bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of the COVID-19 Cases in Gulf Cooperation Council (GCC) countries using ARIMA and MA-ARIMA models
Authors: Yagoub Rahamtalla , Eledum Hussein 
Published: May 2021

AbstractCoronavirus disease 2019 (COVID-19) is still a great pandemic presently spreading all around the world. In Gulf Cooperation Council (GCC) countries, there were 1015269 COVID-19 confirmed cases, 969424 recovery cases, and 9328 deaths as of 30th Nov. 2020. This paper, therefore, subjected the daily reported COVID-19 cases of these three variables to some statistical models including classical ARIMA, kth SMA-ARIMA, kth WMA-ARIMA, and kth EWMA-ARIMA to study the trend and to provide the long-term forecasting of the confirmed, recovery, and death cases of the novel COVID-19 pandemic in the GCC countries. The data analyzed in this study covered the period starting from the first case of coronavirus reported in each GCC country to Nov 30, 2020. To compute the best parameter estimates, each model was fitted for 90% of the available data in each country, which is called the in-sample forecast or training data, and the remaining 10% was used for the out-of-sample forecast or testing model. The AIC was applied to the training data as a criterion method to select the best model. Furthermore, the statistical measure RMSE was utilized for testing data, and the model with the minimum AIC and minimum RMSE was selected. The main finding, in general, is that the two models WMA-ARIMA and EWMA-ARIMA, besides the cubic linear regression model have given better results for in-sample and out-of-sample forecasts than the classical ARIMA models in fitting the confirmed and recovery cases while the death cases haven’t specific models.
Non-pharmaceutical interventions and the emergence of pathogen variants
Authors: Ashby Ben , Smith Cameron A. , Thompson Robin N. 
Published: May 2021

AbstractNon-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, are important public health measures that can reduce pathogen transmission. In addition to playing a crucial role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply, restricting the availability of susceptible hosts, and altering the strength of selection for novel variants. Yet it is unclear how NPIs might affect the emergence of novel variants that are able to escape pre-existing immunity (partially or fully), are more transmissible, or cause greater mortality. We analyse a stochastic two-strain epidemiological model to determine how the strength and timing of NPIs affects the emergence of variants with similar or contrasting life-history characteristics to the wildtype. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross immunity to have a greater probability of emerging at intermediate levels of NPIs. This is because intermediate levels of NPIs allow an epidemic of the wildtype that is neither too small (facilitating high mutation supply), nor too large (leaving a large pool of susceptible hosts), to prevent a novel variant becoming established in the host population. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be implementation of strong, timely NPIs.
Minhee Analysis Package: An Integrated Software Package for Detection and Management of Spontaneous Synaptic Events
Authors: Kim Yong Gyu , Shin Jae Jin , Kim Sang Jeong 
Published: May 2021

ABSTRACTTo understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.
RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells
Authors: Durand Sébastien , Bruelle Marion , Bourdelais Fleur , Bennychen Bigitha , Blin-Gonthier Juliana , Isaac Caroline , Huyghe Aurélia , Seyve Antoine , Vanbelle Christophe , Meyronet David , Catez Frédéric , Diaz Jean-Jacques , Lavial Fabrice , Ricci Emiliano P. , Ducray François , Gabut Mathieu 
Published: May 2021

AbstractEmbryonic stem cell (ESC) fate decisions are regulated by a complex molecular circuitry that requires tight and coordinated gene expression regulations at multiple levels from chromatin organization to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key regulatory pathways that efficiently control stem cell homeostasis. However, the molecular mechanisms underlying the regulation of these pathways remain largely unknown to date. Here, we analyzed the expression, in mouse ESCs, of over 300 genes involved in ribosome biogenesis and we identified RSL24D1 as the most differentially expressed between self-renewing and differentiated ESCs. RSL24D1 is highly expressed in multiple mouse pluripotent stem cell models and its expression profile is conserved in human ESCs. RSL24D1 is associated with nuclear pre-ribosomes and is required for the maturation and the synthesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors, including POU5F1 and NANOG, as well as components of the polycomb repressive complex 2 (PRC2). Consistently, RSL24D1 is required for mouse ESC self-renewal and proliferation. Taken together, we show that RSL24D1-dependant ribosome biogenesis is required to both sustain the expression of pluripotent transcriptional programs and silence developmental programs, which concertedly dictate ESC homeostasis.
A global dataset for the projected impacts of climate change on four major crops
Authors: Hasegawa Toshihiro , Wakatsuki Hitomi , Ju Hui , Vyas Shalika , Nelson Gerald C. , Farrell Aidan , Deryng Delphine , Meza Francisco , Makowski David 
Published: May 2021

