Toxicologic Pathology最新文献

Comparison of an Attention-Based Multiple Instance Learning (MIL) With a Visual Transformer Model: Two Weakly Supervised Deep Learning (DL) Algorithms for the Detection of Histopathologic Lesions in the Rat Liver to Distinguish Normal From Abnormal. 基于注意力的多实例学习（MIL）与视觉变形模型的比较：两种弱监督深度学习（DL）算法用于大鼠肝脏组织病理学病变的检测以区分正常与异常。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-30 DOI: 10.1177/01926233251339653

Juergen Funk, Gregoire Clement, Matteo Togninalli, Yaniv Cohen, Tom Albrecht, Ruth Sullivan, Josep Arus Pous, Marco Tecilla, Fernando Romero-Palomo, Amadeusz Abramowski, Angelo D'Annunzio, Yun Yvonna Li, Trung Nguyen, Fangyao Hu, Vanessa Schumacher

{"title":"Comparison of an Attention-Based Multiple Instance Learning (MIL) With a Visual Transformer Model: Two Weakly Supervised Deep Learning (DL) Algorithms for the Detection of Histopathologic Lesions in the Rat Liver to Distinguish Normal From Abnormal.","authors":"Juergen Funk, Gregoire Clement, Matteo Togninalli, Yaniv Cohen, Tom Albrecht, Ruth Sullivan, Josep Arus Pous, Marco Tecilla, Fernando Romero-Palomo, Amadeusz Abramowski, Angelo D'Annunzio, Yun Yvonna Li, Trung Nguyen, Fangyao Hu, Vanessa Schumacher","doi":"10.1177/01926233251339653","DOIUrl":"https://doi.org/10.1177/01926233251339653","url":null,"abstract":"The histopathologic evaluation of regulatory toxicity studies using artificial intelligence (AI) has the potential to increase study efficiency. For example, AI could initially identify and exclude all organs without histopathologic lesions, allowing pathologists to focus solely on evaluating organs with identified lesions. In this study, whole slide images (WSIs) of liver sections from 58 different rat toxicity studies were collected, along with their corresponding histopathologic lesion diagnoses. Each WSI was labeled as either \"lesion\" or \"no lesion\" based on the presence or absence of reported histopathologic lesions. Multiple instance learning (MIL) approaches, including a transformer variant, were tested to predict lesions within a weakly supervised framework. Both methods achieved acceptable to excellent area under the receiver operating characteristic curve (AUROC) scores. Heatmap overlays were employed to visually assess the MIL model's effectiveness in detecting lesions, confirming the accuracy of targeted areas on the WSIs. In addition, using transfer learning principles, the MIL model initially developed for liver WSIs was adapted to kidney WSIs, demonstrating the model's versatility. This study showcases the application of weakly supervised learning for lesion detection in rat WSIs from toxicity studies, with the potential to significantly enhance the efficiency of the histopathologic evaluation process.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251339653"},"PeriodicalIF":1.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uveodermatologic Syndrome in a Laboratory Beagle Dog: Histological and Immunohistochemical Features. 实验室比格犬葡萄膜皮肤病综合征：组织学和免疫组织化学特征。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-15 DOI: 10.1177/01926233251339116

Giulia Tosi, Elisavet Karamanavi, Zuhal Dincer, Michela Levi

引用次数: 0

2024 International Academy of Toxicologic Pathology (IATP) Satellite Symposium: New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives. 2024国际毒理学病理学会（IATP）卫星研讨会：神经毒性评估和监管前景的新方法方法（NAMs）。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-15 DOI: 10.1177/01926233251335719

Helena T Hogberg, Ellen Fritsche, Sibylle Gröters, Ramesh C Kovi, Deepa B Rao, Andrea Terron, Matthew J Winter

