SBM

SBM
  • 文章类型: Journal Article
    背景:解淀粉芽孢杆菌具有优异的蛋白酶生产能力,在豆粕固态发酵(SBM)中具有广阔的应用前景。
    结果:在八株细菌中,解淀粉芽孢杆菌亚种。plantarumCICC10265,表现出更高的蛋白酶产量,选择作为发酵菌株。该菌株分泌的蛋白酶活性达到106.41UmL-1。自然发酵和接种强化发酵豆粕(FSBM)的微生物群落结构差异显著,后者显示出更大的稳定性和抑制杂项细菌生长。在发酵过程中,豆粕内部的温度升高,FSBM的最佳环境温度为35至40°C。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析和氮溶解度指数(NSI)结果表明,固态发酵对SBM中高度变性蛋白具有降解作用,导致NSI为67.1%。
    结论:解淀粉芽孢杆菌亚种。plantarumCICC10265可以增强固态发酵中SBM的NSI,并抑制杂菌的生长。©2023化学工业学会。
    BACKGROUND: Bacillus amyloliquefaciens has excellent protease production ability and holds great prospects for application in the solid-state fermentation of soybean meal (SBM).
    RESULTS: Among eight strains of bacteria, Bacillus amyloliquefaciens subsp. plantarum CICC 10265, which exhibited higher protease production, was selected as the fermentation strain. The protease activity secreted by this strain reached 106.41 U mL-1 . The microbial community structure differed significantly between natural fermentation and inoculation-enhanced fermented soybean meal (FSBM), with the latter showing greater stability and inhibition of miscellaneous bacterial growth. During fermentation, the temperature inside the soybean meal increased, and the optimal environmental temperature for FSBM was found to be between 35 and 40 °C. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and nitrogen solubility index (NSI) results demonstrated that solid-state fermentation had a degrading effect on highly denatured proteins in SBM, resulting in an NSI of 67.1%.
    CONCLUSIONS: Bacillus amyloliquefaciens subsp. plantarum CICC 10265 can enhance the NSI of SBM in solid-state fermentation and inhibit the growth of miscellaneous bacteria. © 2023 Society of Chemical Industry.
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  • 文章类型: Journal Article
    UNASSIGNED: Voxel-Based Morphometry (VBM) and Source-Based Morphometry (SBM) are widely used techniques for analyzing structural Magnetic Resonance Imaging (MRI) data. VBM compares differences in gray and white matter volume, density, or concentration voxel-wise, while SBM identifies patterns of structural variation using independent component analysis. This study aims to compare the performance of VBM and SBM in detecting differences in brain structure across Parkinson\'s patients and healthy controls, grouped based on their chronotype.
    UNASSIGNED: Thirty-three subjects were divided into three groups: a Parkinson\'s Group (PG), an Early Chronotype Group (EG), and a Late Chronotype Group (LG). Circadian preference, daytime sleepiness, and sleep quality were assessed, and MRI data were acquired using a 3 T scanner. SBM and VBM were used to test differences and similarities in MRI scans and chronotypes.
    UNASSIGNED: Results from SBM revealed significant clusters surviving the analysis, with the 1st component for the PG-EG and the 4th component for the PG-LG analysis showing the lowest p-value (< 0.05). Denser gray matter volume (GMV) or white matter volume (WMV) was observed in the Middle Frontal Gyrus and the Lentiform Nucleus through Talairach Coordinates analysis.
    UNASSIGNED: This study emphasizes the importance of selecting appropriate methods for analyzing structural MRI data. VBM is effective in identifying local differences in brain structure, while SBM provides a more comprehensive view of structural variation, detecting patterns not captured by VBM. Future studies should consider utilizing both VBM and SBM to fully characterize brain structural differences in diverse clinical and cognitive populations. Further studies, with larger sample sizes and more balanced genders, genomic analysis, disease severity and duration, as well as medications\' effect, are warranted.
