bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Challenge Uncovers Temporal Fungibility of Metabolic Homeostasis over a day:night cycle
Authors: Malik Dania M. , Rhoades Seth D. , Zhang Shirley L. , Sengupta Arjun , Barber Annika , Haynes Paula , Arnadottir Erna Sif , Pack Allan , Kibbey Richard G. , Kain Pinky , Sehgal Amita , Weljie Aalim M. 
Published: November 2023

AbstractRhythmicity is a cornerstone of behavioral and biological processes, especially metabolism, yet the mechanisms behind metabolite cycling remain elusive. This study uncovers a robust oscillation in key metabolite pathways downstream of glucose in humans. A purpose-built13C6-glucose isotope tracing platform was used to sampleDrosophilaevery 4h and probe these pathways, revealing a striking peak in biosynthesis shortly after lights-on in wild-type flies. A hyperactive mutant (fumin) demonstrates increased Krebs cycle labelling and dawn-specific glycolysis labelling. Surprisingly, neither underlying feeding rhythms nor the presence of food availability explain the rhythmicity of glucose processing across genotypes, suggesting a robust internal mechanism for metabolic control of glucose processing. These results align with clinical data highlighting detrimental effects of mistimed energy intake. Our approach offers a unique insight into the dynamic range of daily metabolic processing and provides a mechanistic foundation for exploring circadian metabolic homeostasis in disease contexts.
Altered Metabolism During the Dark Period inDrosophilaShort Sleep Mutants
Authors: Malik Dania M. , Sengupta Arjun , Sehgal Amita , Weljie Aalim M. 
Published: November 2023

AbstractSleep is an almost universally required state in biology. Disrupted sleep has been associated with adverse health risks including metabolic perturbations. Sleep is in part regulated via circadian mechanisms, however, metabolic dysfunction at different times of day arising from sleep disruption is unclear. We used targeted liquid chromatography-mass spectrometry to probe metabolic alterations using high-resolution temporal sampling of twoDrosophilashort sleep mutants,fuminandsleepless, across a circadian day. Discriminant analyses revealed overall distinct metabolic profiles for mutants when compared to a wild type dataset. Altered levels of metabolites involved in nicotinate/nicotinamide, alanine, aspartate, and glutamate, glyoxylate and dicarboxylate metabolism, and the TCA cycle were observed in mutants suggesting increased energetic demands. Furthermore, rhythmicity analyses revealed fewer 24 hr rhythmic metabolites in both mutants. Interestingly, mutants displayed two major peaks in phases while wild type displayed phases that were less concerted. In contrast to 24 hr rhythmic metabolites, an increase in the number of 12 hr rhythmic metabolites was observed infuminwhilesleeplessdisplayed a decrease. These results support that decreased sleep alters the overall metabolic profile with short sleep mutants displaying altered metabolite levels associated with a number of pathways in addition to altered neurotransmitter levels.
A foundation model for bioactivity prediction using pairwise meta-learning
Authors: Feng Bin , Liu Zequn , Huang Nanlan , Xiao Zhiping , Zhang Haomiao , Mirzoyan Srbuhi , Xu Hanwen , Hao Jiaran , Xu Yinghui , Zhang Ming , Wang Sheng 
Published: November 2023

AbstractCompound bioactivity plays an important role in different stages of drug development and discovery. Existing machine learning approaches have poor generalization ability in compound bioactivity prediction due to the small number of compounds in each assay and incompatible measurements among assays. Here, we propose ActFound, a foundation model for bioactivity prediction trained on 2.3 million experimentally-measured bioactivity compounds and 50, 869 assays from ChEMBL and BindingDB. The key idea of ActFound is to employ pairwise learning to learn the relative value differences between two compounds within the same assay to circumvent the incompatibility among assays. ActFound further exploits meta-learning to jointly optimize the model from all assays. On six real-world bioactivity datasets, ActFound demonstrates accurate in-domain prediction and strong generalization across datasets, assay types, and molecular scaffolds. We also demonstrated that ActFound can be used as an accurate alternative to the leading computational chemistry software FEP+(OPLS4) by achieving comparable performance when only using a few data points for fine-tuning. The promising results of ActFound indicate that ActFound can be an effective foundation model for a wide range of tasks in compound bioactivity prediction, paving the path for machine learning-based drug development and discovery.
Improved detection of methylation in ancient DNA
Authors: Sawyer Susanna , Gelabert Pere , Yakir Benjamin , Lizcano Alejandro Llanos , Sperduti Alessandra , Bondioli Luca , Cheronet Olivia , Neugebauer-Maresch Christine , Teschler-Nicola Maria , Novak Mario , Pap Ildikó , Szikossy Ildikó , Hajdu Tamás , Meshorer Eran , Carmel Liran , Pinhasi Ron 
Published: November 2023

