bluuebunny/crossref_metadata_2025 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

People 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

Germline 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

Bacteriophages 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

Stickland-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

The 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

Full 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

Type 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

Advancing 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.

Highlights

The 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

Despite 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

Overconfidence 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

Inhibitory 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

Linking 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 Statement

Neurons 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

Purpose

This 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/approach

A 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.

Findings

When 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/value

This 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

Purpose

The 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/approach

This 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.

Findings

There 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/value

This 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.
Asymmetric responses of abundance and diversity of N‐cycling genes to altered precipitation in arid grasslands
Authors: Zhao Mengying , Shen Haihua , Zhu Yankun , Xing Aijun , Kang Jie , Liu Lingli , Fang Jingyun
Published: September 2023

Precipitation changes exert a fundamental effect on the nitrogen (N) cycle in water‐limited grasslands. Soil microbes are essential drivers of N cycle, and the rates and their stabilities of interrelated N‐cycling processes are reflected by the abundance and diversity of N‐cycling genes. Yet, little is known about how altered precipitation affects the genes involved in the entire N‐cycling pathways.

By combining a 6‐year precipitation manipulation experiment (−30%, ambient, +30%, +50%) with metagenomic sequencing, we investigated the responses of N‐cycling gene abundance and diversity to altered precipitation at two soil depths (0–10 and 30–50 cm).

We found that increased precipitation enhanced the abundance of numerous key genes, leading to an acceleration of N turnover, but decreased the diversity of ammonium assimilation genes. Decreased precipitation did not reduce abundance or diversity of N‐cycling genes. Most N‐cycling genes showed generally consistent responses to altered precipitation in the topsoil (0–10 cm) and subsoil (30–50 cm), albeit with clear distinctions in both abundance and diversity by soil depth. These precipitation‐specific responses and depth‐dependent variabilities of functional genes were attributed to the distinct taxonomic composition of each N‐cycling gene. Furthermore, we quantified gross N transformation rates and found that they were well predicted by the abundance of most N‐cycling genes (e.g. genes involved in ammonium assimilation and nitrification).

Our study sheds new light on the soil N cycle under precipitation alterations from the perspective of individual gene abundance and diversity and shows that future increases in precipitation could accelerate soil N turnover in arid and semi‐arid lands.

Read the free Plain Language Summary for this article on the Journal blog.
Grassland degradation alters the effect of nitrogen enrichment on the multidimensional stability of plant community productivity
Authors: Zhang Hongjin , Wang Wei
Published: September 2023

Nitrogen (N) enrichment threatens the ability of grasslands to support sustainable functions. However, we do not know whether grassland degradation can alter the effect of N enrichment on the multidimensional stability of plant community productivity.

Using data from N enrichment experiments at temperate grassland sites (no, moderate and severe degradation) that experienced a flooding event, we tested the impact of N enrichment on multidimensional stability (resistance, resilience, recovery and temporal stability) of plant community productivity.

In non‐degraded and moderately degraded grasslands, N enrichment negatively influenced resistance and temporal stability but positively altered resilience and did not change recovery. Species asynchrony altered all stability dimensions, except for recovery. In severely degraded grasslands, the effects of N enrichment on multidimensional stability shifted. Resilience and recovery were negatively affected by N enrichment, while resistance and temporal stability were not influenced. A decrease in dominant species stability reduced community resilience and recovery in severely degraded grasslands.

Synthesis and application. Grassland degradation regulates the effect of N enrichment on the multidimensional stability of plant community productivity. Thus, our findings highlight the need to consider grassland degradation in future studies for a comprehensive understanding of grassland dynamics.
What is the good life and how do individuals attain it? Meaning of happiness, its assessment, and pathways
Authors: Sarmah Palakshi , Suar Damodar , Patnaik Priyadarshi
Published: September 2023

