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Simulation of murine retinal hemodynamics in response to tail suspension 模拟小鼠视网膜血液动力学对尾部悬浮的反应
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109148

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction.

Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.

TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm).

These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.

太空飞行相关神经眼综合征(SANS)的病因尚不清楚。对固定后的对照组(4 只)和 14 天的尾悬浮(TS)组(4 只)小鼠眼球样本进行染色和成像,以观察血管丛和内皮细胞死亡的共定位区域。定制的工作流程将整体安装和撕裂重建的三维(3D)球形视网膜血管丛模型与计算流体动力学(CFD)模拟结合在一起,计算流体动力学模拟考虑了Fåhræus-Lindqvist效应和边界条件,以适应TS流体压力测量和更深的毛细血管层血流分布。TS 样品的表面积缩小(4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2,P = 0.010),小血管分支间的长度缩短(10 μm,69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm,P <0.001)。与对照组相比,TS 小鼠的血管壁剪切应力(WSS)和压力较高,尤其是在较小的血管中(<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004)。与对照组相比,TS 小鼠视网膜内皮细胞的死亡率各不相同。这些发现表明,模拟微重力与视网膜内皮功能障碍之间可能存在联系,这可能对SANS的发展有影响。今后的工作应考虑增加更大样本量的物种或太空飞行队列。
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引用次数: 0
Dementia risk prediction using decision-focused content selection from medical notes 利用医疗记录中以决策为重点的内容选择预测痴呆症风险
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109144

Several general-purpose language model (LM) architectures have been proposed with demonstrated improvement in text summarization and classification. Adapting these architectures to the medical domain requires additional considerations. For instance, the medical history of the patient is documented in the Electronic Health Record (EHR) which includes many medical notes drafted by healthcare providers. Direct processing of these notes may not be possible because the computational complexity of LMs imposes a limit on the length of input text. Therefore, previous applications resorted to content selection using truncation or summarization of the text. Unfortunately, these text processing techniques may lead to information loss, redundancy or irrelevance. In the present paper, a decision-focused content selection technique is proposed. The objective of this technique is to select a subset of sentences from the medical notes of a patient that are relevant to the target outcome over a predefined observation period. This decision-focused content selection methodology is then used to develop a dementia risk prediction model based on the Longformer LM architecture. The results show that the proposed framework delivers an AUC of 78.43 when the summary is restricted to 1024 tokens, outperforming previously proposed content selection techniques. This performance is notable given that the model estimates dementia risk with a one year prediction horizon, relies on an observation period of only one year and solely uses medical notes without other EHR data modalities. Moreover, the proposed techniques overcome the limitation of machine learning models that use a tabular representation of the text by preserving contextual content, enable feature engineering from raw text and circumvent the computational complexity of language models.

目前已经提出了几种通用语言模型(LM)架构,并在文本摘要和分类方面取得了明显的改进。将这些架构应用于医疗领域需要考虑更多因素。例如,病人的病史记录在电子病历 (EHR) 中,其中包括医疗保健提供者起草的许多医疗笔记。直接处理这些笔记可能是不可能的,因为 LM 的计算复杂性对输入文本的长度有限制。因此,以前的应用采用文本截断或摘要的方式进行内容选择。遗憾的是,这些文本处理技术可能会导致信息丢失、冗余或不相关。本文提出了一种以决策为重点的内容选择技术。该技术的目的是从病人的医疗记录中挑选出与预定观察期内目标结果相关的句子子集。然后,这种以决策为重点的内容选择方法被用于开发基于 Longformer LM 架构的痴呆症风险预测模型。结果表明,当摘要限制为 1024 个标记时,所提出的框架的 AUC 为 78.43,优于之前提出的内容选择技术。鉴于该模型以一年的预测范围来估算痴呆症风险,仅依赖于一年的观察期,并且仅使用医疗笔记而不使用其他电子病历数据模式,因此该性能是值得注意的。此外,所提出的技术通过保留上下文内容,克服了使用文本表格表示的机器学习模型的局限性,实现了原始文本的特征工程,并规避了语言模型的计算复杂性。
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引用次数: 0
Virtual multi-staining in a single-section view for renal pathology using generative adversarial networks 利用生成式对抗网络在单切片视图中对肾脏病理进行虚拟多重染色
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109149

