bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved specificity and efficacy of base-editing therapies with hybrid guide RNAs
Authors: Whittaker Madelynn N. , Brooks Dominique L. , Quigley Aidan , Jindal Ishaan , Said Hooda , Qu Ping , Wang Josh Zhiyong , Ahrens-Nicklas Rebecca C. , Musunuru Kiran , Alameh Mohamad-Gabriel , Peranteau William H. , Wang Xiao
Published: April 2024

Phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI) are autosomal recessive disorders linked to the phenylalanine hydroxylase (PAH) gene, fumarylacetoacetate hydrolase (FAH) gene, and alpha-L-iduronidase (IDUA) gene, respectively. Potential therapeutic strategies to ameliorate disease include corrective editing of pathogenic variants in thePAHandIDUAgenes and, as a variant-agnostic approach, inactivation of the 4-hydroxyphenylpyruvate dioxygenase (HPD) gene, a modifier of HT1, via adenine base editing. Here we evaluated the off-target editing profiles of therapeutic lead guide RNAs (gRNAs) that, when combined with adenine base editors correct the recurrentPAHP281L variant,PAHR408W variant, orIDUAW402X variant or disrupt theHPDgene in human hepatocytes. To mitigate off-target mutagenesis, we systematically screened hybrid gRNAs with DNA nucleotide substitutions. Comprehensive and variant-aware specificity profiling of these hybrid gRNAs reveal dramatically reduced off-target editing and reduced bystander editing. Lastly, in a humanizedPAHP281L mouse model, we showed that when formulated in lipid nanoparticles (LNPs) with adenine base editor mRNA, selected hybrid gRNAs revert the PKU phenotype, substantially enhance on-target editing, and reduce bystander editingin vivo. These studies highlight the utility of hybrid gRNAs to improve the safety and efficacy of base-editing therapies.
Role of m6A RNA methylation in dosage compensation
Authors: Naik Hemant C , Baro Runumi , Sarkar Amritesh , M Muralidhar Nayak , Sunagar Kartik , Gayen Srimonta
Published: April 2024

In therian mammals, inactivation of one of the X-chromosomes in female cells (XX) balances the dosage of X-linked gene expression between the sexes, resulting in monoallelic expression of X-linked genes in females similar to males (XY). Therefore, it creates a dosage imbalance for X-linked genes with respect to the biallelically expressing autosomal genes (AA). X-to-autosome dosage compensation is thought to be achieved by the transcriptional upregulation of many genes from the active X-chromosome in both sexes. Here, we have delineated the role of m6A RNA methylation in the maintenance of dosage compensation in a variety of cell types, including embryonic, extra-embryonic and somatic cells. We show that m6A marks tend to be less enriched on X-linked transcripts compared to the autosomal transcripts in most of the studied cell types. However, our analysis demonstrates that m6A RNA methylation plays a minor role in dosage compensation. We show that the loss of m6A RNA methylation does not affect the maintenance of X-linked gene silencing on the inactive-X in early embryonic lineages, suggesting m6A is dispensable for the maintenance of X-chromosome inactivation. On the contrary, we show that the depletion of m6A affects X-to-autosome dosage compensation, however, the effect is minor and it occurs in a lineage-specific manner. Taken together, our study demonstrates that, although m6A marks are lowly enriched on X-linked transcripts compared to autosomal ones, it is dispensable for the maintenance of X-inactivation and has a minor contribution to the maintenance of X-to-autosome dosage compensation.
Intersectin1 promotes clathrin-mediated endocytosis by organizing and stabilizing endocytic protein interaction networks
Authors: Jin Meiyan , Iwamoto Yuichiro , Shirazinejad Cyna , Drubin David G.
Published: April 2024

During clathrin-mediated endocytosis (CME), dozens of proteins are recruited to nascent CME sites on the plasma membrane. Coordination of endocytic protein recruitment in time and space is important for efficient CME. Here, we show that the multivalent scaffold protein intersectin1 (ITSN1) promotes CME by organizing and stabilizing endocytic protein interaction networks. By live-cell imaging of genome-edited cells, we observed that endogenously labeled ITSN1 is recruited to CME sites shortly after they begin to assemble. Knocking down ITSN1 impaired endocytic protein recruitment during the stabilization stage of CME site assembly. Artificially locating ITSN1 to the mitochondria surface was sufficient to assemble puncta consisting of CME initiation proteins, including EPS15, FCHO, adaptor proteins, the AP2 complex and epsin1 (EPN1), and the vesicle scission GTPase dynamin2 (DNM2). ITSN1 can form puncta and recruit DNM2 independently of EPS15/FCHO or EPN1. Our work redefines ITSN1’s primary endocytic role as organizing and stabilizing the CME protein interaction networks rather than a previously suggested role in initiation and provides new insights into the multi-step and multi-zone organization of CME site assembly.
Infraslow dynamic patterns in human cortical networks track a spectrum of external to internal attention
Authors: Watters Harrison , Davis Aleah , Fazili Abia , Daley Lauren , LaGrow Theodore J , Schumacher Eric H , Keilholz Shella
Published: April 2024

