bioRxiv : the preprint server for biology最新文献

{"title":"How a disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization.","authors":"Tim M Gemeinhardt, Roshan M Regy, Tien M Phan, Nanu Pal, Jyoti Sharma, Olga Senkovich, Andrea J Mendiola, Heather J Ledterman, Amy Henrickson, Daniel Lopes, Utkarsh Kapoor, Ashish Bihani, Djamouna Sihou, Young C Kim, David Jeruzalmi, Borries Demeler, Chongwoo A Kim, Jeetain Mittal, Nicole J Francis","doi":"10.1101/2023.10.26.564264","DOIUrl":"10.1101/2023.10.26.564264","url":null,"abstract":"<p><p>Biomolecular condensates are increasingly appreciated for their function in organizing and regulating biochemical processes in cells, including chromatin function. Condensate formation and properties are encoded in protein sequence but the mechanisms linking sequence to macroscale properties are incompletely understood. Cross species comparisons can reveal mechanisms either because they identify conserved functions or because they point to important differences. Here we use <i>in vitro</i> reconstitution and molecular dynamics simulations to compare <i>Drosophila</i> and human sequences that regulate condensate formation driven by the sterile alpha motif (SAM) oligomerization domain in the Polyhomeotic (Ph) subunit of the chromatin regulatory complex PRC1. We discover evolutionarily diverged contacts between the conserved SAM and the disordered linker that connects it to the rest of Ph. Linker-SAM interactions increase oligomerization and regulate formation and properties of reconstituted condensates. Oligomerization affects condensate dynamics but, in most cases, has little effect on their formation. Linker-SAM interactions also affect condensate formation in <i>Drosophila</i> and human cells, and growth in <i>Drosophila</i> imaginal discs. Our data show how evolutionary sequence changes in linkers connecting conserved structured domains can alter condensate properties.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tree-based differential testing using inferential uncertainty for RNA-Seq.","authors":"Noor Pratap Singh, Euphy Y Wu, Jason Fan, Michael I Love, Rob Patro","doi":"10.1101/2023.12.25.573288","DOIUrl":"10.1101/2023.12.25.573288","url":null,"abstract":"<p><p>Identifying differentially expressed transcripts poses a crucial yet challenging problem in transcriptomics. Substantial uncertainty is associated with the abundance estimates of certain transcripts which, if ignored, can lead to the exaggeration of false positives and, if included, may lead to reduced power. Given a set of RNA-Seq samples, TreeTerminus arranges transcripts in a hierarchical tree structure that encodes different layers of resolution for interpretation of the abundance of transcriptional groups, with uncertainty generally decreasing as one ascends the tree from the leaves. We introduce mehenDi, which utilizes the tree structure from TreeTerminus for differential testing. The nodes output by mehenDi, called the selected nodes are determined in a data-driven manner to maximize the signal that can be extracted from the data while controlling for the uncertainty associated with estimating the transcript abundances. The identified selected nodes can include transcripts and inner nodes, with no two nodes having an ancestor/descendant relationship. We evaluated our method on both simulated and experimental datasets, comparing its performance with other tree-based differential methods as well as with uncertainty-aware differential transcript/gene expression methods. Our method detects inner nodes that show a strong signal for differential expression, which would have been overlooked when analyzing the transcripts alone.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation.","authors":"Célia Guérin, Audrey Vinchent, Marie Fernandes, Isabelle Damour, Agathe Laratte, Rémi Tellier, Gabriella O Estevam, Jean-Pascal Meneboo, Céline Villenet, Clotilde Descarpentries, James S Fraser, Martin Figeac, Alexis B Cortot, Etienne Rouleau, David Tulasne","doi":"10.1101/2023.11.03.565283","DOIUrl":"10.1101/2023.11.03.565283","url":null,"abstract":"<p><p>In hereditary papillary renal cell carcinoma (HPRCC), the hepatocyte growth factor receptor (MET) receptor tyrosine kinase (RTK) mutations recorded to date are located in the kinase domain and lead to constitutive MET activation. This contrasts with MET mutations identified in non-small cell lung cancer (NSCLC), which lead to exon 14 skipping and deletion of a regulatory domain: in this latter case, the mutated receptor still requires ligand stimulation. Sequencing of MET in samples from 158 HPRCC and 2808 NSCLC patients revealed ten uncharacterized mutations. Four of these, all found in HPRCC and leading to amino acid substitutions in the N-lobe of the MET kinase, proved able to induce cell transformation, which was further enhanced by hepatocyte growth factor (HGF) stimulation: His1086Leu, Ile1102Thr, Leu1130Ser