bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screen-based media device use, its associated factors and sleep outcomes among undergraduate health students studying in colleges of Kathmandu valley, Nepal
Authors: Maharjan Karina , Paudel Rajan , Kunwar Kshitij 
Published: September 2023

AbstractPeople of all age groups are engaged with various screen-based devices. Use of screen-based media devices beyond duration considered problematic has become a problem worldwide. Yet, undergraduate students are engaged in various screen-based activities for academic works and entertainment which can influence their sleep.A descriptive cross-sectional study design was used to collect information from 384 undergraduate students using a web-based questionnaire and convenience sampling technique. The data collected was analyzed using IBM SPSS Statistics 20.0. Descriptive and regression analyses were done to explore factors that influence screen-based media use.The average duration of screen-based media use by the participants was found to be 7.12 hours per day. Factors such as sex of the participants, the use of screen-based media during major mealtimes and home-specific rules limiting screen-based media use were found to be associated with screen-based media use. Only 45.3% of participants got the recommended hours of sleep (7 or more hours). Around 9.4% of the participants had long sleep onset latency (more than 45 minutes). Participants who used screen-based media devices during night before sleep were more likely to get insufficient sleep (OR (Odds Ratio) 3.668, 95% CI (Confidence Interval) (1.784-7.539)).A significant association was found between sex of the participants, use of screen-based media devices during major meal times and home rules limiting screen-based media use with the use of screen-based media for five hours or more per day. Screen-based media use and screen-based media use during night influence the quantity of sleep. Overuse of screen-based media is degrading the quality of sleep among undergraduate health students and is an alarming problem. There is a need to promote good sleeping habits through the reduction of this modifiable behaviour, which could be done by promoting home-based rules about screen-based media devices use, especially at night before sleep.
Circular RNA profiling identifiescirc5078as aBMPR2-derived regulator of endothelial proliferation and stress responses
Authors: VandenBroek M. Martin , Sharp Mackenzie C. , Thompson Patrick , Fagbola Emmanuel , Quilty Douglas , Mewburn Jeffrey D. , Theilmann Anne L. , Dunham-Snary Kimberly , Archer Stephen L. , Renwick Neil , Ormiston Mark L. 
Published: September 2023

AbstractGermline loss-of-functionBMPR2mutations are the leading genetic cause of pulmonary arterial hypertension (PAH) and are strongly linked to aberrant endothelial proliferation and impaired translational stress responses. While these effects are generally attributed to a loss of the type-II bone morphogenetic protein receptor (BMPR-II), we used circular RNA profiling to identifycirc5078as a new functional RNA derived from exon 12 of theBMPR2gene.circ5078and linearBMPR2mRNA exert opposing effects on endothelial proliferation and stress granule formation, driving impaired stress responses in PAH patient-derived endothelial cells that are deficient in linearBMPR2transcripts, but notcirc5078. Rebalancing circular to linear transcript abundance bycirc5078depletion rescued stress granule formation in patient-derived endothelial cells, independent of BMPR-II protein levels. Polysome analysis demonstrated a reduction in free ribosomal subunits with the depletion of either linear or circularBMPR2transcripts, and an accumulation of 80S monosomes exclusively with linearBMPR2mRNA loss. These effects did not impact global protein synthesis or stress-induced eIF2α phosphorylation, but did alter the translational efficiency of multiple genes, including a group of nuclear encoded, mitochondrial ribosome proteins that were translationally enhanced withcirc5078silencing. Endothelialcirc5078depletion increased the efficiency of oxidative metabolism while reducing mitochondrial spare capacity, providing a potential link between mitochondrial function, proliferation and translational stress responses. Together, these findings reveal interdependent roles for linear and circularBMPR2transcripts as functional contributors to the endothelial phenotype of PAH.
Genome-wide Characterization of Diverse Bacteriophages Enabled by RNA-Binding CRISPRi
Authors: Adler Benjamin A. , Al-Shimary Muntathar J. , Patel Jaymin R. , Armbruster Emily , Colognori David , Charles Emeric J. , Miller Kate V. , Lahiri Arushi , Trinidad Marena , Boger Ron , Nomburg Jason , Beurnier Sebastien , Cui Michael L. , Barrangou Rodolphe , Mutalik Vivek K. , Schoeniger Joseph S. , Pogliano Joseph A. , Savage David F. , Doudna Jennifer A. , Cress Brady F. 
Published: September 2023