Early efforts to understand the human cerebral cortex focused on localization of function, assigning functional roles to specific brain regions. More recent evidence depicts the cortex as a dynamic system, organized into flexible networks with patterns of spatiotemporal activity corresponding to attentional demands. In functional MRI (fMRI), dynamic analysis of such spatiotemporal patterns is highly promising for providing non-invasive biomarkers of neurodegenerative diseases and neural disorders. However, there is no established neurotypical spectrum to interpret the burgeoning literature of dynamic functional connectivity from fMRI across attentional states. In the present study, we apply dynamic analysis of network-scale spatiotemporal patterns in a range of fMRI datasets across numerous tasks including a left-right moving dot task, visual working memory tasks, congruence tasks, multiple resting state datasets, mindfulness meditators, and subjects watching TV. We find that cortical networks show shifts in dynamic functional connectivity across a spectrum that tracks the level of external to internal attention demanded by these tasks. Dynamics of networks often grouped into a single task positive network show divergent responses along this axis of attention, consistent with evidence that definitions of a single task positive network are misleading. Additionally, somatosensory and visual networks exhibit strong phase shifting along this spectrum of attention. Results were robust on a group and individual level, further establishing network dynamics as a potential individual biomarker. To our knowledge, this represents the first study of its kind to generate a spectrum of dynamic network relationships across such an axis of attention.
Beyond membrane permeability: A role for the small RNA MicF in regulation of chromosome replication and partitioning
Authors: Stibelman Aaron Y. , Sariles Amy Y. , Takahashi Melissa K.
Published: April 2024

Small regulatory RNAs (sRNA) have been shown to play a large role in the management of stress responses inEscherichia coliand other bacteria. sRNAs act post-transcriptionally on target mRNA through an imperfect base pairing mechanism to regulate downstream protein expression. The imperfect base pairing allows a single sRNA to bind and regulate a variety mRNA targets which can form intricate regulatory networks that connect different physiological processes for the cell’s response. Upon exposure to antimicrobials and superoxide generating agents, the MicF sRNA inE. colihas been shown to regulate a small set of genes involved in the management of membrane permeability. Currently, it is unknown whether MicF acts on other processes to mediate the response to these agents. Using an sRNA interaction prediction tool, we identified genes inE. colithat are potentially regulated by MicF. Through subsequent analysis using a sfGFP-based reporter-gene fusion, we have validated two novel targets of MicF regulation: SeqA, a negative modulator of DNA replication, and ObgE, a GTPase crucial for chromosome partitioning. Importantly, the interaction between MicF and these target mRNAs is contingent upon the presence of the RNA chaperone protein, Hfq. Furthermore, our findings affirm the role of MicF’s conserved 5’ seed pairing region in initiating these regulatory interactions. Our study suggests that, beyond its established role in membrane permeability management, MicF exerts control over chromosome dynamics in response to distinct environmental cues, implicating a more multifaceted regulatory function in bacterial stress adaptation.
Estimating heterogeneity of treatment effect in psychiatric clinical trials
Authors: Siegel Joshua S. , Zhong Jinglin , Tomioka Sasagu , Ogirala Ajay , Faraone Stephen V. , Szabo Steven T. , Koblan Kenneth S. , Hopkins Seth C.
Published: April 2024

Currently, placebo-controlled clinical trials report mean change and effect sizes, which masks information about heterogeneity of treatment effects (HTE). Here, we present a method to estimate HTE and evaluate the null hypothesis (H0) that a drug has equal benefit for all participants (HTE=0). We developed measure termed ‘estimated heterogeneity of treatment effect’ oreHTE, which estimates variability in drug response by comparing distributions between study arms. This approach was tested across numerous large placebo-controlled clinical trials. In contrast with variance-based methods which have not identified heterogeneity in psychiatric trials, reproducible instances of treatment heterogeneity were found. For example, heterogeneous response was found in a trial of venlafaxine for depression (peHTE=0.034), and two trials of dasotraline for binge eating disorder (Phase 2, peHTE=0.002; Phase 3, 4mg peHTE=0.011; Phase 3, 6mg peHTE=0.003). Significant response heterogeneity was detected in other datasets as well, often despite no difference in variance between placebo and drug arms. The implications of eHTE as a clinical trial outcomes independent from central tendency of the group is considered and the important of the eHTE method and results for drug developers, providers, and patients is discussed.
Cholesterol distribution among adults in Nigeria: A descriptive cross-sectional study in a rural tertiary hospital
Authors: Asogun Danny , Akyea Ralph K , Osuji Kingsley C , Imafidon Nathaniel O , Qureshi Nadeem , Iyen Barbara
Published: April 2024

Background

There is an increasing burden of cardiovascular disease in the Nigerian population, but very little known about the cholesterol distribution within subgroups of the general population.

Methods

A cross-sectional study of adults was done in a tertiary hospital in the Southern region of Nigeria. Using results of blood tests over an 8-month period, the cholesterol distribution and prevalence of dyslipidaemias were determined.

