bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying cooperative genes causing cancer progression with dynamic causal inference
Authors: Cifuentes-Bernal Andres M. , Liu Lin , Li Jiuyong , Le Thuc Duy 
Published: November 2023

AbstractCancer progression is driven by complex gene interactions, which are not fully understood due to the dynamic and multifaceted nature of the disease. Traditional methods for identifying genes driving cancer typically focus on detecting mutational events, often neglecting other genetic alterations and the temporal dynamics of the cancer development. This study introduces a novel approach that expands our understanding of cancer by identifying cooperative networks of cancer drivers through dynamic causal inference, complementing classical mutation-based methods.We developed a data-driven causal inference method that integrates a temporal dimension to gene expression data through pseudotime analysis. By modelling cancer progression as a dynamic system, the method evaluates gene interactions and their causal relationships using causal kinetic models (CKMs). This approach enables detecting cancer driver genes regardless of their mutational status. The approach was applied to both single cell and bulk sequencing datasets of breast cancer to identify and rank cancer driver genes based on their stability on the causal model.The proposed method effectively identifies and ranks cancer driver genes by considering their dynamic interactions during cancer progression. It systematically identified cancer driver genes in both categories: those with single nucleotide variants (SNVs) and those with other alterations. The method demonstrated a significant overlap with known cancer driver genes from the Cancer Gene Census, validating its effectiveness. Additionally, the method uncovered novel driver genes that act cooperatively to influence cancer development, offering a more comprehensive view of the genetic mechanisms underlying cancer. Our approach, along with the scripts for the experiments and datasets used, can be found athttps://github.com/AndresMCB/DynamicCancerDriverKM
Loss of cardiac PFKFB2 drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart
Authors: Harold Kylene M. , Matsuzaki Satoshi , Pranay Atul , Loveland Brooke L. , Batushansky Albert , Mendez Garcia Maria F. , Eyster Craig , Stavrakis Stavros , Chiao Ying Ann , Kinter Michael , Humphries Kenneth M. 
Published: November 2023

AbstractBackgroundPhosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function.MethodsTo address this, we have generated a mouse model with a cardiomyocyte-specific knockout of PFKFB2 (cKO). Using 9-month-old cKO and control (CON) mice, we characterized impacts of PFKFB2 on cardiac metabolism, function, and electrophysiology.ResultscKO mice have a shortened lifespan of 9 months. Metabolically, cKO mice are characterized by increased glycolytic enzyme abundance and pyruvate dehydrogenase (PDH) activity, as well as decreased mitochondrial abundance and beta oxidation, suggesting a shift toward glucose metabolism. This was supported by a decrease in the ratio of palmitoyl carnitine to pyruvate-dependent mitochondrial respiration in cKO relative to CON animals. Metabolomic, proteomic, and western blot data support the activation of ancillary glucose metabolism, including pentose phosphate and hexosamine biosynthesis pathways. Physiologically, cKO animals exhibited impaired systolic function and left ventricular (LV) dilation, represented by reduced fractional shortening and increased LV internal diameter, respectively. This was accompanied by electrophysiological alterations including increased QT interval and other metrics of delayed ventricular conduction.ConclusionsLoss of PFKFB2 results in metabolic remodeling marked by cardiac ancillary pathway activation. This could delineate an underpinning of pathologic changes to mechanical and electrical function in the heart.Clinical PerspectiveWhat is New?We have generated a novel cardiomyocyte-specific knockout model of PFKFB2, the cardiac isoform of the primary glycolytic regulator Phosphofructokinase-2 (cKO).The cKO model demonstrates that loss of cardiac PFKFB2 drives metabolic reprogramming and shunting of glucose metabolites to ancillary metabolic pathways.The loss of cardiac PFKFB2 promotes electrophysiological and functional remodeling in the cKO heart.What are the Clinical Implications?PFKFB2 is degraded in the absence of insulin signaling, making its loss particularly relevant to diabetes and the pathophysiology of diabetic cardiomyopathy.Changes which we observe in the cKO model are consistent with those often observed in diabetes and heart failure of other etiologies.Defining PFKFB2 loss as a driver of cardiac pathogenesis identifies it as a target for future investigation and potential therapeutic intervention.
Connecting the dots: applying multispecies connectivity in marine park network planning
Authors: Gates Katie , Sandoval-Castillo Jonathan , Barceló Andrea , Bertram Andrea , Pratt Eleanor A. L. , Teske Peter R. , Möller Luciana , Beheregaray Luciano B. 
Published: November 2023

