bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling a Potential Prognostic Biomarker in KRAS-Mutant Lung Adenocarcinoma Using Weighted Gene Co-Expression Network Analysis
Authors: Dodin Yasmeen 
Published: August 2023

AbstractBackgroundGlobally, lung cancer is the leading cause of cancer-related deaths, primarily non-small cell lung cancer (NSCLC). Kirsten Rat Sarcoma Oncogene Homolog (KRAS) mutations are common in NSCLC and linked to a poor prognosis. Covalent inhibitors targeting KRAS-G12C mutation have improved treatment for some patients, but most KRAS-mutant lung adenocarcinoma (KRAS-MT LUAD) cases lack targeted therapies. More research is required to identify prognostic genes in KRAS-MT LUAD.ObjectiveWe aimed to identify hub genes within key co-expression gene network modules specifically associated with KRAS-MT LUAD. These hub genes hold the potential to serve as therapeutic targets or biomarkers, providing insights into the pathogenesis and prognosis of lung cancer.MethodsWe performed a comprehensive analysis on KRAS-MT LUAD using diverse data sources. This included TCGA project data for RNA-seq, clinical information, and somatic mutations, along with RNA-seq data for adjacent normal tissues. DESeq2 identified differentially expressed genes (DEGs), while weighted gene co-expression network analysis (WGCNA) revealed co-expression modules. Overlapping genes between DEGs and co-expression module with the highest significance were analyzed using gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis. Hub genes were identified with the Maximal Clique Centrality (MCC) algorithm in Cytoscape. Prognostic significance was assessed through survival analysis and validated using the GSE72094 dataset from Gene Expression Omnibus (GEO) database.ResultsIn KRAS-MT LUAD, 3,122 DEGs were found (2,131 up-regulated, 985 down-regulated). The blue module, among 25 co-expression modules from WGCNA, had the strongest correlation. 804 genes overlapped between DEGs and the blue module. Among twenty hub genes in the blue module, leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) overexpression correlated with worse overall survival (OS) in KRAS-MT LUAD patients (P=0.012). The prognostic significance of LGR4 was confirmed using GSE72094, but surprisingly, the direction of the association was opposite to what was expected.ConclusionLGR4 is a potential prognostic biomarker in KRAS-MT LUAD. Contrasting associations in TCGA and GSE72094 datasets reveal the complexity of KRAS-MT LUAD. Further investigations are required to understand LGR4’s role in lung adenocarcinoma prognosis, especially in the context of KRAS mutations.
Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection
Authors: Resnick Jessica D. , Wilson Jo L. , Anaya Eddy , Conte Abigail , Li Maggie , Zhong William , Beer Michael A. , Pekosz Andrew 
Published: August 2023

ABSTRACTPrimary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue. In this study, two different expansion medias were evaluated and the impact on the resulting differentiated culture was determined. Use of both Airway and Ex Plus media types resulted in high quality, consistent cultures that were able to be used for these studies. Upon histological evaluation, Airway-grown cultures were more organized and had a higher proportion of basal progenitor cells while Ex Plus-grown cultures had a higher proportion terminally differentiated cell types. In addition to having different cell type proportions and organization, the two different growth medias led to cultures with altered susceptibility to infection with SARS-CoV-2 but not Influenza A virus. RNAseq comparing cultures grown in different growth medias prior to differentiation uncovered a high degree of differentially expressed genes in cultures from the same donor. RNAseq on differentiated cultures showed less variation between growth medias but alterations in pathways that control the expression of human transmembrane proteases includingTMPRSS11andTMPRSS2were documented. Enhanced susceptibility to SARS-CoV-2 cannot be explained by altered cell type proportions alone, rather serine protease cofactor expression also contributes to the enhanced replication of SARS-CoV-2 as inhibition with camostat affected replication of an early SARS-CoV-2 variant and a Delta, but not Omicron, variant showed difference in replication efficiency between culture types. Therefore, it is important for the research community to standardize cell culture protocols particularly when characterizing novel viruses.
Generative Methods for Pediatric Genetics Education
Authors: Waikel Rebekah L. , Othman Amna A. , Patel Tanviben , Hanchard Suzanna Ledgister , Hu Ping , Tekendo-Ngongang Cedrik , Duong Dat , Solomon Benjamin D. 
Published: August 2023

