Toxicity Profile of eBAT, a Bispecific Ligand-Targeted Toxin Directed to EGFR and uPAR, in Mice and a Clinical Dog Model.

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated toxin.

Associations between weight bias internalization, weight status, and health among a diverse cohort of freshman college students.

Mental health concerns are common among college students, especially students with higher body mass index (BMI). Weight bias internalization (WBI) is thought to contribute to these mental health disparities. However, little is known about how WBI differs among more diverse students, and to what extent WBI may explain associations between BMI and health in college populations.

Trap and ambush therapy using sequential primary and tumor escape-selective oncolytic viruses.

In multiple models of oncolytic virotherapy, it is common to see an early anti-tumor response followed by recurrence. We have previously shown that frontline treatment with oncolytic VSV-IFN-β induces APOBEC proteins, promoting the selection of specific mutations that allow tumor escape. Of these mutations in B16 melanoma escape (ESC) cells, a C-T point mutation in the cold shock domain-containing E1 () gene was present at the highest frequency, which could be used to ambush ESC cells by vaccination with the mutant CSDE1 expressed within the virus.

Expression and Prognostic Evaluation of the Receptor Tyrosine Kinase MET in Canine Malignant Melanoma.

The overexpression and activation of the MET receptor tyrosine kinase has been identified in many human malignancies, but its role in canine cancer has only been minimally investigated. In this study we evaluated the expression of MET in two canine malignant melanoma (CMM) cell lines as well as in 30 CMM tissue samples that were collected from the clinical service at our institution. We were able to confirm the expression of the MET protein in both melanoma cell lines, and we demonstrated MET activation by its ligand, HGF, through phosphorylation, in Western blot analysis.

Pretreatment and During-Treatment Weight Trajectories in Black and White Women.

Introduction: Black participants often lose less weight than White participants in response to behavioral weight-loss interventions. Many participants experience significant pretreatment weight fluctuations (between baseline measurement and treatment initiation), which have been associated with treatment outcomes. Pretreatment weight gain has been shown to be more prevalent among Black participants and may contribute to racial differences in treatment responses.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here.

Examination of IgG Fc Receptor CD16A and CD64 Expression by Canine Leukocytes and Their ADCC Activity in Engineered NK Cells.

Human natural killer (NK) cells can target tumor cells in an antigen-specific manner by the recognition of cell bound antibodies. This process induces antibody-dependent cell-mediated cytotoxicity (ADCC) and is exclusively mediated by the low affinity IgG Fc receptor CD16A (FcγRIIIA). Exploiting ADCC by NK cells is a major area of emphasis for advancing cancer immunotherapies.

Correlates of psychological distress among adults with obesity during the COVID-19 pandemic.

Objective: The present study evaluated changes in stress and loneliness among participants with obesity engaged in weight loss self-management in the United States (US) during COVID-19, and identified factors that may increase risk or protect against psychosocial distress during this time.

Design: Participants who were enrolled in a weight self-management program prior to the COVID-19 pandemic ( = 55, 91% female, 36% Caucasian, mean age = 49.8 years) completed an online survey about social, economic and health behaviour changes during COVID-19 and their relationship to changes in perceived stress and loneliness.

Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients.

Background: Both human and veterinary cancer chemotherapy are undergoing a paradigm shift from a "one size fits all" approach to more personalized, patient-oriented treatment strategies. Personalized chemotherapy is dependent on the identification and validation of biomarkers that can predict treatment outcome and/or risk of toxicity. Many cytotoxic chemotherapy agents, including doxorubicin, base their mechanism of action by interaction with DNA and disruption of normal cellular processes.

Weight Discrimination Experienced Prior to Enrolling in a Behavioral Obesity Intervention is Associated with Treatment Response Among Black and White Adults in the Southeastern U.S.

Background: The current study evaluated the associations between history of weight discrimination and race on pre-treatment depressive symptoms, treatment session attendance, and weight loss among Black and White adults enrolled in a 16-week obesity intervention.

Methods: Participants (N = 271; mean BMI = 35.7 kg/m; 59% Black; 92% women) reported prior experiences of weight discrimination and completed the Center for Epidemiological Studies Depression (CES-D) Scale at baseline.

The COVID-19 pandemic and weight management: Effective behaviors and pandemic-specific risk factors.

Background: Obesity and comorbid conditions are associated with worse outcomes related to COVID-19. Moreover, social distancing adherence during the COVID-19 pandemic may predict weight gain due to decreased physical activity, increased emotional eating, and social isolation. While early studies suggest that many individuals struggled with weight management during the pandemic, less is known about healthy eating and weight control behaviors among those enrolled in weight loss programs.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.

