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Modelling cure indicators using the curesurv R package: a tutorial using data from the French cancer registries 使用cururv R软件包对治愈指标进行建模:使用法国癌症登记处数据的教程
Pub Date : 2025-01-01 Epub Date: 2025-10-15 DOI: 10.1016/j.cmpbup.2025.100222
Judith Breaud , Olayidé Boussari , Valérie Jooste , Laura Botta , Juste Goungounga
Cure models are essential in survival analyses because they take into account the fraction of patients who achieve long-term survival and will not experience disease-related death. In a relative survival framework, these models estimate the excess hazard (i.e. the additional death risk attributable to the disease), while assuming that some patients will not experience such excess risk. In 2002, Phillips and colleagues introduced a class of cure models where background mortality is modelled as a scaled version of the general population’s mortality. This tutorial presents the curesurv R package for parametric cure modelling in the relative survival setting, with and without background mortality rescaling. The package supports both the Weibull mixture cure model and the non-mixture cure model proposed by Boussari and colleagues in 2018, offering flexible tools for assessing long-term survival. The curesurv R package application is illustrated using testicular, breast, and prostate cancer datasets from the French FRANCIM cancer registries. This tutorial provides a practical guide to researchers in epidemiology and health economics for implementing cure fraction models and interpreting long-term survival estimates.
治愈模型在生存分析中是必不可少的,因为它们考虑到实现长期生存且不会经历疾病相关死亡的患者比例。在相对生存的框架中,这些模型估计了超额风险(即归因于疾病的额外死亡风险),同时假设一些患者不会经历这种超额风险。2002年,菲利普斯和他的同事们引入了一类治疗模型,其中背景死亡率被建模为普通人群死亡率的缩放版本。本教程介绍了cururv R软件包,用于在相对生存环境中进行参数化治疗建模,并对背景死亡率进行重新缩放。该软件包支持Weibull混合治疗模型和Boussari及其同事在2018年提出的非混合治疗模型,为评估长期生存提供了灵活的工具。cururv R包应用程序使用来自法国franccim癌症登记处的睾丸癌、乳腺癌和前列腺癌数据集进行说明。本教程为流行病学和卫生经济学的研究人员提供了实用指南,用于实施治愈分数模型和解释长期生存估计。
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引用次数: 0
Multipath2.0: Extending Multilayer Reproducible Pathway Models with Omics Data Multipath2.0:用组学数据扩展多层可复制通路模型
Pub Date : 2025-01-01 Epub Date: 2025-03-21 DOI: 10.1016/j.cmpbup.2025.100189
Zaynab Hammoud , Mohammad Al Maaz , Alicia D'Angelo , Frank Kramer

Background

Biological systems are often perceived as independent and consequently analyzed individually. In the field of omics, multiple disciplines target the study of specific types of molecules, such as genomics. The support of more data sources in these analyses is becoming more crucial for understanding the interplay of biological systems. However, this requires integration of heterogeneous knowledge, which is considered highly challenging in bioinformatics and biomedicine. Therefore, the R package Multipath was developed to model biological pathways as multilayered graphs and integrate influencing knowledge including proteins and drugs. In its previous form, Multipath generated multilayer models of BioPAX-encoded pathways and included features to integrate drug and protein information from DrugBank and UniProtKB respectively. Although the model showed remarkable utility, including further data sources ensures enriching and expanding its capabilities.

Results

In this paper, a new version Multipath 2.0 is presented. The update additionally supports the two databases KEGG Genes and OMIM, which serve as the source for gene and disease entries and interactions. Information on the interactions between the previously and newly added nodes are extracted and integrated. The Multipath 2.0 offers features to update the original multilayer model and integrate the corresponding nodes and edges into two additional layers referring to KEGG Genes and OMIM. Furthermore, the embedded nodes are inter- and intra-connected using interactions from the original and newly supported data sources.

