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From traditional to deep learning approaches in whole slide image registration: A methodological review 从传统到深度学习的全幻灯片图像配准方法综述
Q2 Medicine Pub Date : 2025-09-16 DOI: 10.1016/j.jpi.2025.100512
Behnaz Elhaminia , Abdullah Alsalemi , Esha Nasir , Mostafa Jahanifar , Ruqayya Awan , Lawrence S. Young , Nasir M. Rajpoot , Fayyaz Minhas , Shan E. Ahmed Raza
Whole slide image (WSI) registration is an essential task for analyzing the tumor microenvironment (TME) in histopathology. It involves the alignment of spatial information between WSIs of the same section or serial sections of a tissue sample. The tissue sections are usually stained with single or multiple biomarkers before imaging, and the goal is to identify neighboring nuclei along the Z-axis for creating a 3D image or identifying subclasses of cells in the TME. This task is considerably more challenging compared to radiology image registration, such as magnetic resonance imaging or computed tomography, due to various factors. These include gigapixel size of images, variations in appearance between differently stained tissues, changes in structure and morphology between non-consecutive sections, and the presence of artifacts, tears, and deformations. Currently, there is a noticeable gap in the literature regarding a review of the current approaches and their limitations, as well as the challenges and opportunities they present. We aim to provide a comprehensive understanding of the available approaches and their application for various purposes. Furthermore, we investigate current deep learning methods used for WSI registration, emphasizing their diverse methodologies. We examine the available datasets and explore tools and software employed in the field. Finally, we identify open challenges and potential future trends in this area of research.
全切片图像配准是组织病理学中分析肿瘤微环境的一项重要任务。它涉及组织样本的相同切片或连续切片的wsi之间的空间信息对齐。组织切片通常在成像前用单个或多个生物标志物染色,目标是沿z轴识别邻近的细胞核,以创建3D图像或识别TME中的细胞亚类。由于各种因素,与磁共振成像或计算机断层扫描等放射学图像配准相比,这项任务更具挑战性。这些包括图像的十亿像素大小,不同染色组织之间的外观变化,非连续切片之间结构和形态的变化,以及伪影,撕裂和变形的存在。目前,关于审查当前方法及其局限性以及它们所带来的挑战和机遇的文献中存在明显的差距。我们的目标是提供一个全面的了解可用的方法和他们的应用于各种目的。此外,我们研究了当前用于WSI配准的深度学习方法,强调了它们的不同方法。我们检查可用的数据集,并探索在该领域使用的工具和软件。最后,我们确定了这一研究领域的开放挑战和潜在的未来趋势。
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引用次数: 0
The path forward: Evolving standards for a smarter digital pathology ecosystem 前进的道路:为更智能的数字病理生态系统不断发展标准
Q2 Medicine Pub Date : 2025-09-08 DOI: 10.1016/j.jpi.2025.100516
Liron Pantanowitz, Anil Parwani
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引用次数: 0
Deep learning for digital pathology: A critical overview of methodological framework 数字病理学的深度学习:方法框架的关键概述
Q2 Medicine Pub Date : 2025-09-08 DOI: 10.1016/j.jpi.2025.100514
Meghdad Sabouri Rad , Junze (Vincent) Huang , Mohammad Mehdi Hosseini , Rakesh Choudhary , Harmen Siezen , Ratilal Akabari , Tamara Jamaspishvili , Ola El-Zammar , Palak G Patel , Saverio J. Carello , Michel R. Nasr , Bardia Rodd
Deep learning frameworks have transformed the field of digital pathology by automating complex tasks and revealing intricate patterns within histopathological data. These advanced methodologies provide exceptional accuracy and scalability, facilitating the analysis of high-dimensional whole-slide images with unparalleled precision. In this article, we present a comprehensive deep learning framework highlighting recent advancements in computational pathology. We critically examine mathematical innovations and offer a comparative analysis of various models demonstrating the significant and ongoing improvements in the field.
