bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex and age-dependent alterations of drug consumption during the COVID-19 lockdown in Spain: Lessons learned for the future
Authors: Lorente Jesús David , Forte Anabel , Cuitavi Javier , Verdú Francesc , Hipólito Lucía 
Published: May 2023

AbstractIn order to reduce the spread of COVID-19, lockdown has been one of the most implemented measures worldwide. Spain had one of the harshest lockdowns in Europe, impacting the social and psychological health of the population. The aim of this paper is to study how the lockdown has affected drug consumption patterns and the extent to which age and sex are influential factors. We have developed an online survey in which people were asked about their consumption of alcohol, marihuana, cocaine, and sedative and tranquilizers before and during the COVID-19 lockdown. Data revealed a general reduction in the consumption of all the drugs surveyed. Interestingly, when data was analysed by sex or age, we detected alterations in the consumption patterns depending on these variables that were of special relevance in the case of alcohol, marihuana and non-prescription sedatives and tranquilizers. Our data revealed a general decrease in the use of these drugs in the case of young adults, revealing that their use is strongly linked to social life, whereas the middle-aged population has experienced alterations in their consumption patterns, whereby their use has increased to daily. In addition, the use of non-prescription sedatives and tranquilizers has increased in specific populations. In conclusion, our data reveals important alterations during the lockdown in the consumption pattern of both legal and illegal drugs (sex and age dependent) in the Spanish population, and these alterations might be considered for future national strategies of preventative actions.
Selective Enhancer Dependencies inMYC-Intact andMYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma
Authors: Iyer Ashwin R. , Gurumurthy Aishwarya , Kodgule Rohan , Aguilar Athalee R. , Saari Travis , Ramzan Abdullah , Rausch Dylan , Gupta Juhi , Hall Cody N. , Runge John S. , Weiss Matthew , Rahmat Mahshid , Anyoha Rockwell , Fulco Charles P. , Ghobrial Irene M. , Engreitz Jesse , Cieslik Marcin P. , Ryan Russell J.H. 
Published: May 2023

AbstractHigh expression ofMYCand its target genes define a subset of germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) associated with poor outcomes. Half of these high-grade cases show chromosomal rearrangements between theMYClocus and heterologous enhancer-bearing loci, while focal deletions of the adjacent non-coding genePVT1are enriched inMYC-intact cases. To identify genomic drivers ofMYCactivation, we used high-throughput CRISPR-interference (CRISPRi) profiling of candidate enhancers in theMYClocus and rearrangement partner loci in GCB-DLBCL cell lines and mantle cell lymphoma (MCL) comparators that lacked common rearrangements betweenMYCand immunoglobulin (Ig) loci. Rearrangements betweenMYCand non-Ig loci were associated with unique dependencies on specific enhancer subunits within those partner loci. Notably, fitness dependency on enhancer modules within theBCL6super-enhancer (BCL6-SE) cluster regulated by a transcription factor complex of MEF2B, POU2F2, and POU2AF1 was higher in cell lines bearing a recurrentMYC::BCL6-SE rearrangement. In contrast, GCB-DLBCL cell lines withoutMYCrearrangement were highly dependent on a previously uncharacterized 3’ enhancer within theMYClocus itself (GCBME-1), that is regulated in part by the same triad of factors. GCBME-1 is evolutionarily conserved and active in normal germinal center B cells in humans and mice, suggesting a key role in normal germinal center B cell biology. Finally, we show that thePVT1promoter limitsMYCactivation by either native or heterologous enhancers and demonstrate that this limitation is bypassed by 3’ rearrangements that removePVT1from its position inciswith the rearrangedMYCgene.Key pointsCRISPR-interference screens identify a conserved germinal center B cellMYCenhancer that is essential for GCB-DLBCL lackingMYCrearrangements.Functional profiling ofMYCpartner loci reveals principles ofMYCenhancer-hijacking activation by non-immunoglobulin rearrangements.
Richness and density jointly determine context dependence in bacterial interactions
Authors: Dooley Keven D. , Bergelson Joy 
Published: May 2023