Conclusion

The R Package Multipath is presented with the main functions that are newly developed to support the integration of the databases KEGG Genes and OMIM. The model comprises multiple information relevant to the analysis of pathway data, and offers a reproducible and simplified view of complex, intertwined systems. Through the application of such highly integrated models the inference of new knowledge becomes easier and contributes to many fields such as drug repurposing and biomarker discovery.
生物系统通常被认为是独立的,因此被单独分析。在组学领域,多个学科针对特定类型的分子进行研究,例如基因组学。在这些分析中,更多数据源的支持对于理解生物系统的相互作用变得越来越重要。然而,这需要整合异质知识,这在生物信息学和生物医学中被认为是极具挑战性的。因此,开发了R包Multipath,将生物通路建模为多层图,并整合包括蛋白质和药物在内的影响知识。在之前的形式中,Multipath生成了biopax编码通路的多层模型,并包含了分别从DrugBank和UniProtKB中整合药物和蛋白质信息的特征。尽管该模型显示了显著的实用性,但包括进一步的数据源确保了其功能的丰富和扩展。结果本文提出了一个新版本的Multipath 2.0。此次更新还支持两个数据库KEGG Genes和OMIM,这两个数据库是基因和疾病条目和相互作用的来源。提取和集成先前和新添加节点之间的交互信息。Multipath 2.0提供了更新原始多层模型的功能,并将相应的节点和边缘集成到两个额外的层中,参考KEGG Genes和OMIM。此外,使用来自原始和新支持的数据源的交互,嵌入节点可以相互连接和内部连接。结论为支持KEGG基因和OMIM数据库的集成,R包Multipath具有新开发的主要功能。该模型包含与路径数据分析相关的多个信息,并提供了复杂、相互交织的系统的可重复和简化视图。通过这种高度集成的模型的应用,新知识的推断变得更加容易,并有助于许多领域,如药物再利用和生物标志物的发现。
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引用次数: 0
A comprehensive review of the use of Shapley value to assess node importance in the analysis of biological networks 在生物网络分析中使用Shapley值来评估节点重要性的全面回顾
Pub Date : 2025-01-01 Epub Date: 2025-02-21 DOI: 10.1016/j.cmpbup.2025.100185
Giang Pham, Paolo Milazzo

Background:

In 2017, Lundberg and Lee introduced SHAP, a breakthrough in Explainable AI, creatively applying the Shapley value to estimate the importance of input features in machine learning outputs. The Shapley value, from cooperative game theory, fairly distributes system gains among participants. Inspired by SHAP’s success, this survey explores the application of Shapley value-based methods in biological network analysis.

Method:

We conducted a comprehensive literature search on the application of the Shapley value in biological network analysis from 2004 to 2024. From this, we focused on studies that applied the Shapley value in innovative and non-trivial ways, distinct from its typical usage.

Result:

The review identified six original studies that provide novel applications of the Shapley value in analyzing biological networks. These methods have also inspired further development and applications. For each, we discuss the foundational contributions, subsequent advancements, and applications.

Discussion:

