bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel CRISPR-Engineered, Stem Cell-Derived Cellular Vaccine
Authors: Chakraborty Krishnendu , Chandrashekar Abishek , Sidaway Adam , Latta Elizabeth , Yu Jingyou , McMahan Katherine , Giffin Victoria , Manickam Cordelia , Kroll Kyle , Mosher Matthew , Reeves R. Keith , Gam Rihab , Arthofer Elisa , Choudhry Modassir , Barouch Dan H , Henley Tom 
Published: December 2021

ABSTRACTCOVID-19 has forced rapid clinical translation of novel vaccine technologies, principally mRNA vaccines, that have resulted in meaningful efficacy and adequate safety in response to the global pandemic. Notwithstanding this success, there remains an opportunity for innovation in vaccine technology to address current limitations and meet the challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) rationally designed to mimic the natural physiologic immunity induced post viral infection of host cells. Induced pluripotent stem cells were CRISPR engineered to delete MHC-I expression and simultaneously overexpress a NK Ligand adjuvant to increase rapid cellular apoptosis which was hypothesized to enhance viral antigen presentation in the resulting immune microenvironment leading to a protective immune response. Cells were further engineered to express the parental variant WA1/2020 SARS-CoV-2 spike protein as a representative viral antigen prior to irradiation and cryopreservation. The cellular vaccine was then used to immunize non-human primates in a standard 2-dose, IM injected prime + boost vaccination with 1e8 cells per 1 ml dose resulting in robust neutralizing antibody responses (1e3 nAb titers) with decreasing levels at 6 months duration. Similar titers generated in this established NHP model have translated into protective human neutralizing antibody levels in SARS-Cov-2 vaccinated individuals. Animals vaccinated with WA1/2020 spike antigens were subsequently challenged with 1.0 × 105TCID50infectious Delta (B.1.617.2) SARS-CoV-2 in a heterologous challenge which resulted in an approximately 3-log order decrease in viral RNA load in the lungs. These heterologous viral challenge results reflect the ongoing real-world experience of original variant WA1/2020 spike antigen vaccinated populations exposed to rapidly emerging variants like Delta and now Omicron. This cellular vaccine is designed to be a rapidly scalable cell line with a modular poly-antigenic payload to allow for practical, large-scale clinical manufacturing and use in an evolving viral variant environment. Human clinical translation of the UVC is being actively explored for this and potential future pandemics.
A high-throughput 3D bioprinted cancer cell migration and invasion model with versatile and broad biological applicability
Authors: Jung MoonSun , Skhinas Joanna N. , Du Eric Y. , Tolentino M.A. Kristine , Utama Robert H. , Engel Martin , Volkerling Alexander , Sexton Andrew , O’Mahony Aidan P. , Ribeiro Julio C. C. , Gooding J. Justin , Kavallaris Maria 
Published: December 2021

SummaryUnderstanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to developin vitro3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells withinin vivotumor mimicking matrices, (ii)in situand real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.
Pipeline for retrieval of COVID-19 immune signatures
Authors: Newton Adam J.H. , Chartash David , Kleinstein Steven H. , McDougal Robert A. 
Published: December 2021

ObjectiveThe accelerating pace of biomedical publication has made retrieving papers and extracting specific comprehensive scientific information a key challenge. A timely example of such a challenge is to retrieve the subset of papers that report on immune signatures (coherent sets of biomarkers) to understand the immune response mechanisms which drive differential SARS-CoV-2 infection outcomes. A systematic and scalable approach is needed to identify and extract COVID-19 immune signatures in a structured and machine-readable format.Materials and MethodsWe used SPECTER embeddings with SVM classifiers to automatically identify papers containing immune signatures. A generic web platform was used to manually screen papers and allow anonymous submission.ResultsWe demonstrate a classifier that retrieves papers with human COVID-19 immune signatures with a positive predictive value of 86%. Semi-automated queries to the corresponding authors of these publications requesting signature information achieved a 31% response rate. This demonstrates the efficacy of using a SVM classifier with document embeddings of the abstract and title, to retrieve papers with scientifically salient information, even when that information is rarely present in the abstract. Additionally, classification based on the embeddings identified the type of immune signature (e.g., gene expression vs. other types of profiling) with a positive predictive value of 74%.ConclusionCoupling a classifier based on document embeddings with direct author engagement offers a promising pathway to build a semistructured representation of scientifically relevant information. Through this approach, partially automated literature mining can help rapidly create semistructured knowledge repositories for automatic analysis of emerging health threats.
Copper imbalance linked to oxidative stress and cell death during Zika virus infection in human astrocytes
Authors: Puig-Pijuan Teresa , Souza Leticia R. Q. , Pedrosa Carolina da S. G. , Higa Luiza M. , Monteiro Fabio Luis , Tanuri Amilcar , Valverde Rafael H. F. , Einicker-Lamas Marcelo , Rehen Stevens Kastrup 
Published: December 2021