AbstractPairwise interactions are often used to predict features of complex microbial communities due to the challenge of measuring multi-species interactions in high dimensional contexts. This assumes that interactions are unaffected by community context. Here, we used synthetic bacterial communities to investigate that assumption by observing how interactions varied across contexts. Interactions were most often weakly negative and showed clear phylogenetic signal. Community richness and total density emerged as strong predictors of interaction strength and contributed to an attenuation of interactions as richness increased. Population level and per-capita measures of interactions both displayed such attenuation, suggesting factors beyond systematic changes in population size were involved; namely, changes to the interactions themselves. Nevertheless, pairwise interactions retained some predictive value across contexts, provided those contexts were not substantially diverged in richness. These results suggest that understanding the emergent properties of microbial interactions can improve our ability to predict features of microbial communities.
Discovery and characterization of highly potent and selective covalent inhibitors of SARS-CoV-2 PLpro
Authors: Wu Jian , Vaid Tasneem M. , Kim Hoshin , Lu Jun , Demissie Robel , Lee Hyun , Fung Leslie W.-M. , Chen Jia , Xi Chenghao , Yang Zhezhou , Huang Yu , Zhang Zhantao , Zhang Jingqing , Yan Fengfeng , Johnson Michael E. , Li Min 
Published: May 2023

ABSTRACTCoronavirus infections, such as the global COVID-19 pandemic, have had a profound impact on many aspects of our daily life including working style, economy, and the healthcare system. To prevent the rapid viral transmission and speed up recovery from the infection, many academic organizations and industry research labs have conducted extensive research on discovering new therapeutic options for SARS-CoV-2. Among those efforts, RNA-dependent RNA polymerase (RdRp) inhibitors such as Remdesivir, Molnupiravir and 3CLpro inhibitor such as Nirmatrelvir (Paxlovid™) have been widely used as the therapeutic options. Given the recent emergence of several new variants that caused a resurgence of the virus, it would be beneficial to discover more diverse therapeutic options with novel anti-viral mechanisms. In this regard, PLpro has been highlighted since it, along with 3CLpro, is one of the two most important proteases that are required for SARS-CoV-2 viral processing. While 3CLpro inhibitors were extensively investigated in the light of Emergency Use Authorizations of Nirmatrelvir, PLpro inhibitors have not been thoroughly investigated even preclinically. Thus, discovery efforts on antivirals acting against PLpro will be valuable. PLpro inhibitors may exert their activity by inhibiting viral replication and enhancing the host defense system through blocking virus-induced cell signaling events for evading host immune response. In this study, we report the discovery and development of two covalent irreversible PLpro inhibitors, HUP0109 and its deuterated analog DX-027, out of our quest for novel anti-COVID 19 therapeutic agents for the past two and half years. HUP0109 selectively targets the viral catalytic cleft of PLpro and covalently modifies its active site cysteine residue (C111). Promising results from preclinical evaluation suggest that DX-027 can be developed as a potential COVID-19 treatment.
Integrating gene mutation spectra from tumors and the general population with gene expression topological networks to identify novel cancer driver genes
Authors: He Dan , Li Ling , Lu Zhiya , Li Shaoying , Lan Tianjun , Liu Feiyi , Zhang Huasong , Lei Bingxi , Cooper David N. , Zhao Huiying 
Published: May 2023

