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Organizational preparedness for the use of large language models in pathology informatics 在病理学信息学中使用大型语言模型的组织准备。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100338
Steven N. Hart , Noah G. Hoffman , Peter Gershkovich , Chancey Christenson , David S. McClintock , Lauren J. Miller , Ronald Jackups , Vahid Azimi , Nicholas Spies , Victor Brodsky

In this paper, we consider the current and potential role of the latest generation of Large Language Models (LLMs) in medical informatics, particularly within the realms of clinical and anatomic pathology. We aim to provide a thorough understanding of the considerations that arise when employing LLMs in healthcare settings, such as determining appropriate use cases and evaluating the advantages and limitations of these models.

Furthermore, this paper will consider the infrastructural and organizational requirements necessary for the successful implementation and utilization of LLMs in healthcare environments. We will discuss the importance of addressing education, security, bias, and privacy concerns associated with LLMs in clinical informatics, as well as the need for a robust framework to overcome regulatory, compliance, and legal challenges.

在本文中,我们考虑了最新一代大型语言模型(LLM)在医学信息学中的当前和潜在作用,特别是在临床和解剖病理学领域。我们的目标是全面了解在医疗环境中使用LLM时出现的考虑因素,例如确定适当的用例并评估这些模型的优势和局限性。此外,本文将考虑在医疗保健环境中成功实施和利用LLM所需的基础设施和组织要求。我们将讨论解决临床信息学中LLM相关的教育、安全、偏见和隐私问题的重要性,以及克服监管、合规和法律挑战的强大框架的必要性。
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引用次数: 0
Analysis of cellularity in H&E-stained rat bone marrow tissue via deep learning 通过深度学习分析H&E染色的大鼠骨髓组织中的细胞结构。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100333
Smadar Shiffman , Edgar A. Rios Piedra , Adeyemi O. Adedeji , Catherine F. Ruff , Rachel N. Andrews , Paula Katavolos , Evan Liu , Ashley Forster , Jochen Brumm , Reina N. Fuji , Ruth Sullivan

Our objective was to develop an automated deep-learning-based method to evaluate cellularity in rat bone marrow hematoxylin and eosin whole slide images for preclinical safety assessment. We trained a shallow CNN for segmenting marrow, 2 Mask R-CNN models for segmenting megakaryocytes (MKCs), and small hematopoietic cells (SHCs), and a SegNet model for segmenting red blood cells. We incorporated the models into a pipeline that identifies and counts MKCs and SHCs in rat bone marrow. We compared cell segmentation and counts that our method generated to those that pathologists generated on 10 slides with a range of cell depletion levels from 10 studies. For SHCs, we compared cell counts that our method generated to counts generated by Cellpose and Stardist. The median Dice and object Dice scores for MKCs using our method vs pathologist consensus and the inter- and intra-pathologist variation were comparable, with overlapping first-third quartile ranges. For SHCs, the median scores were close, with first-third quartile ranges partially overlapping intra-pathologist variation. For SHCs, in comparison to Cellpose and Stardist, counts from our method were closer to pathologist counts, with a smaller 95% limits of agreement range. The performance of the bone marrow analysis pipeline supports its incorporation into routine use as an aid for hematotoxicity assessment by pathologists. The pipeline could help expedite hematotoxicity assessment in preclinical studies and consequently could expedite drug development. The method may enable meta-analysis of rat bone marrow characteristics from future and historical whole slide images and may generate new biological insights from cross-study comparisons.

我们的目标是开发一种基于深度学习的自动化方法,用于评估大鼠骨髓苏木精和伊红全玻片图像中的细胞密度,以进行临床前安全性评估。我们训练了用于分割骨髓的浅层CNN,用于分割巨核细胞(MKCs)和小造血细胞(SHCs)的2-Mask R-CNN模型,以及用于分割红细胞的SegNet模型。我们将这些模型纳入一个管道中,用于识别和计数大鼠骨髓中的MKCs和SHCs。我们将我们的方法产生的细胞分割和计数与病理学家在10张幻灯片上产生的细胞分裂和计数进行了比较,这些幻灯片具有10项研究中的一系列细胞耗竭水平。对于SHCs,我们将我们的方法生成的细胞计数与Cellpose和Stardist生成的计数进行了比较。使用我们的方法对MKCs的Dice和object Dice评分中值与病理学家的一致性以及病理学家之间和内部的差异具有可比性,前三分位数范围重叠。对于SHCs,中位数得分接近,前三个四分位数的范围部分重叠病理学家内部的变异。对于SHCs,与Cellpose和Stardist相比,我们方法的计数更接近病理学家的计数,一致性范围的95%限制较小。骨髓分析管道的性能支持将其纳入常规用途,以帮助病理学家进行血液毒性评估。该管道有助于加快临床前研究中的血液毒性评估,从而加快药物开发。该方法可以从未来和历史的全玻片图像中对大鼠骨髓特征进行荟萃分析,并可以从交叉研究比较中产生新的生物学见解。
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引用次数: 0
Digital pathology operations at a tertiary cancer center: Infrastructure requirements and operational cost 癌症三级中心的数字化病理手术:基础设施要求和运营成本。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100318
Orly Ardon, Eric Klein, Allyne Manzo, Lorraine Corsale, Christine England, Allix Mazzella, Luke Geneslaw, John Philip, Peter Ntiamoah, Jeninne Wright, Sahussapont Joseph Sirintrapun, Oscar Lin, Kojo Elenitoba-Johnson, Victor E. Reuter, Meera R. Hameed, Matthew G. Hanna

Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago. This experience and the large-scale scan operations led to the identification of required framework components of digital pathology operations. The cost of these components for the 2021 digital pathology operations at MSK were studied and calculated to enable an understanding of the operation and benchmark the accompanying costs.

This paper describes the unique infrastructure cost and the costs associated with the digital pathology clinical operation use cases in a large, tertiary cancer center. These calculations can serve as a blueprint for other institutions to provide the necessary concepts and offer insights towards the financial requirements for digital pathology adoption by other institutions.

全玻片成像正在彻底改变病理学领域,目前正被越来越多的机构用于临床、教育和研究计划。病理学部门对数字病理学系统有着独特的需求,但数字工作流程的成本被认为是许多组织广泛采用的主要障碍。纪念斯隆-凯特琳癌症中心(MSK)是全玻片成像的早期采用者,15年前就开始对资源进行增量投资。这一经验和大规模的扫描操作导致了数字病理学操作所需框架组件的识别。对MSK 2021年数字病理手术的这些组件的成本进行了研究和计算,以了解手术情况并确定相关成本。本文描述了一个大型三级癌症中心独特的基础设施成本和与数字病理临床操作用例相关的成本。这些计算可以作为其他机构提供必要概念的蓝图,并为其他机构采用数字病理学的财务要求提供见解。
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引用次数: 1
The ChatGPT conundrum: Human-generated scientific manuscripts misidentified as AI creations by AI text detection tool ChatGPT难题:人工智能文本检测工具错误地将人类生成的科学手稿识别为人工智能创作
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100342
Hooman H. Rashidi , Brandon D. Fennell , Samer Albahra , Bo Hu , Tom Gorbett

AI Chat Bots such as ChatGPT are revolutionizing our AI capabilities, especially in text generation, to help expedite many tasks, but they introduce new dilemmas. The detection of AI-generated text has become a subject of great debate considering the AI text detector’s known and unexpected limitations. Thus far, much research in this area has focused on the detection of AI-generated text; however, the goal of this study was to evaluate the opposite scenario, an AI-text detection tool's ability to discriminate human-generated text. Thousands of abstracts from several of the most well-known scientific journals were used to test the predictive capabilities of these detection tools, assessing abstracts from 1980 to 2023. We found that the AI text detector erroneously identified up to 8% of the known real abstracts as AI-generated text. This further highlights the current limitations of such detection tools and argues for novel detectors or combined approaches that can address this shortcoming and minimize its unanticipated consequences as we navigate this new AI landscape.

像ChatGPT这样的人工智能聊天机器人正在彻底改变我们的人工智能能力,特别是在文本生成方面,以帮助加快许多任务,但它们引入了新的困境。考虑到人工智能文本检测器已知的和意想不到的局限性,人工智能生成文本的检测已经成为一个非常有争议的话题。到目前为止,这一领域的许多研究都集中在人工智能生成文本的检测上;然而,本研究的目的是评估相反的情况,即人工智能文本检测工具区分人类生成文本的能力。研究人员使用了来自几家最知名科学期刊的数千篇摘要来测试这些检测工具的预测能力,评估了1980年至2023年的摘要。我们发现,人工智能文本检测器错误地将多达8%的已知真实摘要识别为人工智能生成的文本。这进一步强调了这些检测工具目前的局限性,并提出了新的检测器或组合方法,可以解决这一缺点,并在我们导航新的人工智能领域时最大限度地减少其意想不到的后果。
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引用次数: 0
XML-GBM lung: An explainable machine learning-based application for the diagnosis of lung cancer XML-GBM lung:一个可解释的基于机器学习的肺癌诊断应用程序
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100307
Sarreha Tasmin Rikta , Khandaker Mohammad Mohi Uddin , Nitish Biswas , Rafid Mostafiz , Fateha Sharmin , Samrat Kumar Dey

