Manmeet S. Dhiman, Taylor J. Bader, Dragana Ponjevic, Paul T. Salo, David A. Hart, Ganesh Swamy, John R. Matyas, Neil A. Duncan
Introduction
Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD.
Methods
Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section.
Results
Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed.
Discussion and Conclusions
These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.
{"title":"Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide","authors":"Manmeet S. Dhiman, Taylor J. Bader, Dragana Ponjevic, Paul T. Salo, David A. Hart, Ganesh Swamy, John R. Matyas, Neil A. Duncan","doi":"10.1002/jsp2.1359","DOIUrl":"10.1002/jsp2.1359","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increases in mean fluorescence intensity (<i>p</i> = 0.0004) and percentage of positively stained area (<i>p</i> = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (<i>R</i> = 0.98, <i>p</i> = 5E-8) and DDD (<i>R</i> = 0.79, <i>p</i> = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusions</h3>\u0000 \u0000 <p>These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily E. McDonnell, Tara Ní Néill, Niamh Wilson, Stacey L. Darwish, Joseph S. Butler, Conor T. Buckley
<div> <section> <h3> Background</h3> <p>While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor-5 (GDF-5), no results have been publicly released.</p> </section> <section> <h3> Aims</h3> <p>The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF-5 (0.25, 1, and 2 mg) as a therapeutic for disc regeneration.</p> </section> <section> <h3> Materials and methods</h3> <p>Firstly, this work experimentally determined the effects of GDF-5 concentration on the metabolic and matrix synthesis rates of human nucleus pulposus (NP) cells. Secondly, in silico modeling was employed to predict the subsequent regenerative effect of different GDF-5 treatments (± cells).</p> </section> <section> <h3> Results</h3> <p>This study suggests a trend of increased matrix synthesis with 0.25 and 1 mg of GDF-5. However, 2 mg of GDF-5 significantly upregulates oxygen consumption. Despite this, in silico models highlight the potential of growth factors in promoting matrix synthesis compared to cell-only treatments, without significantly perturbing the nutrient microenvironment.</p> </section> <section> <h3> Discussion</h3> <p>This work elucidates the potential of GDF-5 on human NP cells. Although the results did not reveal statistical differences across all doses, the variability and response among donors is an interesting finding. It highlights the complexity of human response to biological treatments and reinforces the need for further human research and personalized approaches. Furthermore, this study raises a crucial question about whether these potential biologics are more regenerative in nature or better suited as prophylactic therapies for younger patient groups.</p> </section> <section> <h3> Conclusion</h3> <p>Biological agents exhibit unique characteristics and features, demanding tailored development strategies and individualized assessments rather than a one-size-fits-all approach. Therefore, the journey to realizing the full potential of biological therapies is long and costly. Nonetheless, it holds the promise of revolutionizing spinal healthcare and improving the quality of life for patients suffering
{"title":"In silico modeling the potential clinical effect of growth factor treatment on the metabolism of human nucleus pulposus cells","authors":"Emily E. McDonnell, Tara Ní Néill, Niamh Wilson, Stacey L. Darwish, Joseph S. Butler, Conor T. Buckley","doi":"10.1002/jsp2.1352","DOIUrl":"10.1002/jsp2.1352","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor-5 (GDF-5), no results have been publicly released.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF-5 (0.25, 1, and 2 mg) as a therapeutic for disc regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Firstly, this work experimentally determined the effects of GDF-5 concentration on the metabolic and matrix synthesis rates of human nucleus pulposus (NP) cells. Secondly, in silico modeling was employed to predict the subsequent regenerative effect of different GDF-5 treatments (± cells).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study suggests a trend of increased matrix synthesis with 0.25 and 1 mg of GDF-5. However, 2 mg of GDF-5 significantly upregulates oxygen consumption. Despite this, in silico models highlight the potential of growth factors in promoting matrix synthesis compared to cell-only treatments, without significantly perturbing the nutrient microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This work elucidates the potential of GDF-5 on human NP cells. Although the results did not reveal statistical differences across all doses, the variability and response among donors is an interesting finding. It highlights the complexity of human response to biological treatments and reinforces the need for further human research and personalized approaches. Furthermore, this study raises a crucial question about whether these potential biologics are more regenerative in nature or better suited as prophylactic therapies for younger patient groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Biological agents exhibit unique characteristics and features, demanding tailored development