Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans.

There are few treatments that slow neurodegeneration in Alzheimer's disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the central nervous system is restricted by the blood-brain barrier. This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (Aβ) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle™ module (trontinemab; RG6102, INN trontinemab). , trontinemab showed a similar binding affinity to fibrillar Aβ and Aβ plaques in human AD brain sections to gantenerumab.

Results of the European Society of Toxicologic Pathology Survey on the Use of Artificial Intelligence in Toxicologic Pathology.

The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption across organizations; (2) technical and methodological aspects; (3) perceived business value and finally; and (4) roadblocks and perspectives.

Toxicologic Pathology Forum: A Roadmap for Building State-of-the-Art Digital Image Data Resources for Toxicologic Pathology in the Pharmaceutical Industry.

Digitization of histologic slides brings with it the promise of enhanced toxicologic pathology practice through the increased application of computational methods. However, the development of these advanced methods requires access to substrate image data, that is, whole slide images (WSIs). Deep learning methods, in particular, rely on extensive training data to develop robust algorithms.

MMO-Net (Multi-Magnification Organ Network): A use case for Organ Identification using Multiple Magnifications in Preclinical Pathology Studies.

Identifying organs within histology images is a fundamental and non-trivial step in toxicological digital pathology workflows as multiple organs often appear on the same whole slide image (WSI). Previous works in automated tissue classification have investigated the use of single magnifications, and demonstrated limitations when attempting to identify small and contiguous organs at low magnifications. In order to overcome these shortcomings, we present a multi-magnification convolutional neural network (CNN), called MMO-Net, which employs context and cellular detail from different magnifications to facilitate the recognition of complex organs.

IT/QA and Regulatory Aspects of Digital Pathology: Results of the 8th ESTP International Workshop.

Digital toxicologic histopathology has been broadly adopted in preclinical compound development for informal consultation and peer review. There is now increased interest in implementing the technology for good laboratory practice-regulated study evaluations. However, the implementation is not straightforward because systems and work processes require qualification and validation, with consideration also given to security.

Scientific and Regulatory Policy Committee Points to Consider: Primary Digital Histopathology Evaluation and Peer Review for Good Laboratory Practice (GLP) Nonclinical Toxicology Studies.

The Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee formed a working group to consider the present and future use of digital pathology in toxicologic pathology in general and specifically its use in primary evaluation and peer review in Good Laboratory Practice (GLP) environments. Digital histopathology systems can save costs by reducing travel, enhancing organizational flexibility, decreasing slide handling, improving collaboration, increasing access to historical images, and improving quality and efficiency through integration with laboratory information management systems. However, the resources to implement and operate a digital pathology system can be significant.

Scientific and Regulatory Policy Committee Brief Communication: 2019 Survey on Use of Digital Histopathology Systems in Nonclinical Toxicology Studies.

Histopathologic evaluation and peer review using digital whole-slide images (WSIs) is a relatively new medium for assessing nonclinical toxicology studies in Good Laboratory Practice (GLP) environments. To better understand the present and future use of digital pathology in nonclinical toxicology studies, the Society of Toxicologic Pathology (STP) formed a working group to survey STP members with the goal of creating recommendations for implementation. The survey was administered in December 2019, immediately before the COVID-19 pandemic, and the results suggested that the use of digital histopathology for routine GLP histopathology assessment was not widespread.

Deep Learning in Toxicologic Pathology: A New Approach to Evaluate Rodent Retinal Atrophy.

Quantification of retinal atrophy, caused by therapeutics and/or light, by manual measurement of retinal layers is labor intensive and time-consuming. In this study, we explored the role of deep learning (DL) in automating the assessment of retinal atrophy, particularly of the outer and inner nuclear layers, in rats. Herein, we report our experience creating and employing a hybrid approach, which combines conventional image processing and DL to quantify rodent retinal atrophy.

