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Background: The importance of undertaking physical activity for functioning of patients with multiple sclerosis (MS) has been repeatedly highlighted. However, the research on the role of physical activity in shaping the quality of life of patients with different disease duration is scarce., Objective: The aim of this study was to identify the mediating role of physical activity in the relationship between health locus of control (HLoC) and health-related quality of life in MS patients with varying disease duration., Methods: The study included 339 patients with MS from rehabilitation centers. The Multiple Sclerosis Impact Scale (MSIS-29) was used to measure health-related quality of life, physical activity was assessed by the Godin Leisure Time Exercise Questionnaire (GLTEQ) and the Health Locus of Control Questionnaire was used to measure HLoC., Results: Physical activity has been shown to be a mediator in the relationship between intrinsic HLoC and health-related quality of life particularly in patients with longer disease duration. Intrinsic HLoC was positively associated with engaging in physical activity, which in turn was positively associated with the physical component of quality of life in patients with longer (indirect effect: β = -0.077, p < 0.05) and moderate (β = -0.040, p < 0.05) duration of illness., Conclusion: The results highlight the importance of psychological resources for undertaking quality-of-life-related physical activity by MS patients with long disease duration. Particularly important here is the internal HLoC, which promotes physical activity that increases the chance of a high quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Regulatory Theory of Temperament distinguishes two traits involving the time course of responses and four relating to how energy is distributed and stored. This theory enables the presentation of entire structures of temperament traits and it is relevant for assessing an individual's ability to process stimulation and influence their performance during competitions. In our cross-sectional study, these structures are examined in relation to the offensive, defensive, and comprehensive effectiveness of an individual player's actions., Methods: The study included 91 football players aged between 20 and 31 years, who had approximately 10 years of training experience. The Formal Characteristics of Behavior - Temperament Inventory was utilized to assess temperamental traits, while a simulation game was employed to evaluate the effectiveness of each individual player's actions., Results: Research demonstrated that football players possessing a temperament structure that is closely aligned harmonized structure with a high capacity to process stimulation showed higher levels of individual efficacy in attack, defence, and comprehensive effectiveness of performance compared to football players with a harmonized temperament structure but a low capacity to process stimulation., Conclusion: The obtained result emphasises the significance of specific temperament structures in terms of matching the individual's stimulation levels and the their ability to process it., Competing Interests: The 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 Bojkowski and Tomczak.)

Objective: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism., Design: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3 + Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction., Results: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3 + Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3 + Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3 + expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis., Conclusion: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This paper describes an application of a machine learning approach for parameter optimization. The method is demonstrated for the elasto-viscoplastic model with both isotropic and kinematic hardening. It is shown that the proposed method based on long short-term memory networks allowed a reasonable agreement of stress-strain curves to be obtained for cyclic deformation in a low-cycle fatigue regime. The main advantage of the proposed approach over traditional optimization schemes lies in the possibility of obtaining parameters for a new material without the necessity of conducting any further optimizations. As the power and robustness of the developed method was demonstrated for very challenging problems (cyclic deformation, crystal plasticity, self-consistent model and isotropic and kinematic hardening), it is directly applicable to other experiments and models.

The main objective of this study was to determine whether hope for success mediates the relationship between personality and goal orientation in high performance and recreational athletes. The cross-sectional study included 289 high performance and recreational athletes of various sports (age: M = 20.34, SD = 1.86). To examine personality, we used the Big Five IPIP-BFM-20 questionnaire. To assess hope for success, we used the Hope for Success Questionnaire. The Task and Ego Orientation in Sport Questionnaire (TEOSQ) was employed to examine goal orientation. Hope for success significantly mediates the relationships between conscientiousness, extraversion, emotional stability, intellect, and task goal orientation in sport. Higher levels of these personality traits are related to athletes' higher hope for success, which, in turn, is positively related to their task orientation. Personality traits may underpin the hope for success that develops from childhood. This, in turn, appears to be an important component on which, combined with the positive interaction and support from coaches, a task goal orientation beneficial to sport can be shaped in athletes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tomczak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Achievement goal models have been successfully applied in sport. In recent years, a framework that has emerged in this area is the 3 × 2 approach, being a natural evolution of years of research into the issue of achievement goals. Nevertheless, it is essential to further validate the abovementioned approach and explore its psychosocial context. Hence, the purpose of this study was to validate the latest 3 × 2 achievement goal model among high-performance and recreational athletes using the Polish version of the 3 × 2 Achievement Goal Questionnaire for Sport (3 × 2 AGQ-S), and to determine the relationship between personality traits and achievement goals of athletes. The study included 413 athletes, with M = 20.62 and SD = 2.72. The 3 × 2 AGQ-S was used to assess achievement goals, the Big Five personality traits were assessed using the IPIP-BFM-20 questionnaire. The model of the Polish version of the 3 × 2 AGQ-S achieved a satisfactory fit to the data (CFI = 0.940, TLI = 0.923, RMSEA = 0.086, SRMR = 0.061). Cronbach's alphas for the subscales were: 0.77-0.96. High-performance athletes obtained higher achievement goals in task and self subscales than recreational athletes. Personality traits explained no more than 3% of variance of achievement goals in sport. Research involving the Polish version of the 3 × 2 AGQ-S supports the validity of the 3 × 2 model in sport among high-performance and recreational athletes. Nevertheless, the small relationships between the personality traits and achievement goals prompt searching for other psychosocial determinants of goals in sport., (© 2024. The Author(s).)