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  • 文章类型: Journal Article
    近年来,多元脑形态测量模式的检查引起了人们的关注,特别是他们在研究患者和对照组之间的差异方面的强大探索能力。在许多现有的基于结构磁共振成像数据的脑解剖分析方法和工具中,数据驱动的基于源的形态计量学(SBM)专注于对此类模式的探索性检测。这里,我们实现了SBM的半盲扩展,称为约束源形态测量(约束SBM),这使得能够使用约束独立分量分析(ICA)方法提取最大独立的类似参考源。要做到这一点,我们将SBM与一组覆盖整个大脑的参考组件相结合,从大型独立数据集(UKBiobank)派生,提供一个完全自动化的SBM框架。这也使我们能够实现约束SBM(cSBM)的联合版本,以允许分析本地无法访问的数据。在我们提出的基于分散约束源的形态计量学(DCSBM)中,原始数据永远不会离开本地网站。每个站点使用通用分布式计算平台对其私有本地数据进行约束的ICA操作。接下来,聚合器/主节点聚合从每个本地站点估计的结果,并应用统计分析来估计源的重要性。最后,我们通过比较cSBM和dcSBM得出的组差异估计值,利用另外两个多站点患者数据集来验证我们的模型.
    The examination of multivariate brain morphometry patterns has gained attention in recent years, especially for their powerful exploratory capabilities in the study of differences between patients and controls. Among the many existing methods and tools for the analysis of brain anatomy based on structural magnetic resonance imaging data, data-driven source-based morphometry (SBM) focuses on the exploratory detection of such patterns. Here, we implement a semi-blind extension of SBM, called constrained source-based morphometry (constrained SBM), which enables the extraction of maximally independent reference-alike sources using the constrained independent component analysis (ICA) approach. To do this, we combine SBM with a set of reference components covering the full brain, derived from a large independent data set (UKBiobank), to provide a fully automated SBM framework. This also allows us to implement a federated version of constrained SBM (cSBM) to allow analysis of data that is not locally accessible. In our proposed decentralized constrained source-based morphometry (dcSBM), the original data never leaves the local site. Each site operates constrained ICA on its private local data using a common distributed computation platform. Next, an aggregator/master node aggregates the results estimated from each local site and applies statistical analysis to estimate the significance of the sources. Finally, we utilize two additional multisite patient data sets to validate our model by comparing the resulting group difference estimates from both cSBM and dcSBM.
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  • 文章类型: Journal Article
    背景:作为促进头发健康的补充剂,Shi-Bi-Man(SBM)是一种包含各种中药的处方。虽然据报道SBM可以促进头发再生,其分子机制尚不清楚。食蟹猴(Macacafascicularis)是非人类灵长类动物,其基因表达谱与人类相似。本研究的目的是评估SBM促进食蟹猴毛发再生的作用,并揭示其潜在机制。
    方法:通过对6只食蟹猴进行皮肤给药,观察SBM对毛发再生的影响。采用单细胞RNA测序(scRNA-seq)结合定量聚合酶链反应(qPCR)检测基因转录水平研究SBM的分子机制,蛋白水平的免疫荧光染色验证。
    结果:SBM显著诱导食蟹猴毛发再生,毛囊数量增加,促进毛囊发育。ScRNA-seq显示毛囊干细胞(HFSCs)的数量增加,具有较高的激活状态,如与代谢相关的活化标志物LDHA和增殖标志物MKI67的较高表达所证明的。蛋白质水平的免疫荧光分析和mRNA水平的qPCR证实了测序数据。Cellchat分析揭示了在层粘连蛋白相关途径中参与细胞间通讯的配体-受体对的富集。
    结论:SBM显著促进食蟹猴的毛发再生。机械上,SBM可以上调LDHA介导的乳酸代谢并驱动HFSC活化,进而促进HFSCs的增殖和分化。
    BACKGROUND: As a supplement for promoting hair health, Shi-Bi-Man (SBM) is a prescription comprising various traditional Chinese medicines. Though SBM has been reported to promote hair regeneration, its molecular mechanism remains unclear. Cynomolgus monkeys (Macaca fascicularis) are non-human primates with a gene expression profile similar to that of humans. The purpose of this research is to evaluate the effect of SBM on promoting hair regeneration in cynomolgus monkeys and to reveal the underlying mechanism.
