bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep mutational scanning reveals the functional constraints and evolutionary potential of the influenza A virus PB1 protein
Authors: Li Yuan , Arcos Sarah , Sabsay Kimberly R. , te Velthuis Aartjan J.W. , Lauring Adam S. 
Published: August 2023

AbstractThe influenza virus polymerase is central to influenza virus evolution. Adaptive mutations within the polymerase are often a prerequisite for efficient spread of novel animal-derived viruses in human populations. The polymerase also determines fidelity, and therefore the rate at which the virus will acquire mutations that lead to host range expansion, drug resistance, or antigenic drift. Despite its importance to viral replication and evolution, our understanding of the mutational effects and associated constraints on the influenza RNA-dependent RNA polymerase (RdRp) is relatively limited. We performed deep mutational scanning of the A/WSN/1933(H1N1) PB1, generating a library of 95.4% of amino acid substitutions at 757 sites. After accuracy filters, we were able to measure replicative fitness for 13,354 (84%) of all possible amino acid substitutions, and 16 were validated by results from pairwise competition assays. Functional and structural constraints were better revealed by individual sites involved in RNA or protein interactions than by major subdomains defined by sequence conservation. Mutational tolerance, as defined by site entropy, was correlated with evolutionary potential, as captured by diversity in available H1N1 sequences. Of 29 beneficial sites, many have either been identified in the natural evolution of PB1 or shown experimentally to have important impacts on replication and adaptation. Accessibility of amino acid substitutions by single nucleotide mutation was a key factor in determining whether mutations appeared in natural PB1 evolution. Our work provides a comprehensive map of mutational effects on a viral RdRp and a valuable resource for subsequent studies of influenza replication and evolution.
Evolvability of cancer-associated genes under APOBEC3A/B selection
Authors: Song Joon-Hyun , Dávalos Liliana M. , MacCarthy Thomas , Damaghi Mehdi 
Published: August 2023

SummaryEvolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and, ultimately, genetic variation. Mutations generated by APOBEC3 cytidine deaminases can contribute to genetic variation and the consequences of APOBEC activation differ depending on the stage of cancer, with the most significant impact observed during the early stages. However, how APOBEC activity shapes evolutionary patterns of genes in the host genome and differential impacts on cancer-associated and non-cancer genes remain unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer-related genes and controls, suggesting unique associations with cancer. Studying a bat species with many more APOBEC3 genes, we found diverse motif patterns in orthologs of cancer genes compared to controls, similar to humans and suggesting APOBEC evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC-induced heterogeneity enhances cancer evolution, shaping clonal dynamics through bimodal introduction of mutations in certain classes of genes. Our results suggest that a major consequence of the bimodal distribution of APOBEC affects greater cancer heterogeneity.HighlightsUsing a measure of the extent which genes are affected by APOBEC activity, we found that many genes aremaximally robustin the human genome. Interestingly, the distribution in the genome of a bat that has many APOBEC genes was similar.In contrast, when analyzing the subset of cancer-associated genes the distribution is bimodal with many genes appearing to susceptible to APOBEC activity.Analysis of orthologs of human genes and other species showed a wide range in the extent to which APOBEC affects genes having the same function.The bimodal distribution of susceptibility to APOBEC drives greater heterogeneity in simulated clonal evolution of cancer.
The glucocorticoid receptor is a critical regulator of muscle satellite cell quiescence
Authors: Rajgara Rashida , AlSudais Hamood , Saleh Aisha , Brown Alex , Barrakad Ines , Blais Alexandre , Wiper-Bergeron Nadine 
Published: August 2023

