bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotational worker vaccination provides indirect protection to vulnerable groups in regions with low COVID-19 prevalence
Authors: Martignoni Maria M. , Rahman Proton , Hurford Amy 
Published: October 2021

AbstractAs COVID-19 vaccines become available, different model-based approach have been developed to evaluate strategic priorities for vaccine allocation to reduce severe illness. One strategy is to directly prioritize groups that are likely to experience medical complications due to COVID-19, such as older adults. A second strategy is to limit community spread by reducing importations, for example by vaccinating members of the mobile labour force, such as rotational workers. This second strategy may be appropriate for regions with low disease prevalence, where importations are a substantial fraction of all cases and reducing the importation rate reduces the risk of community outbreaks, which can provide significant indirect protection for vulnerable individuals. Current studies have focused on comparing vaccination strategies in the absence of importations, and have not considered allocating vaccines to reduce the importation rate. Here, we provide an analytical criteria to compare the reduction in the risk of hospitalization and intensive care unit (ICU) admission over four months when either older adults or rotational workers are prioritized for vaccination. Vaccinating rotational workers (assumed to be 6,000 individuals and about 1% of the Newfoundland and Labrador (NL) population) could reduce the average risk of hospitalization and ICU admission by 42%, if no community spread is observed at the time of vaccination, because epidemic spread is reduced and vulnerable individuals are indirectly protected. In contrast, vaccinating all individuals aged 75 and older (about 43,300 individuals, or 8% of the NL population) would lead to a 24% reduction in the average risk of hospitalization, and to a 45% reduction in the average risk of ICU admission, because a large number of individuals at high risk from COVID-19 are now vaccinated. Therefore, reducing the risk of hospitalization and ICU admission of the susceptible population by reducing case importations would require a significantly lower number of vaccines. Benefits of vaccinating rotational workers decrease with increasing infection prevalence in the community. Prioritizing members of the mobile labour force should be considered as an efficient strategy to indirectly protect vulnerable groups from COVID-19 exposure in regions with low disease prevalence.
Inactivated Poliovirus Vaccine Induces Antibodies that Inhibit RNA Synthesis of SARS-CoV-2: An open-label, pre-post vaccine clinical trial
Authors: Comunale Brittany A. , Jackson-Ward Erin , Jiang Yong , Ward Laura P. , Liu Qianna , Ji Lyuqing , Lai Michelle , Engineer Lilly , Comunale Roderick A. , Xie Qiyi 
Published: October 2021

AbstractBackgroundPoliovirus vaccination induces an adaptive humoral immune response; in vitro experiments show polio-immune sera contain antibodies against the poliovirus RNA transcriptase that cross-react with SARS-CoV-2. While structural similarities between poliovirus and SARS-CoV-2 could have major implications for the COVID-19 response worldwide, polio-induced immune responses against SARS-CoV-2 have not been confirmed in prospective clinical trials.ObjectiveTo evaluate whether immune sera from adults who recently received inactivated poliovirus vaccination (IPV) can block SARS-CoV-2’s ability to synthesize RNA.InterventionIPV intramuscular injection.MeasurementsPre-inoculation and 4-weeks post-inoculation sera were tested for anti-3Dpol (RNA-dependent RNA polymerase, RdRp) antibodies using enzyme-linked immunosorbent assays (ELISA). To assess IPV’s ability to induce antibodies that inhibit SARS-CoV-2 RNA synthesis, immune-based detection assays tested RdRp enzymatic activity in polio-immune sera.Results298 of the 300 enrolled participants completed both on-site visits. Comparing pre-inoculation to 4-week samples, 85.2% of participants demonstrated an increase in anti-3Dpolantibodies against RdRp proteins. Among tested post-inoculation samples, 94.4% demonstrated inhibition of SARS-CoV-2 RNA synthesis. Few inoculation-related side effects were reported (2.0%), all were minor.LimitationsParticipants were not systematically tested for COVID-19, though known exposures were reported and positive results (1.7%) were documented.ConclusionIPV can induce antibodies that inhibit SARS-CoV-2 RNA synthesis, minimizing the risk of viral replication in infected individuals. This finding has practical implications for resource-deficient areas that may have limited access to newly developed COVID-19 vaccines and/or areas with low COVID-19 vaccination rates due to hesitancy.Funding SourcePrivate donors.RegistrationClinicalTrials.gov: NCT04639375.
Molecular Prognosis of Endometrial Adenocarcinoma by Expression Patterns of the V-ATPase C1 Subunit
Authors: Chacur Abdalla Dib , Couto-Viera Juliana , Façanha Anna Okorokova , Baptista Glenerson , Façanha Arnoldo Rocha 
Published: October 2021