    METHODS: The effect of SBM on hair regeneration was observed by skin administration on 6 cynomolgus monkeys with artificial back shaving. The molecular mechanism of SBM was studied using single-cell RNA sequencing (scRNA-seq) in combination with quantitative polymerase chain reaction (qPCR) detection for gene transcription level, and immunofluorescence staining verification for protein level.
    RESULTS: SBM significantly induced hair regeneration in cynomolgus monkeys, increased hair follicle number and facilitated hair follicle development. ScRNA-seq revealed an increase in the number of hair follicle stem cells (HFSCs) with a higher activation state, as evidenced by the higher expression of activation marker LDHA related to metabolism and the proliferation marker MKI67. Immunofluorescence analysis at the protein level and qPCR at the mRNA level confirmed the sequencing data. Cellchat analysis revealed an enrichment of ligand-receptor pairs involved in intercellular communication in Laminin-related pathways.
    CONCLUSIONS: SBM significantly promotes hair regeneration in cynomolgus monkeys. Mechanically, SBM can up-regulate LDHA-mediated lactic acid metabolism and drive HFSC activation, which in turn promotes the proliferation and differentiation of HFSCs.
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  • 文章类型: Journal Article
    在绿色发展的大背景下,城市群空间结构对城市土地利用效率具有重要影响,但很少有研究探讨两者之间的影响机制。本研究探讨了多中心发展对UAULUE的影响,使用2004-2019年中国十大关键UA中140个城市的数据。通过估计ULUE决定因素的模型,探索了多中心发展与ULUE之间的联系。本研究还通过使用适度的中介模型研究了UA在ULUE上的多中心空间结构的机制。研究的主要发现可以总结如下。东部UA表现出主要是多中心的空间结构,而中部和西部的UA表现出弱的多中心空间结构。UA的多中心空间结构对ULUE有积极影响。倒U形曲线描绘了UA和ULUE的多中心空间结构之间的关系。然而,中介变量,产业结构与要素流动的整合在UA和ULUE的多中心空间结构之间具有积极的部分中介作用。基础设施层面具有正向U型调节效应,其中交通基础设施的影响系数更为显著。研究结果为我国区域空间规划与ULUE协调发展提供了实证依据。
    Under the background of green development, the spatial structure of urban agglomerations (UA) has an important impact on urban land use efficiency (ULUE), but few studies have explored the impact mechanism between the two. This research explores the impacts of polycentric development on ULUE of UA, using data for 140 cities in China\'s top ten key UA covering the period from 2004-2019. The linkage between polycentric development and ULUE is explored by estimating models of determinants of ULUE. This research also examines the mechanism of the polycentric spatial structure of UA on ULUE by using a moderated mediation model. The main findings of the research can be concluded as below. The eastern UAs show a mostly polycentric spatial structure, whereas the central and western UAs show a weak polycentric spatial structure. The polycentric spatial structure of UA has a positive impact on ULUE. An inverted U-shape curve depicts the relationship between the polycentric spatial structure of UA and ULUE. However, the mediating variables, integration of industrial structure and factor mobility have a positive and partially mediating effect between the polycentric spatial structure of UA and ULUE. The infrastructure level has a positive U-shaped regulation effect, in which the impact coefficient of transport infrastructure is more significant. These findings provide empirical evidence for the coordinated development of China\'s regional space planning and ULUE.