AbstractMarine ecosystems are highly dynamic, and their connectivity is affected by a complex range of biological, spatial, and oceanographic factors. Incorporating connectivity as a factor in the planning and management of marine protected areas (MPAs) is important yet challenging. Here, we used intraspecific genetic and genomic data for five marine species with varying life histories to characterise connectivity across a recently established South Australian MPA network. We generated connectivity networks, estimated cross-species concordance of connectivity patterns, and tested the impact of key spatial and oceanographic factors on each species. Connectivity patterns varied markedly among species, but were most correlated among those with similar dispersal strategies. Ordination analyses revealed significant associations with both waterway distances and oceanographic advection models. Notably, waterway distances provided better predictive power in all-species combined analyses. We extended the practical relevance of our findings by employing spatial prioritisation with Marxan, using node values derived from both genetic and geographic connectivity networks. This allowed the identification of several priority areas for conservation, and substantiated the initial decision to employ spatial distance as a proxy for biological connectivity for the design of the South Australian marine park network. Our study establishes a baseline for connectivity monitoring in South Australian MPAs, and provides guidelines for adapting this framework to other protected networks with intraspecies genetic data.
Investigation of microglial diversity in a mouse model of Parkinson’s disease pathology
Authors: Iovino L , VanderZwaag J , Kaur G , Khakpour P , Giusti V , Chiavegato A , Tenorio-Lopes L , Greggio E , Tremblay ME , Civiero L 
Published: November 2023

AbstractMicroglia, the central nervous system resident immune cells, are now recognized to critically impact homeostasis maintenance and contribute to the outcomes of various pathological conditions including Parkinson’s disease (PD). Microglia are heterogenous, with a variety of states recently identified in aging and neurodegenerative disease models, including the ‘disease-associated microglia’ (DAM) which present a selective enrichment ofCLEC7Aencoding the CLEC7A or DECTIN1 protein, and the ‘dark microglia’ (DM) displaying markers of cellular stress at the ultrastructural level. However, the roles of CLEC7A-positive microglia and DM in the pathology of PD have remained largely elusive. By applying immunofluorescence and scanning electron microscopy, we aimed to characterize 1) the CLEC7A -positive cell population, and 2) their possible relationships to DM in a mouse model harboring a G2019S pathogenic mutation of the LRRK2 gene, the most common mutation linked to PD. We examined 18-month-old mice, comparing between LRRK2 G2019S knock-in mice and wild-type controls. In the dorsal striatum, a region affected by PD pathology, extensive ultrastructural features of cellular stress (e.g., endoplasmic reticulum and Golgi apparatus dilation), as well as reduced direct cellular contacts, were observed for microglia from LRRK2 G2019S miceversuscontrols. CLEC7A-positive microglia exhibited extensive phagocytic ultrastructural characteristics in the LRRK2 G2019S mice. Additionally, the LRRK2 G2019S mice presented a higher proportion of DM. Lastly, immunofluorescence and biochemical analysis revealed higher number of CLEC7A-positive cells in Lrrk2 G2019S genotypeversuscontrols both in tissues and in primary microglia cells. Of note, CLEC7A-positive cells present a selective enrichment of ameboid morphology and tend to cluster in the pathogenic animal. In summary, we provide novel insights into the involvement of recently-defined microglial states, CLEC7A-positive cells and DM, in the context of LRRK2 G2019S PD pathology.
A liquid-like coat mediates chromosome clustering during mitotic exit
Authors: Hernandez-Armendariz Alberto , Sorichetti Valerio , Hayashi Yuki , Brunner Andreas , Ellenberg Jan , Šarić Anđela , Cuylen-Haering Sara 
Published: November 2023

SummaryThe individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase. We show that Ki-67 dephosphorylation during mitotic exit and the simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface. Experiments and coarse-grained simulations support a model in which the coalescence of chromosome surfaces driven by phase separation promote clustering of chromosomes. Our study reveals how the switch of Ki-67 from a surfactant to a liquid-like condensed phase can generate the mechanical forces during genome segregation that are required for re-establishing nuclear-cytoplasmic compartmentalization after mitosis.
A Novel AI-Designed Antimicrobial Peptide Synergistically Potentiates Aminoglycosides against Colistin- and Carbapenem-ResistantAcinetobacter baumannii
Authors: Thakur Vipasha , Gupta Varsha , Sharma Prince , Gupta Anvita , Capalash Neena 
Published: November 2023