Sections stained in periodic acid-Schiff (PAS), periodic acid-methenamine silver (PAM), hematoxylin and eosin (H&E), and Masson's trichrome (MT) stain with minimal morphological discordance are helpful for pathological diagnosis in renal biopsy. Here, we propose an artificial intelligence-based re-stainer called PPHM-GAN (PAS, PAM, H&E, and MT-generative adversarial networks) with multi-stain to multi-stain transformation capability. We trained three GAN models on 512 × 512-pixel patches from 26 training cases. The model with the best transformation quality was selected for each pair of stain transformations by human evaluation. Frechet inception distances, peak signal-to-noise ratio, structural similarity index measure, contrast structural similarity, and newly introduced domain shift inception score were calculated as auxiliary quality metrics. We validated the diagnostic utility using 5120 × 5120 patches of ten validation cases for major glomerular and interstitial abnormalities. Transformed stains were sometimes superior to original stains for the recognition of crescent formation, mesangial hypercellularity, glomerular sclerosis, interstitial lesions, or arteriosclerosis. 23 of 24 glomeruli (95.83 %) from 9 additional validation cases transformed to PAM, PAS, or MT facilitated recognition of crescent formation. Stain transformations to PAM (p = 4.0E-11) and transformations from H&E (p = 4.8E-9) most improved crescent formation recognition. PPHM-GAN maximizes information from a given section by providing several stains in a virtual single-section view, and may change the staining and diagnostic strategy.

经周期性酸-希夫(PAS)、周期性酸-甲胺银(PAM)、苏木精和伊红(H&E)以及马森三色染色(MT)染色的切片形态差异最小,有助于肾活检的病理诊断。在此,我们提出了一种基于人工智能的再染色器,称为 PPHM-GAN(PAS、PAM、H&E 和 MT 生成对抗网络),具有多染色到多染色的转换能力。我们在来自 26 个训练案例的 512 × 512 像素斑块上训练了三个 GAN 模型。通过人工评估,为每对染色转换选择了转换质量最好的模型。我们计算了弗雷谢特起始距离、峰值信噪比、结构相似性指数测量、对比度结构相似性和新引入的域偏移起始得分作为辅助质量指标。我们使用 10 个验证病例的 5120 × 5120 补丁对主要肾小球和间质异常的诊断效用进行了验证。在识别新月体形成、系膜细胞过多、肾小球硬化、间质病变或动脉硬化方面,转化染色有时优于原始染色。另外 9 个验证病例的 24 个肾小球中有 23 个(95.83%)转化为 PAM、PAS 或 MT 染色,有助于识别新月体形成。将染色转换为 PAM(p = 4.0E-11)和从 H&E 转换(p = 4.8E-9)最能提高新月体形成的识别率。PPHM-GAN 通过在虚拟的单切片视图中提供多种染色,最大限度地利用了给定切片的信息,并可能改变染色和诊断策略。
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引用次数: 0
Modeling of joint extraction of entity relationships in clinical electronic medical records 临床电子病历实体关系联合提取建模
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109161

The advancement of medical informatization necessitates extracting entities and their relationships from electronic medical records. Presently, research on electronic medical records predominantly concentrates on single-entity relationship extraction. However, clinical electronic medical records frequently exhibit overlapping complex entity relationships, thereby heightening the challenge of information extraction. To rectify the absence of a clinical medical relationship extraction dataset, this study utilizes electronic medical records from 584 patients in a hospital to create a compact clinical medical relationship extraction dataset. To address the pipelined relationship extraction model’s limitation in overlooking the one-to-many correlation problem between entities and relationships, this paper introduces a cascading relationship extraction model. This model integrates the MacBERT pre-training model, gated recurrent network, and multi-head self-attention mechanism to enhance the extraction of text features. Simultaneously, adversarial learning is incorporated to bolster the model’s robustness. In scenarios involving one-to-many relationships between entities, a two-phase task is employed. Initially, the main entity is predicted, followed by predicting the associated object and their correspondences. Employing this cascade-structured approach enables the model to flexibly manage intricate entity relationships, thereby enhancing extraction accuracy. Experimental results demonstrate the model’s efficiency, yielding F1-scores of 82.8%, 76.8%, and 88.2% for fulfilling relational extraction requirements and tasks on DuIE, CHIP-CDEE, and private datasets, respectively. These scores represent improvements over the benchmark model. The findings indicate the model’s applicability in practical domains, particularly in tasks such as biomedical information extraction.