深度学习框架通过自动化复杂任务和揭示组织病理学数据中的复杂模式,改变了数字病理学领域。这些先进的方法提供了卓越的准确性和可扩展性,以无与伦比的精度促进高维全幻灯片图像的分析。在这篇文章中,我们提出了一个全面的深度学习框架,突出了计算病理学的最新进展。我们批判性地审视数学创新,并提供各种模型的比较分析,展示了该领域的重大和持续改进。
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引用次数: 0
Digital pathology enabling lean management of HER2/neu testing in breast Cancer 数字病理学使乳腺癌HER2/neu检测精益管理
Q2 Medicine Pub Date : 2025-09-05 DOI: 10.1016/j.jpi.2025.100515
Aishwarya Sharma , Prarthna Shah , Manali Ranade , Trupti Pai , Ayushi Sahay , Asawari Patil , Tanuja Shet , Heena Gupta , Devika Chauhan , Puneet Somal , Sankalp Sancheti , Sangeeta Desai

Introduction

Invasive breast carcinomas with an equivocal result of HER2/neu on immunohistochemistry (IHC) are reflex tested by fluorescent in situ hybridisation (FISH). Molecular testing is often not available in rural laboratories, from where it is routinely outsourced to central laboratories. Histopathology review (HPR) and IHC analysis of the tissue sample is thus repeated at the central laboratory before molecular testing which increases the turnaround time (TAT) and cost incurred by both the patient and the hospital. We aimed to assess the reduction in TAT and the cost effectiveness after introducing Digital Pathology (DP).

Methods

The tumours with equivocal HER2/neu results were outsourced for FISH from HBCH, Sangrur (rural laboratory) to Molecular Pathology Laboratory, TMH, Mumbai (central laboratory). The Haematoxylin-Eosin (HE) and IHC slides of 47 cases were virtually shared after scanning by Philips SG 60 digital slide scanner. Paraffin blocks of these cases were sent for FISH testing only. TAT of these prospectively shared cases were compared with a retrospective cohort in which virtual slides were not available. The cost benefits were also assessed.

Results

With the availability of DP, we were able to obviate repeat IHC testing. We were able to achieve a 43.9 % reduction in the TAT (15.65 days to 8.775 days). We also achieved a 30 % reduction in cost.

Conclusion

This is a prototype study highlighting the utility of DP in the lean management of HER2/neu testing. The integration of DP in the referral process reduces the TAT and expenditure optimizing resource utilisation.
浸润性乳腺癌的免疫组化(IHC)结果HER2/neu模棱两可,采用荧光原位杂交(FISH)反射检测。农村实验室通常不提供分子检测,通常将其外包给中央实验室。因此,在分子检测之前,组织样本的组织病理学检查(HPR)和免疫组化分析在中心实验室重复进行,这增加了周转时间(TAT)和患者和医院的费用。我们的目的是评估引入数字病理学(DP)后TAT的降低和成本效益。方法将HER2/neu结果不明确的肿瘤从桑格尔HBCH(农村实验室)外包给孟买TMH分子病理学实验室(中心实验室)进行FISH检测。47例患者经Philips SG 60型数字切片机扫描后,HE和IHC切片虚拟共享。这些箱子的石蜡块仅用于FISH检测。这些前瞻性共享病例的TAT与没有虚拟载玻片的回顾性队列进行比较。成本效益也进行了评估。结果由于DP的可用性,我们能够避免重复IHC检测。我们能够实现43.9 %的TAT减少(15.65 天到8.775 天)。我们还实现了30% %的成本降低。结论这是一项原型研究,突出了DP在HER2/neu检测精益管理中的应用。DP在转诊过程中的整合降低了TAT和支出,优化了资源利用。
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引用次数: 0
Quantification of HER2-low and ultra-low expression in breast cancer specimens by quantitative IHC and artificial intelligence 定量免疫组化和人工智能技术定量测定乳腺癌标本中her2低表达和超低表达
Q2 Medicine Pub Date : 2025-08-26 DOI: 10.1016/j.jpi.2025.100513
Frederik Aidt , Elad Arbel , Itay Remer , Oded Ben-David , Amir Ben-Dor , Daniela Rabkin , Kirsten Hoff , Karin Salomon , Sarit Aviel-Ronen , Gitte Nielsen , Jens Mollerup , Lars Jacobsen , Anya Tsalenko
Recent results of clinical trials in antibody drug conjugate (ADC) therapies have significantly broadened treatment options for the HER2 low and ultra-low breast cancer patients. However, sensitive, accurate and quantitative evaluation of HER2 expression based on current immunohistochemistry (IHC) assays remains challenging, especially in low and ultra-low HER2 expression ranges.