AbstractThe urgent necessity for new antibiotics becomes glaringly evident with the relentless rise of multidrug-resistant (MDR)Acinetobacter baumanniiin clinical environments, where its infections lead to alarmingly high mortality rates. Antimicrobial peptides (AMPs) represent a promising novel option to combat nosocomial infections caused by MDRA. baumannii. In this study, six novel synthetic peptides were designed through generative artificial intelligence (AI) and synthesized for further experiments. Peptides AIG-R1, AIG-R4, and AIG-R5 showed potent broad-spectrum antibacterial activity against Gram positive and Gram negative pathogens. One of the peptides, AIG-R5, was effective even against colistin and carbapenem-resistant strains ofA. baumannii,prevented biofilm formation, and eradicated established biofilms by 60%. Notably, AIG-R5 enhanced the activity of different antibiotics and was found to exhibit synergistic activity with antibiotics from the Aminoglycoside class. The combination of AIG-R5 and Tobramycin at 1/8×MIC and 1/4×MIC effectively reduced pre-formed biofilms of carbapenem resistantA. baumanniimore than either component alone, as documented by confocal laser scanning microscopy (CLSM). Significant dose reduction and negligible cytotoxicity exhibited by AIG-R5 with aminoglycosides further encourages evaluation of the combination’s therapeutic potentialin vivoagainst MDRA. baumanniiinfections.
Identification of conserved cross-species B-cell linear epitopes in human malaria: A subtractive proteomics and immuno-informatics approach targeting merozoite stage proteins
Authors: Musundi Sebastian D. , Gitaka Jesse , Kanoi Bernard N. 
Published: November 2023

AbstractHuman malaria, caused by five Plasmodium species (P. falciparum, P. vivax, P. malariae, P. ovale, andP. knowlesi), remains a significant global health burden. While most interventions targetP. falciparum, the species associated with high mortality rates and severe clinical symptoms, non-falciparum species exhibit different transmission dynamics, remain hugely neglected, and pose a significant challenge to malaria elimination efforts. Recent studies have reported the presence of antigens associated with cross-protective immunity, which can potentially disrupt the transmission of various Plasmodium species. With the sequencing of the Plasmodium genome and the development of immunoinformatic tools, in this study, we sought to exploit the evolutionary history of Plasmodium species to identify conserved cross-species B-cell linear epitopes in merozoite proteins. We retrieved Plasmodium proteomes associated with human malaria and applied a subtractive proteomics approach focusing on merozoite stage proteins. Bepipred 2.0 and Epidope were used to predict B-cell linear epitopes usingP. falciparumas the reference species. The predictions were further compared against human and non-falciparum databases and their antigenicity, toxicity, and allergenicity assessed. Subsequently, epitope conservation was carried out using locally sequenced isolates from a malaria-endemic region in western Kenya (n=27) and Kenyan isolates from MalariaGEN version 6 (n=131). Finally, physiochemical characteristics and tertiary structure of the B-cell linear epitopes were determined. The analysis revealed eight epitopes that showed high similarity (70-100%) between falciparum and non-falciparum species. These epitopes were highly conserved when assessed across local isolates and those from the MalariaGEN database and showed desirable physiochemical properties. Our results show the presence of conserved cross-species B-cell linear epitopes that could aid in targeting multiple Plasmodium species. Nevertheless, validating their efficacyin-vitroandin-vivoexperimentally is essential.
Busy CEO and financial statement footnotes readability: evidence from Indonesia
Authors: Harymawan Iman , Ratri Melinda Cahyaning , Ayuningtyas Eka Sari 
Published: November 2023

PurposeThis study aims to investigate the correlation between a CEO's business background and the readability of financial statement footnotes in Indonesia.Design/methodology/approachThis study utilizes a sample period spanning from 2010 to 2018 and employs various statistical tests, including Propensity Score Matching (PSM), Coarsened Exact Matching (CEM) and the Heckman Model, to demonstrate that it can address issues of causality and endogeneity without introducing bias.FindingsAs a result, the findings of this study indicate a statistically significant negative relationship between CEOs with busy schedules and the readability of financial statement footnotes. This suggests that companies led by busy CEOs are more likely to have financial statement footnotes that are easier to read.Research limitations/implicationsThese findings hold significance for clarifying research related to the challenges of contextual analysis in financial statement footnotes, which are distributed by companies on a sentence-by-sentence basis.Practical implicationsThe practical implications of the findings pertain to actionable steps that management can undertake and also offer regulators opportunities to monitor the potential for standard setting.Originality/valueBased on the results presented, the authors are optimistic that the findings will pave the way for broader research on the impact of a busy CEO, encompassing not only financial aspects but also non-financial dimensions. The growing popularity of readability is driven by the proliferation of textual reports that pose challenges in analysis and raise numerous inquiries.
Does family incivility trigger suicidal ideation? The role of emotional exhaustion at work and regulation of emotion
Authors: Ballekura Balakrishna , Vilvanathan Lavanya 
Published: November 2023

Purpose
Despite the prevalence of uncivil behaviors across families and past studies attributing work stressors to suicidal ideation (SI), there is no conclusive evidence of the interactive effect of family incivility (FI) aggravating SI. Hence, the purpose of this study is to explore the association between FI and SI through emotional exhaustion (EE) in the workplace and regulation of emotion.