AbstractBackgroundUnderstanding the genetics underlying cancer development and progression is the most important goal of biomedical research to improve patient survival rates. Recently, researchers have proposed computationally combining the mutational burden with biological networks as a novel means to identify cancer driver genes. However, these approaches treated all mutations as having the same functional impact on genes and incorporated gene-gene interaction networks without considering tissue specificity, which may have hampered our ability to identify novel cancer drivers.MethodsWe have developed a framework, DGAT-cancer that integrates the predicted pathogenicity of somatic mutation in cancers and germline variants in the healthy population, with topological networks of gene expression in tumor tissues, and the gene expression levels in tumor and paracancerous tissues in predicting cancer drivers. These features were filtered by an unsupervised approach, Laplacian selection, and those selected were combined by Hotelling and Box-Cox transformations to score genes. Finally, the scored genes were subjected to Gibbs sampling to determine the probability that a given gene is a cancer driver.ResultsThis method was applied to nine types of cancer, and achieved the best area under the precision-recall curve compared to three commonly used methods, leading to the identification of 571 novel cancer drivers. One of the top genes,EEF1A1was experimentally confirmed as a cancer driver of glioma. Knockdown ofEEF1A1led to a ~ 41-50% decrease in glioma size and improved the temozolomide sensitivity of glioma cells.ConclusionBy combining the pathogenic status of mutational spectra in tumors alongside the spectrum of variation in the healthy population, with gene expression in both tumors and paracancerous tissues, DGAT-cancer has significantly improved our ability to detect novel cancer driver genes.
Building Trust in Deep Learning-based Immune Response Predictors with Interpretable Explanations
Authors: Borole Piyush , Rajan Ajitha 
Published: May 2023

AbstractThe ability to predict whether a peptide will get presented on Major Histocompatibility Complex (MHC) class I molecules has profound implications in designing vaccines. Numerous deep learning-based predictors for peptide presentation on MHC class I molecules exist with high levels of accuracy. However, these MHC class I predictors are treated as black-box functions, providing little insight into their decision making. To build turst in these predictors, it is crucial to understand the rationale behind their decisions with human-interpretable explanations. We present MHCXAI, eXplainable AI (XAI) techniques to help interpret the outputs from MHC class I predictors in terms of input peptide features. In our experiments, we explain the outputs of four state-of-the-art MHC class I predictors over a large dataset of peptides and MHC alleles. Additionally, we evaluate the reliability of the explanations by comparing against ground truth and checking their robustness. MHCXAI seeks to increase understanding of deep learning-based predictors in the immune response domain and build trust with validated explanations
Evaluation of Expanded 2-Aminobenzothiazole Library for Inhibition ofPseudomonas aeruginosaVirulence Phenotypes
Authors: Fihn Conrad A. , Lembke Hannah K. , Gaulin Jeffrey , Bouchard Patricia , Villarreal Alex R. , Penningroth Mitchell R. , Crone Kathryn K. , Vogt Grace A. , Gilbertsen Adam J. , Ayotte Yann , Couthino de Oliveira Luciana , Serrano-Wu Michael H. , Drouin Nathalie , Hung Deborah T. , Hunter Ryan C. , Carlson Erin E. 
Published: May 2023

AbstractBacterial resistance to antibiotics is a rapidly increasing threat to human health. New strategies to combat resistant organisms are desperately needed. One potential avenue is targeting two-component systems, which are the main bacterial signal transduction pathways used to regulate development, metabolism, virulence, and antibiotic resistance. These systems consist of a homodimeric membrane-bound sensor histidine kinase, and a cognate effector, the response regulator. The high sequence conservation in the catalytic and adenosine triphosphate-binding (CA) domain of histidine kinases and their essential role in bacterial signal transduction could enable broad-spectrum antibacterial activity. Through this signal transduction, histidine kinases regulate multiple virulence mechanisms including toxin production, immune evasion, and antibiotic resistance. Targeting virulence, as opposed to development of bactericidal compounds, could reduce evolutionary pressure for acquired resistance. Additionally, compounds targeting the CA domain have the potential to impair multiple two-component systems that regulate virulence in one or more pathogens. We conducted structure-activity relationship studies of 2-aminobenzothiazole-based inhibitors designed to target the CA domain of histidine kinases. We found these compounds have anti-virulence activities inPseudomonas aeruginosa, reducing motility phenotypes and toxin production associated with the pathogenic functions of this bacterium.
Evolution and genetics of accessory gland transcriptome divergence betweenDrosophila melanogasterand D.simulans
Authors: Majane Alex C. , Cridland Julie M. , Begun David J. 
Published: May 2023

