bioRxiv : the preprint server for biology最新文献

{"title":"Comparative transcriptomics of iPSC-derived cardiomyocytes in a high and a low altitude population.","authors":"O A Gray, D B Witonsky, A Di Rienzo","doi":"10.1101/2025.06.04.657917","DOIUrl":"10.1101/2025.06.04.657917","url":null,"abstract":"<p><p>Tibetan adaptation to high-altitude hypoxia remains a classic example of Darwinian selection in humans. To identify adaptive traits that might have evolved in Tibetans in response to long-term exposure to hypoxia, we previously established a library of induced pluripotent stem cells (iPSCs), derived from Tibetan and Han Chinese individuals, as a robust model system for the exploration of condition-specific molecular and cellular responses. We used this system to characterize and compare the transcriptome of iPSC-derived endothelial cells and found that angiogenesis, energy metabolism and immune pathways differ between the cell lines from these two populations. Here, we harness the same experimental system to characterize and compare the transcriptome of iPSC-derived cardiomyocytes in Tibetan and Han Chinese in hypoxia. We find that several pathways, such as the hypoxia, myogenesis and glycolysis pathways, are significantly enriched for differentially expressed genes across populations. These pathways are candidate targets of natural selection due to exposure to the high-altitude hypoxic environment and point to adaptive cardiac traits such as sustained cardiac function in hypoxia. A better understanding of these adaptations may offer insights into novel therapeutic strategies for hypoxia-related cardiovascular conditions, such as pulmonary hypertension and ischemic heart disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277448","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":"Identification of chromatin-associated RNAs at human centromeres.","authors":"Kelsey Fryer, Charles Limouse, Aaron F Straight","doi":"10.1101/2025.06.05.658139","DOIUrl":"10.1101/2025.06.05.658139","url":null,"abstract":"<p><p>Centromeres are a specialized chromatin domain that are required for the assembly of the mitotic kinetochore and the accurate segregation of chromosomes. Non-coding RNAs play essential roles in regulating genome organization including at the unique chromatin environment present at human centromeres. We performed Chromatin-Associated RNA sequencing (ChAR-seq) in three different human cell lines to identify and map RNAs associated with centromeric chromatin. Centromere enriched RNAs display distinct contact behaviors across repeat arrays and generally belong to three categories: centromere encoded, nucleolar localized, and highly abundant, broad-binding RNAs. Most centromere encoded RNAs remain locally associated with their transcription locus with the exception of a subset of human satellite RNAs. This work provides a comprehensive identification of centromere bound RNAs that may regulate the organization and activity of the centromere.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277563","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":"Generation and characterization of a mouse model of conditional <i>Chd4</i> knockout in the endometrial epithelium.","authors":"Shannon K Harkins, Hilary J Skalski, Abigail Z Bennett, Laura Pavliscak, Amelia R Arendt, Lauren Wood, Genna E Moldovan, Ronald L Chandler","doi":"10.1101/2025.06.05.658183","DOIUrl":"10.1101/2025.06.05.658183","url":null,"abstract":"<p><p>Chromatin remodeling plays an integral part in endometrial homeostasis, having roles in the maintenance of cell identity, epithelial integrity, and prevention of endometrial disease. Chromodomain-helicase-DNA-binding protein 4 (<i>CHD4</i>) is a chromatin remodeling protein and member of the NuRD complex, which predominantly represses transcription. <i>CHD4</i> is mutated in endometrial carcinoma, with most mutations leading to loss of function. <i>CHD4</i> has been identified as a tumor suppressor and regulator of stemness in endometrial carcinoma cells, but little is known about the tissue-specific roles of <i>CHD4</i> in the endometrial epithelia <i>in vivo.</i> We generated a conditional <i>Chd4</i> floxed allele and combined it with <i>BAC-Sprr2f-Cre</i> to drive <i>Chd4</i> loss in the endometrial epithelium. Consistent with previous reports, <i>BAC-Sprr2f-Cre</i> expression is absent in the oviducts, ovaries, and kidneys, and it shows variegated expression within the endometrial epithelium. Loss of CHD4 was confirmed by immunohistochemistry, and stained cells were quantified to determine the percentage of endometrial epithelial cells with and without CHD4. Compared to the glandular epithelium, the extent of CHD4 loss was higher in the luminal epithelium and unaffected by age. Mice with conditional knockout of <i>Chd4</i> had normal endometrial histology. A 6-month breeding trial was performed to assess the functional effects of endometrial epithelial <i>Chd4</i> loss on fertility. No difference in litter size, mean number of pups per litter per dam, or pup weight was found between genotypes. These findings demonstrate that <i>Chd4</i> conditional loss using <i>BAC-Sprr2f-Cre</i> is not sufficient to alter the structure and function of the endometrial epithelium or drive tumorigenesis. As <i>CHD4</i> is frequently co-mutated with other cancer driver genes such as <i>TP53</i>, <i>PIK3CA</i>, and <i>PTEN</i>, future mouse modeling efforts emulating patient mutational profiles might provide insight into the role of <i>CHD4</i> in endometrial carcinoma.