AbstractThe Zika virus (ZIKV) caused neurological abnormalities in more than 3500 Brazilian newborns between 2015 and 2020. Data have pointed to oxidative stress in astrocytes as well as to dysregulations in neural cell proliferation and cell cycle as important events accounting for the cell death and neurological complications observed in Congenital Zika Syndrome. Copper imbalance has been shown to induce similar alterations in other pathologies, and disturbances in copper homeostasis have already been described in viral infections. For this reason, we investigated copper homeostasis imbalance as a factor that could contribute to the cytotoxic effects of ZIKV infection in iPSC-derived human astrocytes. Our results show that ZIKV infection leads to a downregulation of one of the transporters mediating copper release, ATP7B protein. We also observed the activation of mechanisms that counteract high copper levels, including the synthesis of copper chaperones and the reduction of the copper importer protein CTR1. Finally, we show that chelator-mediated copper sequestration in ZIKV-infected astrocytes reduces the levels of reactive oxygen species and improves cell viability, but does not change the overall percentage of infected cells. In summary, our results show that copper homeostasis imbalance plays a role in the pathology of ZIKV in astrocytes, indicating that it may also be a factor accounting for the developmental abnormalities in the central nervous system following viral infection. Evaluating micronutrient levels and the use of copper chelators in pregnant women susceptible to ZIKV infection may be promising strategies to manage novel cases of congenital ZIKV syndrome.
Genome-wide identification and expression analysis of the invertase gene family in common wheat (Triticum aestivum L.)
Authors: Wang Chao , Wang Guanghao , Qu Xiaojian , Zhang Xiangyu , Deng Pingchuan , Ji Wanquan , Zhang Hong 
Published: December 2021

AbstractBackgroundThe degradation of sucrose plays an important role in the process of crop biomass allocation and yield formation. Invertase (INV) irreversibly catalyzes the conversion of sucrose into glucose and fructose, which doomed its’ important role in plant development and stress tolerance. However, the functions of INV genes in wheat, one of the most important crops, were less studied due to the polyploidy.ResultsHere, we systematically analyzed the INV gene family based on the latest published wheat reference genomic information. A total of 126 TaINV genes were identified and classified into three classes based on the phylogenetic relationship and their gene structure. Of which, 11 and 83 gene pairs were identified as tandem and segmental duplication genes respectively, while the Ka/Ks ratios of tandem and segmental duplication TaINV genes were less than 1. Expression profile analysis shows that 18 TaINV genes have tissue-specific expression, and 54 TaINV genes were involved in stress response. Furthermore, RNA-seq showed that 35 genes are differentially expressed in grain weight NILs N0910-81L/N0910-81S, in which 9 TaINVs were stably detected by qRT-PCR at three time-points, 4, 7 and 10 DPA. Four of them (TaCWI47, TaCWI48, TaCWI50 and TaVI27) different expressed between the NILs resided in 4 QTL segments (QTGW.nwafu-5DL.1, QTGW.nwafu-5DL.2, QTGW.nwafu-7AS.1 and QTGW.nwafu-7AS.2). These findings facilitate function investigations of the wheat INV gene family and provide new insights into the grain development mechanism in wheat.ConclusionsOur results showed that allopolyploid events were the main reason for the expansion of the TaINV gene family in hexaploid wheat, and duplication genes might undergo purifying selection. The expression profiling of TaINV genes implied that they are likely to play an important role in wheat growth and development and adaption to stressful environments. And TaCWI47, TaCWI48, TaCWI50 and TaVI27 may have more important roles in grain developments. Our study lay a base for further dissecting the functional characterization of TaINV family members.
Single-cell monitoring of dry mass and dry density reveals exocytosis of cellular dry contents in mitosis
Authors: Miettinen Teemu P. , Ly Kevin S. , Lam Alice , Manalis Scott R. 
Published: December 2021

