Pet Dogs Research Articles

Pet Attachment, Empathy and Mindful Self Care among Young Adults

The study investigated the relationship between pet attachment, empathy and mindful self-care in young adult owners of pet dogs (n=226, 151 female) aged 18-45 years. The Lexington Attachment to Pets Scale (LAPS), Toronto Empathy Questionnaire (TEQ) and Mindful Self-Care Scale (MSCS-Brief) were used. Results showed that while women have significantly higher pet attachment and empathy, there were no gender differences in mindful self-care. In terms of magnitude of correlation, the correlation between pet attachment and empathy is higher in men than in women, and the correlation between empathy and mindful self-care was found to be significantly higher in women than in men. The relationship between pet attachment and mindful self-care is found to be similar in men and women. Further research is needed to study the potential of a causal relationship between pet attachment and the development of empathy and self-care practices, particularly in the Indian context.

Incidence of human rabies following bite or exposure to laboratory confirmed rabid animals

Background: Rabies is one of the important endemic fatal zoonotic viral disease afflicting humans and animals in Punjab, India. The present study investigated the incidence of rabies in humans bitten/exposed to laboratory confirmed rabid animals, as well as incidence after use of vaccine or rabies immunoglobulin (RIG) and clinico-epidemiological studies. Methods: A study was conducted during August 2021 to September 2022 on forty (40) rabies suspected animals presented to diagnose rabies by direct fluorescent antibody test (dFAT) at rabies diagnostic laboratory (RDL), Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Punjab, India. A detailed questionnaire was prepared for obtaining information about exposure/bite of humans by rabid animals, death of humans, demographic and epidemiological information of victims. Results: Out of total forty (40) suspected rabies cases, 30(75%) were found positive for rabies by dFAT. Laboratory confirmed rabies (LCR) incidence was 60.80% and 21.73% in stray and pet dogs, respectively. All pet dogs were vaccinated but no stray dog was vaccinated. The LCR incidence in buffaloes and cattle was 77.77% and 100%, respectively. Further in humans exposed to rabid animals (59), males were at more risk than females. The human rabies incidence was 3.38% (2/59). Highest incidence of dog bites in adult males on lower limb was observed from urban stray dogs (60.80%) followed by children. Post exposure vaccination was given to 98.3% humans exposed to rabid animals. Human’s rabies in two cases was due to no vaccination or RIG. Conclusions: Vaccination is an important step in controlling rabies in India. There is a need for integrated and comprehensive management of street dogs and bite management.

Об уголовной ответственности владельца за вред, причиненный домашним животным (собакой) третьим лицам

The laws of Russia and some foreign states have no special criminal law provisions that establish the liability of the owner for damage caused by his/her pet (dog) to third parties. The article reviews issues of qualification of such acts under the laws of Russia and foreign countries. A comparative analysis of laws of some foreign states and Russia that regulate the bases and procedure for bringing pet dog owners to the legal liability for damage caused by them to health of third parties has shown the unity of approaches towards strict legal liability including criminal liability of such owners in cases of gross violation of rules for handling their pets. At the same time, countries apply different approaches within their jurisdiction to solving the issue of specification of criminal laws applicable to the cases under consideration by singling out or refusing to single out special elements of crimes for violation of pet handling rules. The task of determination of legally relevant attributes of the link between the crime subject (dog owner), behavior of his/her pet and actions/inactivity of the victim seems relevant for the Russian criminal law practice.

