bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Combination of Neuropsychiatric Symptoms and Blood-based biomarkers for Early Detection of Cognitive Disorders
Authors: Leow Yi Jin , Ismail Zahinoor , Saffari Seyed Ehsan , Sandhu Gurveen Kaur , Tanoto Pricilia , Hui En Lee Faith Phemie , Ghildiyal Smriti , Liew Shan Yao , Bhalla Gursimar , Ying Sim Xin , Mohammed Adnan Azam , Vipin Ashwati , Dang Chao , Kandiah Nagaendran 
Published: December 2024

AbstractBackgroundIntegrating behavioural assessments with blood-based biomarkers (BBM) could improve diagnostic accuracy for Mild Cognitive Impairment (MCI) linked to early-stage neurodegenerative disease (NDD). This study investigates the potential of combining neuropsychiatric symptoms (NPS) with BBM to enhance the differentiation between older adults with MCI and those with Normal Cognition (NC) in a multi-ethnic Southeast Asian cohort.MethodsThis cross-sectional study analyzed baseline data from the Biomarkers and Cognition Study, Singapore(BIOCIS). Data from 678 participants (mean[SD]age 59.16[11.02]years, 39.50% males) with NC and MCI were included. Behavioral symptoms were assessed using the Mild Behavioral Impairment Checklist (MBI-C) and Depression, Anxiety, and Stress Scales (DASS). Blood samples were analyzed for amyloid-beta (Aβ40, Aβ42), phosphorylated Tau (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Regression models adjusted for age, education, gender, cognitive status (CS) and APOE-ε4 status were used. Discriminative power was evaluated using the area under the curve (AUC) to assess the combined predictive accuracy of behavioral and biological markers for CS, i.e., MCI status over CN.ResultsThe study included MBI-C scores (total, interest, mood, control) and BBM levels (Aβ40, NfL, GFAP) were significantly higher in MCI group, compared to CN group. Elevated GFAP (OR:3.636, 95% CI:1.959, 6.751, p<0.001) and higher MBI-C-Mood scores (OR:2.614, 95% CI:1.538, 4.441, p<0.001) significantly increased the likelihood of MCI. The combined model, integrating NPS and BBM markers, showed strong discriminative ability for MCI (AUC = 0.786), with 64.7% sensitivity and 84.9% specificity at a threshold of 0.616, compared to NPS markers (AUC: 0.593) or BBM (AUC: 0.697) alone.Conclusions and RelevanceThe combined use of BBM and NPS achieved optimal accuracy in distinguishing MCI from NC, with strong associations between GFAP, MBI-C Mood scores, and CS. These findings underscore neuroinflammation and mood disturbances as critical factors in early NDD, supporting the importance of dual-dimension screening strategies. Integrating NPS and BBM represents a novel and effective diagnostic approach for detection of MCI due to AD or other dementias. The integrated framework, leveraging both pathophysiological and neuropsychiatric markers, facilitates earlier diagnosis, potentially improving clinical decision-making and enabling targeted disease-modifying therapies for individuals with neurodegenerative disorders.
EXTRA-seq: a genome-integrated extended massively parallel reporter assay to quantify enhancer-promoter communication
Authors: Kribelbauer-Swietek Judith F. , Gardeux Vincent , Llimos-Aubach Gerard , Faltejskova Katerina , Russeil Julie , Grenningloh Nadia , Levassor Lucas , Steiner Clémence , Vondrasek Jiri , Deplancke Bart 
Published: December 2024

Precise control of gene expression is essential for cellular function, but the mechanisms by which enhancers communicate with promoters to coordinate this process are not fully understood. While sequence-based deep learning models show promise in predicting enhancer-driven gene expression, experimental validation and human-interpretable mechanistic insights lag behind.Here, we presentEXTRA-seq, a novelEXTendedReporterAssay followed bysequencing designed to quantify enhancer activity in endogenous contexts over kilobase-scale distances. We demonstrate that EXTRA-seq can be targeted to disease-relevant loci and captures expression changes at the resolution of individual transcription factor binding sites, enabling mechanistic discovery. Using engineered synthetic enhancer-promoter combinations, we reveal that the TATA-box acts as a dynamic range amplifier, modulating expression levels in function of enhancer strength. Importantly, we find that integrating state-of-the-art deep learning models with plasmid-based enhancer assays improves the prediction of gene expression as measured by EXTRA-seq. These findings open new avenues for predictive modeling and therapeutic applications.Overall, our work provides a powerful experimental platform to interrogate the complex interplay between enhancers and promoters, bridging the gap betweenin silicopredictions and human-interpretable biological mechanisms.
Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons
Authors: Kittilukkana Aiyarin , Carmona Asuncion , Somogyi Andrea , Pilapong Chalermchai , Ortega Richard 
Published: December 2024