Results

A total of 46.8% of patients had raised total cholesterol (mean total cholesterol 198.93mg/dl (SD 57.81)), 14.6% had raised low-density lipoprotein cholesterol (LDL-C) (mean LDL-C 120.83mg/dl (SD 51.62)), and 27.9% of patients had raised triglycerides (mean triglycerides 128.83mg/dl (SD 75.26). Women had higher mean values than men, of total cholesterol (203.3mg/dl vs 193.4mg/dl), LDL-C (125.1mg/dl vs 115.5mg/dl), and non-HDL cholesterol (148.4mg/dl vs 141.1mg/dl). The 95thpercentile values of total cholesterol and LDL-C in the general population were 294mg/dl (7.6mmol/L) and 205.7mg/dl (5.3mmol/L) respectively.

Conclusion

Hypercholesterolaemia is highly prevalent in the Nigerian general population, with a higher prevalence in women compared to men. The 95thpercentile identified is likely to represent the thresholds associated with elevated risk of atherosclerotic cardiovascular disease risk within this population.

What is already known on this topic

There is a rising prevalence of cardiovascular disease (CVD) and CVD-related deaths in Nigeria, and a pressing need for targeted strategies and interventions to reduce this burden. However, there is lack of robust evidence on cholesterol distribution within subgroups of the Nigerian population.

What this study adds

This study described the distribution of cholesterol concentration in Nigerian adults by sex and age groups, and also determined the cholesterol 95thpercentile thresholds which are likely to be associated with elevated risks of atherosclerotic cardiovascular disease risk within this population

How this study might affect research, practice or policy

Evidence from this study will aid appropriate targeting of interventions to reduce the burden of hypercholesterolaemia and consequent risk of atherosclerotic cardiovascular disease.
Performance of low-cost non-invasive blood markers of liver cirrhosis in adults with chronic hepatitis B infection with and without comorbid alcohol use in Zambia
Authors: Mpisa Sydney , Kahere Morris , Kanunga Annie , Vinikoor Michael , Sinkala Edford
Published: April 2024

Background

Diagnosis of liver cirrhosis in patients with chronic hepatitis B is challenging given rare use of biopsy. In low and middle-income countries, transient elastography (TE), a recommended non-invasive imaging test for cirrhosis is rarely accessible. We therefore investigated the performance of multiple low-cost and more accessible blood-based liver fibrosis markers in patients with chronic hepatitis B infection in Zambia. As alcohol use complicates the assessment and outcomes of hepatitis B, we also considered alcohol use patterns in our evaluation.

Methods

We performed a hospital-based cross-sectional study, in Lusaka, Zambia, among consecutive treatment-naive adults with chronic hepatitis B mono-infection (i.e., HIV-negative) presenting to our hospital. The reference test for cirrhosis was TE of >/=9.6 kPa. Low-cost markers were the AST-to-platelet ratio index (APRI) at recommended threshold >2, as well as lower proposed alternative thresholds for Africa, >0.5 and >0.65, AST/ALT ratio and FIB-4 index >3.25. We evaluated the performance of each marker versus TE. In a secondary analysis, we evaluated marker performance in participants with current alcohol use versus lifetime abstinence.

Results

Among 239 adults with HBV mono-infection analyzed, the mean age was 34.7 years and 53 (22.2%) reported current alcohol use. The prevalence of cirrhosis by TE was 16.3% (95% CI: 11.87-21.63). The area under the receiver operating characteristic curve was 0.83, 0.80, 0.79 and 0.73 for FIB-4, APRI >0.5, APRI >0.65 and APRI >2 respectively. Virtually all indices performed less well in people with current alcohol use.

Conclusion

These data support the adoption of a lower APRI threshold in Africa, and the use of the FIB-4 index, for diagnosis of cirrhosis among patients with chronic hepatitis B infection. The currently-recommended APRI threshold may exclude people with cirrhosis who need antiviral therapy. Clinicians adopting these markers should screen for alcohol use and consider re-assessment of cirrhosis after alcohol reduction.
Essential conserved neuronal motors kinesin-1 and kinesin-3 regulate Aβ42 toxicity in vivo
Authors: Francis Deepthy , Paonessa Francesco , Fabre Caroline C.G. , Hewitt Victoria L. , Giannakou Maria E. , Peset Isabel , Whitworth Alexander J. , Livesey Frederick J. , Palacios Isabel M.
Published: April 2024

