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The complication of element design performance of artificial structures leads to the need for more detailed superstructure modeling, since simplified models don`t always allow taking into account deformation features of elements. In addition, during the building period, the actual stress-strain state of structures can be significantly influenced by factors that are difficult or impossible to account for at the design stage. Correct modeling of deformation of elements is one of the essential conditions for the prevention of emergencies during construction, maintenance or timely elimination of the consequences of such incidents with minimal losses. When performing this kind of work, attention should be focused on the most significant design parameters, which comprehensively reflect the nature of the structure operation. This will make it possible to effectively carry out control and promptly make appropriate adjustments to the building process, if it is necessary. The article describes an example of the simplified model modernization to more fully match its actual deformation and the experience of eliminating the consequences of emergency that arose during erection of unique bridge. Thus, the importance of adapting the computational model to the actual nature of the engineering design is confirmed.

Introduction: Osteoarthritis (OA) is a progressive degenerative disease of synovial joints which is highly prevalent in dogs and results in lameness, loss of joint function and mobility, chronic pain, and reduced quality of life. Traditional OA management consist of non-steroidal anti-inflammatory drugs and remains challenging because of significant side effects, thus there is an urgent need for new effective and safe therapeutics for OA., Methods: Here we present the results of our one-arm open-label pilot clinical study of our novel biologics, a DNA plasmid encoding SQSTM/p62, in 17 companion dogs suffering from OA. The dogs were injected intramuscular with p62-plasmid once a week for 10 weeks, and pain relief was measured using the CBPI (canine brief pain inventory) validated scale. Assessment by the owners was done weekly. The 11 parameters of CBPI are grouped in three major domains: pain severity score (PSS), pain interference score (PIS) and overall impression of the quality of life (QoL)., Results: Treatment with the p62-plasmid improved all 11 parameters of CBPI as well as PSS, PIS and QoL: mean PSS score after the treatment decreased from 5.25 to 3.25, PIS score - from 7.0 to 3.27, and number of dogs with excellent and good QoL due to treatment increased from 1 to 12. Overall, the treatment success rate (i.e. a reduction ≥1 in PSS and ≥ 2 in PIS) was 90%. Importantly, similar to our previous studies with dogs and humans, no significant side effects of the p62-plasmid during the whole treatment period were observed., Discussion: We believe that anti-inflammatory effects of the p62-plasmid, which we described in our previous works, may play an important role in observed clinical benefits and it is worthy of further studies as a novel OA treatment modality.

Background: The purpose of this trial is to evaluate the safety and efficacy of ELENAGEN, a novel anticancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine (GEM) in patients with advanced platinum-resistant ovarian cancer., Methods: This open-label prospective randomized study with two arms. GEM (1000 mg/m 2 ) on days 1 and 8 every 3 weeks was administered in both arms: in the Chemo arm (n = 20), GEM was the only treatment, and in the ELENAGEN arm (n = 20), GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1, and criteria safety was assessed according to NCI CTCAE version 5.0., Results: According to the cutoff data, the median follow-up was 13.8 months. There were no serious adverse events related to ELENAGEN treatment. The median PFS was 2.8 and 7.2 months in the Chemo and ELENAGEN arms, respectively (p Log-Rank = 0.03). Notably, at the time of cutoff, 9 patients (45%) in the ELENAGEN arm did not progress, with the longest PFS recorded thus far being 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of ELENAGEN in patients with worse prognostic factors: high pretreatment levels of CA125 and progression after platinum-free interval <3 months., Conclusions: The addition of ELENAGEN to gemcitabine is effective in patients with platinum-resistant ovarian cancer, including those with a worse prognosis., Clinical Trial Registration: https://www.clinicaltrials.gov/study/NCT05979298, identifier NCT05979298, 2023-08-07., Competing Interests: VG and AS are employees of CureLab Oncology, which holds the intellectual property (IP) to the Elenagen treatment. The clinical trial registration was retrospective. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Krasny, Baranau, Polyakov, Zharkova, Streltsova, Filimonava, Siarheyeva, Kazlouskaya, Khorau, Gabai and Shneider.)

Objective: Recent studies have utilized innovative techniques to investigate the neural mechanisms underlying social and individual decision-making, aiming to understand how individuals respond to the world. Method : In this review, we summarized current scientific evidence concerning the neural underpinnings of social decision-making and their impact on social behavior. Results: Critical brain regions involved in social cognition and decision-making are integral to the process of social decision-making. Notably, the medial prefrontal cortex (mPFC) and temporoparietal junction (TPJ) contribute to the comprehension of others' mental states. Similarly, the posterior superior temporal sulcus (pSTS) shows heightened activity when individuals observe faces and movements. On the lateral surface of the brain, the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS) play a role in social cognition. Furthermore, the medial surface of the brain, including the amygdala, anterior cingulate cortex (ACC), and anterior insula (AI), also participates in social cognition processes. Regarding decision-making, functional magnetic resonance imaging (fMRI) studies have illuminated the involvement of a network of brain regions, encompassing the ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and nucleus accumbens (NAcc). Conclusion: Dysfunction in specific subregions of the prefrontal cortex (PFC) has been linked to various psychiatric conditions. These subregions play pivotal roles in cognitive, emotional, and social processing, and their impairment can contribute to the development and manifestation of psychiatric symptoms. A comprehensive understanding of the unique contributions of these PFC subregions to psychiatric disorders has the potential to inform the development of targeted interventions and treatments for affected individuals., Competing Interests: None., (Copyright © 2024 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo., Objective: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo., Design, Setting, and Participants: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted., Intervention: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy., Outcome Measurements and Statistical Analysis: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study., Results and Limitations: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26-0.55]; PSADT ≤6 mo, 0.41 [0.33-0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations., Conclusions: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability., Patient Summary: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)