{"title":"2024 International Academy of Toxicologic Pathology (IATP) Satellite Symposium: New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives.","authors":"Helena T Hogberg, Ellen Fritsche, Sibylle Gröters, Ramesh C Kovi, Deepa B Rao, Andrea Terron, Matthew J Winter","doi":"10.1177/01926233251335719","DOIUrl":"https://doi.org/10.1177/01926233251335719","url":null,"abstract":"The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on \"New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives,\" organized in Spain, addressed the growing need for improved assessment of neurotoxicity. Traditional neurotoxicity assessment using in vivo animal studies are impractical for testing the substantial number of environmental chemicals that currently lack data and in the early detection of neuro-related adverse reactions in drug discovery. The NAMs, including human in vitro assays and small model organisms, have been developed for faster and cost-effective assessment of neurotoxic potential. While NAMs offer improved practicality, utility, and valuable mechanistic insights, their integration into regulatory decision-making requires robust scientific validation and technical characterization. Confidence in and regulatory application of NAMs data can be supported by mapping cellular outcomes to neuropathological findings in mammals, including humans, through the Adverse Outcome Pathway (AOP) framework, and the Integrated Approach to Testing and Assessment (IATA). Case studies presented demonstrated the application of NAMs in chemical and drug safety evaluations, focusing on developmental neurotoxicity (DNT), Parkinson's disease, and drug-induced seizures. In conjunction with in vivo toxicology studies, NAMs represent a significant step toward advancing chemical and drug toxicity assessment via hazard identification and drug screening safety assessments.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251335719"},"PeriodicalIF":1.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurodegenerative Diseases: Pathogenesis and Preclinical Models for Translational Drug Discovery. 神经退行性疾病：转化药物发现的发病机制和临床前模型。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-15 DOI: 10.1177/01926233251339105

Laura Fusaro, Dinesh S Bangari, R Jeroen Pasterkamp, Javier Fernández-Ruiz, Sameh A Youssef, Alok K Sharma

{"title":"Neurodegenerative Diseases: Pathogenesis and Preclinical Models for Translational Drug Discovery.","authors":"Laura Fusaro, Dinesh S Bangari, R Jeroen Pasterkamp, Javier Fernández-Ruiz, Sameh A Youssef, Alok K Sharma","doi":"10.1177/01926233251339105","DOIUrl":"https://doi.org/10.1177/01926233251339105","url":null,"abstract":"The fourth session of the 2024 European Society of Toxicologic Pathology (ESTP) Congress brought together lectures focused on the use of in vitro and in vivo models to investigate neurodegenerative diseases. Four presentations highlighted various aspects of neurodegenerative diseases including dementia, immune-mediated conditions, and neuromuscular disorders. The session began with an overview of animal models of dementia underscoring their critical role in understanding disease pathogenesis and supporting the development of effective therapeutic drugs. Subsequent presentations investigated immunological self-tolerance in autoimmune neurodegenerative diseases, such as multiple sclerosis and Guillain-Barré syndrome, and the application of in vitro models to study neuromuscular diseases such as amyotrophic lateral sclerosis. The final presentation examined cannabinoid-based therapeutic options for treating neurodegenerative diseases, highlighting their potential in neuroprotection and neurorepair. This session provided valuable insights into the latest research and advancements in neurodegenerative disease modeling and therapy, offering promising directions for improved modeling and therapeutic strategies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251339105"},"PeriodicalIF":1.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Fandango of Form and Function: The Interplay Between Clinical Neurology and Neuropathology Evaluation. 形式与功能的方丹戈：临床神经病学与神经病理学评估之间的相互作用。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-13 DOI: 10.1177/01926233251332210

