Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation and destruction, leading to significant pain and disability. Adenosine deaminase (ADA) is identified as a biomarker for RA’s inflammatory process. This study aims to investigate the potential of flavonoids and phenolic acids to inhibit ADA activity (in silico) and evaluate their anti-inflammatory effects in a RA model (in vivo). Methods: The molecular docking study was conducted using YASARA Structure 19.12.14. software following the Auto Dock 4.2 protocol. A rat model with pristane-induced arthritis was used to test the anti-inflammatory effect of selected polyphenols. The consistency of the development of the rat model was evaluated through the following indicators artistic score, paw volume, and body weight. Quercetin was administered intragastrically at doses of 150 and 400 mg/kg over 15 days. The C-reactive protein (CRP) level in serum was measured with an automatic biochemical analyzer. Statistical analyses were performed using SPSS 29.0.2.0. Results: Molecular docking simulations showed flavonoids inhibited ADA activity with inhibition constants ranging from 0.012 mM to 0.190 mM. In the in vivo RA model, quercetin significantly reduced joint inflammation and serum CRP levels at a higher dose of 400 mg/kg. Conclusion: Quercetin shows promise as an anti-inflammatory agent for RA by targeting ADA, suggesting that flavonoid-rich plant extracts could enhance RA treatment.

Simulations have long been part of hardware-centric system domains. Similarly, architecture design is a common practice for complex industrial systems, which comprise many components that can be arranged in different layouts according to given requirements. Configuring simulation models and choosing the architecture design can be time-consuming activities. This paper presents a model-driven approach to automate the simulation configuration and architecture layouting engineering activities by leveraging model-driven optimisation techniques. The approach leverages a research solution, MOMoT (Marrying Optimisation and Model Transformations), an academic tool that combines search-based algorithms and model transformations. MOMoT is extended with two software modules, leveraging the Functional Mock-up Interface standard for simulation configuration and an architectural description language to design architecture layouts. Our solution is presented in the context of Volvo Construction Equipment's industrial use case, which is part of the European-funded project AIDOaRt. Our approach contributes to automated decision support to simulation and architecture design through model-driven optimisation while preserving the organisation's engineering practices.

This paper illustrates the utility of the heat kernel on Z as the discrete analogue of the Gaussian density function. The heat kernel on Z is the two-variable function KZ(t,x)=e−2tIx(2t) where Ix(2t) is a Bessel function, with variables x∈Z and t⩾0. Like its classic counterpart, KZ(t,x) appears in many mathematical and physical contexts and has a wealth of applications. Some of these applications will be reviewed here, and they concern Bessel integrals, trigonometric sums, hypergeometric functions and asymptotics of discrete models appearing in statistical and quantum physics. Moreover, we prove a new local limit theorem for sums of integer-valued random variables, obtain novel special values of the spectral zeta function of Bethe lattices, and provide a discussion on how e−2tIx(2t) could be useful in differential privacy.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published. They include the following: new faster simulation engines, accessible user interfaces for convenient workflows, and a vast array of simulation and analysis methods that encompass quantum mechanical, atomistic, and coarse-grained levels, as well as extensive coverage of force fields. In addition to providing the current snapshot of the CHARMM development, this review may serve as a starting point for exploring relevant theories and computational methods for tackling contemporary and emerging problems in biomolecular systems. CHARMM is freely available for academic and nonprofit research at https://academiccharmm.org/program.

Metamaterials, synthetic materials with customized properties, have emerged as a promising field due to advancements in additive manufacturing. These materials derive unique mechanical properties from their internal lattice structures, which are often composed of multiple materials that repeat geometric patterns. While traditional inverse design approaches have shown potential, they struggle to map nonlinear material behavior to multiple possible structural configurations. This paper presents a novel framework leveraging video diffusion models, a type of generative artificial Intelligence (AI), for inverse multi-material design based on nonlinear stress-strain responses. Our approach consists of two key components: (1) a fields generator using a video diffusion model to create solution fields based on target nonlinear stress-strain responses, and (2) a structure identifier employing two UNet models to determine the corresponding multi-material 2D design. By incorporating multiple materials, plasticity, and large deformation, our innovative design method allows for enhanced control over the highly nonlinear mechanical behavior of metamaterials commonly seen in real-world applications. It offers a promising solution for generating next-generation metamaterials with finely tuned mechanical characteristics.