AbstractArtificial intelligence (AI) is used in an increasing number of areas, with recent interest in generative AI, such as using ChatGPT to generate programming code or DALL-E to make illustrations. We describe the use of generative AI in medical education. Specifically, we sought to determine whether generative AI could help train pediatric residents to better recognize genetic conditions. From publicly available images of individuals with genetic conditions, we used generative AI methods to create new images, which were checked for accuracy with an external classifier. We selected two conditions for study, Kabuki (KS) and Noonan (NS) syndromes, which are clinically important conditions that pediatricians may encounter. In this study, pediatric residents completed 208 surveys, where they each classified 20 images following exposure to one of 4 possible educational interventions, including with and without generative AI methods. Overall, we find that generative images perform similarly but appear to be slightly less helpful than real images. Most participants reported that images were useful, although real images were felt to be more helpful. We conclude that generative AI images may serve as an adjunctive educational tool, particularly for less familiar conditions, such as KS.
A versatile framework for drug-target interaction prediction by considering domain specific features
Authors: Liu Shuo , Yu Jialiang , Ni Ningxi , Wang Zidong , Chen Mengyun , Li Yuquan , Xu Chen , Ding Yahao , Zhang Jun , Yao Xiaojun , Liu Huanxiang 
Published: August 2023

AbstractPredicting drug-target interaction (DTI) is a critical and rate-limiting step in drug discovery. Traditional wet-lab experiments are reliable but expensive and time-consuming. Recently, deep learning has revealed itself as a new and promising tool for accelerating the DTI prediction process because its powerful performance. Due to the vast chemical space, the DTI prediction models are typically expected to discover drugs or targets that are absent from the training set. However, generalizing prediction performance to novel drug-target pairs that belong to different distributions is a challenge for deep learning methods. In this work, we propose an Ensemble of models that capture both Domain-generIc and domain-Specific features (E-DIS) to learn diversity domain features and adapt to out-of-distribution (OOD) data. We employed Mixture-of-Experts (MOE) as a domain-specific feature extractor for the raw data to prevent the loss of any crucial features by the encoder during the learning process. Multiple experts are trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. We evaluate our approach using four benchmark datasets under both in-domain and cross-domain settings and compare it with advanced approaches for solving OOD generalization problems. The results demonstrate that E-DIS effectively improves the robustness and generalizability of DTI prediction models by incorporating diversity domain features.
Tremors in Time: Mechanically Induced Motor Tremors Influence Time Perception
Authors: Gladhill Keri Anne , De Kock Rose , Zhou Weiwei , Joiner Wilsaan Mychal , Wiener Martin 
Published: August 2023

AbstractContemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates, in accordance with Bayesian cue combination. However, a critical test of this framework is that by introducing “noise” into movements, sensory estimates of time should similarly become noisier in a manner predicted by cue combination equations. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities (n=24, ea.). Crucially, we introduced an artificial “tremor” in the arm while subjects were moving, that varied across three levels of amplitude (1-3 N) or frequency (4-12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration, but in such a way that higher levels of noise saturated the impact, consistent with optimal integration. Further, the effect of noise varied with the base precision of the interval, such that a naturally less precise timing (i.e. visual) was more influenced by the tremor than a naturally more precise modality (i.e. auditory). To explain these findings, we fit the data with a recently developed drift-diffusion model of perceptual decision making, in which the momentary, within-trial variance was allowed to vary across conditions. Here, we found that the model could recapitulate the observed findings, further supporting the theory that movements influence perception directly. Overall, our findings support the proposed framework, and demonstrate the utility of inducing motor noise via artificial tremors, thus providing clinical utility in their connection to movement disorders characterized by tremors.
Inhibition of Topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats
Authors: Amoiridis Michalis , Meaburn Karen , Verigos John , Gittens William H , Ye Tao , Neale Matthew J , Soutoglou Evi 
Published: August 2023

AbstractDNA replication and transcription generate DNA supercoiling, which can cause topological stress and intertwining of daughter chromatin fibers, posing challenges to the completion of DNA replication and chromosome segregation. Type II topoisomerases (Top2s) are enzymes that relieve DNA supercoiling and decatenate braided sister chromatids. How Top2 complexes deal with the topological challenges in different chromatin contexts, and whether all chromosomal contexts are subjected equally to torsional stress and require Top2 activity is unknown. Here we show that catalytic inhibition of the Top2 complex in interphase has a profound effect on the stability of heterochromatin and repetitive DNA elements. Mechanistically, we find that catalytically inactive Top2 is trapped around heterochromatin leading to DNA breaks and unresolved catenates, which necessitate the recruitment of the structure specific endonuclease, Ercc1-XPF, in an Slx4- and SUMO-dependent manner. Our data are consistent with a model in which Top2 complex resolves not only catenates between sister chromatids but also inter-chromosomal catenates between clustered repetitive elements.
Integration of Euclidean and path distances in hippocampal maps
Authors: Ottink L. , de Haas N. , Doeller C.F. 
Published: August 2023

