bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trial-to-trial variability of spiking delay activity in prefrontal cortex constrains burst-coding models of working memory
Authors: Li Daming , Constantinidis Christos , Murray John D. 
Published: February 2021

AbstractA hallmark neuronal correlate of working memory (WM) is stimulus-selective spiking activity of neurons in prefrontal cortex (PFC) during mnemonic delays. These observations have motivated an influential computational modeling framework in which WM is supported by persistent activity. Recently this framework has been challenged by arguments that observed persistent activity may be an artifact of trial-averaging, which potentially masks high variability of delay activity at the single-trial level. In an alternative scenario, WM delay activity could be encoded in bursts of selective neuronal firing which occur intermittently across trials. However, this alternative proposal has not been tested on single-neuron spike-train data. Here, we developed a framework for addressing this issue by characterizing the trial-to-trial variability of neuronal spiking quantified by Fano factor (FF). By building a doubly stochastic Poisson spiking model, we first demonstrated that the burst-coding proposal implies a significant increase in FF positively correlated with firing rate, and thus loss of stability across trials during the delay. Simulation of spiking cortical circuit WM models further confirmed that FF is a sensitive measure that can well dissociate distinct WM mechanisms. We then tested these predictions on datasets of single-neuron recordings from macaque prefrontal cortex during three WM tasks. In sharp contrast to the burst-coding model predictions, we only found a small fraction of neurons showing increased WM-dependent burstiness, and stability across trials during delay was strengthened in empirical data. Therefore, reduced trial-to-trial variability during delay provides strong constraints on the contribution of single-neuron intermittent bursting to WM maintenance.Significance StatementThere are diverging classes of theoretical models explaining how information is maintained in working memory by cortical circuits. In an influential model class, neurons fire exhibit persistent elevated memorandum-selective firing, whereas a recently developed class of burst-coding models suggests that persistent activity is an artifact of trial-averaging, and spiking is sparse in each single trial, subserved by brief intermittent bursts. However, this alternative picture has not been characterized or tested on empirical spike-train data. Here we combine mathematical analysis, computational model simulation and experimental data analysis to test empirically theses two classes of models and show that the trial-to-trial variability of empirical spike trains is not consistent with burst coding. These findings provide constraints for theoretical models of working memory.
Pupillary aperture is a potential biomarker of movement preparation
Authors: Pandey Pragya , Ray Supriya 
Published: February 2021

ABSTRACTIn response to variable light intensity, the pupils reflexively constrict or dilate to maintain a uniform retinal illumination. The pupillary light reflex (PLR) pathway receives projections from two important areas in primates’ brain that plan rapid saccadic eye-movement – frontal eye field (FEF) and superior colliculus (SC). The speed with which neurons in these areas increase firing rate to a threshold determines latency of a saccade. Micro-stimulation of FEF/SC neurons below this threshold modulates the magnitude of PLR. Nonetheless, how the saccade latency and pupil dynamics are related remains unknown. Our study shows that the appearance of a bright stimulus evokes pupil constriction at higher rate when the latency of impending saccade to the stimulus is shorter. This inverse relationship between the rate of pupil constriction and the saccade latency is robust irrespective of the reward outcome. In a homeomorphic biomechanical model of pupil, we have projected build-up signal similar to FEF and SC activity to the parasympathetic and sympathetic divisions of the PLR pathway, respectively. Model simulation mimics the observed data to indicate that the FEF and SC activity for eye movement modulates autonomic input to the pupillary muscle plant. A striking similarity between the dynamics of pupil constriction and stochastic rise in neural activity for saccade elicitation suggests that PLR is a potential proxy of movement preparation, and not mere an indicator of attentional orientation. Our study suggests a mechanism of how the retinal luminosity is timely regulated to aid perception by minimizing visual transients due to gaze orientation.
Prognosis and hematological findings in patients with COVID-19 in an Amazonian population of Peru
Authors: Iglesias-Osores Sebastian , Rafael-Heredia Arturo , Rojas-Tello Eric Ricardo , Ortiz-Uribe Washington A. , Román Leveau-Bartra Walter , Armando Leveau-Bartra Orison , Miguel Alcántara-Mimbela , Córdova-Rojas Lizbeth M. , López-López Elmer , Failoc-Rojas Virgilio E. 
Published: February 2021