AbstractReconstructing premortem DNA methylation levels in ancient DNA (aDNA) has led to breakthrough studies such as the prediction of anatomical features of the Denisovan, as well as the castration status of ancient horses. These studies relied on computationally inferring methylation levels from damage signals in naturally deaminated cytosines. Because of statistical constraints, this inference requires high-coverage sequencing, and is thus not only expensive but also restricted to samples with exceptional DNA preservation. Instead, a method to directly measure methylation levels in aDNA, as exists in modern DNA samples, would open the door to a more thorough and cost effective ability to study ancient DNA methylation. We have tested two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. We find that both methods preserve sufficient DNA yields to allow for methylation measurement. Bisulfite treatment, combined with a single stranded library preparation, shows the least reduction in DNA yields compared to no methylation treatment, as well as the least biases during methylation conversion. In addition, we show that applying bisulfite treatment to ∼0.4-fold coverage sample provides a methylation signal that is comparable to, or even better, than the computationally inferred one. We thus present a method to directly measure methylation in ancient DNA that is cost effective and can be used on a wide variety of ancient samples.
Encoding of the colorectal cancer metabolic program through MICU2
Authors: Robert Alison , Crottès David , Bourgeais Jérôme , Gueguen Naig , Chevrollier Arnaud , Dumas Jean-François , Servais Stéphane , Domingo Isabelle , Chadet Stéphanie , Sobilo Julien , Hérault Olivier , Lecomte Thierry , Vandier Christophe , Raoul William , Guéguinou Maxime 
Published: November 2023

SummaryThe mitochondrial Ca2+uniporter (MCU) plays crucial role in intramitochondrial Ca2+uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated. Here, we describe the role of MICU2 in cell proliferation and migration usingin vitroandin vivomodels of colorectal cancer (CRC). Transcriptomic analysis demonstrated an increase in MICU2 expression and the MICU2/MICU1 ratio in advanced CRC and CRC-derived metastases. We report that expression of MICU2 is necessary for mitochondrial Ca2+uptake and quality of the mitochondrial network. Our data reveal the interplay between MICU2 and MICU1 in the metabolic flexibility between anaerobic glycolysis and OXPHOS. Overall, our study sheds light on the potential role of the MICUs in diseases associated with metabolic reprogramming.HighlightsMICU2 plays a pivotal role in the balance between anaerobic glycolysis and oxidative phosphorylationMICU2 stabilizes the mitochondrial network and endoplasmic reticulum–mitochondrial calcium fluxMICU2 expression and the MICU2/MICU1 ratio control proliferation and metastasis formation in colorectal cancerGraphical Abstract
Network size affects the complexity of activity in human iPSC-derived neuronal populations
Authors: Uzun Yavuz Selim , Santos Renata , Marchetto Maria C. , Padmanabhan Krishnan 
Published: November 2023

SUMMARYMulti-electrode recording of neural activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Although it is hypothesized that network size is critical for determining the dynamics of activity, this relationship in human neural cultures remains largely unexplored. By applying new methods for analyzing neural activity to human iPSC derived cultures at either low-densities or high-densities, we uncovered the significant impacts that neuron number has on the individual neurophysiological properties of cells (such as firing rates), the collective behavior of the networks these cultures formed (as measured by entropy), and the relationship between the two. As a result, simply changing the densities of neurons generated dynamics and network behavior that differed not just in degree, but in kind. Beyond revealing the relationship between network structure and function, our findings provide a novel analytical framework to study diseases where network level activity is affected.
How product hedonism affects the Country-of-Origin effect on product perceived quality and price in the China market
Authors: Chow Clement S.F. , Chow Wing Chi , Leong Weng I. , Zheng Shizhe 
Published: November 2023

