Transition from Positive to Neutral in Mutation Fixation along with Continuing Rising Fitness in Thermal Adaptive Evolution

It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution

Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy

Impact of peritraumatic distress on posttraumatic stress disorder symptoms at 6 months after acute coronary syndrome: a prospective cohort study

Background: Posttraumatic stress disorder (PTSD) symptoms are known to occur after acute coronary syndrome (ACS). Peritraumatic distress has been indicated as a risk factor for PTSD and can be measured by the Peritraumatic Distress Inventory (PDI). However, no studies have yet measured peritraumatic distress after ACS using the PDI to predict PTSD. Objectives: This prospective cohort study examined the impact of peritraumatic distress on PTSD symptoms at 6 months after ACS. Methods: We used the PDI to assess peritraumatic distress in patients treated for ACS at a teaching hospital in Tokyo within 7 days after percutaneous coronary intervention. They were followed up over the next 6 months and were assessed for PTSD symptoms at 6 months using the Impact of Event Scale-Revised. The association between peritraumatic distress and PTSD symptoms was examined by multiple linear regression analysis. Results: The study enrolled 101 ACS patients, and 97 completed the follow-up assessment. PDI total score was an independent predictor of PTSD symptoms after adjustment for potential covariates (beta = 0.38; p < 0.01). Limitations: The results were obtained from a single teaching hospital and assessment of PTSD symptoms was questionnaire based. Conclusion: We provide the first evidence that PDI score can predict the development of PTSD symptoms in ACS patients. Assessing peritraumatic distress after ACS with the PDI may be useful for initiating early intervention against PTSD symptoms