Walk with me? Part 2: Dogs synchronize with an unfamiliar person who first synchronized with their owner

Dogs exhibit sensitivity to human behaviours directed towards them (see Part 1), but dogs’ sensitivity to human third-party interactions, i.e. eavesdropping or indirect sensitivity, remains unclear. This study aimed to investigate dogs' indirect sensitivity in an ecological context devoid of food incentives. We thus explored dogs’ responsiveness to interactions between their owner and an unfamiliar person during a synchronous walk in an outdoor environment. To do so, we delineated two experimental groups of pet dogs: an unfamiliar experimenter either walked and talked with the owner for 15 minutes, maintaining a 1-metre proximity and aligning speed (n = 16 dogs) or stayed away from the owner for 15 minutes (n = 16 dogs) in the dog’s presence. We then compared the dogs’ locomotor synchronization with the experimenter and the dogs’ gaze behaviour during a straight-line walk. Dogs for which the experimenter had interacted with the owner displayed enhanced location, temporal and activity synchronization with the experimenter during the straight-line walk compared to dogs for which the experimenter had not interacted with the owner. Specifically, these dogs were closer to the experimenter, had a smaller speed difference compared to the experimenter’s speed at the beginning of the straight-line walk, and more dogs from this group adjusted their speed directly after the experimenter’s change of speed. Regarding dogs’ gaze behaviour, we did not find significant differences between the two experimental groups. Finally, we found that dogs from both experimental groups were attracted to their owner during the straight-line walk. Our results demonstrate, for the first time, that dogs’ behavioural synchronization with an unfamiliar person occurs subsequently to the dogs’ perception of intraspecific behavioural synchronization between their owner and the unfamiliar person. This third-party sensitivity may result from an automatic process of reproducing perceived behaviours, suggesting interspecific motor contagion when dogs perceive synchronous behaviour of two human agents; and/or from a transitivity of familiarity, the unfamiliar person becoming indirectly familiar to the dogs through their interaction with the dogs’ owners. These findings bear practical significance, as encounters between unfamiliar people and dog-owner dyads can be enhanced if those people first synchronize and talk with dogs’ owners before interacting with dogs.

Many direct-to-consumer canine genetic tests can identify the breed of purebred dogs.

To compare pedigree documentation and genetic test results to evaluate whether user-provided photographs influence the breed ancestry predictions of direct-to-consumer (DTC) genetic tests for dogs. 12 registered purebred pet dogs representing 12 different breeds. Each dog owner submitted 6 buccal swabs, 1 to each of 6 DTC genetic testing companies. Experimenters registered each sample per manufacturer instructions. For half of the dogs, the registration included a photograph of the DNA donor. For the other half of the dogs, photographs were swapped between dogs. DNA analysis and breed ancestry prediction were conducted by each company. The effect of condition (ie, matching vs shuffled photograph) was evaluated for each company's breed predictions. As a positive control, a convolutional neural network was also used to predict breed based solely on the photograph. Results from 5 of the 6 tests always included the dog's registered breed. One test and the convolutional neural network were unlikely to identify the registered breed and frequently returned results that were more similar to the photograph than the DNA. Additionally, differences in the predictions made across all tests underscored the challenge of identifying breed ancestry, even in purebred dogs. Veterinarians are likely to encounter patients who have conducted DTC genetic testing and may be asked to explain the results of genetic tests they did not order. This systematic comparison of commercially available tests provides context for interpreting results from consumer-grade DTC genetic testing kits.

Infection with Clonorchis sinensis (Cobbold, 1875) Metacercariae in Fish from the East Lake of Wuhan: Freshwater Fish in Urban Lakes May Act as Infection Sources of Liver Fluke.

The liver fluke disease caused by Clonorchis sinensis is one of the most serious food-borne parasitic diseases in China. Many freshwater fish and shrimps can be infected with C. sinensis metacercariae as the second intermediate hosts in endemic regions. Owing to the lack of infected humans and the good administration of pet dogs and cats in cities of non-endemic regions, few fish are expected to be infected with C. sinensis metacercariae in urban lakes. To determine the infection of C. sinensis metacercariae in freshwater fish and shrimps in urban lakes, a total of 18 fish species and one shrimp species were investigated in the East Lake of Wuhan City. Metacercariae were isolated by artificial digestive juice and identified using morphology and rDNA-ITS2 sequences. Five species of fish, Pseudorasbora parva, Ctenogobius giurinus, Squalidus argentatus, Hemiculter leuciclus, and Rhodeus spp., were infected with C. sinensis metacercariae. The overall prevalence of C. sinensis was 32.5%. The highest prevalence was found in P. parva with 57.9%, while S. argentatus exhibited the highest mean abundance (13.9). Apart from the C. sinensis metacercariae, four species of other trematode metacercariae were also identified across twelve fish species in total. Owing to the consumption of undercooked fish and feeding cats with small fish caught by anglers, there is a potential risk that the small fish infected with C. sinensis metacercariae may act as an infection source to spread liver fluke. Given the complete life cycle of C. sinensis, stray cats and rats were inferred to act as the important final hosts of C. sinensis in urban lakes in non-endemic areas.

Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk.

Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

Factors associated with behavioral euthanasia in pet dogs.

When pet dogs demonstrate certain serious problem behaviors, this may lead owners to choose behavioral euthanasia. However, research on behavioral euthanasia of pet dogs is sparse and previously published papers have not specifically sampled owners who made the decision to euthanize for behavior. The Behavioral Euthanasia in Pet Dogs Questionnaire was created to collect a wide range of information from dog owners who made behavioral euthanasia decisions. Using this survey, we explored the types of behaviors associated with behavioral euthanasia. Human-directed aggression, especially toward adults living in the household, was the most frequently reported reason for choosing behavioral euthanasia; followed by aggression toward other animals, especially other dogs living in the same household. The majority of dogs displaying human-directed or other animal-directed aggression were reported to have bitten and broken skin, and many of these had bitten in multiple or severe incidents. Most dogs had lived in their homes and displayed problem behaviors for over a year prior to behavioral euthanasia, and the euthanasia occurred at a variety of ages, from less than 1 year old to 18 years old. Additional research is required to understand environmental or nonbehavioral factors contributing to the behavioral euthanasia of companion animals, as well as the psychosocial and emotional impact of behavioral euthanasia on the human experience. Understanding the behavioral factors associated with behavioral euthanasia can direct resources toward problem behavior interventions, improve public education about animal behavior, and strengthen the human-animal bond.

Human Perception of Emotions from Canis familiaris Barks: An Auditory-Perceptual Study

This study investigates how experience and gender influence the perception of emotions in dog barks. Drawing from Morton's structural-motivational rule and previous research on mammalian vocalizations, we aimed to discern whether humans, especially those experienced with dogs, can accurately identify emotions such as stranger, anger, lonely, and play in dog barks. Using recordings of Indian Lesser Spitz barks in various contexts, we conducted auditory-perceptual experiments with two groups: experienced listeners (with more than 2- 3 years of pet dog experience) and non-experienced listeners. Participants listened to bark sequences and identified the corresponding emotions. Results revealed that experienced listeners consistently outperformed non- experienced ones in identifying emotions, except for 'play,' where no significant difference was observed. Gender did not significantly affect emotion perception. Interestingly, 'anger' was most accurately identified across both groups, followed by 'stranger,' 'play,' and 'lonely' emotions. Analyzing open-ended responses, we found that acoustic cues such as pitch and inter-bark intervals strongly influenced emotional perception. 'Stranger' barks were described as low-pitched, while 'anger' barks had shorter inter-bark intervals. 'Lonely' barks were characterized by high pitch and longer inter- bark intervals than 'play' barks. These findings suggest that experience plays a crucial role in accurately perceiving emotions in dog barks, aligning with the concept of a common mammalian heritage in emotional communication. Gender differences were negligible in this context. Understanding the acoustic cues underlying emotional expression in dogs enhances our comprehension of canine behavior and has implications for fields like animal welfare and neuroscience. Further research could delve deeper into the mechanisms underlying emotional perception in non-verbal communication across mammalian species.