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277586","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":"Engineering gene expression dynamics via self-amplifying RNA with drug-responsive non-structural proteins.","authors":"Parisa Yousefpour, Justin R Gregory, Kristen Si, Jan Lonzaric, Yingzhong Li, Junmin Wang, Kashif Qureshi, Amir Ledbetter, Ashley A Lemnios, Jonathan Dye, Tanaka K Remba, Rachel Yeung, Melissa Güereca, Linette Rodriguez, Yuebao Zhang, Shengwei Wu, Yizhou Dong, Ron Weiss, Darrell J Irvine","doi":"10.1101/2025.06.08.658495","DOIUrl":"10.1101/2025.06.08.658495","url":null,"abstract":"<p><p>The design of gene therapies with drug-regulatable expression of therapeutic payloads is of interest for diverse applications. We hypothesized that a regulated expression system based on alphavirus-derived self-amplifying RNAs (saRNAs), which encode 4 non-structural proteins (nsPs) that copy the RNA backbone to enable sustained expression, would have advantages in safety and simplicity of delivery. Here we designed saRNAs where payload expression is regulated by the FDA-approved drug trimethoprim (TMP), by fusing TMP-responsive degradation domains (DDs) to nsPs to regulate RNA self-amplification. Screening a library of nsP-DD fusions, we identified an optimal design with DDs fused to nsP2, nsP3, and the payload, achieving a high fold-change in expression level in response to TMP and low expression in the off state. In mice, this saRNA circuit enabled diverse dynamic expression patterns in response to oral TMP. Implementing this circuit for controlled expression of an HIV antigen, an escalating TMP regimen significantly enhanced germinal center responses critical for B cell affinity maturation. This drug-regulated RNA technology holds potential for vaccines, immunotherapies, and gene therapies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277539","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":"The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice.","authors":"Siyuan Sun, Seth Herr, Anna Alford, Rachel Stingle, Zaiyang Zhang, Timothy Dong, Riyi Shi","doi":"10.1101/2025.06.08.658505","DOIUrl":"10.1101/2025.06.08.658505","url":null,"abstract":"<p><p>Oxidative stress and lipid peroxidation-derived aldehydes, such as acrolein, play a central role in the pathology of spinal cord injury (SCI) and have emerged as promising therapeutic targets. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is a key oxidoreductase responsible for detoxifying reactive aldehydes. Pharmacological activation of ALDH2 using Alda-1, a selective agonist, has been shown to reduce aldehyde accumulation, alleviate inflammation, and enhance functional recovery in experimental SCI models. However, approximately 8% of the global population carries the ALDH2*2 mutation, which severely impairs this detoxification pathway. In this study, we used a transgenic ALDH2*2 mouse model to investigate the role of ALDH2 in SCI pathology. This model mimics the human ALDH2*2 condition, allowing us to examine the impact of impaired aldehyde clearance on acrolein accumulation and its pathological consequences. We modulated endogenous aldehyde detoxification through both genetic deficiency and pharmacological activation with Alda-1. Our results showed that ALDH2 deficiency led to significantly elevated acrolein levels, which were associated with increased microglial activation, cytokine storm, neuronal loss, demyelination, and tissue damage compared to wild-type (WT) mice. Treatment with Alda-1 enhanced ALDH2 activity and significantly reduced acrolein levels in both ALDH2*2 and WT mice from 2 to 28 days post-SCI. This was accompanied by reduced inflammation, improved preservation of myelin, and marked improvements in locomotor and sensory function, especially in ALDH2*2 mice. Notably, even beyond the traditionally ideal treatment window, Alda-1 treatment remained effective in promoting recovery, particularly in motor function and to a greater extent in ALDH2*2 mice. Our study comprehensively evaluated ALDH2's role in SCI by both genetically impairing and pharmacologically enhancing its activity, highlighting ALDH2 as a critical modulator of acrolein-mediated damage and suggesting its potential as a therapeutic target, especially for individuals with the ALDH2*2 mutation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277920","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":"Topical