AbstractGlucocorticoids are powerful anti-inflammatory medications that are associated with muscle atrophy. The effect of glucocorticoids in myofibers is well-studied, yet the role of the glucocorticoid receptor (GR), the primary mediator of glucocorticoid transcriptional responses, and the impact of glucocorticoid signalling in muscle stem cells (MuSCs), the adult progenitors responsible for regeneration, remain unknown. We developed a conditional null mouse model to knock out glucocorticoid receptor (GR) expression in MuSCs (GRMuSC-/-) and established that while GR is dispensable for muscle regeneration, it is a critical regulator of MuSC homeostasis. Loss of GR significantly increased cycling MuSCs as compared to controls in injury-naïve mice and on single EDL myofiber cultures, and as such, loss of GR in MuSCs leads to precocious activation and subsequent proliferation as compared to controls. Bulk RNA-sequencing fromin situfixed MuSCs from injury-naïve GRMuSC-/-muscle identified a gene signature consistent with cells that have exited quiescence and undergone activation, with evidence of sexual dimorphism. Using ATAC-seq and footprinting we identify putative GR targets that promote quiescence. Thus, we advance the GR as a previously unrecognized crucial transcriptional regulator of gene expression in MuSCs whose activity is highest in quiescent cells and is essential to maintain that state.
The International Cardiac Arrest Research (I-CARE) Consortium Electroencephalography Database
Authors: Amorim Edilberto , Zheng Wei-Long , Ghassemi Mohammad M. , Aghaeeaval Mahsa , Kandhare Pravinkumar , Karukonda Vishnu , Lee Jong Woo , Herman Susan T. , Sivaraju Adithya , Gaspard Nicolas , Hofmeijer Jeannette , van Putten Michel J. A. M. , Sameni Reza , Reyna Matthew A. , Clifford Gari D. , Westover M. Brandon 
Published: August 2023

AbstractObjectiveTo develop a harmonized multicenter clinical and electroencephalography (EEG) database for acute hypoxic-ischemic brain injury research involving patients with cardiac arrest.DesignMulticenter cohort, partly prospective and partly retrospective.SettingSeven academic or teaching hospitals from the U.S. and Europe.PatientsIndividuals aged 16 or older who were comatose after return of spontaneous circulation following a cardiac arrest who had continuous EEG monitoring were included.Interventionsnot applicable.Measurements and Main ResultsClinical and EEG data were harmonized and stored in a common Waveform Database (WFDB)-compatible format. Automated spike frequency, background continuity, and artifact detection on EEG were calculated with 10 second resolution and summarized hourly. Neurological outcome was determined at 3-6 months using the best Cerebral Performance Category (CPC) scale. This database includes clinical and 56,676 hours (3.9 TB) of continuous EEG data for 1,020 patients. Most patients died (N=603, 59%), 48 (5%) had severe neurological disability (CPC 3 or 4), and 369 (36%) had good functional recovery (CPC 1-2). There is significant variability in mean EEG recording duration depending on the neurological outcome (range 53-102h for CPC 1 and CPC 4, respectively). Epileptiform activity averaging 1 Hz or more in frequency for at least one hour was seen in 258 (25%) patients (19% for CPC 1-2 and 29% for CPC 3-5). Burst suppression was observed for at least one hour in 207 (56%) and 635 (97%) patients with CPC 1-2 and CPC 3-5, respectively.ConclusionsThe International Cardiac Arrest Research (I-CARE) consortium database provides a comprehensive real-world clinical and EEG dataset for neurophysiology research of comatose patients after cardiac arrest. This dataset covers the spectrum of abnormal EEG patterns after cardiac arrest, including epileptiform patterns and those in the ictal-interictal continuum.
Nurses and Midwives’ Perspectives on Technology-Enhanced Learning and Continuous Professional Development on Emergency Obstetric and Neonatal Care in Rwanda
Authors: Uhawenimana Thierry Claudien , Gakwerere Mathias , Ngabonzima Anaclet , Yamuragiye Assumpta , Harindimana Florien , Ndayisenga Jean Pierre 
Published: August 2023