ABSTRACTCell mass and composition change with cell cycle progression. Our previous work characterized buoyant mass accumulation dynamics in mitosis (Miettinen et al., 2019), but how dry mass and cell composition change in mitosis has remained unclear. To better understand mitotic cell growth and compositional changes, we develop a single-cell approach for monitoring dry mass and the density of that dry mass every ∼75 seconds with 1.3% and 0.3% measurement precision, respectively. We find that suspension grown mammalian cells lose dry mass and increase dry density following mitotic entry. These changes display large, non-genetic cell-to-cell variability, and the changes are reversed at metaphase-anaphase transition, after which dry mass continues accumulating. The change in dry density causes buoyant and dry mass to differ specifically in early mitosis, thus reconciling existing literature on mitotic cell growth. Mechanistically, the dry composition changes do not require mitotic cell swelling or elongation. Instead, cells in early mitosis increase lysosomal exocytosis, and inhibition of exocytosis prevents the dry composition from changing. Overall, our work provides a new approach for monitoring single-cell dry mass and composition and reveals that mitosis is coupled to extensive exocytosis-mediated secretion of cellular contents.
Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody
Authors: Li Cheng , Zhan Wuqiang , Yang Zhenlin , Tu Chao , Zhu Yuanfei , Song Wenping , Huang Keke , Gu Xiaodan , Kong Yu , Zhang Xiang , Zhang Meng , Zhang Yi , Xie Youhua , Deng Qiang , Chen Zhenguo , Lu Lu , Jiang Shibo , Sun Lei , Wu Yanling , Ying Tianlei 
Published: December 2021

AbstractThe effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.
The transition toward the business formality of the Peruvian MSEs: How does the perception of entrepreneurs and the sector influence?
Authors: Silupu Brenda , Usero Belen , Montoro-Sánchez Ángeles 
Published: December 2021

PurposeThe formalization of a company is a process that requires compliance with standards established by government institutions. In developing countries, many businesses start this process, but do not finish it, with different levels of formality. The objective of this research is to analyze how the perception of entrepreneurs about bureaucratic procedures and the sector determine the level of formality regarding an established company that has taken the first step to formality.Design/methodology/approachThe National Survey of Micro and Small Enterprises (MSEs) is used with a sample of 4,619 Peruvian MSEs with more than three years of operation within the manufacturing and services sector. The data are analyzed with the ordered logistic regression technique.FindingsThe results show that the more favorable the perception of entrepreneurs about the ease of bureaucratic procedures, the higher the level of business formality; and companies in the manufacturing sector are less formal than those in the services sector. In addition, the perceptions of entrepreneurs positively moderate the level of formality in the case of companies in the manufacturing sector.Originality/valueLevels of formality in established companies are analyzed, defined by the compliance degree with the requirements to be a formal company. The literature on business informality in emerging countries is expanded, particularly in Latin America, incorporating the analysis of the formalization process.
Entrepreneurial leadership and employee innovative behavior in the software development firms: do employees' epistemic curiosity and creative process engagement matter?
Authors: Khan Muhammad Awais 
Published: December 2021

PurposeBuilding on self-determination theory, this study empirically examined the influence of entrepreneurial leadership (EL) style on employee innovative behavior (EIB) in the context of software development firms located in the twin cities of Pakistan (Rawalpindi and Islamabad).Design/methodology/approachFor the present study, an employee survey (online questionnaire) was used for data collection. The data were collected through an adopted questionnaire by using emails and messaging applications. Structural Equation Modeling (PLS-SEM) was used to analyze data collected from 245 respondents.FindingsThe findings of this study delineate that entrepreneurial leadership positively and significantly influences employee innovative behavior. Moreover, the relationship between entrepreneurial leadership and employee innovative behavior was partially mediated by employee epistemic curiosity (EC) and creative process engagement (CPE). The sequential mediation by the employee epistemic curiosity and creative process engagement between the link of entrepreneurial leadership and employee innovative behavior was also confirmed.Practical implicationsIn innovation-intensive organizations like software development firms, entrepreneurial leadership style can foster employee innovative behavior that is critical for organizational innovation success. This study provides information to the strategic leaders on how leadership behaviors can drive employee innovative behavior, particularly in the context of software development companies.Originality/valueThis study is an attempt to extend the scarce literature on the mechanisms through which leadership styles impact employee innovative behavior. Specifically, the mediating roles of employee epistemic curiosity and creative process engagement have been explored through a self-determination perspective.
Comparative study on performance of different artificial neural network methods for prediction of the Covid19
Authors: Sedighi Fard Alireza 
Published: December 2021

Purpose
This study aims to compare many artificial neural network (ANN) methods to find out which method is better for the prediction of Covid19 number of cases in N steps ahead of the current time. Therefore, the authors can be more ready for similar issues in the future.

Design/methodology/approach
The authors are going to use many ANNs in this study including, five different long short-term memory (LSTM) methods, polynomial regression (from degree 2 to 5) and online dynamic unsupervised feedforward neural network (ODUFFNN). The authors are going to use these networks over a data set of Covid19 number of cases gathered by World Health Organization. After 1,000 epochs for each network, the authors are going to calculate the accuracy of each network, to be able to compare these networks by their performance and choose the best method for the prediction of Covid19.