Design/methodology/approach
A time lag (T1 and T2) study is applied for primary data collection using a survey questionnaire. The partial least squares–structural equational modeling algorithm tests reliability, validity and hypotheses.

Findings
Experiencing FI exacerbates SI, while the regulation of emotion and EE mediate the association between FI and SI.

Practical implications
Professionals are advised to adopt regulation of emotion that fosters desirable behavior and shields targets from FI and EE, minimizing the intensity of SI.

Originality/value
This study significantly adds to how FI and EE aggravate SI and contribute to the body of knowledge on the regulation of emotion in stress and coping mechanisms.
A benchmark model for the process of post-migration social adjustment: exploring the views of young people from forced-migration backgrounds in Australia
Authors: Ahmadi Forooshani Sayedhabibollah , Murray Kate , Khawaja Nigar , Izadikhah Zahra 
Published: November 2023

Purpose
The purpose of this study was to propose a benchmark model for the process of post-migration social adjustment based on the points of view and experiences of young individuals from forced-migration backgrounds.

Design/methodology/approach
Twelve young adults (18–24 years) living in Australia with an experience of forced migration and from various ethnic and cultural backgrounds were recruited. Semi-structured interviews were conducted and analyzed through thematic analysis.

Findings
The results showed that post-migration social adjustment requires effective interactions within individual, family and community domains. The participants proposed specific characteristics, enablers and barriers for each domain that can affect the process of social adjustment after the experience of forced migration.

Originality/value
Based on the reported points of view and experiences of participants in this study, the authors proposed an ecological model that can be considered as a preliminary benchmark to inform policymaking, research and services focusing on the social adjustment of young refugees. The practical implications for resettlement programs are discussed.
A salutary welcome: the role of Sense of Coherence and Generalized Resistance Resources in refugee settlement
Authors: Fries Christopher J. , Serieux John , Oranye Nelson 
Published: November 2023

Purpose
Guided by the salutogenic model of health and well-being, this study aims to use empirical measures of sense of coherence (SOC) and generalized resistance resources (GRRs) to gain a better understanding of the facilitators of successful transition and integration of refugees to Canada and relate these findings to current program development and delivery for the settlement of refugees.

Design/methodology/approach
Survey research and structural equation modeling.

Findings
The authors found that newcomers with a stronger SOC were more likely to report successful integration outcomes. GRRs were found to have both direct and indirect effects on the positive settlement of refugees, with the SOC acting as a strong mediator of indirect effects.

Research limitations/implications
Owing in part, to the disruption caused by the global pandemic, the authors’ data collection period was protracted and the final sample size of 263 is smaller than the authors would have preferred. Another limitation of this study has to do with its cross-sectional design, which limits the articulation of cause-and-effect relationships among the variables.

Practical implications
In terms of program development and delivery for the settlement of refugees, the authors’ results provide further evidence that refugee participation in socially valued decision-making represents a key determinant of healthy resettlement.

Originality/value
Much research on refugee settlement originates within “a pathogenic paradigm” that focuses on the stressors and obstacles encountered by people who have been displaced. Taking its cue from Israeli health sociologist, Aaron Antonovsky’s salutogenic model of health and well-being, this study uses empirical measures of Antonovsky’s interrelated concepts of SOC and GRRs to gain a better understanding of the facilitators of successful transition and integration of refugees to a prairie province in Canada and relate these findings to current program development and delivery for the settlement of refugees.
Process capability index Cpm under autoregressive process AR (2)
Authors: Ghute Vikas , Deshpande Mahesh 
Published: November 2023

PurposeThe paper aims to identify the effect of ignorance of correlatedness among process observations and to implement new sampling schemes; skip and mixed sampling, in order to reduce the effect of autocorrelation on process capability index (PCI) Cpm.Design/methodology/approachAutocorrelated observations are generated using autoregressive process of order two (AR (2)) using Monte Carlo simulations. The PCI is computed based on these observations assuming the independence. The skip and mixed sampling schemes are then used to form sub-groups among correlated observations. The PCI obtained using sub-groups from skip and mixed sampling schemes are assessed using sample mean and sample standard deviation.FindingsThe paper provides empirical insights into how the effect of autocorrelation decreases in the estimated value of PCI Cpm. The use of new sampling schemes, skip and mixed sampling, reduces the effect of autocorrelation on estimates of PCI Cpm.Originality/valueThis paper fulfills an identified need to study how to reduce the effect of autocorrelation on PCI Cpm.