AbstractIron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated in neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular iron, plays a prominent role in iron-induced neurological damage. However, the mechanisms governing the detoxification and transport of labile iron within neurons are not fully understood. This study investigates the storage and transport of labile ferrous iron Fe(II) in cultured primary rat hippocampal neurons. Iron distribution was studied using live cell confocal microscopy with a selective labile Fe(II) fluorescent dye, and synchrotron X-ray fluorescence microscopy (SXRF) for total iron distribution. Fluorescent labelling of the axon initial segment and of lysosomes allowed iron distribution to be correlated with these subcellular compartments. The results show that labile Fe(II) is stored in lysosomes within somas, axons and dendrites and that lysosomal labile Fe(II) is transported retrogradely and anterogradely along axons and dendrites. In addition, we have developed a methodological workflow to quantify labile Fe(II) relative to total iron in neurites. This method is based on correlative imaging of fluorescence microscopy of labile Fe(II) combined with quantitative elemental mapping of total iron by SXRF. Quantitative analysis revealed that after Fe(II) exposure, lysosomal Fe(II) accounts for a small but significant percentage of the total iron content in neurites. These result suggest that after exposure to labile Fe(II), iron is mainly present in a non-reactive form in neurons, while the smaller fraction of reactive labile Fe(II) is stored in lysosomes and can be transported along dendrites and axons.
GWAS significance thresholds in large cohorts
Authors: Cheruiyot Evans K , Yang Tingyan , McRae Allan F 
Published: December 2024

AbstractWhile the p-value threshold of 5.0 × 10−8remains the standard for genome-wide association studies (GWAS) in humans and other species, it still needs to be updated to reflect the current era of large-scale GWAS, where tens of thousands of sample sizes are used to discover genetic associations at loci with smaller minor allele frequencies. In this study, we used a dataset of 348,501 individuals of European ancestry from the UK Biobank to determine the GWAS thresholds required for multiple testing corrections when considering rare and common variants in additive and dominant GWAS models. Additionally, we employed conditional and joint (COJO) analysis to quantify the proportion of false significant hits in the GWAS results for 72 traits in the UK Biobank when applying the traditional GWAS cut-off versus our newly proposed p-value thresholds. Overall, the results indicate that the conventional GWAS significance threshold of 5.0 × 10−8yields a false positive rate of between 20% and 30% in GWAS studies that utilize large sample sizes and less common variants. Instead, a more stringent GWAS p-value threshold of 5.0 × 10−9is needed when rare variants (with minor allele frequency > 0.1%) are included in the association test for both additive and dominance models within the European ancestry population.
Differences in the serum metabolomic profile of progressive alcohol-related liver disease in comparison to non-progressive alcohol-related liver disease: a cross sectional metabolomics study
Authors: Puhakka Eemeli , Ahmed Hany , Haikonen Retu , Leclercq Sophie , Hanhineva Kati , Maccioni Luca , Amadieu Camille , Lehtonen Marko , Männistö Ville , Rysä Jaana , Stärkel Peter , Kärkkäinen Olli 
Published: December 2024

AbstractAlcohol-related liver disease (ALD) is a major cause of mortality and disability adjusted life years. It is not fully understood why a small proportion of patients develop progressive forms of ALD (e.g. fibrosis, cirrhosis). Differences in the metabolic processes could be behind the individual progression of ALD. Our aim was to examine differences in serum metabolome between patients with non-progressive ALD and patients with an early form of progressive ALD.The study had three study groups: progressive ALD (alcohol-related steatohepatitis or early-stage fibrosis, n=50), non-progressive ALD (simple steatosis, n=50) and healthy controls (n=32). Both ALD groups took part in a voluntary alcohol rehabilitation program. A non-targeted metabolomics analysis and targeted analysis of short chain fatty acids was done to the serum samples taken on the day of admission.We found 111 significantly (p<0.0005) altered identified metabolites between the study groups. Our main finding was that levels of glycine conjugated bile acids, glutamic acid, 7-methylguanine and several phosphatidylcholines were elevated in the progressive ALD group in comparison to both the non-progressive ALD group and the controls. Glycine conjugated bile acid, glutamic acid and 7-methylguanine also positively correlated with increased levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, cell death biomarker M65, and liver stiffness.Our results indicate that the enterohepatic cycle of glycine conjugated bile acids as well as lipid and energy metabolism are altered in early forms of progressive ALD. These metabolic processes could be a target for preventing progression of ALD.
Identifying causal genotype-phenotype relationships for population-sampled parent-child trios
Authors: Tang Yushi , Cabreros Irineo , Storey John D. 
Published: December 2024

