bluuebunny/crossref_metadata_2025_split huggingface dataset:
Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner
Authors: Brocke Stephanie A. , Billings Grant T. , Taft-Benz Sharon , Alexis Neil E. , Heise Mark T. , Jaspers Ilona 
Published: August 2021

AbstractWe have previously shown that exposure to particulate air pollution, both from natural and anthropogenic sources, alters gene expression in the airways and increases susceptibility to respiratory viral infection. Additionally, we have shown that woodsmoke particulates (WSP) affect responses to influenza in a sex-dependent manner. In the present study, we used human nasal epithelial cells (hNECs) from both sexes to investigate how particulate exposure could modulate gene expression in the context of SARS-CoV-2 infection. We used diesel exhaust particulate (DEP) as well as WSP derived from eucalyptus or red oak wood. HNECs were exposed to particulates at a concentration of 22 μg/cm2 for 2 h then immediately infected with SARS-CoV-2 at a MOI (multiplicity of infection) of 0.5. Exposure to particulates had no significant effects on viral load recovered from infected cells. Without particulate exposure, hNECs from both sexes displayed a robust upregulation of antiviral host response genes, though the response was greater in males. However, WSP exposure before infection dampened expression of genes related to the antiviral host response by 72 h post infection. Specifically, red oak WSP downregulated IFIT1, IFITM3, IFNB1, MX1, CCL3, CCL5, CXCL11, CXCL10, and DDX58, among others. After sex stratification of these results, we found that exposure to WSP prior to SARS-CoV-2 infection downregulated anti-viral gene expression in hNECs from females more so than males. These data indicate that WSP, specifically from red oak, alter virus-induced gene expression in a sex-dependent manner and potentially suppress antiviral host defense responses following SARS-CoV-2 infection.
Unique spatiotemporal fMRI dynamics in the awake mouse brain
Authors: Atulkumar Singh Neha , Gutierrez-Barragan Daniel , Alvino Filomena , Coletta Ludovico , Rocchi Federico , De Guzman Elizabeth , Galbusera Alberto , Panzeri Stefano , Uboldi Mauro , Gozzi Alessandro 
Published: August 2021

AbstractHuman imaging studies have shown that spontaneous brain activity exhibits stereotypic spatiotemporal reorganization in awake, conscious conditions with respect to minimally conscious states. However, whether and how this phenomenon can be generalized to lower mammalian species, remains unclear. Leveraging a robust protocol for resting-state fMRI (rsfMRI) mapping in non-anesthetized, head-fixed mice, we investigated functional network topography and dynamic structure of spontaneous brain activity in wakeful animals. We found that rsfMRI networks in the awake state, while anatomically comparable to those observed under anesthesia, are topologically configured to maximize interregional communication, departing from the underlying community structure of the mouse axonal connectome. We further report that rsfMRI activity in wakeful animals exhibits unique spatiotemporal dynamics characterized by a state-dependent, dominant occurrence of coactivation patterns encompassing a prominent participation of arousal-related forebrain nuclei, and functional anti-coordination between visual-auditory and polymodal cortical areas. We finally show that rsfMRI dynamics in awake mice exhibits a stereotypical temporal structure, in which state-dominant coactivation patterns are configured as network attractors. These findings suggest that spontaneous brain activity in awake mice is critically shaped by state-specific involvement of basal forebrain arousal systems, and document that its dynamic structure recapitulates distinctive, evolutionarily-relevant principles that are predictive of conscious states in higher mammalian species.
Discovery of novel potent, cell-permeable inhibitors of P. falciparum cGMP-dependent protein kinase
Authors: Yadav Bheemanaboina Rammohan R. , Gonzalez Mariana Lozano , Mahmood Shams Ul , Eck Tyler , Kreiss Tamara , de Souza Mariana Laureano , Aylor Samantha O. , Roth Alison , Lee Patricia , Pybus Brandon S. , Bhanot Purnima , Colussi Dennis J. , Childers Wayne E. , Gordon John , Siekierka John J. , Rotella David P. 
Published: August 2021

