Toxicologic Pathology最新文献_第2页

Toxicologic Pathology Forum*: Opinion on the Interpretation of Statistical Significance Testing Results From Anatomic and Clinical Pathology Data in Nonclinical Safety Studies. 毒理学病理学论坛*：对非临床安全性研究中解剖和临床病理数据统计显著性检验结果的解释的意见。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2025-08-01 Epub Date: 2025-05-31 DOI: 10.1177/01926233251339113

Lila Ramaiah, Tara Arndt, Gareth Thomas, Norimitsu Shirai, Manu Sebastian, Cory Sims, Steven Bailey

{"title":"Toxicologic Pathology Forum*: Opinion on the Interpretation of Statistical Significance Testing Results From Anatomic and Clinical Pathology Data in Nonclinical Safety Studies.","authors":"Lila Ramaiah, Tara Arndt, Gareth Thomas, Norimitsu Shirai, Manu Sebastian, Cory Sims, Steven Bailey","doi":"10.1177/01926233251339113","DOIUrl":"10.1177/01926233251339113","url":null,"abstract":"Toxicologic pathologists assess large data sets from nonclinical studies to identify treatment-related effects to assist in predicting human safety hazards. Statistical testing can facilitate data interpretation by highlighting group differences that have a low probability of random occurrence based on a pre-determined P-value cut-off (eg, P < .05). While this method has been used in the interpretation of pathology data for decades, the appropriateness of utilizing statistical testing in this way has been challenged. Here, we discuss common statistical pitfalls in the analysis of toxicologic pathology data, with emphasis on clinical pathology, reaffirming that appropriate use of statistical analysis requires an understanding of (1) the parameters assessed; (2) the inherent strengths and weaknesses of the statistical method used; and (3) that appropriate interpretation of pathology data is based on the pathologist's expertise. The presence or absence of statistical significance should not supersede expert judgment but should be one of many tools used to reach a conclusion.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"571-581"},"PeriodicalIF":1.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192168","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

Intrahepatic Cholangiocarcinoma With Pulmonary Metastasis in a Rhesus Macaque (Macaca mulatta). 恒河猴肝内胆管癌伴肺转移。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-20 DOI: 10.1177/01926233251353515

Andressa Varella Gonsioroski, Mayra Tsoi, Meredith Leigh Cronin, Nicholas Vetter

引用次数: 0

Rare Occurrence of an Acute Myeloid Leukemia in a Cynomolgus Macaque (Macaca fascicularis). 食蟹猕猴（Macaca fascularis）急性髓系白血病的罕见发生。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-20 DOI: 10.1177/01926233251350661

Heather Priest, Julie Schwartz, Angela Wilcox, A Eric Schultze

{"title":"Rare Occurrence of an Acute Myeloid Leukemia in a Cynomolgus Macaque (Macaca fascicularis).","authors":"Heather Priest, Julie Schwartz, Angela Wilcox, A Eric Schultze","doi":"10.1177/01926233251350661","DOIUrl":"https://doi.org/10.1177/01926233251350661","url":null,"abstract":"This report presents the findings of a spontaneous case of acute myeloid leukemia (AML) in a 6-year-old male cynomolgus macaque enrolled in a 9-month repeat dose-toxicity and toxicokinetic study. Abnormal hematology findings occurred approximately 6 months into daily oral dosing that included markedly decreased red blood cell mass and reticulocyte count, moderately decreased platelet counts, and the identification of abnormal cells in blood that were interpreted as neoplastic. Cytologic characteristics of the neoplastic cells included a moderate to high nucleus to cytoplasm ratio, medium to deep blue cytoplasm, and a round to oval nucleus with fine chromatin, often with multiple, irregularly shaped nucleoli. Following humane euthanasia, evaluation of bone marrow smears and formalin fixed paraffin embedded tissues revealed neoplastic cells of similar morphology. A panel of immunohistochemistry and cytochemical stains demonstrated expression of CD68 and myeloperoxidase, with weaker and less consistent expression of CD11c and CD45. No staining was detected for CD34, CD14, and T (CD3) and B (CD20) lymphoid markers. The neoplastic cells did not stain for any of the cytochemical stains applied (Periodic Acid Schiff, α-naphthyl acetate esterase, Sudan Black B, α-naphthyl butyrate esterase, and chloroacetate esterase). An interpretation of AML was made suggestive of a myelomonocytic lineage.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251350661"},"PeriodicalIF":1.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668571","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