Brad Bolon, Joe N Kornegay

{"title":"A Fandango of Form and Function: The Interplay Between Clinical Neurology and Neuropathology Evaluation.","authors":"Brad Bolon, Joe N Kornegay","doi":"10.1177/01926233251332210","DOIUrl":"https://doi.org/10.1177/01926233251332210","url":null,"abstract":"The central (CNS) and peripheral (PNS) nervous systems of vertebrates represent divisions of a continuous, body-wide communication grid based on conserved principles of structural organization. Discrete neuroanatomic regions within this grid are associated with specific neural functions, so distinct patterns of neurological dysfunction (\"problems\") can provide guidance regarding neural regions to evaluate beyond those in published sampling schemes or institutional standard operating procedures. Each neurological problem or syndrome (i.e., a group of in-life signs indicating that a given neuroanatomic region is damaged) is associated with a particular list of differential diagnoses and causes. Vulnerability of neural cells and tissues is influenced by intrinsic tissue properties (e.g., high metabolic rates of neurons, presence of blood:tissue barriers, degree of collateral vascular supply) and extrinsic factors (bone protuberances and connective tissue partitions impinging on neural surfaces, fluid flow patterns in the cerebroventricular system and meninges, etc.). In the toxicologic pathology setting, expansion (when warranted) of routine neural sampling protocols to collect additional anatomic regions correlated to a specific neurological problem improves the likelihood that a neuropathological evaluation will identify lesions and causes responsible for neurological conditions as well as detect findings related to potential test item-related neurotoxicity.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251332210"},"PeriodicalIF":1.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inaugural Special Issue Celebrating the 21st Annual Congress of the European Society of Toxicologic Pathology. 首期特刊庆祝第21届欧洲毒理学病理学会年会。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251337033

Dinesh S Bangari, Saravanan Kaliyaperumal

引用次数: 0

Bilateral Basal Nuclei Vacuolar Lesions: A Novel and Emerging Potential Background Finding in Beagle Dogs. 双侧基底核空泡病变：在比格犬中发现的一种新的潜在背景。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251335320

Stefanie Arms, Stephen D Cahalan, Felix Goulet, Katja Hempel, Giovanni Pellegrini, Sophie Rau, Julia Schlichtiger, Thomas Nolte

引用次数: 0

Neurobiomarkers: Basic Aspects and Their Relevance in Nonclinical Studies. 神经生物标志物：基本方面及其在非临床研究中的相关性。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251335849

Andrea Greiter-Wilke, Nicolau Beckmann, Warren E Glaab, Diethilde J Theil, Ingrid D Pardo

{"title":"Neurobiomarkers: Basic Aspects and Their Relevance in Nonclinical Studies.","authors":"Andrea Greiter-Wilke, Nicolau Beckmann, Warren E Glaab, Diethilde J Theil, Ingrid D Pardo","doi":"10.1177/01926233251335849","DOIUrl":"https://doi.org/10.1177/01926233251335849","url":null,"abstract":"The second session of the 2024 European Society of Toxicologic Pathology (ESTP) Congress highlighted the significance of neural biomarkers and functional endpoints in nonclinical studies for detecting acute or delayed peripheral (PNS) and central nervous system (CNS) alterations and /or injury caused by drugs during development. The session emphasized the potential clinical translation of these biomarkers and endpoints and critical role of pathologists in correlating these biomarkers with the microscopic findings. Key neural biomarkers discussed included fluid-based biomarkers such as Neurofilament Light Chain (NF-L), Nonspecific Enolase (NSE), Tubulin Associated Unit (TAU), and Glial Fibrillar Associated Protein (GFAP) in blood and/or cerebrospinal fluid (CSF). These were evaluated in 15 in-vivo studies conducted with CNS and PNS toxicants. Safety pharmacology evaluation, such as the Irwin screen/the functional observation battery (FOB), were presented for detecting drug effects on behavior, motor and sensory functions in both rodents and nonrodent species, with or without histopathological correlate. Follow-up tests like nerve conduction velocity assessment were also highlighted. The session underscored the usefulness of noninvasive imaging modalities, including magnetic resonance imaging (MRI), nuclear imaging techniques, X-ray computed tomography, and ultrasound in preclinical studies. Overall, integrating neural biomarkers, safety pharmacology endpoints, advanced imaging modalities, and detailed histopathological analysis aids in better predicting neurotoxicity.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251335849"},"PeriodicalIF":1.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicologic Pathology Forum: Opinion on Addressing Gaps in INHAND Terminology for Medical Devices-A Proposal to Add New Diagnostic Nomenclature. 毒理学病理学论坛：关于解决医疗器械INHAND术语差距的意见-增加新的诊断术语的建议。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-05 DOI: 10.1177/01926233251331580

JoAnn C L Schuh, Lyn M Wancket, Brad Bolon, Kathleen A Funk, Nicole Kirchhof, Joanna M Rybicka