Although the reviewed methods share the common objective of using the Shapley value to estimate an element’s contribution within a system, each one takes a distinct approach to modeling the cooperative game. Some methods employ game settings that enable more efficient Shapley value calculations, albeit with a narrower scope, as they are tailored to specific problems. Other methods offer broader applicability but encounter the usual computational challenges associated with calculating the exact Shapley value due to its time complexity. Fortunately, these challenges can be mitigated through the use of approximation techniques. Despite the computational challenges, Shapley value-based methods demonstrate to be beneficial for the interpretation of biological networks.
背景:2017年,Lundberg和Lee引入了SHAP,这是可解释人工智能的突破,创造性地应用Shapley值来估计机器学习输出中输入特征的重要性。合作博弈论中的Shapley值将系统收益公平地分配给参与者。受Shapley的成功启发,本调查探讨了基于Shapley值的方法在生物网络分析中的应用。方法:对2004 ~ 2024年Shapley值在生物网络分析中的应用进行了全面的文献检索。由此,我们将重点放在以创新和非琐碎的方式应用Shapley值的研究上,这与它的典型用法不同。结果:该综述确定了六项原始研究,这些研究提供了Shapley值在分析生物网络中的新应用。这些方法也激发了进一步的开发和应用。对于每一个,我们讨论了基础的贡献,随后的进展和应用。讨论:尽管这些方法都有一个共同的目标,即使用Shapley值来评估系统中某个元素的贡献,但每种方法都采用了不同的方法来模拟合作博弈。有些方法采用了能够更有效地进行Shapley值计算的游戏设置,尽管范围较窄,因为它们是针对特定问题量身定制的。其他方法提供了更广泛的适用性,但由于其时间复杂性,在计算精确的Shapley值时遇到了通常的计算挑战。幸运的是,这些挑战可以通过使用近似技术得到缓解。尽管存在计算方面的挑战,基于Shapley值的方法证明对生物网络的解释是有益的。
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引用次数: 0
Time series analysis and prediction of the trends of COVID-19 epidemic in Singapore based on machine learning 基于机器学习的新加坡新冠肺炎疫情趋势时间序列分析与预测
Pub Date : 2025-01-01 Epub Date: 2025-04-04 DOI: 10.1016/j.cmpbup.2025.100190
Wenbin Yang , Xin Chang
The COVID-19 pandemic has posed a significant threat to global health, with ongoing rises in new cases and deaths in Singapore, profoundly affecting public health, social activities, and the economy. This study compares the performance of LSTM, GRU, and a composite prediction model (LSTM-GRU) using a dataset of new and cumulative COVID-19 cases in Singapore, provided by the World Health Organization. The analysis uses weekly cumulative data from 2020 to January 21, 2024, to forecast new cases for the upcoming weeks. Model performance is evaluated using RMSE, MAE, MAPE, and R2. The results show that the LSTM model outperforms others, particularly in capturing significant data fluctuations. This research provides insights into the trends of the pandemic in Singapore and offers a basis for further epidemiological control efforts in the region.
COVID-19 大流行对全球健康构成了重大威胁,新加坡的新增病例和死亡人数持续上升,严重影响了公共卫生、社会活动和经济。本研究使用世界卫生组织提供的新加坡 COVID-19 新发病例和累计病例数据集,比较了 LSTM、GRU 和复合预测模型(LSTM-GRU)的性能。分析使用 2020 年至 2024 年 1 月 21 日的每周累积数据来预测未来几周的新增病例。使用 RMSE、MAE、MAPE 和 R2 对模型性能进行了评估。结果表明,LSTM 模型优于其他模型,尤其是在捕捉重大数据波动方面。这项研究有助于深入了解新加坡的疫情趋势,并为该地区进一步的流行病控制工作提供依据。
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引用次数: 0
Diagnosis of Alzheimer's disease using non-linear features of ERP signals through a hybrid attention-based CNN-LSTM model 通过基于注意力的CNN-LSTM混合模型利用ERP信号的非线性特征诊断阿尔茨海默病
Pub Date : 2025-01-01 Epub Date: 2025-05-10 DOI: 10.1016/j.cmpbup.2025.100192
Elias Mazrooei Rad , Sayyed Majid Mazinani , Seyyed Ali Zendehbad
Biological signals have a dynamic and non-linear nature, and hence nonlinear analysis is important for understanding the signals. In this study, a hybrid Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) model is proposed for the diagnosis of Alzheimer’s disease (AD) from the Event-Related Potential (ERP) signals obtained from the Electroencephalogram (EEG) data. The P300 component of the ERP signal, derived from acoustic stimulation, is a key indicator of AD, and its amplitude and latency are characterized. By using nonlinear features such as phase diagrams, correlation dimension, entropy, and Lyapunov exponents, the proposed model classifies AD stages. The hybrid CNN-LSTM architecture, enhanced