AbstractThe process by which genes are transmitted from parent to child provides a source of randomization preceding all other factors that may causally influence any particular child phenotype. Because of this, it is natural to consider genetic transmission as a source of experimental randomization. In this work, we show how parent-child trio data can be leveraged to identify causal genetic loci by modeling the randomization during genetic transmission. We develop a new test, the transmission mean test (TMT), together with its unbiased estimator of the average causal effect, and derive its causal properties within the potential outcomes framework. We also prove that the transmission disequilibrium test (TDT) is a test of causality as a complementary case of the TMT for the affected-only design. The TMT and the TDT differ in the types of traits that they can handle and the study designs for which they are appropriate. The TMT handles arbitrarily distributed traits and is appropriate when trios are randomly sampled; the TDT handles dichotomous traits and is appropriate when sampling is based on a child’s trait status. We compare the transmission-based methods with established approaches for genotype-phenotype analyses to clarify conditions appropriate for each method, what conclusions can be drawn by each one, and how these methods can be used together.
How does CEO personality affect new product development performance? The partial mediating role of strategic schema change
Authors: Ding Xiaozhou 
Published: December 2024

Purpose
This study aims to explore the direct impact of various personality traits of the CEO on new product development (NPD) performance, as well as the mediating role of strategic schema changes in the relation among these key variables.

Design/methodology/approach
The research focuses on Chinese science and technology enterprises. A total of 659 valid responses from CEOs and senior managers have been analyzed to test the hypotheses.

Findings
The results reveal that CEO’s conscientiousness and agreeableness negatively correlate with NPD performance and strategic schema changes. CEO traits such as extroversion, openness to experience and emotional stability are positively associated with both variables. Furthermore, the study confirms that strategic schema changes partially mediate the relation between CEO personality traits and NPD performance.

Research limitations/implications
This study focuses only on the relation between CEOs’ Big Five personality traits and NPD performance. However, other personality traits such as narcissism or dark personality traits may also influence NPD performance. Future research should explore the effect of a broader range of CEO personality traits on corporate performance. And, this paper primarily investigates the mediating role of strategic schema change between CEO personality and NPD performance, drawing on personality psychology and strategic cognition. However, other important theoretical perspectives, such as organizational resources and binary learning, may offer additional insights into the relation between CEO personality and NPD performance. Future research could delve deeper into these perspectives at multiple levels for a more comprehensive understanding.

Originality/value
The findings broaden the application of personality psychology within innovation management, offering valuable practical insights and new perspectives for technology enterprises seeking to enhance new product performance.
Educate Northwest Helvetia: a Delphi study on public schooling in Switzerland
Authors: Quesel Carsten , Mittag Michael , Moeser Guido 
Published: December 2024

Purpose
The Delphi study Educate Northwest Helvetia is part of a multi-stakeholder approach to define common challenges and priorities for public schooling in a federal setting. This paper aims to take stock of the outcome of expert ratings and group discussions.

Design
Based on a literature review of megatrends, 21st century skills and sustainable development goals, the study focused on four domains: digital change, economic change, sociocultural change and ecological change. Opinions of teachers, principals and other experts were collected in the first wave via an online survey (n = 707). In the second wave, findings of the survey were discussed in ten online workshops, and participants refined priorities for schooling 2030 via real-time online scoring. Quantitative data were analyzed using exploratory and confirmatory factor analysis.

Findings
Analysis of quantitative data shows an emphasis on soft skills, self-organization, equity and transversal competencies. The enhancement of computational thinking and teaching on sciences, technology, engineering and mathematics are important minority concerns.

Practical implications
The study delivers a manageable set of 12 priorities addressed to cantonal ministries of education, teacher unions, associations of principals and other stakeholders.

Research limitations/implications
Since these priorities are rather abstract, qualitative in-depth research concerning uptake and impact is needed.

Originality/value
This study provides new perspectives for the dialogue on evidence-based policymaking in settings of consensus democracy. It also provides valuable pointers for school improvement and teacher education that can be further explored.
Insights into mobile app experience: a systematic literature review using TCCM framework
Authors: Vyas Samiksha , Rathore Jitendra Singh , Kumar Vinod 
Published: December 2024

Purpose
This study aims to conduct a systematic literature review on mobile application experience, recognizing its growing importance in research and practical applications. The purpose is to address the factors influencing customer mobile application experience in this dynamic environment.

Design/methodology/approach
The study uses the theories, context, characteristics, methodology (TCCM) review framework. This research meticulously analyzes 42 articles published between 2015 and 2023. The selected articles are sourced from prominent journals in widely recognized databases, including Scopus and the Australian Business Deans Council.

Findings
The examination of the pertinent literature culminates in the formulation of the TCCM framework, shedding light on the antecedents, mediators, moderators and outcomes, related to the mobile application experience.