AbstractReliable estimates of the impacts of climate change on crop production are critical for assessing the sustainability of food systems. Global, regional, and site-specific crop simulation studies have been conducted for nearly four decades, representing valuable sources of information for climate change impact assessments. However, the wealth of data produced by these studies has not been made publicly available. Here, we develop a global dataset by consolidating previously published meta-analyses and data collected through a new literature search covering recent crop simulations. The new global dataset builds on 8314 simulations from 203 studies published between 1984 and 2020. It contains projected yields of four major crops (maize, rice, soybean, and wheat) in 91 countries under major emission scenarios for the 21st century, with and without adaptation measures, along with geographical coordinates, current temperatures, local and global warming levels. This dataset provides a basis for a comprehensive understanding of the impacts of climate change on crop production and will facilitate the rapidly developing data-driven machine learning applications.
BRD9-containing non-canonical BAF complexes safeguard cell identity and prevent reprogramming
Authors: Sevinç Kenan , Sevinç Gülben Gürhan , Cavga Ayşe Derya , Philpott Martin , Kelekçi Simge , Can Hazal , Cribbs Adam P. , Ayar Enes Sefa , Arabacı Dilşad H. , Dunford James E. , Demir Ata B. , Sigua Logan H. , Qi Jun , Oppermann Udo , Onder Tamer T. 
Published: May 2021

AbstractEpigenetic reprogramming requires extensive remodeling of chromatin landscapes to silence cell-type specific gene expression programs. ATP-dependent chromatin-remodeling complexes are important regulators of chromatin structure and gene expression; however, the role of Bromodomain-containing protein 9 (BRD9) and the associated ncBAF (non-canonical BRG1-associated factors) complex in reprogramming remains unknown. Here, we show that genetic suppression of BRD9 as well as ncBAF complex subunit GLTSCR1, but not the closely related BRD7, increase the efficiency by which induced pluripotent stem cells (iPSCs) can be generated from human somatic cells. Chemical inhibition and acute degradation of BRD9 phenocopied this effect. Interestingly, we find that BRD9 is dispensable for establishment and maintenance of human pluripotency but required for mesendodermal lineage commitment during differentiation. Mechanistically, BRD9 inhibition downregulates somatic cell type-specific genes and decreases chromatin accessibility at somatic enhancers. Collectively, these results establish BRD9 as an important safeguarding factor for somatic cell identity whose inhibition lowers chromatin-based barriers to reprogramming.
Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples
Authors: Paluoja Priit , Teder Hindrek , Ardeshirdavani Amin , Bayindir Baran , Vermeesch Joris , Salumets Andres , Krjutškov Kaarel , Palta Priit 
Published: May 2021

AbstractMotivationNon-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no comprehensive and direct accuracy comparison of these tools is published. Here, we evaluate and determine the precision of five commonly used computational NIPT aneuploidy analysis tools, considering diverse sequencing depth (coverage) and fetal DNA fraction (FF) on clinically validated NIPT samples.MethodsWe evaluated computational NIPT aneuploidy analysis tools WisecondorX, NIPTeR, NIPTmer, RAPIDR, and GIPseq, on the same set of clinically validated samples, subsampled to different sequencing coverages between 1.25–20M reads per sample (RPS). These clinically validated samples consisted of 423 samples, including 19 samples with fetal chromosome 21 trisomy (T21, Down syndrome), eight trisomy 18 (T18, Edwards syndrome) and three trisomy 13 (T13, Patau syndrome) samples. For each software and sequencing coverage, we determined the number of false-negative and false-positive trisomy/euploidy calls. For a uniform trisomy detection interpretation, we defined a framework based on the percent-point function for determining the cut-off threshold for calling aneuploidy based on the sample Z-score and the reference group Z-score distribution. We also determined the effect of the naturally occurring arbitrary read placement driven uncertainty on T21 detection at very low sequencing coverage and the effect of cell-free fetal DNA fraction (FF) on the accuracy of these computational tools in the case of various sequencing coverages.ResultsThis is the first head-to-head comparison of NIPT aneuploidy detection tools for the low-coverage whole-genome sequencing approach. We determined that, with the currently available software tools, the minimum sequencing coverage with no false-negative trisomic cases was 5M RPS. Secondly, for these compared tools, the number of false-negative trisomic cases could be reduced if the trisomy call cut-off threshold considers the Z-score distribution of euploid reference samples. Thirdly, we observed that in the case of low FF, both aneuploidy Z-score and FF inference was considerably less accurate, especially in NIPT assays with 5M RPS or lower coverage.ConclusionsWe determined that all compared computational NIPT tools were affected by lower sequencing depth, resulting in systematically increasing the proportions of false-negative trisomy results as the sequencing depth decreased. Trisomy detection for lower coverage NIPT samples (e.g. 2.5M RPS) is technically possible but can increase the proportion of false-positive and false-negative trisomic cases, especially in the case of low FF.
Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold
Authors: Tan Yaw Bia , Lello Laura Sandra , Liu Xin , Law Yee-Song , Kang Congbao , Lescar Julien , Zheng Jie , Merits Andres , Luo Dahai 
Published: May 2021