ABSTRACTThe discovery of new targets for treatment of malaria advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, we recently reported the discovery and optimization of novel, potent isoxazole-based PfPKG inhibitors that lacked any obvious safety warnings. This manuscript presents representative in vitro ADME, hERG characterization and cell-based antiparasitic activity of these PfPKG inhibitors. We also report the discovery and structure-activity relationships of a new series with good potency, low hERG activity and cell-based anti-parasitic activity comparable to a literature standard.
A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency
Authors: Huang Xin , Bashkenova Nazym , Hong Yantao , Guallar Diana , Hu Zhe , Malik Vikas , Li Dan , Shen Xiaohua , Zhou Hongwei , Wang Jianlong 
Published: August 2021

SUMMARYTET1 maintains hypomethylation at bivalent promoters through its catalytic activity in embryonic stem cells (ESCs). However, whether and how TET1 exerts catalytic activity-independent functions in regulating bivalent genes is not well understood. Using a proteomics approach, we mapped the TET1 interactome in mouse ESCs and identified PSPC1 as a novel TET1 partner. Genome-wide location analysis reveals that PSPC1 functionally associates with TET1 and Polycomb repressive complex-2 (PRC2) complex. We establish that PSPC1 and TET1 repress, and Neat1, the PSPC1 cognate lncRNA, activates the bivalent gene expression. In ESCs, Neat1 tethers the TET1-PSPC1 pair with PRC2 at bivalent promoters. During the ESC-to-formative epiblast-like stem cell (EpiLC) transition, PSPC1 and TET1 promote PRC2 chromatin occupancy at bivalent gene promoters while restricting Neat1 functions in facilitating PRC2 binding to bivalent gene transcripts. Our study uncovers a novel TET1-PSPC1-Neat1 molecular axis that modulates PRC2 binding affinity to chromatin and bivalent gene transcripts in controlling stem cell bivalency.In BriefTET1 is a transcriptional repressor for bivalent genes in pluripotent stem cells, but its mechanistic action on stem cell bivalency is unclear. Huang et al. use proteomics and genetic approaches to reveal that catalytic activity-independent functions of TET1, coordinated with the paraspeckle components PSPC1 and its cognate lncRNA Neat1, dynamically regulates stem cell bivalency by modulating PRC2 binding affinity to chromatin and bivalent gene transcripts in pluripotent state transition.HighlightsThe TET1 interactome identifies PSPC1 as a novel partner in ESCsTET1 and PSPC1 repress bivalent genes by promoting PRC2 chromatin occupancyNeat1 facilitates bivalent gene activation by promoting PRC2 binding to their mRNAsNeat1 bridges the TET1-PSPC1 and PRC2 complexes in regulating bivalent gene transcription
Beehives possess their own distinct microbiomes
Authors: Santorelli Lorenzo , Wilkinson Toby , Abdulmalik Ronke , Rai Yuma , Creevey Christopher J. , Huws Sharon , Gutierrez-Merino Jorge 
Published: August 2021

AbstractHoney bees use plant material to manufacture their own food. These insect pollinators visit flowers repeatedly to collect nectar and pollen, which are shared with other hive bees to produce honey and beebread. While producing these products, beehives accumulate a tremendous amount of microbes, including bacteria that derive from plants and different parts of the honey bees’ body. In this study, we conducted 16S rDNA metataxonomic analysis on honey and beebread samples that were collected from 15 beehives in the southeast of England in order to quantify the bacteria associated with beehives. The results highlighted that honeybee products carry a significant variety of bacterial groups that comprise bee commensals, environmental bacteria and pathogens of plants and animals. Remarkably, this bacterial diversity differs amongst the beehives, suggesting a defined fingerprint that is affected, not only by the nectar and pollen gathered from local plants, but also from other environmental sources. In summary, our results show that every hive possesses their own distinct microbiome, and that honeybee products are valuable indicators of the bacteria present in the beehives and their surrounding environment.
Prediction of standard cell types and functional markers from flow cytometry gating definitions using machine learning
Authors: Rodriguez-Esteban Raul , Duarte José , Teixeira Priscila C. , Richard Fabien , Koltsova Svetlana , Venus So W. 
Published: August 2021

