JOR Spine最新文献_第4页

Nucleus pulposus structure and function assessed in shear using magnetic resonance elastography, quantitative MRI, and rheometry 利用磁共振弹性成像、定量磁共振成像和流变仪评估剪切力作用下的髓核结构和功能

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-05-13 DOI: 10.1002/jsp2.1335

Megan Co, Brian Raterman, Brett Klamer, Arunark Kolipaka, Benjamin Walter

Background

In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI.

Method

MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters.

Results

MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content.

Conclusion

This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue.

背景通过定量磁共振成像（MRI）对椎间盘（IVD）的结构-功能关系进行活体量化，有可能有助于对疾病进行客观分层和评估修复疗法。磁共振弹性成像（MRE）是一种评估组织剪切特性的成像技术，它与反映成分的定量 MRI 指标相结合，可为 IVD 的结构-功能提供信息。本研究的目的是：(1) 比较琼脂糖凝胶和髓核（NP）组织中的 MRE 和流变学衍生剪切模量；(2) 将 NP 组织的 MRE 和流变学测量与成分和定量 MRI 相关联。方法对琼脂糖样品（2%、3% 和 4% (w/v)；n = 3-4/%）和在 5% 或 25% PEG（n = 13/PEG%）中平衡透析后的牛尾 IVD 进行 MRE 和 MRI 评估（即 T1ρ 和 T2 映像）。随后，对琼脂糖和 NP 组织进行了扭转机械测试，包括在 0.05% 的旋转应变下进行 1 到 100 Hz 的频率扫描。此外，还在蠕变和应力松弛条件下对 NP 组织进行了评估。线性混合效应模型和单变量回归分析评估了测试方法、琼脂糖或聚乙二醇百分比和频率的影响以及参数之间的相关性。结果在所有琼脂糖和 NP 组织样本中，MRE 和流变仪得出的剪切模量在 100 Hz 时均大于 80 Hz。此外，所有含水量较低的样本都具有较高的复合剪切模量。对于均质琼脂糖样品，MRE 和流变仪得出的模量值之间存在明显的相关性。琼脂糖和组织的 T1ρ 和 T2 松弛时间与这两种技术得出的复合剪切模量呈负相关。对于 NP 组织，剪切模量与凝胶体/湿重呈正相关，与含水率呈负相关。结论这项研究表明，MRE 可以评估水合引起的 IVD 剪切特性的变化，并进一步强调了 NP 组织的组成和剪切机械行为之间的结构-功能关系。

{"title":"Nucleus pulposus structure and function assessed in shear using magnetic resonance elastography, quantitative MRI, and rheometry","authors":"Megan Co, Brian Raterman, Brett Klamer, Arunark Kolipaka, Benjamin Walter","doi":"10.1002/jsp2.1335","DOIUrl":"https://doi.org/10.1002/jsp2.1335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); <i>n</i> = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (<i>n</i> = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914790","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}

引用次数: 0

Improving how orthopedic journals report research outcomes based on sex and gender 改进骨科期刊根据性别报告研究成果的方式

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-05-06 DOI: 10.1002/jsp2.1334

Seth S. Leopold, Robert N. Hensinger, Andrew J. Schoenfeld, Marc Swiontkowski, Michael J. Rossi, Kimberly J. Templeton, Sex and Gender Research in Orthopaedic Journals Group

Sex-based differences in cell biology, tissue function, and anatomy impact disease risk, presentation, and treatment outcomes,¹ including in musculoskeletal care.^2-4 As such, these differences should influence how orthopedic surgeons and other healthcare professionals conduct research and provide care for patients who have musculoskeletal disease and injury. In addition, gender roles influence interactions with people who conduct research and healthcare professionals, as well as the likelihood that patients will seek care and how they will respond to treatment.^{1, 5, 6}

Musculoskeletal research, similar to research in other areas of healthcare, does not always disaggregate results based on a patient's sex or gender.⁷ Although some orthopedic surgery journals have explicit editorial standards on the topic of sex and gender in scientific reporting, and although international entities have published sensible guidelines about it,⁸ we have observed that these standards are inconsistently applied.⁷

Inattention to high-quality standards of scientific reporting can harm patients.^{9, 10} Women have been underrepresented in medical research,¹¹ and this trend continues to varying degrees even today, despite mandates to remedy this disparity, at least in federally funded research.^{12, 13} However, these mandates include no guidance about how data should be analyzed or reported, thereby limiting the impact of including more women in clinical studies. The care of women has been substantially compromised as a result^14-18; not getting this right has sometimes harmed men with certain diagnoses as well.¹⁹ As such, it is no stretch to say that doing better research—and improving how that research is reported in journals—would benefit our patients regardless of their sex or gender.