Lung cancer has been the leading cause of cancer-related deaths worldwide. Early detection and diagnosis of lung cancer can greatly improve the chances of survival for patients. Machine learning has been increasingly used in the medical sector for the detection of lung cancer, but the lack of interpretability of these models remains a significant challenge. Explainable machine learning (XML) is a new approach that aims to provide transparency and interpretability for machine learning models. The entire experiment has been performed in the lung cancer dataset obtained from Kaggle. The outcome of the predictive model with ROS (Random Oversampling) class balancing technique is used to comprehend the most relevant clinical features that contributed to the prediction of lung cancer using a machine learning explainable technique termed SHAP (SHapley Additive exPlanation). The results show the robustness of GBM's capacity to detect lung cancer, with 98.76% accuracy, 98.79% precision, 98.76% recall, 98.76% F-Measure, and 0.16% error rate, respectively. Finally, a mobile app is developed incorporating the best model to show the efficacy of our approach.

肺癌一直是全球癌症相关死亡的主要原因。肺癌的早期发现和诊断可以大大提高患者的生存机会。机器学习已越来越多地用于医疗部门的肺癌检测,但这些模型缺乏可解释性仍然是一个重大挑战。可解释机器学习(XML)是一种旨在为机器学习模型提供透明性和可解释性的新方法。整个实验都是在从Kaggle获得的肺癌数据集中进行的。使用ROS(随机过采样)类平衡技术的预测模型的结果用于理解最相关的临床特征,这些特征有助于使用称为SHAP (SHapley加性解释)的机器学习可解释技术预测肺癌。结果表明,GBM检测肺癌的能力具有稳健性,准确率为98.76%,精密度为98.79%,召回率为98.76%,F-Measure为98.76%,错误率为0.16%。最后,我们开发了一款手机应用程序,并结合最佳模型来展示我们方法的有效性。
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引用次数: 2
Proceedings of the Association for Pathology Informatics Bootcamp 2022 病理学信息学训练营协会会议记录2022
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100331
Amrom E. Obstfeld , Victor Brodsky , Alexis B. Carter , Peter Gershkovich , Shannon Haymond , Bruce Levy , John Sinard , Devereaux Sellers , Michelle Stoffel , Ronald Jackups

The Pathology Informatics Bootcamp, held annually at the Pathology Informatics Summit, provides pathology trainees with essential knowledge in the rapidly evolving field of Pathology Informatics. With a focus on data analytics, data science, and data management in 2022, the bootcamp addressed the growing importance of data analysis in pathology and laboratory medicine practice. The expansion of data-related subjects in Pathology Informatics Essentials for Residents (PIER) and the Clinical Informatics fellowship examinations highlights the increasing significance of these skills in pathology practice in particular and medicine in general. The curriculum included lectures on databases, programming, analytics, machine learning basics, and specialized topics like anatomic pathology data analysis and dashboarding.

病理信息学训练营每年在病理信息学峰会上举行,为病理学员提供快速发展的病理信息学领域的基本知识。2022年,该训练营将重点关注数据分析、数据科学和数据管理,强调数据分析在病理学和实验室医学实践中日益重要。住院医师病理学信息学要点(PIER)和临床信息学奖学金考试中数据相关科目的扩展突出了这些技能在病理学实践中的重要性,特别是在医学上。课程包括数据库、编程、分析、机器学习基础知识,以及解剖病理学数据分析和仪表板等专业主题。
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引用次数: 0
Accurate diagnostic tissue segmentation and concurrent disease subtyping with small datasets 用小数据集准确诊断组织分割和并发疾病亚型
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2022.100174
Steven J. Frank

Purpose

To provide a flexible, end-to-end platform for visually distinguishing diseased from undiseased tissue in a medical image, in particular pathology slides, and classifying diseased regions by subtype. Highly accurate results are obtained using small training datasets and reduced-scale source images that can be easily shared.

Approach

An ensemble of lightweight convolutional neural networks (CNNs) is trained on different subsets of images derived from a relatively small number of annotated whole-slide histopathology images (WSIs). The WSIs are first reduced in scale in a manner that preserves anatomic features critical to analysis while also facilitating convenient handling and storage. The segmentation and subtyping tasks are performed sequentially on the reduced-scale images using the same basic workflow: generating and sifting tiles from the image, then classifying each tile with an ensemble of appropriately trained CNNs. For segmentation, the CNN predictions are combined using a function to favor a selected similarity metric, and a mask or map for a a candidate image is produced from tiles whose combined predictions exceed a decision boundary. For subtyping, the resulting mask is applied to the candidate image, and new tiles are derived from the unoccluded regions. These are classified by the subtyping CNNs to produce an overall subtype prediction.