Informing Modifications to Social Participation and Navigation (SPAN) for Adolescents with Social Anxiety Incorporating Pet Dogs

Informing Modifications to Social Participation and Navigation (SPAN) for Adolescents with Social Anxiety Incorporating Pet Dogs

Pawsome Detect: Harnessing Pattern Recognition and Data Mining for Canine Age and Breed Detection

PAWSOMEDETECT leverages pattern recognition to revolutionize canine age and breed detection. Determining a dog's age and breed from photos has become vital due to rising popularity of dogs as pets and the demand for personalized, data-driven pet care. Traditional methods rely on manual inspection and judgment, prone to errors. Furthermore, mating compatibility among breeds is a consideration for dog owners. This aids users in identifying compatible breeds for mating, increasing successful mating chances. To achieve accurate age and breed, deep learning models are trained on a vast collection of annotated dog photos. These models use Convolutional Neural Networks (CNNs) and transfer learning to improve performance and generalize knowledge, revealing age and breed patterns. Researchers, breeders, and owners can benefit from this data. Following ISO-25010 guidelines, the study confirms the system's accuracy in age and breed determination, as well as its ability to detect user locations for successful mating. It meets response time and resource utilization requirements, ensuring timely operations. In conclusion, "PAWSOMEDETECT" a groundbreaking pattern recognition-based method for accurate age and breed identification in dogs. It provides data-driven solutions for pet care, mating compatibility, and more, benefiting users and dogs. The study's continued enhancements promise even greater accuracy and functionality.

Investigating the Status of Contamination With Pulex irritans and Xenopsylla cheopis in Pets, Guard and Stray Dogs in Tabriz, Iran

Introduction: Fleas are the most prevalent ectoparasites indoors and outdoors due to their high reproductive rate, ability to feed on different hosts, and the unpleasant effects of their bites. Methods: This study was conducted on 360 dogs in and around Tabriz to find the rate and type of human flea contamination in these dogs, which were divided into three categories: pets, guards, and stray dogs. After fleas were identified in the dogs’ skin, they were taken with glue and fixed on the slide with glue. When the number of fleas was large, the captured fleas were transported to a test tube and treated with 70% alcohol. Dehydration of fleas was performed with ascending percentages of ethanol from 50 to 100% absolute and was kept inside each alcohol percentage for 10 to 20 minutes. Results: Regarding the dogs studied in this research, the rate of actual contamination in guard dogs was 76.67% (92 dogs were contaminated with flea feces). However, 74 dogs (about 15%) were infested with different fleas. Unfortunately, the rate of contamination in stray dogs was 100%. The rate of real contamination based on the separation of fleas and flea excrement from the body of this group of dogs was equal. The rate of flea infestation in pet dogs was 14 out of 100 dogs, representing 14% contamination. Conclusion: It should be acknowledged that, unfortunately, flea infestation is expected in the region’s dogs, depending on the type of dogs kept. Infestation with these insidious skin parasites with varying rates and symptoms is common, which, in addition to the economic damage of spending time and money on medicine for disease in animals, causes environmental pollution, increases the likelihood of disease transmission by these parasites, and increases the possibility of human infection and disease transmission from them to humans, as well as environmental pollution.

Applications and Opportunities for Immune Cell CAR Engineering in Comparative Oncology.

Chimeric antigen receptor (CAR) T-adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously. Moreover, their large size, outbred genetic background, shared environment with humans, and immunocompetency make dogs ideal for investigating and optimizing CAR therapies before human trials. Here, we will outline how challenges in early clinical trials in patients with canine lymphoma, including issues related to autologous CAR T-cell manufacturing, limited CAR T-cell persistence, and tumor antigen escape, mirrored challenges observed in human CAR T trials. We will then highlight emerging adoptive cell therapy strategies currently under investigation in dogs with hematological and solid cancers, which will provide crucial safety and efficacy data on novel CAR T regimens that can be used to support clinical trials. By drawing from ongoing studies, we will illustrate how canine patients with spontaneous cancer may serve as compelling screening platforms to establish innovative CAR therapy approaches and identify predictive biomarkers of response, with a specific emphasis on solid tumors. With increased funding for canine immunotherapy studies, multi-institutional investigations are poised to generate highly impactful clinical data that should translate into more effective human trials, ultimately benefiting both human and canine cancer patients.