AbstractAlphaviruses such as Ross River virus (RRV), chikungunya virus, Sindbis virus (SINV), and Venezuelan equine encephalitis virus are mosquito-borne pathogens that can cause arthritis or encephalitis diseases. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA polymerase (RdRp) activity essential for viral RNA replication. No 3D structure has been available for nsP4 of any alphaviruses despite its importance for understanding alphaviral RNA replication and for the design of antiviral drugs. Here, we report crystal structures of the RdRp domain of nsP4 from both RRV and SINV determined at resolutions of 2.6 and 1.9 Å. The structure of the alphavirus RdRp domain appears most closely related to RdRps from pestiviruses, noroviruses, and picornaviruses. Hydrogendeuterium exchange mass spectrometry (HDX-MS) and nuclear magnetic resonance (NMR) methods, showed that in solution, nsP4 is highly dynamic with an intrinsically disordered N-terminal domain. Both full-length nsP4 and the RdRp domain were capable to catalyze RNA polymerization. Structure-guided mutagenesis using atrans-replicase system identified nsP4 regions critical for viral RNA replication.Key PointsCrystal structures of alphavirus nsP4 RNA polymerase domain from RRV and SINV.nsP4 protein is highly dynamic with an intrinsically disordered N-terminal domain.Optimized RNA elongation activity assay to facilitate antiviral discovery.
The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate
Authors: Gee Sarah , Chandiramani Manju , Seow Jeffrey , Modestini Carlotta , Das Abhishek , Doores Katie J , Tribe Rachel M , Gibbons Deena L 
Published: May 2021

AbstractDespite extensive and ongoing studies of SARS-CoV-2 and evidence that pregnant women are at increased risk of severe COVID-19, the effect of maternal infection on the developing infant remains unclear. To determine the potential impact of exposure to SARS-CoV-2in uteroon the neonate, we have assessed the immunological status of infants born to mothers with confirmed SARS-CoV-2 infection during gestation. No evidence of vertical transmission of SARS-CoV-2 was observed, but transfer of maternal SARS-CoV-2 specific IgG to infants was apparent, although to a lesser extent in cases of active or recent maternal infection. Infants born to mothers with recent/ongoing infection had elevated circulating pro-inflammatory cytokines and enhanced percentages of innate immune cells compared to that seen in infants born to uninfected mothers. In tandem, higher frequencies of FOXP3+regulatory T cells and circulating IL-10 demonstrated a further nuance to the neonatal effector response. Interestingly, cytokine functionality was enhanced in infants born to mothers exposed to SARS-CoV-2 at any time during pregnancy. This indicates that maternal SARS-CoV-2 infection influencesin uteropriming of the fetal immune system.
Cellular-resolution monitoring of ischemic stroke pathologies in the rat cortex
Authors: Chornyy Sergiy , Das Aniruddha , Borovicka Julie A. , Patel Davina , Chan Hugh H. , Hermann John K. , Jaramillo Thomas C. , Machado Andre G. , Baker Kenneth B. , Dana Hod 
Published: May 2021

