bluuebunny/crossref_metadata_2025_split huggingface dataset:
TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase
Authors: Cheng Niangmei , Zheng Xiaoyuan , Huang Jingyun , Wang Fei , Wang Yang , Zhong Yue , Wang Yingchao , Wang Gaoxiong , Zhao Bixing 
Published: June 2024

Abstract

Background
The role of TROVE domain family member 2 (TROVE2) has been well-demonstrated in autoimmune diseases; however, its involvement in liver cancer remains unclear. Therefore, this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma (HCC).

Methods
The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction. The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting. High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes. Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.

Results
TROVE2 exhibited significant overexpression in liver cancer tissue, correlating with shorter overall survival. Overexpression of TROVE2 facilitated the invasion, metastasis, and epithelial-mesenchymal transition (EMT) process of HCC cells, whereas TROVE2 knockdown restrained migration, invasion, and EMT in these cells. Transcriptome sequencing and bioinformatics analysis identified heparanase (HPSE) as a downstream target protein of TROVE2. Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects. Moreover, the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3β phosphorylation.

Conclusions
TROVE2 facilitated the invasion, migration, and EMT process of HCC cells through phosphorylation of the HPSE/GSK-3β axis, indicating its significance as an important protein in tumor progression.
Prevalence and Correlates of SARS-CoV-2 Vaccine Uptake and Hesitancy Among People With HIV Across the United States
Authors: Spinelli Matthew A. , Johnson Mallory O. , Lisha Nadra E. , Jain Jennifer P. , Moreira Carlos V. , Glidden David V. , Burkholder Greer A. , Crane Heidi M. , Jacobson Jeffrey M. , Cachay Edward R. , Mayer Kenneth H. , Napravnik Sonia , Moore Richard D. , Gandhi Monica , Christopoulos Katerina A. 
Published: June 2024

Background:
People with HIV (PWH) have higher risk of COVID-19 mortality. SARS-CoV-2 vaccination is highly effective among PWH, although vaccine hesitancy could limit the population-level impact.

Setting:
From February 2021 to April 2022, PWH from 8 sites in the Centers for AIDS Research Network of Integrated Clinical Systems completed a vaccine hesitancy instrument as part of routine care.

Methods:
Participants were defined as vaccine hesitant if they had not received the SARS-CoV-2 vaccine and would probably/definitely not receive it. We assessed factors associated with SARS-CoV-2 vaccine hesitancy using logistic regression adjusted for demographics, unsuppressed viral load (VL > 200 copies/mL), month, and time on ART; using inverse probability weighting for survey nonresponse.

Results:
Overall, 3288 PWH with a median age of 55 were included; 18% were female and 94% were virally suppressed. At the time of survey, 27% reported they had not received the SARS-CoV-2 vaccine, and 9% (n = 279) reported vaccine hesitancy. Factors associated with vaccine hesitancy included female sex (adjusted odds ratio [AOR] = 2.3; 95% confidence interval (CI): 1.6–3.2), Black vs. White race (AOR 1.7; 95% CI: 1.2 to 2.4), younger age (AOR 1.4; 95% CI: 1.2 to 1.5), and unsuppressed VL (AOR 1.9; 95% CI: 1.3 to 3.0).

Conclusion:
Overall, over one-quarter of PWH in this multisite cohort were unvaccinated for SARS-CoV-2 when interviewed February 21–April 22. Vaccine hesitancy was reported by approximately 9% of PWH and was higher among women, Black PWH, younger PWH, PWH with unsuppressed VL, and those in the South/Midwest. Renewed efforts are needed to address concerns of PWH about vaccinations against COVID-19 as the pandemic evolves, and vaccines in general, given the potential for future pandemics.
Compositional Differential Abundance Testing: Defining and Finding a New Type of Health-Microbiome Associations
Authors: Ma Siyuan , Huttenhower Curtis , Janson Lucas 
Published: June 2024

