bioRxiv : the preprint server for biology最新文献

{"title":"Human deleterious mutation rate slows adaptation and implies high fitness variance.","authors":"Joseph Matheson, Ulises Hernández, Jason Bertram, Joanna Masel","doi":"10.1101/2023.09.01.555871","DOIUrl":"10.1101/2023.09.01.555871","url":null,"abstract":"<p><p>Each new human has an expected <math> <mrow><msub><mi>U</mi> <mi>d</mi></msub> <mo>=</mo> <mn>2</mn> <mo>-</mo> <mn>10</mn></mrow> </math> new deleterious mutations. Using a novel approach to capture complex linkage disequilibria from high <math> <mrow><msub><mi>U</mi> <mi>d</mi></msub> </mrow> </math> using genome-wide simulations, we confirm that fitness decline due to the fixation of many slightly deleterious mutations can be compensated by rarer beneficial mutations of larger effect. The evolution of increased genome size and complexity have previously been attributed to a similarly asymmetric pattern of fixations, but we propose that the cause might be high <math> <mrow><msub><mi>U</mi> <mi>d</mi></msub> </mrow> </math> rather than the small population size posited as causal by drift barrier theory. High within-population variance in relative fitness is an inevitable consequence of high <math> <mrow><msub><mi>U</mi> <mi>d</mi></msub> <mo>∼</mo> <mn>2</mn> <mo>-</mo> <mn>10</mn></mrow> </math> combined with inferred human deleterious effect sizes; two individuals will typically differ in fitness by 15-40%. The need to compensate for the deluge of deleterious mutations slows net adaptation (i.e. to the external environment) by ~13%-55%. The rate of beneficial fixations is more sensitive to changes in the mutation rate than the rate of deleterious fixations is. As a surprising consequence of this, an increase (e.g. 10%) in overall mutation rate leads to faster adaptation; this puts to rest dysgenic fears about increasing mutation rates due to rising paternal age.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163941","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":"Knowledge of task duration affects energetic cost during split-belt adaptation and retention of walking patterns during post-adaptation.","authors":"S N Jeffcoat, A Aragon, A Kuch, S Farrokhi, A Hooyman Gstat, N Sanchez","doi":"10.1101/2024.05.24.595558","DOIUrl":"10.1101/2024.05.24.595558","url":null,"abstract":"<p><p>Humans continuously adapt locomotor patterns. Whether energetic cost reduction is the primary objective or a by-product of locomotor adaptation is not known. If energetic cost is the primary objective, then manipulating energetic cost will affect the locomotor pattern. Our study aims to determine if information about task duration affects energetic cost and locomotor adaptation during split-belt walking. We hypothesize that information about a longer adaptation duration will result in lower metabolic costs and lower mechanical work. N=52 participants walked for 10 minutes with the belts moving at 1.5 and 0.5 m/s, followed by 6 minutes of walking with both belts at 1.0 m/s. Nineteen participants walked on the split-belt while we provided True information about time remaining every minute (Group T). Nineteen participants received False information that split-belt adaptation duration was around 30 minutes (Group F). Fourteen participants walked on a split-belt with accurate information about task duration, and one update at 5 minutes remaining (Group C). Participants in Groups C and F had a lower rate of change in metabolic cost from baseline (p=0.002) and generated less positive work (p=0.012) than individuals in Group T. Changes in positive work by the fast leg predicted metabolic cost reductions only in Group F (R²=0.18, p=0.040). Participants in Group F showed greater split-belt aftereffects than the C and T groups (p<0.001). We conclude that walking biomechanics are adapted to support an energetic cost reduction when maintaining an energetic reserve is needed, as is the case for Group F, but not Group T.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201453","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":"nELISA: A high-throughput, high-plex platform enables quantitative profiling of the inflammatory secretome.","authors":"Milad Dagher, Grant Ongo, Nathaniel Robichaud, Jinglin Kong, Woojong Rho, Ivan Teahulos, Arya Tavakoli, Samantha Bovaird, Shahem Merjaneh, Andrew Tan, Kiran Edwardson, Christelle Scheepers, Andy Ng, Andy Hajjar, Baly Sow, Michael Vrouvides, Andy Lee, Philippe DeCorwin-Martin, Shafqat Rasool, Jiamin Huang, Timothy Erps, Spencer Coffin, Yu Han, Srinivas Niranj Chandrasekaran, Lisa Miller, Maria Kost-Alimova, Adam Skepner, Shantanu Singh, Anne E Carpenter, Jeffrey Munzar, David Juncker","doi":"10.1101/2023.04.17.535914","DOIUrl":"10.1101/2023.04.17.535914","url":null,"abstract":"<p><p>We present the nELISA, a high-throughput, high-fidelity, and high-plex protein profiling platform. DNA oligonucleotides are used to pre-assemble antibody pairs on spectrally encoded microparticles and perform displacement-mediated detection. Spatial separation