PurposeWestern manufacturers have often benefited from the Country-of-Origin (COO) effect when a product is launched into emerging markets. The authors examine if this still holds true in the China market. The authors believe that the degree of perceived hedonism associated with the product does matter and, therefore, conducted an experiment to test how this influences the effect of COO on perceived quality and price of the product. This paper aims to discuss the aforementioned objective.Design/methodology/approachA lab experiment with a 2 (COO: Western vs. Local) x 2 (Hedonism: High vs. Low) factorial design was conducted with Chinese consumers as subjects. The dependent variables were perceived quality and price of the products.FindingsIt was found that Western COO has a positive effect on the product perceived quality and price in the China market, but the effect was significantly moderated by the degree of perceived hedonism of the products.Originality/valueThe study used an experiment to investigate the different prominence of the COO effect on perceived quality and price in terms of hedonic vs. utilitarian products which has not been done previously. The findings provide implications concerning allocation of marketing resources to product positioning in the presence of different degrees of perceived hedonism and suggest additional areas for future examination.
The moderating effect of environmental performance on the relationship between sustainability assurance quality and firm value: a simultaneous equations approach
Authors: Kheireddine Hanene , Lacombe Isabelle , Jarboui Anis 
Published: November 2023

PurposeThis study elucidates the interactive relationship of sustainability assurance (SA) quality with corporate environmental sustainability performance (CESP) and firm value and explores the moderating impact of CESP on the SA quality–firm value relationship.Design/methodology/approachThe sample comprises 320 firm-year observations of 40 companies listed on the Cotation Assistée en Continu (CAC 40) from 2010 to 2019. The authors use the simultaneous equations model to capture the CESP and SA quality–firm value relationship and apply the three-stage regression and generalised method of moments approaches to address possible endogeneity.FindingsThe results show that CESP, as assessed by International Organisation for Standardisation (ISO) 14001 certification, has a significant positive effect on firm value, the relevance of which implies that in the case of good environmental performance, society's perception of a firm is much more favourable; consequently, the firm is likely to be rewarded with a premium value in capital markets. In addition, environmental performance has a stronger interaction with SA quality, acting as a moderator variable; thus, greater SA quality signals credibility owing to increased eco-efficiency. The authors interpret their findings within a multi-theoretical framework that draws insights from legitimacy, stakeholders and signalling theoretical perspectives.Originality/valueThis study contributes to the literature by re-examining the relationship between SA quality and firm value. It also provides new evidence of the moderating effect of CESP on the SA quality–firm value nexus. Specifically, this study explores the joint effects of credibility and eco-efficiency on market confidence in sustainability information. The authors use a simultaneous equation model to capture the reciprocal association between SA quality and firm value, whereas prior studies on SA quality and market performance have frequently used single-equation regression. The authors also find that CESP positively moderates the relationship between SA quality and firm value. Including CESP and exploring the moderating impact of eco-efficiency on the SA quality–firm value relationship is a novel approach.
Subsidiary political embeddedness: mechanisms for leveraging local competences
Authors: Botella-Andreu Ana , Villar Cristina , Pla-Barber José , Andersson Ulf 
Published: November 2023

Purpose
This study aims to investigate the drivers of political embeddedness and the possible outcome in terms of autonomy and subsidiary unique competences.

Design/methodology/approach
This study draws on resource dependence theory and applies structural equation modeling on a sample of 193 subsidiaries.

Findings
Political embeddedness is confirmed as a source of potential autonomy and the development of competences and is usually boosted by previous existing networks at the internal and external levels.

Originality/value
The authors investigate and discuss how multinational corporations can leverage political resources in host-country political arenas, extending their understanding of the interplay between political activities and market strategies.
Nurses’ MOOCs continuance intention and task performance: antecedents and mediators
Authors: Cheng Yung-Ming 
Published: November 2023

Purpose
The purpose of this study is to propose a research model based on the stimulus-organism-response (S-O-R) model to explore whether media richness and social interaction as environmental feature antecedents to nurses’ learning engagement (LE) can affect their continuance intention of massive open online courses (MOOCs) and task performance.

Design/methodology/approach
Sample data for this study were collected from nurses at five university-/medical university-affiliated hospitals in Taiwan. A total of 500 questionnaires were distributed, and 303 (60.6%) usable questionnaires were analyzed using structural equation modeling in this study.

Findings
This study proved that nurses’ perceived media richness and social interaction in MOOCs positively influenced their behavioral LE and psychological LE elicited by MOOCs, which jointly caused their continuance intention of MOOCs and, in turn, enhance their task performance. The results support all proposed hypotheses and the research model, respectively, explains 84.3% and 63.7% of the variance in nurses’ continuance intention of MOOCs and task performance.