by an attention mechanism, captures both spatial and temporal dependencies in the ERP signals, achieving high accuracy: For healthy people, 95 %, for mild AD patients, 92.5 %, and for severe AD patients, 97.5 %. The model achieves 75 % accuracy in recall mode for healthy individuals, 72.5 % for mild AD, and 87.5 % for severe AD. Results show that the proposed model outperforms traditional methods and provides a robust and accurate diagnostic framework for AD. The result of this approach is to show that the combination of non-linear EEG analysis with advanced deep learning methods could provide early and precise AD detection.
生物信号具有动态和非线性的性质,因此非线性分析对于理解信号非常重要。本研究提出了一种卷积神经网络(CNN)和长短期记忆(LSTM)混合模型,用于从脑电图(EEG)数据中获得的事件相关电位(ERP)信号诊断阿尔茨海默病(AD)。ERP信号的P300分量来源于声刺激,是AD的关键指标,其振幅和潜伏期具有特征。该模型利用相图、相关维数、熵和李亚普诺夫指数等非线性特征对AD阶段进行分类。CNN-LSTM混合架构,通过注意机制增强,捕获ERP信号的空间和时间依赖性,达到很高的准确性:健康人95%,轻度AD患者92.5%,重度AD患者97.5%。在回忆模式下,该模型对健康个体的准确率为75%,对轻度AD的准确率为72.5%,对重度AD的准确率为87.5%。结果表明,该模型优于传统方法,提供了一个鲁棒性和准确性较高的AD诊断框架。该方法的结果表明,将非线性脑电图分析与先进的深度学习方法相结合可以提供早期和精确的AD检测。
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引用次数: 0
Efficient synthesis of 3D MR images for schizophrenia diagnosis classification with generative adversarial networks 基于生成对抗网络的精神分裂症诊断分类三维MR图像的高效合成
Pub Date : 2025-01-01 Epub Date: 2025-06-17 DOI: 10.1016/j.cmpbup.2025.100197
Sebastian King , Yasmin Hollenbenders , Alexandra Reichenbach
Schizophrenia and other psychiatric disorders can greatly benefit from objective decision support in diagnosis and therapy. Machine learning approaches based on neuroimaging, e.g. magnetic resonance imaging (MRI), have the potential to serve this purpose. However, the medical data sets these algorithms can be trained on are often rather small, leading to overfit, and the resulting models can therewith not be transferred into a clinical setting. The generation of synthetic images from real data is a promising approach to overcome this shortcoming. Due to the small data set size and the size and complexity of medical images, i.e. their three-dimensional nature, those algorithms are challenged on several levels. We develop four generative adversarial network (GAN) architectures that tackle these challenges and evaluate them systematically with a data set of 193 MR images of schizophrenia patients and healthy controls. The best architecture, a GAN with spectral normalization regulation and an additional encoder (α-SN-GAN), is then extended with an auxiliary classifier into an ensemble of networks capable of generating distinct image sets for the two diagnostic categories. The synthetic images increase the accuracy of a diagnostic classifier from a baseline accuracy of around 61 % to 79 %. This novel end-to-end pipeline for schizophrenia diagnosis demonstrates a data and memory efficient approach to support clinical decision-making that can also be transferred to support other psychiatric disorders.
精神分裂症和其他精神疾病在诊断和治疗中可以从客观决策支持中获益。基于神经成像的机器学习方法,例如磁共振成像(MRI),有可能服务于这一目的。然而,这些算法可以训练的医疗数据集往往相当小,导致过拟合,因此产生的模型不能转移到临床环境中。从真实数据生成合成图像是克服这一缺点的一种很有前途的方法。由于数据集规模小,医学图像的大小和复杂性,即它们的三维性质,这些算法在几个层面上受到挑战。我们开发了四个生成对抗网络(GAN)架构来解决这些挑战,并使用193个精神分裂症患者和健康对照的MR图像数据集系统地评估它们。最佳结构是具有光谱归一化调节和附加编码器(α-SN-GAN)的GAN,然后通过辅助分类器扩展为能够为两种诊断类别生成不同图像集的网络集成。合成图像将诊断分类器的准确度从大约61%的基线准确度提高到79%。这种新型的端到端精神分裂症诊断管道展示了一种数据和记忆有效的方法来支持临床决策,也可以转移到支持其他精神疾病。
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引用次数: 0
Fostering digital health literacy to enhance trust and improve health outcomes 培养数字卫生素养,增强信任并改善卫生成果
Pub Date : 2024-02-01 DOI: 10.1016/j.cmpbup.2024.100140
Kristine Sørensen
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引用次数: 0
Delayed matrix pencil method for local shear wave viscoelastographic estimation 用于局部剪切波粘弹性估算的延迟矩阵铅笔法
Pub Date : 2024-01-01 Epub Date: 2024-04-23 DOI: 10.1016/j.cmpbup.2024.100156
X. Li, S. Turco, R.M. Aarts, H. Wijkstra, M. Mischi