strategies and individualized assessments rather than a one-size-fits-all approach. Therefore, the journey to realizing the full potential of biological therapies is long and costly. Nonetheless, it holds the promise of revolutionizing spinal healthcare and improving the quality of life for patients suffering","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, tissue homeostasis, and optimization of biomechanical tissue functions. Perlecan-mediated osmotic mechanotransduction serves to regulate the metabolic activity of cells in tissues subjected to tension, compression, or shear. Perlecan interacts with a vast array of extracellular matrix (ECM) proteins through which it stabilizes tissues and regulates the proliferation or differentiation of resident cell populations. Here we examine the roles of the HS-proteoglycan perlecan in the normal and destabilized intervertebral disc. The intervertebral disc cell has evolved to survive in a hostile weight bearing, acidic, low oxygen tension, and low nutrition environment, and perlecan provides cytoprotection, shields disc cells from excessive compressive forces, and sequesters a range of growth factors in the disc cell environment where they aid in cellular survival, proliferation, and differentiation. The cells in mechanically destabilized connective tissues attempt to re-establish optimal tissue composition and tissue functional properties by changing the properties of their ECM, in the process of chondroid metaplasia. We explore the possibility that perlecan assists in these cell-mediated tissue remodeling responses by regulating disc cell anabolism. Perlecan's mechano-osmotic transductive property may be of potential therapeutic application.
{"title":"Diverse and multifunctional roles for perlecan (HSPG2) in repair of the intervertebral disc","authors":"James Melrose, Farshid Guilak","doi":"10.1002/jsp2.1362","DOIUrl":"10.1002/jsp2.1362","url":null,"abstract":"<p>Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, tissue homeostasis, and optimization of biomechanical tissue functions. Perlecan-mediated osmotic mechanotransduction serves to regulate the metabolic activity of cells in tissues subjected to tension, compression, or shear. Perlecan interacts with a vast array of extracellular matrix (ECM) proteins through which it stabilizes tissues and regulates the proliferation or differentiation of resident cell populations. Here we examine the roles of the HS-proteoglycan perlecan in the normal and destabilized intervertebral disc. The intervertebral disc cell has evolved to survive in a hostile weight bearing, acidic, low oxygen tension, and low nutrition environment, and perlecan provides cytoprotection, shields disc cells from excessive compressive forces, and sequesters a range of growth factors in the disc cell environment where they aid in cellular survival, proliferation, and differentiation. The cells in mechanically destabilized connective tissues attempt to re-establish optimal tissue composition and tissue functional properties by changing the properties of their ECM, in the process of chondroid metaplasia. We explore the possibility that perlecan assists in these cell-mediated tissue remodeling responses by regulating disc cell anabolism. Perlecan's mechano-osmotic transductive property may be of potential therapeutic application.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The annulus fibrosus (AF) of the Intervertebral disc (IVD) is composed of concentric lamellae of helically wound collagen fibers. Understanding the spatial variation of collagen fiber orientations in these lamellae, and the resulting material anisotropy, is crucial to predicting the mechanical behavior of the complete IVD.
Methods
This study builds on a prior model predicated on path-independent displacement of fiber endpoints during vertebral body growth to predict a complete, three-dimensional annulus fibrosus fiber network from a small number of subject-independent input parameters and vertebral endplate topographies obtained from clinical imaging. To evaluate the model, it was first fit to mid-plane fiber orientations obtained using polarized light microscopy in a population of bovine caudal discs for which computed tomography images vertebral endplates were also available. Additionally, the model was used to predict the trajectories based on human lumbar disc geometries and results were compared to previously reported data. Finally, the model was employed to investigate potential disc-related variations in fiber angle distributions.
Results
The model was able to accurately predict experimentally measured fiber distributions in both bovine and human discs using only endplate topography and three input parameters. Critically, the model recapitulated previously observed asymmetry between the inclinations of right- and left-handed fibers in the posterolateral aspect of the human AF. Level to level variation of disc height and aspect ratio in the human lumbar spine was predicted to affect absolute values of fiber inclination, but not this asymmetry.
Conclusion
Taken together these results suggest that patient-specific distributions of AF fiber orientation may be readily incorporated into computational models of the spine using only disc geometry and a small number of subject-independent parameters.