Evaluation of Biomarkers to Detect Early Prothrombotic Imbalance in Rat Models of Hypercoagulability Induced by Thromboplastin Infusion and Hypofibrinolysis Induced by Tranexamic Acid. 凝血活素输注致高凝和氨甲环酸致低纤溶大鼠模型早期血栓前失衡的生物标志物评价。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2025-07-15 DOI: 10.1177/01926233251349767

Marjory B Brooks, Cindy E Fishman, Mohanapriya Kamalakannan, Paula Katavolos, Claire E O'Brien, Jennifer B Pierson, Florence Poitout-Belissent, Michael K Pugsley, Kurex Sidik, Brett R Winters, A Eric Schultze

{"title":"Evaluation of Biomarkers to Detect Early Prothrombotic Imbalance in Rat Models of Hypercoagulability Induced by Thromboplastin Infusion and Hypofibrinolysis Induced by Tranexamic Acid.","authors":"Marjory B Brooks, Cindy E Fishman, Mohanapriya Kamalakannan, Paula Katavolos, Claire E O'Brien, Jennifer B Pierson, Florence Poitout-Belissent, Michael K Pugsley, Kurex Sidik, Brett R Winters, A Eric Schultze","doi":"10.1177/01926233251349767","DOIUrl":"10.1177/01926233251349767","url":null,"abstract":"Thrombotic complications including myocardial infarction, stroke, venous thrombosis and pulmonary thromboembolism are common causes of drug attrition often discovered at late stages of drug development. Current nonclinical safety assessments include screening tests that detect hemorrhagic complications but do not identify conditions signaling a risk of thrombosis. Our study aimed to identify sensitive tests for detecting prothrombotic imbalance, without overt thrombosis, for use in early nonclinical drug safety assessments in rodents. Sprague Dawley rats were administered different doses of thromboplastin or tranexamic acid to induce variable intensity hypercoagulable or hypofibrinolytic states, respectively. A panel of functional and quantitative assays measuring hemostatic proteins and pathways were evaluated, in concert with traditional coagulation screening tests and blood cell counts. Profound changes were observed with different patterns of test abnormalities for the different stimuli. Measurements of D-dimer and thrombin antithrombin complex concentrations, plasminogen activator inhibitor-1 and Factor VIIa activity were among the most sensitive tests of hypercoagulability. In contrast, hypofibrinolysis was best characterized in a kinetic, turbidimetric assay. Traditional coagulation screening tests were relatively insensitive, and no single test defined the cause of prothrombotic imbalance. Our results demonstrate that customized biomarker panels can detect early drug-induced prothrombotic states in rats arising from distinct mechanisms.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251349767"},"PeriodicalIF":1.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643637","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

Immunotoxicology From a Pathology Perspective: A Continuing Education Course Presented at the Annual STP Meeting in Baltimore, MD, Held June 16-19, 2024. 从病理学角度看免疫毒理学：在2024年6月16日至19日在马里兰州巴尔的摩举行的STP年度会议上提出的继续教育课程。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-01 Epub Date: 2025-03-31 DOI: 10.1177/01926233251328970

Tracey L Papenfuss, Ashwini Phadnis Moghe, Lauren E Himmel, Ana Goyos, Daniel Weinstock

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 : 2025-07-01 Epub 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":"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":"488-493"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","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

Toxicologic Pathology Forum*: Opinion on New Technologies and Trends Disrupting Drug Discovery and Development: How Can the Next Generation of Toxicologic Pathologists Be Prepared for Evolving Roles? 毒理学病理学论坛*：新技术和趋势对药物发现和开发的影响：下一代毒理学病理学家如何为不断变化的角色做好准备？

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-01 Epub Date: 2025-03-31 DOI: 10.1177/01926233251321805