AbstractThe hippocampus is a key region for forming mental maps of our environment. These maps represent spatial information such as distances between landmarks. A cognitive map can allow for flexible inference of spatial relationships that have never been directly experienced before. Previous work has shown that the human hippocampus encodes distances between locations, but it is unclear how Euclidean and path distances are distinguished. In this study, participants performed an object-location task in a virtual environment. We combined functional magnetic resonance imaging with representational similarity analysis to test how Euclidean and path distances are represented in the hippocampus. We observe that hippocampal neural pattern similarity for objects scales with Euclidean as well as path distance between object locations, suggesting that the hippocampus integrates both types of distances. One key characteristic of cognitive maps is their adaptive and flexible nature. We therefore subsequently modified path distances between objects using roadblocks in the environment. We found that hippocampal pattern similarity between objects adapted as a function of these changes in path distance, selectively in egocentric navigators but not in allocentric navigators Taken together, our study supports the idea that the hippocampus creates integrative and flexible cognitive maps.
High-throughput and genome-scale targeted mutagenesis using CRISPR in a non-model multicellular organism,Bombyx mori
Authors: Ma Sanyuan , Zhang Tong , Wang Ruolin , Wang Pan , Liu Yue , Chang Jiasong , Wang Aoming , Lan Xinhui , Sun Le , Sun Hao , Shi Run , Lu Wei , Liu Dan , Zhang Na , Hu Wenbo , Wang Xiaogang , Xing Weiqing , Jia Ling , Xia Qingyou 
Published: August 2023

AbstractLarge-scale genetic mutant libraries are powerful approaches to interrogating genotype-phenotype correlations and identifying genes responsible for certain environmental stimuli, both of which are the central goal of life science study. We produced the first large-scale CRISPR/Cas9-induced library in a non-model multicellular organism,Bombyx mori. We developed apiggyBac-delivered binary genome editing strategy, which can simultaneously meet the requirements of mixed microinjection, efficient multi-purpose genetic operation, and preservation of growth-defect lines. We constructed a single-guide RNA (sgRNA) plasmid library containing 92,917 sgRNAs targeting promoters and exons of 14,645 protein-coding genes, established 1726 transgenic sgRNA lines following microinjection of 66,650 embryos, and generated 300 mutant lines with diverse phenotypic changes. Phenomic characterization of mutant lines identified a large set of genes responsible for visual phenotypic or economically valuable trait changes. Next, we performed pooled context-specific positive screens for tolerance to environmental pollute cadmium exposure, and identified KWMTBOMO12902 as a strong candidate gene for breeding applications in sericulture industry. Collectively, our results provide a novel and versatile approach for functionalB. morigenomics, and a powerful resource for identifying key candidate genes potential for improving various economic traits. This study also demonstrates the effectiveness, practicality, and convenience of large-scale mutant libraries in other non-model organisms.
Molecular profiling of sponge deflation reveals an ancient relaxant-inflammatory response
Authors: Ruperti Fabian , Becher Isabelle , Stokkermans Anniek , Wang Ling , Marschlich Nick , Potel Clement , Maus Emanuel , Stein Frank , Drotleff Bernhard , Schippers Klaske , Nickel Michael , Prevedel Robert , Musser Jacob M , Savitski Mikhail M , Arendt Detlev 
Published: August 2023

A hallmark of animals is the coordination of whole-body movement. Neurons and muscles are central to this, yet coordinated movements also exist in sponges that lack these cell types. Sponges are sessile animals with a complex canal system for filter-feeding. They undergo whole-body movements resembling “contractions” that lead to canal closure and water expulsion. Here, we combine 3D optical coherence microscopy, pharmacology, and functional proteomics to elucidate anatomy, molecular physiology, and control of these movements. We find them driven by the relaxation of actomyosin stress fibers in epithelial canal cells, which leads to whole-body deflation via collapse of the incurrent and expansion of the excurrent system, controlled by an Akt/NO/PKG/A pathway. A concomitant increase in reactive oxygen species and secretion of proteinases and cytokines indicate an inflammation-like state reminiscent of vascular endothelial cells experiencing oscillatory shear stress. This suggests an ancient relaxant-inflammatory response of perturbed fluid-carrying systems in animals.HighlightsSponge deflation is driven by tension release in actomyosin stress fibers of epithelial pinacocytesAkt kinase/Nitric oxide/Protein kinase G/A regulate actomyosin relaxationAgitation-induced deflation coincides with an inflammatory stateThe sponge relaxant-inflammatory response is evolutionary related to similar responses in the vertebrate vascular system
Molecular Basis of Cell Membrane Adaptation in Daptomycin-ResistantEnterococcus faecalis
Authors: Nguyen April H. , Tran Truc T. , Panesso Diana , Hood Kara , Polamraju Vinathi , Zhang Rutan , Khan Ayesha , Miller William R. , Mileykovskaya Eugenia , Shamoo Yousif , Xu Libin , Vitrac Heidi , Arias Cesar A. 
Published: August 2023

