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The spread of the gameable personal computers and game consoles resulted in the diversification of the video game genre, and from the 7th generation of the gaming consoles, the experience support of the games became largely enhanced. These games are now consumable owing to their resolution, the content, the plots are so fascinating so that they tie the gamer to the seat. Gamers seek experiences in the games. Still, such a special genre called roguelike was established, which is characterized by the constant termination of this world of experience in such a way that the gamer, as a results of the high level of difficulty, is obliged to start the game again and again. These new genre games are now leading titles of the new generation consoles, such as Demon’s Souls or the Returnal, gaining huge role in the introduction and sale of the new gaming console PS5. This study aims to reveal specifications of this genre, moreover, aims to describe through empirical research how gamers relate to it, and whether features of these games contribute to the devotion to them or lead to the disappointment from this world of experience.

Objective: S100A4 is a DAMP protein. S100A4 is overexpressed in patients with systemic sclerosis (SSc), and levels correlate with organ involvement and disease activity. S100A4−/− mice are protected from fibrosis. The aim of this study was to assess the antifibrotic effects of anti‐S100A4 monoclonal antibody (mAb) in murine models of SSc and in precision cut skin slices of patients with SSc. Methods: The effects of anti‐S100A4 mAbs were evaluated in a bleomycin‐induced skin fibrosis model and in Tsk‐1 mice with a therapeutic dosing regimen. In addition, the effects of anti‐S100A4 mAbs on precision cut SSc skin slices were analyzed by RNA sequencing. Results: Inhibition of S100A4 was effective in the treatment of pre‐established bleomycin‐induced skin fibrosis and in regression of pre‐established fibrosis with reduced dermal thickening, myofibroblast counts, and collagen accumulation. Transcriptional profiling demonstrated targeting of multiple profibrotic and proinflammatory processes relevant to the pathogenesis of SSc on targeted S100A4 inhibition in a bleomycin‐induced skin fibrosis model. Moreover, targeted S100A4 inhibition also modulated inflammation‐ and fibrosis‐relevant gene sets in precision cut SSc skin slices in an ex vivo trial approach. Selected downstream targets of S100A4, such as AMP‐activated protein kinase, calsequestrin‐1, and phosphorylated STAT3, were validated on the protein level, and STAT3 inhibition was shown to prevent the profibrotic effects of S100A4 on fibroblasts in human skin. Conclusion: Inhibition of S100A4 confers dual targeting of inflammatory and fibrotic pathways in complementary mouse models of fibrosis and in SSc skin. These effects support the further development of anti‐S100A4 mAbs as disease‐modifying targeted therapies for SSc. [ABSTRACT FROM AUTHOR]

Objectives Our previous studies have demonstrated that the Damage Associated Molecular Pattern (DAMP) protein, S100A4, is overexpressed in the involved skin and peripheral blood of patients with SSc. It is associated with skin and lung involvement, and disease activity. By contrast, lack of S100A4 prevented the development of experimental dermal fibrosis. Herein we aimed to evaluate the effect of murine anti-S100A4 mAb 6B12 in the treatment of preestablished experimental dermal fibrosis. Methods The effects of 6B12 were assessed at therapeutic dosages in a modified bleomycin-induced dermal fibrosis mouse model by evaluating fibrotic (dermal thickness, proliferation of myofibroblasts, hydroxyproline content, phosphorylated Smad3-positive cell count) and inflammatory (leukocytes infiltrating the lesional skin, systemic levels of selected cytokines and chemokines) outcomes, and transcriptional profiling (RNA sequencing). Results Treatment with 7.5 mg/kg 6B12 attenuated and might even reduce pre-existing dermal fibrosis induced by bleomycin as evidenced by reduction in dermal thickness, myofibroblast count and collagen content. These antifibrotic effects were mediated by the downregulation of TGF-β/Smad signalling and partially by reducing the number of leukocytes infiltrating the lesional skin and decrease in the systemic levels of IL-1α, eotaxin, CCL2 and CCL5. Moreover, transcriptional profiling demonstrated that 7.5 mg/kg 6B12 also modulated several profibrotic and proinflammatory processes relevant to the pathogenesis of SSc. Conclusion Targeting S100A4 by the 6B12 mAb demonstrated potent antifibrotic and anti-inflammatory effects on bleomycin-induced dermal fibrosis and provided further evidence for the vital role of S100A4 in the pathophysiology of SSc. [ABSTRACT FROM AUTHOR]