This research investigates the contents, antecedents, and mediators of happiness in the Indian state of Assam. The first study examines the content and meanings of happiness in Assamese culture. Posing exploratory questions, a thematic analysis of the narrations of 53 participants revealed 18 themes, grouped into intrinsic or content and extrinsic or context factors of happiness. The content and meanings of happiness embrace a blend of ancient Indian, Eastern, and Western concepts. Based on these results, a culture‐sensitive happiness scale is constructed in the second study. It further tests whether life skills mediate the relationship between character strength and happiness. Data from 503 Assamese participants showed that the one‐factor model of happiness, combining all 14 items of intrinsic and extrinsic factors, is acceptable. It has measurement invariance across male and female genders and high‐ and low‐income groups. To ensure criterion‐related validity, the happiness of people is associated with their well‐being profiles. Adjusting the confounding effects of age and sex of participants, it is observed that character strengths do not promote happiness but pass through life skills fully to promote happiness.
Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios
Authors: Sugimura Yukiharu , Bauer Sebastian , Immohr Moritz Benjamin , Mehdiani Arash , Rellecke Philipp , Tudorache Igor , Horn Patrick , Westenfeld Ralf , Boeken Udo , Aubin Hug , Lichtenberg Artur , Akhyari Payam
Published: September 2023

Background

Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS.

Methods

This single‐center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis.

Results

In‐hospital and 30‐day mortality rates were 56.7% (n = 51) and 48.9% (n = 44), respectively. In‐hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non‐AMI patients (p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in‐hospital mortality by multivariate analysis (n = 0.02).

Conclusions

Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.
Artificial intelligence in clinical decision‐making: Rethinking personal moral responsibility
Authors: Smith Helen , Birchley Giles , Ives Jonathan
Published: September 2023

Artificially intelligent systems (AISs) are being created by software developing companies (SDCs) to influence clinical decision‐making. Historically, clinicians have led healthcare decision‐making, and the introduction of AISs makes SDCs novel actors in the clinical decision‐making space. Although these AISs are intended to influence a clinician's decision‐making, SDCs have been clear that clinicians are in fact the final decision‐makers in clinical care, and that AISs can only inform their decisions. As such, the default position is that clinicians should hold responsibility for the outcomes of the use of AISs. This is not the case when an AIS has influenced a clinician's judgement and their subsequent decision. In this paper, we argue that this is an imbalanced and unjust position, and that careful thought needs to go into how personal moral responsibility for the use of AISs in clinical decision‐making should be attributed. This paper employs and examines the difference between prospective and retrospective responsibility and considers foreseeability as key in determining how personal moral responsibility can be justly attributed. This leads us to the view that moral responsibility for the outcomes of using AISs in healthcare ought to be shared by the clinical users and SDCs.
The effectiveness of self: A meta‐analysis of using self‐referential encoding techniques in education
Authors: Liu Zheng , Wen Jiahui , Liu Yikang , Hu Chuan‐Peng
Published: September 2023

Background

Self‐related information is difficult to ignore and forget, which brings valuable implications for educational practice. Self‐referential encoding techniques involve integrating self‐referencing cues during the processing of learning material. However, the evidence base and effective implementation boundaries for these techniques in teaching and learning remain uncertain due to research variability.

Aims

The present meta‐analysis aims to quantitatively synthesize the results from studies applying self‐referential encoding techniques in education.

Methods

The analysis was based on data from 20 independent samples, including 1082 students from 13 primary studies identified through a systematic literature search.

Results

Results from random effect models show that incorporating self‐referential encoding techniques improved learning (g = .40, 95% CI [.18, .62]). Subgroup analysis showed that the valence of learning material serves as a significant boundary condition for this strategy. The students' cohorts, types of learning materials, and research context did not moderate the effect sizes.