AbstractA major task of microbiome epidemiology is association analysis, where the goal is to identify microbial features related to host health. This is commonly performed by differential abundance (DA) analysis, which, by design, examines each microbe as isolated from the rest of the microbiome. This does not properly account for the microbiome’s compositional nature or microbe-microbe ecological interactions, and can lead to confounded findings, i.e., microbes that only appear to associate with health through their confounding association with health-related, biologically informative microbes. To remedy these issues, we present Compositional Differential Abundance (CompDA) analysis, a novel approach for health-microbiome association. CompDA provides a novel approach to identify health-related microbes by examining the microbiome holistically, which a) accounts for the data’s compositionality and ecological interactions, and b) has clear interpretations corresponding to host health as affected by microbiome-based interventions. CompDA prioritizes health-related microbes and controls false discoveries by implementing recent advances from high-dimensional statistics, and can be flexibly adapted to many common tasks in modern microbiome epidemiology, including enhancing microbiome-based machine learning by providing rigorous p-values to prioritize important features. We validate the performance of CompDA, and compare against canonical microbiome association methods including DA with extensive, real-data-informed simulation studies. Lastly, we report novel and consistent findings of CompDA in application, based on re-examination of recently reported microbial signatures of colorectal cancer in a meta-analysis.
IMMUNOTAR - Integrative prioritization of cell surface targets for cancer immunotherapy
Authors: Shraim Rawan , Mooney Brian , Conkrite Karina L. , Weiner Amber K. , Morin Gregg B. , Sorensen Poul H. , Maris John M. , Diskin Sharon J. , Sacan Ahmet 
Published: June 2024

AbstractCancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of less toxic immunotherapies; however, identifying targets for immunotherapies remains a challenge in the field. To address this challenge, we developed IMMUNOTAR, a computational tool that systematically prioritizes and identifies candidate immunotherapeutic targets. IMMUNOTAR integrates user-provided RNA-sequencing or proteomics data with quantitative features extracted from publicly available databases based on predefined optimal immunotherapeutic target criteria and quantitatively prioritizes potential surface protein targets. We demonstrate the utility and flexibility of IMMUNOTAR using three distinct datasets, validating its effectiveness in identifying both known and new potential immunotherapeutic targets within the analyzed cancer phenotypes. Overall, IMMUNOTAR enables the compilation of data from multiple sources into a unified platform, allowing users to simultaneously evaluate surface proteins across diverse criteria. By streamlining target identification, IMMUNOTAR empowers researchers to efficiently allocate resources and accelerate immunotherapy development.
Aligning Brains into a Shared Space Improves their Alignment to Large Language Models
Authors: Bhattacharjee Arnab , Zada Zaid , Wang Haocheng , Aubrey Bobbi , Doyle Werner , Dugan Patricia , Friedman Daniel , Devinsky Orrin , Flinker Adeen , Ramadge Peter J. , Hasson Uri , Goldstein Ariel , Nastase Samuel A. 
Published: June 2024

AbstractRecent studies have shown that large language models (LLMs) can accurately predict neural activity measured using electrocorticography (ECoG) during natural language processing. To predict word-by-word neural activity, most prior work has estimated and evaluated encoding models within each electrode and subject—without evaluating how these models generalize across individual brains. In this paper, we analyze neural responses in 8 subjects while they listened to the same 30-minute podcast episode. We use a shared response model (SRM) to estimate a shared information space across subjects. We show that SRM significantly improves LLM-based encoding model performance. We also show that we can use this shared space to denoise the individual brain responses by projecting back into the individualized electrode space, and this process achieves a mean 38% improvement in encoding performance. The strongest improvement was observed for brain areas specialized for language comprehension, specifically in the superior temporal gyrus (STG) and inferior frontal gyrus (IFG). Critically, estimating a shared space allows us to construct encoding models that better generalize across individuals.
Passive droplet microfluidic platform for high-throughput screening of microbial proteolytic activity
Authors: Potenza Luca , Kozon Łukasz , Drewniak Lukasz , Kaminski Tomasz S. 
Published: June 2024