Alzheimer’s Disease is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of Alzheimer’s Disease may help identify new ways to reduce neuronal damage. In the past decadesDrosophilahas become a powerful tool in modelling mechanisms underlying human diseases. Here we investigate how the expression of the human 42-residue β-amyloid (Aβ) carrying the E22G pathogenic “Arctic” mutation (Aβ42Arc) affects axonal health and behaviour ofDrosophila. We find that Aβ42Arcflies present aberrant neurons, with altered axonal transport of mitochondrial and an increased number of terminal boutons at neuromuscular junctions. We demonstrate that the major axonal motor proteins kinesin-1 and kinesin-3 are essential for the correct development of neurons inDrosophilalarvae and similar findings are replicated in human iPSC-derived cortical neurons. We then show that the over-expression of kinesin-1 or kinesin-3 restores the correct number of terminal boutons in Aβ42Arcexpressing neurons and that this is associated with a rescue of the overall neuronal function, measured by negative geotaxis locomotor behavioural assay. We therefore provide new evidence in understanding the mechanisms of axonal transport defects in Alzheimer’s Disease, and our results indicate that kinesins should be considered as potential drug targets to help reduce dementia-associated disorders.
Silversol®(a colloidal nanosilver formulation) inhibits growth of antibiotic-resistantStaphylococcus aureusby disrupting its physiology in multiple ways
Authors: Thakkar Nidhi , Gajera Gemini , Godse Chhaya , DeSouza Anselm , Mehta Dilip , Kothari Vijay
Published: April 2024

Antibacterial effect of a colloidal nanosilver formulation Silversol®was investigated against an antibiotic-resistant strain ofStaphylococcus aureus. Lower concentrations of the test formulation exerted bacteriostatic and, its higher concentrations exerted bactericidal effect against this pathogen. Silversol®at sub-lethal concentration was found to disturb multiple physiological traits ofS. aureussuch as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis to get expressed differently under influence of the test formulation. Genes (argGandargH) involved in arginine biosynthesis emerged among the major targets of Silversol®inS. aureus.
Infrared spectroscopy across scales in length and time at BESSY II
Authors: Veber Alexander , Puskar Ljiljana , Kneipp Janina , Schade Ulrich
Published: April 2024

The infrared beamline at BESSY II storage ring was upgraded recently to extend the capabilities of infrared microscopy. The endstations available at the beamline are now facilitating improved characterization of molecules and materials at different length scales and time resolutions. Here, the current outline of the beamline is reported and an overview of the endstations available is given. In particular, the first results obtained by using a new microscope for nano-spectroscopy that was implemented are presented. The capabilities of the scattering-type near-field optical microscope (s-SNOM) are demonstrated by investigating cellulose microfibrils, representing nanoscopic objects of a hierarchical structure. It is shown that the s-SNOM coupled to the beamline allows imaging to be performed with a spatial resolution of less than 30 nm and infrared spectra to be collected from an effective volume of less than 30 nm × 30 nm × 12 nm. Potential steps for further optimization of the beamline performance are discussed.
Deutsche Bank Restart: Goodbye Goldman Sachs of Europe?
Authors: Allayannis George (Yiorgos) , Yemen Gerry , Holtz Paul
Published: April 2024

This public-sourced case describes the latest restructuring efforts by Deutsche Bank (DB) and gives a short history of prior restructuring efforts from the decade before. In July 2019, Christian Sewing, the new CEO of DB, announced a series of measures that included, among others, the elimination of global equity trading, the layoff of 18,000 employees, the creation of a “bad bank” to transfer noncore assets, and the suspension of dividends until 2022. The case describes key decisions a bank CEO makes when a bank needs to change course to return to profitability and growth. The case offers an opportunity to debate these key decisions, as well as discuss some of the prior ones during earlier restructuring efforts, and put the students in the CEO's shoes: What would you do and why? The case also describes key banking performance metrics (e.g., ROE, ROA) and other critical variables such as those reflecting capital health (Tier 1 ratio), as well as gives an overview of the bank business model and factors impacting bank profitability and value.
Revenue Recognition (Topic 606) at Salesforce.com, Inc.
Authors: Haskins Mark E. , Lynch Luann J. , Coleman Almand R.
Published: April 2024

This case uses an array of carefully selected and excerpted revenue recognition related information contained in Salesforce.com's January 31, 2019, 10-K. Maria, the fictional protagonist, is seeking to understand those disclosures as part of her preparation for an upcoming job interview with the company. As such, she is relying on those disclosures to provide insights as to the company's main product/service lines, the events that signal when and how much revenue the company has earned (i.e., the essence of its business model), along with the related official generally accepted accounting principles (GAAP) criteria pertinent to the valuing and timing of recorded revenues.
Safety in context: routines and the effect of a balanced safety and operations focus on worker perceptions and performance
Authors: Roberts Matthew D. , Douglas Matthew A. , Overstreet Robert E.
Published: April 2024

Purpose

To investigate the influence of logistics and transportation workers’ perceptions of their management’s simultaneous safety and operations focus (or lack thereof) on related worker safety and operational perceptions and behaviors.

Design/methodology/approach

This multi-method research consisted of two studies. Study 1 aimed to establish correlational relationships by evaluating the impact of individual-level worker perceptions of operationally focused routines (as a moderator) on the relationship between worker perceptions of safety-related routines and workers’ self-reported safety and in-role operational behaviors using a survey. Study 2 aimed to establish causal relationships by evaluating the same conceptual relationships in a behavioral-type experiment utilizing vehicle simulators. After receiving one of four pre-task briefings, participants completed a driving task scenario in a driving simulator.

