Levels Of Activities Research Articles

Effects of Square Stepping Exercise on cognitive, physical, psychological, and group functioning in sedentary older adults: A center-based hybrid trial

BackgroundThe Square Stepping Exercise (SSE) is an exercise training program that integrates physical exercise and cognitive elements and can be conducted in a group setting. The potential of SSE in delaying cognitive decline in older adults is promising. However, the coronavirus pandemic has made it more difficult for older adults worldwide to exercise together in person. To address this issue, this study conducted a wholistic evaluation of the effects of a center-based hybrid SSE trial on cognitive, physical, psychological, and group functioning in sedentary older adults.MethodsA total of 93 older adults (19 men, 74 women) participated in the study. Fifty-eight participants (9 men, 49 women) completed center-based hybrid SSE sessions over 12 weeks under coronavirus pandemic circumstances, whereas other 35 participants in the control group maintained their current level of daily activities. Cognitive functions focused on executive functions assessed by the Stroop Color-Word Test (inhibition) and the Trail Marking Test (TMT) (set-shifting). Psychological and group functioning were assessed by the Subjective Vitality Scale and the Physical Activity Group Environment Questionnaire. Physical function was evaluated by measuring gait speeds. A repeated ANOVA was conducted on the measured variables separately for the intervention and control groups to focus on the change of participant’s performance over data collection points.ResultsOutcomes of the Stroop Color-Word Test and the TMT revealed that the hybrid SSE was highly effective in improving executive function. Stroop performance (correct trials) was significantly improved in the incongruent condition, as well as both TMT-A and -B over the intervention period in the intervention group. The hybrid SSE was also beneficial to improve physical (gait speed at usual pace and at the maximum pace) as well as psychological functioning (subjective vitality). Furthermore, SSE participants reported increased engagement with the SSE task, social communication, and increased bonding and closeness with their group members through the hybrid SSE.ConclusionsIn this study, hybrid SSE was found to be effective in enhancing cognitive, physical, psychological, and group functioning in sedentary older adults. The findings of this study are crucial to provide older adults with a safer and efficient option to exercise.

Circulating levels of potential markers of ischemic stroke in patients with the different forms of atrial fibrillation and chronic heart failure

Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings­ demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events. Keywords: angiostatins, atrial fibrillation, biomarkers, iNOS, ischemic stroke, MMP-9, VEGF

Activities of daily living, self-efficacy and motor skill related fitness and the interrelation in children with moderate and severe Developmental Coordination Disorder.

Children with Developmental Coordination Disorder (DCD) are diagnosed based on poor motor skills that impact their daily activities. However, this may also lead to lower predilection and participation in physical activities and a higher risk to develop health problems. To determine motor skill related levels in children with moderate and severe DCD and compare that to typically developing children (TD). The study also aimed to determine the level of activities of daily living (ADL) as reported by their parent and self-efficacy as reported by the children. Lastly, the relation of motor skill related fitness, ADL, and self-efficacy has been examined. A cross-sectional study has compared TD children (n = 105) and children with DCD (n = 109; 45 moderate DCD and 64 severe DCD) from elementary schools in Tunisia between 7 and 10 years of age. The DCDDaily-Questionnaire and Children's Self-perceptions of Adequacy in and Predilection for Physical Activity Questionnaire have been used to determine ADL and adequacy towards physical activity, respectively. The PERF-FIT has been used to measure motor skill related fitness levels. Large group differences (p = 0.001) were found for ADL and all domains of self-efficacy between TD and DCD children. However, ADL and self-efficacy were not different between moderate and severe DCD. Motor skill related fitness was significantly lower (p = 0.01) for children with DCD than TD children, and between children with moderate and severe DCD. The relation between self-efficacy and DCDDaily-Q was different in the two DCD groups. Slow motor learning was associated with lower perceived enjoyment in physical education in the moderate DCD group, and with lower perceived adequacy in physical education in the severe DCD group. Children with DCD participate and enjoy physical activity less than their peers. This combination of lower participation, lower predilection to physical activity and lowered motor skill-related fitness is a concern for the present and future health status of children with DCD.