We developed a novel methodology for quantifying HER2 protein expression, targeting breast cancer cases in the HER2 IHC 0 and 1+ categories. We measured HER2 expression using quantitative IHC (qIHC) that enables precise and tunable HER2 detection across different expression levels as demonstrated in formalin-fixed paraffin-embedded cell lines. Additionally, we developed an AI-based interpretation of HercepTest™ mAb pharmDx (Dako Omnis) (HercepTest™ mAb) using qIHC measurements as the ground truth. Both methodologies allowed spatial resolution and visualization of low and ultra-low levels of HER2 expression across entire tissue sections to demonstrate and enable quantification of heterogeneity of HER2 expression.
Serial sections of 82 formalin-fixed paraffin-embedded tissue blocks of invasive breast carcinoma with HER2 IHC scores 0 or 1+ were stained with H&E, HercepTest™ (mAb), qIHC and p63, then scanned and digitally aligned. Tumor areas were manually selected and reviewed by expert pathologists. HER2 expression was quantitatively evaluated based on the qIHC assay in each 128x128μm2 area within tumor regions. We observed statistically significant differences in HER2 expression between IHC 0, 0 < IHC < 1+, and IHC 1+ groups, and a high degree of spatial heterogeneity of the HER2 expression levels within the same tissue, up to five-fold in some cases. We demonstrated high slide-level tumor region agreement of estimates of HER2 expression between the AI-based interpretation of HercepTest™ mAb and the qIHC ground truth with a Pearson correlation of 0.94, and R2 of 0.87.
The developed methodologies can be used to stratify HER2 low-expression patient groups, potentially improving the interpretation of IHC assays and maximizing therapeutic benefits. This method can be implemented in histology labs without requiring a specialized workflow.
抗体药物偶联(ADC)疗法的最新临床试验结果显著拓宽了HER2低和超低乳腺癌患者的治疗选择。然而,基于当前免疫组织化学(IHC)检测的HER2表达的敏感、准确和定量评估仍然具有挑战性,特别是在低和超低HER2表达范围内。我们开发了一种新的方法来定量HER2蛋白表达,针对HER2 IHC 0和1+类别的乳腺癌病例。我们使用定量免疫组化(qIHC)测量了HER2的表达,这种方法能够在不同的表达水平上进行精确和可调的HER2检测,正如在福尔马林固定石蜡包埋细胞系中所证明的那样。此外,我们开发了一种基于人工智能的解释HercepTest™mAb pharmDx (Dako Omnis) (HercepTest™mAb),使用qIHC测量作为基础事实。这两种方法都允许在整个组织切片上进行低水平和超低水平HER2表达的空间分辨率和可视化,以证明和量化HER2表达的异质性。采用H&;E、HercepTest™(mAb)、qIHC和p63染色,对82例HER2 IHC评分为0或1+的浸润性乳腺癌用福尔马林固定石蜡包埋组织块的连续切片进行扫描和数字对齐。肿瘤区域由病理学专家手工选择和检查。采用qIHC法定量评价肿瘤区域内每个128x128μm2区域的HER2表达。我们观察到,在IHC 0、0 <; IHC <; 1+和IHC 1+组之间,HER2表达有统计学上的显著差异,并且在同一组织内,HER2表达水平具有高度的空间异质性,在某些情况下高达5倍。我们证明基于人工智能的HercepTest™mAb解释与qIHC基本事实之间的HER2表达估计在肿瘤区域高度一致,Pearson相关系数为0.94,R2为0.87。开发的方法可用于对HER2低表达患者群体进行分层,潜在地改善免疫组化分析的解释,并最大限度地提高治疗效果。这种方法可以在组织学实验室中实施,而不需要专门的工作流程。
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引用次数: 0
Digital Pathology Standards: A Response to WG-26 数字病理学标准:对WG-26的回应
Q2 Medicine Pub Date : 2025-08-22 DOI: 10.1016/j.jpi.2025.100510
Peter Gershkovich
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引用次数: 0
Raining on the WSI interoperability parade – incorrect assertions with respect to DICOM and fur coats in the summertime 在WSI互操作性游行上下雨-关于DICOM和夏季毛皮大衣的错误断言
Q2 Medicine Pub Date : 2025-08-20 DOI: 10.1016/j.jpi.2025.100511
