bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of Favipiravir in treatment of COVID-19: A systematic review and meta-analysis of clinical trials
Authors: Hassanipour Soheil , Arab-Zozani Morteza , Amani Bahman , Heidarzad Forough , Fathalipour Mohammad , Martinez-de-Hoyo Rudolph 
Published: February 2021

AbstractThe novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid hub/PubMed, Scopus, ISI web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR=1.24, 95% CI: 1.09-1.41; P=0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR=1.11, 95% CI: 0.98-1.25; P=0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR=0.93, 95% CI: 0.67-1.28; P=0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.
Subjective impact of the COVID-19 pandemic on schizotypy and general mental health in Germany and the UK, for independent samples in May and in October 2020
Authors: Daimer Sarah , Mihatsch Lorenz , Ronan Lisa , Murray Graham K. , Knolle Franziska 
Published: February 2021

AbstractStudies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March–June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizoptypal traits in two independent general population samples of the UK (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the UK was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation.
Interrogating structural inequalities in COVID-19 Mortality in England and Wales
Authors: Griffith Gareth J , Smith George Davey , Manley David , Howe Laura D , Owen Gwilym 
Published: February 2021

AbstractBackgroundNumerous observational studies have highlighted structural inequalities in COVID-19 mortality in the UK. Such studies often fail to consider the complex spatial nature of such inequalities in their analysis, leading to the potential for bias and an inability to reach conclusions about the most appropriate structural levels for policy intervention.MethodsWe use publicly available population data on COVID-19 related- and all-cause mortality between March and July 2020 in England and Wales to investigate the spatial scale of such inequalities. We propose a multiscale approach to simultaneously consider four spatial scales at which processes driving inequality may act and apportion inequality between these.ResultsAdjusting for population age structure, number of care homes and residing in the North we find highest regional inequality in March and June/July. We find finer-grained within-region increased steadily from March until July. The importance of spatial context increases over the study period. No analogous pattern is visible for non-COVID mortality. Higher relative deprivation is associated with increased COVID-19 mortality at all stages of the pandemic but does not explain structural inequalities.ConclusionsResults support initial stochastic viral introduction in the South, with initially high inequality decreasing before the establishment of regional trends by June and July, prior to reported regionality of the “second-wave”. We outline how this framework can help identify structural factors driving such processes, and offer suggestions for a long-term, locally-targeted model of pandemic relief in tandem with regional support to buffer the social context of the area.Key MessagesRegional inequality in COVID-19 mortality declined from an initial peak in April, before increasing again in June/July.Within-region inequality increased steadily from March until July.Strong regional trends are evident in COVID-19 mortality in June/July, prior to wider reporting of regional differences in “second wave”.Analogous spatial inequalities are not present in non-COVID related mortality over the study period.These inequalities are not explained by age structure, care homes, or deprivation.
Rapid active-reflection display on dorsal stripes ofAtherinomorus lacunosus
Authors: Iwasaka Masakazu 
Published: February 2021

AbstractA large number of living creatures are able to use environmental light effectively as a biological display. The biological structural colors are very attractive not only within the coloring species but also to humans. However, the detailed function of bio-reflectors, which constitute the structural color with respect to communication, remains unknown.Atherinomorus lacunosushas alignments of iridophore spots on its dorsal part. Here it is found that a spot with a diameter of approximately 0.1 mm causes a rhythmic blinking of light owing to rapid reflection changes in iridophores existing inside the spot. The iridophores contain reflecting particles which show similar rotational responses to magnetic field under a light exposure. The speed of the intensity change of light at a frequency of approximately 1 Hz is proposed to be controlled by the nervous system ofA. lacunosus. This kind of passive illumination may contribute to the development of a new optical device with low energy consumption.
NECAB2 participates in an endosomal pathway of mitochondrial stress response at striatal synapses
Authors: Bueno Diones , Dey Partha Narayan , Schacht Teresa , Wolf Christina , Wüllner Verena , Morpurgo Elena , Rojas-Charry Liliana , Sessinghaus Lena , Leukel Petra , Sommer Clemens , Radyushkin Konstantin , Schäfer Michael K.E. , Florin Luise , Baumgart Jan , Stamm Paul , Daiber Andreas , Horta Guilherme , Nardi Leonardo , Vasic Verica , Schmeisser Michael J. , Hellwig Andrea , Oskamp Angela , Bauer Andreas , Anand Ruchika , Reichert Andreas S. , Ritz Sandra , Nocera Gianluigi , Jacob Claire , Peper Jonas , Silies Marion , Frauenknecht Katrin B. M. , Methner Axel 
Published: February 2021

AbstractSynaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control and repair. We found that global knockout of the neuronal calcium-binding protein 2 (NECAB2) in the mouse causes loss of striatal synapses and behavioral phenotypes related to striatal dysfunction such as reduced motivation and altered sensory gating. Striatal mitochondria fromNecab2knockout mice are more abundant and smaller. They are characterized by increased respiration and superoxide production resulting in oxidative stress. This accumulation of dysfunctional mitochondria is caused by a defective assembly of mitochondria with early endosomes in a pathway that involves the small GTPase Rab5 and its guanine nucleotide exchange factor Alsin/ALS2. NECAB2 therefore participates in an endosomal pathway of mitochondrial stress response and repair important for striatal function.
Nicotine-mediated recruitment of GABAergic neurons to a dopaminergic phenotype attenuates motor deficits in alpha-synuclein Parkinson’s model
Authors: Lai I-Chi , Romoli Benedetto , Keisler Maria , Manfredsson Fredric P. , Powell Susan B. , Dulcis Davide 
Published: February 2021

ABSTRACTBACKGROUNDPrevious work revealed an inverse correlation between smoking and Parkinson’s disease (PD) that is associated with nicotine-induced neuroprotection of dopaminergic (DA) neurons against nigrostriatal damage in PD primates and rodent models. Nicotine, a neuroactive component of tobacco, can directly alter the activity of midbrain DA neurons and induce non-DA neurons in the substantia nigra (SN) to acquire a DA phenotype. We investigated the recruitment mechanism of nigrostriatal GABAergic neurons to express DA phenotypes, such as transcription factor Nurr1 and DA-synthesizing enzyme tyrosine hydroxylase (TH), and the concomitant effects on motor function.METHODSWild-type and α-syn-overexpressing (PD) mice treated with chronic nicotine were assessed by behavioral pattern monitor (BPM) and immunohistochemistry/in-situhybridization to measure behavior and the translational/transcriptional regulation of neurotransmitter phenotype following selective Nurr1 overexpression or DREADD-mediated chemogenetic activation.RESULTSNicotine treatment led to a transcriptional TH and translational Nurr1 upregulation within a pool of SN GABAergic neurons in wild-type animals. In PD mice, nicotine increased Nurr1 expression, reduced the number of α-syn-expressing neurons, and simultaneously rescued motor deficits. Hyperactivation of GABA neurons alone was sufficient to elicitde novotranslational upregulation of Nurr1 in non-DA neurons. Retrograde labeling revealed that a fraction of these GABAergic neurons projects to the dorsal striatum.CONCLUSIONSNicotine exposure initiates neuroprotective mechanisms counteracting the neurodegenerative effects of α-syn accumulation in DA neurons and contributing to Nurr1-mediated therapeutic effects. Revealing the mechanism of nicotine-induced DA plasticity protecting SN neurons against nigrostriatal damage could contribute to developing new strategies for neurotransmitter replacement in PD.
Neural entrainment facilitates duplets: Frequency-tagging differentiates musicians and non-musicians when they tap to the beat
Authors: Celma-Miralles A. , Kleber B.A. , Toro J.M. , Vuust P. 
Published: February 2021