AbstractBacteriophages constitute one of the largest sources of unknown gene content in the biosphere. Even for well-studied model phages, robust experimental approaches to identify and study their essential genes remain elusive. We uncover and exploit the conserved vulnerability of the phage transcriptome to facilitate genome-wide protein expression knockdown via programmable RNA-binding protein dRfxCas13d (CRISPRi-ART) across diverse phages and their host. Establishing the first broad-spectrum phage functional genomics platform, we predict over 90 essential genes across four phage genomes, a third of which have no known function. These results highlight hidden infection strategies encoded in the most abundant biological entities on earth and provide a facile platform to study them.
HRMAS13C NMR and genome-scale metabolic modeling identify threonine as a preferred dual redox substrate forClostridioides difficile
Authors: Pavao Aidan , Zhang Ella , Monestier Auriane , Peltier Johann , Dupuy Bruno , Cheng Leo , Bry Lynn 
Published: September 2023

AbstractStickland-fermentingClostridiapreferentially ferment amino acids to generate energy and anabolic substrates for growth. In gut ecosystems, these species prefer dual redox substrates, particularly mucin-abundant leucine. Here, we establish how theronine, a more prevalent, mucin-abundant substrate, supports dual redox metabolism in the pathogenClostridioides difficile. Real-time, High-Resolution Magic Angle Spinning NMR spectroscopy, with dynamic flux balance analyses, inferred dynamic recruitment of four distinct threonine fermentation pathways, including ones with intermediate accrual that supported changing cellular needs for energy, redox metabolism, nitrogen cycling, and growth. Model predictions with13C isotopomer analyses of [U-13C]threonine metabolites inferred threonine’s reduction to butyrate through the reductive leucine pathway, a finding confirmed by deletion of thehadA2-hydroxyisocaproate CoA transferase.In vivometabolomic and metatranscriptomic analyses illustrate how threonine metabolism inC. difficileand the protective commensalParaclostridium bifermentansimpacts pathogen colonization and growth, expanding the range of dual-redox substrates that modulate host risks for disease.
High-resolution 7T fMRI reveals the visual sensory zone of the human claustrum
Authors: Coates Adam , Linhardt David , Windischberger Christian , Ischebeck Anja , Zaretskaya Natalia 
Published: September 2023

AbstractThe claustrum is a thin subcortical gray matter structure located between the insula and the putamen. It has numerous bilateral connections with the cortex and is thought to play an important role in higher-level aspects of perception and cognition, with hypotheses including multisensory integration, attention and consciousness. The claustrum’s thin shape makes it difficult to investigate, leaving the hypothesis regarding its function largely untested. In the current study, we used high-resolution ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI) to measure claustrum activity in human participants, while they were presented with visual, auditory or audiovisual naturalistic stimuli. We found distinct visual responses in the claustrum at a spatial location that was consistent across participants, hemispheres and scanning sessions. This is the first study to demonstrate evoked sensory responses within the human claustrum. It opens the possibility for future noninvasive investigation of the claustrum’s role in sensory processing.
Eukaryotic-driven directed evolution of Cas9 nucleases
Authors: Ruta Giulia Vittoria , Ciciani Matteo , Kheir Eyemen , Gentile Michele Domenico , Amistadi Simone , Casini Antonio , Cereseto Anna 
Published: September 2023

ABSTRACTFull exploitation of the natural reservoir of CRISPR-Cas nucleases from prokaryotes for genome editing is limited by the suboptimal activity of these enzymes in mammalian cells. Here we developed aEukaryoticPlatform to ImproveCasActivity (EPICA) to steer weakly active Cas9 nucleases into highly active enzymes by directed evolution. The EPICA platform is obtained by coupling Cas nuclease activity with yeast auxotrophic selection followed by mammalian cell selection through a sensitive reporter system. EPICA was validated with a poorly efficient Cas9 nuclease fromCampylobacter jejuni, CjCas9, generating an enhanced variant, UltraCjCas9, following directed evolution rounds. UltraCjCas9 was up to 12-fold more active in mammalian endogenous genomic loci, while preserving high genome-wide specificity.Here we report a eukaryotic pipeline allowing enhancement of Cas9 systems, setting the ground to unlock the multitude of RNA-guided nucleases existing in nature.
Substrate selectivity and catalytic activation of the type III CRISPR ancillary nuclease Can2
Authors: Jungfer Kenny , Sigg Annina , Jinek Martin 
Published: September 2023