医疗信息化的发展要求从电子病历中提取实体及其关系。目前,有关电子病历的研究主要集中在单一实体关系提取方面。然而,临床电子病历经常表现出重叠的复杂实体关系,从而增加了信息提取的难度。为了弥补临床医学关系提取数据集的缺失,本研究利用某医院 584 名患者的电子病历创建了一个紧凑的临床医学关系提取数据集。为了解决流水线式关系提取模型在实体和关系之间一对多关联问题上的局限性,本文引入了级联式关系提取模型。该模型集成了 MacBERT 预训练模型、门控递归网络和多头自注意机制,以增强文本特征的提取。同时,该模型还加入了对抗学习,以增强其鲁棒性。在涉及实体间一对多关系的场景中,采用了两阶段任务。首先预测主要实体,然后预测相关对象及其对应关系。采用这种级联结构的方法使模型能够灵活地管理错综复杂的实体关系,从而提高提取的准确性。实验结果证明了该模型的高效性,在DuIE、CHIP-CDEE和私人数据集上完成关系提取要求和任务的F1分数分别为82.8%、76.8%和88.2%。与基准模型相比,这些分数都有所提高。研究结果表明,该模型适用于实际领域,尤其是生物医学信息提取等任务。
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引用次数: 0
Improving electrocardiographic imaging solutions: A comprehensive study on regularization parameter selection in L-curve optimization in the Atria 改进心电图成像解决方案:心房 L 曲线优化中正则化参数选择的综合研究
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109141

Background

In electrocardiographic imaging (ECGI), selecting an optimal regularization parameter (λ) is crucial for obtaining accurate inverse electrograms. The effects of signal and geometry uncertainties on the inverse problem regularization have not been thoroughly quantified, and there is no established methodology to identify when λ is sub-optimal due to these uncertainties. This study introduces a novel approach to λ selection using Tikhonov regularization and L-curve optimization, specifically addressing the impact of electrical noise in body surface potential map (BSPM) signals and geometrical inaccuracies in the cardiac mesh.

Methods

Nineteen atrial simulations (5 of regular rhythms and 14 of atrial fibrillation) ensuring variability in substrate complexity and activation patterns were used for computing the ECGI with added white Gaussian noise from 40 dB to -3dB. Cardiac mesh displacements (1–3 cm) were applied to simulate the uncertainty of atrial positioning and study its impact on the L-curve shape. The regularization parameter, the maximum curvature, and the most horizontal angle of the L-curve (β) were quantified. In addition, BSPM signals from real patients were used to validate our findings.

Results

The maximum curvature of the L-curve was found to be inversely related to signal-to-noise ratio and atrial positioning errors. In contrast, the β angle is directly related to electrical noise and remains unaffected by geometrical errors. Our proposed adjustment of λ, based on the β angle, provides a more reliable ECGI solution than traditional corner-based methods. Our findings have been validated with simulations and real patient data, demonstrating practical applicability.

Conclusion

Adjusting λ based on the amount of noise in the data (or on the β angle) allows finding optimal ECGI solutions than a λ purely found at the corner of the L-curve. It was observed that the relevant information in ECGI activation maps is preserved even under the presence of uncertainties when the regularization parameter is correctly selected. The proposed criteria for regularization parameter selection have the potential to enhance the accuracy and reliability of ECGI solutions.