Conclusions

Our results suggest that incorporating self‐referential encoding techniques on negative materials shows an aversive effect. Overall, there is a universal benefit to using self‐referential encoding techniques as an appropriate design guideline in educational contexts. Implications for teaching practice and future directions are discussed. Further studies are needed to investigate the effectiveness in more diverse educational and teaching situations.
Combination therapy with WEE1 inhibition and trifluridine/tipiracil against esophageal squamous cell carcinoma
Authors: Nguyen Vu Trang H. , Kikuchi Osamu , Ohashi Shinya , Saito Tomoki , Ida Tomomi , Nakai Yukie , Cao Yang , Yamamoto Yoshihiro , Kondo Yuki , Mitani Yosuke , Kataoka Shigeki , Kondo Tomohiro , Katada Chikatoshi , Yamada Atsushi , Matsubara Junichi , Muto Manabu
Published: September 2023

Despite advanced therapeutics, esophageal squamous cell carcinoma (ESCC) remains one of the deadliest cancers. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and MK1775 (WEE1 inhibitor) as a treatment for ESCC. This study demonstrates that trifluridine induces single‐strand DNA damage in ESCC cells, as evidenced by phosphorylated replication protein 32. The DNA damage response includes cyclin‐dependent kinase 1 (CDK1) (Tyr15) phosphorylation as CDK1 inhibition and a decrease of the proportion of phospho‐histone H3 (p‐hH3)‐positive cells, indicating cell cycle arrest at the G2 phase before mitosis entry. The WEE1 inhibitor remarkedly suppressed CDK1 phosphorylation (Try15) and reactivated CDK1, and also increased the proportion of p‐hH3‐positive cells, which indicates an increase of the number of cells into mitosis. Trifluridine combined with a WEE1 inhibitor increased trifluridine‐mediated DNA damage, namely DNA double‐strand breaks, as shown by increased γ‐H2AX expression. Moreover, the combination treatment with trifluridine/tipiracil and a WEE1 inhibitor significantly suppressed tumor growth of ESCC‐derived xenograft models. Hence, our novel combination treatment with trifluridine/tipiracil and a WEE1 inhibitor is considered a candidate treatment strategy for ESCC.
Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta‐analysis
Authors: Bai Jiang , Yin Xinyu , Li Jiaqi , Li Jia‐Qi , Niu Yanna , Li Zhenhua , Li Jing , Zhou Yun
Published: September 2023

Background

Focal segmental glomerulosclerosis is the most prevalent acquired kidney disease leading to end‐stage renal disease in children and has a propensity for recurring in the transplanted kidney. The recurrence of FSGS after kidney transplantation in children varies greatly. In addition, the risk factors and outcomes of recurrence of FSGS remain controversial. This study evaluated the recurrence rate, risk factors, and prognosis of FSGS after kidney transplantation in order to provide advice and assistance in clinical decision‐making for pediatric kidney transplantation.

Methods

PubMed, Embase, Web of Science, CNKI, and other databases were searched from the establishment of the repository to March 2022. We extracted data on incidence, risk factors, and outcomes.

Results

The results showed that the recurrence rate of primary FSGS in children after renal transplantation was 48% (95% CI 36%–59%) and the recurrence rate of FSGS (all forms) was 35% (95% CI 17%–52%). The graft loss rate of primary FSGS in children after kidney transplantation was 29% (95% CI 17%–42%) and the graft loss rate of FSGS (all forms) was 29% (95% CI 4%–62%). 57% (95% CI 42%–73%) of pediatric patients with recurrent primary FSGS showed complete remission. Risk factor analyses showed that age of onset (SMD .69, 95% CI .20–1.19, p = .006) was related to the recurrence of primary FSGS, whereas the living related donor was not a risk factor for recurrent primary FSGS in pediatrics after kidney transplantation (OR 1.22, 95% CI .48–3.10, p = .674).

Conclusions

The recurrence rate and graft loss rate of FSGS in children after kidney transplantation were relatively high. Age at onset was associated with a risk for recurrent primary FSGS, whereas the living related donor was not a risk factor for recurrent FSGS in pediatric kidney recipients.
Expecting to achieve against the odds: Anti‐immigrant sentiment and immigrants' educational and occupational expectations in Europe
Authors: Chykina Volha
Published: September 2023

