Deep Learning-based Modeling for Preclinical Drug Safety Assessment.

In drug development, assessing the toxicity of candidate compounds is crucial for successfully transitioning from preclinical research to early-stage clinical trials. Drug safety is typically assessed using animal models with a manual histopathological examination of tissue sections to characterize the dose-response relationship of the compound - a time-intensive process prone to inter-observer variability and predominantly involving tedious review of cases without abnormalities. Artificial intelligence (AI) methods in pathology hold promise to accelerate this assessment and enhance reproducibility and objectivity.

A multicentric intermediate-size B-cell lymphoma with epitheliotropism in a Freiberger mare.

This report describes a multicentric intermediate-size B-cell lymphoma with epitheliotropism in a Freiberger mare affecting multiple mucous membranes, skin and internal organs. The clonal neoplastic B-cell population was accompanied by numerous reactive polyclonal small T cells. Differential diagnoses for these unusual findings are discussed.

H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours.

Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation.

Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization.

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs.

LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus.

Wild-type canine distemper virus (CDV) is an important pathogen of dogs as well as wildlife that can infect immune and epithelial cells through two known receptors: the signaling lymphocytic activation molecule (SLAM) and nectin-4, respectively. Conversely, the ferret and egg-adapted CDV-Onderstepoort strain (CDV-OP) is employed as an effective vaccine for dogs. CDV-OP also exhibits promising oncolytic properties, such as its abilities to infect and kill multiple cancer cells .

Organoids of patient-derived medullary thyroid carcinoma: The first milestone towards a new in vitro model in dogs.

Organoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period.

Prognostic clinical and histopathological features of canine cutaneous epitheliotropic T-cell lymphoma.

Canine cutaneous epitheliotropic T-cell lymphoma is a neoplasm with heterogeneous clinical and histopathological presentations. Survival times and responses to therapy are variable, and indicators to predict outcomes are lacking. Clinical and histopathological parameters from 176 archival cases from the University of Pennsylvania and University of Bern (2012-2018) were investigated for associations with clinical outcomes.

A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer.

Mammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts. We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (CMT), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors. We established the long-term culture of 24 organoid lines from 16 dogs, including organoids derived from normal mammary epithelium or benign lesions.

Feline gastrointestinal eosinophilic sclerosing fibroplasia presenting as a rectal mass.

Case Summary: A 9-year-old neutered male cat was referred owing to dyschezia and weight loss. Abdominal CT revealed a heterogeneous mass in the rectum and thickening of one caudal mesenteric lymph node. The mass induced a focal rectal obstruction.

Computer-assisted mitotic count using a deep learning-based algorithm improves interobserver reproducibility and accuracy.

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC.

Gammaherpesvirus Infections in Cattle in Europe.

The genus Macavirus, subfamily Gammaherpesvirinae, comprises ungulate viruses that infect domestic and wild ruminants and swine. They cause asymptomatic latent infections in reservoir hosts and malignant catarrhal fever in susceptible species. Lung, spleen, bronchial lymph node, and tongue were collected from 448 cattle (348 necropsied, 100 slaughtered) in Switzerland, United Kingdom, Finland, Belgium, and Germany to determine their infection with bovine herpesvirus-6 (BoHV-6) and gammaherpesviruses of other ruminants, i.

Validation of Immunohistochemistry for Canine Proteins Involved in Thyroid Iodine Uptake and Their Expression in Canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-Derived Organoids.

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC.

Transcriptional Differences between Canine Cutaneous Epitheliotropic Lymphoma and Immune-Mediated Dermatoses.

Canine cutaneous epitheliotropic T-cell lymphoma (CETL) and immune-mediated T-cell predominant dermatoses (IMD) share several clinical and histopathological features, but differ substantially in prognosis. The discrimination of ambiguous cases may be challenging, as diagnostic tests are limited and may prove equivocal. This study aimed to investigate transcriptional differences between CETL and IMD, as a basis for further research on discriminating diagnostic biomarkers.

Deep learning algorithms out-perform veterinary pathologists in detecting the mitotically most active tumor region.

Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how significantly the area selection could impact the mitotic count, which has a known high inter-rater disagreement.

Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity.

Insect bite hypersensitivity (IBH) is a Th-2, IgE-mediated dermatitis of horses caused by bites of insects of the genus Culicoides that has common features with human atopic dermatitis. Together with Th-2 cells, the epithelial barrier plays an important role in development of type I hypersensitivities. In order to elucidate the role of the epithelial barrier and of the skin immune response in IBH we studied the transcriptome of lesional whole skin of IBH-horses (IBH-LE; n = 9) in comparison to non-lesional skin (IBH-NL; n = 8) as well as to skin of healthy control horses (H; n = 9).