ABSTRACTMotor coordination to an isochronous beat improves when it is subdivided into equal intervals. Here, we study if this subdivision benefit (i) varies with the kind of subdivision, (ii) is enhanced in individuals with formal musical training, and (iii), is an inherent property of neural oscillations. We recorded electroencephalograms of musicians and non-musicians during: (a) listening to an isochronous beat, (b) listening to one of 4 different subdivisions, (c) listening to the beat again, and (d) listening and tapping the beat with the same subdivisions as in (b). We found that tapping consistency and neural entrainment in condition (d) was enhanced in non-musicians for duplets (1:2) compared to the other types of subdivisions. Musicians showed overall better tapping performance and were equally good at tapping together with duplets, triplets (1:3) and quadruplets (1:4), but not with quintuplets (1:5). This group difference was reflected in enhanced neural responses in the triplet and quadruplet conditions. Importantly, for all participants, the neural entrainment to the beat and its first harmonic (i.e. the duplet frequency) increased after listening to each of the subdivisions (c compared to a). Since these subdivisions are harmonics of the beat frequency, the observed preference of the brain to enhance the simplest subdivision level (duplets) may be an inherent property of neural oscillations. In sum, a tapping advantage for simple binary subdivisions is reflected in neural oscillations to harmonics of the beat, and formal training in music can enhance it.Highlights-The neural entrainment to periodic sounds only differs between musicians and non-musicians when they perform a predictive sensorimotor synchronization task.-After listening to a subdivided beat, the frequencies related to the beat and its first harmonic are enhanced in the EEG, likely stabilizing the perception of the beat.-There is a natural advantage for binary structures in sensorimotor synchronization, observed in the tapping of duplets by non-musicians, which can be extended to other subdivisions after extensive musical training.
Audiovisual adaptation is expressed in spatial and decisional codes
Authors: Aller Máté , Mihalik Agoston , Noppeney Uta 
Published: February 2021

AbstractThe brain adapts dynamically to the changing sensory statistics of its environment. The neural circuitries and representations that support this cross-sensory plasticity remain unknown. We combined psychophysics and model-based representational fMRI and EEG to characterize how the adult human brain adapts to misaligned audiovisual signals. We show that audiovisual adaptation moulds regional BOLD-responses and fine-scale activity patterns in a widespread network from Heschl’s gyrus to dorsolateral prefrontal cortices. Crucially, audiovisual recalibration relies on distinct spatial and decisional codes that are expressed with opposite gradients and timecourses across the auditory processing hierarchy. Early activity patterns in auditory cortices encode sounds in a continuous space that flexibly adapts to misaligned visual inputs. Later activity patterns in frontoparietal cortices code decisional uncertainty consistent with these spatial transformations. Our findings demonstrate that regions throughout the auditory processing hierarchy multiplex spatial and decisional codes to adapt flexibly to the changing sensory statistics in the environment.
DNA translocase repositions a nucleosome by the lane-switch mechanism
Authors: Nagae Fritz , Brandani Giovanni B. , Takada Shoji , Terakawa Tsuyoshi 
Published: February 2021

ABSTRACTTranslocases such as DNA/RNA polymerases, replicative helicases, and exonucleases are involved in eukaryotic DNA transcription, replication, and repair. Since eukaryotic genomic DNA wraps around histone core complexes and forms nucleosomes, translocases inevitably encounter nucleosomes. Previous studies have shown that a histone core complex repositions upstream (downstream) when SP6RNA or T7 RNA polymerase (bacterial exonuclease, RecBCD) partially unwraps nucleosomal DNA. However, the molecular mechanism of the downstream repositioning remains unclear. In this study, we identify the lane-shift mechanism for downstream nucleosome repositioning via coarse-grained molecular dynamics simulations, which we validated by restriction enzyme digestion assays and deep sequencing assays. In this mechanism, after a translocase unwraps nucleosomal DNA up to the site proximal to the dyad, the remaining wrapped DNA switches its binding region (lane) to that vacated by the unwrapping, and the downstream DNA rewraps, completing downstream repositioning. This mechanism may have crucial implications for transcription through nucleosomes, histone recycling, and nucleosome remodeling.SIGNIFICANCEEukaryotic chromosomes are composed of repeating subunits termed nucleosomes. Thus, proteins that translocate along the chromosome, DNA translocases, inevitably collide with nucleosomes. Previous studies revealed that a translocase repositions a nucleosome upstream or downstream upon their collision. Though the molecular mechanisms of the upstream repositioning have been extensively studied, that of downstream repositioning remains elusive. In this study, we performed coarse-grained molecular dynamics simulations, proposed the lane-shift mechanism for downstream repositioning, and validated this mechanism by restriction enzyme digestion assays and deep sequencing assays. This mechanism has broad implications for how translocases deal with nucleosomes for their functions.
Global detection of DNA repair outcomes induced by CRISPR-Cas9
Authors: Liu Mengzhu , Zhang Weiwei , Xin Changchang , Yin Jianhang , Shang Yafang , Ai Chen , Li Jiaxin , Meng Fei-long , Hu Jiazhi 
Published: February 2021