AbstractComparative analysis of expression patterns of ATP6V1C1 encoding C1 subunit of V-H+-ATPase revealed that molecular alterations correlated with endometrial cancer of better prognosis were grouped with low ATP6V1C1 expression while those correlated with worse prognosis were clustered with high ATP6V1C1 expression levels.Expression patterns of C1 subunit in endometrial adenocarcinoma are associated with molecular malignancy signatures shared by histological subtypes of highest mortality rate suggesting that G3 adenocarcinoma exhibits molecular changes resembling endometrial serous carcinoma.ATP6V1C1 might serve as novel prognostic marker allowing identification of targetable pathways for high-risk endometrial cancer.
In vivo reprogramming of murine host immune response genes following Leishmania major infection
Authors: Venugopal Gopinath , Bird Jordan T. , Washam Charity L. , Roys Hayden , Bowlin Anne , Byrum Stephanie D. , Weinkopff Tiffany 
Published: October 2021

AbstractLeishmaniaparasites cause cutaneous leishmaniasis (CL), a pathologic disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with variousLeishmaniaspecies has been investigated in vitro, but global transcriptional analysis followingL. majorinfection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing (RNA-Seq) and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo followingL. majorinfection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls. scRNA-Seq analyses revealed cellular heterogeneity including distinct resident and recruited cell types in the skin following murineL. majorinfection. Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages (Gbp2, H2-K1, H2-Aa, H2-Ab1), resident macrophages (H2-K1, H2-D1, Gbp4, Gbp8, Gbp2), and inflammatory monocytes (Gbp2, Gbp5, Gbp7, Gbp3). Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, BECs, and LECs. Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a previously undefined role for EIF2 signaling in murineL. majorinfection in vivo.Author summaryLeishmania majorcause cutaneous leishmaniasis, which is characterized by disfiguring, ulcerative skin lesions. Here, we show murineL. major-directed reprogramming of the host transcriptome in vivo. Our bulk RNA-Seq analyses revealed upregulation of antigen processing and presentation pathway, while the host ribosomal pathway was downregulated followingL. majorinfection. Similarly, scRNA-Seq analyses revealed the upregulation of transcripts responsible for antigen presentation and host defense proteins like guanylate binding proteins (GBPs) alongside the downregulation of EIF2 signalling at the site ofL. majorinfection. Overall, our transcriptomic dataset not only provides the comprehensive list of gene expression at the single-cell resolution, and highlights a previously undefined role for EIF2 signalling during murineL. majorinfection in vivo.
Bacteriocinogenic lactic acid bacteria in the traditional cereal-based beverage Boza: a genomic and functional approach
Authors: Queiroz Luciano Lopes , Hoffmann Christian , Lacorte Gustavo Augusto , Franco Bernadette Dora Gombossy de Melo , Todorov Svetoslav Dimitrov 
Published: October 2021

AbstractBoza is a traditional low-alcohol fermented beverage from the Balkan Peninsula, frequently explored as a functional food product. The product is rich in Lactic Acid Bacteria (LAB) and some of them can produce bacteriocins. In this study, a sample of Boza from Belogratchik, Bulgaria, was analyzed for the presence of bacteriocinogenic LAB, and after analyses by RAPD-PCR, three representative isolates were characterized by genomic analyses, using whole genome sequencing. Isolates identified as Pediococcus pentosaceus ST75BZ and Pediococcus pentosaceus ST87BZ contained operons encoding for bacteriocins pediocin PA-1 and penocin A, while isolate identified as P. acidilactici ST31BZ contained only the operon for pediocin PA-1 and a CRISPR/Cas system for protection against bacteriophage infection. The antimicrobial activity of bacteriocins produced by the three isolates was inhibited by treatment of the cell-free supernatants with proteolytic enzymes. The produced bacteriocins inhibited the growth of Listeria monocytogenes, Enterococcus spp. and some Lactobacillus spp., among other tested species. The levels of bacteriocin production varied from 3200 AU/ml to 12800 AU/ml recorded against L. monocytogenes 104, 637 and 711, measured at 24 h of incubation at 37°C. All bacteriocins remained active after incubation at pH 2.0 to 10.0. The activity mode of the studied bacteriocins was bactericidal, as determined against L. monocytogenes 104, 637 and 711. In addition, bactericidal activity was demonstrated using a cell leakage β-galactosidase assay, indicating a pore formation mechanism as a mode of action. The present study highlights the importance of combining metagenomic analyses and traditional microbiological approaches as way of characterizing microbial interactions in fermented foods.
Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function
Authors: Wu Qianyi , Akhter Azman , Pant Shashank , Cho Eunjoo , Zhu Jin Xin , Garner Alastair , Ohyama Tomoko , Tajkhorshid Emad , van Meyel Donald J. , Ryan Renae M. 
Published: October 2021

AbstractGlutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory Amino Acid Transporters (EAATs) regulate extracellular glutamate by transporting it into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs are also chloride (Cl−) channels, but the physiological role of Cl− conductance through EAATs is poorly understood. Mutations of human EAAT1 (hEAAT1) have been identified in patients with episodic ataxia type 6 (EA6). One mutation showed increased Cl− channel activity and decreased glutamate transport, but the relative contributions of each function of hEAAT1 to mechanisms underlying the pathology of EA6 remain unclear. Here we investigated the effects of five additional EA6-related mutations on hEAAT1 function in Xenopus laevis oocytes, and on CNS function in a Drosophila melanogaster model of locomotor behavior. Our results indicate that mutations with decreased hEAAT1 Cl− channel activity and functional glutamate transport can also contribute to the pathology of EA6, highlighting the importance of Cl− homeostasis in glial cells for proper CNS function. We also identified a novel mechanism involving an ectopic sodium (Na+) leak conductance in glial cells. Together, these results strongly support the idea that EA6 is primarily an ion channelopathy of CNS glia.
Clinically applicable rapid susceptibility testing of multi-drug resistant Staphylococcus aureus by mass spectrometry and extreme gradient boosting machine
Authors: Wang Zhuo , Wang Hsin-Yao , Pang Yuxuan , Chung Chia-Ru , Horng Jorng-Tzong , Lu Jang-Jih , Lee Tzong-Yi 
Published: October 2021

AbstractMulti-drug resistant Staphylococcus aureus is one of the major causes of severe infections. Due to the delays of conventional antibiotic susceptibility test (AST), most cases were prescribed by experience with a lower recovery rate. Linking a 7-year study of over 20,000 Staphylococcus aureus infected patients, we incorporated mass spectrometry and machine learning technology to predict the susceptibilities of patients for 4 different antibiotics that can enable early antibiotic decisions. The predictive models were externally validated in an independent patient cohort, resulting in an area under the receiver operating characteristic curve of 0.94, 0.90, 0.86, 0.91 and an area under the precision-recall curve of 0.93, 0.87, 0.87, 0.81 for oxacillin (OXA), clindamycin (CLI), erythromycin (ERY) and trimethoprim-sulfamethoxazole (SXT), respectively. Moreover, our pipeline provides AST 24–36 h faster than standard workflows, reduction of inappropriate antibiotic usage with preclinical prediction, and demonstrates the potential of combining mass spectrometry with machine learning (ML) to assist early and accurate prescription. Therapies to individual patients could be tailored in the process of precision medicine.
A spiking neural network model of the Superior Colliculus that is robust to changes in the spatial-temporal input
Authors: Alizadeh Arezoo , Van Opstal A. John 
Published: October 2021

AbstractPrevious studies have indicated that the location of a large neural population in the Superior Colliculus (SC) motor map specifies the amplitude and direction of the saccadic eye-movement vector, while the saccade trajectory and velocity profile are encoded by the population firing rates. We recently proposed a simple spiking neural network model of the SC motor map, based on linear summation of individual spike effects of each recruited neuron, which accounts for many of the observed properties of SC cells in relation to the ensuing eye movement. However, in the model, the cortical input was kept invariant across different saccades. Electrical microstimulation and reversible lesion studies have demonstrated that the saccade properties are quite robust against large changes in supra-threshold SC activation, but that saccade amplitude and peak eye-velocity systematically decrease at low input strengths. These features are not accounted for by the linear spike-vector summation model. Here we show that the model’s input projection strengths and intra-collicular lateral connections can be tuned to generate saccades that follow the experimental results.Author statementThe midbrain SC generates fast saccadic eye movements through a large population of cells within a topographically organized motor map, in which the location, spike count and temporal firing patterns of recruited cells determine saccade metrics and kinematics. According to the dynamic ensemble-coding model, each recruited SC cell contributes to the saccade by linear vector summation of all its spike contributions. Our previous spiking neural network model used invariant cortical inputs to the SC cells for all saccades. We here improved the robustness of the model to large spatial-temporal variations in the input patterns, by tuning its top-down and lateral synaptic connections, to generate saccades with properties observed in electrophysiological experiments.
Seed banks alter the molecular evolutionary dynamics ofBacillus subtilis
Authors: Shoemaker William R. , Polezhaeva Evgeniya , Givens Kenzie B. , Lennon Jay T. 
Published: October 2021