The behavioural effect of short-term cognitive and physical intervention therapies in old dogs

Efforts to counteract age-related decline have resulted in the emergence of various interventions. However, everyday benefits are rarely reported in elderly people. Dogs provide an excellent model for studying aging and interventions due to their similarities to humans. Our aim was to investigate whether a combined physical and cognitive intervention (most effective in humans) could enhance the performance of pet dogs and lead to far transfer effects (improvement in not just the trained specific task). We examined the impact of three-month-long intervention therapies (cognitive, physical, combined) on the cognitive performance and behaviour of old, healthy dogs (N = 72; aged 7.68–14.54 years) using a 12-subtest behavioural test battery. We did not find the combined intervention group outperforming either the cognitive-only or physical-only therapy groups. Physical interventions, either alone or in combination, improved dogs' behavioural flexibility and social behaviour. Cognitive interventions, either alone or in combination, increased neophilia. Furthermore, all intervention therapies made dogs more engaged with their environment. Moreover, less old, around eight years old dogs, exhibited improved social behaviour, problem solving ability, and increased neophilia by their second test occasion. Additionally, dogs' performance was influenced by their health, training, daily play with the owner, and activity/excitability traits. In sum, both cognitive and physical intervention therapies can have an impact on the behaviour of old, healthy pet dogs. However, these therapies may be more effective when longer or applied at a younger age, as the healthy older dogs were less likely to show improvement.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4–132.6; 79.2–114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5–12; 7–9]; sCr, 57.2 µmol/L [35.2–212.2; 52.8–92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7–13; 8–10]; sCr, 70.4 µmol/L [61.6–79.2; 61.6–70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

338 Non-occupational herbicide and VOC exposures detected in dogs with multicentric lymphoma: a model for human non-Hodgkin lymphoma

OBJECTIVES/GOALS: The objective of this study was to determine whether pet dogs with multicentric lymphoma (ML), a spontaneous, immunocompetent model for human non-Hodgkin lymphoma (NHL), are exposed to higher concentrations of herbicides and volatile organic compounds (VOCs) compared to matched unaffected control dogs. METHODS/STUDY POPULATION: We are prospectively enrolling dogs with ML within a single high-risk breed, the boxer dog, along with age-matched control boxers sampled within the same season. We are measuring urinary concentrations of the herbicides glyphosate (in Roundup®) and 2,4-D, as well as stable urinary metabolites of the VOCs benzene and 1,3-butadiene. To assess the genotoxic potential of herbicide and VOC exposures, we are using reverse dosimetry to estimate plasma exposures, and exposing healthy canine PBMC’s to these concentrations of herbicides and VOCs in vitroto assess double stranded DNA damage using the Comet Chip assay. RESULTS/ANTICIPATED RESULTS: Preliminary data show significantly higher benzene exposures, measured by the stable benzene metabolite PHMA, and significantly higher 2,4-D exposures at the time of diagnosis in cases versus controls. All dogs had measurable exposures to 1,3-butadiene (measured as its stable metabolite DHBM) and glyphosate.In vitro results show significant genotoxicity thresholds of 0.1 uM for both glyphosate and 2,4-D in dog lymphoid cells. To date, these predicted plasma exposures have not been reached in vivo in boxer dogs with ML or unaffected control boxers. DISCUSSION/SIGNIFICANCE: Canine multicentric lymphoma resembles human NHL and is a potentially useful model of non-occupational chemical risk for NHL in people. The goal of this research is to identify potentially preventable non-occupational chemical risk for lymphoma and support evidence-based remediation strategies to decrease lymphoma risk in both humans and dogs.

