Search

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding of irAEs and develop effective treatment options, there is pressing need for preclinical models recapitulating the clinical settings. In this review, we describe current preclinical models and immune implications of ICI-induced skin toxicities, colitis, neurological and endocrine toxicities, pneumonitis, arthritis, and myocarditis along with their management. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the influence of demographic factors on the development of innovations in the regions of Russia. The relevance of the study is associated with the fact that the Russian economy is distinguished by the presence of a large number of various problems that impede the rapid activation of innovative mechanisms. Not every region has opportunities for an innovative breakthrough. The purpose of the article is to compare the Russian regions (Kalmykia, Buryatia) in terms of the characteristics of the main demographic processes and their influence on the innovative development of regions. The article analyzes the following demographic indicators: population size, birth and death rates, age structure, working-age population, etc. The main research methods are the comparative method, analysis of statistical information. Analysis of the data presented showed that complex demographic processes are taking place in the republics. High migration outflow of the population, high mortality rate, a decrease in the share of the working-age population, migration of the rural population — all this affects the demographic potential of the region and, accordingly, the indicators of innovation development.