ABSTRACTStudies of allele-specific expression in interspecific hybrids have provided important insights into gene-regulatory divergence and hybrid incompatibilities. Many such investigations in Drosophila have used transcriptome data from whole animals or gonads, however, regulatory divergence may vary widely among species, sex, and tissues. Thus, we lack sufficiently broad sampling of tissues to be confident about the general principles of regulatory divergence. Here we seek to fill some of these gaps in the literature by characterizing regulatory evolution and hybrid misexpression in a somatic male sex organ, the accessory gland, in F1 hybrids betweenDrosophila melanogasterandD. simulans.The accessory gland produces seminal fluid proteins, which play an important role in male and female fertility and may be subject to adaptive divergence due to male-male or male-female interactions. We find thattransdifferences are relatively more abundant thancis, in contrast to most of the interspecific hybrid literature, though large effect-sizetransdifferences are rare. Seminal fluid protein genes have significantly elevated levels of expression divergence and tend to be regulated through bothcisandtransdivergence. We find limited misexpression in this organ compared to other Drosophila studies. As in previous studies, male-biased genes are overrepresented among misexpressed genes and are much more likely to be underexpressed. ATAC-Seq data show that chromatin accessibility is correlated with expression differences among species and hybrid allele-specific expression. This work identifies unique regulatory evolution and hybrid misexpression properties of the accessory gland and suggests the importance of tissue-specific allele-specific expression studies.
Generation Z, tourism and hospitality: the legacy of COVID-19
Authors: Morrone Domenico , Tarulli Annunziata , Silvestri Raffaele , Santovito Savino 
Published: May 2023

PurposeAs Generation Z (Gen Z) represents one of the most important segments in the travel and tourism sector, the present work aims to analyse Gen Z's behaviour in a post-pandemic scenario. In particular, the present work deepens the factors that may influence future accommodation choices.Design/methodology/approachThis study uses data from a web-based questionnaire targeting Italian tourists belonging to Generation Z, reaching 221 complete responses. After the statistical analysis of the sample, an exploratory factor analysis (EFA) was then carried out.FindingsData provided evidence about the main factors affecting Gen Z tourist choices. In particular, these young consumers are positively influenced by the information (especially from institutional and verifiable sources), more flexible purchase terms (e.g. full refund in case of cancellation due to contagion of the coronavirus disease 2019 (COVID-19) and digital payments) and structure features (e.g. cleanliness, sanitisation, digitalisation and sustainability).Originality/valueThis work attempts to contribute to the academic literature by looking at the tourism experience from Gen Z's perspective. From this angle, this work underlines the influence some factors exert on the final accommodation choice, especially in the presence of exogenous events. Moreover, as this study focusses on a post-pandemic scenario, the study seeks to provide valuable indications, both at the theoretical and managerial level, for the tourism sector to boost the sector's recovery and prepare the sector to face similar events.
The dark side of high-performance work systems and self-sacrificial leadership: an empirical examination
Authors: Bai Peipei , Heidarian Ghaleh Hossein , Chang Huikun , Li Longzhen , Pak Jongwook 
Published: May 2023

PurposeThe study aims to offer a nuanced, fine-grained understanding of how the relationship between high-performance work systems (HPWSs) and negative employee outcomes can be attenuated under self-sacrificial leadership (SSL).Design/methodology/approachHierarchical linear modeling (HLM) was used to test the proposed multilevel model on a sample of 37 first-line managers (FLMs) and 209 employees working in a large Chinese company.FindingsThe results showed that HPWS is positively related to emotional exhaustion and turnover intention. Most conspicuously, the authors found that such adverse effects of HPWS are mitigated with a high level of SSL.Practical implicationsThe dark side of HPWS can be alleviated if practitioners complement their practices with sufficient support for employees. Particularly, FLMs who exhibit subordinate-serving attitudes consider followers' well-being and provide them with resources can lessen the high pressure of HPWS in pursuit of performance enhancement.Originality/valuePrior studies on the relationships between HPWS and employee outcomes have produced somewhat mixed results. This study extended the current discourse by explicating instead why HPWS could potentially impair employee outcomes and how the negative effects of HPWS can be mitigated under positive leader behaviors.
How does restaurant experienscape affect solo diners' emotions and dining satisfaction in Korea?
Authors: Im Soo Yeon , Seo Sunhee 
Published: May 2023

Purpose
This study aims to explore the role of restaurant experienscape in affecting diners' emotions and satisfaction with solo dining, considering the moderating role of solo dining willingness and public self-consciousness (PSC).