The Application, Challenges, and Advancement Toward Regulatory Acceptance of Digital Toxicologic Pathology: Results of the 7th ESTP International Expert Workshop (September 20-21, 2019).

With advancements in whole slide imaging technology and improved understanding of the features of pathologist workstations required for digital slide evaluation, many institutions are investigating broad digital pathology adoption. The benefits of digital pathology evaluation include remote access to study or diagnostic case materials and integration of analysis and reporting tools. Diagnosis based on whole slide images is established in human medical pathology, and the use of digital pathology in toxicologic pathology is increasing.

Toxicologic Pathology Forum*: Opinion on Integrating Innovative Digital Pathology Tools in the Regulatory Framework.

Digital pathology is defined as the ability to examine digitized microscopic slides and to generate qualitative and quantitative data. The field of digital pathology is rapidly evolving and has the potential to revolutionize toxicologic pathology. Techniques such as automated 2-D image analysis, whole slide imaging, and telepathology are already considered "mature" technologies and have been used for decades in exploratory studies; however, many organizations are reluctant to use digital pathology in regulatory toxicology studies.

Meeting Report: Tissue-based Image Analysis.

Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives.

Development and characterization of a largemouth bass cell line.

Abstract The development and characterization of a new cell line, derived from the ovary of Largemouth Bass Micropterus salmoides, is described. Gonad tissue was collected from Largemouth Bass that were electrofished from Oneida Lake, New York. The tissue was processed and grown in culture flasks at approximately 22°C for more than 118 passages during an 8-year period from 2004 to 2011.

Bilateral ovarian cystadenoma in a geriatric African elephant (Loxodonta africana).

A 59-yr-old, captive female African elephant (Loxodonta africana) died of a cardiovascular collapse. Necropsy revealed bilateral replacement of the ovarian tissue by multiple cystic formations of up to 10 cm in diameter. The cysts were thin walled and filled with clear watery fluid.

Mycobacterium avium Subsp. avium infection in four veal calves: differentiation from intestinal tuberculosis.

Mycobacterium avium subsp. avium (Maa) is an intracellular pathogen belonging to the Mycobacterium avium-intracellulare complex (MAC). Reservoirs of MAC are the natural environment, wildlife and domestic animals.

Sulawesi tortoise adenovirus-1 in two impressed tortoises (Manouria impressa) and a Burmese star tortoise (Geochelone platynota).

Sulawesi tortoise adenovirus-1 (STAdV-1) is a newly discovered virus infecting endangered and threatened tortoises. It was initially described from a confiscated group of 105 Sulawesi tortoises (Indotestudo forsteni) obtained by the Turtle Survival Alliance and distributed to five sites with available veterinary care across the United States. In a 3-yr period from the initial outbreak, one multi-species collection that rehabilitated and housed adenovirus-infected Sulawesi tortoises experienced deaths in impressed tortoises (Manouria impressa) and a Burmese star tortoise (Geochelone platynota).

Meningitis caused by Mycoplasma mycoides subspecies capri in a goat.

A 2-year-old, female goat from Connecticut was submitted for necropsy with a 5-day history of pyrexia and intermittent neurologic signs, including nystagmus, seizures, and circling. Postmortem examination revealed suppurative meningitis. Histologic examination of the brain revealed that the meninges were diffusely infiltrated by moderate numbers of lymphocytes, macrophages, and fibrin, with scattered foci of dense neutrophilic infiltrate.

Actinomyces hyovaginalis-associated lymphadenitis in a Nubian goat.

A 6-year-old Nubian goat with a history of progressive weight loss and cough was presented for necropsy. The goat tested negative for antibodies to caseous lymphadenitis and caprine arthritis and encephalitis by hemagglutination inhibition assay and enzyme-linked immunosorbent assay, respectively. Postmortem examination revealed marked enlargement and, with histopathology, a fibrinopurulent necrotizing lymphadenitis of a tracheobronchial lymph node, with an appearance similar to that reported in cases of caseous lymphadenitis.