Delivery of 4-Aminopyridine Enhances Skin Regeneration in Burn Wounds.","authors":"Govindaraj Ellur, Meenakshi Kamaraj, John Elfar, Prem Kumar Govindappa, Johnson V John","doi":"10.1101/2025.06.05.658142","DOIUrl":"https://doi.org/10.1101/2025.06.05.658142","url":null,"abstract":"<p><p>Burn wounds are a common traumatic injury that impair cellular function and hinder the healing process, often resulting in significant skin loss. While autologous skin grafting is considered the gold standard for treating burns, its widespread use is limited due to donor site morbidity and the requirement for large amounts of tissue. Traditional wound dressings and treatments often fail to ensure complete recovery. Being initially FDA-approved to treat multiple sclerosis, 4-aminopyridine (4-AP) has also been shown to accelerate burn wound closure by transforming keratinocytes and fibroblasts when administered systemically. However, prolonged systemic use of 4-AP can lead to significant side effects. In this study, we aimed to repurpose 4-AP for treating skin burn wounds by delivering it topically using a laponite-gelatin gel formulation. This method allows for non-invasive and localized drug delivery on burn wound site. We evaluated the physical properties of the 4-AP gel shear thinning behavior, drug release kinetics, biocompatibility, and functional wound closure using a scratch assay. Moreover, our in vivo experiments showed that the 4-AP loaded gel accelerates wound healing by enhancing re-epithelialization and hair follicle regeneration and promoting fibroblast to myofibroblast transformation, which supports extracellular matrix remodeling after skin burns. This novel application of the 4-AP gel could offer a promising alternative to current burn wound therapies, potentially leading to improved outcomes for burn patients.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277927","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":"An origin for a eukaryotic lipid transfer protein fold in Asgard archaea.","authors":"Nicolas-Frédéric Lipp, Itay Budin","doi":"10.1101/2025.05.16.653879","DOIUrl":"10.1101/2025.05.16.653879","url":null,"abstract":"<p><p>The evolution of eukaryotic cells necessitated the advent of machinery to transport molecular building blocks for organelles to proliferate. Extant eukaryotes share several classes of highly conserved lipid transfer proteins (LTP) that associate with donor membranes, bind individual lipid molecules, and shuttle them to acceptor membranes. Because cells lacking organelles do not require extensive lipid transport networks, it is not known if this machinery pre-dated eukaryotic organelles or had to evolve alongside them. Here we describe a class of putative lipid transporters in the Asgard archaeota superphylum that share a common ancestry with eukaryotic LTPs in the START domain superfamily. We identified three classes of Asgard START proteins, StarAsg1-3, which are conserved across most Asgard phyla. Of these, StarAsg1 family proteins contain the predicted structural features necessary for lipid transfer: large, hydrophobic binding pockets lined with amphipathic motifs for membrane docking. In contrast, StarAsg2 and StarAsg3 family proteins contain smaller binding cavities and minimal predicted membrane interactions. We found that StarAsg1 from Lokiarcheota interacts with anionic membranes both in vitro and in yeast cells and can transfer sterols between liposomes. Phylogenetic analysis of START domains across the tree of life indicates that eukaryotic LTPs share a common ancestry with StarAsg1 homologs, while StarAsg2 and StarAsg3 form a monophyletic group with eukaryotic heat shock protein cochaperones. We propose that the emergence of proteins for inter-membrane lipid transporters in the ancestors of eukaryotic cells could have facilitated the subsequent development of intracellular organelles.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236414","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":"Integrated Histology and Molecular Profiling of Postmortem Human Auditory and Vestibular Organs via a Poly(Methyl Methacrylate)-Based Workflow.","authors":"David Bächinger, Brock Peyton, Jacqueline Neubauer, Anbuselvan Dharmarajan, MengYu Zhu, Jennifer T O'Malley, Venus Kallupurackal, Steven Senese, Alison Brown, Sabina Wunderlin, Susanne Kreutzer, Nora M Weiss, Heiko Richter, Adrian Dalbert, Christof Röösli, Anja Kipar, Zsuzsanna Varga, Brigitte von Rechenberg, Sami S Amr, Andreas H Eckhard","doi":"10.1101/2025.06.04.657716","DOIUrl":"10.1101/2025.06.04.657716","url":null,"abstract":"<p><p>Hearing and balance disorders are the most prevalent sensory impairments, affecting hundreds of millions worldwide, yet their underlying cellular and molecular pathologies remain poorly understood. This knowledge gap stems from the inaccessibility of the ear's sensory organs-embedded within the temporal