Analisis Tingkat Resiko Kecelakaan Kerja pada Galangan Kapal Logistik di PT X dengan Metode HIRARC

Logistics companies are very important in managing materials for smooth operations. In this company, which specializes in logistics through ocean shipping, faces risks when carrying out tasks such as lifting logistics goods in containers, moving oil, coal, and machine tools. To minimize the possibility of accidents, is necessary to identify, analyze, and manage potential hazards using the HIRARC method. Risk assessment shows variations in risk levels for different activities and control efforts. Hazard control is carried out through measures such as being exposed to embers that cause blisters, which can be prevented by controlling them using complete personal protective equipment, falling from stairs can be prevented by routine inspection of the condition of the stairs, triggering fires in the combustion chamber can be prevented by providing training to oil pump operators, bumping heads can be prevented by wearing safety helmets, and Being crushed by goods can be prevented by neat arrangement of goods.

The influence of personality traits on engagement in lifelong learning

ABSTRACT Today, adult individuals must be able to continuously learn and adapt to the rapid changes occurring in society. However, little is known about the individual characteristics, particularly personality traits, that make adults more likely to engage in learning activities. Moreover, few studies have longitudinally and objectively investigated the influence of personality on engagement in lifelong learning throughout working age. This study therefore used longitudinal data (15 years) to examine which personality traits predicted level and long-term changes in learning activities among 1329 Swedish adults aged 30–60. The results from growth curve modelling showed that over the follow-up period, novelty seeking and self-transcendence were both positively related to overall level of engagement in learning activities, although not to rate of change. Regarding specific activities, novelty seeking was related to higher levels of engagement in attending courses, taking on new education, and making occupational changes, while harm avoidance was negatively related to the likelihood of changing occupation. The results of this study underscore the importance of considering personality in relation to engagement in lifelong learning activities. Insights from this study can potentially increase the likelihood of finding methods to promote lifelong learning, which can be beneficial for educators, policymakers, and companies.

A calmodulin-like protein PvCML9 negatively regulates salt tolerance

Calmodulin-like proteins (CMLs) are unique Ca2+ sensors and play crucial roles in response to abiotic stress in plants. A salt-repressed PvCML9 from halophyte seashore paspalum (Paspalum vaginatum O. Swartz) was identified. PvCML9 was localized in the cytoplasm and nucleus and highly expressed in roots and stems. Overexpression of PvCML9 led to reduced salt tolerance in rice and seashore paspalum, whereas downregulating expression of PvCML9 showed increased salt tolerance in seashore paspalum as compared with the wild type (WT), indicating that PvCML9 regulated salt tolerance negatively. Na+ and K+ homeostasis was altered by PvCML9 expression. Lower level of Na+/K+ ratio in roots and shoots was maintained in PvCML9-RNAi lines compared with WT under salt stress, but higher level in overexpression lines. Moreover, higher levels of SOD and CAT activities and proline accumulation were observed in PvCML9-RNAi lines compared with WT under salt stress, but lower levels in overexpression lines, which altered ROS homeostasis. Based on the above data, mutation of its homolog gene OsCML9 in rice by CRISPR/Cas9 was performed. The mutant had enhanced salt tolerance without affecting rice growth and development, suggesting that OsCML9 gene is an ideal target gene to generate salt tolerant cultivars by genome editing in the future.

Bisphenol A Exposure Interferes with Reproductive Hormones and Decreases Sperm Counts: A Systematic Review and Meta-Analysis of Epidemiological Studies.

Bisphenol A (BPA), an acknowledged endocrine disrupter, is easily exposed to humans via food packaging and container. However, a consensus has not been reached on the extent to which BPA exposure affects the reproductive system. We therefore conducted this systematic review and meta-analysis to elucidate the relationship between BPA exposure and male reproduction-related indicators. Up to October 2023, a comprehensive search was carried out in the PubMed, Embase, Cochrane and Web of Science, and 18 studies were ultimately included. β coefficients from multivariate linear regression analyses were pooled using a random effects model. The results showed that the urinary BPA concentration was negatively correlated with the sperm concentration (β coefficient = -0.03; 95% CI: -0.06 to -0.01; I2 = 0.0%, p = 0.003) and total sperm count (β coefficient = -0.05; 95% CI: -0.08 to -0.02; I2 = 0.0%, p < 0.001). In addition, BPA concentrations were associated with increased sex hormone-binding globulin (SHBG) levels, increased estradiol (E2) levels, and reduced biologically active androgen levels. However, the relationship between an increased risk of below-reference sperm quality and BPA exposure was not robust. This systematic review revealed that BPA exposure disrupts reproductive hormones, reduces sperm counts and may ultimately adversely affect male reproduction.

