bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear and organelle genome assemblies of fiveCucumis meloL. accessions, Ananas, Canton, PI 414723, Vedrantais and Zhimali, belonging to diverse botanical groups
Authors: Belinchon-Moreno Javier , Berard Aurelie , Canaguier Aurelie , Le-Clainche Isabelle , Rittener-Ruff Vincent , Lagnel Jacques , Hinsinger Damien , Boissot Nathalie , Faivre-Rampant Patricia 
Published: October 2024

AbstractThe construction of accurate whole genome sequences is pivotal for characterizing the genetic diversity of plant species, identifying genes controlling important traits, or understanding their evolutionary dynamics. Here, we generated the nuclear, mitochondrial and chloroplast high- quality assemblies of five melon (Cucumis meloL.) accessions representing five diverse botanical groups, using the Oxford Nanopore sequencing technology. The accessions here studied included varied origins, fruit shapes, sizes, and resistance traits, providing a holistic view of melon genomic diversity.The final chromosome-level genome assemblies ranged in size from 359 to 365 Mb, with approximately 25x coverage for four of them multiplexed in half of a PromethION flowcell, and 48x coverage for the fifth, sequenced individually in another half of a PromethION flowcell. Contigs N50 ranged from seven to 15 Mb for all the assemblies, and very long contigs reaching sizes of 20-25 Mb, almost compatible with complete chromosomes, were assembled in all the accessions. Quality assessment through BUSCO and Mercury indicated the high completeness and accuracy of the assemblies, with BUSCO values exceeding 96% for all accessions, and Mercury QV values ranging between 32 and 47.We focused on the complex NLR resistance gene clusters to validate the accuracy of the assemblies in highly complex and repetitive regions. Through Nanopore adaptive sampling, we generated accurate targeted assemblies of these regions with a significantly higher coverage, enabling the comparison to our whole genome assemblies.Overall, these chromosome-level assembled genomes constitute a valuable resource for research focused on melon diversity, disease resistance, evolution, and breeding applications.Article SummaryThis study presents high-quality nuclear, mitochondrial, and chloroplast genome assemblies for five diverse melon (Cucumis meloL.) accessions, using Oxford Nanopore sequencing. The assemblies represent a broad spectrum of melon diversity, including differences in origin, fruit morphology, or resistance traits. The genomes, ranging from 359 to 365 Mb, were assembled at a chromosome level with high contiguity, and verified using different validation approaches. This study provides valuable insights for research on melon genetic diversity, disease resistance, and breeding applications. The genome data will be especially valuable for plant geneticists, breeders, and researchers working on crop improvement and resistance traits.
Spatiotemporal coordination of actin regulators generates invasive protrusions in cell-cell fusion
Authors: Lu Yue , Walji Tezin , Ravaux Benjamin , Pandey Pratima , Yang Changsong , Li Bing , Luvsanjav Delgermaa , Lam Kevin H. , Zhang Ruihui , Luo Zhou , Zhou Chuanli , Habela Christa W. , Snapper Scott B. , Li Rong , Goldhamer David J. , Schmidtke David W. , Pan Duojia , Svitkina Tatyana M. , Chen Elizabeth H. 
Published: October 2024

AbstractInvasive membrane protrusions play a central role in a variety of cellular processes. Unlike filopodia, invasive protrusions are mechanically stiff and propelled by branched actin polymerization. However, how branched actin filaments are organized to create finger-like invasive protrusions is unclear. Here, by examining the mammalian fusogenic synapse, where invasive protrusions are generated to promote cell membrane juxtaposition and fusion, we have uncovered the mechanism underlying invasive protrusion formation. We show that two nucleation promoting factors (NPFs) for the Arp2/3 complex, WAVE and N-WASP, exhibit different localization patterns in the protrusions. While WAVE is closely associated with the plasma membrane at the leading edge of the protrusive structures, N-WASP is enriched with WIP along the actin bundles in the shafts of the protrusions. During protrusion initiation and growth, the Arp2/3 complex nucleates branched actin filaments to generate low density actin clouds, in which the large GTPase dynamin organizes the new branched actin filaments into bundles, followed by actin-bundle stabilization by WIP, the latter functioning as a novel actin-bundling protein. Disrupting any of these components results in defective protrusions and failed myoblast fusion in cultured cells and mouse embryos. Taken together, our study has revealed the intricate spatiotemporal coordination between two NPFs and two actin-bundling proteins in building invasive protrusions at the mammalian fusogenic synapse, and has general implications in understanding invasive protrusion formation in cellular processes beyond cell-cell fusion.
A liver function test score identifies high-risk MASLD patients based on the pattern of liver enzymes
Authors: Hajaj Emma , Bendersky Ahinoam Glusman , Braun Marius , Shlomai Amir 
Published: October 2024