and Cis1125Gly. Similar to the variant resulting in MET exon 14 skipping, the two N-lobe MET variants His1086Leu and Ile1102Thr were found to require stimulation by HGF in order to strongly activate downstream signaling pathways and epithelial cell motility. The Ile1102Thr mutation also displayed transforming potential, promoting tumor growth in a xenograft model. In addition, the N-lobe-mutated MET variants were found to trigger a common HGF-stimulation-dependent transcriptional program, consistent with an observed increase in cell motility and invasion. Altogether, this functional characterization revealed that N-lobe variants still require ligand stimulation, in contrast to other RTK variants. This suggests that HGF expression in the tumor microenvironment is important for tumor growth. The sensitivity of these variants to MET inhibitors opens the way for use of targeted therapies for patients harboring the corresponding mutations.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107593017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Location- and feature-based selection histories make independent, qualitatively distinct contributions to urgent visuomotor performance.","authors":"Emily E Oor, Emilio Salinas, Terrence R Stanford","doi":"10.1101/2024.05.29.596532","DOIUrl":"10.1101/2024.05.29.596532","url":null,"abstract":"<p><p>Attention mechanisms guide visuomotor behavior by weighing physical salience and internal goals to prioritize stimuli as choices for action. Although less well studied, selection history, which reflects multiple facets of experience with recent events, is increasingly recognized as a distinct source of attentional bias. To examine how selection history impacts saccadic choices, we trained two macaque monkeys to perform an urgent version of an oddball search task in which a red target appeared among three green distracters, or vice versa. By imposing urgency, performance could be tracked continuously as it transitioned from uninformed guesses to informed choices as a function of processing time. This, in turn, permitted assessment of attentional control as manifest in motor biases, processing speed, and asymptotic accuracy. Here, we found that the probability of making a correct choice was strongly modulated by the histories of preceding target locations and target colors. Crucially, although both effects were gated by success (or reward), their dynamics were clearly distinct: whereas location history promoted a motor bias, color history modulated perceptual sensitivity, and these influences acted independently. Thus, combined selection histories can give rise to enormous swings in visuomotor performance even in simple tasks with highly discriminable stimuli.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automatic learning mechanisms for flexible human locomotion.","authors":"Cristina Rossi, Kristan A Leech, Ryan T Roemmich, Amy J Bastian","doi":"10.1101/2023.09.25.559267","DOIUrl":"10.1101/2023.09.25.559267","url":null,"abstract":"<p><p>Movement flexibility and automaticity are necessary to successfully navigate different environments. When encountering difficult terrains such as a muddy trail, we can change how we step almost immediately so that we can continue walking. This flexibility comes at a cost since we initially must pay deliberate attention to how we are moving. Gradually, after a few minutes on the trail, stepping becomes automatic so that we do not need to think about our movements. Canonical theory indicates that different adaptive motor learning mechanisms confer these essential properties to movement: explicit control confers rapid flexibility, while forward model recalibration confers automaticity. Here we uncover a distinct mechanism of treadmill walking adaptation - an automatic stimulus-response mapping - that confers both properties to movement. The mechanism is flexible as it learns stepping patterns that can be rapidly changed to suit a range of treadmill configurations. It is also automatic as it can operate without deliberate control or explicit awareness by the participants. Our findings reveal a tandem architecture of forward model recalibration and automatic stimulus-response mapping mechanisms for walking, reconciling different findings of motor adaptation and perceptual realignment.