A sequential three-way risk sorting model with the cautionary principle under probabilistic linguistic environment

Risk assessment plays a crucial role in managing risks associated with systems, products and services. In practical risk assessment, the cautionary principle is widely adopted by individuals to prevent accidents, and the degree of caution varies with the risk level of potential hazardous activities (PHAs). Therefore, it is necessary to explore a sequential risk assessment model integrating the cautionary principle. To this end, we design an improved risk assessment model based on sequential three-way decision (STWD) model and cautionary principle. Firstly, a risk distance measure under probabilistic linguistic environment is proposed to effectively reflect varying degrees of caution when individuals analyzed PHAs of different risk levels. Then, a comprehensive risk weight optimization model is constructed on the consideration of the importance ranking and correlations of risk attributes. Subsequently, STWD and the as low as reasonably practicable (ALARP) principle are integrated to build the risk sorting model, and both the risk prioritization and classification of PHAs are obtained from the sequential risk sorting process. Finally, we verify the reliability of our proposed model through an example of a floating offshore wind turbine system. The findings validate the crucial role of cautionary principle in risk assessment.

Intergenerational priming by Trichoderma alleviates drought stress in barley

The escalating global climate anomalies and disruption of ecological equilibrium pose profound threats to agroecosystems and crop productivity. Drought stress, a prominent consequence of climate change, exert detrimental effects on plant physiology, thereby reducing crop yield. This study explores the implementation of Trichoderma-mediated defence priming in barley under drought stress. Through a comprehensive evaluation of encompassing morphological, stomatal, biochemical, and yield parameters, Trichoderma- primed barley is compared with non-primed barley under drought stress conditions. Our results revealed that Trichoderma-primed barley exhibits heightened tolerance to drought stress in comparison to non-primed barley. The improved stomatal characteristics indicate that Trichoderma priming enables the plant to better adapt to drought conditions. Biochemical analysis showed enhanced photosynthetic pigments and reduced MDA in primed barley under drought, suggesting that primed barley experiences less oxidative stress compared to non-primed barley. Additionally, Trichoderma-primed plants displayed heightened levels of both non-enzymatic and enzymatic antioxidant activities, aiding in ROS detoxification. Stress responses are activated upon encountering a triggering stimulus (drought stress), but not after Trichoderma priming. This means there was no wasteful diversion of resources towards resistance mechanisms in the absence of stressful situations, leading to enhanced yield for primed barley compared to non-primed barley under stressful conditions. Furthermore, our investigation into the heritability of priming effects in the succeeding generation demonstrates that the progeny of primed barley retains enhanced protection akin to their primed parents. In contrast the progeny of non-primed barley exhibits greater vulnerability under water-deficit conditions. The expression of the epigenetic regulator gene HvDME was more enhanced in primed barley and its subsequent generations than in non-primed barley. This research emphasizes the potential of Trichoderma priming as a cost-effective strategy to enhance barley production amidst climate change challenges. The priming defense approach offers an intelligent plant health management solution devoid of adverse environmental or yield-related implications. This discovery holds significant promise, particularly in regions with limited water resources where crops are highly susceptible to drought stress. The findings contribute to the advancement of sustainable and climate-resilient agriculture, offering insights for practitioners and policymakers aiming to address the adverse impacts of climate change on crop production.

Relationships between Resident Activities and Physical Space in Shrinking Cities in China—The Case of Chaoyang City

Shrinking cities suffer from a decreased level of resident activities. As a result, areas with low levels of resident activities may become breeding grounds for social issues. To ease and prevent social issues, it is important to deploy physical space optimisation strategies to effectively guide the distribution of resident activities in shrinking cities. To support the development of such spatial strategies, this paper introduces machine learning-based methods for analysing the nuanced non-linear relationship between resident activities and physical space in shrinking cities. Utilising dual-scale grids, this study calculates multi-source spatial elements, which are subsequently integrated with resident activity data to construct a gradient boosting decision tree model. It then analyses the weight of different spatial elements’ impacts on resident activities and their nonlinear relationships. The model proposed in this study demonstrates good precision in construing the relationship between resident activities and physical space. Based on the research findings, strategies for different types of spatial development in shrinking cities are drawn out. This paper advocates for the application of this analytical approach before conducting spatial planning in shrinking cities to maximise the effectiveness of spatial development in guiding resident activities.