Retrospective evaluation of thrombocytopenia and tumor stage as prognostic indicators in dogs with splenic hemangiosarcoma.

Objective: To identify physical examination and perioperative CBC variables in dogs with splenic hemangiosarcoma (HSA) that could aid in predicting progression-free interval (PFI) and overall survival time (OST) in affected dogs.

Animals: 70 client-owned dogs with splenic HSA treated with splenectomy and chemotherapy between September 2004 and October 2016.

Procedures: A retrospective search of the University of Minnesota Veterinary Medical Center medical records database was performed to identify dogs with splenic HSA treated with splenectomy and with evidence in the medical records of intent to treat with chemotherapy.

Associations Between Social Network Characteristics and Loneliness During Pregnancy in a Sample of Predominantly African American, Largely Publicly-Insured Women.

Objectives: Most research evaluating relationships between social network attributes and loneliness have focused on older adult and adolescent networks. The present study examines the relationships between social network size (number of relationships), social network density (whether named relationships are connected to one another) and maternal loneliness during pregnancy.

Methods: Eligible women were enrolled at the time of their dating ultrasound (between 8 and 12 weeks of gestation).

Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma.

We previously reported that eBAT, an EGF-targeted angiotoxin, was safe and it improved the overall survival for dogs with splenic haemangiosarcoma when added to the standard of care in a single cycle of three administrations in the minimal residual disease setting. Our objective for the SRCBST-2 trial was to assess whether increased dosing through multiple cycles of eBAT would be well tolerated and would further enhance the benefits of eBAT. Eligibility was expanded to dogs with stage 3 haemangiosarcoma, provided that gross lesions could be surgically excised.

Qualitative analysis of the Meals, Mindfulness, & Moving Forward (M ) lifestyle programme: Cultivating a 'safe space' to start on a 'new path' for youth with early episode psychosis.

Aim: The Meals, Mindfulness, & Moving Forward (M ) programme included nutrition education, hands-on cooking classes, mindfulness meditation practice, physical activities and facilitated group sharing. M was designed as a supplement to standard care for youths (age 15-25 years) with first-episode psychosis (FEP) who were clients of coordinated specialty care teams. M 's primary aim was feasibility by demonstrating high programme attendance; secondary aims included cardiometabolic measures.

Predicting program attendance and weight loss in obesity interventions: Do triggering events help?

Medical events that "trigger" motivation to lose weight may improve treatment outcomes compared to non-medical or no triggering events. However, previous findings include only long-term successful participants, not those initiating treatment. The current study compared those with medical triggering events or non-medical triggering events to no triggering events on attendance and weight loss during a weight management program.

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional.

Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low-grade sarcomas and remains the standard therapeutic approach. For advanced, high-grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches.

Use of computed tomography and radiation therapy planning software to develop a novel formula for body surface area calculation in dogs.

Background: Body surface area (BSA) can reflect metabolic rate that might normalize dosing of chemotherapeutics across widely variable weights within a species. The current BSA formula for dogs lacks height, length, and body condition.

Hypothesis: Computed tomography (CT) imaging will allow inclusion of morphometric variables in allometric modeling of BSA in dogs resulting in an improved formula for BSA estimation.

Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian adenocarcinoma with a bispecific ligand-directed toxin.

Purpose: Human sarcomas are rare and difficult to treat cancerous tumors typically arising from soft tissue or bone. Conversely, carcinomas are the most common cancer subtype in humans and the primary cause of mortality across all cancer patients. While conventional therapeutic modalities can prolong disease-free intervals and survival in some cases, treatment of refractory or recurrent solid tumors is challenging, and tumor-related mortality remains unacceptably high.

Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma.

Background: Chemotherapeutic options for the treatment of canine lymphoma have not changed in several decades necessitating the identification of new therapeutics to improve patient outcome. KPT-335 (verdinexor) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) that exhibited anti-tumor activity against non-Hodgkin lymphoma in a prior phase I study. The objective of this phase II study was to expand upon the initial findings and assess the activity and safety in a larger population of dogs with lymphoma.

Habit formation intervention to prevent obesity in low-income preschoolers and their mothers: A randomized controlled trial protocol.

Background: Low-income and racial/ethnic minority mothers and their young children are at increased risk for obesity. Lack of access to evidence-based obesity prevention and treatment services further contributes to these disparities.

Methods: This two-arm, parallel, randomized controlled trial (RCT) tests the effectiveness of a simple obesity intervention (HABITS) delivered as part of ongoing home visitation services, compared to the existing home visitation services without obesity-related content on mothers' and children's obesity risks.