bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylation Signatures in Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Trasierras-Fresco Antonio Manuel , Virués-Morales Alejandro , Gómez-Martínez Helena , Dolader Rabinad Beatriz , del Rey Díez Natalia , Andreu Z , Hidalgo Marta R. , Gómez-Cabañes Borja , Poley Gil Miriam , Malmierca-Merlo Pablo , Romera-Giner Sergio , Crespo Daniel , Serna-Blasco Roberto , Romero Atocha , Lopez-Guerrero Jose A , de la Iglesia-Vaya María , García-García Francisco 
Published: October 2022

AbstractEpigenetic changes are involved in the onset and progression of cancer, and the detection of DNA methylation signatures may foster the improvement of diagnosis and prognosis. While the emergence of innovative technologies has fostered numerous studies in breast cancer, many lack statistical power due to the small sample sizes generally involved. In this study, we present a novel meta-analysis that identifies a common pattern of DNA methylation in all breast cancer subtypes. We obtained DNA methylation signatures at the gene and biological function level, identifying those significant groups of genes and functional pathways affected. To achieve this, we conducted a thorough systematic review following PRISMA statement guidelines for the selection of studies on DNA methylation in breast cancer. In total, we gathered four studies (GSE52865, GSE141338, GSE59901 and GSE101443) that were split into 13 comparisons comprising a set of 144 individuals. We discovered that most breast cancer subtypes share a significant deregulation in the immune system and alterations to the cell cycle. This integrative approach combines all available information from public data repositories and possesses greater statistical power than any individual study. Further evaluations of the identified differential biological processes and pathways may support the identification of novel biomarkers and therapeutic targets.Simple summaryThe identification of DNA methylation patterns in breast cancer represents a potentially valuable approach in defining more accurate diagnoses and treatment options. In this study, we applied a novel methodology that integrates the DNA methylation profiles of all studies available in public repositories via systematic review and meta-analysis. The results provide evidence of a common DNA methylation signature in distinct breast cancer subtypes, which reflects a significant deregulation of the immune system and alterations to the cell cycle. Overall, these results may support the selection of disease/treatment biomarkers and the identification of therapeutic targets.
Identifying hierarchical cell states and gene signatures with deep exponential families for single-cell transcriptomics
Authors: Ferreira Pedro F. , Kuipers Jack , Beerenwinkel Niko 
Published: October 2022

AbstractSingle-cell gene expression data characterizes the complex heterogeneity of living systems. Tissues are composed of various cells with diverse cell states driven by different sets of genes. Cell states are often related in a hierarchical fashion, for example, in cell differentiation hierarchies. Clustering which respects a hierarchy, therefore, can improve functional interpretation and be leveraged to remove noise and batch effects when inferring gene signatures. For this task, we present single-cell Deep Exponential Families (scDEF), a multi-level Bayesian matrix factorization model for single-cell RNA-sequencing data. The model can identify hierarchies of cell states and be used for dimension reduction, gene signature identification, and batch integration. Additionally, it can be guided by known gene sets to jointly type cells and identify their hierarchical structure, or to find higher resolution states within the provided ones. In simulated and real data, scDEF outperforms alternative methods in finding cell populations across biologically distinct batches. We show that scDEF recovers cell type hierarchies in a whole adult animal, identifies a signature of response to interferon stimulation in peripheral blood mononuclear cells, and finds both patient-specific and shared cell states across nine high-grade serous ovarian cancer patients.
CMOT: Cross Modality Optimal Transport for multimodal inference
Authors: Alatkar Sayali , Wang Daifeng 
Published: October 2022

AbstractBiological mechanisms are complex spanning multiple facets, each providing a unique view of the underlying mechanism. Recent single-cell technologies such as scRNA-seq and scATAC-seq have facilitated parallel probing into each of these facets, providing multimodal measurements of individual cells. An integrative analysis of these single-cell modalities can therefore provide a comprehensive understanding of specific cellular and molecular mechanisms. Despite the technological advances, simultaneous profiling of multiple modalities of single cells continues to be challenging as opposed to single modality measurements, and therefore, it may not always be feasible to conduct such profiling experiments (e.g., missing modalities). Furthermore, even with the available multimodalities, data integration remains elusive since modalities may not always have paired samples, leaving partial to no correspondence information.To address those challenges, we developed Cross-Modality Optimal Transport (CMOT), a computational approach to infer missing modalities of single cells based on optimal transport (OT). CMOT first aligns a group of cells (source) within available multi-modal data onto a common latent space. Then, it applies optimal transport to map the cells with a single modality (target) to the aligned cells in source from the same modality by minimizing their cost of transportation using Wasserstein distance. This distance can be regularized by prior knowledge (e.g., cell types) or induced cells clusters to improve mapping, and an entropy of transport to speed up OT computations. Once transported, CMOT uses K-Nearest-Neighbors to infer the missing modality for the cells in target from another modality of mapped cells in source. Furthermore, the alignment of CMOT works for partially corresponding information from multi-modalities, i.e., allowing a fraction of unmatched cells in source. We evaluated CMOT on several emerging multi-modal datasets, e.g., gene and protein expression and chromatin accessibility in developing brain, cancers, and immunology. We found that not only does CMOT outperform existing state-of-art methods, but its inferred gene expression is biologically interpretable such as classifying cell types and cancer types. Finally, CMOT is open source and available on our github:https://github.com/daifengwanglab/CMOT
Immature Myeloid Cell Deposition in Old Bone Marrow Revealed by Single-Cell Transcriptome Analysis
Authors: Kim Woo Jin , Kim Ki-Tae , Moon Jae-I , Park Seung Gwa , Cho Young-Dan , Kim Hyun Jung , Shin Hye-Rim , Yoon Heein , Ryoo Hyun-Mo 
Published: October 2022

