HTLV-1 Hbz protein, but not hbz mRNA secondary structure, is critical for viral persistence and disease development.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently expressed in asymptomatic carriers and ATL patients, suggesting its importance in the development and maintenance of HTLV-1 leukemic cells. Our previous work found Hbz protein is dispensable for virus-mediated T-cell immortalization but enhances viral persistence. We and others have also shown that hbz mRNA promotes T-cell proliferation. In our current studies, we evaluated the role of hbz mRNA on HTLV-1-mediated immortalization in vitro as well as in vivo persistence and disease development. We generated mutant proviral clones to examine the individual contributions of hbz mRNA, hbz mRNA secondary structure (stem-loop), and Hbz protein. Wild-type (WT) and all mutant viruses produced virions and immortalized T-cells in vitro. Viral persistence and disease development were also evaluated in vivo by infection of a rabbit model and humanized immune system (HIS) mice, respectively. Proviral load and sense and antisense viral gene expression were significantly lower in rabbits infected with mutant viruses lacking Hbz protein compared to WT or virus with an altered hbz mRNA stem-loop (M3 mutant). HIS mice infected with Hbz protein-deficient viruses showed significantly increased survival times compared to animals infected with WT or M3 mutant virus. Altered hbz mRNA secondary structure, or loss of hbz mRNA or protein, has no significant effect on T-cell immortalization induced by HTLV-1 in vitro; however, the Hbz protein plays a critical role in establishing viral persistence and leukemogenesis in vivo

Interim Analysis of Attrition Rates in Palliative Care Study on Dignity Therapy

A routine threat to palliative care research is participants not completing studies. The purpose of this analysis was to quantify attrition rates mid-way through a palliative care study on Dignity Therapy and describe the reasons cited for attrition. Enrolled in the study were a total of 365 outpatients with cancer who were receiving outpatient specialty palliative care (mean age 66.7 ± 7.3 years, 56% female, 72% White, 22% Black, 6% other race/ethnicity). These participants completed an initial screening for cognitive status, performance status, physical distress, and spiritual distress. There were 76 eligible participants who did not complete the study (58% female, mean age 67.9 ± 7.3 years, 76% White, 17% Black, and 7% other race). Of those not completing the study, the average scores were 74.5 ± 11.7 on the Palliative Performance Scale and 28.3 ± 1.5 on the Mini-Mental Status Examination, whereas 22% had high spiritual distress scores and 45% had high physical distress scores. The most common reason for attrition was death/decline of health (47%), followed by patient withdrawal from the study (21%), and patient lost to follow-up (21%). The overall attrition rate was 24% and within the a priori projected attrition rate of 20%-30%. Considering the current historical context, this interim analysis is important because it will serve as baseline data on attrition prior to the outbreak of the COVID-19 pandemic. Future research will compare these results with attrition throughout the rest of the study, allowing analysis of the effect of the COVID-19 pandemic on the study attrition