Shear wave (SW) elastography is an ultrasound imaging modality that provides quantitative viscoelastic measurements of tissue. The phase difference method allows for local estimation of viscoelasticity by computing the dispersion curve using phases from two laterally-spaced pixels. However, this method is sensitive to measurement noise in the estimated SW particle velocities. Hence, we propose the delayed matrix pencil method to investigate this problem, and validated its feasibility both in-silico and in-vitro. The performance was compared with the original phase difference method and other two alternative techniques based on lowpass filtering and discrete wavelet transform denoising. The estimated viscoelastic values are summarized in box plots and followed by statistical analysis. Results from both studies show the proposed method to be more robust to noise with the smallest interquartile range in both elasticity and viscosity.

剪切波(SW)弹性成像是一种超声成像模式,可对组织的粘弹性进行定量测量。相位差法利用两个横向间隔像素的相位来计算频散曲线,从而对粘弹性进行局部估计。然而,这种方法对估计的 SW 粒子速度中的测量噪声很敏感。因此,我们提出了延迟矩阵铅笔法来研究这个问题,并在实验室和体外验证了其可行性。我们将其性能与原始相位差法和其他两种基于低通滤波和离散小波变换去噪的替代技术进行了比较。估计的粘弹性值以盒图的形式汇总,然后进行统计分析。这两项研究的结果表明,建议的方法对噪声的鲁棒性更强,弹性和粘度的四分位数间距最小。
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引用次数: 0
An evaluation of the commonly used portable medical sensors performance in comparison to clinical test results for telehealth systems 将常用便携式医疗传感器的性能与远程医疗系统的临床测试结果进行对比评估
Pub Date : 2024-01-01 Epub Date: 2024-03-05 DOI: 10.1016/j.cmpbup.2024.100147
Rafiqul Islam Maruf , Saori Tou , Rieko Izukura , Yoko Sato , Mariko Nishikitani , Kimiyo Kikuchi , Fumihiko Yokota , Subaru Ikeda , Rakibul Islam , Ashir Ahmed , Masashi Miyazaki , Naoki Nakashima

Background and Objective

One of the primary challenges faced by telehealth systems is the accurate transmission of patient information to remote doctors. In this context, portable medical sensors deployed at the remote patients' end play a crucial role in measuring vital information. There are many sensors available in the market. However, the accuracy of the sensors has been always a concern. The objective of this study is to verify different sensors and create awareness for using accurate sensors to avoid misdiagnosis for the patients’ safety.

Methods

This study considered the test result of a Japanese clinical pathology laboratory as the reference gold standard. The clinical pathology laboratory uses 1) Hexokinase UV method for blood glucose, 2) Enzymatic Determination method for cholesterol, 3) Automatic Analyzer (EDTA-2 K) of Hemoglobin, and 4) Uricase POD method for uric acid. To assess the performance of a medical sensor, its test results were compared to the gold standard test results obtained from the laboratory using the same sample. A Normalized Root Mean Square Error (NRMSE) threshold of less than 0.2 was established as the criterion for determining whether the medical sensor's performance fell within an acceptable range.

Results

Among the eight most commonly used blood glucose devices in the Asian market, only one device was deemed acceptable with NRMSE less than 0.2. However, all four devices found in the Japanese market showed their acceptability. In the case of cholesterol, hemoglobin, and uric acid devices, only a limited number of items were available in Asian markets. Some of the hemoglobin and uric acid devices were found to be somewhat acceptable, while all the cholesterol sensors were found erroneous.

Conclusions

This study has clearly shown the issues with the portable medical sensors and recommends the device approval authority of each country to approve sales of the quality sensors only for patients’ safety.