David A. Clunie
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引用次数: 0
Neighborhood clustering analysis to define epithelial–stromal interface for tumor infiltrating lymphocyte evaluation 邻域聚类分析定义肿瘤浸润淋巴细胞评价的上皮-基质界面
Q2 Medicine Pub Date : 2025-08-06 DOI: 10.1016/j.jpi.2025.100465
Tony Yeung , Yi Zhang , Qianghua Zhou , Richard Burack
Evaluation of tumor infiltrating lymphocytes as recommended by current guidelines is largely based on stromal regions within the tumor. In the context of epithelial malignancies, the epithelial region and the epithelial–stromal interface are not assessed, because of technical difficulties in manually discerning lymphocytes when admixed with epithelial tumor cells. The inability to quantify immune cells in epithelial-associated areas may negatively impact evaluation of patient response to immune checkpoint therapies. Innovative spatial analysis techniques have emerged that can directly address challenges associated with quantification of lymphocytes in specialized regions like the interface. In this study, we apply supervised neighborhood clustering analysis (via an open-source application CytoMAP) to assess the spatial distribution of CD8+ T cells, CD8+ TIM3+ (T cell immunoglobulin and mucin-domain containing-3) exhausted T cells, and TIM3+ CD8- macrophages on a gynecological tumor microarray. Neighborhood clustering analysis is adept at objectively mapping the epithelial–stromal interface alongside the epithelial and stromal region of each tumor under a three-compartment model. When tumors are partitioned by the conventional two-compartment model (epithelial and stromal region only), the highest density of total CD8+ T cells is found in the stromal region in a slight majority of tumors. In contrast, the interface region surpasses both the epithelial and stromal region in holding the highest density of CD8+ T cells when this unique region is incorporated into the three-compartment model. Further subset analysis shows higher proportion of CD8+ TIM3+ exhausted T cells within the interface and epithelial region, as compared to CD8+ TIM3- T cells which span from the stroma to the interface. These results highlight the utility of implementing quantitative spatial technique and immune subset analysis in the assessment of tumor infiltrating lymphocytes, and underscore the potential significance of the under-reported tumor epithelial–stromal interface.
目前指南中推荐的肿瘤浸润淋巴细胞的评估主要基于肿瘤内的基质区域。在上皮恶性肿瘤的背景下,由于人工识别淋巴细胞与上皮肿瘤细胞混合在一起的技术困难,因此不评估上皮区域和上皮-基质界面。无法量化上皮相关区域的免疫细胞可能会对评估患者对免疫检查点疗法的反应产生负面影响。创新的空间分析技术已经出现,可以直接解决与特定区域(如界面)淋巴细胞定量相关的挑战。在这项研究中,我们应用监督邻域聚类分析(通过开源应用程序CytoMAP)来评估CD8+ T细胞,CD8+ TIM3+ (T细胞免疫球蛋白和粘蛋白结构域-3)耗尽T细胞和TIM3+ CD8-巨噬细胞在妇科肿瘤微阵列上的空间分布。邻域聚类分析擅长于在三室模型下客观地绘制上皮-基质界面以及每个肿瘤的上皮和基质区域。当用传统的双室模型(仅上皮和间质区)对肿瘤进行分割时,在绝大多数肿瘤中,CD8+ T细胞总密度最高的是间质区。相比之下,当这个独特的区域被纳入三室模型时,界面区域在容纳CD8+ T细胞密度方面超过了上皮和基质区域。进一步的亚群分析显示,与从基质到界面的CD8+ TIM3- T细胞相比,CD8+ TIM3- T细胞在界面和上皮区域内的比例更高。这些结果强调了实施定量空间技术和免疫亚群分析在评估肿瘤浸润淋巴细胞中的效用,并强调了未被报道的肿瘤上皮-基质界面的潜在意义。
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引用次数: 0
Wearing a fur coat in the summertime: Should digital pathology redefine medical imaging? 夏天穿着皮大衣:数字病理学应该重新定义医学成像吗?