Background - Organ donation and organ transplantation refer to a medical treatment approach that involves substituting a diseased or damaged organ or tissue in the human body with a healthy one. Progress in surgical techniques, immunology, and medical science has facilitated the advancement of transplant procedures. Nowadays, a wide range of organs, organ parts, and tissues can be successfully transplanted. Depending on the part of the body in question, the organs that are donated can come from a deceased donor or from a living person. Factors that influence the individual in a positive direction in terms of donating their organs have been presented in previous studies as the socio-economic status of informants, education level, being young, gender, donation to family members and social support. Aim - of this study is to synthesize qualitative and quantitative research on individuals' attitudes and decisions regarding organ donation, as well as the factors influencing these matters. Materials and Methods - A systematic search was conducted on the PubMed, Embase, CINAHL, and Web of Science databases for qualitative and quantitative literature regarding factors influencing an individual to donate their organs to other individuals. An inductive thematic analysis was conducted to generate themes and supporting subthemes. Fifteen studies were included. Results - The three main themes were: socioeconomic and cultural factors, dissatisfaction with, and mistrust of the healthcare system. Unspecified donors demonstrated a deep sense of different factors that influenced the individual to donate their organs to other individuals. Religious factors, fear and prejudices, gender differences, the influence of family members and not being treated well by healthcare professionals were only a few of the factors that were stated in the present study. Conclusion - The results of the present study show that there were many different factors that influenced an individual to decide whether to donate organs. Even though the individuals belong to different religions, come from different cultures, look at family relationships differently and have different degrees of knowledge, the opinions and factors that influence their decision regarding organ donation are the same. Healthcare should work more actively to inform and increase knowledge and consciousness about organ donation among people who are prospective donors. This can mean more information in several different languages, as well as where different religions stand on organ donation. Key words: Organ donation, transplantation, influence, factors, decision, review.

Metamaterials, synthetic materials with customized properties, have emerged as a promising field due to advancements in additive manufacturing. These materials derive unique mechanical properties from their internal lattice structures, which are often composed of multiple materials that repeat geometric patterns. While traditional inverse design approaches have shown potential, they struggle to map nonlinear material behavior to multiple possible structural configurations. This paper presents a novel framework leveraging video diffusion models, a type of generative artificial Intelligence (AI), for inverse multi-material design based on nonlinear stress-strain responses. Our approach consists of two key components: (1) a fields generator using a video diffusion model to create solution fields based on target nonlinear stress-strain responses, and (2) a structure identifier employing two UNet models to determine the corresponding multi-material 2D design. By incorporating multiple materials, plasticity, and large deformation, our innovative design method allows for enhanced control over the highly nonlinear mechanical behavior of metamaterials commonly seen in real-world applications. It offers a promising solution for generating next-generation metamaterials with finely tuned mechanical characteristics.

ABSTRACT Research suggests that serious games can be used as supplementary training tools for young people with complex mental health needs. This study aimed to co-produce a mobile-accessible serious game, ReGoal, in collaboration with young people (11–16 years) and an interdisciplinary team of academic experts and practitioners. ReGoal is aimed to serve as a supplementary tool for improving emotion regulation, goal-orientation, and executive functioning skills. This study consisted of three interlinked co-production phases. First, 122 participants, of which 34% had moderate to high conduct problems, completed an online survey about the role of gaming in managing their emotions. During the second phase, 16 young people attended three focus groups in which their lived experiences shaped the narrative of ReGoal. In the third phase, an online user survey gathered feedback from 72 young people playing the most recent prototype of ReGoal. The key findings suggest that young people valued playing ReGoal as a supplementary aid to improving their mood, increasing empathy towards peers and family, reducing anxiety, anger, and impulsivity, and understanding other people’s emotions. Future research should test the applicability and feasibility of ReGoal in reducing behavioural problems with clinical and non-clinical samples.

Adsorption for uranium removal from aqueous systems has been extensively studied, due to its many advantages. However, the great costs and complexity of many sorbent preparation methods are still restricting the progress. Hence, this research aimed to introduce a novel, simple and green method for enhancing Amberlite IR-120 properties for U(VI) removal. Adsorption process parameters were evaluated by batch method and sorbent was characterized before and after uranium adsorption by FTIR, SEM and EDS analysis. The results demonstrated that sorbent was effective for U(VI) removal at pH 5, 100 mg dose with 60 mg/L of U(VI) concentration within 40 min at higher temperatures. The removal efficiency was 87.7% and process was found feasible according to thermodynamic data. Kinetic modelling showed best correlation with pseudo-second order model (r2 = 0.999) and applied isotherms could all describe investigated process suggesting a complex mechanism of U(VI) uptake. Effect of interfering ions (Pb(II), Ni(II) and Co(II)) in a concentration of 45 and 60 mg/L decreased U(VI) removal to 45%. Additionally, AAS method confirmed that used sorbent has significant affinity towards Pb(II). Desorption study revealed successful uranium recovery in up to 3 cycles of sorption/desorption. The EDS analysis revealed the uranium presence with 4.7% and FTIR analysis revealed bands characteristic for stretching vibrations of O=U=O. Proposed mechanism involved U(VI) uptake via non-covalent interactions, inter/intra-molecular hydrogen bonding and intraparticle diffusion. Techno-economic analysis showed that with used preparation method 1 g of ASP costs 0.022 $. Hence, this study offers a novel method for sorbents properties enhancements.