{"title":"Three-dimensional fiber patterning in the annulus fibrosus can be derived from vertebral endplate topography","authors":"Ali Raza, Gwynneth T. Howell, Arthur J. Michalek","doi":"10.1002/jsp2.1361","DOIUrl":"10.1002/jsp2.1361","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The annulus fibrosus (AF) of the Intervertebral disc (IVD) is composed of concentric lamellae of helically wound collagen fibers. Understanding the spatial variation of collagen fiber orientations in these lamellae, and the resulting material anisotropy, is crucial to predicting the mechanical behavior of the complete IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study builds on a prior model predicated on path-independent displacement of fiber endpoints during vertebral body growth to predict a complete, three-dimensional annulus fibrosus fiber network from a small number of subject-independent input parameters and vertebral endplate topographies obtained from clinical imaging. To evaluate the model, it was first fit to mid-plane fiber orientations obtained using polarized light microscopy in a population of bovine caudal discs for which computed tomography images vertebral endplates were also available. Additionally, the model was used to predict the trajectories based on human lumbar disc geometries and results were compared to previously reported data. Finally, the model was employed to investigate potential disc-related variations in fiber angle distributions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The model was able to accurately predict experimentally measured fiber distributions in both bovine and human discs using only endplate topography and three input parameters. Critically, the model recapitulated previously observed asymmetry between the inclinations of right- and left-handed fibers in the posterolateral aspect of the human AF. Level to level variation of disc height and aspect ratio in the human lumbar spine was predicted to affect absolute values of fiber inclination, but not this asymmetry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together these results suggest that patient-specific distributions of AF fiber orientation may be readily incorporated into computational models of the spine using only disc geometry and a small number of subject-independent parameters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fei Liu, Min Zhong, Lei Yang, Chao Song, Chaoqi Chen, Zhiwei Xu, Chi Zhang, Zhifa Li, Xiaofei Wu, Chen Jiang, Feng Chen, Qian Yan
<div> <section> <h3> Background</h3> <p>Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended.</p> </section> <section> <h3> Objective</h3> <p>The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum.</p> </section> <section> <h3> Methods</h3> <p>The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting.</p> </section> <section> <h3> Results</h3> <p>Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine–cytokine receptor interaction, and TGF-β signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group.</p> </section> <section> <h3> Conclusion</h3> <p>The TGF-β signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.</p>
背景：黄韧带肥厚症是一种常见的慢性脊柱疾病，多发于中老年人。然而，人们对这种疾病背后的分子途径还不甚了解：这项工作的目的是采用生物信息学技术，以确定与黄韧带肥厚有关的关键生物标记和免疫浸润。此外，该研究还旨在通过实验证实黄韧带肥厚的分子机制：方法：从全面的基因表达数据库中筛选出相应的基因表达谱（GSE113212）。黄韧带肥厚的基因数据集来自 GeneCards。建立了蛋白质之间的相互作用网络，并利用京都基因和基因组百科全书（KEGG）和基因本体（GO）数据库进行了功能富集分析。对枢纽基因进行了研究，以评估与对照组组织相比，患者样本中免疫细胞的浸润情况。最后，还采集了黄韧带样本，以验证重要基因在临床环境中的表达情况：结果：通过分子生物学研究，共发现了 27 个表达不同的中心基因。通过 GO 和 KEGG 研究发现，这些中心基因主要集中在免疫反应、趋化因子介导的信号通路、炎症、骨化和纤维化过程中。涉及的主要信号通路包括 TNF 信号通路、细胞因子-细胞因子受体相互作用和 TGF-β 信号通路。对免疫细胞浸润的研究显示，肥厚性黄韧带患者与健康人对照组之间在 B 细胞（幼稚细胞和记忆细胞）和活化 T 细胞（CD4 记忆细胞）方面存在明显差异。体外验证显示，与正常组相比，黄韧带肥厚组的骨化和纤维化相关成分水平明显升高：结论：TGF-β信号通路、TNF信号通路及相关枢纽基因在黄韧带肥大症的进展中起着关键作用。我们的研究可为今后有关黄韧带纤维化的研究提供指导。
{"title":"Experimental confirmation and bioinformatics reveal biomarkers of immune system infiltration and hypertrophy ligamentum flavum","authors":"Fei Liu, Min Zhong, Lei Yang, Chao Song, Chaoqi Chen, Zhiwei Xu, Chi Zhang, Zhifa Li, Xiaofei Wu, Chen Jiang, Feng Chen, Qian Yan","doi":"10.1002/jsp2.1354","DOIUrl":"10.1002/jsp2.1354","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine–cytokine receptor interaction, and TGF-β signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The TGF-β signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.</p>\u0000 ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parham Foroutan, Ryan D. Quarrington, Michael Pyrros Russo, Boyin Ding, Peter A. Cripton, John J. Costi, Claire F. Jones
Background
Facet fractures are frequently associated with clinically observed cervical facet dislocations (CFDs); however, to date there has only been one experimental study, using functional spinal units (FSUs), which has systematically produced CFD with concomitant facet fracture. The role of axial compression and distraction on the mechanical response of the cervical facets under intervertebral motions associated with CFD in FSUs has previously been shown. The same has not been demonstrated in multi-segment lower cervical spine specimens under flexion loading (postulated to be the local injury vector associated with CFD).