Findings

In Study 1, the relationship between perceived safety focus and safety behavior/in-role operational behavior was strengthened at higher levels of perceived operations focus. In Study 2, participants who received the balanced pre-task briefing committed significantly fewer safety violations than the other 3 treatment groups. However, in-role driving deviations were not impacted as hypothesized.

Originality/value

This research is conducted at the individual (worker) level of analysis to capture the little-known perspectives of logistics and transportation workers and explore the influence of balanced safety and operational routines from a more micro perspective, thus contributing to a deeper understanding of how balanced routines might influence worker behavior when conducting dynamic tasks to ensure safe, effective outcomes.
Impacts of digital technology innovation for social responsibility of platform enterprises on shareholder value
Authors: Gao Peiyuan , Li Yongjian , Liu Weihua , Yuan Chaolun , Lee Paul Tae Woo , Long Shangsong
Published: April 2024

Purpose

Considering rapid digitalization development, this study examines the impacts of digital technology innovation on social responsibility in platform enterprises.

Design/methodology/approach

The study applies the event study method and cross-sectional regression analysis, taking 168 digital technology innovations for social responsibility issued by 88 listed platform enterprises from 2011 to 2022 to study the impact of digital technology innovations for social responsibility announcements of different announcement content and platform attributes on the stock market value of platform enterprises.

Findings

The results show that, first, the positive stock market reaction is produced on the same day as the digital technology innovation announcement. Second, the announcement of the platform’s public social responsibility and the announcement of co-innovation and radical innovation bring more positive stock market reactions. In addition, the announcements mentioned above issued by trading platforms bring more positive stock market reactions. Finally, the social responsibility attribution characteristics of the announcement did not have a significant differentiated impact on the stock market reaction.

Originality/value

Most scholars have studied digital technology innovation for social responsibility through modeling rather than second-hand data to empirically examine. This study uses second-hand data with the instrumental stakeholder theory to provide a new research perspective on platform social responsibility. In addition, in order to explore the different impacts of digital technology innovation on social responsibility, this study has classified digital technology innovation for social responsibility according to its social responsibility and digital technology innovation characteristics.
Are legal experts better decision makers than jurors? A psychological evaluation of the role of juries in the 21st century
Authors: Curley Lee , Neuhaus Till
Published: April 2024

Purpose

The Scottish Government hope to pilot judge only rape trials to increase the woefully low rape conviction rates in Scotland. The reasoning is that by removing jurors, the court will be attenuating the role that rape myths and other cognitive and social biases have on conviction rates. However, a plethora of research from cognitive and social psychology, legal literature and decision-making science has shown that experts, including judges and other legal professionals, may be no less biased than laypeople. This paper aims to outline the research highlighting that experts may also be biased, why biases in judges can be elicited, and potential alternative recommendations (i.e. deselecting jurors who score highly on rape myths and providing training/education for jurors). Furthermore, piloting with real judges, in real trials, may not be best practice. Therefore, the authors recommend that any piloting is preceded by experimental research.

Design/methodology/approach

N/A

Findings

Furthermore, piloting with real judges, in real trials, may not be best practice; therefore, the authors recommend that any piloting is preceded by experimental research.

Originality/value

To the best of the authors’ knowledge, this research is the first of its kind to directly compared the decision-making of jurors and judges within the current Scottish legal context.
New growth in cross-border E-business: evidence from gray forecasting to cross-border E-business in China
Authors: Huo Da , Ouyang Rihui , Tang Aidi , Gu Wenjia , Liu Zhongyuan
Published: April 2024

Purpose

This paper delves into cross-border E-business, unraveling its intricate dynamics and forecasting its future trajectory.

Design/methodology/approach

This paper projects the prospective market size of cross-border E-business in China for the year 2023 using the GM (1,1) gray forecasting model. Furthermore, to enhance the analysis, the paper attempts to simulate and forecast the size of China’s cross-border E-business sector using the GM (1,3) gray model. This extended model considers not only the historical trends of cross-border E-business but also the growth patterns of GDP and the digital economy.

Findings

The forecast indicates a market size of 18,760 to 18,934 billion RMB in 2023, aligning with the consistent growth observed in previous years. This suggests a sustained positive trajectory for cross-border E-business.

Originality/value

Cross-border e-commerce critically shapes China’s global integration and traditional industry development. The research in this paper provides insights beyond statistical trends, contributing to a nuanced understanding of the pivotal role played by cross-border e-commerce in shaping China’s economic future.
Game on for learning: a holistic exploration of Gamification’s impact on student engagement and academic performance in educational environments
Authors: Neerupa C. , Naveen Kumar R. , Pavithra R. , John William A.
Published: April 2024

Purpose

The research paper examines the complex relationship between gamification, student engagement and academic performance in educational environments. The study employed a structural equation model that highlights important connections among key constructs within the educational setting.

Design/methodology/approach

This research aims to explore the connection between gamification, student engagement and academic performance in educational settings. The study employs various statistical techniques such as factor analysis, Kaiser–Meyer–Olkin (KMO), Bartlett’s test, component transformation matrix, correlation and regression analysis, descriptive statistics, ANOVA, coefficients and coefficient correlations, residual statistics and confirmatory factor analysis (CFA) to analyze the data.