Design/methodology/approach
In total, 403 Korean customers who had dined alone at restaurants in the past three months participated in this study. Structural equation modeling, including multiple group analysis, was conducted to examine the hypotheses.

Findings
The dining atmosphere influenced solo diners' positive emotions but not their negative emotions. Responses from other guests and the interactional fairness of employees affected solo diners' negative emotions but not their positive emotions. Food sensory influences both positive and negative emotions. This study found that PSC significantly moderated the effect of the dining atmosphere on positive emotions, and solo dining willingness significantly moderated the impact of food sensory on positive emotions.

Practical implications
This study suggests that restaurant managers should pay close attention to providing fair service to all customers by training and educating employees because the unfair treatment that solo diners receive from employees affects focal customers' negative emotions.

Originality/value
The experienscape model was applied to the solo dining context based on Mehrabian and Russell's (1974) stimulus–organism–response paradigm and Pizam and Tasci's (2019) experienscape concept, which reflects the growing trend in solo dining.
Virtual communication adoption by educational leaders: moderating role of perceived risk and benefits
Authors: Gupta Saurabh , Mathur Nidhi 
Published: May 2023

PurposeThe objective of this study was to analyse the effects of major determinants on VCT adoption intention among higher educational leaders. Also, this study aims to investigate how perceived risk and perceived benefits influence the educational leaders, VCT actual use intention.Design/methodology/approachThe authors used the online survey method to collect the 440 responses through purposive sampling procedure. Structural equation modelling (SEM) technique and Multi Group Analysis procedure were used to test the proposed model and moderating effects.FindingsThe findings revealed that all the four determinants (PE, EE, SI and FC) based on UTAUT model have positive and significant effects on intention to use VCT. Besides this there is a significant and positive effect of intention to use VCT on actual usage of VCT by the educational leaders. The moderating effect of perceived risk and perceived benefits on actual usage of virtual communication also found significant.Research limitations/implicationsThis paper makes its contribution to the literature related to virtual communication technology adoption by including two moderator variables (perceived risk and benefits) that are expected to affect educational leaders' actual usage of VCT. The results can also help researchers and practitioners better understanding the factors that influence higher educational leaders to adopt VCT.Originality/valueThis study proposed a model incorporating the perceived risk and perceived benefits in the UTAUT model to predict the actual use of VCT. The study endeavours to investigate the moderating effects of perceived risk and perceived benefits between ITUVCT and AUVCT in Indian educational context.
Application of microcredentials to validate human capabilities in a large telecommunications organisation: strategic transformation to a future-ready workforce
Authors: Bowles Marcus , Brooks Benjamin , Curnin Steven , Anderson Helen 
Published: May 2023

PurposeThe value of transverse skills, including human capabilities, has been acknowledged for a significant period of time by major organisations such as UNESCO and the World Economic Forum. This paper reports on the application of microcredentials linked to the Human Capability Framework in a major telecommunications organisation that has a vision to establish a baseline to develop the levels of capability for both individual employees and the entire workforce. In this case study, capability is evidenced through learning and applied performance specified in a microcredential that carries a credit-entry score into higher education qualifications. The value of the microcredentials lies not in recognising learning outcomes; rather, it lies in an individual's ability to validate their full potential, open sustainable employment opportunities and prepare for emergent new roles.Design/methodology/approachThis commentary offers a case study of how a major Australian telecommunications organisation implemented microcredentials that are aligned to the Human Capability Framework Standards reference model.FindingsThe approach in this case study demonstrates how a company that confidently invests in non-traditional learning approaches that increase the value of human capital can tangibly grow the capacity of the workforce to deliver not only its strategy but also its cultural values.Originality/valueThe multi-award-winning model described in this case study is novel and clearly informs current research and thinking addressing this topic.