ABSTRACTTraditional bacterial isolation methods are often costly, have limited throughput, and may not accurately reflect the true microbial community composition. Consequently, identifying rare or slow-growing taxa becomes challenging. Over the last decade, a new approach has been proposed to replace traditional flasks or multi-well plates with ultrahigh-throughput droplet microfluidic screening assays. In this study, we present a novel passive droplet-based method designed for isolating proteolytic microorganisms, which are crucial in various biotechnology industries. Following the encapsulation of single cells in gelatin microgel compartments and their subsequent clonal cultivation, microcultures are passively sorted at high throughput based on the deformability of droplets. Our novel chip design offers a 50-fold improvement in throughput compared to previously developed deformability-based droplet sorter. This method expands an array of droplet-based microbial enrichment assays and significantly reduces the time and resources required to isolate proteolytic bacteria strains.
GLARE: Discovering hidden patterns in spaceflight transcriptome using representation learning
Authors: Seo DongHyeon , Strickland Hunter F. , Zhou Mingqi , Barker Richard , Ferl Robert J , Paul Anna-Lisa , Gilroy Simon 
Published: June 2024

ABSTRACTSpaceflight studies present novel insights into biological processes through exposure to stressors outside the evolutionary path of terrestrial organisms. Despite limited access to space environments, numerous transcriptomic datasets from spaceflight experiments are now available through NASA’s GeneLab data repository, which allows public access to these datasets, encouraging further analysis. While various computational pipelines and methods have been used to process these transcriptomic datasets, learning-model-driven analyses have yet to be applied to a broad array of such spaceflight-related datasets. In this study, we propose an open-source framework, GLARE: GeneLAb Representation learning pipelinE, which consists of training different representation learning approaches from manifold learning to self-supervised learning that enhances the performance of downstream analytical tasks such as pattern recognition. We illustrate the utility of GLARE by applying it to gene-level transcriptional values from the results of the CARA spaceflight experiment, an Arabidopsis root tip transcriptome dataset that spanned light, dark, and microgravity treatments. We show that GLARE not only substantiated the findings of the original study concerning cell wall remodeling but also revealed additional patterns of gene expression affected by the treatments, including evidence of hypoxia. This work suggests there is great potential to supplement the insights drawn from initial studies on spaceflight omics-level data through further machine-learning-enabled analyses.
Directionality bias underpins divergent spatiotemporal progression of Alzheimer-related tauopathy in mouse models
Authors: Torok Justin , Mezias Christopher , Raj Ashish 
Published: June 2024

AbstractMounting evidence implicates trans-synaptic connectome-based spread as a shared mechanism behind different tauopathic conditions, yet also suggests there is divergent spatiotemporal progression between them. A potential parsimonious explanation for this apparent contradiction could be that different conditions incur differential rates and directional biases in tau transmission along fiber tracts. In this meta-analysis we closely examined this hypothesis and quantitatively tested it using spatiotemporal tau pathology patterns from 11 distinct models across 4 experimental studies. For this purpose, we extended a network-based spread model by incorporating net directionality along the connectome. Our data unambiguously supports the directional transmission hypothesis. First, retrograde bias is an unambiguously better predictor of tau progression than anterograde bias. Second, while spread exhibits retrograde character, our best-fitting biophysical models incorporate the mixed effects of both retrograde- and anterograde-directed spread, with notable tau-strain-specific differences. We also found a nontrivial association between directionality bias and tau strain aggressiveness, with more virulent strains exhibiting less retrograde character. Taken together, our study implicates directional transmission bias in tau transmission along fiber tracts as a general feature of tauopathy spread and a strong candidate explanation for the diversity of spatiotemporal tau progression between conditions. This simple and parsimonious mechanism may potentially fill a critical gap in our knowledge of the spatiotemporal ramification of divergent tauopathies.
RADIP technology comprehensively identifies H3K27me3-mediated RNA-chromatin interactions
Authors: Shu Xufeng , Kato Masaki , Takizawa Satoshi , Suzuki Yutaka , Carninci Piero 
Published: June 2024