AbstractBackground & AimsA cholestatic pattern of liver enzymes is associated with progressive liver disease and major adverse liver-related outcomes (MALO) among patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We aimed to authenticate the efficacy of a newly formulated liver function test (LFT) score for distinguishing patients with cholestatic vs. hepatocellular patterns and to evaluate its prognostic utility in MASLD patients.MethodsA retrospective longitudinal study on a dataset of over 250,000 individuals diagnosed with MASLD and/or obesity with cardiovascular risk factors. Patients were categorized into cholestatic (C), mixed (M), or hepatocellular (H) patterns according to the LFT score, or the well-known R score. Long-term MALO, major adverse cardiovascular events (MACE), and all-cause mortality were tracked.ResultsThe LFT score excelled in differentiating patients into C, M, or H groups accurately. While about two-thirds of our cohort initially showed a low FIB4 (<1.3), patients in the C category experienced a higher incidence of MALO and MACE compared to those in the H category (0.5% vs. 0.2% and 7.1% vs. 3.6%, respectively) over the span of 10 years post-diagnosis. Additionally, the 15-year overall survival rate was notably lower for C patients compared to their H counterparts (63% vs. 77%, p<0.0001). The LFT score was more effective than the R score in distinguishing between H and C patients for prognostic purposes, and a baseline cholestatic pattern indicates poorer outcomes regardless of subsequent LFT changes.ConclusionsThe LFT score accurately categorizes cholestatic MASLD patients and may serve as a useful prognostic tool.
Integrating explainable machine learning and transcriptomics data reveals cell-type specific immune signatures underlying macular degeneration
Authors: Ma Khang , Nakajima Hosei , Basak Nipa , Barman Arko , Ratnapriya Rinki 
Published: October 2024

ABSTRACTGenome-wide association studies (GWAS) have established a key role of dysfunctional immune response in the etiology of Age-related Macular Degeneration (AMD). However, immune cells constitute a small proportion of the retina, and their role in AMD is not completely resolved. Here we develop an explainable machine learning pipeline using transcriptome data 453 donor retinas, identifying 81 genes distinguishing AMD from controls with an AUC-ROC of 0.80 (CI 0.70-0.92). These genes show enrichment for pathways involved in immune response, complement and extracellular matrix and connected to known AMD genes through co-expression networks and gene expression correlation. The majority of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where several of these candidate genes exhibited differential expression. Finally, the integration of AMD-GWAS data identified a common regulatory variant, rs4133124 atPLCG2, as a novel AMD-association. Collectively, our study provides molecular insights into the recurring theme of immune dysfunction in AMD and highlights the significance of glial cell differences as an important determinant of AMD progression.
Systematic standardization of organ-on-a-chip under controlled flow conditions: use case with Caki-1 and A549 cell lines
Authors: Balsa-Díaz Andrea , Vázquez-Vázquez Laura , Ferreiro-Vila Elías , Rivas-Meizoso Lois , Martínez Antón L. , Brea José Manuel , Loza María Isabel , Rodriguez Santiago Pérez , Sinde Esteban , Alvarez Ezequiel , Rodiño-Janeiro Bruno K. 
Published: October 2024