With this background in mind, leaders of the editorial boards of six orthopedic journals, along with leaders of funding agencies, as well as National Institutes of Health officials, met in November 2023 to discuss these issues. Following that meeting, those editors reached out to the Editors-in-Chief of all indexed orthopedic surgery journals, seeking concurrence on a few key themes pertaining to the reporting of sex and gender in musculoskeletal research.

We hope that by sharing these resolutions with readers, many of whom are also researchers and representatives on institutional review boards, institutional animal care and use committees, and/or funding agencies and organizations, the orthopedic research of the future will be both better designed and better reported.

Funding for this conference was made possible (in part) by (1R13AR082710–01) from the National Institute of Arthritis and Musculoskeleta

细胞生物学、组织功能和解剖学方面的性别差异会影响疾病的风险、表现和治疗效果，1 包括肌肉骨骼方面的治疗效果。2-4 因此，这些差异会影响骨科医生和其他医疗保健专业人员如何开展研究以及如何为患有肌肉骨骼疾病和损伤的患者提供治疗。此外，性别角色还会影响与研究人员和医护人员之间的互动，以及患者寻求治疗的可能性和他们对治疗的反应。1, 5, 6 肌肉骨骼研究与其他医疗保健领域的研究类似，并不总是根据患者的性别对研究结果进行分类。9, 10 女性在医学研究中的代表性一直不足，11 而且这种趋势至今仍在不同程度上持续，尽管有规定要求弥补这种差距，至少在联邦政府资助的研究中是如此。12, 13 然而，这些规定并不包括关于如何分析或报告数据的指导，从而限制了将更多女性纳入临床研究的影响。有鉴于此，六家骨科期刊编辑部的领导、资助机构的领导以及美国国立卫生研究院的官员于 2023 年 11 月召开会议，讨论这些问题。我们希望，通过与读者分享这些决议，未来的骨科研究将得到更好的设计和更好的报告，而读者中的许多人也是研究人员以及机构审查委员会、机构动物护理和使用委员会和/或资助机构和组织的代表。临床骨科及相关研究》、《小儿骨科杂志》和《脊柱》主编；《关节镜》助理主编的所有 ICMJE 潜在利益冲突披露表：The Journal of Arthroscopic & Related Surgery》杂志的副主编、《JBJS Case Connector》杂志的副主编和《JBJS Case Connector》杂志的副主编的申请表已在各刊物存档，可应要求查看。骨与关节外科杂志》主编的 "潜在利益冲突披露表 "随文章在线版（http://links.lww.com/XXXXXXX）一起提供。会议书面材料或出版物以及演讲者和主持人所表达的观点不一定反映美国卫生与公众服务部的官方政策，提及的商品名称、商业行为或组织也不意味着美国政府的认可。