Scholars have identified many factors that lead to changes in anti‐immigrant sentiment. Less is known, however, about the effects of anti‐immigrant sentiment on the academic experiences and outcomes of immigrant students. This manuscript examines the relationship between anti‐immigrant sentiment and immigrants’ expectations to achieve a college degree and career success in Europe. Consistent with established literature on immigrant optimism, this study finds that immigrants generally have higher educational and occupational expectations than their nonimmigrant peers. However, these positive associations decrease in countries with higher levels of anti‐immigrant sentiment. These patterns manifest for both first‐ and second‐generation immigrants, indicating that the potential deleterious effects of anti‐immigrant sentiment span generations of immigrants. These findings shed light on the out‐of‐family and out‐of‐school factors that shape the educational trajectories of immigrant youth and show that increases in anti‐immigrant sentiment might bring about long‐term damage to the success of immigrants in their host countries. They also suggest that school administrators and policymakers interested in immigrant success in the host countries should take anti‐immigrant sentiment into account when devising approaches to aid immigrant incorporation.
Serum neurofilament light chain: a promising early diagnostic biomarker for hereditary transthyretin amyloidosis?
Authors: Romano Angela , Primiano Guido , Antonini Giovanni , Ceccanti Marco , Fenu Silvia , Forcina Francesca , Gentile Luca , Inghilleri Maurizio , Leonardi Luca , Manganelli Fiore , Obici Laura , Sabino Andrea , Sciarrone Maria Ausilia , Tozza Stefano , Vitali Francesca , Luigetti Marco
Published: September 2023

Background and purpose

Hereditary transthyretin amyloidosis (ATTRv) is a life‐threatening disease caused by mutations in the gene encoding transthyretin (TTR). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL). In this study, the aim was to determine serum NfL (sNfL) levels in a late‐onset ATTRv population and evaluate whether it might represent a reliable biomarker of disease onset (i.e., ‘conversion’ from the asymptomatic status to symptomatic disease in TTR mutation carriers).

Methods

In all, 111 individuals harbouring a pathogenic TTR variant (61 symptomatic ATTRv patients and 50 presymptomatic carriers) were consecutively enrolled. Fifty healthy volunteers were included as the control group. Ella™ apparatus was used to assess sNfL levels.

Results

Serum NfL levels were increased in ATTRv patients compared to both presymptomatic carriers and healthy controls, whilst not differing between carriers and healthy controls. An sNfL cut‐off of 37.10 pg/mL could discriminate between asymptomatic and symptomatic individuals with high diagnostic accuracy (area under the curve 0.958; p < 0.001), sensitivity (81.4%) and specificity (100%).

Conclusions

Serum NfL seems to be a promising biomarker of peripheral nerve involvement in ATTRv amyloidosis and might become a reliable, objective measure to detect the transition from the presymptomatic stage to the onset of symptomatic disease. Further longitudinal studies are needed to confirm such a role and determine whether it could equally represent a biomarker of disease progression and response to therapy.
Altered actin dynamics is possibly implicated in the inhibition of mechanical stimulation‐induced dermal fibroblast differentiation into myofibroblasts
Authors: Kuroda Kazuya , Kiya Koichiro , Matsuzaki Shinsuke , Takamura Hironori , Otani Naoya , Tomita Koichi , Kawai Kenichiro , Fujiwara Toshihiro , Nakai Kunihiro , Onishi Ayako , Katayama Taiichi , Kubo Tateki
Published: September 2023

The formation of hypertrophic scars and keloids is strongly associated with mechanical stimulation, and myofibroblasts are known to play a major role in abnormal scar formation. Wounds in patients with neurofibromatosis type 1 (NF1) become inconspicuous and lack the tendency to form abnormal scars. We hypothesized that there would be a unique response to mechanical stimulation and subsequent scar formation in NF1. To test this hypothesis, we investigated the molecular mechanisms of differentiation into myofibroblasts in NF1‐derived fibroblasts and neurofibromin‐depleted fibroblasts and examined actin dynamics, which is involved in fibroblast differentiation, with a focus on the pathway linking LIMK2/cofilin to actin dynamics. In normal fibroblasts, expression of α‐smooth muscle actin (α‐SMA), a marker of myofibroblasts, significantly increased after mechanical stimulation, whereas in NF1‐derived and neurofibromin‐depleted fibroblasts, α‐SMA expression did not change. Phosphorylation of cofilin and subsequent actin polymerization did not increase in NF1‐derived and neurofibromin‐depleted fibroblasts after mechanical stimulation. Finally, in normal fibroblasts treated with Jasplakinolide, an actin stabilizer, α‐SMA expression did not change after mechanical stimulation. Therefore, when neurofibromin was dysfunctional or depleted, subsequent actin polymerization did not occur in response to mechanical stimulation, which may have led to the unchanged expression of α‐SMA. We believe this molecular pathway can be a potential therapeutic target for the treatment of abnormal scars.
Observation of flaking process in rolling contact fatigue of bearing steel with spheroidal inclusions by laminography using ultrabright synchrotron radiation X‐rays
Authors: Nakai Yoshikazu , Shiozawa Daiki , Kikuchi Shoichi , Nishina Takashi , Kobayashi Hiroshi , Kurahashi Masanori , Makino Taizo , Neishi Yutaka
Published: September 2023