AbstractBackgroundOne of the targets for the third sustainable development goals is to reduce worldwide maternal mortality ratio (MMR) to less than 70 deaths per 100,000 live births by 2030. To address issues affecting women and the newborns during childbirth and postnatal period, concerted efforts from governments and their stakeholders are crucial to maximize the use of technology to enhance frontline health professionals’ skills to provide the emergency obstetric and newborn care (EmONC). However, no study has garnered nurses’ and midwives’ perspectives regarding the application of technology-enhanced learning approach to provide on-job CPDs and factors that may influence the application of this training approach in the Rwandan context.MethodsThe study collected data from nurses and midwives from forty (40) public health facilities in remote areas nationwide. The study applied a qualitative descriptive design to explore and describe nurses’ and midwives’ perspectives on the feasibility and acceptability of technology enhanced learning approaches such as e-learning, phone-based remote training, and other online methods to provide trainings in EmONC. Two focus group discussions with EmONC mentor, two with nurses and midwives were conducted. Twelve key informant interviews were conducted. Participants were selected purposively. In total, 54 individuals were included in this study. A thematic approach was used to analyse data.ResultsNurses and midwives highlighted the need to provide refresher trainings about the management of pre-eclampsia. Most of the EmONC trainings are still provided face to face and the use of technology enhanced learning approaches have not yet been embraced in delivering EmONC CPDs for nurses and midwives in remote areas. Nurses and midwives found the first developed prototype of smartphone app training of the EmONC acceptable as it met the midwives’ expectations in terms of the knowledge and skills’ gap in EmONC.ConclusionAlthough the newly developed application was found acceptable, further research involving practical sessions by nurses and midwives using the developed application is needed to garner views about the ease of use of the application, relevance of the EmONC uploaded content on the app, and needed improvements on the app to address their needs in EmONC.
Non-random Rotation Matching Algorithm
Authors: Lodha Roshan , Mehta Neil , Nielsen Craig 
Published: August 2023

AbstractAssigning clerkship positions to third-year medical students is crucial for their professional development. However, the process is challenging due to limited positions and the requirement to align students with suitable clerkships matching their interests and career goals. In this paper, we explain our approach of treating clerkship assignments as a linear-sum optimization problem. This optimizes position assignments, minimizing costs. We believe this approach could enhance the clerkship assignment process and improve medical students’ learning.
Epigenetic Reshaping through Damage: Promoting Cell Fate Transition by BrdU and IdU Incorporation
Authors: Li Chuang , Chen Shuyan , Xu Xiaoduo , Guan Tongxing , Xu Anchun , Li Chen , Yu Shengyong , Wu Haokaifeng , Pei Duanqing , Liu Jing 
Published: August 2023

AbstractThymidine analogs have long been recognized for their ability to randomly incorporate into DNA. However, their significance in the chemical induction of pluripotency (CIP) remains unclear. Here, we investigated the impact of BrdU/IdU incorporation on the transition of cell fate through DNA damage repair (DDR). Our findings reveal a substantial upregulation of reprogramming mediator gene H3K27ac and H3K9ac, as well as global DNA demethylation in response to DDR. This process creates a hypomethylated environment that promotes cell fate transition. We term this mechanism as Epigenetic Reshaping through Damage (ERD). Overall, our study sheds light on the dynamic interplay between thymidine analogs, DDR, and epigenetic modifications, providing valuable insights into the mechanisms underlying cell fate transition.
Fungal hacking of the plant sex-determination pathway via interference withAGL24inSilene latifolia
Authors: Fujita Naoko , Hood Michael E. , Komoda Yuka , Akagi Takashi 
Published: August 2023

AbstractPlants have evolved lineage-specific sex-determination systems that is determined not only by genetic factors, but also the surrounding environmental conditions, including interactions with pathogens.Silene latifoliais a model dioecious plant whose sexuality is genetically regulated by X/Y chromosomes; however, anther smut fungus mimics the plant Y chromosome and forcibly converts female plants to male. Here, transcriptome analyses of healthy or fungus-infectedS. latifoliainflorescence meristems suggested that an orthologue ofAGL24(SlAGL24), a flowering activator, is a key factor in sex conversionviafungus infection. Overexpression ofSlAGL24inArabidopsis thalianasuppressed stamen development, whereas knock-down ofSlAGL24inS. latifoliaconverted males into hermaphrodites. Furthermore,SlAGL24expression affected sexual dimorphisms inS. latifolia. Our results propose an adaptive scenario wherein the anther smut fungus targetsSlAGL24, as a master regulator connecting the fungal signal to sex determination, to confer male and potentially male-beneficial traits, effectively transmitting its teliospores.
From failure to success: a framework for successful deployment of Industry 4.0 principles in the aerospace industry
Authors: Gupta Sumit , Joshi Deepika , Jagtap Sandeep , Trollman Hana , Haddad Yousef , Atescan Yuksek Yagmur , Salonitis Konstantinos , Raut Rakesh , Narkhede Balkrishna 
Published: August 2023