AbstractNewin vitromodels are an urgent need for to improve both the research data and the preclinical development of new drugs. Current standardized cellular models are mainly based in 2D cell culture, which lacks flow conditions and with complex co-culture settings. In this way, advanced cell culture models, such as organ-on-a-chip (OoC), aim to solve these limitations. OoC systems are composed by a microfluidic chip functionalized with different combinations of extracellular matrixes, coatings and cell cultures to mimic the physiological conditions of human organs. Advantages of OoC include the possibility to add 3D structures, delimited regions for co-culture and dynamic flow conditions to cell cultures. However, to perform reproducible and controlled experiments with OoC, it is necessary to systematically standardize the cell culture conditions in the microfluidic channels. For this is necessary to test both the combination of flow and extracellular matrix (ECM) coating to reliably mimic the human organ physiology. In this work, we standardized both conditions, ECM coating and the flow conditions to functionalize OoC with cell lines from kidney (Caki-1) and from lung (A549) to develop OoC systems beyond the Vessel-on-a-chip setting. In this way, the protocol detailed in this work will allow to standardize cell culture on different optimized OoC types with different cell types from different origins.
Autocatalytic assembly of a chimeric aminoacyl-RNA synthetase ribozyme
Authors: Radakovic Aleksandar , Todisco Marco , Mishra Anmol , Szostak Jack W. 
Published: October 2024

AbstractAutocatalytic reactions driving the self-assembly of biological polymers are important for the origin of life, yet few experimental examples of such reactions exist. Here we report an autocatalytic assembly pathway that generates a chimeric, amino acid-bridged aminoacyl-RNA synthetase ribozyme. The noncovalent complex of ribozyme fragments initiates low level aminoacylation of one of the fragments, which after loop-closing ligation generates a highly active covalently-linked chimeric ribozyme. The generation of this ribozyme is increasingly efficient over time due to the autocatalytic assembly cycle that sustains the ribozyme over indefinite cycles of serial dilution. Due to itstransactivity, this ribozyme also assembles ribozymes distinct from itself, such as the hammerhead, suggesting that RNA aminoacylation, coupled with nonenzymatic ligation, could have facilitated the emergence and propagation of ribozymes.
Personalized azithromycin treatment rules for children with watery diarrhea using machine learning
Authors: Kim Sara S , Codi Allison , Platts-Mills James A. , Pavlinac Patricia , Manji Karim , Sudfeld Chris , Duggan Christopher P. , Dube Queen , Bar-Zeev Naor , Kotloff Karen , Sow Samba O , Sazawal Sunil , Singa Benson O , Walson Judd , Qamar Farah , Ahmed Tahmeed , De Costa Ayesha , Benkeser David , Rogawski McQuade Elizabeth T 
Published: October 2024

AbstractIntroductionWe used machine learning to identify novel strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit.MethodsUsing data from a randomized trial of azithromycin for watery diarrhea, we developed personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. For each rule, we estimated the proportion treated under the rule and the average benefits of treatment.ResultsAmong 6,692 children, treatment was recommended on average for approximately one third of children. The risk of diarrhea on day 3 was 10.1% lower (95% CI: 5.4, 14.9) with azithromycin compared to placebo among children recommended for treatment. For day 90 re-hospitalization and death, risk was 2.4% lower (95% CI: 0.6, 4.1) with azithromycin compared to placebo among those recommended for treatment. While pathogen diagnostics were strong determinants of azithromycin effects on diarrhea duration, host characteristics were more relevant for predicting benefits for re-hospitalization or death.ConclusionThe ability of host characteristics to predict which children benefit from azithromycin with respect to the most severe outcomes suggests appropriate targeting of antibiotic treatment among children with watery diarrhea may be possible without access to pathogen diagnostics.
Targeting ADORA-PDE10 cAMP Microdomain: A Novel Therapeutic Approach for Pulmonary Hypertension
Authors: Valasarajan Chanil , Hesami Golnaz , Maroli Giovanni , Cherian Anoop V. , Laria Julio Castro-palomino , Laria Nahomi Castro-Palomino , Wietelmann Astrid , Gnatzy-Feik Leoni , Rosenkranz Stephan , Savai Rajkumar , Seeger Werner , Pullamsetti Soni Savai 
Published: October 2024

