bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically encoded transcriptional plasticity underlies stress adaptation in Mycobacterium tuberculosis
Authors: Bei Cheng , Zhu Junhao , Culviner Peter H , Rubin Eric J. , Fortune Sarah M , Gao Qian , Liu Qingyun 
Published: August 2023

AbstractTranscriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) remains largely unexplored. In this study, we investigate the genome-wide TP profiles ofMycobacterium tuberculosis(Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal thatMtbgenes exhibit significant TP variation that correlates with gene function and gene essentiality. We also found that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two otherMycobacteriumspecies --M. smegmatisandM. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.
Cannabinoid Combination TargetsNOTCH1-Mutated T-ALL Through the Integrated Stress Response Pathway
Authors: Besser Elazar , Gelfand Anat , Procaccia Shiri , Berman Paula , Meiri David 
Published: August 2023

AbstractIn T-cell acute lymphoblastic leukemia (T-ALL) more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation. We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, Cannabidiol (CBD) and Cannabidivarin (CBDV); whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study. We demonstrated that these cannabinoids act through Cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca2+. This is followed by increased mRNA and protein expression of ATF4, CHOP and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2α. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis. Treatment with the three isolated molecules resulted in reduced tumor size and weight in-vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treatingNOTCH1-mutated diseases and cancers such as T-ALL.
Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives
Authors: Haber Daniella An , Arien Yael , Lamdan Lee Benjamin , Alcalay Yehonathan , Zecharia Chen , Krsticevic Flavia , Yonah Elad Shmuel , Avraham Rotem Daniel , Krzywinska Elzbieta , Krzywinski Jaroslaw , Marois Eric , Windbichler Nikolai , Papathanos Philippos Aris 
Published: August 2023

AbstractEngineered sex ratio distorters (SRDs) have been proposed as a powerful component of genetic control strategies designed to suppress harmful insect pests. Two types of CRISPR-based SRD mechanisms have been proposed: X-shredding eliminates X-bearing sperm, while X-poisoning eliminates daughters inheriting disrupted X-chromosomes. These differences can have a profound impact on the population dynamics of SRDs when linked to the Y-chromosome: an X-shredder is invasive constituting a classical meiotic Y-drive, whereas X-poisoning is self-limiting, unable to invade but also insulated from selection. Here, we established the first X-poisoning strains in the malaria vectorAnopheles gambiaetargeting three X-linked genes during spermatogenesis resulting in male bias. Surprisingly, we found that sex distortion was primarily driven by a loss of X-bearing sperm with limited evidence for postzygotic lethality of daughters. By leveraging aDrosophila melanogastermodel, we show unambiguously that engineered SRD traits can operate differently in these two insects. Unlike X-shredding, X-poisoning could theoretically operate at early stages of spermatogenesis. We therefore explored premeiotic Cas9 expression to target the mosquito X-chromosome. We find that, by pre-empting the onset of meiotic sex chromosome inactivation, this approach may enable the development of Y-linked SRDs if mutagenesis of spermatogenesis-essential genes is functionally balanced.
A maximum of two readily releasable vesicles per docking site at a cerebellar single active zone synapse
Authors: Silva Melissa , Tran Van , Marty Alain 
Published: August 2023

AbstractRecent research suggests that in central mammalian synapses, active zones contain several docking sites acting in parallel. Before release, one or several synaptic vesicles (SVs) are thought to bind to each docking site, forming the readily releasable pool (RRP). Determining the RRP size per docking site has important implications for short-term synaptic plasticity. Here, we take advantage of recently developed methods to count the number of released SVs at single glutamatergic synapses in response to trains of action potentials. In each recording, the number of docking sites was determined by fitting with a binomial model the number of released SVs in response to individual action potentials. After normalization with respect to the number of docking sites, the summed number of released SVs following a train of action potentials was used to estimate of the RRP size per docking site. To improve this estimate, various steps were taken to maximize the release probability of docked SVs, the occupancy of docking sites, as well as the extent of synaptic depression. Under these conditions, the RRP size reached a maximum value close to two SVs per docking site. The results indicate that each docking site contains two distinct SV binding sites that can simultaneously accommodate up to one SV each. They further suggest that under special experimental conditions, as both sites are close to full occupancy, a maximal RRP size of two SVs per docking site can be reached. More generally, the results validate a sequential two-step docking model previously proposed at this preparation.
Iron biomarkers predict peripheral artery disease in females: a cross-sectional analysis of HEIST-DiC and NHANES participants
Authors: Ruban Agarvas Anand , Kopf Stefan , Lopes Tiago J.S. , Thalmann Paul , Fernández-Real José Manuel , Nawroth Peter , Muckenthaler Martina U. 
Published: August 2023

