bioRxiv : the preprint server for biology最新文献

{"title":"MPAC: a computational framework for inferring pathway activities from multi-omic data.","authors":"Peng Liu, David Page, Paul Ahlquist, Irene M Ong, Anthony Gitter","doi":"10.1101/2024.06.15.599113","DOIUrl":"10.1101/2024.06.15.599113","url":null,"abstract":"<p><p>Fully capturing cellular state requires examining genomic, epigenomic, transcriptomic, proteomic, and other assays for a biological sample and comprehensive computational modeling to reason with the complex and sometimes conflicting measurements. Modeling these so-called multi-omic data is especially beneficial in disease analysis, where observations across omic data types may reveal unexpected patient groupings and inform clinical outcomes and treatments. We present Multi-omic Pathway Analysis of Cells (MPAC), a computational framework that interprets multi-omic data through prior knowledge from biological pathways. MPAC leverages network relationships encoded in pathways through a factor graph to infer consensus activity levels for proteins and associated pathway entities from multi-omic data, runs permutation testing to eliminate spurious activity predictions, and groups biological samples by pathway activities to allow identifying and prioritizing proteins with potential clinical relevance, e.g., associated with patient prognosis. Using DNA copy number alteration and RNA-seq data from head and neck squamous cell carcinoma patients from The Cancer Genome Atlas as an example, we demonstrate that MPAC predicts a patient subgroup related to immune responses not identified by analysis with either input omic data type alone. Key proteins identified via this subgroup have pathway activities related to clinical outcome as well as immune cell compositions. Our MPAC R package, available at https://bioconductor.org/packages/MPAC, enables similar multi-omic analyses on new datasets.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474583","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":"GraphVelo allows for accurate inference of multimodal velocities and molecular mechanisms for single cells.","authors":"Yuhao Chen, Yan Zhang, Jiaqi Gan, Ke Ni, Ming Chen, Ivet Bahar, Jianhua Xing","doi":"10.1101/2024.12.03.626638","DOIUrl":"10.1101/2024.12.03.626638","url":null,"abstract":"<p><p>RNA velocities and generalizations emerge as powerful approaches for extracting time-resolved information from high-throughput snapshot single-cell data. Yet, several inherent limitations restrict applying the approaches to genes not suitable for RNA velocity inference due to complex transcriptional dynamics, low expression, or lacking splicing dynamics, or data of non-transcriptomic modality. Here, we present GraphVelo, a graph-based machine learning procedure that uses as input the RNA velocities inferred from existing methods and infers velocity vectors lying in the tangent space of the low-dimensional manifold formed by the single cell data. GraphVelo preserves vector magnitude and direction information during transformations across different data representations. Tests on synthetic and experimental single-cell data including viral-host interactome, multi-omics, and spatial genomics datasets demonstrate that GraphVelo, together with downstream generalized dynamo analyses, extends RNA velocities to multi-modal data and reveals quantitative nonlinear regulation relations between genes, virus and host cells, and different layers of gene regulation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11642879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831809","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":"A Brain Reward Circuit Inhibited By Next-Generation Weight Loss Drugs.","authors":"Elizabeth N Godschall, Taha Bugra Gungul, Isabelle R Sajonia, Aleyna K Buyukaksakal, Orien Dong-Ang Li, Sophia Ogilvie, Austin B Keeler, Guilian Tian, Omar Koita, Yu Shi, Tyler C J Deutsch, Maisie Crook, YuChen Zhang, Nicholas J Conley, Addison N Webster, O Yipkin Calhan, Weile Liu, Amani Akkoub, Karan Malik, Kaleigh I West, Sara Michel-Le, Arun Karthikeyan, Grace van Gerven, Kevin T Beier, Larry S Zweifel, Manoj K Patel, John N Campbell, Christopher D Deppmann, Ali D Güler","doi":"10.1101/2024.12.12.628169","DOIUrl":"https://doi.org/10.1101/2024.12.12.628169","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes, yet established peptide-based therapies require injections and complex manufacturing. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies. Here, we developed humanized GLP1R mouse models to investigate how small-molecule GLP1RAs influence feeding behavior. This approach revealed that these compounds regulate both homeostatic and hedonic feeding through parallel neural circuits. Beyond engaging canonical hypothalamic and hindbrain networks that control metabolic homeostasis, GLP1RAs recruit a discrete population of Glp1r-expressing neurons in the central amygdala, which selectively suppress the consumption of palatable foods by reducing dopamine release in the nucleus accumbens. Stimulating these central amygdalar neurons curtail hedonic feeding, whereas targeted deletion of the receptor in this cell population specifically diminishes the anorectic efficacy of GLP1RAs for reward-driven intake. These findings reveal a dedicated neural circuit through which small molecule GLP1RAs modulate reward processing, suggesting broad therapeutic potential in conditions of dysregulated dopamine signaling including substance use disorder and binge eating.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556423","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":"Rhagovelia uses interfacial run-and-tumble locomotion to improve food capture in flowing environments.","authors":"Ishant Tiwari, Nithil Nagappan, Jacob S Harrison, Saad Bhamla","doi":"10.1101/2025.04.03.647112","DOIUrl":"10.1101/2025.04.03.647112","url":null,"abstract":"<p><p><i>Rhagovelia oriander</i> is a freshwater water strider native to the rivers and streams of North and South America, known for its distinctive skating movement on the water's surface. This movement resembles the correlated random-walk pattern seen in microorganisms such as <i>Escherichia coli</i> . Previous studies have primarily focused on limb adaptations and biomechanics, leaving the ecological significance inadequately addressed. We combine field observations with controlled laboratory experiments using a flow mill to investigate the dynamics of <i>R. oriander</i> under typical flow conditions. Our findings indicate that this insect exhibits a two-dimensional run-and-tumble motion, often incorporating lateral tumbles following straight runs (run distance: 30.7 ± 9.3 mm). We find that this behavior is resilient to changes in flow speed. In-silico simulations of particle interception demonstrated that this locomotion method enhances encounter rates compared to linear movement, particularly when the simulated food particle is following a rapid flow field. Our results document run-and-tumble locomotion in a millimeter-scale organism, showcasing a unique example of convergent behavior across diverse taxonomic groups and providing valuable insights into locomotion ecology while serving as a source of inspiration for bioinspired robotics and environmental exploration algorithms.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059674","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":"Mechanistic insights into Down syndrome comorbidities via convergent RNA-seq and TWAS signals.","authors":"Marc Subirana-Granés, Haoyu Zhang, Prashant Gupta, Milton Pividori","doi":"10.1101/2025.06.05.658129","DOIUrl":"10.1101/2025.06.05.658129","url":null,"abstract":"<p><p>Down syndrome (DS) is caused by trisomy of chromosome 21 and is associated with diverse clinical manifestations, yet the molecular pathways linking chromosome-21 dosage effects to DS comorbidities remain poorly defined. Here we address this gap by applying a network-based, integrative framework that combines whole-blood transcriptomic data with gene-trait associations to uncover mechanistic insights into DS-associated conditions. First, we performed matrix factorization using PLIER on Human Trisome Project (HTP) RNA-Seq profiles from 304 trisomy-21 (T21) and 95 euploid (D21) individuals, deriving 156 biologically interpretable gene modules. We then identified 92 modules whose activity differed significantly between T21 and D21 and annotated these with prior-knowledge and KEGG pathways. To connect modules to clinical traits, we integrated PrediXcan-derived TWAS results from the UK Biobank, revealing 25 T21-specific modules with significant gene-trait associations (FDR < 0.1), including modules linked to cardiovascular, hematological, immune, metabolic, and neurological phenotypes relevant to DS. Using HTP clinical records as a replication cohort, 13 of these modules reliably predicted comorbidity status (AUC > 0.65, mAPS > 0.65). Most notably module 37, an interferon-stimulated gene network, whose elevated expression robustly distinguished DS individuals with pulmonary hypertension (AUC = 0.76, mAPS = 0.73). Overall, our study demonstrates that integrating blood-derived gene modules with population-scale genetic data uncovers coherent molecular signatures underlying DS comorbidities, identifies candidate biomarkers and therapeutic targets (e.g., <i>ISG15, IFITs, MX1</i> ), and highlights the power of combining transcriptomic and genetic evidence to elucidate complex disease mechanisms.