背景在心电图成像(ECGI)中,选择最佳正则化参数(λ)对于获得精确的反向电图至关重要。信号和几何不确定性对逆问题正则化的影响尚未被彻底量化,也没有既定的方法来确定λ何时因这些不确定性而成为次优参数。本研究介绍了一种使用 Tikhonov 正则化和 L 曲线优化来选择 λ 的新方法,特别解决了体表电位图 (BSPM) 信号中的电噪声和心脏网格中的几何不准确性的影响。方法 19 个心房模拟(5 个常规节律和 14 个心房颤动)确保了基质复杂性和激活模式的可变性,用于计算 ECGI,并添加了 40 dB 到 -3dB 的白高斯噪声。应用心脏网格位移(1-3 厘米)来模拟心房定位的不确定性,并研究其对 L 曲线形状的影响。量化了正则化参数、最大曲率和 L 曲线的最大水平角度 (β)。结果发现 L 型曲线的最大曲率与信噪比和心房定位误差成反比。相反,β 角与电噪声直接相关,不受几何误差的影响。与传统的基于转角的方法相比,我们提出的基于 β 角的 λ 调节方法能提供更可靠的心电图成像解决方案。结论根据数据中的噪声量(或 β 角)调整 λ 可找到最佳的心电图成像解决方案,而不是纯粹在 L 曲线的拐角处找到 λ。据观察,如果正则化参数选择正确,即使存在不确定性,ECGI 激活图中的相关信息也能得到保留。所提出的正则化参数选择标准有望提高心电图成像解决方案的准确性和可靠性。
{"title":"Improving electrocardiographic imaging solutions: A comprehensive study on regularization parameter selection in L-curve optimization in the Atria","authors":"","doi":"10.1016/j.compbiomed.2024.109141","DOIUrl":"10.1016/j.compbiomed.2024.109141","url":null,"abstract":"<div><h3>Background</h3><p>In electrocardiographic imaging (ECGI), selecting an optimal regularization parameter (λ) is crucial for obtaining accurate inverse electrograms. The effects of signal and geometry uncertainties on the inverse problem regularization have not been thoroughly quantified, and there is no established methodology to identify when λ is sub-optimal due to these uncertainties. This study introduces a novel approach to λ selection using Tikhonov regularization and L-curve optimization, specifically addressing the impact of electrical noise in body surface potential map (BSPM) signals and geometrical inaccuracies in the cardiac mesh.</p></div><div><h3>Methods</h3><p>Nineteen atrial simulations (5 of regular rhythms and 14 of atrial fibrillation) ensuring variability in substrate complexity and activation patterns were used for computing the ECGI with added white Gaussian noise from 40 dB to -3dB. Cardiac mesh displacements (1–3 cm) were applied to simulate the uncertainty of atrial positioning and study its impact on the L-curve shape. The regularization parameter, the maximum curvature, and the most horizontal angle of the L-curve (β) were quantified. In addition, BSPM signals from real patients were used to validate our findings.</p></div><div><h3>Results</h3><p>The maximum curvature of the L-curve was found to be inversely related to signal-to-noise ratio and atrial positioning errors. In contrast, the β angle is directly related to electrical noise and remains unaffected by geometrical errors. Our proposed adjustment of λ, based on the β angle, provides a more reliable ECGI solution than traditional corner-based methods. Our findings have been validated with simulations and real patient data, demonstrating practical applicability.</p></div><div><h3>Conclusion</h3><p>Adjusting λ based on the amount of noise in the data (or on the β angle) allows finding optimal ECGI solutions than a λ purely found at the corner of the L-curve. It was observed that the relevant information in ECGI activation maps is preserved even under the presence of uncertainties when the regularization parameter is correctly selected. The proposed criteria for regularization parameter selection have the potential to enhance the accuracy and reliability of ECGI solutions.</p></div>","PeriodicalId":10578,"journal":{"name":"Computers in biology and medicine","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0010482524012265/pdfft?md5=00ba75c411a8220b072c6a47be025ff1&pid=1-s2.0-S0010482524012265-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
RetVes segmentation: A pseudo-labeling and feature knowledge distillation optimization technique for retinal vessel channel enhancement 视网膜血管分割:用于视网膜血管通道增强的伪标记和特征知识提炼优化技术
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109150