AbstractBackgroundIron overload has been proposed as a risk factor for atherosclerosis but the available data are controversial. Here we investigated whether iron biomarkers within physiological limits that frequently differ between sexes are associated with peripheral arterial disease (PAD)MethodsUsing two different analytical approaches (machine-learning and logistic regression), we studied the association between blood iron biomarkers and PAD in 368 individuals from the Heidelberg Study on Diabetes and Complications (HEIST-DiC) and in 5101 individuals from the National Health and Nutrition Examination Survey (NHANES 1999-2004).ResultsWe found that iron biomarkers were among the top predictors of PAD in the machine-learning classification in both cohorts. In the HEIST-DiC cohort, ferritin, iron, and transferrin were ranked among the top predictive markers, while in the NHANES cohort ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT) and iron showed high predictive power. In the regression analysis ferritin showed a positive interaction among females in the HEIST-DiC (OR 2.68, 95% CI 0.94-7.61,p=0.057) and NHANES cohorts (OR 1.76, 95% CI 1.16-2.67,p=0.008). The multivariable regression analysis of the NHANES cohort, detected a nonlinear relationship between ferritin and PAD in that certain ferritin ranges (48-97 ng/mL: OR 14.59, 95% CI 1.6-135.93, p= 0.019; 98-169 ng/mL: OR 171.07, 95% CI 1.27-23404, p=0.039) in females associated positively with PAD.ConclusionTaken together our data show that iron biomarkers, importantly, elevated ferritin is associated with clinically apparent PAD in females. These findings add to the body of evidence suggesting sex differences in PAD and highlight a possible role of iron (directly or indirectly) in this relationship.
Resting state fMRI reveals pervasive thalamic hyperactivity and default mode network hypoactivity in epilepsy: Systematic review and meta-analysis
Authors: Qiao Yang , Fu Cong , Zhao Na , Lock Matthew , Yuan Zhen , Zang Yu-Feng 
Published: August 2023

AbstractObjectiveThis coordinate-based meta-analysis incorporates studies employing local metrics like amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo), and studies utilizing independent component analysis (ICA) to probe the default mode network (DMN) in epilepsy.MethodsA comprehensive literature search was conducted in PubMed, Embase, and Web of Science to identify relevant studies published up to July 2022. We included all studies that compared RS-fMRI local activity in epileptic patients and healthy controls.ResultsFrom 644 identified studies, 54 were included in the meta-analyses. Our analysis revealed a consistent increase in local activity in the right mediodorsal thalamus (MDT), bilateral medial temporal lobe, and bilateral sensorimotor cortex. Conversely, a notable decrease in local activity was observed within the DMN regions, including the posterior cingulate cortex (PCC)/precuneus, medial prefrontal cortex, and bilateral inferior parietal lobule. Furthermore, a significant negative correlation between abnormal activity in the right MDT and PCC was identified through our meta-correlation analysis.ConclusionsThe findings from our study provide compelling evidence of increased local activity in the mediodorsal thalamus and decreased activity in the default mode network in epilepsy. These observations could potentially advance our understanding of epilepsy’s neural underpinnings and guide targeted intervention strategies.What is already known on this topic?Epilepsy involves abnormal brain activity, recurrent seizures, and possible thalamic and DMN involvement.What this study adds?This study reveals consistent thalamic hyperactivity, DMN hypoactivity in various epilepsy types, and a significant negative correlation between these activities.How this study might affect research, practice, and/or policy?Decreased DMN activity and increased thalamus activity could clarify epilepsy pathogenesis and suggest precise, targeted interventions.
Uncovering Spatiotemporal Dynamics of the Corticothalamic Network during Seizures
Authors: Panchavati Saarang , Daida Atsuro , Edmonds Benjamin , Miyakoshi Makoto , Oana Shingo , Ahn Samuel S. , Arnold Corey , Salamon Noriko , Sankar Raman , Fallah Aria , Speier William , Nariai Hiroki 
Published: August 2023