Purpose: An increasing number of studies support the beneficial relationship between physical activity and stress coping in people with multiple sclerosis (MS). However, there has been limited understanding of the variables that may influence the nature of this relationship. Therefore, based on the social-cognitive framework and previous research, we aimed to examine the association between the habitual physical activity of people with MS and their coping effectiveness. Furthermore, we sought to determine the extent to which self-efficacy acts as a mediator in this relationship, considering the level of disability as a moderator variable., Methods: In this cross-sectional study, a total of 351 people with MS participated. The participants were asked to complete several assessment tools, including the Mini-COPE Inventory for Measurement-Coping with Stress, the Generalized Self-Efficacy Scale, and the Godin Leisure-Time Exercise Questionnaire. Additionally, a neurologist assessed the severity of the disease using the Expanded Disability Status Scale. Information on the demographic and clinical characteristics of the participants was collected via a self-report survey. Two moderated mediation analyses were conducted as part of the study., Results: The study findings indicated a positive correlation between engagement in physical activity and self-efficacy among participants with high and medium disability levels. This, in turn, demonstrated a positive association with effective stress-coping strategies and a negative association with ineffective coping methods. In particular, a significant relationship was observed between involvement in physical activity and self-efficacy in participants with high disability, while it was not statistically significant in participants with low disability., Conclusion: Physical activity was associated with improved psychosocial functioning in people with high levels of disability caused by MS. This association may be attributed to factors such as increased self-efficacy and improved stress coping. However, the relationship between physical activity and psychosocial functioning was less evident in people with low disability caused by MS., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Published by Elsevier B.V.)

Antimicrobial peptides (AMPs) often display guanidinium functionalities, and hence robust synthetic procedures are needed to facilitate access to analogues with unnatural homologues of arginine (Arg = R). Initially, a resin-bound Arg/Pro-rich fluoren-9-yl-methyloxycarbonyl-protected fragment (Fmoc-RPRPPR) of the AMP oncocin (i.e., VDKPPYLPRPRPPRRIYNR-NH 2 ) was employed in a comparative on-resin assessment of commercial guanidinylation reagents head-to-head with the recently studied bis-Boc-protected triazole-based reagent, 1H-triazole-1-[N,N'-bis(tert-butoxycarbonyl)]-carboxamidine, which was synthesized by a chromatography-free procedure. This reagent was found to enable quantitative conversion in solid-phase peptide synthesis (SPPS) of peptides displaying homoarginine (Har) residues and/or an N-terminal guanidinium group. SPPS was used to obtain analogues of the 18-mer oncocin with single as well as multiple Arg → Har modifications. In addition, the effect of replacement of proline (Pro) residues in oncocin was explored by incorporating single or multiple trans-4-hydroxy-l-proline (Hyp) or 4,4-difluoro-l-proline (Dfp) residues, which both affected hydrophobicity. The resulting peptide library was tested against both Gram-negative and Gram-positive bacteria. Analysis of the minimal inhibitory concentrations (MICs) showed that analogues, displaying modifications at positions 4, 5 and 12 (originally Pro residues), had retained or slightly improved antimicrobial activity. Next, an oncocin analogue with two stabilizing l-Arg → d-Arg replacements in the C-terminal part was further modified by triple-replacement of Pro by either Dfp or Hyp in positions 4, 5, and 12. The resulting analogue displaying three Pro → Dfp modifications proved to possess the best activity profile: MICs of 1-2 µg/mL against E. coli and Klebsiella pneumoniae, less than 1% hemolysis at 800 µg/mL, and an IC 50 above 1280 µg/mL in HepG2 cells. Thus, incorporation of bis-fluorinated Pro residues appears to constitute a novel tool in structure-activity studies aimed at optimization of Pro-rich AMPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that have influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study compared external training load (ETL) and its temporal changes across repetitions during a speed endurance production (SEP) training comprised of 1 × 1 short-bout, small-sided games (SSGs) in elite youth soccer players. Twenty U18 players were divided into two groups (SEP1 and SEP2) performing six 30 s and 45 s bouts of SSG (work-to-rest ratio 1:4) on a 10 by 15 m field. ETL was characterized by the total distance covered, Player Load, the total number of accelerations/decelerations, and their relative values (per minute). Significant overall decreases in the ETL parameter values across six repetitions in both SSG groups were observed relative to the measurement in the first set beginning in 3rd (SEP1) or 4th (SEP2) repetitions. Significant greater decreases in Player Load (F(5.90) = 2.99, p < 0.05, η P2 = 0.14), Player Load per minute (F(5,90) = 11.32, p < 0.001, η P2 = 0.39), total distance per minute (F(3.43,61.73) = 7.72, p < 0.001, η P2 = 0.30) and accelerations per minute (F(5,90) = 2.59, p < 0.05, η P2 = 0.13) were observed in the 30-s games than in the 45-s games. In conclusion, the use of SSGs in SEP training is associated with a decrease in the effectiveness of physical work performed across repetitions. In practice, due to the decrease in the measured ETL indicators already in the 3rd or 4th repetition (especially in the SEP1 group), the work-to-rest ratio could be increased from the applied 1:4 to 1:6., (© 2023. Springer Nature Limited.)