AbstractObjectiveThis study examined the laboratory results of COVID-19 patients from a hospital in the Peruvian Amazon and their clinical prognosis.MethodsAn analytical cross-sectional study was carried out whose purpose was to identify the laboratory tests of patients with COVID-19 and mortality in a hospital in Ucayali, Peru during the period from March 13 to May 9, 2020, selecting a total of 127 with Covid-19. Mean and the standard deviation was described for age, leukocytes, neutrophils, platelets, RDW-SD; median and interquartile range for the variables lymphocyte, RN / L, fibrinogen, CRP, D-dimer, DHL, hematocrit, monocytes, eosinophils.ResultsNo differences were observed in this population regarding death and sex (OR: 1.31; 95% CI 0.92 to 1.87), however, it was observed that, for each one-year increase, the probability of death increased by 4% (PR: 1.04, 95% CI 1.03 to 1.05). The IRR (Incidence Risk Ratio) analysis for the numerical variables showed results strongly associated with hematological values such as Leukocytes (scaled by 2500 units) (IRR: 1.08, 95% CI 1.03 to 1.13), neutrophils (scaled by 2500 units) (IRR: 1.08; 95% CI 1.03 to 1.13), on the contrary, it is observed that the increase of 1000 units in lymphocytes, the probability of dying decreased by 48% (IRR: 0.52; 95% CI 0.38 to 071).ConclusionParameters such as leukocytes and neutrophils were statistically much higher in patients who died.
Dysgraphic features in motor neuron disease: a review
Authors: Nicolò Aiello Edoardo , Feroldi Sarah , Preti Alice Naomi , Zago Stefano , Appollonio Ildebrando Marco 
Published: February 2021

AbstractBackgroundMotor neuron disease (MND) patients can show oral language deficits mimicking those of frontotemporal degenerations (FTD). Although dysgraphic features have been also reported within the MND-FTD continuum, their characteristics and clinical relevance are still largely unexplored.AimsTo profile writing disorders in MND patients can help further define their cognitive semiology and thus conveys relevant clinical entailments. Therefore, this study aimed at reviewing evidence of writing impairment in MND patients. This review was implemented and reported by consulting Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Qualitative/quantitative measures of writing abilities in MND patients was the primary outcome. Both group studies and case reports/series were taken into consideration. Twenty-four contributions were included out of an initial N=83. Potential biases in generalizing results were qualitatively controlled for by extracting background, disease-related, neuropsychological and neuroanatomofunctional secondary outcomes.Main ContributionFifteen studies assessed writing abilities in Japaneses patients, whereas the remaining eight in western patients. Central dysgraphic features were reported in both neuropsychologically-impaired and –unimpaired MND patients. Phonetic/phonological paragraphias and morpho-syntactic errors were frequently reported. Although FTD was frequently co-occurent, neither cognitive nor language impairment fully accounted for writing impairment in some patients. By contrast, evidence of peripheral dysgraphia was scarce. Patients displaying writing deficits often presented with bulbar signs and perisylvian cortices involvement (including Exner’s area and the left angular gyrus). Writing deficits proved to be associated with abnormalities in executive functioning and its neural substrates. Writing-to-dictation tasks as well as writing samples assessment proved to be useful to detect writing errors.ConclusionsDysgraphic features in MND patients might be due to dysfunctions of the graphemic buffer – and possibly the phonological route. The lexico-semantic route appeared to be less involved. However, a mixed peripheral/central involvement cannot be ruled out. In this population, executive/attentive deficits are likely to contribute to writing errors as well. Writing deficits might thus be specific of MND patients’ cognitive/language impairment profile. The evaluation of writing abilities via writing-to-dictation/narrative writing tasks may be useful when assessing cognition/language in both neuropsychological-impaired and -unimpaired MND patients - especially when severe dysarthria/anarthria is present and prevents clinicians from assessing oral language.
Stay Home and Stay Active? The impact of stay-at-home restrictions on physical activity routines in the UK during the COVID-19 pandemic
Authors: Eshelby Victoria , Sogut Muhammed , Jolly Kate , Vlaev Ivo , Elliott Mark T. 
Published: February 2021