Findings
The authors concluded that for most of the cases LSTM could predict Covid19 cases with an accuracy of more than 85% after LSTM networks ODUFFNN had medium accuracy of 45% but this network is highly flexible and fast computing. The authors concluded that polynomial regression cant is a good method for the specific purpose.

Originality/value
Considering the fact that Covid19 is a new global issue, less studies have been conducted with a comparative approach toward the prediction of Covid19 using ANN methods to introduce the best model of the prediction of this virus.
Analysing the impact of artificial intelligence on the competitiveness of tourism firms: a modified total interpretive structural modeling (m-TISM) approach
Authors: Sharma Kamakshi , Jain Mahima , Dhir Sanjay 
Published: December 2021

PurposeThis study explores the variables that drive the impact of artificial intelligence (AI) on the competitiveness of a tourism firm. The relationship between the variables is established using the modified total interpretive structural modelling (m-TISM) methodology. The factors are identified through literature review and expert opinion. This study investigates the hierarchical relationship between these variables.Design/methodology/approachThe modified total interpretive structural modelling (m-TISM) method is used to develop a hierarchical interrelationship among variables that display direct and indirect impact. The competitiveness of a tourism firm is measured by investigating the effect of variables on the firm's financial performance.FindingsThe study identifies ten key factors essential for analysing the impact of AI on a firm's competitiveness. The m-TISM methodology gave us the hierarchical relationship between the factors and their interpretation. A theoretical TISM model has been constructed based on the hierarchy and relationship of the elements. The elements that fall in Level V are “AI Skilled Workforce”, “Infrastructure” and “Policies and Regulations”. Level IV includes the elements “AI Readiness”, “AI-Enabled Technologies” and “Digital Platforms”. Elements that fall under Level III are “Productivity” and “AI Innovation”. Level II and Level I comprise “Tourist Satisfaction” and “Financial Performance”, respectively. The levels indicate the elements' hierarchical level, with Level I the highest and Level V the lowest.Research limitations/implicationsTourism and AI scholars can analyse the given variables by including the transitive links and incorporate new variables depending upon future research. The m-TISM model constructed from literature review and expert opinion can act as a theoretical base for future studies to be conducted by researchers.Practical implicationsManagement/Practitioners can focus on the available characteristics and capitalise on them while working on the factors lacking in their organisation to enhance their competitiveness. Entrepreneurs starting their own business can utilise the elements in understanding the ecosystem of strengthening a firm's competitiveness. They can work to improve on the aspects which are crucial and trigger the impact on competitiveness. The government and management can devise policies and strategies that encompass the essential factors that positively impact the competitiveness of the firms. The approach can then be looked at with a holistic approach to cater to the other related components of the tourism industry.Originality/valueThis study is the first of its kind to use the modified TISM methodology to understand the impact of AI on the competitiveness of tourism firms.
Geometric imperfect preventive maintenance and replacement (GIPMAR) model for aging repairable systems
Authors: Udoh Nse , Effanga Effanga 
Published: December 2021

PurposeThis work seeks to develop a geometric imperfect preventive maintenance (PM) and replacement model (GIPMAR) for aging repairable systems due to age and prolong usage that would meet users need in three phases: within average life span, beyond average life span and beyond initial replacement age of system.Design/methodology/approachThe authors utilized the geometric process (GP) as the hazard function to characterize the increasing failure rate (IFR) of the system. The GP hazard function was incorporated into the hybridized preventive and replacement model of Lin et al. (2000). The resultant expected cost rate function was optimized to obtain optimum intervals for PM/replacement and required numbers of PM per cycle. The proposed GIPMAR model was applied to repairable systems characterized by Weibull life function and the results yielded PM/replacement schedules for three different phases of system operation.FindingsThe proposed GIPMAR model is a generalization of Lin et al. (2000) PM model that were comparable with results of earlier models and is adaptive to situations in developing countries where systems are used across the three phases of operation depicted in this work. This may be due to economic hardship and operating environment.Practical implicationsThe proposed model has provided PM/Replacement schedules for different phases of operation which was never considered. This would provide a useful guide to maintenance engineers and end-users in developing countries with a view to minimizing the average cost of maintenance as well as reducing the number of down times of systems.Social implicationsA duly implemented GIPMAR model would ensure efficient operation of systems, optimum man-hour need in the organization and guarantee customer's goodwill in a competitive environment.Originality/valueIn this work, the authors have extended Lin et al. (2000) PM model to provide PM/replacement schedules for aging repairable systems which was not provided for in earlier existing models and literature.