ABSTRACTMany RNAs associate with chromatin, either directly or indirectly. Several technologies for mapping regions where RNAs interact across the genome have been developed to investigate the function of these RNAs. Obtaining information on the proteins involved in these RNA–chromatin interactions is critical for further analysis. Here, we developed RADIP (RNA and DNA interacting complexes ligated and sequenced (RADICL-seq) with immunoprecipitation), a novel technology that combines RADICL-seq technology with chromatin immunoprecipitation to characterize RNA–chromatin interactions mediated by individual proteins. Building upon the foundational principles of RADICL-seq, RADIP extends its advantages by increasing genomic coverage and unique mapping rate efficiency compared to existing methods. To demonstrate its effectiveness, we applied an anti-H3K27me3 antibody to the RADIP technology and generated libraries from mouse embryonic stem cells (mESCs). We identified a multitude of RNAs, including RNAs from protein-coding genes and non-coding RNAs, that are associated with chromatin via H3K27me3 and that likely facilitate the spread of Polycomb repressive complexes over broad regions of the mammalian genome, thereby affecting gene expression, chromatin structures and pluripotency of mESCs. Our study demonstrates the applicability of RADIP to investigations of the functions of chromatin-associated RNAs.GRAPHICAL ABSTRACT
An Updated Structure of Oxybutynin Hydrochloride
Authors: Lin Jieye , Bu Guanhong , Unge Johan , Gonen Tamir 
Published: June 2024

AbstractOxybutynin (Ditropan), a widely distributed muscarinic antagonist for treating the overactive bladder, has been awaiting a definitive crystal structure for nearly 50 years due to the sample and technique limitations. Past reports used powder X-ray diffraction (PCRD) to shed light on the possible packing of the molecule however a 3D structure remained elusive. Here we used Microcrystal Electron Diffraction (MicroED) to successfully unveil the 3D structure of oxybutynin hydrochloride. We identify several inconsistencies between the reported PXRD analyses and the experimental structure. Using the improved model, molecular docking was applied to investigate the binding mechanism between M3muscarinic receptor (M3R) and (R)-oxybutynin, revealing essential contacts/residues and conformational changes within the protein pocket. A possible universal conformation was proposed for M3R antagonists, which is valuable for future drug development and optimization. This study underscores the immense potential of MicroED as a complementary technique for elucidating the unknown pharmaceutical crystal structures, as well as for the protein-drug interactions.
A DNA-based molecular clamp for probing protein interactions and structure under force
Authors: Chung Minhwan , Zhou Kun , Powell John , Lin Chenxiang , Schwartz Martin A. 
Published: June 2024

AbstractCellular mechanotransduction, a process central to cell biology, embryogenesis, adult physiology and multiple diseases, is thought to be mediated by force-driven changes in protein conformation that control protein function. However, methods to study proteins under defined mechanical loads on a biochemical scale are lacking. We report the development of a DNA based device in which the transition between single-stranded and double-stranded DNA applies tension to an attached protein. Using a fragment of the talin rod domain as a test case, negative-stain electron microscopy reveals programmable extension while pull down assays show tension-induced binding to two ligands, ARPC5L and vinculin, known to bind to cryptic sites inside the talin structure. These results demonstrate the utility of the DNA clamp for biochemical studies and potential structural analysis.
Military-experienced directors, CEO busyness and financial statement footnotes readability: evidence from Indonesia
Authors: Abdul Wahab Effiezal Aswadi , Harymawan Iman , Wardani Damara Ardelia Kusuma , Nasih Mohammad 
Published: June 2024

