bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of the Visual Field Parameters of SITA Faster and SITA Standard Strategies in Glaucoma
Authors: Lavanya Raghavan , Riyazuddin Mohammed , Dasari Srilakshmi , Puttaiah Narendra K. , Venugopal Jayasree P. , Pradhan Zia S. , Devi Sathi , Sreenivasaiah Shruthi , Ganeshrao Shonraj B. , Rao Harsha L. 
Published: May 2020

Purpose:
To compare the visual field (VF) parameters of the new Swedish Interactive Thresholding Algorithm (SITA), SITA Faster (SFR) with that of SITA Standard (SS) on the Humphrey Field Analyzer.

Methods:
Ninety-seven eyes of 97 subjects (63 glaucoma, 26 glaucoma suspects, and 8 normal eyes) underwent VF examination with SFR and SS strategies on the same day in random order. Agreement in VF parameters between SFR and SS strategies was assessed by Bland and Altman plots. In addition, some subjects underwent a second VF examination with SFR strategy to evaluate its test-retest variability.

Results:
The median test duration of SS strategy was 6 minutes 14 seconds, whereas SFR was 2 minutes 49 seconds (55% shorter, P<0.001). Median mean deviation (−7.3 vs. −7.6 dB, P=0.73) and VF index (88 vs. 88%, P=0.32) were similar between the 2 strategies, whereas pattern standard deviation was significantly higher (4.8 vs. 4.7 dB, P=0.01) with SS strategy. Overall average threshold sensitivity and Garway-Heath sector-wise threshold sensitivities were similar between the 2 strategies except for the nasal sector where SFR strategy had higher sensitivity (26 vs. 25 dB, P=0.02). Bland-Altman plots showed the mean difference in all VF parameters between the SS and SFR strategies were small (ranging from −1.0 dB for the nasal sector to −0.01 dB for superotemporal sector sensitivity). The test-retest variability of VF parameters with SFR strategy was low.

Conclusions:
VF parameters with SFR showed good agreement with that of SS strategy. This, combined with low test-retest variability, suggests that SFR can be considered for diagnosis and monitoring of glaucoma.
Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs
Authors: Brilhante Raimunda Sâmia Nogueira , Silva José Alexandre Telmos , Araújo Géssica dos Santos , Pereira Vandbergue Santos , Gotay Wilker Jose Perez , Oliveira Jonathas Sales de , Guedes Glaucia Morgana de Melo , Pereira-Neto Waldemiro Aquino , Castelo-Branco Débora de Souza Collares Maia , Cordeiro Rossana de Aguiar , Sidrim José Júlio Costa , Rocha Marcos Fábio Gadelha 
Published: May 2020

Introduction.Cryptococcusspecies are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS.Aim.The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms ofCryptococcusspecies.Methodology.Susceptibility testing of darunavir and the common antifungals against 12 members of theCryptococcus neoformans/Cryptococcus gattiispecies complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively.Results.Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. AllCryptococcusspecies strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05).Conclusion.Darunavir presents antifungal activity against planktonic cells ofCryptococcusspecies and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms ofCryptococcusspecies. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.
Use of vestibular galvanic stimulation for correction of the position and of the gaze in a flight simulator
Authors: Vega Rosario , Gordillo Jorge , Alexandrov Vladimir , Alexandrova Tamara , Soto Enrique 
Published: May 2020

SummaryGalvanic Vestibular Stimulation(GVS) induce the sensation of movement in subjects in flight simulators and in cosmonauts, creating a cognitive simulation of movement. The system consists of a control unit, a function generator, and a power amplifier. GVS is capable of activating the neurons of the vestibular system and inducing the sensation of movement. When applied in coordination with a flight simulation program GVS modifies the eye movement control responses, electrically activating the vestibular-ocular, vestibule-colic, and vestibule-spinal reflexes. The ultimate goal of this type of stimulation is to generate augmented reality in the pilots during training or potentially also during a flight in microgravity.
Flexible comparison of batch correction methods for single-cell RNA-seq using BatchBench
Authors: Chazarra-Gil Ruben , van Dongen Stijn , Kiselev Vladimir Yu , Hemberg Martin 
Published: May 2020

AbstractAs the cost of single-cell RNA-seq experiments has decreased, an increasing number of datasets are now available. Combining newly generated and publicly accessible datasets is challenging due to non-biological signals, commonly known as batch effects. Although there are several computational methods available that can remove batch effects, evaluating which method performs best is not straightforward. Here we present BatchBench (https://github.com/cellgeni/batchbench), a modular and flexible pipeline for comparing batch correction methods for single-cell RNA-seq data. We apply BatchBench to eight methods, highlighting their methodological differences and assess their performance and computational requirements through a compendium of well-studied datasets. This systematic comparison guides users in the choice of batch correction tool, and the pipeline makes it easy to evaluate other datasets.
Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets
Authors: Castle Brian T. , Dock Carissa , Hemmat Mahya , Kline Susan , Tignanelli Christopher , Rajasingham Radha , Masopust David , Provenzano Paolo , Langlois Ryan , Schacker Timothy , Haase Ashley , Odde David J. 
Published: May 2020