Recent advancements in retinal vessel segmentation, which employ transformer-based and domain-adaptive approaches, show promise in addressing the complexity of ocular diseases such as diabetic retinopathy. However, current algorithms face challenges in effectively accommodating domain-specific variations and limitations of training datasets, which fail to represent real-world conditions comprehensively. Manual inspection by specialists remains time-consuming despite technological progress in medical imaging, underscoring the pressing need for automated and robust segmentation techniques. Additionally, these methods have deficiencies in handling unlabeled target sets, requiring extra preprocessing steps and manual intervention, which hinders their scalability and practical application in clinical settings. This research introduces a novel framework that employs semi-supervised domain adaptation and contrastive pre-training to address these limitations. The proposed model effectively learns from target data by implementing a novel pseudo-labeling approach and feature-based knowledge distillation within a temporal convolutional network (TCN) and extracts robust, domain-independent features. This approach enhances cross-domain adaptation, significantly enhancing the model's versatility and performance in clinical settings. The semi-supervised domain adaptation component overcomes the challenges posed by domain shifts, while pseudo-labeling utilizes the data's inherent structure for enhanced learning, which is particularly beneficial when labeled data is scarce. Evaluated on the DRIVE and CHASE_DB1 datasets, which contain clinical fundus images, the proposed model achieves outstanding performance, with accuracy, sensitivity, specificity, and AUC values of 0.9792, 0.8640, 0.9901, and 0.9868 on DRIVE, and 0.9830, 0.9058, 0.9888, and 0.9950 on CHASE_DB1, respectively, outperforming current state-of-the-art vessel segmentation methods. The partitioning of datasets into training and testing sets ensures thorough validation, while extensive ablation studies with thorough sensitivity analysis of the model's parameters and different percentages of labeled data further validate its robustness.

最近在视网膜血管分割方面取得的进展表明,采用基于变压器和域自适应的方法有望解决糖尿病视网膜病变等眼科疾病的复杂性。然而,当前的算法在有效适应特定领域的变化和训练数据集的局限性方面面临着挑战,因为这些数据集无法全面反映真实世界的状况。尽管医学成像技术在不断进步,但由专家进行人工检查仍然非常耗时,这凸显了对自动化和强大的分割技术的迫切需要。此外,这些方法在处理无标记目标集方面存在缺陷,需要额外的预处理步骤和人工干预,这阻碍了它们在临床环境中的可扩展性和实际应用。这项研究引入了一个新颖的框架,利用半监督领域适应和对比预训练来解决这些局限性。所提出的模型通过在时序卷积网络(TCN)中实施新颖的伪标记方法和基于特征的知识提炼,有效地从目标数据中学习,并提取稳健的、与领域无关的特征。这种方法增强了跨领域适应性,大大提高了模型在临床环境中的通用性和性能。半监督领域适应组件克服了领域转移带来的挑战,而伪标记则利用数据的固有结构来增强学习,这在标记数据稀缺的情况下尤为有益。在包含临床眼底图像的DRIVE和CHASE_DB1数据集上进行评估,所提出的模型取得了出色的性能,在DRIVE数据集上的准确度、灵敏度、特异度和AUC值分别为0.9792、0.8640、0.9901和0.9868,在CHASE_DB1数据集上的准确度、灵敏度、特异度和AUC值分别为0.9830、0.9058、0.9888和0.9950,优于目前最先进的血管分割方法。将数据集划分为训练集和测试集确保了彻底的验证,而广泛的消融研究以及对模型参数和不同百分比标记数据的彻底敏感性分析进一步验证了其稳健性。
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引用次数: 0
Discovery of novel MLK4 inhibitors against colorectal cancer through computational approaches 通过计算方法发现新型 MLK4 大肠癌抑制剂
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109136

