OBJECTIVES CLIPPER2 was an 8-year, open-label extension of the phase 3 b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with juvenile idiopathic arthritis (JIA), categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS Participants with eoJIA (2-17 years old), ERA, or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA American College of Rheumatology (ACR) 30/50/70/90/100 criteriaand ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis Disease Activity Score (JADAS) ≤1. RESULTS Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 (n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 [78%] on active treatment); 84 (66%) completed 120 months' follow-up (32 [25%] on active treatment). One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates [events per 100 patient-years] of TEAEs (excluding infections/ISRs) decreased from 193 [173.81] in Year 1-9 [27.15] in Year 10; TE infections and serious infections also decreased. Over 45% of participants (N = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 17 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favorable. CLINICALTRIALS.GOV IDS CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).

ABSTRACT Lower fine motor performance in childhood has been associated with poorer cognitive development and neurodevelopmental conditions such as autism spectrum disorder, yet, biological underpinnings remain unclear. DNA methylation (DNAm), an essential process for healthy neurodevelopment, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm with childhood fine motor ability and further examined the replicability of epigenetic markers in an independent cohort. The discovery study was embedded in Generation R, a large population-based prospective cohort, including a subsample of 924 ~ 1026 European-ancestry singletons with available data on DNAm in cord blood and fine motor ability at a mean (SD) age of 9.8 (0.4) years. Fine motor ability was measured using a finger-tapping test (3 subtests including left-, right-hand and bimanual), one of the most frequently used neuropsychological instruments of fine motor function. The replication study comprised 326 children with a mean (SD) age of 6.8 (0.4) years from an independent cohort, the INfancia Medio Ambiente (INMA) study. Four CpG sites at birth were prospectively associated with childhood fine motor ability after genome-wide correction. Of these, one CpG (cg07783800 in GNG4) was replicated in INMA, showing that lower levels of methylation at this site were associated with lower fine motor performance in both cohorts. GNG4 is highly expressed in the brain and has been implicated in cognitive decline. Our findings support a prospective, reproducible association between DNAm at birth and fine motor ability in childhood, pointing to GNG4 methylation at birth as a potential biomarker of fine motor ability.

The aim of this research was to determine the effects of a six-week preparatory period on the development of speed and agility in female soccer players of “Emina” Women’s Soccer Team of Mostar (n=18), who competed in the Premier League of Bosnia and Herzegovina in the season 2021/22. In the research, variables were applied to determine the basic characteristics of female soccer players: Age (years), Height (cm), Mass (kg), BMI (kg/m2), to assess speed ability: Sprint 5m (s), 10m (s), 20m (s) and agility: 10x5 m test (s), Zig-Zag test (s) and 505 test (s). The average age of female soccer players was 21.27 ± 4.57 years, average height 167.2 cm ± 5.82 cm and average weight 60.4 kg ± 7.36 kg. The dependent samples T-test was run to determine the statistical significance of the differences in arithmetic means between the initial and final measurements. The reported results of the T-test showed that after the six-week preparatory period, the test subjects had a lower mass (t=3.027; df=17; sig.= 0.008; p≤ 0.05) and BMI (t=2.253; df=17; sig.= 0.038; p≤ 0.05). Statistically significant differences at the level of p≤ 0.05, after the program had been completed, were reported for the agility tests 10x5m (t=3.125; df=17; sig.=0.006) and 505 test (t=3.028; df=17; sig.= 0.008). In other variables, positive changes were reported, but they were not statistically significant at the p≤ 0.05 level. We concluded that the six-week preparatory period program produced statistically significant changes in the area of ​​agility and that the training should focus more on improving speed and speed endurance in the given sample of female football players.