AbstractAging causes dysfunction of innate immunity, although hematopoietic stem cells of aged bone marrow (BM) show an increased differentiation potential to myeloid lineage cells. The alteration of cellular heterogeneity and intercellular communications between BM immune cells may provide important clues to understanding age-dependent immune dysfunction. Here, we provide a deep single-cell transcriptomic analysis of total immune cell populations of young and old BM. We identified the well-organized differentiation status of 11 myeloid/lymphoid lineage cell populations and age-dependent alterations in the proportions of cells. The neutrophil lineages showed the most prominent alteration by aging, and subclustering of neutrophils indicated that the specific immature neutrophils are increased in old BM. In addition, we identified age-dependent alterations in secretory phenotypes associated with a decline in innate immunity and immune cell differentiation. Among these secretory phenotypes, SPP1 could be suggested as a representative signal that triggers myeloid skewing and immature neutrophil deposition in aged BM. Collectively, these results provide a novel link between the altered immune cell proportions in BM and age-dependent dysregulation of innate immunity.
Deep learning algorithms reveal a new visual-semantic representation of familiar faces in human perception and memory
Authors: Shoham Adva , Grosbard Idan , Patashnik Or , Cohen-Or Daniel , Yovel Galit 
Published: October 2022

SummaryRecent studies show significant similarities between the representations humans and deep neural networks (DNNs) generate for faces. However, two critical aspects of human face recognition are overlooked by these networks. First, human face recognition is mostly concerned with familiar faces, which are encoded by visual and semantic information, while current DNNs solely rely on visual information. Second, humans represent familiar faces in memory, but representational similarities with DNNs were only investigated for human perception. To address this gap, we combined visual (VGG-16), visual-semantic (CLIP), and natural language processing (NLP) DNNs to predict human representations of familiar faces in perception and memory. The visual-semantic network substantially improved predictions beyond the visual network, revealing a new visual-semantic representation in human perception and memory. The NLP network further improved predictions of human representations in memory. Thus, a complete account of human face recognition should go beyond vision and incorporate visual-semantic, and semantic representations.
Chromosome-length genome assemblies of cactophilicDrosophilailluminate links between structural and sequence evolution
Authors: Benowitz Kyle M. , Allan Carson W. , Jaworski Coline C. , Sanderson Michael J. , Diaz Fernando , Chen Xingsen , Matzkin Luciano M. 
Published: October 2022

AbstractA thorough understanding of adaptation and speciation requires model organisms with both a history of ecological and phenotypic study as well as a robust set of genomic resources. For decades, the cactophilicDrosophilaspecies of the southwestern US and northern Mexico have fit this profile, serving as a crucial model system for understanding ecological adaptation, particularly in xeric environments, as well as the evolution of reproductive incompatibilities and speciation. Here, we take a major step towards gaining a complete molecular description of this system by assembling and annotating seven chromosome-lengthde novogenomes across the three speciesD. mojavensis, D. arizonae, andD. navojoa. Using this data, we present the most accurate reconstruction of the phylogenetic history of this clade to date. We further demonstrate a relationship between structural evolution and coding evolution both within and between species in this clade, and use this relationship to generate novel hypotheses for adaptation genes. All of our data are presented in a new public database (cactusflybase.arizona.edu), providing one of the most in-depth resources for the analysis of inter- and intraspecific evolutionary genomic data.
Timing of TORC1 inhibition dictates Pol III involvement in longevity inCaenorhabditis elegans
Authors: Malik Yasir , Silva Isabel Goncalves , Diazgranados Rene Rivera , Selman Colin , Alic Nazif , Tullet Jennifer M. A. 
Published: October 2022