Methods
This study investigated the mechanical response of the bilateral inferior C6 facets of thirteen C5-C7 specimens (67±13 yr, 6 male) during non-destructive constrained flexion, superimposed with each of five axial conditions: (1) 50 N compression (simulating weight of the head); (2-4) 300, 500, and 1000 N compression (simulating the spectrum of intervertebral compression resulting from neck muscle bracing prior to head-first impact and/or externally applied compressive forces); and, (5) 2 mm of C6/C7 distraction (simulating the intervertebral distraction present during inertial loading of the cervical spine by the weight of the head). Linear mixed-effects models (α = 0.05) assessed the effect of axial condition.
Results
Increasing amounts of intervertebral compression superimposed on flexion rotations, resulted in increased facet surface strains (range of estimated mean difference relative to Neutral: maximum principal = 77 to 110 με, minimum principal = 126 to 293 με, maximum shear = 203 to 375 με) and angular deflection of the bilateral inferior C6 facets relative to the C6 vertebral body (range of estimated mean difference relative to Neutral = 0.59° to 1.47°).
Conclusions
These findings suggest increased facet engagement and higher load transfer through the facet joint, and potentially a higher likelihood of facet fracture under the compressed axial conditions.
背景：面骨骨折经常与临床观察到的颈椎面骨脱位（CFDs）有关；然而，迄今为止只有一项实验研究使用功能脊柱单元（FSUs）系统地产生了伴有面骨骨折的颈椎面骨脱位。在功能性脊柱单元中，轴向压缩和牵张对颈椎面在与 CFD 相关的椎间运动下的机械响应的作用已被证实。但在屈曲负荷（推测为与 CFD 相关的局部损伤矢量）下的多节段下颈椎标本中，尚未发现同样的情况：本研究调查了 13 个 C5-C7 标本（67±13 岁，6 名男性）的双侧 C6 下椎面在非破坏性约束屈曲时的机械响应，并分别叠加了五种轴向条件：(1) 50 N 压缩（模拟头部重量）；(2-4) 300、500 和 1000 N 压缩（模拟头先撞击和/或外部施加压缩力之前颈部肌肉支撑导致的椎间压缩谱）；以及，(5) 2 mm C6/C7 牵张（模拟头部重量对颈椎造成惯性负载时出现的椎间牵张）。线性混合效应模型（α = 0.05）评估了轴向条件的影响：结果：在屈曲旋转的基础上，椎间压缩量的增加导致切面表面应变增加（相对于中立位的估计平均差范围：最大本构=77至110με，最小本构=126至293με，最大剪切=203至375με），以及双侧下C6切面相对于C6椎体的角度偏移（相对于中立位的估计平均差范围=0.59°至1.47°）：这些研究结果表明，在压缩轴向条件下，关节面啮合增加，通过关节面传递的负荷增加，关节面骨折的可能性也可能增加。
{"title":"Facet deflection and strain are dependent on axial compression and distraction in C5–C7 spinal segments under constrained flexion","authors":"Parham Foroutan, Ryan D. Quarrington, Michael Pyrros Russo, Boyin Ding, Peter A. Cripton, John J. Costi, Claire F. Jones","doi":"10.1002/jsp2.1360","DOIUrl":"10.1002/jsp2.1360","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Facet fractures are frequently associated with clinically observed cervical facet dislocations (CFDs); however, to date there has only been one experimental study, using functional spinal units (FSUs), which has systematically produced CFD with concomitant facet fracture. The role of axial compression and distraction on the mechanical response of the cervical facets under intervertebral motions associated with CFD in FSUs has previously been shown. The same has not been demonstrated in multi-segment lower cervical spine specimens under flexion loading (postulated to be the local injury vector associated with CFD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study investigated the mechanical response of the bilateral inferior C6 facets of thirteen C5-C7 specimens (67±13 yr, 6 male) during non-destructive constrained flexion, superimposed with each of five axial conditions: (1) 50 N compression (simulating weight of the head); (2-4) 300, 500, and 1000 N compression (simulating the spectrum of intervertebral