{"title":"Improving how orthopedic journals report research outcomes based on sex and gender","authors":"Seth S. Leopold, Robert N. Hensinger, Andrew J. Schoenfeld, Marc Swiontkowski, Michael J. Rossi, Kimberly J. Templeton, Sex and Gender Research in Orthopaedic Journals Group","doi":"10.1002/jsp2.1334","DOIUrl":"https://doi.org/10.1002/jsp2.1334","url":null,"abstract":"<p>Sex-based differences in cell biology, tissue function, and anatomy impact disease risk, presentation, and treatment outcomes,<span><sup>1</sup></span> including in musculoskeletal care.<span><sup>2-4</sup></span> As such, these differences should influence how orthopedic surgeons and other healthcare professionals conduct research and provide care for patients who have musculoskeletal disease and injury. In addition, gender roles influence interactions with people who conduct research and healthcare professionals, as well as the likelihood that patients will seek care and how they will respond to treatment.<span><sup>1, 5, 6</sup></span></p><p>Musculoskeletal research, similar to research in other areas of healthcare, does not always disaggregate results based on a patient's sex or gender.<span><sup>7</sup></span> Although some orthopedic surgery journals have explicit editorial standards on the topic of sex and gender in scientific reporting, and although international entities have published sensible guidelines about it,<span><sup>8</sup></span> we have observed that these standards are inconsistently applied.<span><sup>7</sup></span></p><p>Inattention to high-quality standards of scientific reporting can harm patients.<span><sup>9, 10</sup></span> Women have been underrepresented in medical research,<span><sup>11</sup></span> and this trend continues to varying degrees even today, despite mandates to remedy this disparity, at least in federally funded research.<span><sup>12, 13</sup></span> However, these mandates include no guidance about how data should be analyzed or reported, thereby limiting the impact of including more women in clinical studies. The care of women has been substantially compromised as a result<span><sup>14-18</sup></span>; not getting this right has sometimes harmed men with certain diagnoses as well.<span><sup>19</sup></span> As such, it is no stretch to say that doing better research—and improving how that research is reported in journals—would benefit our patients regardless of their sex or gender.</p><p>With this background in mind, leaders of the editorial boards of six orthopedic journals, along with leaders of funding agencies, as well as National Institutes of Health officials, met in November 2023 to discuss these issues. Following that meeting, those editors reached out to the Editors-in-Chief of all indexed orthopedic surgery journals, seeking concurrence on a few key themes pertaining to the reporting of sex and gender in musculoskeletal research.</p><p>We hope that by sharing these resolutions with readers, many of whom are also researchers and representatives on institutional review boards, institutional animal care and use committees, and/or funding agencies and organizations, the orthopedic research of the future will be both better designed and better reported.</p><p>Funding for this conference was made possible (in part) by (1R13AR082710–01) from the National Institute of Arthritis and Musculoskeleta","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844786","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}

引用次数: 0

Automatic Lenke classification of adolescent idiopathic scoliosis with deep learning 利用深度学习对青少年特发性脊柱侧凸进行伦克自动分类

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-30 DOI: 10.1002/jsp2.1327

Baolin Zhang, Kanghao Chen, Haodong Yuan, Zhiheng Liao, Taifeng Zhou, Weiming Guo, Shen Zhao, Ruixuan Wang, Peiqiang Su

Purpose

The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer-induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms.

Methods

Using the database from the First Affiliated Hospital of Sun Yat-sen University, the whole spinal x-rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key-point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed.

Results

In the study, a total of 2082 spinal x-ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1-score of 0.809 for curve type evaluation and an F1-score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1-score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1-score for ultimate Lenke type classifier was 0.885.

Conclusions

This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future.

目的 Lenke分类系统被广泛用作青少年特发性脊柱侧凸（AIS）的术前评估方案。然而，人工测量容易受到观察者引起的变异的影响，从而影响对进展的评估。本研究的目标是利用创新的深度学习算法开发一种自动伦克分类系统。方法使用中山大学附属第一医院的数据库，回顾性地收集整个脊柱的 X 光图像。具体来说，图像收集分为 AIS 组和对照组。对照组由接受常规健康检查且没有脊柱侧弯的人组成。之后，对所有图像的相对特征进行注释。利用基于关键点的检测方法实现深度学习，从而实现脊椎检测，并根据相关标准进行 Cobb 角度测量和脊柱侧弯分类。此外，还采用分割方法实现了腰椎椎弓根的识别，以确定腰椎改建者的类型。最后，进一步对模型性能进行了定量分析。结果研究共收集了 407 名 AIS 患者和 227 名对照组患者的 2082 张脊柱 X 光图像。脊椎检测模型在曲线类型评估方面的 F1 分数为 0.809，在胸椎矢状剖面方面的 F1 分数为 0.901。Cobb角测量的类内相关效率（ICC）为0.925。在椎体椎弓根分割模型的性能分析中，腰椎修正剖面的 F1 分数为 0.942，目标像素的交点大于结合点（IOU）为 0.827，豪斯多夫距离（HD）为 6.565 ± 2.583 毫米。具体来说，终极伦克类型分类器的 F1 分数为 0.885。结论本研究通过采用深度学习网络来实现识别模式和特征提取，构建了一个自动化的伦克分类系统。我们的模型还需要在未来的更多案例中进一步验证。