PurposeThe paper proposes a framework for the successful deployment of Industry 4.0 (I4.0) principles in the aerospace industry, based on identified success factors. The paper challenges the perception of I4.0 being aligned with de-skilling and personnel reduction and instead promotes a route to successful deployment centred on upskilling and retaining personnel for future role requirements.Design/methodology/approachThe research methodology involved a literature review and industrial data collection via questionnaires to develop and validate the framework. The questionnaire was sent to a purposive sample of 50 respondents working in operations, and a response rate of 90% was achieved. Content analysis was used to identify patterns, themes, or biases, and the data were tabulated based on specific common attributes. The proposed framework consists of a series of gates and criteria that must be met before progressing to the next gate.FindingsThe proposed framework provides a feedback mechanism to review minimum standards for successful deployment, aligned with new developments in capability and technology, and ensures quality assessment at each gate. The paper highlights the potential benefits of I4.0 implementation in the aerospace industry, including reducing operational costs and improving competitiveness by eliminating variation in manufacturing processes. The identified success factors were used to define the framework, and the identified failure points were used to form mitigation actions or controls for inclusion in the framework.Originality/valueThe paper provides a framework for the successful deployment of I4.0 principles in the aerospace industry, based on identified success factors. The framework challenges the perception of I4.0 as being aligned with de-skilling and personnel reduction and instead promotes a route to successful deployment centred on upskilling and retaining personnel for future role requirements. The framework can be used as a guideline for organizations to deploy I4.0 principles successfully and improve competitiveness.
Subscription-based business models in the context of tech firms: theory and applications
Authors: Lindström Christoffer Weland Johannes , Maleki Vishkaei Behzad , De Giovanni Pietro 
Published: August 2023

PurposeThis study analyzes how tech firms can implement the modern wave of subscription-based business model (SBBM), including value proposition, value creation, value capture and performance. In fact, these elements push tech firms to move from traditional to SBBMs.Design/methodology/approachTo achieve the objectives of this study, we initially construct a theoretical framework for applying SBBM. Subsequently, we employ qualitative research to examine the current implementation of the subscription-based economy within tech firms.FindingsA successful SBBM necessitates capturing value through sustainable revenue transactions and revising aspects of the value proposition, creation and capture. Continuous improvement through business value analysis is imperative. Additionally, an agile operations system is vital to address revenue complexities, enable data collection and enhance value proposition, service innovation, churn rate and customer retention, which are essential for SBBM maintenance.Originality/valueThis study delves into how the subscription-based economy is reshaping the business models of tech firms. Beyond exploring the theoretical foundation of this transformative path, this study offers actionable insights on enhancing the value proposition, creation, capture and business value within subscription-based economy frameworks.
Exploring stationary and major modular construction challenges in developing countries: a case study of Egypt
Authors: Ali Ali Hassan , Kineber Ahmed Farouk , Elyamany Ahmed , Hussein Ibrahim Ahmed , Daoud Ahmed Osama 
Published: August 2023

Purpose
This study aims to identify the most significant barriers and the stationary barrier to modular construction (MC) implementation and promote MC widespread use. By doing so, the construction industry can leverage the benefits of MC, such as faster construction times, improved quality control, reduced waste and increased sustainability.

Design/methodology/approach
This study uses a Gini’s mean analysis approach to identify the stationary barriers hindering the MC adoption in residential projects. The research focuses on the Egyptian context and uses a questionnaire survey to gather data from professionals in the construction industry.

Findings
According to the survey findings, the top five significant MC barriers are inability to modify the design; contractors asking for high bidding prices (higher initial cost); scepticism, conservation and resistance of clients to innovation and change; transportation restrictions; and lack of a one-size-fits-all tool for the design. In addition, Gini’s mean of dispersion demonstrated that the stationary barrier that faces MC adoption is the apprehension that architectural creativity will suffer because of MC.