Insufficient physical activity and sedentary lifestyle have exposed most of the population with chronicle diseases, to higher risk of infection of COVID-19, with extremely severe consequences and exhausting and long recovery after the illness. Regular physical activity, as one way of prevention and faster recovery from COVID-19, is an important priority for improvement health and quality of life in people. The aim of this paper is to determine the connection between regular physical activity of the population with the presence of symptoms and duration of recovery from COVID-19. Total number of subjects was 100 people of both genders (male 32 and female 68) of younger age (age: 30-44) without existing chronicle diseases and healed from COVID. Data of regularity of exercising, symptoms, and recovery period were obtained by survey of this study: Active group of subjects (A=53) in continuity at least 3 months, two times a week, 60 minutes and Inactive group (N=47), who never exercised, nor they are physically active. Chi-square test was used (χ2 test differences between groups), to determine differences of extensive frequencies. Results of the research showed that there are statistically significant differences between two groups (p0.001) on the behalf of group with active subjects, in terms of severity of symptoms of COVID-19 and their recovery lasted shorter than in inactive group of subjects. Study shows that regular physical exercise has significant impact on human body and is important factor of enhancing immune system, which enables faster recovery and easier dealing with symptoms of COVID-19.

Abstract Racism has implicit and explicit manifestations that perpetuate disparities and negatively influence patient-centered health outcomes. Subsequently, a list of action items was provided to assist medical schools in becoming anti-racist institutions. A deep subject matter knowledge, beliefs, and reflections were a driving force for the management of medical schools or faculty members involved in undergraduate and postgraduate medical education to move forward toward inclusion of anti-racism in traditional medical curriculum or adapting existing training modules on diversity, equity, and inclusion. This paper proposes twelve practical and specific tips for implementing and teaching anti-racism in medical education. These twelve tips elaborate on the proposed actions for leaders in undergraduate and postgraduate medical education, valuable for designing future curricula and educational activities.

ABSTRACT Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

PurposeThis paper explores how entrepreneurial culture (EC) and organizational learning (OL) determine the entrepreneurial orientation (EO) of new technology-based firms (NTBFs). These NTBFs are located in Isfahan Science and Technology Town (ISTT), Iran. These entities face substantial challenges in a highly-sanctioned economy, which makes adopting, acquiring or transferring new technologies daunting.Design/methodology/approachThis paper analyzes a sample of 200 NTBFs. The participants were trained chief executive officers and observed by applying pre-test and post-test designs. As a final step, empirical data were collected using questionnaires and analyzed accordingly. The structural equation modeling (SEM) with the partial least squares (PLS) approach was used by the SmartPLS2 software.Findings OL was found to mediate the relationship between EC and EO in the studied NTBFs. Additionally, the indirect effect of EC on EO and the direct impact of OL on EO were significant (=1.96). Therefore, this study focuses on selected NTBFs within Iran's particular and distinctive context.Research limitations/implicationsThis study has several limitations. These were the time consuming nature, the lack of cooperation by managers and the COVID-19 pandemic-related challenges. Nonetheless, the findings offer several important implications for practitioners, scholars and policymakers.Originality/valueThe paper sought to explore how EC and OL determine EO in Iranian NTBFs. It, thus, investigates the case of a highly-sanctioned context during the coronavirus pandemic, which imposed several basic and technological limitations on their practices.

This research examines the factors contributing to the exterior material degradation of subsea oil and gas pipelines monitored with autonomous underwater systems (AUS). The AUS have a role of gathering image data that is further analyzed with artificial intelligence data analysis methods. Corrosion and potential ruptures on pipeline surfaces are complex processes involving several competing elements, such as the geographical properties, composition of soil, atmosphere, and marine life, whose eflt in substantial environmental damage and financial loss. Despite extensive research, corrosion monitoring and prediction remain a persistent challenge in the industry. There is a lack of knowledge map that can enable image ausing an AUS to recognize ongoing degradation processes and potentially prevent substantial damage. The main contribution of this research is the knowledge map for increased context and risk awareness to improve the reliability of image-based monitoring and inspection by autonomous underwater systems in detecting hazards and early signs of material degradation on subsea pipeline surfaces.