Q2 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.jpi.2025.100450
Peter Gershkovich
<div><div>Slides are data. Once digitized, they function like any enterprise asset: accessible anywhere, ready for AI, and integrated into cloud workflows. But in pathology, they enter a realm of clinical complexity—demanding systems that handle nuance, integrate diverse data streams, scale effectively, enable computational exploration, and enforce rigorous security.</div><div>Although the Digital Imaging and Communications in Medicine (DICOM) standard revolutionized radiology, it is imperative to explore its adequacy in addressing modern digital pathology's orchestration needs. Designed more than 30 years ago, DICOM reflects assumptions and architectural choices that predate modular software, cloud computing, and AI-driven workflows.</div><div>This article shows that by embedding metadata, annotations, and communication protocols into a unified container, DICOM limits interoperability and exposes architectural vulnerabilities. The article begins by examining these innate design risks, then challenges DICOM's interoperability claims, and ultimately presents a modular, standards-aligned alternative.</div><div>The article argues that separating image data from orchestration logic improves scalability, security, and performance. Standards such as HL7 FHIR (Health Level Seven Fast Healthcare Interoperability Resources) and modern databases manage clinical metadata; formats like Scalable Vector Graphics handle annotations; and fast, cloud-native file transfer protocols, and microservices support tile-level image access. This separation of concerns allows each component to evolve independently, optimizes performance across the system, and better adapts to emerging AI-driven workflows—capabilities that are inherently constrained in monolithic architectures where these elements are tightly coupled.</div><div>It further shows that security requirements should not be embedded within the DICOM standard itself. Instead, security must be addressed through a layered, format-independent framework that spans systems, networks, applications, and data governance. Security is not a discrete feature but an overarching discipline—defined by its own evolving set of standards and best practices. Overlays such as those outlined in the National Institute of Standards and Technology SP 800-53 support modern Transport Layer Security, single sign-on, cryptographic hashing, and other controls that protect data streams without imposing architectural constraints or restricting technological choices.</div><div>Pathology stands at a rare inflection point. Unlike radiology, where DICOM is deeply entrenched, pathology workflows still operate in polyglot environments—leveraging proprietary formats, hybrid standards, and emerging cloud-native tools. This diversity, often seen as a limitation, offers a clean slate: an opportunity to architect a modern, modular infrastructure free from legacy constraints. While a full departure from DICOM is unnecessary, pathology is uniquely position