between non-cognate antibodies prevents the rise of reagent-driven cross-reactivity, while read-out is performed cost-efficiently and at high-throughput using flow cytometry. nELISA can measure both protein concentration and their post-translational modifications. We assembled an inflammatory panel of 191 targets that were multiplexed without cross-reactivity nor impact on performance vs 1-plex signals, with sensitivities as low as 0.1 pg/mL and measurements spanning 7 orders of magnitude. We then performed a large-scale inflammatory-secretome perturbation screen of peripheral blood mononuclear cells (PBMCs), with cytokines as both perturbagens and readouts, measuring 7,392 samples and generating ~1.4M protein data points in under a week; a significant advance in throughput compared to other highly multiplexed immunoassays. We uncovered 447 significant cytokine responses, including multiple putatively novel ones, that were conserved across donors and stimulation conditions. We validate nELISA for phenotypic screening, where its capacity to faithfully report hundreds of proteins make it a powerful tool across multiple stages of drug discovery.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153206/pdf/nihpp-2023.04.17.535914v2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9986488","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 neuron contributions to the auditory brainstem EEG.","authors":"Paula T Kuokkanen, Ira Kraemer, Christine Koeppl, Catherine E Carr, Richard Kempter","doi":"10.1101/2024.05.29.596509","DOIUrl":"10.1101/2024.05.29.596509","url":null,"abstract":"<p><p>The auditory brainstem response (ABR) is an acoustically evoked EEG potential that is an important diagnostic tool for hearing loss, especially in newborns. The ABR originates from the response sequence of auditory nerve and brainstem nuclei, and a click-evoked ABR typically shows three positive peaks ('waves') within the first six milliseconds. However, an assignment of the waves of the ABR to specific sources is difficult, and a quantification of contributions to the ABR waves is not available. Here, we exploit the large size and physical separation of the barn owl first-order cochlear nucleus magnocellularis (NM) to estimate single-cell contributions to the ABR. We simultaneously recorded NM neurons' spikes and the EEG in owls of both sexes, and found that ≳ 5,000 spontaneous single-cell spikes are necessary to isolate a significant spike-triggered average response at the EEG electrode. An average single-neuron contribution to the ABR was predicted by convolving the spike-triggered average with the cell's peri-stimulus time histogram. Amplitudes of predicted contributions of single NM cells typically reached 32.9 ± 1.1 nV (mean ± SE, range: 2.5 - 162.7 nV), or 0.07 ± 0.02% (median ± SE; range from 0.01% to 1%) of the ABR amplitude. The time of the predicted peak coincided best with the peak of the ABR wave II, independent of the click sound level. Our results suggest that individual neurons' contributions to an EEG can vary widely, and that wave II of the ABR is shaped by NM units.</p><p><strong>Significance statement: </strong>The auditory brainstem response (ABR) is a scalp potential used for the diagnosis of hearing loss, both clinically and in research. We investigated the contribution of single action potentials from auditory brainstem neurons to the ABR and provide direct evidence that action potentials recorded in a first order auditory nucleus, and their EEG contribution, coincide with wave II of the ABR. The study also shows that the contribution of single cells varies strongly across the population.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297468","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":"Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.","authors":"Maria C Sterrett, Lauryn A Cureton, Lauren N Cohen, Ambro van Hoof, Sohail Khoshnevis, Milo B Fasken, Anita H Corbett, Homa Ghalei","doi":"10.1101/2023.10.18.562946","DOIUrl":"10.1101/2023.10.18.562946","url":null,"abstract":"<p><p>The RNA exosome is a multi-subunit, evolutionarily conserved ribonuclease complex that is essential for processing, decay and surveillance of many cellular RNAs. Missense mutations in genes encoding the structural subunits of the RNA exosome complex cause a diverse range of diseases, collectively known as RNA exosomopathies, often involving neurological and developmental defects. The varied symptoms suggest that different mutations lead to distinct <i>in vivo</i> consequences. To investigate these functional consequences and distinguish whether they are unique to each RNA exosomopathy mutation, we generated a collection of <i>in vivo</i> models by introducing pathogenic missense mutations in orthologous <i>S. cerevisiae</i> genes. Comparative RNA-seq analysis assessing broad transcriptomic changes in each mutant model revealed that three yeast mutant models, <i>rrp4-G226D, rrp40-W195R</i> and <i>rrp46-L191H,</i> which model mutations in the genes encoding EXOSC2, EXOSC3 