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  • 文章类型: Journal Article
    纵向MRI研究对于记录神经退行性疾病的时程以及临床试验中候选药物的神经保护作用越来越重要。然而,手动纵向图像评估是耗时的,传统的评估程序通常会带来不令人满意的研究结果.这里,我们提出了一个深刻的分析流程,包括以下协调步骤:(1)自动化和高度精确的图像处理流,包括使用最新的高度详细的脑图集(例如具有360个皮质ROI的HCPMMP1.0图集)的体素和基于表面的形态计量学;(2)使用年度百分比变化(APC)的乘法模型进行深刻的统计评估;(3)从全基因组关联研究中采用的多重测试校正,该校正最适合纵向神经我们对25名阿尔茨海默病患者和25名年龄匹配的认知正常受试者进行了基线和1年随访的ADNI-3研究的常规MRI扫描,测试了该分析管道。即使在这个小群人中,在SBM的多次测试校正后,我们能够报告22个显著的测量值(包括皮质体积,面积和厚度)仅补充了VBM发现的三个统计学上显着的体积变化(左/右海马和左杏仁核)。通过MMSE测量,大脑形态计量学的1年下降与患者临床残疾和认知能力下降的增加相吻合,CDRGLOBAL,常见问题TOTAL和NPI总分。这项工作表明,高度精确的图像评估,即使对于较小的研究规模,APC计算和足够的多次测试校正也可以产生重要的研究结果。有了这个,自动MRI处理现在是可用的和可靠的常规使用和临床试验。
    Longitudinal MRI studies are of increasing importance to document the time course of neurodegenerative diseases as well as neuroprotective effects of a drug candidate in clinical trials. However, manual longitudinal image assessments are time consuming and conventional assessment routines often deliver unsatisfying study outcomes. Here, we propose a profound analysis pipeline that consists of the following coordinated steps: (1) an automated and highly precise image processing stream including voxel and surface based morphometry using latest highly detailed brain atlases such as the HCP MMP 1.0 atlas with 360 cortical ROIs; (2) a profound statistical assessment using a multiplicative model of annual percent change (APC); and (3) a multiple testing correction adopted from genome-wide association studies that is optimally suited for longitudinal neuroimaging studies. We tested this analysis pipeline with 25 Alzheimer\'s disease patients against 25 age-matched cognitively normal subjects with a baseline and a 1-year follow-up conventional MRI scan from the ADNI-3 study. Even in this small cohort, we were able to report 22 significant measurements after multiple testing correction from SBM (including cortical volume, area and thickness) complementing only three statistically significant volume changes (left/right hippocampus and left amygdala) found by VBM. A 1-year decrease in brain morphometry coincided with an increasing clinical disability and cognitive decline in patients measured by MMSE, CDR GLOBAL, FAQ TOTAL and NPI TOTAL scores. This work shows that highly precise image assessments, APC computation and an adequate multiple testing correction can produce a significant study outcome even for small study sizes. With this, automated MRI processing is now available and reliable for routine use and clinical trials.
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  • 文章类型: Journal Article
    随着全球对环境和能源问题的日益关注,有许多学者将其纳入全要素生产率(TFP)分析框架。本文旨在勾勒出中国服务业14个细分行业绿色全要素生产率(GTFP)的动态变化趋势和收敛特征。这对我国服务业细分行业的协调发展和绿色转型具有重要意义。本文通过前沿的基于ε的测度(EBM),基于松弛的测度(SBM)和径向测度以及全球Malmquist-Luenberger(GML)生产率指数,开始对中国服务业的GTFP进行测度和分解。并检验了中国服务业趋同假说的存在性。主要结论如下:(1)我国服务业GTFP年均增长率为1.00%,不同子行业的GTFP存在异质性;(2)存在σ收敛现象,绝对β收敛,中国整体服务业GTFP的条件β收敛,生产性服务业,和面向消费者的服务业。主要政策建议包括:加大服务业绿色技术创新投入,制定更有效的工业发展规划和能源政策,优化服务业的能源结构和产业结构。
    With the rising global concern over environment and energy issues, there are many scholars incorporating them into total factor productivity (TFP) analytical framework. This paper aims to outline the dynamic change trend and convergence characteristics of green total factor productivity (GTFP) of 14 sub-sectors in China\'s service industry. This is of great significance to the coordinated development and green transformation of sub-sectors of China\'s service industry. This paper commences to gauge and decompose GTFP of China\'s service industry by cutting-edge epsilon-based measure (EBM) generalizing slacks-based measure (SBM) and radial measure as well as Global Malmquist-Luenberger (GML) productivity index, and to examine the existence of convergence hypothesis in China\'s service industry. The core conclusions are as follows: (1) the average annual growth rate of GTFP in China\'s service industry is 1.00%, and there exists heterogeneity for GTFP in different sub-sectors; (2) there are phenomena of σ-convergence, absolute β-convergence, and conditional β-convergence in GTFP of China\'s overall service industry, producer service industry, and consumer-oriented service industry. The main policy suggestions include: increasing investment in green technology innovation of the service industry, formulating more effective industrial development planning and energy policies, and optimizing energy structure and industry structure of the service industry.