Results and conclusion

This approach was applied successfully to two very different datasets of large WSIs, one (PAIP2020) involving multiple subtypes of colorectal cancer and the other (CAMELYON16) single-type breast cancer metastases. Scored using standard similarity metrics, the segmentations outperformed more complex models typifying the state of the art.

目的提供一个灵活的端到端平台,用于在医学图像(特别是病理切片)中视觉区分病变组织和未病变组织,并按亚型对病变区域进行分类。使用易于共享的小型训练数据集和缩减规模的源图像可以获得高精度的结果。方法轻量级卷积神经网络(cnn)的集合在来自相对少量注释的全切片组织病理学图像(wsi)的不同图像子集上进行训练。wsi首先以一种保留对分析至关重要的解剖特征的方式缩小规模,同时也便于处理和存储。使用相同的基本工作流程,在降尺度图像上依次执行分割和子类型任务:从图像中生成和筛选图像块,然后使用经过适当训练的cnn集合对每个图像块进行分类。对于分割,CNN预测使用一个函数组合以支持选定的相似性度量,并且从组合预测超过决策边界的块中生成候选图像的掩码或地图。对于子类型,将结果掩码应用于候选图像,并从未包含的区域派生出新的贴片。这些被分型cnn分类,以产生一个整体的分型预测。结果和结论该方法成功应用于两个非常不同的大型wsi数据集,一个(PAIP2020)涉及结直肠癌的多个亚型,另一个(CAMELYON16)涉及单一类型的乳腺癌转移。使用标准的相似性度量评分,分割优于更复杂的模型代表的艺术状态。
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引用次数: 1
Analysis of application of digital image analysis in histopathology quality control 数字图像分析在组织病理学质量控制中的应用分析
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100322
Riya Singh, Shakti Kumar Yadav, Neelkamal Kapoor

Introduction

A correct histopathological diagnosis is dependent on an array of technical variables. The quality and completeness of a histological section on a slide is extremely prudent for correct interpretation. However, this is mostly done manually and depends largely on the expertise of histotechnician. In this study, we analysed the application of digital image analysis for quality control of histological section as a proof-of-concept.

Material and methods

Images of 1000 histological sections and their corresponding blocks were captured. Area of the section was measured from these digital images of tissue block (Digiblock) and slide (Digislide). The data was analysed to calculate DigislideQC score, dividing the area of tissue on the slide by the tissue area on the block and it was compared with the number of recuts done for incomplete section.

Results

Digislide QC score ranged from 0.1 to 0.99. It showed an area under curve (AUC) of 98.8%. A cut-off value of 0.65 had a sensitivity of 99.6% and a specificity of 96.7%.

Conclusion

Digiblock and Digislide images can provide information about quality of sections. DigislideQC score can correctly identify the slides which require recuts before it is sent for reporting and potentially reduce histopathologists’ slide screening effort and ultimately turnaround time. These can be incorporated in routine histopathology workflows and lab information systems. This simple technology can also improve future digital pathology and telepathology workflows.

引言正确的组织病理学诊断取决于一系列技术变量。幻灯片上组织学切片的质量和完整性对于正确解释是非常谨慎的。然而,这主要是手动完成的,并且在很大程度上取决于组织技术人员的专业知识。在这项研究中,我们分析了数字图像分析在组织学切片质量控制中的应用,作为一种概念验证。材料和方法捕获了1000个组织学切片及其相应块的图像。根据这些组织块(Digiblock)和载玻片(Digislide)的数字图像测量切片的面积。对数据进行分析以计算DigislideQC评分,将载玻片上的组织面积除以块上的组织区域,并将其与不完整切片的切片次数进行比较。结果Digislide QC评分范围为0.1~0.99。曲线下面积(AUC)为98.8%,截断值0.65,灵敏度为99.6%,特异性为96.7%。DigislideQC评分可以正确识别在发送报告之前需要重新切片的载玻片,并可能减少组织病理学家的载玻片筛查工作和最终周转时间。这些可以纳入常规组织病理学工作流程和实验室信息系统。这项简单的技术还可以改善未来的数字病理学和远程病理学工作流程。
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引用次数: 0
Deep Interactive Learning-based ovarian cancer segmentation of H&E-stained whole slide images to study morphological patterns of BRCA mutation 基于深度交互学习的卵巢癌h&e染色全片图像分割研究BRCA突变的形态学模式
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2022.100160
David Joon Ho , M. Herman Chui , Chad M. Vanderbilt , Jiwon Jung , Mark E. Robson , Chan-Sik Park , Jin Roh , Thomas J. Fuchs