{"title":"Automatic Lenke classification of adolescent idiopathic scoliosis with deep learning","authors":"Baolin Zhang, Kanghao Chen, Haodong Yuan, Zhiheng Liao, Taifeng Zhou, Weiming Guo, Shen Zhao, Ruixuan Wang, Peiqiang Su","doi":"10.1002/jsp2.1327","DOIUrl":"https://doi.org/10.1002/jsp2.1327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer-induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the database from the First Affiliated Hospital of Sun Yat-sen University, the whole spinal x-rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key-point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the study, a total of 2082 spinal x-ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1-score of 0.809 for curve type evaluation and an F1-score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1-score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1-score for ultimate Lenke type classifier was 0.885.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814269","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}

引用次数: 0

Can axial loading restore in vivo disc geometry, opening pressure, and T2 relaxation time? 轴向加载能否恢复体内椎间盘的几何形状、开放压力和T2弛豫时间？

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-25 DOI: 10.1002/jsp2.1322

Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott

Background

Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc.

Methods

We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition.

Results

We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species.

Conclusion

To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.

背景尸体椎间盘经常被用来研究各种研究问题，研究结果根据活体情况进行解释。遗憾的是，尸体椎间盘本质上并不代表活体状态，因此在尸体上测量的椎间盘结构（几何形状）、组成（T2弛豫时间）和机械功能（打开压力，OP）并不一定代表活体椎间盘。方法我们在尤卡坦小型猪体内对椎间盘的几何形状、T2弛豫时间和OP进行了连续评估，以量化进行性解剖时发生的变化，并使用轴向加载来恢复体内状态。结果我们发现，在任何参数上，LIVE 和 TORSO 都没有差异；因此，在牺牲后 2 小时内，TORSO 椎间盘可以代表 LIVE 状态。通过连续解剖和样本制备，椎间盘高度增加（SEGMENT高度比TORSO高18%），OP减少（POTTED比TORSO低67%），T2时间不变。在轴向加载时，0.20-0.33 兆帕的外加应力可使椎间盘恢复到体内状态、LIVE 椎间盘几何形状和 OP，但 T2 时间有所缩短。施加的应力与OP之间呈线性相关，这在多项研究和物种中都是一致的。结论为了在人体研究或其他动物模型中恢复椎间盘的活体状态，我们建议测量 OP/应力关系，并利用这种关系选择恢复活体状态所需的外加应力。

{"title":"Can axial loading restore in vivo disc geometry, opening pressure, and T2 relaxation time?","authors":"Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott","doi":"10.1002/jsp2.1322","DOIUrl":"https://doi.org/10.1002/jsp2.1322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648159","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}

引用次数: 0

Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk 评估髓核置换装置脱出风险的四种体外测试方法比较

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-23 DOI: 10.1002/jsp2.1332

Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell

Background

Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.

Methods

Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.

Results

NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.

Conclusions

Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.

背景核替代装置（NRD）尚未在临床上常规使用，主要原因是存在装置脱落的风险。严格的体外测试可在临床试验前确定失效机制；然而，目前的测试标准并未规定特定的挤出测试。因此开发了多种方法，使 NRD 设计之间的比较变得复杂。因此，本研究评估了之前报道的四种剥离测试协议的有效性：呼啦圈（协议 1）、改良呼啦圈（协议 2）、偏心循环（协议 3）和斜坡至失效（协议 4），这四种协议适用于两种 NRD，一种是预制的，另一种是原位固化的。方法从 40 个牛尾椎间盘中取出髓核材料。将一个 NRD 从后方插入每个椎间盘，然后对椎间盘进行四种驱逐方案中的一种。结果 NRD 的反应取决于 NRD 的设计和加载方案。与方案 2 相比，方案 1 导致两种 NRD 的移位率更高，失效率更早。当加载方案包含旋转时，预制 NRD 更容易发生迁移。采用单侧弯曲和斜坡测试时，NRD的移位率（60%）和剥离率（60%）相同。综合多项测试结果，可以发现有关 NRD 反应的补充信息。结论经改良的呼啦圈测试（方案 2）和斜坡失效测试（方案 4）结合透视分析，揭示了有关移位和失效风险的补充信息。因此，在采用本研究中使用的手术方法和动物模型时，建议同时使用循环加载和斜坡加载方案来评估 NRD 性能。

{"title":"Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk","authors":"Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell","doi":"10.1002/jsp2.1332","DOIUrl":"https://doi.org/10.1002/jsp2.1332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639615","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}

引用次数: 0

Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk 犬椎间盘中免疫细胞促炎作用的特征和调节作用

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-23 DOI: 10.1002/jsp2.1333

Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur

Background

Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.