Colorectal cancer (CRC) is a significant health issue globally, affecting approximately 10 % of the world's population. The prevalence of CRC highlights the need for effective treatments and prevention strategies. The current therapeutic option, such as chemotherapy, has significant side effects. Thus, this study investigated the anticancer properties of Sanguinarine derivatives, an alkaloid found in traditional herbs via chemoinformatic approaches. Six Sanguinarine derivatives were discovered through virtual screening and molecular docking to determine their binding affinities against the mixed lineage kinase (MLK4) protein which is responsible for CRC. All the compounds were found to be more effective than standard drug used for colorectal cancer treatment, with Sanguinarine derivative 11 showing the highest affinity. The stability of the drug was confirmed through molecular dynamics simulations at 500 ns. This suggests that compound 11 has a higher chance of replacing 5-Fluorouracil, which is currently a widely used chemotherapy drug. Before molecular dynamics simulations, the pharmacokinetic and chemical properties of Sanguinarine derivatives were determined using pkCSM server and DFT method, respectively. The results support that compound 11 is a good drug candidate, as evidenced by Lipinski's Rule of Five. Therefore, compound 11 is recommended for further analysis via in vivo and in vitro studies to confirm its efficacy and safety.

结肠直肠癌(CRC)是一个全球性的重大健康问题,影响着全球约 10% 的人口。大肠癌的发病率凸显了对有效治疗和预防策略的需求。目前的治疗方法,如化疗,有很大的副作用。因此,本研究通过化学信息学方法研究了传统草药中的一种生物碱--Sanguinarine 衍生物的抗癌特性。通过虚拟筛选和分子对接,研究人员发现了六种Sanguinarine衍生物,以确定它们与导致癌症的混合系激酶(MLK4)蛋白的结合亲和力。结果发现,所有化合物都比治疗结直肠癌的标准药物更有效,其中番荔枝碱衍生物 11 的亲和力最高。通过 500 ns 的分子动力学模拟证实了药物的稳定性。这表明化合物 11 有更大的机会取代目前广泛使用的化疗药物 5-氟尿嘧啶。在进行分子动力学模拟之前,分别使用 pkCSM 服务器和 DFT 方法测定了 Sanguinarine 衍生物的药代动力学和化学特性。结果表明,化合物 11 是一种很好的候选药物,Lipinski's Rule of Five 也证明了这一点。因此,建议通过体内和体外研究对化合物 11 进行进一步分析,以确认其疗效和安全性。
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引用次数: 0
High-frequency chest wall oscillation devices: An umbrella review and bibliometric analysis 高频胸壁振荡装置:综述和文献计量分析
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.compbiomed.2024.109135

Introduction

High-frequency chest wall oscillation (HFCWO) devices are used to improve airway clearance in various respiratory conditions. This study comprehensively assesses the evidence on efficacy and safety and identifies trends in scientific publications and patents across geographic regions.

Methods

This study utilized an integrated approach, combining bibliographic and bibliometric research with artificial intelligence (AI) tools. Four databases – PubMed, Europe Pubmed Central, Cochrane Database of Systematic Reviews, and CINAHL – were searched for systematic reviews on the effectiveness of treatment options for HFCWO. The AMSTAR-2 tool was used to evaluate the risk of bias in systematic reviews. Bibliographic research synthesized the evidence following PRISMA and Cochrane guidelines. The Dimensions platform was used for bibliometric analysis to provide insights into the global landscape. AI tools with prompt engineering tools Chain-of-Thoughts (CoT) and Tree of Thoughts (ToT) were used to enhance data extraction capabilities.

Results

The umbrella review identified 12 systematic reviews supporting the effectiveness of HFCWO in improving pulmonary function parameters, sputum characteristics, dyspnea, health scores, and quality of life in conditions including cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease (COPD), or neuromuscular diseases, with varying evidence of certainty. Eight of the twelve reviews had a moderate to high AMSTAR-2 confidence level, while several studies lacked sufficient descriptions of methods, treatment regimens, outcome measures, and adverse effects. Despite the absence of adverse events, the overall evidence quality between studies is evaluated as low to very low. Bibliometric analysis found a significant increase in global interest over the past two decades, with 230 research publications, 137 patents, and 56 clinical trials.