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  • 文章类型: Journal Article
    目的:通过表面形态学(SBM)测量带状疱疹(HZ)和带状疱疹后遗神经痛(PHN)患者大脑皮层厚度的变化,并进一步评估其与临床评分的相关性。
    方法:29位HZ患者,包括30名PHN患者和30名匹配良好的健康对照(HC)。收集所有受试者的磁共振成像(MRI)数据,然后通过SBM进行分析。HZ之间皮质厚度的变化,PHN和HC组通过ANOVA分析并与临床评分相关。
    结果:双侧初级视觉皮层(V1,V2)和右侧初级视觉皮层(V3)的厚度,左体感皮层(L3A),PHN组右前扣带回和内侧前额叶皮质(RS32)增加,以及左岛和额叶皮层(LFOP4)的厚度,左运动皮层(L3B),与HC组相比,HZ和PHN组的右颞上视觉皮层(RSTV)降低。HZ和PHN患者的RS32,LFOP4和(L3B)的厚度测量与疾病持续时间相关。在HZ和PHN患者中,汉密尔顿焦虑量表(HAMA)与汉密尔顿抑郁量表(HAMD)评分呈显著正相关。
    结论:与感觉相关的区域皮质厚度的变化,电机,PHN患者的认知/情绪变化会影响大脑的神经可塑性过程,这可能是HZ转化为PHN的原因,并为PHN患者疼痛持续的神经病理学机制提供了可能的解释。
    OBJECTIVE: To measure the changes in cerebral cortical thickness in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) by surface-based morphometry (SBM) and further estimate its correlation with clinical scores.
    METHODS: Twenty-nine HZ patients, 30 PHN patients and 30 well-matched healthy controls (HCs) were included. Magnetic resonance imaging (MRI) data from all subjects were collected and then analyzed by SBM. The changes in cortical thickness among the HZ, PHN and HC groups were analyzed by ANOVA and correlated with clinical scores.
    RESULTS: The thickness of the bilateral primary visual cortex (V1, V2) and right primary visual cortex (V3), left somatosensory cortex (L3A), right anterior cingulate gyrus and medial prefrontal cortex (RS32) increased in PHN group, and the thickness the left insular and frontal opercular cortex (LFOP4), left motor cortex (L3B), and right superior temporal visual cortex (RSTV) were decreased in the HZ and PHN groups compared to the HC group. The thickness measurements of RS32, LFOP4, and (L3B) in HZ and PHN patients were correlated with the duration of disease. In HZ and PHN patients, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were significantly positively correlated.
    CONCLUSIONS: Changes in cortical thickness in the areas related to sensory, motor, and cognitive/emotional changes in patients with PHN affect the neuroplasticity process of the brain, which may be the reason for the transformation of HZ into PHN and provide a possible explanation for the neuropathological mechanism of pain persistence in PHN patients.
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  • 文章类型: Journal Article
    我们旨在描述与临床症状学相关的皮质下前庭电路梗塞后重组的共同原则。我们的假设是,特定症状的恢复与核心前庭内不同区域的变化有关,体感,和视觉皮层和皮层下网络。
    我们使用基于体素和表面的形态学来研究42例单侧皮质下和皮质脑区的结构重组,急性期皮质下梗死伴前庭和眼运动缺陷。患者接受结构神经影像学和临床监测两次(急性期和6个月后),以检测受试者随时间的变化。
    在急性期有前庭体征如主观视觉垂直(SVV)倾斜和眼扭转的患者中,在随访中发现顶眼(后)岛叶前庭皮质(PIVC)周围的浅表白质体积显着增加。在SVV倾斜的患者中,自发性眼球震颤,急性期的旋转性眩晕,随访时,灰质体积的减少位于小脑和视觉皮层的两侧。有扫视病理的患者表现为小脑体积减少,丘脑,和用于眼运动控制的皮质中枢。
    研究结果支持PIVC作为前庭处理和重组的关键枢纽的作用。体积减小代表前庭的相互作用,视觉,和眼运动系统在自定位和自运动检测。前庭和眼运动以及视觉网络的调节独立于前庭病变部位。
    We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks.