For the successful prevention of chronic diabetic complications, it is crucial to identify novel etiopathogenetic factors that contribute to their development. We evaluated the association of hypothalamus pituitary adrenal axis activity (HPA) with the presence of chronic diabetic complications and glycemic control in 107 patients with type 2 diabetes and 29 healthysubjects, matched for age and sex. The study included 107 type 2 diabetic patients and 29 healthy control subjects who were hospitalized at the Internal Medicine Clinic of the University Clinical Center Tuzla. Patients with diabetes were evaluated for chronic complications and divided into two groups according to the presence (group 1, n = 57) and absence (group 2, n = 50) of complications. We determined the parameters of the HPA axis as follows: a level of 08 h cortisol and ACTH and a level of 09 hcortisol after a short dexamethasone test (DEX cortisol) and compared those among the groups. We determined the parameters of glycemic control and compared them with the parameters of the hypothalamus pituitary adrenal axis. In group 1, the values of cortisol were 454 (368–561), ACTH 12.6 (8.7–23), and DEX cortisol 37.5 (23-52), significantly higher compared to group 2 [320 (230–387), 7.9 (3.3–16.4), 26 (22–36), p <0.05, and higher compared to healthy subjects [312 (233–342), p = 0.001, 12 (6–16.7), p = 0.1, 24 (19–29), p = 0.126, respectively]. Evaluating the parameters of glycemic control, we found a higher HbA1C in group 1, 7.9 (6.55-9.45) compared to group 2, 7.5 (5.97-10), p = 0.498, while correlation analyses showed a significant positive relationship between HbA1C and cortisol (R = 0.242, p = 0.012). CONCLUSION: Patients with type 2 diabetes have HPA axis dysfunction. Higher cortisol levels are associated with poor glycemic control and the presence of diabetic complications. To better understand the etiology and provide practical solutions for addressing this issue, additional studies are required.

BACKGROUND AND OBJECTIVES: Despite advances in cranial base techniques, surgery of the sellar and parasellar regions remains challenging because of complex neurovascular relationships. Lesions within this region frequently present with progressive visual deterioration caused by distortion and compression of the optic chiasm and nerves. In addition to the direct mass effect from mechanical forces acting on the optic apparatus, these lesions alter blood supply and reduce vascular perfusion, prompting surgical treatment to remove the lesion, alleviate compression, and improve blood flow to the optic nerve. We sought to describe a 2-stage, 4-by-4-step approach, broken down and described as a “four-by-four” technique for optic apparatus decompression and a wide approach to different sellar and parasellar lesions. METHODS: We describe the operative nuances and key anatomic points in the microsurgical removal of sellar and parasellar lesions. The technique is illustrated with examples of different cases with pre- and follow-up MRI imaging and a brief overview of visual outcomes. RESULTS: The described technique has been demonstrated in various lesions in 5 patients. Patients presented with bilateral visual loss in 4 (80.0%) cases and with unilateral visual loss in 1 (20.0%) case. Improvement in visual function was noted in all cases, confirmed with visual acuity and visual field testing. DISCUSSION: The transcranial approach (“from above”) remains an important surgical option for patients with excellent exposure and visualization of the sellar and parasellar regions. It permits early access to the optic canal for careful microsurgical decompression and relaxation of the optic nerve to preserve and improve its microvascularization and ultimately vision. CONCLUSION: The authors augmented the 2-stage, 4-by-4-step technique of decompression with elaborate illustrations of diverse sellar and parasellar lesions to demonstrate the versatility of this approach.

Background: The adipose-derived stromal vascular fraction (SVF) plays a crucial role in regenerative medicine owing to its regenerative and immunomodulatory properties. However, the effective utilization of SVF in therapeutic applications requires careful consideration of storage conditions to maintain cell viability. Methods: We conducted a research on 43 patients of different ages and sexes who were older than 18 years. This study explored the impact of different temperatures (‐80, ‐20, and 4 °C) on SVF storage in platelet-poor plasma for 1 and 6 months. SVF extracted using a semi-UNISTATION™ system was subjected to rigorous analysis of cell count and viability using a LUNA-STEM™ Dual Fluorescence Cell Counter. Results: The results indicated a significant correlation between the storage conditions and SVF viability. Notably, storing SVF at 4 °C demonstrated the highest cell viability and count, while ‐80 °C storage exhibited the least favorable outcomes. This study emphasizes the importance of minimizing storage time to preserve SVF viability, as evidenced by a decline in both cell count and viability over a 6-month period. Comparisons with the existing literature underscore the need for precise protocols for SVF storage, with considerations for temperature and cryoprotective agents. These findings provide valuable insights for developing optimal SVF storage protocols to enhance therapeutic outcomes and reduce the need for repeated adipose tissue harvesting. Despite the limitations of the study, such as the use of a cell counter instead of flow cytometry, the results establish the foundation for further research on refining SVF storage methods. Conclusion: The ideal storage temperature is from 4 °C, while the length of storage time inversely affects the viability of SVF; the longer the storage time, the lower the number and the viability of SVF cells, regardless of the temperature at which they are preserved.