AbstractDaptomycin is a last-resort lipopeptide antibiotic that disrupts cell membrane (CM) and peptidoglycan homeostasis. Enterococcus faecalis has developed a sophisticated mechanism to avoid daptomycin killing by re-distributing CM anionic phospholipids away from the septum. The CM changes are orchestrated by a three-component regulatory system, designated LiaFSR, with a possible contribution of cardiolipin synthase (Cls). However, the mechanism by which LiaFSR controls the CM response and the role of Cls are unknown. Here, we show that cardiolipin synthase activity is essential for anionic phospholipid redistribution and daptomycin resistance since deletion of the two genes (cls1andcls2) encoding Cls abolished CM remodeling. We identified LiaY, a transmembrane protein regulated by LiaFSR, as an important mediator of CM remodeling required for re-distribution of anionic phospholipid microdomains via interactions with Cls1. Together, our insights provide a mechanistic framework on the enterococcal response to cell envelope antibiotics that could be exploited therapeutically.
Introduction to special issue on ethnographies of accountability
Authors: Cordery Carolyn J. , De Loo Ivo , Letiche Hugo 
Published: August 2023

PurposeThis paper aims to outline the motivation for this Accounting, Auditing and Accountability Journal (AAAJ) Special Issue, providing an overview of the six selected papers. This study seeks to inspire further ethnographic research on accountability.Design/methodology/approachThe authors reflect on why ethnographic investigation is essential to accountability research and the boundaries that constrained and enabled both this Special Issue and which occur in ethnographic research.FindingsThe contents of this issue do not merely describe or analyse one or more “accounts”, but also consider how the accounted for reflects its surroundings and its role in the social world. The authors argue that such research should progress from ethnographic descriptive data to infer meaningful conclusions and move from the everyday natural settings of behaviour to examine inter-relatedness. This requires the researcher to maintain their intra-relatedness. These boundaries, inherent to human existence, are actively created and operate at different aggregation levels to include and exclude.Research limitations/implicationsIn this introduction and the papers selected for this AAAJ special issue, with few exceptions, accountability shifts from the researched to the researcher as research accounts are produced. Yet, ethnographies of accountability are epistemologically and ontologically weighted towards accepting the possibility of shared social meaning requiring researchers to manage the interactions, relationalities and presuppositions between these places. The authors urge future researchers to experiment more explicitly than has often been the case with published accounts of these demands.Originality/valueThis AAAJ Special Issue provides a set of original empirical and theoretical contributions to support and advance further ethnographic research into accountability which acknowledges the boundaries that may include and exclude.
An ontological assessment proposal for architectural outputs of generative adversarial network
Authors: Uzun Can , Cangür Raşit Eren 
Published: August 2023

PurposeThis study presents an ontological approach to assess the architectural outputs of generative adversarial networks. This paper aims to assess the performance of the generative adversarial network in representing building knowledge.Design/methodology/approachThe proposed ontological assessment consists of five steps. These are, respectively, creating an architectural data set, developing ontology for the architectural data set, training the You Only Look Once object detection with labels within the proposed ontology, training the StyleGAN algorithm with the images in the data set and finally, detecting the ontological labels and calculating the ontological relations of StyleGAN-generated pixel-based architectural images. The authors propose and calculate ontological identity and ontological inclusion metrics to assess the StyleGAN-generated ontological labels. This study uses 300 bay window images as an architectural data set for the ontological assessment experiments.FindingsThe ontological assessment provides semantic-based queries on StyleGAN-generated architectural images by checking the validity of the building knowledge representation. Moreover, this ontological validity reveals the building element label-specific failure and success rates simultaneously.Originality/valueThis study contributes to the assessment process of the generative adversarial networks through ontological validity checks rather than only conducting pixel-based similarity checks; semantic-based queries can introduce the GAN-generated, pixel-based building elements into the architecture, engineering and construction industry.