背景与目标 远程医疗系统面临的主要挑战之一是向远程医生准确传输病人信息。在这种情况下,部署在远程患者端的便携式医疗传感器在测量重要信息方面发挥着至关重要的作用。市场上有许多传感器。然而,传感器的准确性一直是个问题。本研究的目的是验证不同的传感器,提高人们使用准确传感器的意识,以避免误诊,保障患者的安全。该临床病理实验室使用 1) 紫外光六磷酸酶法检测血糖,2) 酶法测定胆固醇,3) 自动分析仪(EDTA-2 K)检测血红蛋白,4) 尿酸酶 POD 法检测尿酸。为评估医疗传感器的性能,将其测试结果与实验室使用相同样本获得的金标准测试结果进行比较。结果在亚洲市场最常用的八种血糖设备中,只有一种设备的归一化均方根误差(NRMSE)小于 0.2,被认为是可以接受的。然而,日本市场上的所有四种血糖仪都显示出其可接受性。至于胆固醇、血红蛋白和尿酸检测仪,亚洲市场上只有少量产品。这项研究清楚地表明了便携式医疗传感器存在的问题,建议各国的设备审批机构只批准销售高质量的传感器,以确保患者的安全。
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引用次数: 0
S-1 plus oxaloplatin (S-1OX) versus capecitabine plus oxaloplatin (CAPOX) for advanced gastric cancer: A systematic review and meta-analysis S-1加奥沙利铂(S-1OX)与卡培他滨加奥沙利铂(CAPOX)治疗晚期胃癌:系统综述与荟萃分析
Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI: 10.1016/j.cmpbup.2024.100151
S.M.Zeeshan Qadar , Zhiyong Dong , Sheikh Mohammed Shariful Islam , Jianxue Wang , Xiling Xu , Fakhsheena Anjum , Sana Shamim , Bafreen Sherif , Sundas Ali

Purpose

Several therapeutic combinations are available for the treatment of advanced gastric cancer (AGC). It is unclear which combinations are most beneficial to the patients. The purpose of this study was to compare the efficacy and safety of Tegafur/ gimeracil/ oteracil (S-1) plus oxaliplatin (S-1OX) with capecitabine plus oxaliplatin (CAPOX) in patients with AGC.

Materials and Methods

Relevant randomized controlled trials were searched in MEDLINE, EMBASE, The Cochrane Library (CENTRAL), two major Chinese biomedical databases (CBM, CNKI), and registry centers until July 22, 2019, with no language restrictions. Data were extracted for overall response rate (ORR), time to progression (TTP), overall survival time (OST), and toxicity. The systematic review was performed according to the recommendations of the Cochrane collaboration. RevMan 5.3.1 was used for statistical analysis.

Results

A total of 6 randomized controlled trials involving 911 patients were included. The quality of the trials was less than 3 points. All the trials demonstrated a significantly improved toxicity (hand-foot syndrome and neuropathy) in the S-1OX trials (p < 0.05). There was no statistically significant difference (p > 0.05) between S-1OX versus CAPOX in terms of ORR, OST, TTP. Any of the subgroup analyses did not exhibit heterogeneity, so the fixed-effects model be used to execute the subgroup meta-analysis.

Conclusions

Both S-1OX and CAPOX showed similar efficacy for treatment of AGC. However, S1-OX appeared to present less toxicity in terms of hand-foot syndrome and neuropathy as compared to CAPOX.

目的 目前有多种治疗组合可用于晚期胃癌(AGC)的治疗。目前尚不清楚哪种联合疗法对患者最有益。本研究旨在比较替加氟(Tegafur)/吉莫拉嘧啶(Gimeracil)/奥特拉西(Oteracil)(S-1)加奥沙利铂(S-1OX)与卡培他滨加奥沙利铂(CAPOX)对AGC患者的疗效和安全性。材料与方法截至2019年7月22日,在MEDLINE、EMBASE、The Cochrane Library(CENTRAL)、两大中文生物医学数据库(CBM、CNKI)和注册中心检索了相关随机对照试验,无语言限制。提取的数据包括总反应率(ORR)、进展时间(TTP)、总生存时间(OST)和毒性。系统综述根据 Cochrane 协作组织的建议进行。结果 共纳入了 6 项随机对照试验,涉及 911 名患者。试验质量低于 3 分。所有试验均显示,S-1OX 试验的毒性(手足综合征和神经病变)明显改善(p < 0.05)。在 ORR、OST 和 TTP 方面,S-1OX 与 CAPOX 之间的差异无统计学意义(p > 0.05)。结论S-1OX和CAPOX治疗AGC的疗效相似。然而,与 CAPOX 相比,S1-OX 在手足综合征和神经病变方面的毒性似乎更小。
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引用次数: 0
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Computer methods and programs in biomedicine update
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