ABSTRACTGovernment restrictions applied during the COVID-19 pandemic in the UK led to the disruption of many people’s physical activity routines, with sports and leisure facilities closed and outdoor exercise only permitted once per day. In this study we investigated which population groups were impacted most in terms of reduced physical activity levels during these periods, and which groups benefitted in terms of increasing their usual level of physical activity. We surveyed UK residents, sampled through users of a rewards-for-exercise app (Sweatcoin; n=749) and an online panel (Prolific; n=907). Of the app users, n=487 further provided daily step-count data collected by the app, prior to, and during the periods of restrictions between March and June 2020. Regression models were applied to investigate factors associated with subjective change (perceived change in physical activity) and objective change (log-percentage change in daily step-count) in physical activity during the periods of restrictions. ANOVAs were used to further investigate the significant factors identified. Key factors associated with a substantial subjective reduction in physical activity included those classed as obese, gym users and people living in urban areas. All participants had a reduced step count during restrictions, with Black, Asian and minority ethnic (BAME) groups, students and urban dwellers showing the largest reductions. Therefore, targeted interventions are required to ensure that the physical and mental health impacts of sedentary behaviour are not exacerbated over the long-term by significant reductions in physical activity identified in these groups, particularly those who are also more vulnerable to the COVID-19 virus.
Molecular epidemiology of SARS-CoV-2 in Greece reveals low rates of onward virus transmission after lifting of travel restrictions based on risk assessment during summer 2020
Authors: Kostaki Evangelia Georgia , Pavlopoulos Georgios A. , Verrou Kleio-Maria , Ampatziadis-Michailidis Giannis , Harokopos Vaggelis , Hatzis Pantelis , Moulos Panagiotis , Siafakas Nikolaos , Pournaras Spyridon , Hadjichristodoulou Christos , Chatzopoulou Fani , Chatzidimitriou Dimitrios , Panagopoulos Periklis , Lourida Panagiota , Argyraki Aikaterini , Lytras Theodoros , Sapounas Spyros , Gerolymatos Gerasimos , Panagiotakopoulos Georgios , Prezerakos Panagiotis , Tsiodras Sotirios , Sypsa Vana , Hatzakis Angelos , Anastassopoulou Cleo , Spanakis Nikolaos , Tsakris Athanasios , Dimopoulos Meletios Athanasios , Kotanidou Anastasia , Sfikakis Petros , Kollias Georgios , Magiorkinis Gkikas , Paraskevis Dimitrios 
Published: February 2021

AbstractMolecular epidemiology has provided an additive value to traditional public health tools by identifying SARS-CoV-2 clusters, or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to estimate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in 5 replicates of 3,000 sequences sampled globally, as well as the best hits to our dataset identified by BLAST. Phylogenetic analyses revealed the presence of 70 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on a thorough risk assessment), respectively. These findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic.
Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells
Authors: Pickard Adam , Calverley Ben C. , Chang Joan , Garva Richa , Lu Yinhui , Kadler Karl E. 
Published: February 2021

ABSTRACTCOVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, vaccine escape variants might arise leading to a re-emergence of COVID. In anticipation of such a scenario, the identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2- DOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in- line with reported proteinuria and liver damage in patients with COVID-19. We identified 35 drugs that reduced viral replication in Vero and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.
Protein model accuracy estimation empowered by deep learning and inter-residue distance prediction in CASP14
Authors: Chen Xiao , Liu Jian , Guo Zhiye , Wu Tianqi , Hou Jie , Cheng Jianlin 
Published: February 2021

AbstractThe inter-residue contact prediction and deep learning showed the promise to improve the estimation of protein model accuracy (EMA) in the 13th Critical Assessment of Protein Structure Prediction (CASP13). During the 2020 CASP14 experiment, we developed and tested several EMA predictors that used deep learning with the new features based on inter-residue distance/contact predictions as well as the existing model quality features. The average global distance test (GDT-TS) score loss of ranking CASP14 structural models by three multi-model MULTICOM EMA predictors (MULTICOM-CONSTRUCT, MULTICOM-AI, and MULTICOM-CLUSTER) is 0.073, 0.079, and 0.081, respectively, which are ranked first, second, and third places out of 68 CASP14 EMA predictors. The single-model EMA predictor (MULTICOM-DEEP) is ranked 10th place among all the single-model EMA methods in terms of GDT_TS score loss. The results show that deep learning and contact/distance predictions are useful in ranking and selecting protein structural models.
Environmental enrichment induces epigenomic and genome organization changes relevant for cognitive function
Authors: Espeso-Gil Sergio , Holik Aliaksei , Bonnin Sarah , Jhanwar Shalu , Chandrasekaran Sandhya , Pique-Regi Roger , Albaigès-Ràfols Júlia , Maher Michael , Permanyer Jon , Irimia Manuel , Friedländer Marc R. , Pons-Espinal Meritxel , Akbarian Schahram , Dierssen Mara , Maass Philipp G. , Hor Charlotte N. , Ossowski Stephan 
Published: February 2021

