Current influenza vaccines have modest efficacy. This is especially true for current live attenuated influenza vaccines (LAIV), which have been inferior to the inactivated versions in recent years. Therefore, a new generation of live vaccines may be needed. We previously showed that a mutation at PB1 residue 319 confers enhanced temperature sensitivity and attenuation in an LAIV constructed in the genetic background of the mouse-adapted Influenza A Virus (IAV) strain A/PR/8/34 (PR8). Here, we describe the origin/discovery of this unique mutation and demonstrate that, when combined with the PB2 N265S mutation of LAIV, it conveys an even greater level of temperature sensitivity and attenuation on PR8 than the complete set of attenuating mutations from LAIV. Furthermore, we show that the combined PB1 L319Q and PB2 N265S mutations confer temperature sensitivity on IAV polymerase activity in two different genetic backgrounds, PR8 and A/Cal/04/09. Collectively, these findings show that the PB2 LAIV mutation synergizes with a mutation in PB1 and may have potential utility for improving LAIVs.

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Background In this follow-up study to previous work, the authors survey the availability of key measures and resources pertaining to residency research in U.S. Accreditation Council for Graduate Medical Education–accredited dermatology residency programs, including potential policy changes following the COVID-19 pandemic. Objective The chief objective of this survey was to evaluate and compare dermatology programs’ resident research requirements and guidelines. Methods This cross-sectional study employed a 13-item survey administered online in early 2021 to assess the degree to which dermatology residency programs require and support their new physician graduates in scholarly research endeavors. Results A total of 32 program directors representing 30 dermatology residency programs (30 of 138 accredited programs contacted [22%]) responded to the survey. Almost all programs described quality improvement project requirements for residents and were able to provide funding for resident conference participation. Most programs also reported resident publication requirements and the availability of research electives. However, the vast majority did not have required research rotations or a formal mentorship program. The COVID-19 pandemic did not have a substantial impact on residency research requirements. Conclusion Our survey provides objective data about the current dermatology resident research requirements across the United States. These findings may prove valuable to prospective applicants, residency programs, and accrediting agencies in improving, advancing, and structuring dermatology residency guidelines and resources with the aim of encouraging new physician trainees to pursue research.

Cemiplimab, a monoclonal antibody directed against programmed death receptor 1 (PD-1), has shown promising results in cutaneous squamous cell carcinoma (cSCC). In a nonrandomized trial where cemiplimab 3 mg/kg was given every 2 weeks for up to 96 weeks, a 44% response rate was noted. This case series discusses 3 unique scenarios of patients with advanced cSCC treated with cemiplimab. The first case is of an end stage kidney disease (ESKD) patient with failed living donor kidney transplant who had developed recurrent cSCC despite several excisions and topical 5-flurouracil and acitretin therapy. He received 8 cycles of cemiplimab leading to resolution. This case serves as an example of the safety and efficacy of cemiplimab in a complex patient who is a kidney transplant recipient on hemodialysis. The second case describes an elderly gentleman with inoperable cSCC initially treated with radiotherapy who later received 9 cycles of cemiplimab for recurrent metastatic disease with excellent response. This case supports the safe and effective use of cemiplimab in an elderly patient. In the third case, cSCC presented itself as a large fungating mass that would have otherwise necessitated limb amputation and was successfully treated with 18 cycles of cemiplimab. This case highlights the dramatic response to cemiplimab obviating the need for surgical intervention and resulting in limb salvage.