AbstractFluctuations in the availability of resources constrains the growth and reproduction of individuals, which subsequently effects the evolution of their respective populations. Many organisms contend with such fluctuations by entering a reversible state of reduced metabolic activity, a phenomenon known as dormancy. This pool of dormant individuals (i.e., a seed bank) does not reproduce and is expected to act as an evolutionary buffer, though it is difficult to observe this effect directly over an extended evolutionary timescale. Through genetic manipulation, we analyze the molecular evolutionary dynamics ofBacillus subtilispopulations in the presence and absence of a seed bank over 700 days. The ability of these bacteria to enter a dormant state increased the accumulation of genetic diversity over time and altered the trajectory of mutations, findings that were recapitulated using simulations based on a mathematical model of evolutionary dynamics. While the ability to form a seed bank did not alter the degree of negative selection, we found that it consistently altered the direction of molecular evolution across genes. Together, these results show that the ability to form a seed bank can affect the direction and rate of molecular evolution over an extended evolutionary timescale.
RAxML Grove: An empirical Phylogenetic Tree Database
Authors: Höhler Dimitri , Pfeiffer Wayne , Ioannidis Vassilios , Stockinger Heinz , Stamatakis Alexandros 
Published: October 2021

AbstractThe assessment of novel phylogenetic models and inference methods is routinely being conducted via experiments on simulated as well as empirical data. When generating synthetic data it is often unclear how to set simulation parameters for the models and generate trees that appropriately reflect empirical model parameter distributions and tree shapes. As a solution, we present and make available a new database called ‘RAxML Grove’ currently comprising more than 60,000 inferred trees and respective model parameter estimates from fully anonymized empirical data sets that were analyzed using RAxML (1) and RAxML-NG (2) on two web servers. We also describe and make available two simple applications of RAxML Grove to exemplify its usage and highlight its utility for designing realistic simulation studies and analyzing empirical model parameter and tree shape distributions.RAxML Grove is freely available at https://github.com/angtft/RAxMLGrove.
Fast and compact matching statistics analytics
Authors: Cunial Fabio , Denas Olgert , Belazzougui Djamal 
Published: October 2021

AbstractMotivationFast, lightweight methods for comparing the sequence of ever larger assembled genomes from ever growing databases are increasingly needed in the era of accurate long reads and pan-genome initiatives. Matching statistics is a popular method for computing whole-genome phylogenies and for detecting structural rearrangements between two genomes, since it is amenable to fast implementations that require a minimal setup of data structures. However, current implementations use a single core, take too much memory to represent the result, and do not provide efficient ways to analyze the output in order to explore local similarities between the sequences.ResultsWe develop practical tools for computing matching statistics between large-scale strings, and for analyzing its values, faster and using less memory than the state of the art. Specifically, we design a parallel algorithm for shared-memory machines that computes matching statistics 30 times faster with 48 cores in the cases that are most difficult to parallelize. We design a lossy compression scheme that shrinks the matching statistics array to a bitvector that takes from 0.8 to 0.2 bits per character, depending on the dataset and on the value of a threshold, and that achieves 0.04 bits per character in some variants. And we provide efficient implementations of range-maximum and range-sum queries that take a few tens of milliseconds while operating on our compact representations, and that allow computing key local statistics about the similarity between two strings. Our toolkit makes construction, storage, and analysis of matching statistics arrays practical for multiple pairs of the largest genomes available today, possibly enabling new applications in comparative genomics.Availability ad implementationOur C/C++ code is available at https://github.com/odenas/indexed_ms under GPL-3.0.
A model for the intrinsic limit of cancer therapy: duality of treatment-induced cell death and treatment-induced stemness
Authors: Angelini Erin , Wang Yue , Zhou Joseph X. , Qian Hong , Huang Sui 
Published: October 2021

AbstractIntratumor cellular heterogeneity and non-genetic cell plasticity in tumors pose a recently recognized challenge to cancer treatment. Because of the dispersion of initial cell states within a clonal tumor cell population, a perturbation imparted by a cytocidal drug only kills a fraction of cells. Due to dynamic instability of cellular states the cells not killed are pushed by the treatment into a variety of functional states, including a “stem-like state” that confers resistance to treatment and regenerative capacity. This immanent stress-induced stemness competes against cell death in response to the same perturbation and may explain the near-inevitable recurrence after any treatment. This double-edged-sword mechanism of treatment complements the selection of preexisting resistant cells in explaining post-treatment progression. Unlike selection, the induction of a resistant state has not been systematically analyzed as an immanent cause of relapse. Here, we present a generic elementary model and analytical examination of this intrinsic limitation to therapy. We show how the relative proclivity towards cell death versus transition into a stem-like state, as a function of drug dose, establishes either a window of opportunity for containing tumors or the inevitability of progression following therapy. The model considers measurable cell behaviors independent of specific molecular pathways and provides a new theoretical framework for optimizing therapy dosing and scheduling as cancer treatment paradigms move from “maximal tolerated dose,” which may promote therapy induced-stemness, to repeated “minimally effective doses” (as in adaptive therapies), which contain the tumor and avoid therapy-induced progression.