ABSTRACTObjectiveAlthough the clinical efficacy of deep brain stimulation targeting the anterior nucleus (AN) and centromedian nucleus (CM) of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human EEG recording. This study aims to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci.MethodsWe analyzed ten patients (aged 2.7–28.1) with medication-resistant focal epilepsy who underwent stereotactic EEG evaluation with thalamic coverage. We examined both undirected and directed connectivity, incorporating coherence and spectral Granger causality analysis (GCA) between the diverse seizure foci and thalamic nuclei (AN and CM).ResultsIn our analysis of 36 seizures, coherence between seizure onset and thalamic nuclei increased across all frequencies, especially in slower bands (delta, theta, alpha). GCA showed increased information flow from seizure onset to the thalamus across all frequency bands, but outflows from the thalamus were mainly in slower frequencies, particularly delta. In the subgroup analysis based on various seizure foci, the delta coherence showed a more pronounced increase at CM than at AN during frontal lobe seizures. Conversely, in limbic seizures, the delta coherence increase was greater at AN compared to CM.InterpretationIt appears that the delta frequency plays a pivotal role in modulating the corticothalamic network during seizures. Our results underscore the significance of comprehending the spatiotemporal dynamics of the corticothalamic network during seizures, and this knowledge could guide personalized neuromodulation treatment strategies.Summary for Social MediaTwitter handles:@saarang_p; @BillSpeierWhat is the current knowledge on the topicAlthough the clinical efficacy of deep brain stimulation targeting the anterior nucleus and centromedian nucleus of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human EEG recording.What question did this study addressThis study aimed to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci.What does this study add to our knowledgeThe delta frequency plays a pivotal role in modulating the corticothalamic network during seizures. There are seizure-onset dependent spatiotemporal dynamics of the ictal corticothalamic network.How might this potentially impact on the practice of neurologyThis knowledge could guide personalized neuromodulation treatment strategies.
Effect of temperature on electronucleation and growth mechanism of Zn–Ni alloy in deep eutectic solvent
Authors: Sun Haijing , Cui Jianing , Wang He , Yang Shuai , Xaikoua Souavang , Tan Yong , Zhou Xin , Wang Baojie , Sun Jie 
Published: August 2023

Purpose
The purpose of this paper is to study the effect of temperature on Zn–Ni alloys in ChCl–Urea.

Design/methodology/approach
Based on cyclic voltammetry experiments, the deposition behavior and kinetics of the Zn–Ni alloy are studied. The nucleation process of the Zn–Ni alloy is studied in detail via chronoamperometry experiments. The effects of the deposition temperature on the microstructure, Ni content and phase composition of Zn–Ni alloy coatings are investigated via scanning electron microscopy and X-ray diffraction (XRD) combined with classical thermodynamics.

Findings
The results show that with increasing temperature, the reduction peak shifts toward a more positive electric potential, which is beneficial for the co-electric deposition process, and the diffusion coefficient is estimated. With increasing temperature, the nucleation process of the Zn–Ni alloy becomes a three-dimensional instantaneous nucleation, the typical kinetic parameters are determined using the standard 3D growth proliferation control model and the Gibbs free energy is estimated. The Zn–Ni alloy coatings are prepared via normal co-deposition. With increasing temperature, the degree of crystallinity increases, the coating gradually becomes uniform and compact and the XRD peak intensity increases.

Originality/value
The nucleation process of the Zn–Ni alloy at different temperatures is analyzed. The diffusion coefficient D and Gibbs free energy are calculated. The contribution of the three processes at different temperatures is analyzed. The effect of temperature on the morphology of the Zn–Ni alloy coatings is studied.
Impact of trust in virtual project teams: structural equation modelling approach
Authors: Sagar Sukhwant Kaur , Oladinrin Olugbenga Timo , Arif Mohammed , Kaushik Amit , Islam Rubina 
Published: August 2023

Purpose
This study aims to focus on model development to analyse key factors affecting trust in virtual project teams (VPTs).

Design/methodology/approach
A questionnaire survey was conducted on construction professionals participating in virtual teams. Structural equation modelling technique was performed to establish the effect of relevant factors on trust-building in VPTs.

Findings
Team performance is highly affected by the trust among the team members. Trust building can be enhanced by improving the quality of team communication, organisation culture, team bonding and team members’ characteristics.

Originality/value
The model developed in this study would benefit team productivity and team members’ learning in VPTs.
What resists millennials to adopt hotel booking apps? An empirical analysis based on extended innovation resistance theory
Authors: Kumar Sachin , Dhiman Neeraj , Kanojia Honey , Joshi Richa 
Published: August 2023

PurposeThis study aims to examine the factors determining the discontinuance intentions of millennials to use hotel booking apps.Design/methodology/approachA quantitative technique was followed to collect the data from the tourists, and partial least square structural equation modeling (PLS-SEM) technique was adopted to validate the proposed model.FindingsSignificant predictors of discontinuance intentions of hotel booking apps are usage barrier, values barrier, risk barrier, lack of facilitating conditions and digital self-efficacy.Practical implicationsThe results of this study provide useful insights for tourism stakeholders and app developers to understand in real terms the setbacks that might be a hindrance to the users of such apps for hotel booking.Originality/valueDespite the increasing focus of scholars toward understanding the determinants of technology adoption, the present study has extended innovation resistance theory with three novel constructs: social dependency, lack of facilitating conditions and digital self-efficacy.
Operational excellence of the steel industry using the Lean Six Sigma approach: a case study
Authors: Srinivasan Kumar , Sarulkar Parikshit , Yadav Vineet Kumar 
Published: August 2023