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277716","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":"Direct RNA nanopore sequencing reveals rapid RNA modification changes following glucose stimulation of human pancreatic beta-cell lines.","authors":"Logan Mulroney, Henry J Taylor, Angela Lee, Amy J Swift, Mihail Zdravkov, Lori L Bonnycastle, Shelise Y Brooks, Brian N Lee, Tomas Fitzgerald, Narisu Narisu, Leslie G Biesecker, Michael R Erdos, Francesco Nicassio, Ewan Birney, Francis S Collins, D Leland Taylor","doi":"10.1101/2025.06.12.659352","DOIUrl":"https://doi.org/10.1101/2025.06.12.659352","url":null,"abstract":"<p><p>RNA modifications are critical regulators of gene expression and cellular processes; however, the epitranscriptome is less well studied than the epigenome. Here, we studied transcriptome-wide changes in RNA modifications and expression levels in two human pancreatic beta-cell lines, EndoC-BH1 and EndoC-BH3, after one hour of glucose stimulation. Using direct RNA nanopore sequencing (dRNA-seq), we measured N6-methyladenosine (m6A), 5-methylcytosine (m5C), inosine, and pseudouridine concurrently across the transcriptome. We developed a differential RNA modification method and identified 1,697 differentially modified sites (DMSs) across all modifications. These DMSs were largely independent of changes in gene expression levels and enriched in transcripts for type 2 diabetes (T2D) genes. Our study demonstrates how dRNA-seq can be used to detect and quantify RNA modification changes in response to cellular stimuli at the single-nucleotide level and provides new insights into RNA-mediated mechanisms that may contribute to normal beta-cell response and potential dysfunction in T2D.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500150","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":"A Thiopurine-like Mutagenic Process Defines TGCT Subtypes.","authors":"Kevin M Brown, Jun Zhong, Adriana Morales Miranda, Mengyan Zhang, Joycelyn Williams, Jacob Williams, Haoyu Zhang, Cheng Liang, Wenbo Li, Bin Zhu, Stephen J Chanock, Katherine L Nathanson, Tongwu Zhang","doi":"10.1101/2025.06.12.655573","DOIUrl":"https://doi.org/10.1101/2025.06.12.655573","url":null,"abstract":"<p><p>Testicular germ cell tumors (TGCTs) are the most common malignancy in young men, exhibit a unique developmental origin and exceptional chemosensitivity. However, the molecular distinctions between TGCT subtypes remain poorly understood. Here we present a comprehensive genomic analysis of 252 treatment-naive primary TGCTs, integrating deep whole-genome sequencing with matched transcriptomic and epigenomic data. We identify new driver genes and uncover defining features of TGCTs, including pervasive chromosome X amplification with subtype-specific X chromosome inactivation, and a germ cell-like transcriptional program. Although previously reported, whole genome doubling (WGD) in TGCTs is further characterized here as ubiquitous, developmentally early, and associated with age at onset. Seminomas are enriched for early driver mutations, secondary WGD events, sustained <i>XIST</i> expression and replication stress-associated indel mutational signatures, while non-seminomas show greater structural complexity, subclonal diversity, relatively earlier-onset WGD, extended tumor latency, and telomere elongation. Moreover, we identify a mutational signature, SBS87, that is exceptionally rare across cancers with exception of thiopurine-treated leukemia, but strikingly prevalent in TGCT, especially non-seminomas. SBS87 is linked to extended tumor latency and telomere elongation, implicating possible environmental or endogenous processes that mimic thiopurine-induced DNA damage in TGCT pathogenesis. Collectively, our findings define TGCTs as molecularly distinct tumors shaped by early genomic instability and highlight SBS87 as a novel mutational footprint with potential etiologic and clinical relevance.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500104","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":"Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex.","authors":"Juan Luis Romero-Sosa, Alex Yeghikian, Andrew M Wikenheiser, Hugh T Blair, Alicia Izquierdo","doi":"10.1101/2024.11.05.622092","DOIUrl":"10.1101/2024.11.05.622092","url":null,"abstract":"<p><p>Orbitofrontal cortex (OFC) and secondary motor cortex (M2) are both implicated in flexible reward learning but the conditions that differentially recruit these regions are not fully understood. We imaged calcium activity from single neurons in OFC or M2 during <i>de novo</i> learning of increasingly uncertain reward probability schedules. Predictions of choice were decoded from M2 neurons with high accuracy under all certainty conditions, but were more accurately decoded from OFC neurons under greater uncertainty. The number of choice- and reward-selective neurons was significantly higher in M2 than in OFC across schedules, but these proportions increased across levels of uncertainty only in OFC. Decoding accuracy of choice and outcome was predicted by behavioral strategies Win-Stay and Lose-Shift in OFC, but not M2. We also tested causal involvement of these regions with chemogenetic perturbation as rats learned increasing and then decreasing uncertainty schedules. Whereas inhibition of OFC neurons attenuated learning across all schedules, M2 neurons were found to support learning in the most certain reward schedule. Thus, OFC neurons preferentially encode choices and outcomes that foster a greater reliance on adaptive strategies under uncertainty. This reveals a novel functional heterogeneity within frontal cortex in support of flexible learning.