compression resulting from neck muscle bracing prior to head-first impact and/or externally applied compressive forces); and, (5) 2 mm of C6/C7 distraction (simulating the intervertebral distraction present during inertial loading of the cervical spine by the weight of the head). Linear mixed-effects models (α = 0.05) assessed the effect of axial condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increasing amounts of intervertebral compression superimposed on flexion rotations, resulted in increased facet surface strains (range of estimated mean difference relative to Neutral: <i>maximum principal</i> = 77 to 110 με, <i>minimum principal</i> = 126 to 293 με, <i>maximum shear</i> = 203 to 375 με) and angular deflection of the bilateral inferior C6 facets relative to the C6 vertebral body (range of estimated mean difference relative to Neutral = 0.59° to 1.47°).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest increased facet engagement and higher load transfer through the facet joint, and potentially a higher likelihood of facet fracture under the compressed axial conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianyuan Zhang, Wenyuan Sui, Bin Li, Xiexiang Shao, Yaolong Deng, Zifang Zhang, Jingfan Yang, Zifang Huang, Wenjun Yang, Junlin Yang
Introduction
Prior studies suggested that neuromuscular factors might be involved in the pathogenesis of adolescent idiopathic scoliosis (AIS). The neuromuscular junction (NMJ) is the important pivot where the nervous system interacts with muscle fibers, but it has not been well characterized in the paraspinal muscles of AIS. This study aims to perform the quantitative morphological analysis of NMJs from paraspinal muscles of AIS.
Methods
AIS patients who received surgery in our center were prospectively enrolled. Meanwhile, age-matched congenital scoliosis (CS) and non-scoliosis patients were also included as controls. Fresh samples of paraspinal muscles were harvested intraoperatively. NMJs were immunolabeled using different antibodies to reveal pre-synaptic neuronal architecture and post-synaptic motor endplates. A confocal microscope was used to acquire z-stack projections of NMJs images. Then, NMJs images were analyzed on maximum intensity projections using ImageJ software. The morphology of NMJs was quantitatively measured by a standardized ‘NMJ-morph’ workflow. A total of 21 variables were measured and compared between different groups.
Results
A total of 15 AIS patients, 10 CS patients and 5 normal controls were enrolled initially. For AIS group, NMJs in the convex side of paraspinal muscles demonstrated obviously decreased overlap when compared with the concave side (34.27% ± 8.09% vs. 48.11% ± 10.31%, p = 0.0036). However, no variables showed statistical difference between both sides of paraspinal muscles in CS patients. In contrast with non-scoliosis controls, both sides of paraspinal muscles in AIS patients demonstrated significantly smaller muscle bundle diameters.
Conclusions
This study first elucidated the morphological features of NMJs from paraspinal muscles of AIS patients. The NMJs in the convex side showed smaller overlap for AIS patients, but no difference was found in CS. This proved further evidence that neuromuscular factors might contribute to the mechanisms of AIS and could be considered as a novel potential therapeutic target for the treatment of progressive AIS.
