Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic

Status quo after one year of COVID-19 pandemic in otolaryngological hospital-based departments and private practices in Germany

PURPOSE: The COVID-19 pandemic has affected healthcare systems worldwide. Data on the impact on otolaryngological clinics and private practices is sparse. This study aimed to present data on healthcare worker (HCW) screening, status of HCW, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic. METHODS: Otolaryngological private practices and hospital-based departments were surveyed nationwide using an online questionnaire. Participating facilities were recruited via the German Society for Oto-Rhino-Laryngology and the German Association for Otolaryngologists in Bavaria. RESULTS: 365 private practices (2776 employees) and 65 hospitals (2333 employees) were included. Significantly more hospitals (68.7%) than practices (40.5%) performed pre-interventional testing in their outpatients (p < 0.00). Most inpatients were tested in practices and hospitals (100.0% and 95.0%; p = 0.08). HCW screening was performed in 73.7% of practices and in 77.3% of hospitals (p = 0.54). Significantly more HCW infections were reported in private practices (4.7%) than in hospital (3.6%; p = 0.03). The private or home environment was the most frequent source of infection among HCW in hospitals (44%) and practices (63%). The use of PPE increased over the course of the pandemic. The number of procedures and the revenue decreased in 2020. CONCLUSION: The rate of pre-interventional testing among outpatients in otolaryngological practices is low and HCW infections were found to be more frequent in practices than in hospitals. In addition, a high rate of infections in otolaryngological HCW seems to stem from the private or home environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00405-021-06992-2

Magnetic resonance imaging of diverticular disease and its association with adipose tissue compartments and constitutional risk factors in subjects from a western general population

Purpose To determine the association of asymptomatic diverticular disease as assessed by magnetic resonance imaging (MRI) with adipose tissue compartments, hepatic steatosis and constitutional risk factors within a cohort drawn from a Western general population. Materials and Methods Asymptomatic subjects enrolled in a prospective case-control study underwent a 3 Tesla MRI scan, including an isotropic VIBE-Dixon sequence of the entire trunk. The presence and extent of diverticular disease were categorized according to the number of diverticula in each colonic segment in a blinded fashion. The amount of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) was quantified by MRI. Additionally, the degree of hepatic steatosis, indicated as hepatic proton density fat fraction (hepatic PDFF) was determined using a multi-echo T1w sequence. Constitutional cardiometabolic risk factors were obtained and univariate and multivariate associations were calculated. Results A total of 371 subjects were included in the analysis (58.2% male, 56.2±9.2 years). Based on MRI, 154 participants (41.5%) had diverticular disease with 62 cases (17%) being advanced diverticular disease. Subjects with advanced diverticular disease had a significantly higher body mass index (BMI) (BMI: 29.9±5.1 vs. 27.5±4.6, p&lt;0.001; respectively). Furthermore, all adipose tissue compartments were increased in subjects with advanced diverticular disease (e.g. VAT: 6.0±2.8 vs. 4.2±2.6 and SAT: 9.2±3.6 vs. 7.8±3.6, all p&lt;0.001, respectively). Similarly, subjects with advanced diverticular disease had significantly higher hepatic PDFF (4.9 [2.7, 11.4] vs. 6.1 [5.5, 14.6], p=0.002). Conclusion Advanced diverticular disease is associated with an increased volume of adipose tissue compartments and BMI, which may suggest a metabolic role in disease development. Key Points: Diverticular disease is associated with constitutional risk factors such as BMI. Excess of adipose tissue compartments and hepatic steatosis are associated with the prevalence of diverticular disease. Our results suggest a shared pathological pathway of cardiometabolic alterations and the prevalence of diverticular disease. MRI is feasible for the assessment of adipose tissue compartments, hepatic steatosis, and diverticular disease and allows identification of patients who are at risk but in an asymptomatic disease state. Citation Format Storz C, Rospleszcz S, Askani E etal. Magnetic Resonance Imaging of Diverticular Disease and its Association with Adipose Tissue Compartments and Constitutional Risk Factors in Subjects from a Western General Population. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1212-5669

The Impact of Team Learning Behaviors on Team Innovative Work Behavior

The aim of this review was to get insight into the impact of learning behaviors on innovative behavior in work teams. We addressed this issue by carrying out a systematic literature review. Thirty-one articles that reported studies on learning and innovation development in work teams were included in the review. By integrating the correlational findings of the original studies, we found that, at large, all investigated team learning behaviors had an effect on aspects of team innovative work behavior. Concerning specific team learning behaviors, sharing, team reflection, and team activity had the strongest impact on teams' engagement in innovation development. A central conclusion is that learning and innovation development are mutually dependent aspects of teamwork and that fostering one aspect will also be beneficial for the other. Based on our findings, we draw practical implications for fostering team development through enhancing learning behaviors and innovative work behavior in teams

Clinical anticancer drug development: targeting the cyclin-dependent kinases

Cell division involves a cyclical biochemical process composed of several step-wise reactions that have to occur once per cell cycle. Dysregulation of cell division is a hallmark of all cancers. Genetic and epigenetic mechanisms frequently result in deranged expression and/or activity of cell-cycle proteins including the cyclins, cyclin-dependent kinases (Cdks), Cdk inhibitors and checkpoint control proteins. The critical nature of these proteins in cell cycling raises hope that targeting them may result in selective cytotoxicity and valuable anticancer activity