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690469","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-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth.","authors":"Nicole R West, Kalpana Hanthanan Arachchilage, Sara Knaack, Shawn MacGregor, Masoumeh Hosseini, Ryan D Risgaard, Pubudu Kumarage, Jose L Martinez, Su-Chun Zhang, Daifeng Wang, Andre M M Sousa, Anita Bhattacharyya","doi":"10.1101/2025.02.05.636750","DOIUrl":"10.1101/2025.02.05.636750","url":null,"abstract":"<p><strong>Introduction: </strong>Basal forebrain cholinergic neurons (BFCNs) are integral to learning, attention, and memory, and are prone to degeneration in Down syndrome (DS), Alzheimer's disease, and other neurodegenerative diseases. However, the mechanisms that lead to the degeneration of these neurons are not known.</p><p><strong>Methods: </strong>Single-nucleus gene expression and ATAC sequencing were performed on postmortem human basal forebrain from unaffected control and DS tissue samples at 0-2 years of age (n=4 each).</p><p><strong>Results: </strong>Sequencing analysis of postmortem human basal forebrain identifies gene expression differences in DS early in life. Genes encoding proteins associated with energy metabolism pathways, specifically oxidative phosphorylation and glycolysis, and genes encoding antioxidant enzymes are upregulated in DS BFCNs.</p><p><strong>Discussion: </strong>Multiomic analyses reveal that energy metabolism may be disrupted in DS BFCNs by birth. Increased oxidative phosphorylation and the accumulation of reactive oxygen species byproducts may be early contributors to DS BFCN neurodegeneration.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461761","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":"Measuring renal cortical cell-specific mitochondrial metabolism.","authors":"Kyle Feola, Andrea H Venable, Mina Rasouli, Julie Do, Tatyana McCoy, Claire B Llamas, Dana Straus, Prashant Mishra, Behzad Najafian, Sarah C Huen","doi":"10.1101/2024.11.24.622516","DOIUrl":"10.1101/2024.11.24.622516","url":null,"abstract":"<p><p>The metabolic health of the kidney is a primary determinant of the risk of progressive kidney disease. Our understanding of the metabolic processes that fuel kidney functions is limited by the kidney's structural and functional heterogeneity. As the kidney contains many different cell types, we sought to determine the intra-renal mitochondrial heterogeneity that contributes to cell-specific metabolism. To interrogate this, we utilized a recently developed mitochondrial tagging technique to isolate kidney cell-type specific mitochondria. Here, we investigate mitochondrial functional capacities and the metabolomes of the early and late proximal tubule (PT) and the distal convoluted tubule (DCT). The conditional MITO-Tag transgene was combined with <i>Slc34a1-CreERT2</i> , <i>Ggt1-Cre</i> , or <i>Pvalb-Cre</i> transgenes to generate mouse models capable of cell-specific isolation of hemagglutinin (HA)-tagged mitochondria from the early PT, late PT, or the DCT, respectively. Functional assays measuring mitochondrial respiratory and fatty acid oxidation (FAO) capacities and metabolomics were performed on anti-HA immunoprecipitated mitochondria from kidneys of ad libitum fed and 24-hour fasted male mice. The renal MITO-Tag models targeting the early PT, late PT, and DCT revealed differential mitochondrial respiratory and FAO capacities which dynamically changed during fasting conditions. The renal MITO-Tag model captured differential mitochondrial metabolism and functional capacities across the early PT, late PT, and DCT at baseline and in response to fasting.</p><p><strong>New & noteworthy: </strong>This study described the generation and utilization of mouse models capable of interrogating kidney tubular epithelial cell-specific mitochondrial metabolism. Applying the MITO-Tag system in the kidney, we have for the first time defined the mitochondrial metabolic heterogeneity of renal cortical tubular epithelium and discovered differential mitochondrial functional capacities in response to an acute metabolic stress such as fasting.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804160","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}