Practical implications
The identified obstacles could be useful for decision makers in countries that have not yet adopted MC and may aid in the planning process to manage the risks associated with MC projects. The paper stresses the significance of devising techniques to overcome these barriers and proposes several methods to tackle these challenges.

Originality/value
This study fills the knowledge gap by identifying the stationary barrier and emphasising the potential risks associated with MC barriers. Furthermore, it suggests several strategies for overcoming and reducing these barriers in developing countries residential projects.
Applying Benford’s law to examine earnings management: evidence from emerging ASEAN-5 countries
Authors: Nguyen Loan Hoang To , Nguyen Tri Tri , Le Thanh Vu Ngoc , Mai Nghia Duc 
Published: August 2023

Purpose
This study aims to apply Benford’s law to examine the earnings management of companies listed in emerging ASEAN-5 countries: Indonesia, Malaysia, Philippines, Thailand and Vietnam.

Design/methodology/approach
The authors follow Amiram et al. (2015) to measure deviations from Benford’s law of the first digits of numbers reported in financial statements. The authors use the Jones-modified performance-match model (Jones, 1991; Dechow et al., 1995; Kothari et al., 2005) to estimate accrual earnings management. The authors use a sample of 47,389 observations of listed companies in ASEAN-5 countries from 2006 to 2019. The authors also run ordinary least squares (OLS) regressions to test the hypotheses.

Findings
The authors find that the first digits of numbers reported in the financial statements of companies in the sample closely conform to Benford’s law. Further evidence shows that the deviation from Benford’s law is positively related to abnormal accruals. The relationship between deviation from Benford’s law and abnormal accruals is more pronounced for the post-international financial reporting standards adoption period. The results survive for some robustness checks.

Research limitations/implications
The authors show that Benford’s law holds for financial statements of companies listed in the emerging ASEAN-5 countries.

Practical implications
Auditors could use Benford’s law as an analytical procedure to assess the risks of material misstatements. Also, other users could apply Benford’s law on audited financial statements to foresee undetected misstatements.

Originality/value
The authors provide original evidence that financial statements of ASEAN-5 countries follow Benford’s law. The evidence supports the usefulness of Benford’s law in developing markets.
A mixed-method analysis of Industry 4.0 technologies in value generation for collaborative consumption companies
Authors: Amoozad Mahdiraji Hannan , Sharifpour Arabi Hojatallah , Beheshti Moein , Vrontis Demetris 
Published: August 2023

PurposeThis research aims to extract Industry 4.0 technological building blocks (TBBs) capable of value generation in collaborative consumption (CC) and the sharing economy (SE). Furthermore, by employing a mixed methodology, this research strives to analyse the relationship amongst TBBs and classify them based on their impact on CC.Design/methodology/approachDue to the importance of technology for the survival of collaborative consumption in the future, this study suggests a classification of the auxiliary and fundamental Industry 4.0 technologies and their current upgrades, such as the metaverse or non-fungible tokens (NFT). First, by applying a systematic literature review and thematic analysis (SLR-TA), the authors extracted the TBBs that impact on collaborative consumption and SE. Then, using the Bayesian best-worst method (BBWM), TBBs are weighted and classified using experts’ opinions. Eventually, a score function is proposed to measure organisations’ readiness level to adopt Industry 4.0 technologies.FindingsThe findings illustrated that virtual reality (VR) plays a vital role in CC and SE. Of the 11 TBBs identified in the CC and SE, VR was selected as the most determinant TBB and metaverse was recognised as the least important. Furthermore, digital twins, big data and VR were labelled as “fundamental”, and metaverse, augmented reality (AR), and additive manufacturing were stamped as “discretional”. Moreover, cyber-physical systems (CPSs) and artificial intelligence (AI) were classified as “auxiliary” technologies.Originality/valueWith an in-depth investigation, this research identifies TBBs of Industry 4.0 with the capability of value generation in CC and SE. To the authors’ knowledge, this is the first research that identifies and examines the TBBs of Industry 4.0 in the CC and SE sectors and examines them. Furthermore, a novel mixed method has identified, weighted and classified pertinent technologies. The score function that measures the readiness level of each company to adopt TBBs in CC and SE is a unique contribution.