Recent innovations in adaptive trial designs: A review of design opportunities in translational research.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of "adaptive" clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint.

Effects of Extended Cage Component Sanitation Interval on the Microenvironment, Health, and Gastrointestinal Microbiome of Rats ().

Washing and sanitizing rodent cage components requires costly equipment, significant personnel effort, and use of natural resources. The benchmark frequency for sanitation of individually ventilated caging (IVC) has traditionally been every 2 wk. In this study, we investigated the effects of extending this interval on the cage microenvironment, basic markers of health, and the gastrointestinal microbiota of rats.

Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers.

Background: While immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood.

Method: To better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs.

Characterization of a Jumping Stereotypy in Gerbils () and Assessment of Opaque Tubing Enrichment on Stereotypies and Breeding.

Mongolian gerbils can develop stereotypic behaviors, including corner digging. At our institution, gerbils also engage in repetitive corner jumping, which we sought to characterize as a potentially novel stereotypy in gerbils. We then attempted to mitigate this behavior by mimicking the natural habitat by adding intracage environmental complexity.

Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts.

Background: Antitumor immunity is highly heterogeneous between individuals; however, underlying mechanisms remain elusive, despite their potential to improve personalized cancer immunotherapy. Head and neck squamous cell carcinomas (HNSCCs) vary significantly in immune infiltration and therapeutic responses between patients, demanding a mouse model with appropriate heterogeneity to investigate mechanistic differences.

Methods: We developed a unique HNSCC mouse model to investigate underlying mechanisms of heterogeneous antitumor immunity.

Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15 Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( and loss-of-function mutations of tumor protein p53 (). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME).

Metaphylactic Antibiotic Treatment to Prevent the Transmission of to Immunocompromised Mouse Offspring.

Current methods for eradicating , such as depopulation, embryo transfer, and cesarean rederivation followed by cross fostering, are expensive, complex, and time-consuming. We investigated a novel method to produce immunocompromised offspring free of from infected NOD. Cg-PrkdcIl2rg/SzJ (NSG) breeding pairs.