Research limitations/implications
This study pioneers a unified framework for mobile application experience, shedding light on unexplored territories and shaping the trajectory of future mobile application experience investigations. Its emphasis on a strong academic foundation enriches technological marketing literature, offering managers actionable insights aligned with TCCM. This study marks a pivotal contribution, bridging theoretical advancements with practical strategies for the dynamic landscape of mobile applications experience.

Originality/value
This research uncovers overlooked areas and proposes discerning research directions to advance the understanding of mobile applications experience. It addresses a crucial gap in current knowledge and motivates further investigation into the intricate dynamics of mobile application experience.
Dabbled vs sustained self-employment: exploring educational returns within dynamic employment groups
Authors: Hussein Hiba , Haj Youssef Moustafa , Nolan Steve 
Published: December 2024

PurposeThis study examines the returns from education for three distinct groups: always employees, dabblers in self-employment and sustained self-employed individuals. We aim to understand how educational attainment translates into earnings across these employment types in the UK.Design/methodology/approachUsing data from the British Household Panel Survey (BHPS) and Understanding Society: The UK Household Longitudinal Study (UKHLS), we employ a random effects (RE) model to account for unobserved individual characteristics and the Heckman selection model to address self-selection bias, ensuring accurate estimates of educational returns.FindingsOur findings indicate that sustained self-employed individuals benefit more from education compared to dabblers and, in certain cases, traditional employees. Dabblers with postgraduate education report higher returns than always employees, but those with lower educational levels experience disadvantages due to their intermittent labour market engagement.Originality/valueThis study introduces new evidence on the heterogeneity of educational returns for self-employed individuals in the UK, providing a novel comparative analysis of different employment types and highlighting the unique challenges and outcomes related to educational attainment and earnings.
Gig work, management education and changes in working conditions: a qualitative study
Authors: Mousa Mohamed 
Published: December 2024

Purpose
This paper aims to identify the changes in management education students in business schools prefer since the spread of gig work.

Design/methodology/approach
The empirical data is based on focus groups with 30 management educators working in five public business schools in Egypt. Thematic analysis was subsequently used to determine the main ideas in the transcripts from the interviews.

Findings
The author finds that both curricular changes (indifference to traditional management theories, student calls for more practical case studies, student passion for entrepreneurship-related courses) and structural changes (concentration on student-centred teaching, student preference for short flexible lectures and increasing student doubts regarding the competence of their teachers) are the two main forms of change in management education students prefer since the spread of gig work.

Originality/value
This paper is a pioneering study that specifically investigates how the spread of gig work triggers change in management education in response to calls from students. No previous studies (to the author’s knowledge) have theorized and empirically analysed this specific topic, especially in the under-researched settings of developing countries in North Africa.
Use of unmanned aerial vehicles by the entities of National Firefighting and Rescue System in Poland to search for people – a review of interventions performed in the years 2021–2023
Authors: Kubiak Tomasz , Dudzinski Lukasz , Fellner Radosław , Feltynowski Mariusz , Czyżewski Łukasz 
Published: December 2024

PurposeThe study aims to analyze the interventions of Fire Protection Units (FPUs) to incidents using unmanned aerial vehicles (UAVs) (drones) to search for missing persons in 2021–2023. It comprised some data obtained from the Decision Support System of the State Fire Service, made available to the authors by the Office of Operational Planning. Analyzed were the incidents occurring in the period from 01.01.2021; 00.00 am to 31.12.2023; 11:59 pm. The quantitative data were described by using the mean and the standard deviation (SD). Correlations and differences at a significance level of p < 0.05 were considered statistically significant. The data were de-identified for both the sufferers and officers involved in the interventions.Design/methodology/approachAn analysis of interventions of FPUs in incidents with the use of unmanned aerial vehicles (UAVs/drones) to search for people in the years 2021–2023.FindingsBetween 2021 and 2023, firefighters were dispatched 780 times to operations with the use of UAVs. The incidents observed (search for people) accounted for 36.2% of the total drone-intervention incidents, and the number of incidents increased in each year of analysis. The average drone intervention time was 306.8 ± 176.4 (min.) to search for women and 385.3 ± 187.7 (min.) to search for men. Search operations in forest areas, bodies of water and rivers predominated.Originality/valueThe use of UAVs by National Firefighting and Rescue System entities offers a variety of possibilities in the search for people, increasing thus the rescue potential and effectiveness of operations. Investments in new technologies in rescue activities contribute to the effectiveness of operations where the time criterion is of primary importance. According to the analysis performed, the average time of a drone intervention operation is more than 300 min, which should give rise to further analyses and proposals, such as a greater availability of drones or a specific number of drones dedicated to the search area. The future associated with increased drone performance and efficiency may change the nature of their use.