bioRxiv : the preprint server for biology最新文献

{"title":"Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.","authors":"Ching-Chieh Chou, Ryan Vest, Miguel A Prado, Joshua Wilson-Grady, Joao A Paulo, Yohei Shibuya, Patricia Moran-Losada, Ting-Ting Lee, Jian Luo, Steven P Gygi, Jeffery W Kelly, Daniel Finley, Marius Wernig, Tony Wyss-Coray, Judith Frydman","doi":"10.1101/2023.03.27.534444","DOIUrl":"10.1101/2023.03.27.534444","url":null,"abstract":"<p><p>Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-Tau and Aβ, resembling those in AD patient and APP mouse brains. Quantitative tNeuron proteomics identify aging and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Supporting lysosomal deficits' centrality in AD, compounds ameliorating lysosomal function reduce Aβ deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of aging and AD.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265432","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 multisensory integration follows subjective confidence rather than objective performance.","authors":"Yi Gao, Kai Xue, Brian Odegaard, Dobromir Rahnev","doi":"10.1101/2023.06.07.544029","DOIUrl":"10.1101/2023.06.07.544029","url":null,"abstract":"<p><p>It is well known that sensory information from one modality can automatically affect judgments from a different sensory modality. However, it remains unclear what determines the strength of the influence of an irrelevant sensory cue from one modality on a perceptual judgment for a different modality. Here we test whether the strength of multisensory impact by an irrelevant sensory cue depends on participants' objective accuracy or subjective confidence for that cue. We created visual motion stimuli with low vs. high overall motion energy, where high-energy stimuli yielded higher confidence but lower accuracy in a visual-only task. We then tested the impact of the low- and high-energy visual stimuli on auditory motion perception. We found that the high-energy visual stimuli influenced the auditory motion judgments more strongly than the low-energy visual stimuli, consistent with their higher confidence but contrary to their lower accuracy. A computational model assuming common principles underlying confidence reports and multisensory integration captured these effects. Our findings show that automatic multisensory integration follows subjective confidence rather than objective performance and suggest the existence of common computations across vastly different stages of perceptual decision making.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666325","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":"PDZ Domains from the Junctional Proteins Afadin and ZO-1 Act as Mechanosensors.","authors":"Vipul T Vachharajani, Matthew P DeJong, Soumya Dutta, Jonathan Chapman, Eashani Ghosh, Abhishek Singharoy, Alexander R Dunn","doi":"10.1101/2023.09.24.559210","DOIUrl":"10.1101/2023.09.24.559210","url":null,"abstract":"<p><p>Intercellular adhesion complexes must withstand mechanical forces to maintain tissue cohesion while also retaining the capacity for dynamic remodeling during tissue morphogenesis and repair. Many cell-cell adhesion complexes contain at least one PSD95/Dlg/ZO-1 (PDZ) domain situated between the adhesion molecule and the actin cytoskeleton. However, PDZ-mediated interactions are characteristically nonspecific, weak, and transient, with multiple binding partners per PDZ domain, micromolar dissociation constants, and bond lifetimes of seconds or less. Here, we demonstrate that the bonds between the PDZ domain of the cytoskeletal adaptor protein afadin and the intracellular domains of the adhesion molecules nectin-1 and JAM-A form molecular catch bonds that reinforce in response to mechanical load. In contrast, the bond between the PDZ3-SH3-GUK (PSG) domain of the cytoskeletal adaptor ZO-1 and the JAM-A intracellular domain becomes dramatically weaker in response to ∼2 pN of load, the amount generated by single molecules of the cytoskeletal motor protein myosin II. Thus, physiologically relevant forces can exert dramatic and opposite effects on the stability of two of the major linkages between cell-cell adhesion proteins and the F-actin cytoskeleton. Our data demonstrate that that PDZ domains can serve as force-responsive mechanical anchors at cell-cell adhesion complexes. More broadly, our findings suggest that mechanical force may serve as a previously unsuspected regulator of the hundreds of PDZ-ligand interactions present in animal cells.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157874","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":"BIBSNet: A Deep Learning Baby Image Brain Segmentation Network for MRI Scans.","authors":"Timothy J Hendrickson, Paul Reiners, Lucille A Moore, Jacob T Lundquist, Begim Fayzullobekova, Anders J Perrone, Erik G Lee, Julia Moser, Trevor K M Day, Dimitrios Alexopoulos, Martin Styner, Omid Kardan, Taylor A Chamberlain, Anurima Mummaneni, Henrique A Caldas, Brad Bower, Sally Stoyell, Tabitha Martin, Sooyeon Sung, Ermias A Fair, Kenevan Carter, Jonathan Uriarte-Lopez, Amanda R Rueter, Essa Yacoub, Monica D Rosenberg, Christopher D Smyser, Jed T Elison, Alice Graham, Damien A Fair, Eric Feczko","doi":"10.1101/2023.03.22.533696","DOIUrl":"10.1101/2023.03.22.533696","url":null,"abstract":"<p><strong>Objectives: </strong>Brain segmentation of infant magnetic resonance (MR) images is vitally important for studying typical and atypical brain development. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here we introduce a deep neural network BIBSNet ( <b>B</b> aby and <b>I</b> nfant <b>B</b> rain <b>S</b> egmentation Neural <b>Net</b> work), an open-source, community-driven model for robust and generalizable brain segmentation leveraging data augmentation and a large sample size of manually annotated images.