AbstractEffective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (162= 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in most viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.
RepeatProfiler: a pipeline for visualization and comparative analysis of repetitive DNA profiles
Authors: Negm S. , Greenberg A. , Larracuente A.M. , Sproul J.S. 
Published: May 2020

AbstractStudy of DNA repeats in model organisms highlights the role of repetitive DNA in many processes that drive genome evolution and phenotypic change. Because repetitive DNA is much more dynamic than single-copy DNA, repetitive sequences can reveal signals of evolutionary history over short time scales that may not be evident in sequences from slower-evolving genomic regions. Many tools for studying repeats are directed toward organisms with existing genomic resources, including genome assemblies and repeat libraries. However, signals in repeat variation may prove especially valuable in disentangling evolutionary histories in diverse non-model groups, for which genomic resources are limited. Here we introduceRepeatProfiler, a tool for generating, visualizing, and comparing repetitive DNA profiles from low-coverage, short-read sequence data.RepeatProfilerautomates the generation and visualization of repetitive DNA coverage depth profiles and allows for statistical comparison of profile shape across samples. In addition,RepeatProfilerfacilitates comparison of profiles by extracting signal from sequence variants across profiles which can then be analyzed as molecular morphological characters using phylogenetic analysis. We validateRepeatProfilerwith data sets from ground beetles (Bembidion), flies (Drosophila), and tomatoes (Solanum). We highlight the potential of repetitive DNA profiles as a high-resolution data source for studies in species delimitation, comparative genomics, and repeat biology.
Protective Effects of Edaravone Against Hypoxia-Induced Lethality in Male Swiss Albino Mice
Authors: Shaki Fatemeh , Mokhtaran Mina , Raei Maedeh , Shamshirian Amir , Eslami Shahram , Shamshirian Danial , Ebrahimzadeh Mohammad Ali 
Published: May 2020

AbstractEdaravone has been recently used for the treatment of acute cerebral infarction. However, there is no data on the protective effects of this drug against hypoxia-induced lethality. Here, we aimed to evaluate the protective effects of edaravone against hypoxia-induced lethality and oxidative stress in mice through three experimental models of hypoxia.Materials and Methodsmale Swiss albino mice were randomly housed in groups of 10. Mice received single i.p. injections of edaravone for four consecutive days. Three experimental models of hypoxia: asphyctic, circulatory, and haemic were applied in this study. Oxidative stress, lipid peroxidation and glutathione content were assessed after hypoxia induction.ResultsSignificant protective activities were observed in all models of hypoxia. Antihypoxic activities were highly significant in asphytic and circulatory hypoxia. These effects were dose-dependent. Edaravone, at 5 mg kg−1, showed statistically significant activities concerning the control groups. Edaravone significantly prolonged the latency for death. At 2.5 mg kg−1, it prolonged survival time (26.08 ± 0.79 min). This effect was statistically significant (P<0.05). Also, edaravone significantly inhibited hypoxia-induced oxidative stress (lipid peroxidation and glutathione oxidation) in three models of hypoxia.ConclusionsEdaravone showed an excellent protective effect against hypoxia in all tested models and decreased the oxidative stress in the brain tissue of hypoxic mice. Notably, results showed significant and dose-dependent effects on the models of asphytic and circulatory hypoxia. The antioxidant activity itself might be a proposed mechanism for the antihypoxic activities of this drug.Impact statementThis study provides a novel proof-of-concept for a FDA approved drug, which will open a new area of research in the field and drug repurposing.
Sex and Power: sexual dimorphism in trait variability and its eco-evolutionary and statistical implications
Authors: Zajitschek S.R.K. , Zajitschek F. , Bonduriansky R. , Brooks R.C. , Cornwell W. , Falster D.S. , Lagisz M. , Mason J. , Senior A. M. , Noble D. A. W. , Nakagawa S. 
Published: May 2020

ABSTRACTBiomedical and clinical sciences are experiencing a renewed interest in the fact that males and females differ in many anatomic, physiological, and behavioral traits. Sex differences in trait variability, however, are yet to receive similar recognition. In medical science, mammalian females are assumed to have higher trait variability due to estrous cycles (the ‘estrus-mediated variability hypothesis’); historically in biomedical research, females have been excluded for this reason. Contrastingly, evolutionary theory and associated data support the ‘greater male variability hypothesis’. Here, we test these competing hypotheses in 218 traits measured in >26,900 mice, using meta-analysis methods. Neither hypothesis could universally explain patterns in trait variability. Sex-bias in variability was trait-dependent. While greater male variability was found in morphological traits, females were much more variable in immunological traits. Sex-specific variability has eco-evolutionary ramifications including sex-dependent responses to climate change, as well as statistical implications including power analysis considering sex difference in variance.
Decomposition in mixed beech forests in the south-western Alps under severe summer drought
Authors: Jourdan Marion , Hättenschwiler Stephan 
Published: May 2020