    We used voxel- and surface-based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within-subject changes over time.
    In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto-opercular (retro-)insular vestibular cortex (PIVC) were found at follow-up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow-up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control.
    The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self-location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site.
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  • 文章类型: Journal Article
    方法:回顾性分析在一家机构中接受脊柱转移治疗和照射的注册患者队列。
    目的:这是第一项开发并内部验证影像组学功能的研究,用于预测脊柱骨转移(SBM)患者六个月的生存概率。
    背景:从常规临床CT图像中提取的放射组学特征可用于识别人类观察者无法感知的基于纹理和强度的特征,并将其与患者生存概率或疾病进展相关联。
    方法:在马斯特里赫特的MAASTRO诊所,对2014年至2016年首次接受照射的250例脊柱转移瘤患者进行了研究。荷兰。前150名可用患者用于开发模型,随后的100名患者被视为模型的测试集。引导(B=400)逐步模型选择,它结合了正向和反向变量消除过程,用于根据Akaike信息标准(AIC)从训练数据中选择最有用的预测特征。逐步选择程序应用于400个引导样本,并将结果绘制为直方图,以可视化选择每个变量的频率。仅在引导运行中选择了超过90%的时间的变量用于构建最终模型。计算每位患者的预后指数(PI),称为放射组学评分(radscore)和临床评分(clinscore)。预后指数没有缩放,使用的原始值可以直接从模型中提取,或者作为模型中变量的线性组合乘以每位患者各自的β值进行计算.
    结果:临床模型具有良好的辨别能力。影像组学模型,另一方面,表现较差,没有增加临床模型的预测能力。内部成像特征似乎在预测生存方面没有价值。然而,在我们的研究中,形状特征被排除在进一步分析之外,因为所有活检都具有标准形状,因此没有变异性.
    METHODS: Retrospective analysis of a registered cohort of patients treated and irradiated for metastases in the spinal column in a single institute.
    OBJECTIVE: This is the first study to develop and internally validate radiomics features for predicting six-month survival probability for patients with spinal bone metastases (SBM).
    BACKGROUND: Extracted radiomics features from routine clinical CT images can be used to identify textural and intensity-based features unperceivable to human observers and associate them with a patient survival probability or disease progression.
    METHODS: A study was conducted on 250 patients treated for metastases in the spinal column irradiated for the first time between 2014 and 2016, at the MAASTRO clinic in Maastricht, the Netherlands. The first 150 available patients were used to develop the model and the subsequent 100 patient were considered as a test set for the model. A bootstrap (B = 400) stepwise model selection, which combines both the forward and backward variable elimination procedure, was used to select the most useful predictive features from the training data based on the Akaike information criterion (AIC). The stepwise selection procedure was applied to the 400 bootstrap samples, and the results were plotted as a histogram to visualize how often each variable was selected. Only variables selected more than 90 % of the time over the bootstrap runs were used to build the final model.A prognostic index (PI) called radiomics score (radscore) and clinical score (clinscore) was calculated for each patient. The prognostic index was not scaled, the original values were used which can be extracted from the model directly or calculated as a linear combination of the variables in the model multiplied by the respective beta value for each patient.
    RESULTS: The clinical model had a good discrimination power. The radiomics model, on the other hand, had an inferior performance with no added predictive power to the clinical model. The internal imaging characteristics do not seem to have a value in the prediction of survival. However, the Shape features were excluded from further analyses in our study since all biopsies had a standard shape hence no variability.
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