Rebecca Kohnken, Lauren Himmel, Magali Guffroy, Eric A G Blomme

{"title":"Toxicologic Pathology Forum*: Opinion on New Technologies and Trends Disrupting Drug Discovery and Development: How Can the Next Generation of Toxicologic Pathologists Be Prepared for Evolving Roles?","authors":"Rebecca Kohnken, Lauren Himmel, Magali Guffroy, Eric A G Blomme","doi":"10.1177/01926233251321805","DOIUrl":"10.1177/01926233251321805","url":null,"abstract":"The pace of technological innovation in the pharmaceutical industry, like in many other sectors, is accelerating rapidly. This is not only reshaping how pharmaceutical Research and Development (R&D) is conducted (e.g., introduction of novel models, endpoints, and instrumentation) but also influencing the types of therapeutic modalities being developed. In addition, societal and regulatory expectations have evolved to emphasize approaches that align with the 4Rs principles (Replacement, Reduction, Refinement, and Responsibility) and to encourage the replacement of animal testing with new approach methods (NAMs) through the FDA Modernization Act 2.0. While innovation, societal changes, and regulatory evolution are not new, what stands out is the unprecedented speed and scale at which these transformations are occurring. This acceleration is fueled predominantly by groundbreaking technological advancements (e.g., artificial intelligence, deep learning, communication tools, and digital pathology) in the context of rapidly changing societal dynamics such as globalization, social networking, and the increase in remote working. Given these potentially disruptive changes, it is essential to consider how toxicologic pathologists need to adapt. More importantly, how can they leverage these advancements to contribute even more significantly to the discovery and development of novel, safe, and effective medicines? In essence, what types of toxicologic pathologists will the pharmaceutical industry require in the future?","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"484-487"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754580","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

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 : 2025-07-01 Epub 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":"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":"456-478"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","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

Case Report: Glioneuronal Hamartoma in the Cerebral Cortex of a Juvenile Cynomolgus Monkey (Macaca fascicularis). 病例报告：幼食蟹猴（Macaca fascicularis）大脑皮层胶质神经元错构瘤。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-01 Epub Date: 2025-03-13 DOI: 10.1177/01926233251320080

Elaine Debien, Felix Goulet, Lee Silverman, Esther Millette, Qian Wu

引用次数: 0

Scientific and Regulatory Policy Committee Points to Consider* for Determining and Reporting Cause of Death/Moribundity in Non-Rodent Species in Toxicity Studies. 科学和监管政策委员会指出，考虑在毒性研究中确定和报告非啮齿动物物种的死亡/死亡原因。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-07-01 Epub Date: 2025-03-20 DOI: 10.1177/01926233251321781

Karyn Colman, Kathleen A Funk, Michael Boyle, Sebastian Brennan, Gary Cain, Curtis Colleton, Laura Dill Morton, Anna Maria Giusti, Eric Jacquinet, Lisa LaFranco-Scheuch, Luann McKinney, Elizabeth Neyens, Annette Romeike, Shim-Mo Hayashi, John L Vahle, Lindsay Tomlinson

{"title":"Scientific and Regulatory Policy Committee Points to Consider* for Determining and Reporting Cause of Death/Moribundity in Non-Rodent Species in Toxicity Studies.","authors":"Karyn Colman, Kathleen A Funk, Michael Boyle, Sebastian Brennan, Gary Cain, Curtis Colleton, Laura Dill Morton, Anna Maria Giusti, Eric Jacquinet, Lisa LaFranco-Scheuch, Luann McKinney, Elizabeth Neyens, Annette Romeike, Shim-Mo Hayashi, John L Vahle, Lindsay Tomlinson","doi":"10.1177/01926233251321781","DOIUrl":"10.1177/01926233251321781","url":null,"abstract":"The Cause of Death in Non-Rodents (CODN) Working Group is an initiative under the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP), focused on understanding existing practices and expectations among pharmaceutical companies, academic entities, and contract research organizations (CROs) when it comes to identifying and reporting the \"Cause of Death\" (COD) or moribundity for early or unplanned necropsies in non-rodent animal species (mainly non-human primates [NHP] and dogs) within both GLP (Good Laboratory Practice) and non-GLP toxicity studies. A survey was sent out to STP members to collect data on industry practices for determining COD in animals that underwent unscheduled euthanasia or were found deceased. Other non-rodent animals (such as pigs and rabbits) were also included to evaluate different approaches taken with various species. The insights obtained led to the development of \"Points to Consider\" for establishing and documenting the COD in large animal toxicity studies. Four key considerations include utilizing information from both control and treated animals in the study, consideration of COD for cohabiting or co-shipped non-study animals, including additional evaluations to help rule-in or rule-out specific causes, and recording the COD consistently in pathology databases or reports as a standard practice.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"501-510"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664443","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