ABSTRACTClimate and plant litter diversity are major determinants of carbon (C) and nitrogen (N) cycling rates during decomposition. Yet, how these processes will be modified with combined changes in climate and biodiversity is poorly understood. With a multisite field experiment, we studied the interactive effects of summer drought (using rainout shelters) and tree species mixing in beech forests in the French Alps. Forests included monospecific stands ofFagus sylvatica, Abies alba, andQuercus pubescensand two-species mixtures composed of beech and one of the other species. We hypothesized (1) negative effects of summer drought on C and N loss during decomposition and (2) mitigation of these negative effects in mixed tree species stands. Litter lost 35% of initial C, and 15% of N on average across all sites and litter types over 30 months of decomposition. Summer drought consistently, but weakly, reduced C loss but had no effect on N loss. Tree species mixing did not alter drought effects on decomposition but had non-additive effects on C and N loss, which were dominated by direct litter mixing rather than indirect tree canopy effects. Our data suggest relatively small drought effects on decomposition, possibly because process rates are generally slow during summer and because microsite variability exceeds that in response to rain exclusion. The dominant contribution of litter mixing to biodiversity effects supports the importance of microsite conditions for C and N dynamics during decomposition, which should be accounted for more explicitly in climate and biodiversity change predictions.
Precise detection of Acrs in prokaryotes using only six features
Authors: Dong Chuan , Pu Dong-Kai , Ma Cong , Wang Xin , Wen Qing-Feng , Zeng Zhi , Guo Feng-Biao 
Published: May 2020

ABSTRACTAnti-CRISPR proteins (Acrs) can suppress the activity of CRISPR-Cas systems. Some viruses depend on Acrs to expand their genetic materials into the host genome which can promote species diversity. Therefore, the identification and determination of Acrs are of vital importance. In this work we developed a random forest tree-based tool, AcrDetector, to identify Acrs in the whole genomescale using merely six features. AcrDetector can achieve a mean accuracy of 99.65%, a mean recall of 75.84%, a mean precision of 99.24% and a mean F1 score of 85.97%; in multi-round, 5-fold cross-validation (30 different random states). To demonstrate that AcrDetector can identify real Acrs precisely at the whole genome-scale we performed a cross-species validation which resulted in 71.43% of real Acrs being ranked in the top 10. We applied AcrDetector to detect Acrs in the latest data. It can accurately identify 3 Acrs, which have previously been verified experimentally. A standalone version of AcrDetector is available athttps://github.com/RiversDong/AcrDetector. Additionally, our result showed that most of the Acrs are transferred into their host genomes in a recent stage rather than early.
Discovery of positive and purifying selection in metagenomic time series of hypermutator microbial populations
Authors: Maddamsetti Rohan , Grant Nkrumah A. 
Published: May 2020

ABSTRACTA general method to infer both positive and purifying selection during the real-time evolution of hypermutator pathogens would be broadly useful. To this end, we introduce a simple test to infer mode of selection (STIMS) from metagenomic time series of evolving microbial populations. We test STIMS on metagenomic data generated by simulations of bacterial evolution, and on metagenomic data spanning 62,750 generations of Lenski’s long-term evolution experiment withEscherichia coli(LTEE). In both cases, STIMS recovers signals of positive and purifying selection on gold standard sets of genes. Using STIMS, we find strong evidence of ongoing positive selection on key regulators of theE. coligene regulatory network, even in some hypermutator populations. STIMS also detects positive selection on regulatory genes in hypermutator populations ofPseudomonas aeruginosathat adapted to subinhibitory concentrations of colistin – an antibiotic of last resort – for just twenty-six days of laboratory evolution. Our results show that the fine-tuning of gene regulatory networks is a general mechanism for rapid and ongoing adaptation. The simplicity of STIMS, together with its intuitive visual interpretation, make it a useful test for positive and purifying selection in metagenomic data sets that track the evolution of hypermutator populations in real-time.
DNA methylation mediated downregulation of histone H3 variant H3.3 affects cell proliferation contributing to the development of HCC
Authors: Reddy Divya , Bhattacharya Saikat , Shah Sanket , Rashid Mudasir , Gupta Sanjay 
Published: May 2020