Four’s a Crowd? Attachment Styles in Childless Women and First-Time Mothers Toward Their Pet Dog

ABSTRACT The transition to parenthood is a time of change and challenge, where new attachments are developed and old ones are re-appraised to fit the needs of the new family. Research on how this transition affects parental attachment to the family pet dog is scarce. This study explored attachment orientation differences among female dog owners without children and female dog owners who had recently become new mothers. Factors that may underpin these differences were also explored. New mothers (n = 98) and childless women (n = 93) completed an online survey that measured the degree to which they were anxiously and avoidantly attached to their pet dog. Significant differences in attachment orientations were found: the parent group had more avoidant, and less anxious, attachment styles toward their pet dogs, compared with the childless group. Qualitative insights revealed new mothers suffer from a lack of time, energy, and attention to afford their dog and that the role of the dog in the family may be re-appraised to accommodate the new family member. These outcomes provide insight into how Australian women experience their attachment relationships to their pet dogs. This study has implications for both pet and maternal welfare.

Unleashing potential: Boosting physical activity in children with developmental disabilities via a family-dog-assisted intervention

Abstract In the context of a global crisis, where over 80% of children fail to meet minimum standards of physical activity, children with developmental disabilities may face an even greater health disparity. Despite being disproportionately less physically active than the broader population, those with developmental disabilities are often excluded from mainstream interventions. This study evaluated a novel animal-assisted intervention (AAI) that incorporated the family pet dog, with the goal of increasing physical activity in children with developmental disabilities. The intervention involved teaching child participants to engage in “Do as I Do” (DAID) reciprocal-imitation training with their dog over ten 60-min sessions. After enrollment, 45 child-dog pairs of children and their family dogs were randomly assigned to either the experimental intervention (DAID) group, the active control group (dog walking control [DWC]), or the passive control group (waitlist control [WC]). Physical activity was measured using a 7-day ActiGraph accelerometer monitoring process, and data were analyzed for children who wore the accelerometer for a minimum of 4 days at both assessment time points (N = 14). Participation in the intervention (DAID) group was found to significantly increase moderate-to-vigorous physical activity (MVPA) by 1.2 min/h ( p = 0.0087; Cohen’s d = 1.7) and significantly reduce sedentary behavior by 4.03 min/h ( p = 0.027; d = 1.3), outperforming the waitlist control group. Our findings demonstrate the potential of this novel dog-assisted intervention to improve physical activity in this population, thereby contributing to a reduction in health disparities.

Abstract 3480: Alterations in the tumor microenvironment and key signaling pathways in naturally-occurring canine gliomas mirror those seen in human patients

Abstract Background: Malignant gliomas are the most common type of primary brain tumors, with patient outcomes that are generally dismal. Recently, pet dogs have been assessed as a valuable model in which to study gliomas. Gliomas in pet dogs occur at similar rates to those seen in humans, and a recent study comparing canine and human gliomas identified high similarity in terms of mutational rates, aneuploidy, the timing of mutations, and methylation patterns. Here, we further compare naturally-occurring canine and human gliomas, focusing on the tumor microenvironment (TME) and key pathways dysregulated in human gliomas. Methods: Spontaneously occurring gliomas from adult and pediatric human, and canine patients were utilized for this study. RNA, whole genome/whole exome, and bisulfite sequencing data from adult and canine samples were downloaded from the Genomic Data Commons and the National Cancer Institute’s Integrated Canine Data Commons, respectively. Pediatric tumor RNA-seq and genomic data were obtained from the Gabriella Miller Kids First database. Normal adult human and canine brain tissue served as control tissue. Only tumors with a clear diagnosis of astrocytoma, oligodendroglioma, or oligoastrocytoma were included in this study. Results: Overall, we found that key canonical pathways that are altered in human gliomas are also altered in canine gliomas. A comparison of high-grade gliomas in pet dogs to normal canine brain tissues showed significant abnormal gene expression in 3 canonical oncogenic pathways of human GBM: the TP53, RB1, and RTK/RAS/PI3K pathways. Similarities between species included increased expression of PDGF, and receptors PDGFRA and PDGFRB. Frequent copy number alterations and mutations were also observed in PDGFRA and EGFR. Differences between species include the mutation rate of TP53, which we found to be mutated frequently in adults but not in pediatric or canine gliomas, however, expression of TP53 as assessed by RNA-seq was significantly increased in both adult and canine gliomas. IDH1, which drives methylation, was significantly overexpressed in adults but underexpressed in canine. Correspondingly, each of the promotor regions of TERT, PD1 and MGMT was hypermethylated in adults, but hypomethylated in canine. Although an analysis of the TME from RNA-seq data revealed an influx of immune cells in adult, pediatric and canine gliomas, there was a concurrent influx of immunosuppressive cells. Gene expression profiles of astrocytomas and oligodendrogliomas show differences in alterations of immune-related and TME-specific pathways. Conclusion: We found that similar TME and pathway alterations were observed between human and canine gliomas, and that TME alterations were different between canine astrocytomas and oligodendrogliomas. The canine TME, like that in humans, appears to be immunosuppressive. Citation Format: Nadia A. Lanman, Sagar Utturkar, Harish Kothandaraman, Deepika Dhawan, Danni Liu, Min Zhang, Matthew Beyers, Deborah W. Knapp, R. Timothy Bentley. Alterations in the tumor microenvironment and key signaling pathways in naturally-occurring canine gliomas mirror those seen in human patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3480.