bone (TB), the hardest bone in the body-which cannot be biopsied in living patients without causing irreversible damage. Conventional histopathology workflows rely on postmortem en bloc extraction of TBs, followed by lengthy decalcification, celloidin embedding, and manual serial sectioning of these large specimens-a process that takes one to two years, is labor- and cost-intensive, and lacks compatibility with most modern protein, DNA, and RNA assays. Here, we present a rapid, reversible polymethyl methacrylate (rPMMA) workflow that enables advanced molecular histopathology studies on formalin-fixed, calcified TBs. Our protocol uses low-temperature (-40 °C to +4 °C) resin embedding, precision near-serial sectioning (10-50 µm) via femtosecond laser microtomy or precision diamond wire sawing, and subsequent deacrylation to fully restore tissue accessibility for high-fidelity histomorphology, multiplexed immunofluorescence, whole-genome sequencing, and in situ mRNA detection (RNAscope^™) assays. Compared to the gold-standard celloidin workflow, our method reduces processing time and costs by approximately 90% while integrating equivalent histomorphology with advanced molecular assays, providing a new benchmark for multidimensional studies in human hearing and balance pathologies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277628","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":"Cyclo-stationary distributions of mRNA and Protein counts for random cell division times.","authors":"Syed Yunus Ali, Aditya Saran, Ashok Prasad, Abhyudai Singh, Dibyendu Das","doi":"10.1101/2025.06.06.658238","DOIUrl":"10.1101/2025.06.06.658238","url":null,"abstract":"<p><p>There is a long history of using experimental and computational approaches to study noise in single-cell levels of mRNA and proteins. The noise originates from a myriad of factors: intrinsic processes of gene expression, partitioning errors during division, and extrinsic effects, such as, random cell-cycle times. Although theoretical methods are well developed to analytically understand full statistics of copy numbers for fixed or Erlang distributed cell cycle times, the general problem of random division times is still open. For any random (but uncorrelated) division time distribution, we present a method to address this challenging problem and obtain exact series representations of the copy number distributions in the cyclo-stationary state. We provide explicit cell age-specific and age-averaged results, and analyze the relative contribution to noise from intrinsic and extrinsic sources. Our analytical approach will aid the analysis of single-cell expression data and help in disentangling the impact of variability in division times.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277468","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":"Short chain fatty acids regulate the chromatin landscape and distinct gene expression changes in human colorectal cancer cells.","authors":"Tohfa Kabir, Charlotte A Connamacher, Zara Nadeem, Matthew R Paul, Matthew R Smutny, Zoe K Lawler, Annaelle M Djomo, Thomas S Carroll, Leah A Gates","doi":"10.1101/2025.05.07.652677","DOIUrl":"10.1101/2025.05.07.652677","url":null,"abstract":"<p><p>Short chain fatty acids (SCFAs) are small metabolites that are produced through the activity of microbes and have important roles in human physiology. These metabolites have varied mechanisms in interacting with the host, of which one such mode is decorating the chromatin landscape. We previously detected specific histone modifications in the mouse gut that can be derived from SCFAs and are regulated by the microbiota. However, the roles of these SCFAs on chromatin and how they impact gene regulation in human cells is largely unknown. Now, our studies demonstrate these microbiota-dependent histone posttranslational modifications (PTMs) are associated with alterations in gene regulation in human cells. We show that histone butyrylation on H3K27 is detected in human colon samples. Furthermore, histone acetylation, butyrylation, and propionylation on H3K9 and H3K27 are responsive to levels of SCFAs in human colon cancer cell lines and are associated with active gene regulatory elements. In addition, treatment of human cancer cell lines with individual metabolites or combinations of SCFAs replicating the intestinal lumen environment result in distinct and overlapping gene program changes, with butyrate largely driving gene regulatory effects of SCFA combinations. Lastly, we define butyrate effects on gene expression that are independent of HDAC inhibition and are dependent on p300/CBP, suggesting potential gene programs regulated by histone butyrylation. Together, these results demonstrate that SCFAs are key regulators of the chromatin landscape and gene programs in human colorectal cancer cells.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218442","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}