SummaryOrganismal growth and lifespan are inextricably linked. Target of Rapamycin (TOR) signalling regulates protein production for growth and development, but if reduced extends lifespan across species. Reduction of the enzyme RNA polymerase III, which transcribes tRNAs and 5S rRNA, also extends longevity. Here, we identify a temporal genetic relationship between TOR and Pol III inC. elegans, showing that they collaborate to regulate progeny production and lifespan. Interestingly, the lifespan interaction between Pol III and TOR is only revealed when TOR signaling is reduced specifically in adulthood demonstrating the importance of timing to control TOR regulated developmentalvsadult programs. Additionally, we show that Pol III acts inC. elegansmuscle to promote both longevity and healthspan and that reducing Pol III even in late adulthood is sufficient to extend lifespan. This demonstrates the importance of Pol III for lifespan and age-related health in adultC. elegans.
Characterization of the Tau Interactome in Human Brain Reveals Isoform-Dependent Interaction with 14-3-3 Family Proteins
Authors: Betters Ryan K. , Luhmann Emma , Gottschalk Amy C. , Xu Zhen , Ptak Christopher P. , Fiock Kimberly L. , Radoshevich Lilliana C. , Hefti Marco M. 
Published: October 2022

AbstractTau phosphorylation and aggregation is the final common pathway for neuronal toxicity across multiple neurodegenerative diseases including Alzheimer disease, progressive supranuclear palsy, and corticobasal degeneration. We have previously shown that the fetal brain expresses high levels of phosphorylated tau, and even tau aggregates, without apparent toxic effects. The mechanisms for this remarkable resilience, however, remain unclear. In order to identify potential mediators of this resilience, we used bead-linked total tau immunoprecipitation in human fetal, adult, and Alzheimer disease brains. We then used heterologous transfection in HEK 293T cells followed by coimmunoprecipitation, mass photometry, and nuclear magnetic resonance (NMR) to further characterize the interaction of tau with one of our top hits, 14-3-3-β. We found significant differences between the tau interactome in fetal and AD brain, with little difference between adult and AD. There were significant differences in tau interaction with 14-3-3 family proteins between fetal and AD brain. We then determined that the 14-3-3 isoform with the highest difference, 14-3-3-β, preferentially interacts with 4R tauin vitro, forming a complex consisting of two 14-3-3-β, and one tau molecule. NMR studies using15N-labeled phosphorylated tau showed that the binding site for 14-3-3 was in the microtubule binding region of tau, which is truncated in 3R tau through the exclusion of exon 10. Our findings suggest that there are marked differences between the phospho-tau interactome in fetal and Alzheimer disease brain, including differences in interaction with the critical 14-3-3 family of protein chaperones, which may explain, in part, the resilience of fetal brain to tau toxicity.
Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety-like behaviors and electro-acupuncture therapy
Authors: Chen Liying , Liu Zhaoyu , Zhao Ziheng , Du Demin , Pan Weichao , Wei Xiaoyan , Nie Jiaxun , Ge Feifei , Ding Jianhua , Fan Yu , Kim Hee Young , Guan Xiaowei 
Published: October 2022

AbstractAdolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.Methods:ACE male mice model were established by exposing to cocaine during adolescent period. Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice. Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1RCaMKII)in vivo. Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period.Results:We found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1RCaMKIIlevels in claustrum during adulthood. Inhibiting D1R function or knocking-down D1RCaMKIIlevels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety-like behaviors in ACE mice during adulthood. EA treatment alleviated ACE-evoked claustrum activation and anxiety-like behaviors by suppressing claustrum D1RCaMKII.Conclusion:Our findings identified a novel role of claustrum in ACE-induced anxiety-like behaviors, and put new insight into the D1RCaMKIIin the claustrum. The claustrum D1RCaMKIImight be a promising pharmacological target, such as EA treatment, to treat drugs-induced anxiety-like behaviors.Graphic abstract
Do you know when you are the punchline? Gender-based disparagement humor and target perceptions
Authors: Tabassum Ayesha , Karakowsky Len 
Published: October 2022

Purpose
This paper aims to draw upon extant theory and research to delineate the fundamental factors that impact how women evaluate disparaging humor directed at them. The conceptual framework presented outlines the most fundamental organizational-, interpersonal- and individual-level factors that influence the accuracy of such evaluation.

Design/methodology/approach
This is a conceptual paper that offers both a review of extant humor and gender research and theory and the presentation of a theoretical model that classifies sources of influence on evaluations of sexist humor from the perspective of the target.

Findings
Organization-, interpersonal- and individual-level factors are identified as sources of influence on women’s perception and evaluation of sexist humor leveled at them. This classification identifies factors including organizational power dynamics, egalitarian norms, interpersonal trust, target self-esteem and feminist identity.