ABSTRACTType III CRISPR-Cas systems provide adaptive immunity against foreign mobile genetic elements through RNA-guided interference. Sequence-specific recognition of RNA targets by the type III effector complex triggers the generation of cyclic oligoadenylate (cOA) second messengers that activate ancillary effector proteins, thus reinforcing the host immune response. The ancillary nuclease Can2 is activated by cyclic tetra-AMP (cA4); however, the mechanisms underlying cA4-mediated activation and substrate selectivity remain elusive. Here we report crystal structures ofThermoanaerobacter brockiiCan2 (TbrCan2) in substrate- and product-bound complexes. We show that TbrCan2 is a single strand-selective DNase and RNase that binds substrates via a conserved SxTTS active site motif, and reveal molecular interactions underpinning its sequence preference for CA dinucleotides. Furthermore, we identify a molecular interaction relay linking the cA4 binding site and the nuclease catalytic site to enable divalent metal cation coordination and catalytic activation. These findings provide key insights into the molecular mechanisms of Can2 nucleases in type III CRISPR-Cas immunity and may guide their technological development for nucleic acid detection applications.
Attenuating midline thalamus bursting to mitigate absence epilepsy
Authors: Dong Ping , Bakhurin Konstantin , Li Yuhui , Mikati Mohamad A. , Cui Jianmin , Grill Warren M. , Yin Henry H. , Yang Huanghe 
Published: September 2023

AbstractAdvancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing new therapeutics to treat absence epilepsy.HighlightsThe midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis MLT neurons exhibit synchronized bursting during ictal phase. BK channel contributes to MLT burst firing Attenuating MLT bursting increases vigilance and suppresses absence seizures
4D DYNAMIC SPATIAL BRAIN NETWORKS AT REST LINKED TO COGNITION SHOW ATYPICAL VARIABILITY AND COUPLING IN SCHIZOPHRENIA
Authors: Pusuluri Krishna , Fu Zening , Miller Robyn , Pearlson Godfrey , Kochunov Peter , Van Erp Theo G.M. , Iraji Armin , Calhoun Vince D. 
Published: September 2023

ABSTRACTDespite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain net-works in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan. We find that several features of such dynamic spatial brain networks are associated with cognition, with higher dynamic variability in these networks and higher volumetric coupling between network pairs positively associated with cognitive performance. We show that these networks are modulated differently in individuals with schizophrenia versus typical controls, resulting in network growth or shrinkage, as well as altered focus of activity within a network. Schizophrenia also shows lower spatial dynamical variability in several networks, and lower volumetric coupling between pairs of networks, thus upholding the role of dynamic spatial brain networks in cognitive impairment seen in schizophrenia. Our data show evidence for the importance of studying the typically overlooked voxelwise changes within and between brain networks.
From overconfidence to task dropout in a spatial navigation test: evidence for the Dunning-Kruger effect across 46 countries
Authors: Walkowiak S. , Coutrot A. , Wiener J. M. , Hornberger M. , Manley E. , Spiers H. J. 
Published: September 2023

AbstractOverconfidence and the Dunning-Kruger effect have been reported in many cognitive domains. However, there is little examination in the field of spatial navigation. Here, we examined overconfidence in navigation ability in 376,836 participants from 46 countries. We tested navigation using our virtual wayfinding task in the app-based video game Sea Hero Quest, examined self-ratings of navigation ability and how many game levels participants had played before they dropped out. The main goal of this analysis was to investigate how performance of overconfident participants influenced the dropout rate from our experimental task embedded in a video game. First, we measured and modelled overestimation at baseline game levels. Age was found to be the strongest predictor of overestimation across the entire sample. Higher age was associated with increased overconfidence in all 46 countries and 11 distinct cultural clusters. Female participants were more likely to overestimate their performance across most of the life course (19-59 years old), however older men (60-70 years old) displayed highest overconfidence amongst all age-gender groups. Overconfidence also varied widely across countries. Secondly, we estimated performance on follow-up game levels for those who were previously identified as overconfident and we found that those who were more likely to display the Dunning-Kruger effect (i.e., poor performance while being overconfident) were predominantly female and older participants. Finally, survival analysis methods with time-dependent covariates revealed that poor wayfinding performance, while being overconfident, was one of the strongest predictors of task dropout. This Dunning-Kruger bias on participants dropout existed universally across all countries in our data.
Functional networks of inhibitory neurons orchestrate synchrony in the hippocampus
Authors: Bocchio Marco , Vorobyev Artem , Sadeh Sadra , Brustlein Sophie , Dard Robin , Reichinnek Susanne , Emiliani Valentina , Baude Agnes , Clopath Claudia , Cossart Rosa 
Published: September 2023

AbstractInhibitory interneurons are pivotal components of cortical circuits. Beyond providing inhibition, they have been proposed to coordinate the firing of excitatory neurons within cell assemblies. While the roles of specific interneuron subtypes have been extensively studied, their influence on pyramidal cell synchrony in vivo remains elusive. Employing an all-optical approach, we simultaneously recorded hippocampal interneurons and pyramidal cells and probed the network influence of individual interneurons using optogenetics. We demonstrate that CA1 interneurons form a functionally interconnected network that promotes synchrony through disinhibition during awake immobility, while preserving endogenous cell assemblies. Our network model underscores the importance of both cell assemblies and dense, unspecific interneuron connectivity in explaining our experimental findings, suggesting that interneurons may operate not only via division of labor but also through concerted activity.
Mixed representations of sound and action in the auditory midbrain
Authors: Quass GL , Rogalla MM , Ford AN , Apostolides PF 
Published: September 2023