AbstractStroke is a leading cause of disability in the Western world. Current post-stroke rehabilitation treatments are only effective in approximately half of the patients. Therefore, there is a pressing clinical need for developing new rehabilitation approaches for enhancing the recovery process, which requires the use of appropriate animal models. Here we study the activity patterns of multiple cortical regions in the rat brain using two-photon microscopy. We longitudinally recorded the fluorescence signal from thousands of neurons labeled with a genetically-encoded calcium indicator before and after an ischemic stroke injury, and found substantial functional changes across motor, somatosensory, and visual cortical regions during the post-stroke cortical reorganization period. We show that a stroke injury in the primary motor cortex has an effect on the activity patterns of neurons not only in the motor and somatosensory cortices, but also in the more distant visual cortex, and that these changes include modified firing rates and kinetics of neuronal activity patterns in response to a sensory stimulus. Changes in neuronal population activity provided animal-specific, circuit-level information on the poststroke cortical reorganization process, which may be essential for evaluating the efficacy of new approaches for enhancing the recovery process.
Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers
Authors: McCarthy Elizabeth E. , Odorizzi Pamela M. , Lutz Emma , Smullin Carolyn P. , Tenvooren Iliana , Stone Mars , Simmons Graham , Hunt Peter W. , Feeney Margaret E. , Norris Philip J. , Busch Michael P. , Spitzer Matthew H. , Rutishauser Rachel L. 
Published: May 2021

AbstractAlthough the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD-B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune “set-point.” Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.One Sentence SummaryMass cytometry reveals acute ZIKV infection cellular immune signatures that predict high or low neutralizing antibody titers 6 months post-infection.
RNA folding using quantum computers
Authors: Fox Dillion M. , MacDermaid Christopher M. , Schreij Andrea M.A. , Zwierzyna Magdalena , Walker Ross C. 
Published: May 2021

AbstractThe 3-dimensional fold of an RNA molecule is largely determined by patterns of intramolecular hydrogen bonds between bases. Predicting the hydrogen bonding network from the sequence, also referred to as RNA secondary structure prediction or RNA folding, is a nondeterministic polynomial-time (NP)-complete computational problem. The structure of the molecule is strongly predictive of its functions and biochemical properties, and therefore the ability to accurately predict the structure is a crucial tool for biochemists. Many methods have been proposed to efficiently sample possible secondary structure patterns. Classic approaches employ dynamic programming, and recent studies have explored approaches inspired by evolutionary algorithms. This work demonstrates leveraging quantum computing hardware to predict the secondary structure of RNA. A Hamiltonian written in the form of a Binary Quadratic Model (BQM) is derived to drive the system toward maximizing the number of base pairs while simultaneously maximizing the average length of the stems. An Adiabatic Quantum Computer (AQC) is compared to a Replica Exchange Monte Carlo (REMC) algorithm programmed with the same objective function, with the AQC being shown to be highly competitive at rapidly identifying low energy solutions. The method proposed in this study was compared to three algorithms from literature and was found to have the highest success rate.
Subcutaneous infusion of neurosecretory protein GL promotes fat accumulation in mice
Authors: Narimatsu Yuki , Fukumura Keisuke , Iwakoshi-Ukena Eiko , Mimura Ayaka , Furumitsu Megumi , Ukena Kazuyoshi 
Published: May 2021

AbstractWe recently identified a novel small secretory protein, neurosecretory protein GL (NPGL), in the vertebrate hypothalamus. We revealed that NPGL is involved in energy homeostasis using intracerebroventricular infusion in rodents. However, the effect of NPGL through peripheral administration remains to be elucidated and may be important for therapeutic use. In this study, we performed subcutaneous infusion of NPGL in mice for 12 days and found that it accelerated fat accumulation in white adipose tissue (WAT) without increasing in body mass gain and food intake. The mass of the testis, liver, kidney, heart, and gastrocnemius muscle remained unchanged. Analysis of mRNA expression by quantitative reverse transcription-polymerase chain reaction showed that proopiomelanocortin was suppressed in the hypothalamus by the infusion of NPGL. We observed a decreasing tendency in serum triglyceride levels due to NPGL, while serum glucose, insulin, leptin, and free fatty acids levels were unchanged. These results suggest that the peripheral administration of NPGL induces fat accumulation in WAT via the hypothalamus.
Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury
Authors: Fiore Nathan T , Yin Zhuoran , Guneykaya Dilansu , Gauthier Christian D , Hayes Jessica , D’Hary Aaron , Butovsky Oleg , Moalem-Taylor Gila 
Published: May 2021

SUMMARYRecent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis revealed a substantial change in microglial gene expression only within the ipsilateral lumbar spinal cord 7-days after nerve injury. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice, reflecting acute activation. Further, in vitro studies revealed that only male microglia from nerve-injured mice developed a reactive phenotype with increased phagocytotic activity. This study indicates distinct sex differences in spinal microglia and suggests they contribute to the sex-specific pain processing following nerve injury.