</p><p><strong>Experimental design: </strong>Included in model training and testing were MR brain images from 90 participants with an age range of 0-8 months (median age 4.6 months). Using the BOBs repository of manually annotated real images along with synthetic segmentation images produced using SynthSeg, the model was trained using a 10-fold procedure. Model performance of segmentations was assessed by comparing BIBSNet, joint label fusion (JLF) inferred segmentation to ground truth segmentations using Dice Similarity Coefficient (DSC). Additionally, MR data along with the FreeSurfer compatible segmentations were processed with the DCAN labs infant-ABCD-BIDS processing pipeline from ground truth, JLF, and BIBSNet to further assess model performance on derivative data, including cortical thickness, resting state connectivity and brain region volumes.</p><p><strong>Principal observations: </strong>BIBSNet segmentations outperforms JLF across all regions based on DSC comparisons. Additionally, with processed derived metrics, BIBSNet segmentations outperforms JLF segmentations across nearly all metrics.</p><p><strong>Conclusions: </strong>BIBSNet segmentation shows marked improvement over JLF across all age groups analyzed. The BIBSNet model is 600x faster compared to JLF, produces FreeSurfer-compatible segmentation labels, and can be easily included in other processing pipelines. BIBSNet provides a viable alternative for segmenting the brain in the earliest stages of development.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465054","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":"Association of bidirectional network cores in the brain with perceptual awareness and cognition.","authors":"Tomoya Taguchi, Jun Kitazono, Shuntaro Sasai, Masafumi Oizumi","doi":"10.1101/2024.04.30.591001","DOIUrl":"10.1101/2024.04.30.591001","url":null,"abstract":"<p><p>The brain comprises a complex network of interacting regions. To understand the roles and mechanisms of this intricate network, it is crucial to elucidate its structural features related to cognitive functions. Recent empirical evidence suggests that both feedforward and feedback signals are necessary for conscious perception, emphasizing the importance of subnetworks with bidirectional interactions. However, the link between such subnetworks and conscious perception remains unclear due to the complexity of brain networks. In this study, we propose a framework for extracting subnetworks with strong bidirectional interactions-termed the \"cores\" of a network-from brain activity. We applied this framework to resting-state and task-based human fMRI data from participants of both sexes to identify regions forming strongly bidirectional cores. We then explored the association of these cores with conscious perception and cognitive functions. We found that the extracted central cores predominantly included cerebral cortical regions rather than subcortical regions. Additionally, regarding their relation to conscious perception, we demonstrated that the cores tend to include regions previously reported to be affected by electrical stimulation that altered conscious perception, although the results are not statistically robust due to the small sample size. Furthermore, in relation to cognitive functions, based on a meta-analysis and comparison of the core structure with a cortical functional connectivity gradient, we found that the central cores were related to unimodal sensorimotor functions. The proposed framework provides novel insights into the roles of network cores with strong bidirectional interactions in conscious perception and unimodal sensorimotor functions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923773","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":"Engineered bacteria launch and control an oncolytic virus.","authors":"Zakary S Singer, Jonathan Pabón, Hsinyen Huang, William Sun, Hongsheng Luo, Kailyn Rhyah Grant, Ijeoma Obi, Courtney Coker, Charles M Rice, Tal Danino","doi":"10.1101/2023.09.28.559873","DOIUrl":"10.1101/2023.09.28.559873","url":null,"abstract":"<p><p>The ability of bacteria and viruses to selectively replicate in tumors has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy whereby <i>S. typhimurium</i> bacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. \"Encapsidated\" by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumor and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163939","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":"PI(3,5)P ₂ Controls the Signaling Activity of Class I PI3K.","authors":"Jiachen Sun, Julian Zalejski, Seohyeon Song, Ashutosh Sharma, Wei Wang, Yusi Hu, Wen-Ting Lo, Philipp Alexander Koch, Jagriti Singh, Indira Singaram, Baoshu An, Jean J Zhao, Liang-Wei Gong, Volker Haucke, Ruixuan Gao, Wonhwa Cho","doi":"10.1101/2023.01.25.525550","DOIUrl":"10.1101/2023.01.25.525550","url":null,"abstract":"<p><p>3-Phosphoinositides are ubiquitous cellular lipids that play pivotal regulatory roles in health and disease. Among 3-phosphoinositides, phosphatidylinositol-3,5-bisphosphate (PI(3,5)P ₂ ) remains the least understood species in terms of its spatiotemporal dynamics and physiological function due to the lack of a specific sensor that allows spatiotemporally resolved quantitative imaging of PI(3,5)P ₂ . Using a newly developed ratiometric PI(3,5)P ₂ sensor engineered from the C-terminal SH2 domain of Class I phosphoinositide 3-kinases (PI3K)-p85α subunit we demonstrate that a unique pool of PI(3,5)P ₂ is generated on lysosomes and late endosomes in response to growth factor stimulation. This PI(3,5)P ₂ , the formation of which is mediated sequentially by Class II PI3KC2β and PIKfyve, plays a crucial role in terminating the activity of growth factor-stimulated Class I PI3K, one of the most frequently mutated proteins in cancer, via specific interaction with its regulatory p85 subunit. A small molecule inhibitor of p85α-PI(3,5)P ₂ binding specifically blocks the feedback inhibition of Class I PI3K by PI(3,5)P ₂ and thus serves as a PI3K activator that promotes neurite growth. Furthermore, cancer-causing mutations of the Class I PI3K-p85 subunit inhibit p85-PI(3,5)P ₂ interaction and thereby induce sustained activation of Class I PI3K. Our results unravel a hitherto unknown spatiotemporally specific regulatory function of PI(3,5)P ₂ that links Class I and II PI3Ks and modulates the magnitude of PI3K-mediated growth factor signaling. These results also suggest new therapeutic possibilities for treating cancer patients with p85 mutations and promoting wound healing and tissue regeneration.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668142","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":"Electrophysiology and Morphology of Human Cortical Supragranular Pyramidal Cells in a Wide Age Range.","authors":"Pál Barzó, Ildikó Szöts, Martin Tóth, Éva Adrienn Csajbók, Gábor Molnár, Gábor Tamás","doi":"10.1101/2024.06.13.598792","DOIUrl":"10.1101/2024.06.13.598792","url":null,"abstract":"<p><p>The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 years of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition and age-related neurodegenerative diseases.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447709","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":"Dynamic categorization rules alter representations in human visual cortex.","authors":"Margaret M Henderson, John T Serences, Nuttida Rungratsameetaweemana","doi":"10.1101/2023.09.11.557257","DOIUrl":"10.1101/2023.09.11.557257","url":null,"abstract":"<p><p>Everyday perceptual tasks require sensory stimuli to be dynamically encoded and analyzed according to changing behavioral goals. For example, when searching for an apple at the supermarket, one might first find the Granny Smith apples by separating all visible apples into the categories \"green\" and \"non-green\". However, suddenly remembering that your family actually likes Fuji apples would necessitate reconfiguring the boundary to separate \"red\" from \"red-yellow\" objects. This flexible processing enables identical sensory stimuli to elicit varied behaviors based on the current task context. While this phenomenon is ubiquitous in nature, little is known about the neural mechanisms that underlie such flexible computation. Traditionally, sensory regions have been viewed as mainly devoted to processing inputs, with limited involvement in adapting to varying task contexts. However, from the standpoint of efficient computation, it is plausible that sensory regions integrate inputs with current task goals, facilitating more effective information relay to higher-level cortical areas. Here we test this possibility by asking human participants to visually categorize novel shape stimuli based on different linear and non-linear boundaries. Using fMRI and multivariate analyses of retinotopically-defined visual areas, we found that shape representations in visual cortex became more distinct across relevant decision boundaries in a context-dependent manner, with the largest changes in discriminability observed for stimuli near the decision boundary. Importantly, these context-driven modulations were associated with improved categorization performance. Together, these findings demonstrate that codes in visual cortex are adaptively modulated to optimize object separability based on currently relevant decision boundaries.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/2b/nihpp-2023.09.11.557257v1.PMC10515851.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145917","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":"Deletion of Neuroligins from Astrocytes Does Not Detectably Alter Synapse Numbers or Astrocyte Cytoarchitecture by Maturity.","authors":"Samantha R Golf, Justin H Trotter, Jinzhao Wang, George Nakahara, Xiao Han, Marius Wernig, Thomas C Südhof","doi":"10.1101/2023.04.10.536254","DOIUrl":"10.1101/2023.04.10.536254","url":null,"abstract":"<p><p>Astrocytes perform multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved are incompletely understood. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that function as synaptic organizers by binding to presynaptic neurexins. Here we examined the function of neuroligins in astrocytes with a rigorous genetic approach that uses the conditional deletion of all major neuroligins (<i>Nlgn1-3</i>) in astrocytes <i>in vivo</i> and complemented this approach by a genetic deletion of neuroligins in glia cells that are co-cultured with human neurons. Our results show that early postnatal deletion of neuroligins from astrocytes in vivo has no detectable effect on cortical or hippocampal synapses and does not alter the cytoarchitecture of astrocytes when evaluated in young adult mice. Moreover, deletion of astrocytic neuroligins in co-cultures of human neurons produced no detectable consequences for the formation and function of synapses. Thus, astrocytic neuroligins are unlikely to fundamentally shape synapse formation or astrocyte morphogenesis but likely perform other important roles that remain to be discovered.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387213","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}