AbstractBackgroundA key step in clinical flow cytometry data analysis is gating, which involves the identification of cell populations. The process of gating produces a set of reportable results, which are typically described by gating definitions. The non-standardized, non-interpreted nature of gating definitions represents a hurdle for data interpretation and data sharing across and within organizations. Interpreting and standardizing gating definitions for subsequent analysis of gating results requires a curation effort from experts. Machine learning approaches have the potential to help in this process by predicting expert annotations associated with gating definitions.MethodsWe created a gold-standard dataset by manually annotating thousands of gating definitions with cell type and functional marker annotations. We used this dataset to train and test a machine learning pipeline able to predict standard cell types and functional marker genes associated with gating definitions.ResultsThe machine learning pipeline predicted annotations with high accuracy for both cell types and functional marker genes. Accuracy was lower for gating definitions from assays belonging to laboratories from which limited or no prior data was available in the training. Manual error review ensured that resulting predicted annotations could be reused subsequently as additional gold-standard training data.ConclusionsMachine learning methods are able to consistently predict annotations associated with gating definitions from flow cytometry assays. However, a hybrid automatic and manual annotation workflow would be recommended to achieve optimal results.
Structural basis for targeting the human T-cell leukemia virus Tax oncoprotein and syntenin-1 interaction using a small molecule
Authors: Maseko Sibusiso B. , Van Molle Inge , Blibek Karim , Gorgulla Christoph , Olivet Julien , Blavier Jeremy , Vandermeulen Charlotte , Skupiewski Stéphanie , Saha Deeya , Ntombela Thandokuhle , Lim Julianne , Lembo Frederique , Beauvois Aurelie , Hamaidia Malik , Borg Jean-Paul , Zimmermann Pascale , Delvigne Frank , Willems Luc , Van Weyenbergh Johan , Kim Dae-Kyum , Dequiedt Franck , Arthanari Haribabu , Salehi-Ashtiani Kourosh , Ballet Steven , Volkov Alexander N. , Twizere Jean-Claude 
Published: August 2021

ABSTRACTHuman T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). Although ATL is a well-characterized T-cell neoplasm, linked to intermittent expression of the viral Tax-1 protein, there is currently no strategy to target Tax-1 functions using small molecules. Here, we report a comprehensive interaction map between Tax-1 and human PDZ domain-containing proteins (hPDZome). We show that Tax-1 interacts with more than one-third of hPDZome components, including proteins involved in cell cycle, cell-cell junctions, cytoskeleton organization, and membrane complex assembly. Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the structural basis of the interaction between the C-terminal PDZ binding motif (PBM) of Tax-1, and the PDZ domains of syntenin-1, an evolutionary conserved hub that controls exosome trafficking. Finally, we have used confocal imaging, molecular modelling, NMR and mammalian cell-based assays to demonstrate that the Tax-1/syntenin-1 interaction is amenable to small-molecule inhibition. Altogether, our study highlights the biological significance of Tax-PDZ interactome and its interplay with exosome formation. It shows a direct link between extracellular vesicles and HTLV-1 transmission, providing a novel framework for the design of targeted therapies for HTLV-1-induced diseases.
Application of a methodological approach to compare ontologies
Authors: Cardinale Yudith , Cornejo-Lupa Maria Alejandra , Pinto-De la Gala Alexander , Ticona-Herrera Regina 
Published: August 2021

Purpose
This study aims to the OQuaRE quality model to the developed methodology.

Design/methodology/approach
Ontologies are formal, well-defined and flexible representations of knowledge related to a specific domain. They provide the base to develop efficient and interoperable solutions. Hence, a proliferation of ontologies in many domains is unleashed. Then, it is necessary to define how to compare such ontologies to decide which one is the most suitable for the specific needs of users/developers. As the emerging development of ontologies, several studies have proposed criteria to evaluate them.