Abstract 3736: Bridging the gaps: A cross-species approach to PD-1 and OX40 combination immunotherapy

Abstract Monoclonal antibodies (mAbs) targeting immune checkpoints, such as PD-1, PD-L1, and CTLA4, have provided unprecedented clinical benefits to human cancer patients. Novel strategies such as combination therapy with OX40 or 4-1BB agonists are currently under investigation in various pre-clinical studies to enhance the therapeutic benefits of immune checkpoint inhibitors. While syngeneic mouse tumor xenograft models offer valuable insights in pre-clinical testing, they fall short in capturing the nuanced heterogeneity within and between tumors and the dynamic tumor-immune interface. In contrast, canine patients with spontaneous neoplasms possess a closely analogous and intact immune system. These canine patients, who receive sophisticated and advanced medical therapy like their human counterparts, can serve as a vital intermediate pre-clinical model system between rodent studies and human clinical trials, potentially reducing clinical trial failures. In this study, we have developed a novel bispecific fusion protein, denoted BsOXPD, that combines OX40 agonism and PD-1 blockade into a single therapeutic. Our bispecific fusion protein employs an anti-PD-1 nanobody (Nb) to bind and block the PD1 pathway and the extracellular domain (ECD) of the OX40 ligand to stimulate the OX40 receptor. We have developed murinized, caninized, and humanized versions of this protein. All versions of the bispecific fusion protein retain their biochemical and functional properties following the murinization, caninization, and humanization processes. Importantly, all versions effectively disrupt the PD-1/PD-L1 axis in murine, canine, and human systems while concurrently acting as potent OX40 agonists. To further improve the humanized version of the BsOXPD, we partially humanized the anti-PD1 Nb by introducing amino acid substitutions in various framework regions. The humanized anti-PD1 Nb still completely inhibited the binding of human PD-L1 to the PD-1 receptor. The caninized version of BsOXPD exhibits no toxicities or immune-related adverse events (irAEs) following intravenous injection at doses of 1 mg/kg or 3 mg/kg body weight in healthy beagle dogs. In summary, we have designed a cross-species Nb-based fusion protein for PD1 blockade and OX40 agonism. Our next goal is to evaluate the therapeutic efficacy of caninized BsOXPD in pet dogs with oral melanoma in neoadjuvant settings. Therefore, our cross-species approach will offer comprehensive insights into the safety, pharmacokinetic (PK) profile, and clinical benefits associated with the concurrent application of PD1 blockade and OX40 agonism. Citation Format: Maninder Sandey, Damien Ruiz, Jonathan Marable, Deepa Bedi, Payal Agarwal. Bridging the gaps: A cross-species approach to PD-1 and OX40 combination immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3736.