AbstractCRISPR-Cas9 generates double-stranded DNA breaks (DSBs) to activate cellular DNA repair pathways for genome editing. The repair of DSBs leads to small insertions or deletions (indels) and other complex byproducts, including large deletions and chromosomal translocations. Indels are well understood to disrupt target genes, while the other deleterious byproducts remain elusive. We developed a newin silicoanalysis pipeline for the previously described primer-extension-mediated sequencing assay to comprehensively characterize CRISPR-Cas9-induced DSB repair outcomes in human or mouse cells. We identified tremendous deleterious DSB repair byproducts of CRISPR-Cas9 editing, including large deletions, plasmid integrations, and chromosomal translocations. We further elucidated the important roles of microhomology, chromosomal interaction, recurrent DSBs, and DSB repair pathways in the generation of these byproducts. Our findings provide an extra dimension for genome editing safety besides off-targets. And caution should be exercised to avoid not only off-target damages but also deleterious DSB repair byproducts during genome editing.
Identification of differentially distributed gene expression and distinct sets of cancer-related genes identified by changes in mean and variability
Authors: Roberts Aedan G. K. , Catchpoole Daniel R. , Kennedy Paul J. 
Published: February 2021

AbstractThere is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer. Analysis of eight paired tumour–normal datasets from The Cancer Genome Atlas confirms that differential variability and distribution are able to identify cancer-related genes. We further demonstrate that differential variability identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of genes. These results suggest that differential variability analysis may provide insights into genetic aspects of cancer that would not be revealed by differential expression, and that differential distribution analysis may allow for more comprehensive identification of cancer-related genes than analyses based on changes in mean or variability alone.
Correlation between structure and function in phosphatidylinositol lipid-dependent Kir2.2 gating
Authors: Zhang Yuxi , Tao Xiao , MacKinnon Roderick 
Published: February 2021

AbstractInward rectifier K+(Kir) channels regulate cell membrane potential. Different Kir channels respond to unique ligands, but all are regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Using planar lipid bilayers we show that Kir2.2 exhibits bursts of openings separated by long quiescent inter-burst periods. Increasing PI(4,5)P2concentration shortens the Kir2.2 inter-burst duration and lengthens the burst duration without affecting dwell times within a burst. From this, we propose that burst and inter-burst durations correspond to the CTD-docked and CTD-undocked conformations observed in the presence and absence of PI(4,5)P2in atomic structures. We also studied the effect of different phosphatidylinositol lipids on Kir2.2 activation and conclude that the 5’ phosphate is essential to Kir2.2 pore opening. Other phosphatidylinositol lipids can compete with PI(4,5)P2but cannot activate Kir2.2 without the 5’ phosphate. PI(4)P, which is directly interconvertible to and from PI(4,5)P2, might thus be a regulator of Kir channels in the plasma membrane.
Monoclonal antibodies targeting the influenza virus N6 neuraminidase
Authors: Strohmeier Shirin , Amanat Fatima , Carreño Juan Manuel , Krammer Florian 
Published: February 2021

AbstractInfluenza A viruses are a diverse species that include 16 hemagglutinin (HA) subtypes and 9 neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 NA subtypes are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral propertiesin vitroandin vivoand mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding and inhibition of the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 and H5N6 mouse challenge models when the antibodies were given prophylactically.ImportanceThe N6 NA has recently gained prominence due to the emergence of highly pathogenic H5N6 viruses. Currently, there is limited characterization of the antigenicity of avian N6 neuraminidase. Our data is an important first step towards a better understanding of the N6 NA antigenicity.