SummaryIn early development, the environment triggers mnemonic epigenomic programs resulting in memory and learning experiences to confer cognitive phenotypes into adulthood. To uncover how environmental stimulation impacts the epigenome and genome organization, we used the paradigm of environmental enrichment (EE) in young mice constantly receiving novel stimulation. We profiled epigenome and chromatin architecture in whole cortex and sorted neurons by deep-sequencing techniques. Specifically, we studied chromatin accessibility, gene and protein regulation, and 3D genome conformation, combined with predicted enhancer and chromatin interactions. We identified increased chromatin accessibility, transcription factor binding including CTCF-mediated insulation, differential occupancy of H3K36me3 and H3K79me2, and changes in transcriptional programs required for neuronal development. EE stimuli led to local genome re-organization by inducing increased contacts between chromosomes 7 and 17 (inter-chromosomal). Our findings support the notion that EE-induced learning and memory processes are directly associated with the epigenome and genome organization.Highlights-Environmental enrichment (EE) alters chromatin conformation, CTCF binding, and spatially 3D genome changes, thereby regulating cognitive function during the first steps of life after birth.-Transcription-associated gene body marks H3K79me2 and H3K36me3 are differently influenced by EE in cortical brain cells and binding is exacerbated upon stimulation in an age-dependent manner.-EE-induced changes of 3D genome organization increaseinter-chromosomal interactions of genes associated with synaptic transmission and AMPA receptor genes on chromosomes 7 and 17.
Deep learning integration of molecular and interactome data for protein-compound interaction prediction
Authors: Watanabe Narumi , Ohnuki Yuuto , Sakakibara Yasubumi 
Published: February 2021

AbstractMotivationVirtual screening, which can computationally predict the presence or absence of protein-compound interactions, has attracted attention as a large-scale, low-cost, and short-term search method for seed compounds. Existing machine learning methods for predicting protein-compound interactions are largely divided into those based on molecular structure data and those based on network data. The former utilize information on proteins and compounds, such as amino acid sequences and chemical structures, while the latter utilize interaction network data, such as data on protein-protein interactions and compound-compound interactions. However, few attempts have been made to combine both types of data in molecular information and interaction networks.ResultsWe developed a deep learning-based method that integrates protein features, compound features, and multiple types of interactome data to predict protein-compound interactions. We designed three benchmark datasets with different difficulties and evaluated the performance on them. The performance evaluations show that our deep learning framework for integrating molecular structure data and interactome data outperforms state-of-the-art machine learning methods for protein-compound interaction prediction tasks. The performance improvement is proven to be statistically significant by the Wilcoxon signed-rank test. This reveals that the multi-interactome captures different perspectives than amino acid sequence homology and chemical structure similarity, and both type of data have a synergistic effect in improving prediction accuracy. Furthermore, experiments on three benchmark datasets show that our method is more robust than existing methods in accurately predicting interactions between proteins and compounds that are unseen in the training samples.
Expression of human ACE2 N-terminal domain, part of the receptor for SARS-CoV-2, in fusion with maltose binding protein,E. coliribonuclease I and human RNase A
Authors: Xu Shuang-yong , Fomenkov Alexey , Chen Tien-Hao , Yigit Erbay 
Published: February 2021

AbstractThe SARS-CoV-2 viral genome contains a positive-strand single-stranded RNA of ~30 kb. Human ACE2 protein is the receptor for SARS-CoV-2 virus attachment and initiation of infection. We propose to use ribonucleases (RNases) as antiviral agents to destroy the viral genomein vitro.In the virions the RNA is protected by viral capsid proteins, membrane proteins and nucleocapsid proteins. To overcome this protection we set out to construct RNase fusion with human ACE2 receptor N-terminal domain (ACE2NTD). We constructed six proteins expressed inE. colicells: 1) MBP-ACE2NTD, 2) ACE2NTD-GFP, 3) RNase I (6xHis), 4) RNase III (6xHis), 5) RNase I-ACE2NTD (6xHis), and 6) human RNase A-ACE2NTD150 (6xHis). We evaluated fusion expression in differentE. colistrains, partially purified MBP-ACE2NTD protein from the soluble fraction of bacterial cell lysate, and refolded MBP-ACE2NTD protein from inclusion body. The engineered RNase I-ACE2NTD (6xHis) and hRNase A-ACE2NTD (6xHis) fusions are active in cleaving COVID-19 RNAin vitro.The recombinant RNase I (6xHis) and RNase III (6xHis) are active in cleaving RNA and dsRNA in test tube. This study provides a proof-of-concept for construction of fusion protein between human cell receptor and nuclease that may be used to degrade viral nucleic acids in our environment.Graphical AbstractCartoon illustration part of this work (Human ACE2 N-terminal domain tethered to RNase A and RNA degradation by the fusion enzyme).