Evaluation of an investigative model in dairy herds with high calf perinatal mortality rates in Switzerland.

The objective of this study was to evaluate an investigative model which encompassed the risk factors, incidence, timing and causes of perinatal mortality (PM) (0-48 h) on high risk dairy farms (PM of >5% in the previous year) in Switzerland. This pilot-study was carried out on 47 predominantly Holstein PM calves from 21 dairy farms, between September 2016 and January 2018. Gross pathological examinations of calves and placentae as well as histopathological examinations of internal organs and placental tissue were performed.

Computerized Calculation of Mitotic Count Distribution in Canine Cutaneous Mast Cell Tumor Sections: Mitotic Count Is Area Dependent.

Mitotic count (MC) is an important element for grading canine cutaneous mast cell tumors (ccMCTs) and is determined in 10 consecutive high-power fields with the highest mitotic activity. However, there is variability in area selection between pathologists. In this study, the MC distribution and the effect of area selection on the MC were analyzed in ccMCTs.

An unusual case of bovine anthrax in the canton of Jura, Switzerland in 2017.

Background: Anthrax caused by Bacillus anthracis is a zoonotic disease mainly affecting herbivores. The last Swiss outbreak was over 20 years ago. We describe a recent anthrax outbreak involving two cows from the same herd.

Limited added value of fungal ITS amplicon sequencing in the study of bovine abortion.

Bovine mycotic abortion is sporadic and caused by different ubiquitous and opportunistic fungi. Recently, a broad spectrum of bacterial opportunists involved in bovine abortion was revealed by 16S rRNA gene amplicon sequencing. We hypothesized that fungal organisms potentially involved in bovine abortion also might remain undetected by conventional culture.

Cutaneous Tumors in Swiss Dogs: Retrospective Data From the Swiss Canine Cancer Registry, 2008-2013.

Data collected in animal cancer registries comprise extensive and valuable information, even more so when evaluated in context with precise population data. The authors evaluated 11 740 canine skin tumors collected in the Swiss Canine Cancer Registry from 2008-2013, considering data on breed, sex, age, and anatomic locations. Their incidence rate (IR) per 100 000 dogs/year in the Swiss dog population was calculated based on data from the official and mandatory Swiss dog registration database ANIS.

Validation of Digital Microscopy Compared With Light Microscopy for the Diagnosis of Canine Cutaneous Tumors.

Integration of new technologies, such as digital microscopy, into a highly standardized laboratory routine requires the validation of its performance in terms of reliability, specificity, and sensitivity. However, a validation study of digital microscopy is currently lacking in veterinary pathology. The aim of the current study was to validate the usability of digital microscopy in terms of diagnostic accuracy, speed, and confidence for diagnosing and differentiating common canine cutaneous tumor types and to compare it to classical light microscopy.

Immunohistochemical expression of Bax and Bak in canine non-neoplastic tissues.

Apoptosis is critical for embryonic development, maintenance of tissue homeostasis and protection against malignant transformation. The Bcl-2 family of proteins plays a key role in intrinsic apoptosis by controlling the integrity of the outer mitochondrial membrane, and the multidomain pro-apoptotic Bcl-2 family members Bax and Bak are essential components of this pathway. The aim of this study was to provide data on the expression of these proteins in normal canine tissues.

A possible case of caprine-associated malignant catarrhal fever in a domestic water buffalo (Bubalus bubalis) in Switzerland.

Background: Malignant catarrhal fever (MCF) is a fatal herpesvirus infection, affecting various wild and domestic ruminants all over the world. Water buffaloes were reported to be particularly susceptible for the ovine herpesvirus-2 (OvHV-2) causing the sheep-associated form of MCF (SA-MCF). This report describes the first case of possibly caprine-associated malignant catarrhal fever symptoms in a domestic water buffalo in Switzerland.

Ultrasonographic findings in a cow with abomasal lymphosarcoma: case report.

Background: This case report describes the clinical and ultrasonographic findings in a Swiss Braunvieh cow with lymphosarcoma of the abomasum.

Case Presentation: The main clinical findings were vomiting in response to eating and melena. The results of serum biochemistry and rumen fluid analysis were indicative of abomasal reflux syndrome.