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557598/pdf/nihpp-2023.09.25.559267v1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Click-Based Determination of Accumulation of Molecules in <i>Escherichia coli</i>.","authors":"George M Ongwae, Zichen Liu, Shasha Feng, Mahendra D Chordia, Mohammad Sharifian Gh, Rachita Dash, Brianna E Dalesandro, Taijie Guo, Karl Barry Sharpless, Jiajia Dong, M Sloan Siegrist, Wonpil Im, Marcos M Pires","doi":"10.1101/2023.06.20.545103","DOIUrl":"10.1101/2023.06.20.545103","url":null,"abstract":"<p><p>Gram-negative bacterial pathogens pose a significant challenge in drug development due to their outer membranes, which impede the permeation of small molecules. The lack of widely adoptable methods to measure the cytosolic accumulation of compounds in bacterial cells has hindered drug discovery efforts. To address this challenge, we developed the CHloroalkane Azide Membrane Permeability (CHAMP) assay, specifically designed to assess molecule accumulation in the cytosol of Gram-negative bacteria. The CHAMP analysis utilizes biorthogonal epitopes anchored within HaloTag-expressing bacteria and measures the cytosolic arrival of azide-bearing test molecules through strain-promoted azide-alkyne cycloaddition. This workflow allows for robust and rapid accumulation measurements of thousands of azide-tagged small molecules. Our approach consistently yields a large number of accumulation profiles, significantly exceeding the scale of previous measurements in <i>Escherichia coli</i> ( <i>E. coli</i> ). We have validated the CHAMP assay across various chemical and biological contexts, including hyperporinated cells, membrane-permeabilized cells, and E. coli strains with impaired TolC function, a key component of the efflux pump. The CHAMP platform provides a simple, high-throughput, and accessible method that enables the analysis of over 1,000 molecules within hours. This technique addresses a critical gap in antimicrobial research, potentially accelerating the development of effective agents against Gram-negative pathogens.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78168150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure of the Thin Filament in Human iPSC-derived Cardiomyocytes and its Response to Heart Disease.","authors":"Rahel A Woldeyes, Masataka Nishiga, Alison S Vander Roest, Leeya Engel, Prerna Giri, Gabrielle C Montenegro, Alexander R Dunn, James A Spudich, Daniel Bernstein, Michael F Schmid, Joseph C Wu, Wah Chiu","doi":"10.1101/2023.10.26.564098","DOIUrl":"10.1101/2023.10.26.564098","url":null,"abstract":"<p><p>Cardiovascular diseases are a leading cause of death worldwide, but our understanding of the underlying mechanisms is limited, in part because of the complexity of the cellular machinery that controls the heart muscle contraction cycle. Cryogenic electron tomography (cryo-ET) provides a way to visualize diverse cellular machinery while preserving contextual information like subcellular localization and transient complex formation, but this approach has not been widely applied to the study of heart muscle cells (cardiomyocytes). Here, we deploy an optimized cryo-ET platform that enables cellular-structural biology in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using this platform, we reconstructed sub-nanometer resolution structures of the human cardiac muscle thin filament, a central component of the contractile machinery. Reconstructing the troponin complex, a regulatory component of the thin filament, from within cells, we identified previously unobserved conformations that highlight the structural flexibility of this regulatory complex. We next measured the impact of chemical and genetic perturbations associated with cardiovascular disease on the structure of troponin. In both cases, we found changes in troponin structure that are consistent with known disease phenotypes-highlighting the value of our approach for dissecting complex disease mechanisms in the cellular context.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell type analysis of wing premotor circuits in the ventral nerve cord of <i>Drosophila melanogaster</i>.","authors":"Erica Ehrhardt, Samuel C Whitehead, Shigehiro Namiki, Ryo Minegishi, Igor Siwanowicz, Kai Feng, Hideo Otsuna, Geoffrey W Meissner, David Stern, Jim Truman, David Shepherd, Michael H Dickinson, Kei Ito, Barry J Dickson, Itai Cohen, Gwyneth M Card, Wyatt Korff","doi":"10.1101/2023.05.31.542897","DOIUrl":"10.1101/2023.05.31.542897","url":null,"abstract":"<p><p>To perform most behaviors, animals must send commands from higher-order processing centers in the brain to premotor circuits that reside in ganglia distinct from the brain, such as the mammalian spinal cord or insect ventral nerve cord. How these circuits are functionally organized to generate the great diversity of animal behavior remains unclear. An important first step in unraveling the organization of premotor circuits is to identify their constituent cell types and create tools to monitor and manipulate these with high specificity to assess their functions. This is possible in the tractable ventral nerve cord of the fly. To generate such a toolkit, we used a combinatorial genetic technique (split-GAL4) to create 195 sparse transgenic driver lines targeting 196 individual cell types in the ventral nerve cord. These included wing and haltere motoneurons, modulatory neurons, and interneurons. Using a combination of behavioral, developmental, and anatomical analyses, we systematically characterized the cell types targeted in our collection. In addition, we identified correspondences between the cells in this collection and a recent connectomic data set of the ventral nerve cord. Taken together, the resources and results presented here form a powerful toolkit for future investigations of neuronal circuits and connectivity of premotor circuits while linking them to behavioral outputs.