Originality/value
This study uses the S-O-R model as a theoretical base to frame nurses’ continuance intention of MOOCs and task performance as a series of the internal process, which is affected by environmental stimuli (i.e. media richness and social interaction) and organismic states. Noteworthily, while the S-O-R model has been extensively used in prior literature, little research uses this paradigm to expound nurses’ continuance intention of MOOCs in the work settings. Besides, there is a dearth of evidence on the antecedents of nurses’ task performance in the context of MOOCs. Hence, this study’s empirical evidence contributes significantly to the existing literature on bridging the gap of limited evaluation for the research on the impact of nurses’ MOOCs learning on their task performance in the work settings, which is very scarce in the S-O-R view.
The role of universities in Latin American social entrepreneurship ecosystems: a gender perspective
Authors: Macías-Prada John Fernando , Silva Yamila , Zapata Ángela María 
Published: November 2023

PurposeThis study examines the role of universities in the social entrepreneurship ecosystems (SEEs) in Latin America from the perspective of female academic staff, administrators and outreach workers of universities in the region.Design/methodology/approachUsing a qualitative approach, the study scrutinises in-depth interviews conducted with 24 women from eight Latin American universities.FindingsThe findings underscore the pivotal role of universities in promoting social entrepreneurship through knowledge generation, entrepreneur training, network enhancement and the promotion of equity. They also highlight the importance of incorporating a gender perspective into university programmes and practices.Research limitations/implicationsThe qualitative nature and small, diverse sample of this research inherently limit its scope. However, these limitations arise from the exploratory approach adopted, which was confined to eight Latin American countries. Further comparative studies in different contexts are needed to deepen the understanding of the dynamics involved.Practical implicationsUniversities should offer more tangible support and training in social entrepreneurship with a gender focus. Governments can create incentives for universities to prioritise their contribution in this area.Social implicationsThe study emphasises the potential of women-led social entrepreneurship initiatives to generate positive impact, underscoring the need for inclusive supportive environments.Originality/valueBy providing insights on the role of Latin American universities in SEEs from a gender perspective, this study contributes to limited literature on the intersection of social entrepreneurship, gender, higher education and geographic context in the region. The research underscores the need to further explore how gender and regional dynamics influence social entrepreneurial ecosystems.
Workplace mitigators of the negative relationship between stress and health
Authors: Gregory Brian , Moates K. Nathan 
Published: November 2023

PurposeThe purpose of this research is to more deeply understand how stress impacts the physical and mental health of employees and what management can do to attenuate the impact of stress on employee health. While the relationship between stress and employee health has received some empirical support in the literature (e.g. Cooper and Cartwright, 1994), less is known about workplace variables that may mitigate the negative effects of stress on health. This study aims to contribute to the literature by exploring three important workplace variables that could lessen the negative effects of stress on health.Design/methodology/approachA diverse group of employees from two healthcare organizations in the United States of America were surveyed about their work environments, job stress, mental health and physical health. Hierarchical regression analyses were used to investigate three unique workplace mitigators of the stress-health relationship.FindingsResults support perceived organizational support, procedural justice and managerial perspective-taking as variables that serve to make individuals hardier to the health consequences of stressful work. However, different moderating processes seem to account for mental health (perceived organizational support) and physical health (perspective-taking), while procedural justice mitigates the effect of stress on both mental and physical health.Originality/valueThis study contributes to an enhanced understanding of the relationships between stress and mental and physical health in the workplace. In particular, three workplace factors associated with managerial practices were identified that organizations can utilize to protect employees from the negative health consequences of stressful work. These findings can assist managers and organizations who are interested in improving employee health.
Information as a circular resource – facilitating information exchange to extend product-life
Authors: Jørgensen Rasmus , Scarso Enrico 
Published: November 2023

Purpose
This paper aims to study a circular economy business model that offers services with embedded information exchange capabilities to extend product life through maintenance and repair. Information exchange has been identified as a critical factor in advancing the principles of a circular economy, and this research was conducted to illustrate how information exchange can facilitate maintenance and repair.

Design/methodology/approach
The study has a case study approach of collecting data through semi-structured interviews and questionnaires.

Findings
Information exchange on what and when to do something engages end-users in maintenance and facilitates learning. For repair, the problem description and possible solutions are information that must be exchanged. Both types of information exchange are facilitated by simple tech solutions relying on known and inexpensive technology (e.g. e-mail service, video call and text messaging).

Research limitations/implications
The study contributes to the organisational development and knowledge management fields with novel insights on how information exchange and circular economy are related and can be facilitated.

Practical implications
The study provides insights for companies looking for solutions on how to generate revenue from services and reduce resource consumption. The findings of the study suggest that the development of circular business models does not always require expensive high-tech solutions.

Originality/value
To the best of the authors’ knowledge, this study is unique as it is empirically based on insights into how information exchange can extend product life through the use of simple digital tools.