{"title":"The morphological discrepancy of neuromuscular junctions between bilateral paraspinal muscles in patients with adolescent idiopathic scoliosis: A quantitative immunofluorescence assay","authors":"Tianyuan Zhang, Wenyuan Sui, Bin Li, Xiexiang Shao, Yaolong Deng, Zifang Zhang, Jingfan Yang, Zifang Huang, Wenjun Yang, Junlin Yang","doi":"10.1002/jsp2.1358","DOIUrl":"10.1002/jsp2.1358","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Prior studies suggested that neuromuscular factors might be involved in the pathogenesis of adolescent idiopathic scoliosis (AIS). The neuromuscular junction (NMJ) is the important pivot where the nervous system interacts with muscle fibers, but it has not been well characterized in the paraspinal muscles of AIS. This study aims to perform the quantitative morphological analysis of NMJs from paraspinal muscles of AIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AIS patients who received surgery in our center were prospectively enrolled. Meanwhile, age-matched congenital scoliosis (CS) and non-scoliosis patients were also included as controls. Fresh samples of paraspinal muscles were harvested intraoperatively. NMJs were immunolabeled using different antibodies to reveal pre-synaptic neuronal architecture and post-synaptic motor endplates. A confocal microscope was used to acquire z-stack projections of NMJs images. Then, NMJs images were analyzed on maximum intensity projections using ImageJ software. The morphology of NMJs was quantitatively measured by a standardized ‘NMJ-morph’ workflow. A total of 21 variables were measured and compared between different groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 15 AIS patients, 10 CS patients and 5 normal controls were enrolled initially. For AIS group, NMJs in the convex side of paraspinal muscles demonstrated obviously decreased overlap when compared with the concave side (34.27% ± 8.09% vs. 48.11% ± 10.31%, <i>p</i> = 0.0036). However, no variables showed statistical difference between both sides of paraspinal muscles in CS patients. In contrast with non-scoliosis controls, both sides of paraspinal muscles in AIS patients demonstrated significantly smaller muscle bundle diameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study first elucidated the morphological features of NMJs from paraspinal muscles of AIS patients. The NMJs in the convex side showed smaller overlap for AIS patients, but no difference was found in CS. This proved further evidence that neuromuscular factors might contribute to the mechanisms of AIS and could be considered as a novel potential therapeutic target for the treatment of progressive AIS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Nikpasand, Jill M. Middendorf, Vincent A. Ella, Kristen E. Jones, Bryan Ladd, Takashi Takahashi, Victor H. Barocas, Arin M. Ellingson
Background
Degeneration of both intervertebral discs (IVDs) and facet joints in the lumbar spine has been associated with low back pain, but whether and how IVD/joint degeneration contributes to pain remains an open question. Joint degeneration can be identified by pairing T1 and T2 magnetic resonance imaging (MRI) with analysis techniques such as Pfirrmann grades (IVD degeneration) and Fujiwara scores (facet degeneration). However, these grades are subjective, prompting the need to develop an automated technique to enhance inter-rater reliability. This study introduces an automated convolutional neural network (CNN) technique trained on clinical MRI images of IVD and facet joints obtained from public-access Lumbar Spine MRI Dataset. The primary goal of the automated system is to classify health of lumbar discs and facet joints according to Pfirrmann and Fujiwara grading systems and to enhance inter-rater reliability associated with these grading systems.
Methods
Performance of the CNN on both the Pfirrmann and Fujiwara scales was measured by comparing the percent agreement, Pearson's correlation and Fleiss kappa value for results from the classifier to the grades assigned by an expert grader.
Results
The CNN demonstrates comparable performance to human graders for both Pfirrmann and Fujiwara grading systems, but with larger errors in Fujiwara grading. The CNN improves the reliability of the Pfirrmann system, aligning with previous findings for IVD assessment.
Conclusion
The study highlights the potential of using deep learning in classifying the IVD and facet joint health, and due to the high variability in the Fujiwara scoring system, highlights the need for improved imaging and scoring techniques to evaluate facet joint health. All codes required to use the automatic grading routines described herein are available in the Data Repository for University of Minnesota (DRUM).
{"title":"Automated magnetic resonance imaging-based grading of the lumbar intervertebral disc and facet joints","authors":"Maryam Nikpasand, Jill M. Middendorf, Vincent A. Ella, Kristen E. Jones, Bryan Ladd, Takashi Takahashi, Victor H. Barocas, Arin M. Ellingson","doi":"10.1002/jsp2.1353","DOIUrl":"10.1002/jsp2.1353","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Degeneration of both intervertebral discs (IVDs) and facet joints in the lumbar spine has been associated with low back pain, but whether and how IVD/joint degeneration contributes to pain remains an open question. Joint degeneration can be identified by pairing T1 and T2 magnetic resonance imaging (MRI) with analysis techniques such as Pfirrmann grades (IVD degeneration) and Fujiwara scores (facet degeneration). However, these grades are subjective, prompting the need to develop an automated technique to enhance inter-rater reliability. This study introduces an automated convolutional neural network (CNN) technique trained on clinical MRI images of IVD and facet joints obtained from public-access Lumbar Spine MRI Dataset. The primary goal of the automated system is to classify health of lumbar discs and facet joints according to Pfirrmann and Fujiwara grading systems and to enhance inter-rater reliability associated with these grading systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Performance of the CNN on both the Pfirrmann and Fujiwara scales was measured by comparing the percent agreement, Pearson's correlation and Fleiss kappa value for results from the classifier to the grades assigned by an expert grader.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CNN demonstrates comparable performance to human graders for both Pfirrmann and Fujiwara grading systems, but with larger errors in Fujiwara grading. The CNN improves the reliability of the Pfirrmann system, aligning with previous findings for IVD assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study highlights the potential of using deep learning in classifying the IVD and facet joint health, and due to the high variability in the Fujiwara scoring system, highlights the need for improved imaging and scoring techniques to evaluate facet joint health. All codes required to use the automatic grading routines described herein are available in the Data Repository for University of Minnesota (DRUM).</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongzhao Zhao, Qian Xiang, Shuai Jiang, Jialiang Lin, Weishi Li
Backgrounds
The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation.
