Moreover, the high-risk group was characterized by increased infiltration of monocytes and macrophages M1, and decreased T cells CD8 and T cells follicular helper. High-risk group exhibited a higher TMB, and was much more sensitive to immunotherapy and chemotherapy. KLK6 and CSN1S1 expression and the prognostic prediction values were further validated in clinical samples. The derived TP53-associated signature is a specific and independent prognostic biomarker for LUSC patients, and could provide potential prognostic biomarker or therapeutic targets for the development of novel immunotherapies and chemotherapies. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Lactate dehydrogenase (LDH) levels are inversely related with response to checkpoint inhibitors. Elevated LDH levels are the product of enhanced glycolytic activity of the tumor and tumor necrosis due to hypoxia, the latter being associated with high tumor burden. In this review, we elucidate the effects of glycolysis and hypoxia on antitumor immunity and set forth ways to improve response to immunotherapy in cancer patients with elevated LDH levels. We discuss the current knowledge on combining immunotherapy with glycolysis inhibitors, anti-acidifying drugs, anti-angiogenic or cytoreductive therapy. © 2020 Radboudumc. Published with license by Taylor & Francis Group, LLC.A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both P non-linearity less then 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Triple-negative breast cancer is the most aggressive subtype of breast cancer and is difficult to treat. Breast cancer is considered to be poorly immunogenic and hence is less responsive to immunotherapies. We tested whether the oncolytic poxvirus CF33-hNIS-ΔF14.5 could modulate tumor immune microenvironment and make the tumors responsive to the immune checkpoint inhibitor anti-PD-L1. We found that virus infection causes the upregulation of PD-L1 levels on triple-negative breast cancer cells in vitro as well as in vivo in mice. In a mouse model of orthotopic triple-negative breast cancer, the virus was found to increase tumor infiltration by CD8+ T cells. Likewise, in mice treated with CF33-hNIS-ΔF14.5 high levels of proinflammatory cytokines IFNγ and IL-6 were found in the tumors but not in the serum. The levels of immune modulation were even higher in mice that were treated with a combination of the virus and anti-PD-L1 antibody. While CF33-hNIS-ΔF14.5 and anti-PD-L1 antibody failed to exert significant anti-tumor effect as a single agent, a combination of the two agents resulted in significant anti-tumor effect with 50% mice experiencing complete tumor regression when both agents were injected intra-tumorally. Furthermore, the 'cured’ mice did not develop tumor after re-challenge with the same cancer cells suggesting that they developed immunity against those cancer cells. Taken together, our study shows that CF33-hNIS-ΔF14.5 favorably modulates tumor immune microenvironment in triple-negative breast cancer model making them responsive to the immune checkpoint inhibitor anti-PD-L1, and hence warrants further studies to determine the clinical applicability of this combination therapy. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Despite considerable progress, the treatment of acute leukemia continues to be a challenge for a significant majority of patients. Using a well-characterized preclinical mouse model of acute promyelocytic leukemia (APL), we evaluated here the antileukemic efficacy of RT53, an anticancer peptide with potential immunological properties. Our results indicate that RT53 possesses a direct antileukemic effect, even at a late stage. We also demonstrate that a single injection of a vaccine consisting of leukemic blasts exposed to RT53, which induces the hallmarks of immunogenic cell death, was highly effective in preventing leukemia development in both prophylactic and therapeutic settings. The vaccine comprising RT53-treated APL cells generated long-term antileukemic protection and depletion experiments indicated that CD4 + T cells were of crucial importance for vaccine efficacy. Combined, our results provide the rationale for the exploration of RT53-based therapies for the treatment of acute leukemia. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Globally, CPD systems vary widely. In Japan, the Japanese Medical Association (JMA) is responsible for identifying content and developing education for its speciality practice physicians. The JMA was concerned about persistent low levels of participation in its CME activities and wanted to better understand the root causes. The analysis would provide an opportunity to restructure its programme informed by the needs of its practising clinicians. The JMA engaged a global education provider to conduct an independent analysis of its CME programme. Using a mixed-methods approach, the education provider conducted an on-line survey (N = 338) and held two in-person focus groups (N = 24) to better understand the perspectives of physicians in speciality practice. The on-line survey was sent to over 7,000 practising physicians throughout Japan. Respondents reflected a variety of medical and surgical specialities and length in clinical practice. They described factors that influenced or were barriers to participation in JMA-sponsored education. Respondents also suggested changes to the current model of CME in Japan and expressed an ongoing commitment to life-long learning and achieving the goals set forth in Japan’s vision for health care in 2035 Leading the World Through Health. Globally, medical associations are challenged with developing education that meets the needs of a diverse physician workforce. Improved understanding of the perspectives of its physician members and implementation of collaborations with speciality societies may be one strategy to improve quality and address healthcare population needs. Lessons learned from this analysis may help other medical associations with similar challenges. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.On September 13-14, 2019 the eighth annual Cologne Consensus Conference was held in Cologne, Germany. The two-day educational event was organised by the International Academy of CPD Accreditors, a network of colleagues dedicated to promoting and enhancing continuing professional development (CPD) accreditation systems throughout the world. The conference was planned in cooperation with an impressive group of organisations representing leading European and North American institutions the European Cardiology Section Foundation (ECSF), the Accreditation Council for CME (ACCME), the Royal College of Physicians and Surgeons of Canada, and Continuing Medical Education-European Accreditors (CME-EA). For the conference’s eighth iteration, Standards and Guidelines in Accredited CPD was chosen as the program topic and educational focus; a choice reflecting increasing international collaborations and an evolution towards consistency and standards across global accreditation systems. A specific list of domains and criteria (developed under a broader initiative already underway by the Academy) would serve as the core content around which the conference was planned. This conference report describes the initiative, the proposed standards to date, highlights of the Cologne Consensus Conference discussions and feedback, and the ongoing process of achieving consensus on the standards yet to be finalised. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Objective  The objective of this study was to perform a population-based estimation of the preterm birth (PTB) rate in regions surrounding Lilongwe, Malawi. Study Design  We partnered with obstetrician specialists, community health workers, local midwives, and clinicians in a 50 km region surrounding Lilongwe, Malawi, to perform a population-based estimation of the PTB rate during the study period from December 1, 2012 to May 19, 2015. Results  Of the 14,792 births captured, 19.3% of births were preterm, including preterm early neonatal deaths. Additional PTB risk factors were similarly prevalent including domestic violence, HIV, malaria, anemia, and malnutrition. Conclusion  When performing a population-based estimation of the rate of PTB, including women without antenatal care and women delivering at home, the 19.3% rate of PTB is among the highest recorded globally. This is accompanied by a high rate of risk factors and comorbid conditions.Honokiol is one of the main active components of Magnolia officinalis, and has been demonstrated to have multiple pharmacological activities against a variety of diseases. Recently, this phenolic compound is known to have antioxidant activity, but its mechanism of action remains unclear. The purpose of the current study was to evaluate the preventive effects of honokiol against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. The present study found that honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation. The inhibitory effect of honokiol on H2O2-induced apoptosis was associated with the up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, these results demonstrate that honokiol defends C2C12 myoblasts against H2O2-induced DNA damage and apoptosis, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS. © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.