Findings

It was found that active participation by the instructor and good time management skills have a positive impact on student engagement levels (β = 0.380, p < 0.001; β = 0.433 and p < 0.001). However, peer interaction does not significantly predict student engagement (β = −0.068 and p = 0.352). Additionally, there is a positive correlation between student engagement and performance (β = 0.280 and p < 0.001).

Research limitations/implications

The study highlights the importance of innovative design to fully utilize gamification. Future research should consider design, user characteristics and educational context. The findings can guide informed decisions about gamification in education, fostering motivation and learning objectives.

Practical implications

The study presents a reliable tool for assessing student engagement and performance in educational settings, demonstrating high Cronbach’s alpha and robust reliability. It identifies student engagement and time management as significant predictors of Global Learning Outcome. The findings can inform decisions on implementing gamification in educational settings, promoting intrinsic motivation and aligning with learning objectives.

Social implications

The research highlights the transformative impact of gamification on educational practices, highlighting its potential to enhance student experiences, motivate, promote diversity and improve long-term academic performance, highlighting the trend of integrating technology into education.

Originality/value

In today’s ever-changing education landscape, it is essential to incorporate innovative techniques to keep students engaged and enthusiastic about learning. Gamification is one such approach that has become increasingly popular. It is a concept that takes inspiration from the immersive world of games to enhance the overall learning experience.
Applicability of AgNPs/GO/Na2SiO3 nanocomposite as a charged nanosorbent in the removal of cationic and anionic model dyes from water
Authors: Hassanzadeh Ali , Ghorbani-Kalhor Ebrahim , Farhadi Khalil , Abolhasani Jafar
Published: April 2024

Purpose

This study’s aim is to introduce a high-performance sorbent for the removal of both anionic (Congo red; CR) and cationic (methylene blue; MB) dyes from aqueous solutions.

Design/methodology/approach

Sodium silicate is adopted as a substrate for GO and AgNPs with positive charge are used as modifiers. The synthesized nanocomposite is characterized by FTIR, FESEM, EDS, BET and XRD techniques. Then, some of the most effective parameters on the removal of CR and MB dyes such as solution pH, sorbent dose, adsorption equilibrium time, primary dye concentration and salt effect are optimized using the spectrophotometry technique.

Findings

The authors successfully achieved notable maximum adsorption capacities (Qmax) of CR and MB, which were 41.15 and 37.04 mg g−1, respectively. The required equilibrium times for maximum efficiency of the developed sorbent were 10 and 15 min for CR and MB dyes, respectively. Adsorption equilibrium data present a good correlation with Langmuir isotherm, with a correlation coefficient of R2 = 0.9924 for CR and R2 = 0.9904 for MB, and kinetic studies prove that the dye adsorption process follows pseudo second-order models (CR R2 = 0.9986 and MB R2 = 0.9967).

Practical implications

The results showed that the proposed mechanism for the function of the developed sorbent in dye adsorption was based on physical and multilayer adsorption for both dyes onto the active sites of non-homogeneous sorbent.

Originality/value

The as-prepared nano-adsorbent has a high ability to remove both cationic and anionic dyes; moreover, to the high efficiency of the adsorbent, it has been tried to make its synthesis steps as simple as possible using inexpensive and available materials.
The causes, process and result of becoming a digital nomad family: a phenomenological case study
Authors: Günay Fatih , Toksöz Derya , Aslan Zeynep
Published: April 2024

Purpose

The aim of the research is to reveal information with regard to being a digital nomad as a family. Within this brief, the aim is to provide information regarding the reasons for choosing the digital nomad lifestyle of families, the female and male thoughts regarding the experience, destination selection factors and the difficulties and conveniences of digital nomadism for family aspects.

Design/methodology/approach

The data were obtained through a semi-structured interview questionnaire with a British digital nomad family, individually from the wife and husband, using a qualitative research design in the scope of the phenomenological research.

Findings

It was determined that having a better lifestyle, being willing to spend more time with family and traveling with them were the reasons for becoming a digital nomad. The opinions of the woman and man are in parallel. While the main features of being a digital nomad are freedom and flexibility, having time to spend with family is also important. Factors for choosing a destination as a nomad were access to nature, quality of life, cost of living, quality of the food, climate, proximity to other families who are nomads and interest in nonschool education. As a family, they meet their needs and wants, such as going to a local shop or staying in a rented house, but prefer to use restaurants and other facilities if their stay is short. Although having children motivates digital nomadism, it has been determined that families prefer to stay in a fixed place as nomads since it is not appropriate for children over a certain age to travel frequently.

