Microsatellite unstable colorectal cancers (MSI+ CRCs) expressing PD-L1, respond to anti-PD-1 or anti-PD-L1 checkpoint blockade, whereas microsatellite-stable tumors do not respond the same. Our aim was to examine how the immune landscape relates to different aspects of the CRC’s biology, including neoepitope burden. We used TCGA data to stratify patients based on a cytolytic T-cell activity expression index and correlated immune cytolytic activity (CYT) with mutational, structural, and neoepitope features of each tumor sample. The expression of several immune checkpoints was verified in an independent cohort of 72 CRC patients, relative to their MSI status, using immunohistochemistry and RT-qPCR. CRC exhibits a range of intertumoral cytolytic T-cell activity, with lower cytolytic levels in the tumor, compared to the normal tissue. We separated CRC patients into CYT-high and CYT-low subgroups. High cytolytic activity correlated with increased mutational load in colon tumors, the count of MHC-I/−II classically defined and alternatively defined neoepitopes, high microsatellite instability and deregulated expression of several inhibitory immune checkpoints (VISTA, TIGIT, PD-1, IDO1, CTLA-4, and PD-L1, among others). Many immune checkpoint molecules (IDO1, LAG3, TIGIT, VISTA, PD-1, PD-L1 and CTLA-4) expressed significantly higher in MSI+ CRCs compared to MSS tumors. The expression of Treg markers was also significantly higher in CYT-high tumors. Both individual and simultaneous high levels of CTLA-4 and PD-L1 had a positive effect on the patients’ overall survival. On the reverse, simultaneous low expression of both genes led to a significant shift towards negative effect. Assessed globally, CYT-low CRCs contained more recurrent somatic copy number alterations. PD-L1 protein was absent in most samples in the independent cohort and stained lowly in 33% of MSI CRCs. PD-L1+ CRCs stained moderately for CD8 and weakly for FOXP3. CYT-high colon tumors had higher TIL load, whereas CYT-high rectum tumors had higher TAN load compared to their CYT-low counterparts. Overall, we highlight the link between different genetic events and the immune microenvironment in CRC, taking into consideration the status of microsatellite instability. Our data provide further evidence that MSI+ and CYT-high tumors are better candidates for combinatorial checkpoint inhibition.

The recent phenomenon of worldwide declining enrolments in engineering-related degrees has led to the gradual decrease in the number of engineering graduates. This decrease occurs at a time of increasing demand in the labour market for highly qualified engineers, who are necessary for the implementation of fundamental societal functions. This paper initially presents a survey of practices, which are currently employed by academic institutions in Europe in order to increase the attractiveness of their engineering studies. It then provides a detailed analysis of the benefits and proliferation of distance education to increase attractiveness of engineering studies based on a set of interviews. Results of this study, highlight a lack of a distance-learning dimension in the implementation of engineering studies in the European Area and discusses in detail ways in which distance learning can be utilised in engineering studies for the benefit of increasing their attractiveness. It has also been noted that institutions employing distance learning as part of their engineering studies, see this as highly beneficial for their students but also for the academic institution itself with some reservations in terms of the pedagogical adequacy of materials and instructional approaches used in distance education courses.

Wood-boring insect pests pose a significant threat to orchards, potentially leading to tree mortality. In the initial stages of infestation, no visible symptoms are apparent, but as infestations progress, rapid and widespread symptoms emerge, resulting in accelerated tree decline. Therefore, the timely detection of early wood-boring insect symptoms is critical for effective pest control, necessitating advanced methods such as remote sensing. In this study, remote sensing is utilized to identify the early symptoms of peach flatheaded root borer (PFRB) infestation in trees. A multispectral sensor attached to a UAV captures aerial imagery data from stone fruit and pome fruit orchards. These data undergo processing in photogrammetric and GIS programs, where NDVI, NDRE, and the tree crown area are computed. On-site observations confirm PFRB infestations. Various machine-learning models, including logistic regression (LR), artificial neural network (NN), random forest (RF), and extreme gradient boosting (XGBoost), are compared using mean NDVI values, mean NDRE values, crown area, mean temperature, and mean relative humidity. Mean NDVI values emerge as the most crucial factor for predicting PFRB infestation across all machine-learning models. The XGBoost model proves the most effective, achieving an accuracy of 0.85, with marginal variations from the other tested models.