PurposeThis article aims to focus on implementing Lean Six Sigma (LSS) in steel manufacturing to enhance productivity and quality in the galvanizing process line. In recent trends, manufacturing organizations have expressed strong interest in the LSS since they attempt to enhance its overall operations without imposing significant financial burdens.Design/methodology/approachThis article used lean tools and Six Sigma's DMAIC (Define, Measure, Analyze, Improve and Control) with Yin's case study approach. This study tried to implement the LSS for the steel galvanizing process in order to reduce the number of defects using various LSS tools, including 5S, Value stream map (VSM), Pareto chart, cause and effect diagram, Design of experiments (DoE).FindingsResults revealed a significant reduction in nonvalue-added time in the process, which led to improved productivity and Process cycle efficiency (PCE) attributed to applying lean-Kaizen techniques. By deploying the LSS, the overall PCE improved from 22% to 62%, and lead time was reduced from 1,347 min to 501 min. DoE results showed that the optimum process parameter levels decreased defects per unit steel sheet.Practical implicationsThis research demonstrated how successful LSS implementation eliminates waste, improves process performance and accomplishes operational distinction in steel manufacturing.Originality/valueSince low-cost/high-effect improvement initiatives have not been adequately presented, further research studies on adopting LSS in manufacturing sectors are needed. The cost-effective method of process improvement can be considered as an innovation.
Factors influencing attitude and intention to use autonomous vehicles in Vietnam: findings from PLS-SEM and ANFIS
Authors: Iranmanesh Mohammad , Ghobakhloo Morteza , Foroughi Behzad , Nilashi Mehrbakhsh , Yadegaridehkordi Elaheh 
Published: August 2023

PurposeThis study aims to explore and ranks the factors that might determine attitudes and intentions toward using autonomous vehicles (AVs).Design/methodology/approachThe “technology acceptance model” (TAM) was extended by assessing the moderating influences of personal-related factors. Data were collected from 378 Vietnamese and analysed using a combination of “partial least squares” and the “adaptive neuro-fuzzy inference system” (ANFIS) technique.FindingsThe findings demonstrated the power of TAM in explaining the attitude and intention to use AVs. ANFIS enables ranking the importance of determinants and predicting the outcomes. Perceived ease of use and attitude were the most crucial drivers of attitude and intention to use AVs, respectively. Personal innovativeness negatively moderates the influence of perceived ease of use on attitude. Data privacy concerns moderate positively the impact of perceived usefulness on attitude. The moderating effect of price sensitivity was not supported.Practical implicationsThese findings provide insights for policymakers and automobile companies' managers, designers and marketers on driving factors in making decisions to adopt AVs.Originality/valueThe study extends the AVs literature by illustrating the importance of personal-related factors, ranking the determinants of attitude and intention, illustrating the inter-relationships among AVs adoption factors and predicting individuals' attitudes and behaviours towards using AVs.
The leader of the pack: how Chewy became the alpha figure
Authors: Weinstein Art T. , Alegria Christopher , Araujo Daniela , Ramirez Carvallo Diana , Helena Cubides Luz , Salinas Annmarie 
Published: August 2023

Purpose
Chewy, Inc. is a direct-to-consumer seller of pet food and supplies. Their approach involves a deep understanding of pet owners’ needs and behaviors to provide personalized product recommendations and exceptional customer service. This case study aims to describe Chewy’s growth strategies and how the company can remain a market leader.

Design/methodology/approach
Using the customer value assessment tool, the authors examine Chewy’s value proposition, including service, quality, image and price strategies.

Findings
Chewy has built a loyal customer base that values the company’s commitment to their pets’ health and well-being. Future opportunities include focusing on pet wellness products and services, collaborating with veterinary providers in telemedicine and international expansion.

Research limitations/implications
This work is largely conceptual and presents a descriptive case study which reviews Chewy’s marketing strategy based on industry research as well as a customer value assessment via the service-quality-image-price framework.

Practical implications
Corporate leaders must adapt to market change and create business strategies to deliver superior value for customers. This requires innovative products, services and processes. The strategic insights are applicable to retailers, service and technology firms and entrepreneurial companies seeking to scale their businesses.

Originality/value
Chewy’s highly competitive market includes Amazon, e-commerce pet supply companies and big-box pet stores. But it has dominated the online sector and has substantial growth prospects. This paper concludes with recommendations for management and questions for consideration.