Methods

Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.

Results

CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.

Conclusion

There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

背景椎间盘（IVD）退化既影响人类也影响犬类，是腰背痛（LBP）的主要原因。已发现肥大细胞（MC）和巨噬细胞（MØ）浸润是人类和啮齿类动物模型中椎间盘退变（IVDD）的发病机制，但对犬的研究仍然不足。IVD 中的 MC 脱颗粒会导致促炎级联反应，并激活 IVD 细胞上的蛋白酶激活受体 2 (PAR2)。本研究的目的是(1）强调在退行性犬 IVD 中观察到的病理生理变化；（2）进一步描述 MCs 与犬髓核 (NP) 细胞共培养的炎症效应；（3）评估构造硬度对 NP 和 MCs 的影响；以及（4）确定缓解 IVD 微环境病理变化的潜在疗法。方法从健康的解剖研究犬（小猎犬）和因 IVD 椎间盘突出而接受椎板切除术的宠物犬身上分离犬 IVD 组织。对组织形态、蛋白质含量和炎症标记物进行了评估。从健康尸检犬（猎犬）组织中分离出的 NP 细胞与犬 MCs 共同培养在琼脂糖构建体中，并用色甘酸钠（CS）和 PAR2 拮抗剂（PAR2A）处理。对构建体的基因表达、硫酸化氨基糖含量和硬度进行了评估。结果与健康尸检结果相比，变性手术犬组织中的 CD 31+ 血管、肥大细胞胰蛋白酶和巨噬细胞 CD 163+ 均有所增加。当犬 NP 细胞与 MCs 共同培养时，促炎基因上调，而较硬的微环境增强了这些效应。用 CS 和 PAR2 抑制剂处理可介导犬 NP 细胞中的主要促炎标记物。结论退行性犬 IVD 组织中 MC、MØs 和血管生长增加，这与 IVDD 和 LBP 临床人群中的观察结果相似。与犬 NP 细胞共同培养的 MCs 会引发炎症，而 CS 和 PAR2A 是潜在的治疗药物，可减轻体外 IVDD 的病理生理学。

{"title":"Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk","authors":"Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur","doi":"10.1002/jsp2.1333","DOIUrl":"https://doi.org/10.1002/jsp2.1333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639616","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}

引用次数: 0

Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy 阿匹格林能通过调节髓核细胞自噬缓解椎间盘退变

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-17 DOI: 10.1002/jsp2.1325

Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu

Background

Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.

Methods

In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.

Results

In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.

Conclusions

API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

背景椎间盘退行性变（IVDD）是一种常见的脊柱疾病，炎症被认为是其主要发病机制之一。芹菜素（API）是从多种中草药中分离出来的一种天然生物活性黄酮类化合物，具有很强的抗炎和抗氧化作用，但目前还没有研究表明芹菜素具有治疗椎间盘突出症的潜力。在此，我们旨在探讨 API 在体内和体外对 IVDD 的潜在作用。方法在体外，采用 Western 印迹、实时定量聚合酶链反应和免疫荧光分析方法，探讨原料药对白细胞介素-1β（IL-1β）诱导的髓核细胞（NPCs）炎性变化的生物活性。在体内，采用组织学染色和免疫组化方法研究穿刺诱导的 IVDD 大鼠模型椎间盘切片的组织学变化。结果在体外，API 在 IL-1β 诱导的 NPCs 中发挥了抗炎和增强自噬的关键作用。API 通过抑制核因子-kappaB 和丝裂原活化蛋白激酶途径改善炎症，而通过磷脂酰肌醇 3- 激酶/AKT/雷帕霉素哺乳动物靶标途径促进自噬。此外，体内实验表明，在穿刺诱导的 IVDD 模型中，API 可减轻 IVDD 的进展。结论在体内和体外 IVDD 模型中，API 可抑制退行性表型并促进自噬。这表明 API 可能是治疗 IVDD 的潜在药物或靶点。

{"title":"Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy","authors":"Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu","doi":"10.1002/jsp2.1325","DOIUrl":"https://doi.org/10.1002/jsp2.1325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559650","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}

引用次数: 0

Automatic grading of intervertebral disc degeneration in lumbar dog spines 腰犬脊柱椎间盘退变的自动分级

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-17 DOI: 10.1002/jsp2.1326

Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke

Background

Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.