Research limitations/implications
This paper offers a conceptual framework to guide future studies in more systematically examining the sources of influence on female targets’ capacity to recognize when they are the “punchline” of sexist humor.

Practical implications
The conceptual model developed in this paper offers important implications for managers and leaders in organizations in assisting targets to recognize instances of sexist humor directed at them. The aim is to arm potential victims with the knowledge necessary to foster awareness of their treatment in the workplace and to improve the accuracy of evaluation of workplace attitudes that may often nurture a sense of approval or apathy regarding displays of sexist humor.

Originality/value
This paper presents a novel classification of sources of influence on female targets’ evaluation of sexist humor in the workplace.
Reflections on women’s progress into leadership in the UK and suggested areas for future research
Authors: Vinnicombe Susan , Mavin Sharon 
Published: October 2022

Purpose
The paper provides an invited “Viewpoint” from Professor Susan Vinnicombe, along with contributions from Professor Sharon Mavin, on women leaders’ progress on UK company boards and suggests areas for future research.

Design/methodology/approach
Draws on data from the annual UK The Female FTSE Board Report (2021) and The Hidden Truth Report (2022), tracking gender diversity on UK company boards. Professor Vinnicombe outlines reflections on progress, and jointly the authors highlight suggested areas for future women-in-leadership research.

Findings
The authors argue against the continued use of the business case for gender diversity and suggest a research agenda for future women-in-leadership research concerning: gender-aware Chairs of Boards and Chief Executive Officers and men allies; access and appointment to senior board roles; and bias in senior appointments. We suggest a return to examining barriers to women’s progress in middle management, the role of middle managers/leaders and the uptake and impact of established flexible ways of work at executive levels. New research is possible into how women leaders in top positions have a positive influence on gender diversity yet are discriminated against by various publics. The authors recommend further intersectional research as a priority for women-in-leadership research to enable further theorizing and feminist progress.

Originality/value
Professor Sue Vinnicombe has dedicated her academic career to questioning barriers to women’s progress in management/leadership and actively influencing organisational practice. Sue was influential in the field before her first co-authored papers were published in Women in Management Review (our predecessor) in 2001 and 2002. Professor Sharon Mavin is a previous co-editor of Gender in Management: an international journal. Her first papers were published in Women in Management Review in 1999 and 2001. Sharon is co-editor of the Special Issue, women-in-leadership research and feminist futures: new agendas for feminist research and impact on gender equality.
Cash holdings and firm performance: empirical analysis from Shariah-compliant and conventional corporations
Authors: Alnori Faisal , Bugshan Abdullah 
Published: October 2022

Purpose
This paper aims to provide a comprehensive investigation into the different roles of cash holding decisions on Shariah-compliant and non-Shariah-compliant firms’ performance. Therefore, the objective of this study is to analyze the significant relationship of liquidity on Shariah- and non-Shariah-compliant corporations.

Design/methodology/approach
This study sample includes non-financial firms listed in six Gulf Cooperation Council (GCC) markets between 2005 and 2019. The study uses panel fixed effects and the dynamic generalized method of moments (system-GMM) models to test the relationship between cash holding and firm performance. The firms’ performance is measured using four widely used proxies representing book and market measures of performance including return on assets, return on equity, earnings before interest and tax to total assets and Tobin’s Q.

Findings
The results explore that the nature of the relationship between cash holdings and performance varies across Shariah-compliant and non-Shariah-compliant firms. Specifically, cash holdings are positively and significantly related to Shariah-compliant firms’ performance. However, cash reserves are not significantly related to conventional firms’ performance. These findings indicate that Shariah-compliant firms rely more on their cash holdings to avoid costly and less available external financing, meet everyday business needs and invest in profitable projects. In contrast, the value for cash holding is less important for non-Shariah-compliant firms, as their external financing options are less restricted compared to Shariah-compliant firms.

Research limitations/implications
This study is not free from limitations. More specifically, the sample of this study comprises of firms listed in GCC countries, which share common features. It would be interesting for future research to examine the linkage between cash holdings and Shariah-compliant and conventional firms’ performance by applying a larger sample, such as firms located in countries of the Organization of Islamic Cooperation.

Practical implications
The findings of this paper provide useful insights for managers and investors on the important role of cash management for Shariah-compliant firms. Policymakers and bankers need to develop Shariah-based financial products to ease Islamic financing sources. Moreover, the findings of this paper call for more research on the importance of liquidity management for Shariah-compliant firms.

Originality/value
This study extends the Islamic finance literature by exploring the key role of cash holdings to Shariah-compliant firms. To the best of the authors’ knowledge, this study is the first study to investigate cash holdings and performance between Shariah-compliant and non-Shariah-compliant firms.