幻灯片是数据。一旦数字化,它们的功能就像任何企业资产一样:可以在任何地方访问,为人工智能做好准备,并集成到云工作流程中。但在病理学中,它们进入了临床复杂性领域——要求系统处理细微差别,集成不同的数据流,有效扩展,实现计算探索,并执行严格的安全性。尽管医学中的数字成像和通信(DICOM)标准彻底改变了放射学,但探索其在解决现代数字病理学编排需求方面的充足性是必要的。DICOM设计于30多年前 ,反映了在模块化软件、云计算和人工智能驱动的工作流程之前的假设和架构选择。本文展示了通过将元数据、注释和通信协议嵌入到统一的容器中,DICOM限制了互操作性并暴露了体系结构漏洞。本文首先检查这些固有的设计风险,然后挑战DICOM的互操作性声明,最后提出一个模块化的、与标准一致的替代方案。本文认为,将图像数据与编排逻辑分离可以提高可伸缩性、安全性和性能。HL7 FHIR(健康级别7快速医疗互操作性资源)等标准和现代数据库管理临床元数据;可缩放矢量图形等格式处理注释;快速的云原生文件传输协议和微服务支持磁贴级映像访问。这种关注点分离允许每个组件独立发展,优化整个系统的性能,并更好地适应新兴的人工智能驱动的工作流——这些功能在这些元素紧密耦合的单片架构中受到固有约束。它进一步表明,安全需求不应该嵌入到DICOM标准本身中。相反,必须通过跨系统、网络、应用程序和数据治理的分层、格式独立的框架来解决安全性问题。安全性不是一个独立的特性,而是一个包罗万象的学科——由它自己不断发展的一组标准和最佳实践来定义。国家标准与技术研究所SP 800-53中概述的覆盖层支持现代传输层安全、单点登录、加密散列和其他控制,这些控制可以保护数据流,而不会施加架构约束或限制技术选择。病理学正处于一个罕见的拐点。与DICOM根深蒂固的放射学不同,病理学工作流程仍然在多语言环境中运行,利用专有格式、混合标准和新兴的云原生工具。这种多样性通常被视为一种限制,但它提供了一个全新的开端:一个从遗留约束中构建现代模块化基础设施的机会。虽然完全脱离DICOM是没有必要的,但病理学是未来原型的独特定位——定义一个更灵活、更安全、更可互操作的模型,有朝一日医学成像的其他领域可能会效仿。在前瞻性DICOM倡导者的支持下,病理学不仅可以帮助重塑自身的基础设施,还可以帮助重塑医学成像本身的发展轨迹。
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引用次数: 0
Comparative analysis of a 5G campus network and existing networks for real-time consultation in remote pathology 5G校园网与现有远程病理实时会诊网络的对比分析
Q2 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.jpi.2025.100444
Ilgar I. Guseinov, Arnab Bhowmik, Somaia AbuBaker, Anna E. Schmaus-Klughammer, Thomas Spittler
The rapid advancements in digital pathology, particularly in whole-slide imaging (WSI), have transformed remote histological analysis by enabling high-resolution digitization and real-time consultations. However, these workflows place significant demands on network infrastructure, requiring high bandwidth, low latency, and consistent performance. Whereas 5G networks have been extensively studied in controlled lab environments, their real-world applications in clinical settings remain underexplored.
This study provides a comparative analysis of 5G Campus Networks (5G CN) and traditional institutional networks, focusing on their performance during remote pathology tasks. Key metrics such as throughput, latency, and image quality were evaluated under various device loads to simulate real-world conditions. Although 5G CN did not consistently outperform in absolute throughput, it demonstrated superior adaptability, lower latency, and reduced variability, ensuring stable performance even with increasing network demand. These attributes are critical for time-sensitive workflows like frozen section analysis, where reliability and speed are paramount.
The findings highlight the potential of 5G CN to support emerging digital pathology applications, including real-time consultation. Furthermore, the study underscores the need for future research on 5G slicing and its ability to optimize network resources for high-demand medical applications. This work provides valuable insights into optimizing network infrastructure for the evolving demands of remote diagnostics in digital pathology.
数字病理学的快速发展,特别是在全切片成像(WSI)方面,通过实现高分辨率数字化和实时咨询,改变了远程组织学分析。然而,这些工作流对网络基础设施提出了很高的要求,需要高带宽、低延迟和一致的性能。尽管5G网络已在受控实验室环境中进行了广泛研究,但其在临床环境中的实际应用仍未得到充分探索。本研究提供了5G校园网(5G CN)和传统机构网络的比较分析,重点关注它们在远程病理任务中的表现。在各种设备负载下评估吞吐量、延迟和图像质量等关键指标,以模拟现实世界的条件。虽然5G CN在绝对吞吐量方面并不总是优于其他国家,但它表现出了卓越的适应性、更低的延迟和更少的可变性,即使在网络需求不断增加的情况下也能确保稳定的性能。这些属性对于时间敏感的工作流程(如冻结切片分析)至关重要,因为可靠性和速度是至关重要的。研究结果强调了5G网络在支持新兴数字病理学应用(包括实时咨询)方面的潜力。此外,该研究强调了未来对5G切片及其优化网络资源的能力进行研究的必要性,以满足高需求的医疗应用。这项工作为优化网络基础设施提供了宝贵的见解,以满足数字病理学中远程诊断的不断发展的需求。
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Journal of Pathology Informatics
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