Findings
In a previous study, the authors propose a methodological process to qualitatively and quantitatively compare ontologies at Lexical, Structural and Domain Knowledge levels, considering correctness and quality perspectives. As the evaluation methods of the proposal are based on a golden-standard, it can be customized to compare ontologies in any domain.

Practical implications
To show the suitability of the proposal, the authors apply the methodological approach to conduct comparative studies of ontologies in two different domains, one in the robotic area, in particular for the simultaneous localization and mapping (SLAM) problem; and the other one, in the cultural heritage domain. With these cases of study, the authors demonstrate that with this methodological comparative process, we are able to identify the strengths and weaknesses of ontologies, as well as the gaps still needed to fill in the target domains.

Originality/value
Using these metrics and the quality model from OQuaRE, the authors are incorporating a standard of software engineering at the quality validation into the Semantic Web.
MIMO-Orthogonal space time block code system joint with BCH-TC in Rayleigh fading channel for performance of transmit antenna selection
Authors: Deotale Nitin Tejram 
Published: August 2021

PurposeTo enhance the performance transmit antenna selection (TAS) of spatial modulation (SM), systems technique needs to be essential. This TAS is an effective technique for reducing the multiple input multiple output (MIMO) systems computational difficulty, and bit error rate (BER) can increase remarkably by various TAS algorithms. But these selection methods cannot provide code gain, so it is essential to join the TAS with external code to obtain cy -ode gain advantages in BER.Design/methodology/approachIn this paper, Bose–Chaudhuri–Hocquenghem (BCH)-Turbo code TC is combined with the orthogonal space time block code system.FindingsIn some existing work, the improved BER has been perceived by joining forward error correction code and space time block code (STBC) for MIMO systems provided greater code gain. The proposed work can provide increasing code gain and the effective advantages of the TAS-OSTBC system.Originality/valueTo perform the system analysis, Rayleigh channel is used. In the case with multiple TAS-OSTBC systems, better performance can provide by this new joint of the BCH-Turbo compared to the conventional Turbo code for the Rayleigh fading.
Do academic spin-offs outperform young innovative companies? A comparison of survival rates and growth
Authors: Francois Valérie , Belarouci Matthieu 
Published: August 2021

PurposeThis article investigates the distinctive characteristics and the performance of academic spin-offs within young innovative companies (YICs) supported by public regional agencies. Considering that academic spin-offs are characterized by high intensity in innovation and technology transfer, we raise the issue of their performance relative to other YICs.Design/methodology/approachThe authors focus on YICs which receive support from public or semi-public institutions at the early stage of their development as a reward for their innovative business ideas. The study is performed in two steps. First, the authors estimate the growth of the academic spin-offs within a set of YICs supported for fewer than 5 years. This estimation is based on data gathered in 2014. Second, the authors investigate the survival of these supported YICs with the Cox proportional hazards model, 5 years later, at the end of 2019.FindingsResults reveal that academic spin-offs are more able to capture resources in the early stages: These firms have more patents, more external funding and higher increases in the number of employees. The authors also demonstrate that academic spin-offs have the highest survival rates.Research limitations/implicationsThe drawback of the studies on ASOs is the limited sample. The main issue is related to survival analysis. Limitation of the sample sizes precludes from in-depth survival analyses, which may highlight fundamental differences in the development patterns of the firm.Practical implicationsThe study’s results provide evidence on how the identity of academic spin-offs based on technology transfer act as a positive signal to obtain legitimacy. It is of particular interest for entrepreneurs who can rely on trust provided by their parent institution to engage in negotiations with different stakeholders. Moreover, results give insights to policymakers on the usefulness to invest on academic spin-offs because of its outperforming results.Originality/valueThe results provide important insights for designing, conducting and monitoring policies that favor innovation. Moreover, it demonstrates to universities, research institutions and entrepreneurs engaged in technology transfer the economic and social usefulness of their approach.
Examining the factors influencing adoption of over the top (OTT) services among Indian consumers
Authors: Bhattacharyya Som Sekhar , Goswami Shaileshwar , Mehta Raunak , Nayak Bishwajit 
Published: August 2021

Purpose
The purpose of this paper is to identify and predict the key factors that influenced the usage intention of over the top (OTT) services by consumers. This was done by applying the modified unified theory of acceptance and use of technology 2 (UTAUT2) model.

