-competent species in the sonicated HTTex1 fibrils, which preferentially entered human neurons and triggered the amplification of neurotoxic assemblies; astrocytes or epithelial cells were not permissive to the HTTex1 seeding. The aggregation of HTTex1 seeds in neurons depleted endogenous HTT protein with non-pathogenic polyQ repeat, activated apoptotic caspase-3 pathway and induced nuclear fragmentation. Using a panel of novel monoclonal antibodies and genetic mutation, we identified epitopes within the N-terminal 17 amino acids and proline-rich domain of HTTex1 mediating neural seeding. Synaptosome preparations from the brains of HD mice also contained similar neurotoxic seeding-competent mutant HTT species. Our findings suggest that amyloidogenic extracellular mutant HTT assemblies may selectively enter neurons, propagate and produce neurotoxic assemblies.
Thalamocortical mechanisms regulating the relationship between transient beta events and human tactile perception
Authors: Law Robert G. , Pugliese Sarah , Shin Hyeyoung , Sliva Danielle D. , Lee Shane , Neymotin Samuel , Moore Christopher , Jones Stephanie R. 
Published: April 2021

AbstractTransient neocortical events with high spectral power in the 15–29Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100–300ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, non-lemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300ms time scale to suppress sensory information. Further analysis showed that the same beta generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event faciliatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.
Causally informed activity flow models provide mechanistic insight into network-generated cognitive activations
Authors: Sanchez-Romero Ruben , Ito Takuya , Mill Ravi D. , Hanson Stephen José , Cole Michael W. 
Published: April 2021

AbstractBrain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists’ preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.Highlights- Activity flow models provide insight into how neurocognitive effects are generated from brain network interactions.- Functional connectivity methods grounded in statistical causal principles facilitate mechanistic interpretations of task activity flow models.- Mechanistic activity flow models accurately predict task-evoked neural effects across a wide variety of brain regions and cognitive tasks.
Spatially non-continuous relationships between biological invasion and fragmentation of mangrove forests
Authors: Zhang Zhen , Li Jing , Li Yi , Liu Wenwen , Chen Yuxin , Zhang Yihui , Li Yangfan 
Published: April 2021

AbstractRapid and large-scale biological invasion results in widespread biodiversity loss and degradation of essential ecosystem services, especially in mangrove forests. Recent evidence suggests that the establishment and dispersal of invasive species may exacerbated in fragmented landscape, but the influence of mangrove fragmentation on coastal biological invasion at landscape scale remains largely unknown. Here, using the derived 10-m resolution coastal wetland map in southeast coast of China, we examine the relationships between fragmentation of mangrove forests and salt marsh invasion magnitude and quantify the geographical variations of the relationships across a climatic gradient. Our results show that mangrove forests with small size, large edge proportion, and regular boundary shape tend to suffer more serious salt marsh invasions, indicating a positive correlation between mangrove fragmentation and its invaded magnitude. In particular, such fragmentation-invasion relationships in subtropics are shown to be more intensive than in tropic. Our findings provide the first spatially explicit evidence of the relationships between mangrove fragmentation and biological invasion on a landscape scale, and highlight an urgent need for conservation and management actions to improve mangrove connectivity, which will increase resistance to invasions, especially for small-size subtropical mangrove forests.
Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets
Authors: Riddell Shane , Goldie Sarah , McAuley Alexander J. , Kuiper Michael J. , Durr Peter A. , Blasdell Kim , Tachedjian Mary , Druce Julian D. , Smith Trevor R.F. , Broderick Kate E. , Vasan Seshadri S. 
Published: April 2021

AbstractThe ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These “variants-of-concern” have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative ‘G614’, ‘501Y.V1’ and ‘501Y.V2’ virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported byin silicobiomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.