{"title":"Toxicologic Pathology Forum: Opinion on Addressing Gaps in INHAND Terminology for Medical Devices-A Proposal to Add New Diagnostic Nomenclature.","authors":"JoAnn C L Schuh, Lyn M Wancket, Brad Bolon, Kathleen A Funk, Nicole Kirchhof, Joanna M Rybicka","doi":"10.1177/01926233251331580","DOIUrl":"https://doi.org/10.1177/01926233251331580","url":null,"abstract":"Historically, safety and efficacy assessment of medical devices began and has continued as standards under the International Organization for Standardization (ISO) rather than under regulatory agency guidelines applied to developing other biomedical product classes. These parallel and unequal pathways have led to multiple and substantive differences in methods and endpoints to determine adverse biological responses among therapeutic classes. Toxicologic pathologists with medical device experience consider standardized nomenclature and diagnostic criteria for medical devices and device-containing combination products as a critical unmet need for nonclinical pathology evaluations. The International Harmonization of Nomenclature and Diagnostic Criteria for Lesions (INHAND) initiative has established globally accepted terminology for proliferative and nonproliferative lesions in various laboratory animal species. Experienced pathologists have identified that some existing INHAND terms for rodents and particularly nonrodents are already used or can be modified for use in medical device studies, but new terms for diagnostic features unique to medical device studies are needed to close gaps in existing INHAND nomenclature. The best approach to establishing appropriate INHAND terms for medical devices (and by extension, device-containing combination products) will be to develop and implement suitable terminology (modified and new, as warranted) to address unmet needs for this distinctive therapeutic class.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251331580"},"PeriodicalIF":1.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparisons of the Sensitivity of Histopathological and Immunohistochemical Analyses With Blood Hormone Levels for Early Detection of Antithyroid Effects in Rats Treated With Promoters of Thyroid Hormone Metabolism. 甲状腺激素代谢促进剂对大鼠抗甲状腺作用早期检测的组织病理学和免疫组化分析与血激素水平的敏感性比较

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-03-13 DOI: 10.1177/01926233251316880

Hirotoshi Akane, Takeshi Toyoda, Kohei Matsushita, Mizuho Uneyama, Tomomi Morikawa, Tadashi Kosaka, Hitoshi Tajima, Hiroaki Aoyama, Kumiko Ogawa

{"title":"Comparisons of the Sensitivity of Histopathological and Immunohistochemical Analyses With Blood Hormone Levels for Early Detection of Antithyroid Effects in Rats Treated With Promoters of Thyroid Hormone Metabolism.","authors":"Hirotoshi Akane, Takeshi Toyoda, Kohei Matsushita, Mizuho Uneyama, Tomomi Morikawa, Tadashi Kosaka, Hitoshi Tajima, Hiroaki Aoyama, Kumiko Ogawa","doi":"10.1177/01926233251316880","DOIUrl":"10.1177/01926233251316880","url":null,"abstract":"Although blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels are useful for detecting antithyroid compounds in rodent toxicity studies, there are challenges with high variability due to sampling conditions. Here, we compared histopathological and immunohistochemical findings with blood hormone levels in rats treated with promoters of thyroid hormone metabolism to explore useful markers for hypothyroidism. Six-week-old male and female Sprague-Dawley rats (5/group) were administered phenobarbital sodium salt (NaPB) or nicardipine hydrochloride (NCD) by gavage for 28 days. Decreased serum T4 and increased TSH levels were detected at 100 mg/kg NaPB and 150 mg/kg NCD, whereas follicular cell hypertrophy occurred at lower doses of ≥ 30 mg/kg NaPB and ≥ 50 mg/kg NCD. There was no obvious change in T3 or T4 immunostaining in the thyroid unlike thyroid peroxidase (TPO) inhibitors, and uridine diphosphate-glucuronosyltransferase 1A6-positive area in the liver increased at doses lower than those affecting the serum T4 levels and generally the same as those at which hepatocellular hypertrophy and follicular cell hypertrophy were observed, indicating its usefulness in detecting thyroid hormone metabolism promoters. These results indicate that histopathology is useful for sensitive detection of hormone metabolism promoters and can be distinguished from TPO inhibitors by immunohistochemistry.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"251-266"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0