Originality/value

The study provides detailed information regarding a family experience with digital nomadism through a case study.
Cost‐effectiveness analysis of abrocitinib compared with standard of care in adult moderate‐to‐severe atopic dermatitis in Japan
Authors: Tanaka Akio , Yuasa Akira , Kamei Kazumasa , Nagano Mitsuhiro , Murofushi Toshiaki , Bjerke Annika , Nakamura Kouki , Ikeda Shunya
Published: April 2024

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a significant clinical, economic, and human burden. The JAK1 Atopic Dermatitis Efficacy and Safety (JADE) program's Phase 3 trials demonstrated that as a treatment for moderate‐to‐severe AD in adults with previous exposure to immunotherapy, abrocitinib showed superior efficacy and safety compared with standard of care (SoC), consisting of topical corticosteroids. This study assessed the cost‐effectiveness of abrocitinib with SoC versus SoC alone for this patient population in Japan from a societal perspective. A hybrid decision tree and Markov model were used to capture the initial treatment and long‐term maintenance phases. Clinical inputs at 16 weeks were obtained through a Bayesian network meta‐analysis of four pivotal trials from the JADE program. Clinical inputs at 52 weeks were derived from the JADE EXTEND trial. Response‐specific utility inputs were obtained from published literature. Resource use, costs, and productivity inputs were gathered from Japanese claims analysis, literature, public documents, and expert opinion. Costs and quality‐adjusted life years (QALYs) were discounted at 2.0% per year and incremental cost‐effectiveness ratios (ICERs) were calculated. Sensitivity and scenario analyses were performed to validate the base case results and explore a payer perspective. Over a lifetime horizon and with the base‐case societal perspective, abrocitinib produced a mean gain of 0.75 QALYs, incremental costs of JPY (¥) 2 270 386 (USD [$] 17 265.6), and a resulting ICER of ¥3 034 514 ($23 076.5) per QALY compared with SoC. From a payer perspective, the incremental costs increased to ¥4 476 777 ($34 044.4), with an ICER of ¥5 983 495 ($45 502.6) per QALY. The results were most sensitive to treatment‐specific, response‐based utility weights, drug costs, and productivity‐related inputs. From a Japanese societal perspective, abrocitinib demonstrated superior QALYs and with a willingness‐to‐pay threshold of ¥5 000 000 ($38 023.4) per QALY, can be considered cost‐effective compared with SoC as a treatment for moderate‐to‐severe AD in adult patients with previous immunosuppressant exposure.
Resting cells of Skeletonema marinoi assimilate organic compounds and respire by dissimilatory nitrate reduction to ammonium in dark, anoxic conditions
Authors: Stenow Rickard , Robertson Elizabeth K. , Kourtchenko Olga , Whitehouse Martin J. , Pinder Matthew I. M. , Benvenuto Giovanna , Töpel Mats , Godhe Anna , Ploug Helle
Published: April 2024

Diatoms can survive long periods in dark, anoxic sediments by forming resting spores or resting cells. These have been considered dormant until recently when resting cells of Skeletonema marinoi were shown to assimilate nitrate and ammonium from the ambient environment in dark, anoxic conditions. Here, we show that resting cells of S. marinoi can also perform dissimilatory nitrate reduction to ammonium (DNRA), in dark, anoxic conditions. Transmission electron microscope analyses showed that chloroplasts were compacted, and few large mitochondria had visible cristae within resting cells. Using secondary ion mass spectrometry and isotope ratio mass spectrometry combined with stable isotopic tracers, we measured assimilatory and dissimilatory processes carried out by resting cells of S. marinoi under dark, anoxic conditions. Nitrate was both respired by DNRA and assimilated into biomass by resting cells. Cells assimilated nitrogen from urea and carbon from acetate, both of which are sources of dissolved organic matter produced in sediments. Carbon and nitrogen assimilation rates corresponded to turnover rates of cellular carbon and nitrogen content ranging between 469 and 10,000 years. Hence, diatom resting cells can sustain their cells in dark, anoxic sediments by slowly assimilating and respiring substrates from the ambient environment.
Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry
Authors: Niedoszytko Marek , Gorska Aleksandra , Brockow Knut , Bonadonna Patrizia , Lange Magdalena , Kluin‐Nelemans Hanneke , Oude‐Elberink Hanneke , Sabato Vito , Shoumariyeh Khalid , von Bubnoff Dagmar , Müller Sabine , Illerhaus Anja , Doubek Michael , Angelova‐Fischer Irena , Hermine Olivier , Arock Michel , Elena Chiara , Malcovati Luca , Yavuz Akif Selim , Schug Tanja Daniela , Fortina Anna Belloni , Judit Várkonyi , Gotlib Jason , Panse Jens , Vucinic Vladan , Reiter Andreas , Schwaab Juliana , Triggiani Massimo , Mattsson Mattias , Breynaert Christine , Romantowski Jan , Zanotti Roberta , Olivieri Elisa , Zink Alexander , van de Ven Annick , Stefan Alex , Barete Stephane , Caroppo Francesca , Perkins Cecelia , Kennedy Vanessa , Christen Deborah , Jawhar Mohamad , Luebke Johannes , Parente Roberta , Levedahl Kerstin , Hadzijusufovic Emir , Hartmann Karin , Nedoszytko Boguslaw , Sperr Wolfgang R. , Valent Peter
Published: April 2024

Background

Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry.

Methods

Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow‐up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18–91 years).

Results

Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti‐inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy‐sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug‐induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow‐up.