Methods

MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.

Results

The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.

Conclusions

The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.

背景狗的椎间盘经常发生退变，并可能伴有症状和功能障碍。椎间盘退变的程度可通过 T2 加权磁共振成像扫描进行评估，采用的是针对人类脊柱开发的 Pfirrmann 分类方案。不过，它也可用于量化椎间盘再生疗法的效果。我们开发并测试了一种深度学习工具，它能自动对狗脊椎的椎间盘退化程度进行评分，该工具的起点是一个专为处理人类患者图像而设计的现有模型。方法我们收集了 5991 名狗病患者腰椎间盘的 MRI 中矢状面扫描图像，并使用 Pfirrmann 方案和经过修改的带有过渡等级的方案进行人工评估。根据这两种方案训练了一个深度学习模型来对椎间盘图像进行分类，并将其性能与处理人类图像的模型进行了对比测试。结果 Pfirrmann 等级的确定结果显示，除狗脊柱中罕见的 5 级外，所有退变等级的灵敏度均高于 83%，特异性也很高。相比之下，相应的人类模型的灵敏度略高，平均为 90%，而犬模型为 85%。与原始的 Pfirrmann 等级相比，修改后的分数等级方案并没有显示出明显的优势。结论新型工具能够准确可靠地对犬椎间盘退变的严重程度进行评分，但评分结果不如人类模型。该工具可用于犬类患者椎间盘退变的临床治疗，也可用于对作为人类疾病动物模型的犬类进行再生疗法评估的纵向研究。

{"title":"Automatic grading of intervertebral disc degeneration in lumbar dog spines","authors":"Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke","doi":"10.1002/jsp2.1326","DOIUrl":"https://doi.org/10.1002/jsp2.1326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559649","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}

引用次数: 0

Range of international surgical strategies for adolescent idiopathic scoliosis: Evaluation of a multi-center survey 青少年特发性脊柱侧凸的国际手术策略范围：多中心调查评估

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-17 DOI: 10.1002/jsp2.1324

Hans-Joachim Wilke, Maresa Großkinsky, Michael Ruf, Benedikt Schlager

Background

Surgical treatment of adolescent idiopathic scoliosis (AIS) is very complex and modern instrumentation techniques offer multiple possibilities. Despite numerous publications, there is no clear consensus on the optimal strategy for the correction of scoliotic deformities. The goal of this study was to summarize the current surgical strategies for specific AIS cases within various countries.

Method

Thirty-two experienced scoliosis surgeons from 15 countries were asked to plan surgeries on 12 representative AIS cases. All AIS cases had an indication for surgery. A questionnaire was provided to document surgical planning. The surgeons were provided with the patients' age and sex, together with radiographs in the lateral and sagittal planes during upright standing and in lateral bending to the left and right, as well as with clinical images. The angles of the main spinal curvatures were specified in the questionnaire. The surgeons were asked to specify their preferred classification system, their surgical approach, the planned fusion length, the type of implants, the rod type, and the resection steps. The data were analyzed with respect to the inter-rater variability, which was quantified using the Fleiss-Kappa Method.

Results

There was a good agreement (k = 0.61) between the surgeons in choosing the Lenke curve type, and a moderate agreement for the lumbar (0.41) and sagittal (0.56) modifiers. The most frequently planned resection procedure was complete facetectomy (67%). The posterior approach was the most commonly (91%) selected strategy to treat AIS. Anterior approaches were chosen most for Lenke 5 type with a rate of 20%. The upper instrumented vertebra (UIV) varied most for Lenke 1, 5, and 6 cases, with a vertebral level discrepancy of up to 10 levels at Lenke 6. The lowest instrumented vertebra varied most for Lenke 1 and 4 by up to five levels. Polyaxial screws were chosen most (56%), followed by monoaxial (20%) and uniplanar (19%) screws and hooks (5%).