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9791678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Alzheimer's Molecular Pathologies in Large-Scale Connectomics Data: A Publicly Accessible Correlative Microscopy Resource.","authors":"Xiaomeng Han, Peter H Li, Shuohong Wang, Tim Blakely, Sneha Aggarwal, Bhavika Gopalani, Morgan Sanchez, Richard Schalek, Yaron Meirovitch, Zudi Lin, Daniel Berger, Yuelong Wu, Fatima Aly, Sylvie Bay, Benoît Delatour, Pierre Lafaye, Hanspeter Pfister, Donglai Wei, Viren Jain, Hidde Ploegh, Jeff Lichtman","doi":"10.1101/2023.10.24.563674","DOIUrl":"10.1101/2023.10.24.563674","url":null,"abstract":"<p><p>Connectomics using volume-electron-microscopy enables mapping and analysis of neuronal networks, revealing insights into neural circuit function and dysfunction. In Alzheimer's disease (AD), where amyloid-β (Aβ) and hyperphosphorylated-Tau (pTau) are implicated, connectomics offers an approach to unravel how these molecules contribute to circuit alterations by enabling the study of these molecules within the context of the complete local neuronal and glial milieu. We present a volumetric-correlated-light-and-electron microscopy (vCLEM) protocol using fluorescent nanobodies to localize Aβ and pTau within a large-scale connectomics dataset from the hippocampus of the 3xTg AD mouse model. A key outcome of this work is a publicly accessible vCLEM dataset, featuring fluorescent labeling of Aβ and pTau in the ultrastructural context with segmented neurons, glia, and synapses. This dataset provides a unique resource for exploring AD pathology in the context of connectomics and fosters collaborative opportunities in neurodegenerative disease research. As a proof-of-principle, we uncovered new localizations of Aβ and pTau, including pTau-positive spine-like protrusions at the axon initial segment and changes in the number and size of synapses near Aβ plaques. Our vCLEM approach facilitates the discovery of both molecular and structural alterations within large-scale EM data, advancing connectomics research in Alzheimer's and other neurodegenerative diseases.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards a standard benchmark for phenotype-driven variant and gene prioritisation algorithms: PhEval - Phenotypic inference Evaluation framework.","authors":"Yasemin Bridges, Vinicius de Souza, Katherina G Cortes, Melissa Haendel, Nomi L Harris, Daniel R Korn, Nikolaos M Marinakis, Nicolas Matentzoglu, James A McLaughlin, Christopher J Mungall, Aaron Odell, David Osumi-Sutherland, Peter N Robinson, Damian Smedley, Julius Ob Jacobsen","doi":"10.1101/2024.06.13.598672","DOIUrl":"10.1101/2024.06.13.598672","url":null,"abstract":"<p><strong>Background: </strong>Computational approaches to support rare disease diagnosis are challenging to build, requiring the integration of complex data types such as ontologies, gene-to-phenotype associations, and cross-species data into variant and gene prioritisation algorithms (VGPAs). However, the performance of VGPAs has been difficult to measure and is impacted by many factors, for example, ontology structure, annotation completeness or changes to the underlying algorithm. Assertions of the capabilities of VGPAs are often not reproducible, in part because there is no standardised, empirical framework and openly available patient data to assess the efficacy of VGPAs - ultimately hindering the development of effective prioritisation tools.</p><p><strong>Results: </strong>In this paper, we present our benchmarking tool, PhEval, which aims to provide a standardised and empirical framework to evaluate phenotype-driven VGPAs. The inclusion of standardised test corpora and test corpus generation tools in the PhEval suite of tools allows open benchmarking and comparison of methods on standardised data sets.</p><p><strong>Conclusions: </strong>PhEval and the standardised test corpora solve the issues of patient data availability and experimental tooling configuration when benchmarking and comparing rare disease VGPAs. By providing standardised data on patient cohorts from real-world case-reports and controlling the configuration of evaluated VGPAs, PhEval enables transparent, portable, comparable and reproducible benchmarking of VGPAs. As these tools are often a key component of many rare disease diagnostic pipelines, a thorough and standardised method of assessment is essential for improving patient diagnosis and care.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}