SummaryDespite substantial advancements in the treatment of pulmonary arterial hypertension (PAH), obstacles remain in achieving optimal outcomes. In this study, we focus on understanding the therapeutic effect of targeting the ADORA1/PDE10A-regulated cyclic AMP (cAMP) microenvironment in treating pulmonary hypertension. Screening of differentially expressed adenosine receptors in samples derived from healthy individuals and patients with idiopathic pulmonary arterial hypertension (IPAH) showed that ADORA1 expression was significantly upregulated under disease conditions. Functional studies revealed that, upon ADORA1 inhibition, donor hPASMCs showed anti-proliferative, pro-apoptotic features and increased intracellular cAMP levels. Surprisingly, the same effects were not replicated in IPAH PASMCs, suggesting the presence of another cAMP regulatory factor in close proximity to ADORA1 in IPAH PASMCs. To investigate this point, we performed protein-protein interaction studies in IPAH PASMCs and found that Phosphodiestrase 10A (PDE10A) co-localizes with ADORA1 under disease conditions. Moreover, we observed that ADORA1 and PDE10A form a regulatory complex in the A kinase anchoring protein 5 (AKAP5) microdomain. Silencing or dual inhibition of both ADORA1 and PDE10A in IPAH PASMCs induced anti-proliferative and pro-apoptotic effects with increased intracellular cAMP levels. To investigate the effects of the dual inhibitor in vivo, we administered it to both MCT and Sugen5416/hypoxia (SuHx) rat models of PAH, showing improved right ventricle function, reduced pulmonary vascular resistance and decreased lung vascular remodeling. In conclusion, we provide evidence that dual pharmacological targeting of ADORA1 and PDE10A has high therapeutic potential against PAH.
TheNematostellaWnt/β-catenin destruction complex provides insight into the evolution of the regulation of a major metazoan signal transduction pathway
Authors: Sun Hongyan , Zidek Radim , Martindale Mark Q. , Wikramanayake Athula 
Published: October 2024

AbstractThe Wnt/β-catenin (cWnt) signaling pathway is one of the most important intercellular signaling pathways in animals. How cWnt components regulate the pathway in bilaterians is well understood, but these processes are poorly characterized in the earliest branching animal clades. We used the cnidarianNematostella(cnidarians are the closest bilaterian outgroup) to study the cWnt destruction complex (DC) which is the primary mechanism for regulating cytoplasmic concentrations of β-catenin. In bilaterians the DC scaffolding proteins Axin and APC directly interact and bind β-catenin to target it for proteolysis, but all non-bilaterian Axin and APC homologs lack the conserved domains required for bilaterian DC function. Using functional approaches, we show that inNematostellaAxin and APC-like proteins scaffold an active DC that is regulated differently than the bilaterian DC. Additionally, using AlphaFold software we discovered a sequence embedded in the Axin-RGS domain of non-bilaterian Axin that has homology to the bilaterian Axin β-catenin-binding motif (βcatBM). We propose that the bilaterian βcatBM evolved as a low-affinity β-catenin-interacting sequence in the Axin-RGS domain in pre-bilaterians and moved C-terminally in bilaterians where it acquired higher affinity for β-catenin. Our work provides novel insight into how regulatory modules can evolve in metazoan signaling pathways.
Transcriptional profiles of murine oligodendrocyte precursor cells across the lifespan
Authors: Heo Dongeun , Kim Anya A. , Neumann Björn , Doze Valerie N. , Xu Yu Kang T. , Mironova Yevgeniya A. , Slosberg Jared , Goff Loyal A. , Franklin Robin J. M. , Bergles Dwight E. 
Published: October 2024

AbstractOligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system (CNS) that are responsible for generating myelinating oligodendrocytes during development. By also generating new oligodendrocytes in the adult CNS, OPCs allow formation of new myelin sheaths in response to environmental and behavioral changes and play a crucial role in regenerating myelin following demyelination (remyelination). However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination, and adaptive myelination during learning. To determine how aging influences OPCs, we generated a novel transgenic mouse line that expresses membrane-anchored EGFP under the endogenous promoter/enhancer of Matrilin-4 (Matn4-mEGFP) and performed high-throughput single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescence to proliferation and differentiation across the lifespan. Comparative analysis of OPCs isolated from mice aged 30 to 720 days, revealed that aging induces distinct inflammatory transcriptomic changes in OPCs in different states, including enhanced activation of HIF-1α and Wnt pathways. Inhibition of these pathways in acutely isolated OPCs from aged animals restored their ability to differentiate, suggesting that this enhanced signaling may contribute to the decreased regenerative potential of OPCs with aging. ThisMatn4-mEGFPmouse line and single-cell mRNA datasets of cortical OPCs across ages help to define the molecular changes guiding their behavior in various physiological and pathological contexts.
Knowledge hiding, emotional exhaustion and job performance: the role of psychological resilience
Authors: Tran Pham Toan Khanh 
Published: October 2024

Purpose
As an emerging novelty, knowledge hiding has received considerable attention in management literature. Drawing on conversation of resources theory, this study aims to investigate how knowledge hiding impacts job performance among employees through the mediating role of emotional exhaustion. This work further offers deeper insight into the moderating mechanism of psychological resilience in these relationships.

Design/methodology/approach
Three time-lagged sets of data (N = 362) were collected among employees in Vietnamese firms. The partial least squares structural equation modeling method was applied to test the research hypotheses.

Findings
Empirical findings indicate that knowledge hiding positively impacts emotional exhaustion. Furthermore, emotional exhaustion serves a mediating role in the link between knowledge hiding and job performance. The results also show how psychological resilience moderates the relations between knowledge hiding, emotional exhaustion and job performance.

Practical implications
The findings suggest that managers can reduce the harms of knowledge-hiding behaviors by enriching employees’ resources and bolstering their psychological resilience.

Originality/value
This inquiry explores the mechanism linking knowledge-hiding behaviors and job performance through the mediator of emotional exhaustion. In addition, this study extends the current knowledge by investigating the moderating role of psychological resilience in the relations between knowledge-hiding, emotional exhaustion and job performance.
Text analysis and optimization strategy of an app’s privacy policy from the perspective of dual perception: taking Chinese shopping apps as an example
Authors: Wang Xu , Dai Chunyan , Wang Yazhao , Bao Linhao 
Published: October 2024

Purpose
This paper aims to conduct an in-depth analysis of the shortcomings of apps’ privacy policies and to propose improvement and optimization strategies, which are of great significance for establishing a transparent and responsible privacy protection framework that ensures compliant collection and use of users’ information and effective protection of their privacy.

Design/methodology/approach
This paper obtained privacy policy texts for 100 shopping apps through Web crawlers and manual downloads. Based on the perspective of perceived usefulness, thematic analysis is conducted through the latent Dirichlet allocation topic model and comparison with existing policies. Based on the perspective of perceived ease of use, readability analysis is conducted through content analysis and formula calculation.

Findings
The apps privacy policies can be divided into seven themes. The authors benchmark these seven topics with the Personal Information Protection Law of the People’s Republic of China, the E-Commerce Law of the People’s Republic of China and the General Data Protection Regulation. It is found that there are omissions in the information collection and use and juvenile protection of the existing apps. Through the indicators’ readability analysis and calculation, it is found that the existing apps privacy policies have good performance in the readability indicators such as naming method, frame directory and so on. However, text personalization and text readability need to be improved and optimized.

Originality/value
At the theoretical level, this paper constructs a model from the dual perception perspectives of perceived usefulness and perceived ease of use and analyses the apps’ privacy policy texts at a fine-grained level. At the practical level, based on large-scale apps’ privacy policy text data, this paper conducts multi-dimensional research from theme analysis, authoritative law benchmarking analysis, content analysis and text readability calculation and analysis. At the same time, this paper identifies the current problems of apps’ privacy policies and puts forward countermeasure suggestions for their content improvement and optimization.