Deep learning has been widely used to analyze digitized hematoxylin and eosin (H&E)-stained histopathology whole slide images. Automated cancer segmentation using deep learning can be used to diagnose malignancy and to find novel morphological patterns to predict molecular subtypes. To train pixel-wise cancer segmentation models, manual annotation from pathologists is generally a bottleneck due to its time-consuming nature. In this paper, we propose Deep Interactive Learning with a pretrained segmentation model from a different cancer type to reduce manual annotation time. Instead of annotating all pixels from cancer and non-cancer regions on giga-pixel whole slide images, an iterative process of annotating mislabeled regions from a segmentation model and training/finetuning the model with the additional annotation can reduce the time. Especially, employing a pretrained segmentation model can further reduce the time than starting annotation from scratch. We trained an accurate ovarian cancer segmentation model with a pretrained breast segmentation model by 3.5 hours of manual annotation which achieved intersection-over-union of 0.74, recall of 0.86, and precision of 0.84. With automatically extracted high-grade serous ovarian cancer patches, we attempted to train an additional classification deep learning model to predict BRCA mutation. The segmentation model and code have been released at https://github.com/MSKCC-Computational-Pathology/DMMN-ovary.

深度学习已被广泛用于分析数字化苏木精和伊红(H&E)染色的组织病理学整张幻灯片图像。使用深度学习的自动癌症分割可用于诊断恶性肿瘤并发现新的形态模式以预测分子亚型。为了训练逐像素的癌症分割模型,病理学家的手工注释由于其耗时的性质通常是一个瓶颈。在本文中,我们提出了深度交互学习与来自不同癌症类型的预训练分割模型,以减少人工注释时间。与在千兆像素的整张幻灯片图像上标注癌症和非癌症区域的所有像素不同,从分割模型中标注错误标记的区域并使用额外的标注训练/微调模型的迭代过程可以减少时间。特别是,与从头开始标注相比,使用预训练的分割模型可以进一步减少时间。通过3.5小时的人工标注,我们用预训练好的乳腺癌分割模型训练出了一个准确的卵巢癌分割模型,该模型实现了0.74的交叉过合并,0.86的召回率和0.84的精度。通过自动提取高级别浆液性卵巢癌斑块,我们尝试训练一个额外的分类深度学习模型来预测BRCA突变。分割模型和代码已在https://github.com/MSKCC-Computational-Pathology/DMMN-ovary上发布。
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引用次数: 9
Cell projection plots: A novel visualization of bone marrow aspirate cytology 细胞投影图:骨髓抽吸细胞学的新可视化。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jpi.2023.100334
Taher Dehkharghanian , Youqing Mu , Catherine Ross , Monalisa Sur , H.R. Tizhoosh , Clinton J.V. Campbell

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce novel, automatically generated visual summaries of bone marrow aspirate specimens called cell projection plots (CPPs). Encompassing relevant biological patterns such as neutrophil maturation, CPPs provide a compact summary of bone marrow aspirate cytology. To gauge clinical relevance, CPPs were inspected by 3 hematopathologists, who decided whether corresponding diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with a matching degree of 85%. Our finding suggests CPPs can represent clinically relevant information from bone marrow aspirate specimens and may be used to efficiently summarize bone marrow cytology to pathologists. CPPs could be a step toward human-centered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic-support tool for digital pathology workflows.

细胞检测的深度模型已经证明在骨髓细胞学中的实用性,在准确性和计算效率方面显示出令人印象深刻的结果。然而,这些模型尚未在临床诊断工作流程中实施。此外,用于评估细胞检测模型的指标不一定与临床目标和指标一致。为了解决这些问题,我们介绍了一种新的、自动生成的骨髓抽吸标本的视觉摘要,称为细胞投影图(CPPs)。CPPs涵盖了中性粒细胞成熟等相关生物学模式,为骨髓抽吸细胞学提供了一个紧凑的总结。为了评估临床相关性,3名血液病理学家对CPPs进行了检查,他们决定相应的诊断概要是否与生成的CPPs相匹配。病理学家能够将CP与正确的概要进行匹配,匹配度为85%。我们的发现表明,CPPs可以代表骨髓抽吸标本的临床相关信息,并可用于向病理学家有效总结骨髓细胞学。CPPs可能是在血液病理学中实现以人为中心的人工智能的一步,也是数字病理工作流程诊断支持工具的基础。
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引用次数: 0
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Journal of Pathology Informatics
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