Conclusions

The study highlights the potential of HFCWO devices in respiratory care but demands more robust evidence. The increasing interest in airway clearance devices highlights the necessity for HFCWO mechanism and safety research, underlining its therapeutic relevance in respiratory medicine. The interdisciplinary integration of AI tools and prompt engineering contributes to a nuanced understanding of the available evidence.

导言高频胸壁振荡(HFCWO)设备用于改善各种呼吸系统疾病的气道通畅状况。本研究全面评估了有关疗效和安全性的证据,并确定了不同地区科学出版物和专利的趋势。方法本研究采用了一种综合方法,将文献和文献计量学研究与人工智能(AI)工具相结合。在 PubMed、Europe Pubmed Central、Cochrane Database of Systematic Reviews 和 CINAHL 四个数据库中检索了有关 HFCWO 治疗方案有效性的系统综述。AMSTAR-2工具用于评估系统性综述的偏倚风险。文献研究按照 PRISMA 和 Cochrane 指南对证据进行了综合。使用 Dimensions 平台进行文献计量分析,以深入了解全球情况。结果总综述确定了 12 篇系统综述,这些综述支持 HFCWO 在改善囊性纤维化、支气管扩张、慢性阻塞性肺病 (COPD) 或神经肌肉疾病的肺功能参数、痰液特征、呼吸困难、健康评分和生活质量方面的有效性,但证据的确定性各不相同。在 12 篇综述中,有 8 篇的 AMSTAR-2 可信度为中度到高度,而有几项研究缺乏对方法、治疗方案、结果测量和不良反应的充分说明。尽管没有不良反应,但研究之间的总体证据质量被评定为低至极低。文献计量分析发现,在过去二十年中,全球对 HFCWO 设备的兴趣显著增加,共发表了 230 篇研究论文、137 项专利和 56 项临床试验。人们对气道通畅设备的兴趣与日俱增,这凸显了 HFCWO 机制和安全性研究的必要性,同时也强调了其在呼吸医学中的治疗意义。人工智能工具和及时工程学的跨学科整合有助于对现有证据进行细致入微的理解。
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引用次数: 0
CCPred: Global and population-specific colorectal cancer prediction and metagenomic biomarker identification at different molecular levels using machine learning techniques CCPred:利用机器学习技术在不同分子水平上进行全球和特定人群结直肠癌预测和元基因组生物标记物鉴定
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-17 DOI: 10.1016/j.compbiomed.2024.109098

Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related deaths. Recent research highlights the pivotal role of the gut microbiota in CRC development and progression. Understanding the complex interplay between disease development and metagenomic data is essential for CRC diagnosis and treatment. Current computational models employ machine learning to identify metagenomic biomarkers associated with CRC, yet there is a need to improve their accuracy through a holistic biological knowledge perspective. This study aims to evaluate CRC-associated metagenomic data at species, enzymes, and pathway levels via conducting global and population-specific analyses. These analyses utilize relative abundance values from human gut microbiome sequencing data and robust classification models are built for disease prediction and biomarker identification. For global CRC prediction and biomarker identification, the features that are identified by SelectKBest (SKB), Information Gain (IG), and Extreme Gradient Boosting (XGBoost) methods are combined. Population-based analysis includes within-population, leave-one-dataset-out (LODO) and cross-population approaches. Four classification algorithms are employed for CRC classification. Random Forest achieved an AUC of 0.83 for species data, 0.78 for enzyme data and 0.76 for pathway data globally. On the global scale, potential taxonomic biomarkers include ruthenibacterium lactatiformanas; enzyme biomarkers include RNA 2′ 3′ cyclic 3′ phosphodiesterase; and pathway biomarkers include pyruvate fermentation to acetone pathway. This study underscores the potential of machine learning models trained on metagenomic data for improved disease prediction and biomarker discovery. The proposed model and associated files are available at https://github.com/TemizMus/CCPRED.