and EXOSC5, respectively, had the largest transcriptomic differences. While some transcriptomic changes, particularly in transcripts related to ribosome biogenesis, were shared among mutant models, each mutation also induced unique transcriptomic changes. Thus, our data suggests that while there are some shared consequences, there are also distinct differences in RNA exosome function by each variant. Assessment of ribosome biogenesis and translation defects in the three models revealed distinct differences in polysome profiles. Collectively, our results provide the first comparative analyses of RNA exosomopathy mutant models and suggest that different RNA exosome gene mutations result in <i>in vivo</i> consequences that are both unique and shared across each variant, providing further insight into the biology underlying each distinct pathology.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415513","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":"Dynamically shifting from compositional to conjunctive brain representations supports cognitive task learning.","authors":"Ravi D Mill, Michael W Cole","doi":"10.1101/2023.06.27.546751","DOIUrl":"10.1101/2023.06.27.546751","url":null,"abstract":"<p><p>During cognitive task learning, neural representations must be rapidly constructed for novel task performance, then optimized for robust practiced task performance. How the geometry of neural representations changes to enable this transition from novel to practiced performance remains unknown. We hypothesized that practice involves a shift from compositional representations (task-general activity patterns that can be flexibly reused across tasks) to conjunctive representations (task-specific activity patterns specialized for the current task). Functional MRI during learning of multiple complex tasks substantiated this dynamic shift from compositional to conjunctive representations, which was associated with reduced cross-task interference (via pattern separation) and behavioral improvement. Further, we found that conjunctions originated in subcortex (hippocampus and cerebellum) and slowly spread to cortex, extending multiple memory systems theories to encompass cognitive task learning. The strengthening of conjunctive representations hence serves as a computational signature of learning, reflecting cortical-subcortical dynamics that optimize task representations in the human brain.</p><p><strong>Highlights: </strong>Learning shifts multi-task representations from compositional to conjunctive formatsCortical conjunctions uniquely associate with improved behavior and pattern separationThese conjunctions strengthen over separated learning events and index switch costsSubcortical regions are critical for cross-region binding of task rule information.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9865751","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 Basis for Enhanced Strigolactone Sensitivity in KAI2 Triple Mutant.","authors":"Briana L Sobecks, Jiming Chen, Tanner J Dean, Diwakar Shukla","doi":"10.1101/2023.01.18.524622","DOIUrl":"10.1101/2023.01.18.524622","url":null,"abstract":"<p><p><i>Striga hermonthica</i> is a parasitic weed that destroys billions of dollars' worth of staple crops every year. Its rapid proliferation stems from an enhanced ability to metabolize strigolactones (SLs), plant hormones that direct root branching and shoot growth. <i>Striga's</i> SL receptor, <i>Sh</i>HTL7, bears more similarity to the staple crop karrikin receptor KAI2 than to SL receptor D14, though KAI2 variants in plants like <i>Arabidopsis thaliana</i> show minimal SL sensitivity. Recently, studies have indicated that a small number of point mutations to HTL7 residues can confer SL sensitivity to <i>At</i>KAI2. Here, we analyze both wild-type <i>At</i>KAI2 and SL-sensitive mutant Var64 through all-atom, long-timescale molecular dynamics simulations to determine the effects of these mutations on receptor function at a molecular level. We demonstrate that the mutations stabilize SL binding by about 2 kcal/mol. They also result in a doubling of the average pocket volume, and eliminate the dependence of binding on certain pocket conformational arrangements. While the probability of certain non-binding SL-receptor interactions increases in the mutant compared with the wild-type, the rate of binding also increases by a factor of ten. All these changes account for the increased SL sensitivity in mutant KAI2, and suggest mechanisms for increasing functionality of host crop SL receptors.