Methods
A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells.
Results
There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells.
Conclusions
This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.
{"title":"Revealing the novel metabolism-related genes in the ossification of the ligamentum flavum based on whole transcriptomic data","authors":"Yongzhao Zhao, Qian Xiang, Shuai Jiang, Jialiang Lin, Weishi Li","doi":"10.1002/jsp2.1357","DOIUrl":"10.1002/jsp2.1357","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmet Payas, Hikmet Kocaman, Hasan Yıldırım, Sabri Batın
Background
It is known that neuroanatomical and neurofunctional changes observed in the brain, brainstem and cerebellum play a role in the etiology of adolescent idiopathic scoliosis (AIS). This study aimed to investigate whether volumetric measurements of brain regions can be used as predictive indicators for AIS through machine learning techniques.
Methods
Patients with a severe degree of curvature in AIS (n = 32) and healthy individuals (n = 31) were enrolled in the study. Volumetric data from 169 brain regions, acquired from magnetic resonance imaging (MRI) of these individuals, were utilized as predictive factors. A comprehensive analysis was conducted using the twelve most prevalent machine learning algorithms, encompassing thorough parameter adjustments and cross-validation processes. Furthermore, the findings related to variable significance are presented.
Results
Among all the algorithms evaluated, the random forest algorithm produced the most favorable results in terms of various classification metrics, including accuracy (0.9083), AUC (0.993), f1-score (0.970), and Brier score (0.1256). Additionally, the most critical variables were identified as the volumetric measurements of the right corticospinal tract, right corpus callosum body, right corpus callosum splenium, right cerebellum, and right pons, respectively.
Conclusion
The outcomes of this study indicate that volumetric measurements of specific brain regions can serve as reliable indicators of AIS. In conclusion, the developed model and the significant variables discovered hold promise for predicting scoliosis development, particularly in high-risk individuals.
{"title":"Prediction of adolescent idiopathic scoliosis with machine learning algorithms using brain volumetric measurements","authors":"Ahmet Payas, Hikmet Kocaman, Hasan Yıldırım, Sabri Batın","doi":"10.1002/jsp2.1355","DOIUrl":"10.1002/jsp2.1355","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is known that neuroanatomical and neurofunctional changes observed in the brain, brainstem and cerebellum play a role in the etiology of adolescent idiopathic scoliosis (AIS). This study aimed to investigate whether volumetric measurements of brain regions can be used as predictive indicators for AIS through machine learning techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with a severe degree of curvature in AIS (<i>n</i> = 32) and healthy individuals (<i>n</i> = 31) were enrolled in the study. Volumetric data from 169 brain regions, acquired from magnetic resonance imaging (MRI) of these individuals, were utilized as predictive factors. A comprehensive analysis was conducted using the twelve most prevalent machine learning algorithms, encompassing thorough parameter adjustments and cross-validation processes. Furthermore, the findings related to variable significance are presented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among all the algorithms evaluated, the random forest algorithm produced the most favorable results in terms of various classification metrics, including accuracy (0.9083), AUC (0.993), f1-score (0.970), and Brier score (0.1256). Additionally, the most critical variables were identified as the volumetric measurements of the right corticospinal tract, right corpus callosum body, right corpus callosum splenium, right cerebellum, and right pons, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The outcomes of this study indicate that volumetric measurements of specific brain regions can serve as reliable indicators of AIS. In conclusion, the developed model and the significant variables discovered hold promise for predicting scoliosis development, particularly in high-risk individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号