Sergey I. Sologov

Background/Objectives: MEK inhibitors (selumetinib, mirdametinib) are the only approved class of targeted therapy for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN), producing partial responses in a substantial proportion of patients (up to 63.6% in adults; objective response rate 19.7% versus 5.4% with placebo in the KOMET trial). Responses, however, are rarely complete or durable, and in malignant peripheral nerve sheath tumor (MPNST) single-agent MEK inhibition is clinically ineffective. Mechanisms of escape from MEK inhibition in these tumors remain poorly characterized and are reported in the literature as isolated primary studies without an integrative analysis. The aim of this review was to systematize both the established molecular mechanisms of resistance to MEK inhibitors in PN and MPNST and the biologically plausible candidate mechanisms extrapolated from other RAS-driven malignancies. Methods: This is a narrative review. A structured search was performed in PubMed, PubMed Central, NCBI Bookshelf, and Scopus, supplemented by clinical practice guidelines and regulatory documents; it covered publications up to 31 May 2026 and was updated in August 2026. Ninety-six sources are cited, and their composition by publication type is reported; record counts at the intermediate screening steps were not maintained, and no PRISMA flow diagram is presented. Results: Mechanisms were classified within a convergent framework into six categories: reactivation of MAPK signaling within the cascade; parallel (bypass) reactivation through receptor tyrosine kinases and adjacent inputs; epigenetic and transcriptional rewiring; cell survival programs; the tumor microenvironment and immune evasion; and intratumoural heterogeneity. Each mechanism was then graded along two independent axes—the strength of evidence that it confers resistance in PN or MPNST (E1–E3) and its therapeutic tractability (T1–T3)—and annotated with the entity and model constituting its evidence source. Conclusions: Resistance to MEK inhibition in PN and MPNST is convergent rather than mechanism-unique. The principal limitation of the field is the near-absence of clinical resistance data from patients progressing on MEK inhibitors; prospective molecular monitoring, rational combination trials, and mechanism-stratifying biomarkers are the priorities.

Background/Objectives: Modern dentistry increasingly requires biomaterials that not only replace damaged tissues but also actively regulate healing processes, modulate inflammation, and provide controlled delivery of therapeutic agents under the complex physicochemical conditions of the oral cavity. This review aims to analyze the potential of PCHs, particularly methacryloyl gelatin (GelMA), as multifunctional platforms for drug delivery in dental applications. Methods: This review provides a structured narrative synthesis of the literature, focusing on the physicochemical, biological, and translational aspects of photocrosslinkable hydrogels in dentistry. Special attention was given to the key functional requirements for hydrogels used in dentistry, including adhesion in a wet environment, antimicrobial properties, and the ability to provide sustained and localized release of active compounds. Natural, synthetic, and semi-synthetic polymers were comparatively evaluated to justify the selection of GelMA as a leading platform due to its tunable mechanical properties, biocompatibility, and photopolymerization capacity. The review also analyzes mechanisms of drug release activation and provides a comparative assessment of commonly used photoinitiators, including Irgacure 2959, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and camphorquinone, with emphasis on their cytocompatibility with oral tissues. Results: Applications of these hydrogels in endodontics, periodontology, peri-implantitis therapy, and regeneration of bone and dental pulp are summarized. Conclusions: Overall, photocrosslinkable GelMA-based hydrogels (PC-GelMA) represent promising multifunctional platforms for localized drug delivery and regenerative strategies in modern dentistry.

Relevance. In current emergencies, rapid first aid remains critical for saving lives. First aid providers must possess practical skills, as well as demonstrate psychological preparedness critically associated with empathy. The study aim is to identify the relationship between cognitive and affective empathy, as well as the level of preparedness to provide first aid among the six-year medical students and residents. Methods. A cross-sectional online survey was conducted involving 154 students of Sechenov Medical University (46 sixyear students and 108 residents). We used Russian version of the Cognitive and Affective Empathy Questionnaire (QCAE) and the Psychological Preparedness to Provide Assistance to Victims in Emergencies were used. Statistical techniques involved non-parametric tests (Mann–Whitney U-test and Spearman’s rank correlation). Results and discussion. Neither the empathy level nor the preparedness to provide first aid showed any correlation with the tear of studies (p > 0.05). Cognitive empathy positively correlated with preparedness to provide first aid (ρ = 0.521; p < 0.001), while affective empathy showed a weak negative correlation (ρ = –0.274; p < 0.001). Cognitive empathy facilitates readiness to provide first aid, whereas high affective empathy may hinder effective action due to emotional distress. Conclusion. n order to improve first aid capacities among medical students, it is worth incorporating exercises and training into the curriculum to foster cognitive empathy and improve emotional regulation.

Background: Minimally invasive surgery is a key objective in modern medicine, contributing to a more favorable postoperative course. This study aimed to evaluate the effectiveness of laser-assisted surgery, specifically using a 2940-nm erbium (Er:YAG) laser, in the extraction of impacted mandibular third molars compared with conventional scalpel and rotary instrumentation, based on clinical, radiographic, and immunologic parameters. Aim: To assess the clinical efficacy of 2940-nm Er:YAG laser irradiation in the surgical removal of impacted mandibular third molars. Methods: The study was conducted at the Department of Oral Surgery of Borovsky Institute of Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University). A total of 60 patients meeting inclusion and exclusion criteria were randomly assigned to either the laser group (Er:YAG laser) or the control group (scalpel and rotary instruments). Postoperative evaluation included clinical parameters (postoperative pain, collateral soft tissue edema, and maximal mouth opening), radiographic assessment (bone regeneration time), and immunologic markers [tumor necrosis factor-alpha (TNF-α) and human beta-defensin 2 (HBD2)]. Results: Clinical findings demonstrated a more favorable postoperative course in patients treated with the Er:YAG laser, as evidenced by significantly lower levels of postoperative pain, reduced collateral soft tissue edema, and improved maximal mouth opening compared to the control group treated with rotary instruments and a scalpel (p 0.001). Radiologic findings indicated accelerated bone regeneration following the use of Er:YAG laser compared to conventional surgical methods. The expression levels of TNF-α in the buccal epithelium and attached gingiva were lower in the intervention group than in the control group, whereas the expression of HBD2 was higher in the intervention group. Conclusion: Analysis of clinical, radiological, and immunological findings demonstrated that the use of an erbium laser with a 2940-nm wavelength for the extraction of impacted mandibular third molars was more effective than the use of conventional cutting and rotary instruments.