AbstractLinking sensory input and its consequences is a fundamental brain operation. Accordingly, neural activity of neo-cortical and limbic systems often reflects dynamic combinations of sensory and behaviorally relevant variables, and these “mixed representations” are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur in brain regions upstream of the forebrain is less clear. Here, we conduct cellular-resolution 2-photon Ca2+imaging in the superficial “shell” layers of the inferior colliculus (IC), as head-fixed mice of either sex perform a reward-based psychometric auditory task. We find that the activity of individual shell IC neurons jointly reflects auditory cues and mice’s actions, such that trajectories of neural population activity diverge depending on mice’s behavioral choice. Consequently, simple classifier models trained on shell IC neuron activity can predict trial-by-trial outcomes, even when training data are restricted to neural activity occurring prior to mice’s instrumental actions. Thus in behaving animals, auditory midbrain neurons transmit a population code that reflects a joint representation of sound and action.Significance StatementNeurons in IC’s superficial “shell” layers preferentially project to higher-order thalamic nuclei that are strongly activated by sounds and their behavioral consequences. This integrative computation is thought critical for a variety of behaviorally relevant functions, such as establishing learned sound valence. However, whether such “mixed representations” reflect unique properties of thalamocortical networks, or rather are inherited from afferent inputs, is unclear. We show that in behaving mice, many shell IC neurons are modulated by sounds and mice’s actions. Consequently, shell IC population activity suffices to predict behavioral outcomes even prior to the goal-directed action. Our data thus establish shell IC nuclei as a novel, ascending source of mixed representations for the thalamocortical system.
The diffusion process of product-harm misinformation on social media: evidence from consumers and insights from communication professionals
Authors: Chen Zifei Fay , Cheng Yang 
Published: September 2023

PurposeThis study aims to propose a model that delineated the diffusion process of product-harm misinformation on social media. Drawing on theoretical insights from cue diagnosticity and corporate associations, the proposed model mapped out how consumers' information skepticism and perceived content credibility influence their perceived diagnosticity of the product-harm misinformation and corporate ability (CA) associations with the company being impacted, which in turn influenced their trust toward the company and negative word-of-mouth (NWOM) intention.Design/methodology/approachA survey was conducted with 504 US consumers to empirically test the proposed model. Following the survey, in-depth interviews were conducted with 11 communication professionals regarding the applicability of the model.FindingsWhen exposed to product-harm misinformation on social media, consumers' perceived diagnosticity of misinformation was negatively impacted by their information skepticism and positively impacted by perceived content credibility of misinformation. Perceived diagnosticity of product-harm misinformation negatively impacted consumers' CA associations, which then led to decreased trust and increased NWOM intention. Findings from the interviews further supported the diffusion process and provided insights on strategies to combat product-harm misinformation. Strategies shared by the interviewees included preparedness and social listening, proactive outreach and building strong CA associations as preventative measures.Originality/valueThis study incorporates the theoretical frameworks of cue diagnosticity and corporate associations into the scholarship of misinformation and specifically addresses the unique diffusion process of product-harm misinformation on social media. This study provides insights and tangible recommendations for communication professionals to combat product-harm misinformation.
Understanding the enduring shifts in sales strategy and processes caused by the COVID-19 pandemic
Authors: Giovannetti Marta , Sharma Arun , Rangarajan Deva , Cardinali Silvio , Cedrola Elena 
Published: September 2023

PurposeThe COVID-19 pandemic has led to major sales strategy and process changes as many interactions migrated from face-to-face to virtual environments. The nature of the interactions changed, and sales firms, the sales function and salespeople created new processes to excel in virtual environments. As sales processes evolve further, this paper aims to focus on understanding the enduring shifts in sales strategy and processes. In addition, this study seeks to understand the characteristics of enduring shifts and how they are distinct from temporary shifts.Design/methodology/approachThis qualitative analysis provides a comprehensive overview of the sales organizations and salespeople over the period from the start of the pandemic to early 2022. The authors interviewed 66 sales professionals from different countries and industries to better understand the temporary and enduring shifts in sales strategy and processes, adopting ad inductive and narrative approach.FindingsThere are four major findings. First, four key themes emerged: increased digitalization, resistance to digitalization, sales process changes and sales organization transformation. Second, changes are classified as temporary, permanent and accelerated changes. Third, some proposed changes were not supported. Finally, five findings were found that were not discussed in previous literature.Originality/valueThis paper finds distinctive findings that offer additional valuable insights that connect to and extend existing literature. These include emerging themes, classification shifts, unsupported proposed changes and unique findings.