结肠直肠癌(CRC)是全球第三大常见癌症,也是癌症相关死亡的第二大原因。最近的研究突显了肠道微生物群在 CRC 发展和恶化过程中的关键作用。了解疾病发展与元基因组数据之间复杂的相互作用对 CRC 的诊断和治疗至关重要。目前的计算模型采用机器学习来识别与 CRC 相关的元基因组生物标记物,但仍需要从整体生物学知识的角度来提高其准确性。本研究旨在通过开展全球和特定人群分析,在物种、酶和通路层面评估与 CRC 相关的元基因组数据。这些分析利用了人类肠道微生物组测序数据的相对丰度值,并为疾病预测和生物标记物鉴定建立了稳健的分类模型。对于全局性的 CRC 预测和生物标记物鉴定,结合了 SelectKBest (SKB)、Information Gain (IG) 和 Extreme Gradient Boosting (XGBoost) 方法所识别的特征。基于种群的分析包括种群内分析、留出一个数据集(LODO)和跨种群分析。CRC 分类采用了四种分类算法。在全球范围内,随机森林的物种数据AUC为0.83,酶数据为0.78,途径数据为0.76。在全球范围内,潜在的分类生物标志物包括乳酸钌杆菌;酶生物标志物包括 RNA 2′ 3′ 环 3′ 磷酸二酯酶;途径生物标志物包括丙酮酸发酵到丙酮途径。这项研究强调了在元基因组数据上训练的机器学习模型在改进疾病预测和生物标记物发现方面的潜力。建议的模型和相关文件可在 https://github.com/TemizMus/CCPRED 上查阅。
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引用次数: 0
Modelling patient trajectories in emergency department simulations using retrospective patient cohorts 利用回顾性患者队列建立急诊科模拟患者轨迹模型
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-17 DOI: 10.1016/j.compbiomed.2024.109147

Computer simulations of emergency departments (EDs) are tools that can support managing and optimising ED operations. A core component of ED simulation models is patient trajectories, defined as the series of activities patients undergo in the ED from arrival to discharge. The combined duration of these activities, and waiting times between them, determines a patient’s length of stay (LOS). Patient trajectories are often calibrated and validated solely based on the estimated acuity of patients assigned upon arrival. However, acuity is a prospective patient indicator that inconsistently reflects patients’ actual urgency and resource usage as seen retrospectively upon discharge. Here, we propose a data-driven ED simulation model in which patient trajectories are modelled based on both acuity and retrospective patient indicators. We show that including retrospective patient indicators recovers the observed LOS distributions more accurately than when using acuity alone. We also demonstrate how the use of retrospective patient indicators leads to more plausible estimates of the impact of increased stress in the ED on patients’ LOS. Our work exemplifies how we can better utilise ED data to make the development and evaluation of ED simulation models more accurate and robust, enabling them to provide more reliable and useful operational insights.

急诊科(ED)的计算机模拟是一种可支持管理和优化急诊科运作的工具。急诊室模拟模型的一个核心组成部分是病人轨迹,即病人从到达急诊室到出院的一系列活动。这些活动的综合持续时间以及它们之间的等待时间决定了病人的住院时间(LOS)。患者轨迹通常仅根据患者到达时的估计敏锐度进行校准和验证。然而,急性期是一个前瞻性的患者指标,与出院时回溯的患者实际紧急程度和资源使用情况并不一致。在这里,我们提出了一个数据驱动的急诊室仿真模型,在该模型中,病人的轨迹是基于敏锐度和回顾性病人指标来建模的。我们的研究表明,与仅使用敏锐度相比,使用回顾性患者指标能更准确地还原观察到的 LOS 分布。我们还展示了使用回顾性患者指标如何使 ED 压力增加对患者 LOS 影响的估计更加合理。我们的工作体现了如何更好地利用急诊室数据来使急诊室模拟模型的开发和评估更加准确和稳健,从而使其能够提供更可靠、更有用的操作见解。
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引用次数: 0
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