Background Distal occlusions associated with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction, <eTICI 3) may not reperfuse spontaneously and thus prompt ischemia (ie, persistent hypoperfusion). We aimed to assess whether the recently reported Distal Occlusion Tracker (DOT) sign on immediate non-contrast post-interventional flat-panel detector computed tomography (FPDCT) is associated with persistent hypoperfusion. Methods Retrospective registry analysis of patients undergoing endovascular therapy between July 2020 and December 2022, with available immediate post-interventional FPDCT and 24 hours follow-up perfusion imaging. Persistent hypoperfusion was defined as a perfusion deficit at 24 hours directly corresponding to the area of incomplete reperfusion on final angiography run. The DOT sign was defined as a punctiform or tubular hyperdense signal increase on FPDCT indicative of a residual occlusion. Association between the DOT sign (present/absent) with the occurrence of persistent hypoperfusion and poor outcome (modified Rankin scale (mRS) score 3–6) was evaluated using logistic regression analysis. Results Of 292 patients included (median age 73 years; 47% female), 209 had incomplete reperfusion. Among patients with incomplete reperfusion, 61% had a present DOT sign and 46% had persistent hypoperfusion. In the overall cohort, but also within each eTICI stratum, a present DOT sign was associated with persistent hypoperfusion on 24±12 hours follow-up perfusion imaging (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 2.0 to 12.3 for patients with eTICI 2 a-2c). A present DOT sign was also associated with poor outcome (aOR 2.6, 95% CI 1.1 to 6.2). Conclusion Patients with <eTICI 3 and a present DOT sign have a higher likelihood of persistent hypoperfusion and might constitute a subgroup that could particularly benefit from additional reperfusion attempts.

Abstract Avoidable disasters are both saddening and baffling. In 2022, 159 people, mostly in their 20s, and 30s were crushed to death in Itaewon’s narrow alleyway amid South Korea’s first pandemic-restrictions-free Halloween celebration. What is particularly sobering about this tragedy is that although many people called police hotlines as crowds became cramped and static, their calls went unheeded for hours. Rather than order independent investigations into the catastrophe (as of January 2024), the President of South Korea at the time focused on superficial issues such as asking the public to refer to the disaster as an “accident” (which it was not, it was an avoidable disaster) and the casualties as “the dead” (who are casualties indeed, instead of victims of a preventable tragedy). In this paper, we examine how officials’ complacency about public health and safety dangers, ineffective disaster prevention, and preparedness systems, as well as the government’s chronic lack of prioritization of public health and safety may have contributed to the disaster. Furthermore, we discuss the importance of creating integrated public health and safety protection systems to prevent similar tragedies from happening.

Objective: Iris species are widely used in pharmaceutical and cosmetic applications owing to their high content of bioactive compounds with anti-inflammatory and antimicrobial properties. This study aimed to investigate the potential antibacterial effect of crude extracts (aqueous, 50% and 80% ethanol) of three Iris species ( I. pumila , while I. reichenbachii and I. illyrica are endemic) from Bosnia and Herzegovina against the multiresistant bacterial strain methicillin-resistant Staphylococcus aureus subsp. aureus ATCC 33591 (MRSA strain). Materials and Methods: The antimicrobial compounds in the crude extracts were identified using High-performance liquid chromatography (HPLC), and their effects on the MRSA strain were tested using agar well diffusion and broth microdilution method. The binding affinities were analysed using molecular docking simulations. Results: We identified bioactive targeted compounds in these extracts, mainly flavonoids named isorhamnetin, hesperidin, quercetin, fisetin, genistein, and kaempferol. Antibacterial assays showed that extracts of all three Iris species inhibited MRSA. The binding affinity analysis showed that isorhamnetin and hesperidin had the highest affinity scores, stronger (isorhamnetin) or the same (hesperidin) as the positive control ceftobiprole. Conclusion: This in vitro and in silico study showed that Iris species represent a valuable source of bioactive compounds that can be used against multidrug-resistant strains such as MRSA. The potential use of these agents in multiple drugs is warranted, and further evaluation for human application is needed.