Conclusions

HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.
Developing Asia's fiscal landscape and challenges
Authors: Go Eugenia , Hill Sam , Jaber Maria Hanna , Jinjarak Yothin , Park Donghyun , Ragos Anton
Published: April 2024

While tax revenues steadily rose in the decades prior to the onset of COVID‐19, they continue to lag well behind high‐income countries and some developing peers. The region continues to rely predominantly on indirect taxes, particularly relatively efficient consumption taxes. However, developing Asia's tax structure is less progressive compared to high‐income countries. Government expenditures on education and health, vital for promoting equitable growth, were comparatively modest. Substantial fiscal policy stimulus in response to COVID‐19, combined with the impact of the downturn on revenues, has severely weakened public finances in many countries. The combination of falling revenues and higher spending during COVID‐19 has markedly widened deficits and caused a further rise in debt levels that were already rising. As the pandemic recedes, governments will need to carefully calibrate fiscal consolidation to safeguard fiscal sustainability while protecting the poor and vulnerable.
Editorial: Crystalising the burden of steatotic liver disease
Authors: Bertot Luis Calzadilla , Adams Leon A.
Published: April 2024

LINKED CONTENT

This article is linked to Schneider et al papers. To view these articles, visit https://doi.org/10.1111/apt.17958 and https://doi.org/10.1111/apt.17992
Hepatic inflammation and fibrosis are profiles related to mid‐term mortality in biopsy‐proven MASLD: A multicenter study in Japan
Authors: Tsutsumi Tsubasa , Kawaguchi Takumi , Fujii Hideki , Kamada Yoshihiro , Takahashi Hirokazu , Kawanaka Miwa , Sumida Yoshio , Iwaki Michihiro , Hayashi Hideki , Toyoda Hidenori , Oeda Satoshi , Hyogo Hideyuki , Morishita Asahiro , Munekage Kensuke , Kawata Kazuhito , Sawada Koji , Maeshiro Tatsuji , Tobita Hiroshi , Yoshida Yuichi , Naito Masafumi , Araki Asuka , Arakaki Shingo , Noritake Hidenao , Ono Masafumi , Masaki Tsutomu , Yasuda Satoshi , Tomita Eiichi , Yoneda Masato , Tokushige Akihiro , Ueda Shinichiro , Aishima Shinichi , Nakajima Atsushi , Okanoue Takeshi
Published: April 2024

Aims

A multi‐stakeholder consensus has proposed MASLD (metabolic dysfunction‐associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid‐term mortality of patients with biopsy‐proven MASLD in Japan.

Methods

We enrolled 1349 patients with biopsy‐proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data‐mining analysis.

Results

The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty‐five patients with MASLD died. Of these, liver‐related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9‐fold and 1.8‐fold risk of mortality, respectively. In the decision‐tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid‐term prognosis of patients with MASLD.

Conclusions

In patients with biopsy‐proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver‐related events. Hepatic inflammation and fibrosis were significant factors influencing mid‐term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.
Letter: Bif195 for aspirin‐induced gastric mucosal damage – More to do in further research. Authors' reply
Authors: Løn Nina , Engel Sara , Damholt Anders , Wellejus Anja , Knop Filip K.
Published: April 2024

LINKED CONTENT

This article is linked to Løn et al papers. To view these articles, visit https://doi.org/10.1111/apt.17817 and https://doi.org/10.1111/apt.17984
Nipping cytomegalovirus in the bud for umbilical cord blood transplantation
Authors: Paviglianiti Annalisa
Published: April 2024

Real data confirm an excellent toxicity profile and effectiveness of letermovir prophylaxis with decreased cytomegalovirus reactivation and resistance in umbilical cord blood transplantation for both paediatric and adult patients.

Commentary on: Yan et al. Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation. Br J Haematol 2024;204:2378‐2389.
Larger comfortable interpersonal distances in adults exposed to child maltreatment: The role of depressive symptoms and social anxiety
Authors: Hautle Lara‐Lynn , Kurath Jennifer , Jellestad Lena , Lüönd Antonia M. , Wingenbach Tanja S. H. , Jansson Billy , Pfaltz Monique C.
Published: April 2024

Previous studies report a preference for larger comfortable interpersonal distance (CIPD) in individuals with child maltreatment (CM) when being approached by others. Yet, research on approaching others, as opposed to being approached, as well as on potential effects of social anxiety and depression is lacking. We investigated if CM and depressive symptoms influence CIPD and if social anxiety mediates the possible association of CM and CIPD when approaching a female stranger. One hundred ten participants with CM (CM) and 58 participants without CM (non‐CM) experiences performed the stop‐distance paradigm and stopped first when feeling uncomfortable (D1) and again when feeling very uncomfortable (D2). CM experiences were associated with a preference for larger CIPD, independent of depressive symptoms. All CM subtypes were associated with a larger D2. The relationship between CM and CIPD was partially mediated by social anxiety. These novel findings can help to develop interventions strengthening socially relevant skills and processes in those affected by CM, targeting alterations in social anxiety and depression.