Design/methodology/approach
An online survey questionnaire assessed the proposed motivational factors for the adoption of OTT services. Confirmatory factor analysis and structural equation modelling were conducted on collected data (n = 598) to demonstrate the reliability and validity of the measurement and structural model.

Findings
The model consisted of nine factors, namely, value expectancy (VE), ease of effort (EE), social influence (SI), favourable infrastructure conditions (FIC), hedonistic motivation for usage (HMU), favourable economic position (FEP), content quality (CQ), habitual behaviour (HB) and security conditions (SC). SC, VE, SI, HB and EE were the antecedent variables. FEP, CQ and FIC were the mediating variables and HMU was the dependant variable. SI and CQ of OTT services were positively associated with HMU of OTT services, FEP had no significant effects on HMU. The results also supported the explanatory strength and predictability of UTAUT2 as a model. It further extended UTAUT2 boundaries and paved the way for an extended UTAUT2 model to be developed.

Originality/value
The promising role of OTT services in the entertainment and media industry had gained consumer attention, however, limited empirical investigations had been conducted on explicating how user attitude and usage intention were shaped regarding the use of OTT services in the Indian context. This study served as one of the first attempts to empirically examine the adoption process, with implications for the HMU regarding OTT services. This was one of the first studies to extend the UTAUT2 theoretical model.
Increased 28‐day mortality due to fluid overload prior to continuous renal replacement in sepsis associated acute kidney injury
Authors: Fang Junjun , Wang Minjia , Gong Shijin , Cui Nannan , Xu Liang 
Published: August 2021

AbstractPatients with sepsis are prone to fluid overload (FO) due to fluid resuscitation, irrespective of stage of acute kidney injury (AKI). The aim of our study was to analyze the association between FO at continuous renal replacement therapy (CRRT) initiation and 28‐day mortality in patients with sepsis associated AKI (S‐AKI). In this retrospective study, data for patient characteristics were collected and 28‐day mortality were studied. We also analyze association of variables, including FO degrees with 28‐day mortality. Earlier commencement of CRRT showed better outcome. Non‐survivors had higher FO than survivor (9.17% vs. 5.20%; p = 0.016). Survival in patients with FO > 10% over 28 days was significantly worse compared to those with FO ≤ 10% (p = 0.006). Multivariate analysis showed, FO > 10% (95%CI [1.721, 17.195], p = 0.004) was significantly associated with increased 28‐day mortality. In S‐AKI requiring CRRT, FO > 10% at CRRT initiation was independently associated with 28‐day mortality.
Elastic priors to dynamically borrow information from historical data in clinical trials
Authors: Jiang Liyun , Nie Lei , Yuan Ying 
Published: August 2021

AbstractUse of historical data and real‐world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is to effectively borrow information from historical data while maintaining a reasonable type I error and minimal bias. We propose the elastic prior approach to address this challenge. Unlike existing approaches, this approach proactively controls the behavior of information borrowing and type I errors by incorporating a well‐known concept of clinically significant difference through an elastic function, defined as a monotonic function of a congruence measure between historical data and trial data. The elastic function is constructed to satisfy a set of prespecified criteria such that the resulting prior will strongly borrow information when historical and trial data are congruent, but refrain from information borrowing when historical and trial data are incongruent. The elastic prior approach has a desirable property of being information borrowing consistent, that is, asymptotically controls type I error at the nominal value, no matter that historical data are congruent or not to the trial data. Our simulation study that evaluates the finite sample characteristic confirms that, compared to existing methods, the elastic prior has better type I error control and yields competitive or higher power. The proposed approach is applicable to binary, continuous, and survival endpoints.