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/6f/nihpp-2023.01.18.524622v1.PMC9882355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657155","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":"Image-based identification and isolation of micronucleated cells to dissect cellular consequences.","authors":"Lucian DiPeso, Sriram Pendyala, Heather Z Huang, Douglas M Fowler, Emily M Hatch","doi":"10.1101/2023.05.04.539483","DOIUrl":"10.1101/2023.05.04.539483","url":null,"abstract":"<p><p>Recent advances in isolating cells based on visual phenotypes have transformed our ability to identify the mechanisms and consequences of complex traits. Micronucleus (MN) formation is a frequent outcome of genome instability, triggers extensive changes in genome structure and signaling coincident with MN rupture, and is almost exclusively defined by visual analysis. Automated MN detection in microscopy images has proved challenging, limiting discovery of the mechanisms and consequences of MN. In this study we describe two new MN segmentation modules: a rapid model for classifying micronucleated cells and their rupture status (VCS MN), and a robust model for accurate MN segmentation (MNFinder) from a broad range of cell lines. As proof-of-concept, we define the transcriptome of non-transformed human cells with intact or ruptured MN after chromosome missegregation by combining VCS MN with photoactivation-based cell isolation and RNASeq. Surprisingly, we find that neither MN formation nor rupture triggers a strong unique transcriptional response. Instead, transcriptional changes appear correlated with small increases in aneuploidy in these cell classes. Our MN segmentation modules overcome a significant challenge with reproducible MN quantification, and, joined with visual cell sorting, enable the application of powerful functional genomics assays to a wide-range of questions in MN biology.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9610318","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":"How Occam's razor guides human decision-making.","authors":"Eugenio Piasini, Shuze Liu, Pratik Chaudhari, Vijay Balasubramanian, Joshua I Gold","doi":"10.1101/2023.01.10.523479","DOIUrl":"10.1101/2023.01.10.523479","url":null,"abstract":"<p><p>Occam's razor is the principle that, all else being equal, simpler explanations should be preferred over more complex ones. This principle is thought to guide human decision-making, but the nature of this guidance is not known. Here we used preregistered behavioral experiments to show that people tend to prefer the simpler of two alternative explanations for uncertain data. These preferences match predictions of formal theories of model selection that penalize excessive flexibility. These penalties emerge when considering not just the best explanation but the integral over all possible, relevant explanations. We further show that these simplicity preferences persist in humans, but not in certain artificial neural networks, even when they are maladaptive. Our results imply that principled notions of statistical model selection, including integrating over possible, latent causes to avoid overfitting to noisy observations, may play a central role in human decision-making.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10790279","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 distinct roles of MSH2 and MLH1 in basal-like breast cancer and immune modulation.","authors":"Tanzia Islam Tithi, Jiao Mo, Nicholas Borcherding, Sung Jo, Heather R Kates, Edward Cho, Kailey E Cash, Masayoshi Honda, Lei Wang, Kawther K Ahmed, Kalyanee Shirlekar, Li Chen, Katherine Gibson-Corley, Ronald Weigel, Maria Spies, Ryan Kolb, Weizhou Zhang","doi":"10.1101/2023.07.20.549745","DOIUrl":"10.1101/2023.07.20.549745","url":null,"abstract":"<p><p>The mismatch repair (MMR) pathway is known as a tumor suppressive pathway and genes involved in MMR are commonly mutated in hereditary colorectal or other cancer types. However, the function of MMR genes/proteins in breast cancer progression and metastasis are largely undefined. We found that MSH2, but not MLH1, is highly enriched in basal-like breast cancer (BLBC) and that its protein expression is inversely correlated with overall survival time (OS). <i>MSH2</i> expression is frequently elevated due to genomic amplification or gain-of-expression in BLBC, which results in increased MSH2 protein to pair with MSH6 (collectively referred to as MutSα). Genetic deletion of <i>MSH2</i> or <i>MLH1</i> results in a contrasting phenotype in metastasis, with <i>MSH2</i> -deletion leading to reduced metastasis and <i>MLH1</i> -deletion to enhanced liver or lung metastasis. Mechanistically, MSH2 - but not MLH1 - binds to the promoter region of interferon α receptor 1 ( <i>IFNAR1</i> ) and suppresses its expression in BLBC. Deletion of MSH2 initiates a chain of immune reactions via the upregulation of IFNAR1 expression and the activation of type 1 interferon signaling, which explains a highly immune active tumor microenvironment in tumors with MSH2-deficiency. Our study supports the contrasting functions of MSH2 and MLH1 in BLBC progression and metastasis due to the differential regulation of IFNAR1 expression, which challenges the paradigm of the MMR pathway as a universal tumor suppressive mechanism.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/bd/nihpp-2023.07.20.549745v2.PMC10515760.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142416","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}