PurposeThis study examines the relationship between the characteristics of militarily experienced directors and financial statement footnote readability. The second research question considers whether CEO busyness impacts the relationship between military-experienced directors and financial statement footnotes readability.Design/methodology/approachWe use nonfinancial listed firms on the Indonesian Stock Exchange from 2010 to 2018, which amounted to 1,002 firm-year observations. We test the hypotheses and use fixed effects and Heckman's two-stage regression.FindingsThis study documents a negative relationship between military directors and financial statement footnote readability. We extend this relationship by factoring board busyness into the equation. We find that the presence of military-connected and busy CEOs negatively impacts the readability of financial statement footnotes. The results remain robust after additional analyses.Research limitations/implicationsFuture research should consider a more robust measure of military-experienced directors. A broader context of directors' busyness should be considered, such as including multiple directorships.Originality/valueWe revisit the literature on military-experienced directors by considering political connections as one of the proxies for military connections in Indonesia. The findings largely support the convergence of the political connections literature in which rent-seeking activities are prevalent and prevent sound financial reporting.
Bank financial distress and earnings management strategies: evidence from MENA countries
Authors: Ben Rejeb Mouna , Alzyadat Safwan , Merzki Nozha 
Published: June 2024

PurposeThis study investigates and compares the earnings management strategies of financially distressed and non-distressed banks.Design/methodology/approachUsing a regression analysis, this study examines a sample of banks operating in the MENA region. We focus on real earnings management strategies via commission and fee income (CF) and accrual-based earnings management strategies via loan loss provisions (LLP). A subsample analysis was performed, lagged dependent variables and additional control variables were included as a robustness check.FindingsThe findings consistently reveal a more extensive use of real earnings management strategies via CF among distressed banks than among non-distressed ones. Specifically, banks smooth their income via CF under distress conditions. However, LLP-based earnings management strategies are only implemented in healthy banks. These behaviors persist in banks that operate under different monitoring systems and institutional settings.Research limitations/implicationsThis study marks its entry into the literature debate on accounting and non-accounting decisions that influence bank financial reporting. It argues that, in the presence of financial difficulties, bank managers define earnings management strategies based on the probability of being detected, rather than looking at their costs.Practical implicationsFrom a prudential perspective, the findings suggest the need for prudential rules to supervise the reporting of CF income associated with high fees or discount incentives used intentionally by bank managers to convince clients to delay or accelerate payments and, consequently, affect reported earnings.Originality/valueThis study adds to the literature by investigating the effect of bank financial distress on both real and accrual-based earnings management to provide a comprehensive analysis of bank earnings management strategies in the presence of financial difficulties.
The mediating role of organizational culture between transformational leadership and organizational performance in SMEs
Authors: Peña Jorge , Caruajulca Percy 
Published: June 2024

PurposeConsidering the entrepreneurship nature and the high number of small and medium enterprises (SMEs) in the Latin American region, this study seeks to empirically test the relationship between organizational culture (OC), transformational leadership (TF) and organizational performance (OP) to support their long-term survival.Design/methodology/approachUnder a post-positivism paradigm, quantitative approach and correlational scope, this research analyzed the interrelationship between OC, TF and OP across Peruvian SMEs. Confirmatory factor analysis (CFA) and structural equation modeling (SEM) were used to test the hypotheses based on the responses of 276 SMEs’ top executives from the commerce, services, manufacturing, construction and agriculture industries.FindingsOC fully mediates the relationship between TL and OP. Although TF solely does not drive OP, the mediating effect of OC is crucial for SMEs’ long-term survival, especially considering their contribution to employment, poverty reduction and GDP in developing countries. Entrepreneurial transformational leaders inspire their followers to achieve goals, strive to develop individual skills, transmit confidence and leave aside their own interests to focus on the common goal of growing their entrepreneurship competitively.Originality/valueThe three variables under analysis have been applied to large companies and SMEs. However, this research enriches previous findings, highlighting the necessity for an adequate OC derived from an entrepreneur with TL, contributing to the survival of SMEs, whose results are critical for developing countries’ economies.