Conclusions

The results highlight the commonalities and discrepancy in the surgical treatment of AIS in between surgeons. The selected LIV and UIV can vary depending on the curve type and surgeon. Hook constructs appear to be generally replaced by transpedicular screws. The survey indicates open questions in the AIS treatment and in the understanding of scoliosis biomechanics.

背景青少年特发性脊柱侧凸（AIS）的手术治疗非常复杂，现代器械技术提供了多种可能性。尽管发表了大量文献，但对于矫正脊柱侧弯畸形的最佳策略仍未达成明确共识。本研究旨在总结目前各国针对特定 AIS 病例的手术策略。方法来自 15 个国家的 32 名经验丰富的脊柱侧弯外科医生应邀为 12 个具有代表性的 AIS 病例制定手术计划。所有 AIS 病例均有手术指征。我们提供了一份调查问卷，用于记录手术计划。外科医生获得了患者的年龄和性别、直立时的侧位和矢状位X光片、向左和向右侧弯时的侧位和矢状位X光片以及临床图像。问卷中明确指出了主要脊柱弯曲的角度。外科医生被要求说明其偏好的分类系统、手术方法、计划的融合长度、植入物类型、杆类型和切除步骤。数据分析采用弗莱斯-卡帕法（Fleiss-Kappa Method）对评分者之间的差异性进行量化。结果在选择 Lenke 曲线类型方面，外科医生之间的一致性很好（k = 0.61），而在腰椎（0.41）和矢状（0.56）曲线修饰方面的一致性则处于中等水平。最常见的切除手术是全椎面切除术（67%）。后路是治疗 AIS 最常用的方法（91%）。Lenke 5 型最多选择前路，比例为 20%。Lenke 1、5 和 6 型病例的上部器械椎体（UIV）差异最大，Lenke 6 型病例的椎体水平差异高达 10 个水平。Lenke 1 和 4 的最低器械椎体差异最大，最多相差 5 个级别。选择多轴螺钉最多（56%），其次是单轴螺钉（20%）和单平面螺钉（19%）以及钩针（5%）。结论这些结果凸显了不同外科医生在 AIS 手术治疗中的共性和差异。所选的 LIV 和 UIV 可因曲线类型和外科医生而异。钩式结构似乎普遍被经关节螺钉所取代。调查显示，在AIS治疗和对脊柱侧凸生物力学的理解方面还存在一些问题。

{"title":"Range of international surgical strategies for adolescent idiopathic scoliosis: Evaluation of a multi-center survey","authors":"Hans-Joachim Wilke, Maresa Großkinsky, Michael Ruf, Benedikt Schlager","doi":"10.1002/jsp2.1324","DOIUrl":"https://doi.org/10.1002/jsp2.1324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Surgical treatment of adolescent idiopathic scoliosis (AIS) is very complex and modern instrumentation techniques offer multiple possibilities. Despite numerous publications, there is no clear consensus on the optimal strategy for the correction of scoliotic deformities. The goal of this study was to summarize the current surgical strategies for specific AIS cases within various countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Thirty-two experienced scoliosis surgeons from 15 countries were asked to plan surgeries on 12 representative AIS cases. All AIS cases had an indication for surgery. A questionnaire was provided to document surgical planning. The surgeons were provided with the patients' age and sex, together with radiographs in the lateral and sagittal planes during upright standing and in lateral bending to the left and right, as well as with clinical images. The angles of the main spinal curvatures were specified in the questionnaire. The surgeons were asked to specify their preferred classification system, their surgical approach, the planned fusion length, the type of implants, the rod type, and the resection steps. The data were analyzed with respect to the inter-rater variability, which was quantified using the Fleiss-Kappa Method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a good agreement (<i>k</i> = 0.61) between the surgeons in choosing the Lenke curve type, and a moderate agreement for the lumbar (0.41) and sagittal (0.56) modifiers. The most frequently planned resection procedure was complete facetectomy (67%). The posterior approach was the most commonly (91%) selected strategy to treat AIS. Anterior approaches were chosen most for Lenke 5 type with a rate of 20%. The upper instrumented vertebra (UIV) varied most for Lenke 1, 5, and 6 cases, with a vertebral level discrepancy of up to 10 levels at Lenke 6. The lowest instrumented vertebra varied most for Lenke 1 and 4 by up to five levels. Polyaxial screws were chosen most (56%), followed by monoaxial (20%) and uniplanar (19%) screws and hooks (5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results highlight the commonalities and discrepancy in the surgical treatment of AIS in between surgeons. The selected LIV and UIV can vary depending on the curve type and surgeon. Hook constructs appear to be generally replaced by transpedicular screws. The survey indicates open questions in the AIS treatment and in the understanding of scoliosis biomechanics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559651","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}

