Objectives/Hypothesis Human papillomavirus (HPV) is a highly stable DNA virus that causes disease in human organ systems, including the larynx and oropharynx. The treatment of HPV‐associated diseases with scalpels, lasers, and other surgical instruments has the potential to release infectious particles, placing healthcare workers at risk. The objectives of this study were to create a reproducible in vivo animal model of papillomavirus infectivity and to compare the infectivity of byproducts of surgically treated mouse papillomavirus (MmuPV1) warts. Study Design Animal study. Methods Nude laboratory mice (Mus musculus) with established MmuPV1 tail warts were treated with scalpel excision, potassium titanyl phosphate (KTP) laser ablation, and coblator treatment. Uninfected nude mice were challenged with surgical byproducts, including ablated and heated tissue, and surgical smoke products. The incidence and time course of the appearance of warts was recorded. Results There was rapid transmission of virus in mice challenged with scalpel‐treated warts, with 50% penetrance of infection at day 13 and 100% at day 32. For KTP‐treated warts, there was the slower development of infection (50% by day 35) but 100% penetrance by day 52. Coblator‐treated tissue reached 50% penetrance at day 59 and a maximum of 73% penetrance. Smoke plume captured during treatment with the KTP laser and coblator was highly infectious, as was the material captured in a laser filter. Conclusions MmuPV1 remains infectious in all modes of surgically treated tissue, and the smoke plume is capable of transmitting infection. Healthcare workers should use appropriate precautions to lower their risk of infection when treating papillomavirus‐associated diseases. Level of Evidence NA Laryngoscope, 130:712–717, 2020

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is an open access repository that collects the work of Arts et Métiers ParisTech researchers and makes it freely available over the web where possible. Abstract: This article presents a kansei design methodology. It is placed at the very beginning of the design process and aims to influence the following steps in order to improve the user's understanding and experiencing of the designed product. The experimentation combines in a subtle way the design thinking approach of learning by doing and the kansei engineering quantitative approach. The research presented is based on the results of a previous study that defined the semantic and emotional scope of future hybrid cars for European using visual stimuli. Building on this scope this kansei design methodology creates and assesses multisensory atmospheres is order to provide tangible direction composed of vision, touch, hearing and smell stimuli. From the cognitive and affective responses of the 42 participants we were able to detail 3 directions for future cars interiors that aim to enrich the styling design briefs and to influence the design strategies such as the management of the different grades. The research presented here was supported by the Kansei Design department from Toyota Motor Europe (TME-KD). This collaboration also brought an industrial context to it.

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Due to the crucial role that dendritic cells (DCs) play in uptaking antigens following vaccination and cross presenting these antigens for the activation of antigen-specific immunity, a strategy that can induce potent expansion and activation of cross-presenting DCs may serve as a potential strategy to enhance the efficacy of therapeutic and prophylactic vaccinations. Flt3L is a cytokine known to expand cross-presenting DCs, but is limited by its global distribution and short half-life in vivo. To overcome these shortcomings, we generated a novel immunostimulatory molecule by fusing Flt3L to Albumin; a protein known for its long half-life and trafficking to lymph nodes. Our results revealed that Albumin-Flt3L (Alb-Flt3L) retains Flt3L’s endogenous capabilities to increase total CD11c+MHCII+, CD11c+MHCII+B220+SiglecH+, and CD11c+MHCII+CD8a+ DC populations in vitro, and in vivo following a single injection, compared to Flt3L. Our data also demonstrates that following vaccination with whole Ovalbumin protein (OVA), Alb-Flt3L treated mice saw an increase in antigen-specific immunity, measured by OVA-tetramer-positive CD8+ T cells, CD4+ and CD8+ cells producing IFN-g following ex vivo restimulation, and serum OVA specific IgG2a. When vaccinated with HPV-associated antigen E7 as a long peptide that requires uptake and cross-presentation to effectively load on MHCI and subsequently activate CD8+ T cells, E7-specific T cell populations significantly increased in Alb-Flt3L treated mice compared to controls. Further investigation is underway to study the ability of Alb-Flt3L to enhance vaccination induced immune responses as well as to study the mechanism by which these phenomena occur.

Central to the long-term success of essentially all cancer treatment strategies is the generation of durable tumor specific cytotoxic CD8+ T cell immunity, which requires uptake and potent antigen cross-presentation by dendritic cells (DCs) since tumor cells do not efficiently present relevant CD8+ T cell epitopes. FMS-like tyrosine kinase 3 ligand (Flt3L) is a cytokine that expands and differentiates DC precursors to murine cross-presenting CD103+ and CD8a+ DCs, but the therapeutic potential of Flt3L is limited because of its short half-life and global distribution in vivo. We have overcome the described issues by generating a novel genetic fusion of Albumin (Alb) to Flt3L, named Albumin-Flt3L (Alb-Flt3L), since Alb has a long half-life and exhibits trafficking to the lymph node (LN) and tumor (TM) as a serum protein. The novel immunotherapeutic Alb-Flt3L fusion protein exhibits increased half-life measured by ELISA, selective accumulation in LN and TM by IVIS imaging compared to native Flt3L, and potently expands cross-presenting DCs with no detectable toxicities. Challenging mice with HPV-associated TC-1 and MC38 adenocarcinoma tumor model, Alb-Flt3L + targeted radiation therapy to release tumor antigen and enhance tumor immunogenicity is able to control tumor progression and extend survival. When analyzing the immune response in mice challenged with MC38 tumor, significant intratumoral neoantigen specific CD8+ T cell responses are seen by tetramer staining, suggesting that Alb-Flt3L expanded DCs are able to engender neoantigen specific T cells without additional peptide vaccination. The therapeutic potential, mechanism of action, and subsequent implications of Alb-Flt3L use are under further investigation.