Background: The role of host immune system in carcinogenesis and response to treatment is increasingly studied, including predictive potential of circulating neutrophils and lymphocytes. The objective of the study was to evaluate the prognostic value of pre- and post-treatment neutrophil-to-lymphocyte (NLR) for treatment outcome in patients diagnosed with squamous cell carcinoma of head and neck (HNSCC) treated with definitive chemoradiation., Materials and Methods: Electronic medical records of patients were evaluated and NLR was calculated. Cox regression was used to assess the impact of selected variables on overall survival (OS), disease specific survival (DSS), progression free survival (PFS) and distant failure free survival (DFFS). Logistic regression was used to estimate odds ratios of complete response with NLR., Results: 317 patients' records were included in the study. Increases in both pre-and post-NLR were associated with decreased OS in univariable analysis [hazard ratio (HR): 2.26 (1.25-4.07), p = 0.0068 and HR: 1.57 (1.03-2.37), p = 0.035 respectively). Post-NLR remained significant for OS in multivariable analysis [HR: 1.93 (1.22-3.1), p = 0.005] as well as for unfavorable DSS [HR: 2.31 (1.22-4.4), p = 0.01]. Pre-treatment NLR and nodal status correlated with shorter DFFS in multivariable analysis [HR 4.1 (1.14-14), p = 0.03 and HR 5.3: (1.62-18), p = 0.0062, respectively]. Strong correlation of increased both pre- and post-NLR with probability of clinical tumor response (CR) was found [odds ratio (OR): 0.23 (0.08-0.6), p = 0.003, and OR: 0.39 (0.2-0.8), p = 0.01 respectively]., Conclusion: NLR evaluated before and post treatment was a strong predictor of unfavorable treatment outcome and can be used for risk evaluation and clinical decision about treatment and post-treatment surveillance., Competing Interests: Conflict of interests None declared., (© 2023 Greater Poland Cancer Centre.)

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown., Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages., Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice., Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC., Competing Interests: The 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 © 2023 Giannou, Kempski, Zhang, Lücke, Shiri, Zazara, Belios, Machicote, Seeger, Agalioti, Tintelnot, Sagebiel, Tomczak, Bauditz, Bedke, Kocheise, Mercanoglu, Fard-Aghaie, Giorgakis, Lykoudis, Pikouli, Grass, Wahib, Bardenhagen, Brunswig, Heumann, Ghadban, Duprée, Tachezy, Melling, Arck, Stringa, Gentilini, Gondolesi, Nakano, Thomson, Perez, Li, Mann, Izbicki, Gagliani, Maroulis and Huber.)

The alarming increase in the resistance of bacteria to the currently available antibiotics necessitates the development of new effective antimicrobial agents that are active against bacterial pathogens causing major public health problems. For this purpose, our in-house libraries were screened against a wide panel of clinically relevant Gram-positive and Gram-negative bacteria, based on which compound I was selected for further optimization. Synthetic efforts in a group of arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines, followed with an in vitro evaluation of the activity against multidrug-resistant strains identified compound 44 (1-(3-chlorophenyl)-3-(1-{3-phenyl-3-[3-(trifluoromethyl)phenoxy] propyl}piperidin-4-yl)urea). Compound 44 showed antibacterial activity against Gram-positive bacteria including fatal drug-resistant strains i.e., Staphylococcus aureus (methicillin-resistant, MRSA; vancomycin-intermediate, VISA) and Enterococcus faecium (vancomycin-resistant, VREfm) at low concentrations (0.78-3.125 μg/mL) comparable to last resort antibiotics (i.e., vancomycin and linezolid). It is also potent against biofilm-forming S. aureus and Staphylococcus epidermidis (including linezolid-resistant, LRSE) strains, but with no activity against Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa). Compound 44 showed strong bactericidal properties against susceptible and drug-resistant Gram-positive bacteria. Depolarization of the bacterial cytoplasmic membrane induced by compound 44 suggests a dissipation of the bacterial membrane potential as its mechanism of antibacterial action. The high antimicrobial activity of compound 44, along with its selectivity over mammalian cells (lung MCR-5 and skin BJ fibroblast cell lines) and no hemolytic properties toward horse erythrocytes, proposes arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines for development of novel antibacterial agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)