Shear thickening fluids (STF) are the materials of future to be used in numerous high-tech applications, including protection against impact. The researchers have investigated the effect of particle size and their shape on the impact resistance of fabrics using the fixed concentration of particles for STF preparation. In addition to particle shape and size, particle concentration may be an important factor that can contribute to the yarn-to-yarn friction and ultimately enhancing their impact resistance. The objective of this study is to compare the mechanical performance of para-aramid fabric treated with non-Newtonian STF made by using three diffrent percentages of silica particles. The para-aramid fabric was impregnated with STF and needle penetration, tensile strength, and energy absorption were checked in dry and wet state. The microparticles percentage in STF has a direct relation with the mechanical performance of samples. Fabric impregnated in STF with 7% of silica microparticles has higher tensile strength puncture resistance, and impact resistance, 1.4, 3 and 1.75 times respectively as compared to the fabric sample without STF. [ABSTRACT FROM AUTHOR]

The conducted work investigates the correlation between toughness characteristics and metal volume fraction in Fiber Metal Laminates (FMLs) subjected to tensile loads. Aerospace grade Al 7075-T6 was utilized as the varying metal alloy in the study. The metal alloy was combined with glass and carbon fiber layers to create different configurations of FMLs with varying stacking sequences. For better adhesion between metal and composite parts, aluminum layers were etched with sodium hydroxide and chromic-sulfuric acid solutions. The laminate sheets were prepared using the hand layup method which was followed by a vacuum bagging process. Specimens were cut and tested as per ASTM standard. Results of the experimentation showed that the aluminum volume fraction is directly related to the failure strain and modulus of toughness, however, inversely proportional to the stiffness characteristics of the laminates. The highest improvement of 111% in toughness parameter in comparison to pure composite laminate was reported. Finally, a comprehensive analysis on the type of fracture behavior in comparison to classical laminate theory was critically discussed. [ABSTRACT FROM AUTHOR]

Aims: ARIADNE aimed to assess the association between effects of sacubitril/valsartan and no sacubitril/valsartan treatment and clinical characteristics, functional capacity, and clinical outcomes (cause‐specific mortality and hospitalizations) in outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods: ARIADNE was a prospective European registry of 9069 patients with HFrEF treated by office‐based cardiologists or selected primary care physicians. Of the 8787 eligible for analysis, 4173 patients were on conventional HF treatment (non‐S/V group), whereas 4614 patients were either on sacubitril/valsartan treatment at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). We also generated a restricted analysis set (rS/V) including only those 2108 patients who started sacubitril/valsartan treatment within the month prior to or after enrolment. Results: At the baseline, average age of patients enrolled in the study was 68 years, and 23.9% (2099/8787) were female. At the baseline, the proportions of patients with New York Heart Association (NYHA) Class III symptoms were 30.9 (1288/4173), 42.8 (1974/4614), and 48.2% (1015/2108), in non‐S/V, S/V, and rS/V groups, respectively. After 12 months of treatment, the proportion of patients with NYHA Class III at baseline who improved to Class II was 32.0% (290/907) in the non‐S/V group vs. 46.3% (648/1399) in S/V group and 48.7% (349/717) in rS/V group. The overall mortality rate was 5.0 per 100 patient‐years. Rates of HF hospitalizations were high (20.9, 20.3, and 21.2 per 100 patient‐years in the non‐S/V, S/V, and rS/V groups, respectively). Emergency room visits without hospitalization occurred in 3.9, 3.2, and 3.9% of patients in the non‐S/V, S/V, and rS/V groups, respectively. Conclusions: This large HFrEF European registry provides a contemporary outcome profile of outpatients with HFrEF treated with or without sacubitril/valsartan. In a real‐world setting, sacubitril/valsartan was associated with an improvement of symptoms in patients with HFrEF compared with the conventional HFrEF treatment. [ABSTRACT FROM AUTHOR]

In the title compound, C12H15N3O3S, the 4-nitro and carbonyl groups are nearly coplanar with the benzene ring [C—C—N—O = −175.72 (14) and C—C—C—O = 172.75 (14)°]. The diethylcarbamothioyl group is twisted significantly from the plane of the benzene ring [C—N—C—N = −89.79 (15)°] with the S atom pointing away from each of these groups [C—N—C—S = 91.12 (14)°]. In the crystal, an intermolecular N—H...O hydrogen bond, which forms an infinite polymeric chain along the c axis, and weak C—H...O and C—H...S hydrogen bonds are observed.