AbstractH3.3 variant is a versatile histone important for development and disease. We report a DNA methylation dependent decrease of histone H3 variant H3.3 in hepatocellular carcinoma (HCC) development and an increase in the level of the H3.2 variant. The loss of H3.3 correlates with a decrease in the histone PTMs associated with active transcription. The overexpression of H3.3 and H3.2 did not affect global PTMs and cell physiology, probably owing to the deregulation of specific histone chaperones CAF-1 (for H3.2) and HIRA (for H3.3) that we observed in HCC. Notably, upon P150 (CAF-1 subunit) knockdown in HCC cell lines, a cell cycle arrest in S-phase was observed, possibly due to the decrease in the histone levels necessary for DNA packaging. Furthermore, H3.3 knockdown in a preneoplastic liver cell line led to an increase in cell proliferation and a decreased transcription of tumor suppressor genes, recapitulating the tumor cell phenotype. Importantly, our data suggest that the use of DNA Methyl Transferase (DNMT) and Histone Deacetylase (HDAC) inhibitors to restore the expression of H3.3 and the altered chromatin state for the better clinical management of the disease.
Identification and physiological significance of temporal NFκB signaling codewords deployed by macrophages to classify immune threats
Authors: Taylor Brooks , Adelaja Adewunmi , Liu Yi , Luecke Stefanie , Hoffmann Alexander 
Published: May 2020

AbstractAcute and chronic inflammatory pathologies involve misregulation of macrophage functions. Physiologically, macrophages are immune sentinels that initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed, suggesting that a temporal signaling code specifies a stimulus-appropriate immune response. To identify the signaling codewords, we developed tools to enable high-throughput analysis of live, primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features that constitute codewords that convey stimulus information to the nucleus. In particular, “oscillatory” trajectories are a hallmark of the responses to host cytokine TNF. Remarkably, examining macrophages derived from a systemic autoimmune disease model suggests that confusion of two NFκB signaling codewords, and thus miscoding of TNF as a pathogen-derived stimulus, may underlie sporadic inflammatory pathology. Overall, this study identifies six codewords of the temporal NFκB signaling code for classifying immune threats and demonstrates their biological significance.
Functional analysis of theteosinte branched 1gene in the tetraploid switchgrass (Panicum virgatum L.) by CRISPR/Cas9-directed mutagenesis
Authors: Liu Yang , Wang Weiling , Yang Bing , Currey Christopher , Fei Shui-zhang 
Published: May 2020

AbstractTillering is an important biomass yield component trait in switchgrass (Panicum virgatum L.).Teosinte branched 1(tb1)/Branched 1(BRC1) gene is a known regulator for tillering/branching in several plant species; however, its role on tillering in switchgrass remains unknown. Here, we report physiological and molecular characterization of mutants created by CRISPR/Cas9. We successfully obtained non-chimericPvtb1aandPvtb1bmutants from chimeric T0 mutants using nodal culture. The biallelicPvtb1a-Pvtb1bmutant plants produced significantly more tillers and higher fresh weight biomass than the wild-type plants. The increased tiller production in the mutant plants resulted primarily from hastened outgrowth of lower axillary buds. Increased tillers were also observed in transgene-free T1 monoallelic mutants for eitherPvtb1a-Pvtb1borPvtb1bgene alone, suggestingPvtb1genes act in a dosage-dependent manner. Transcriptome analysis showed 831 genes were differentially expressed in thePvtb1a-Pvtb1bdouble knockdown mutant. Gene Ontology analysis revealed downregulation ofPvtb1genes affected multiple biological processes, including transcription, flower development, cell differentiation, and stress/defense responses in edited plants. This study demonstrates thatPvtb1genes play a pivotal role in tiller production as a negative regulator in switchgrass and provides opportunities for further research aiming to elucidate the molecular pathway regulating tillering in switchgrass.HighlightSolid non-chimeric mutants were successfully isolated from CRISPR/Cas9-induced chimeric mutants using nodal culture.Teosinte branched 1(tb1) genes are involved in various pathways to regulate tillering in switchgrass.
Integrated hiPSC-based liver and heart microphysiological systems predict unsafe drug-drug interaction
Authors: Lee-Montiel Felipe T. , Laemmle Alexander , Dumont Laure , Lee Caleb S. , Huebsch Nathaniel , Charwat Verena , Okochi Hideaki , Hancock Matthew J. , Siemons Brian , Boggess Steven C. , Goswami Ishan , Miller Evan W. , Willenbring Holger , Healy Kevin 
Published: May 2020

AbstractMicrophysiological systems (MPSs) mimicking human organ functionin vitroare an emerging alternative to conventional cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both built with the same hiPSC line—to study drug-drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS. These results establish functional integration of isogenic hiPSC-based liver and cardiac MPSs, which allows screening for DDI, and thus drug efficacy and toxicity, in the same genetic background.