引用次数: 0

Analysis of the value of potential biomarker S100-A8 protein in the diagnosis and pathogenesis of spinal tuberculosis 潜在生物标志物 S100-A8 蛋白在脊柱结核诊断和发病机制中的价值分析

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-10 DOI: 10.1002/jsp2.1331

Zhibo Ren, Jinke Ji, Caili Lou, Yuxin Gao, Xueyan Feng, Qiang Ye, Wei Jia, Xu Zhang, Ningkui Niu

Objectives

The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).

Methods

The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.

Results

S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (p < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (p < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (p < 0.05), 0.754 (p < 0.01), 0.716 (p < 0.01), 0.656 (p < 0.05), and 0.681 (p < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.

Conclusion

S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.

摘要】目的评价S100-A8蛋白作为脊柱结核诊断标志物的价值，探讨其在脊柱结核（STB）潜在发病机制中的作用。方法采集2018年9月至2021年6月宁夏医科大学总医院收治的100例脊柱结核患者外周血作为观察组，采集30例健康体检者外周血作为对照组。选取观察组和对照组各3份样本进行蛋白质组学检测，筛选差异蛋白。利用京都基因百科全书（KEGG）对相关信号通路进行富集和分析，以确认目标蛋白。使用酶联免疫吸附试验（ELISA）测定并比较两组患者血清中目标蛋白的表达水平。采用统计方法评估靶蛋白作为 STB 诊断标志物的价值。构建了结核分枝杆菌感染的巨噬细胞模型，并使用 S100-A8 小干扰 RNA 研究了目标蛋白的分子机制。结果 S100-A8蛋白具有诊断脊柱结核的价值（AUC = 0.931，p <0.001），观察组外周血中的表达水平（59.04 ± 19.37 ng/mL）明显高于对照组（43.16 ± 10.07 ng/mL）（p <0.05）。S100-A8 蛋白表达与 CRP 和 ESR 值均呈显著正相关（p < 0.01）。其与细菌学检测、T-SPOT 结果、影像学诊断、抗酸染色结果和病理学结果的综合 AUC 分别为 0.705 (p < 0.05)、0.754 (p < 0.01)、0.716 (p < 0.01)、0.656 (p < 0.05) 和 0.681 (p < 0.01)。缺乏 S100-A8 会导致受感染巨噬细胞中 TLR4 和 IL-17A 的表达水平显著下降。结论 S100-A8 蛋白在脊柱结核患者和健康人外周血中的表达存在差异，可能是诊断脊柱结核的新型候选生物标志物。S100-A8-TLR4-IL-17A 轴的反馈回路可能在脊柱结核的炎症机制中发挥重要作用。

{"title":"Analysis of the value of potential biomarker S100-A8 protein in the diagnosis and pathogenesis of spinal tuberculosis","authors":"Zhibo Ren, Jinke Ji, Caili Lou, Yuxin Gao, Xueyan Feng, Qiang Ye, Wei Jia, Xu Zhang, Ningkui Niu","doi":"10.1002/jsp2.1331","DOIUrl":"https://doi.org/10.1002/jsp2.1331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of <i>Mycobacterium tuberculosis</i> infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, <i>p</i> < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (<i>p</i> < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (<i>p</i> < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (<i>p</i> < 0.05), 0.754 (<i>p</i> < 0.01), 0.716 (<i>p</i> < 0.01), 0.656 (<i>p</i> < 0.05), and 0.681 (<i>p</i> < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.</p>\u0000 </se","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140544432","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}

引用次数: 0

首页上一页

1
2
3
4
5
6
7
...
10

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

JOR Spine

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