Rolling contact fatigue tests were performed on specimens containing spheroidal inclusions to clarify the effect of the orientation of inclusions, and the results were compared with those of specimens containing stringer‐shaped inclusions. For all types of inclusion, cracks first formed on the rolling surface and then propagated in the depth direction, and an internal crack parallel to the rolling surface formed from the deepest point of the vertical crack, which led to flaking. The flaking life of the specimens with spheroidal inclusions was longer than that of the specimens with stringer‐shaped inclusions, where the initiation and propagation lives of cracks were affected by the inclusion shape and size. The surface crack initiation life was shorter for specimens with longer surface inclusions, whereas the crack propagation life decreased with the depth of surface inclusion. The greater the scatter of the size of inclusions, the greater the scatter of flaking life.
What's a School Worth to a Neighborhood? A Spatial Hedonic Analysis of Property Prices in the Context of Accommodation Reviews in Ontario
Authors: Merrall John , Higgins Christopher D. , Paez Antonio
Published: September 2023

Due to a change in capital funding formula, many school boards across the Province of Ontario engaged in Accommodation Reviews to rationalize the supply of school capacity. This process led to numerous school closures and raised important policy questions regarding the economic value of a school in terms of its capitalization into property values and, by extension, how the closure of a school might affect local neighborhoods. To explore these questions, this research uses spatial hedonic methods to estimate the implicit value of accessibility to schools in the City of Hamilton, Ontario. Spatial Durbin model results provide evidence of a significant negative correlation between distance to schools and housing prices in the Canadian context. This suggests that accessibility to schools is capitalized into property values and that the closure of a neighborhood school may result in potentially significant losses of economic value in communities.
Psychometric properties of the Cultural Intelligence Scale based on item response theory
Authors: Darandari Eqbal , Khayat Shatha
Published: September 2023

The aim of this study was to investigate the psychometric properties of Cultural Intelligence Scale (CQS), based on item response theory (IRT) using the graded response model (GRM). The study calibration sample included 400, while the study sample included 1000, male and female Saudi participants, aged between 18 and 62 years. IRT‐GRM results supported the quality of the psychometric properties of CQS, and its appropriateness to measure cultural intelligence (CQ) for the majority of individuals. CQS well‐distinguished people at different ability levels along the CQ latent trait, particularly with middle and low abilities. However, CQS full scale and subscales had less accurate measurement precision at high levels of CQ, and some subscales had more precision at low level abilities. CQS items had medium ability to differentiate among subjects, and they provided more information in evaluating individuals with medium CQ. Therefore, CQS might be more suitable for identification and development purposes, where low to med‐levels of CQ are expected. Additional assessment procedures need to be added, for selection or promotion purposes to increase the measurement precision. Confirmatory factor analysis results confirmed the multidimensional construct of CQS with four specific‐related factors at the first level, and an aggregate factor at the second level. This model provided better model fit using IRT‐GRM approach, and it was supported by classical test theory analysis results. Therefore, it is important to rely on subscale scores, besides the total score to interpret CQ for individuals. The study stressed the importance of examining CQS item parameters and information based on the country it is adapted for, to investigate how they interact with country culture; and to take into account ability level, when selecting optimal measures.