Overexpression of Rhodiola crenulata glutathione peroxidase 5 increases cold tolerance and enhances the pharmaceutical value of the hairy roots

Rhodiola crenulata, a plant of great medicinal value found in cold high-altitude regions, has been excessively exploited due to the difficulty in cultivation. Understanding Rhodiola crenulata's adaptation mechanisms to cold environment can provide a theoretical basis for artificial breeding. Glutathione peroxidases (GPXs), critical enzymes found in plants, play essential roles in antioxidant defense through the ascorbate–glutathione cycle. However, it is unknown whether GPX5 contributes to Rhodiola crenulata's cold tolerance. In this study, we investigated the role of GPX5 in Rhodiola crenulata's cold tolerance mechanisms. By overexpressing Rhodiola crenulata GPX5 (RcGPX5) in yeast and Arabidopsis thaliana, we observed down-regulation of Arabidopsis thaliana GPX5 (AtGPX5) and increased cold tolerance in both organisms. Furthermore, the levels of antioxidants and enzyme activities in the ascorbate–glutathione cycle were elevated, and cold-responsive genes such as AtCBFs and AtCORs were induced. Additionally, RcGPX5 overexpressing lines showed insensitivity to exogenous abscisic acid (ABA), suggesting a negative regulation of the ABA pathway by RcGPX5. RcGPX5 also promoted the expression of several thioredoxin genes in Arabidopsis and interacted with two endogenous genes of Rhodiola crenulata, RcTrx2-3 and RcTrxo1, located in mitochondria and chloroplasts. These findings suggest a significantly different model in Rhodiola crenulata compared to Arabidopsis thaliana, highlighting a complex network involving the function of RcGPX5. Moreover, overexpressing RcGPX5 in Rhodiola crenulata hairy roots positively influenced the salidroside synthesis pathway, enhancing its pharmaceutical value for doxorubicin-induced cardiotoxicity. These results suggested that RcGPX5 might be a key component for Rhodiola crenulata to adapt to cold stress and overexpressing RcGPX5 could enhance the pharmaceutical value of the hairy roots.

Responses of nesting greater white‐fronted geese to oil development in the Arctic

AbstractOil and gas exploration and development is expanding across the Arctic Coastal Plain (ACP) of Alaska, USA. To examine the effects of industrial development on greater white‐fronted geese (Anser albifrons), we monitored nests and nesting behavior within a 4‐km2 study area within 4 km of gravel roads and pads during pre‐development, construction, and operation activities at a new oil development in the National Petroleum Reserve‐Alaska in 2013−2019. We examined distribution, incubation constancy, and nest survival in relation to distance to gravel roads or pads, year and status of development, presence of an ice road the previous winter, and land cover type. Nest density increased throughout the study period, which was consistent with surveys of this species in other regions of the ACP. There was no direct evidence that oil extraction infrastructure and the associated human activity adversely influenced the abundance, distribution, or daily nest survival of greater white‐fronted goose nests. Geese avoided nesting in the alignments of ice roads from the previous winter, and land cover type influenced their nest distribution. Nest age and incubation constancy were important predictors of daily nest survival. The incubation constancy of successful nesters (98.5 ± 0.1% [SE]) was significantly greater than for failed nesters (94.7 ± 0.6%) for all years combined and tended to be greater during the pre‐construction and construction years of 2014 and 2015, compared to when oilfield operations began in 2017 and 2019. Greater‐white fronted geese appear to be tolerant of some levels of industrial activities and the presence of gravel roads did not have a significant effect on nest distribution, incubation constancy, or nest survival. We recommend, however, that indirect effects from ice roads should be explicitly considered in impact assessments because white‐fronted geese avoid nesting in the footprints of the previous winter's ice roads and pads.

Innovation, researcher and creativity: A complex indicator for territorial evaluation capacity

Innovation, research, and creativity are crucial elements to guarantee countries' competitiveness and promote sustainable economic and social progress. The evolution of these elements influences and guides the strategic choices of policymakers to develop potential improvements. Measures of economic and social well-being are widely studied in the literature as essential tools for understanding and promoting more equitable, sustainable and inclusive social and economic progress; they provide a more complete and holistic view of people's well-being, enabling more informed policies and decisions that meet a country's needs.Investments in scientific research and innovation, the human capital available for knowledge economy processes and the diffusion of Information and Communication Technologies are fundamental elements of social well-being and economic development. The literature highlights the need for indicators that analyze the efficiency levels of innovation, research and creativity activities to guide policies that promote better resource use. In light of this, the study aims to formulate a composite index that summarizes the "Innovation, research and creativity" dimension of the Equitable and Sustainable Wellbeing (BES) Report. The analysis focuses on Italy and provides a detailed measure of the situation in research, creativity, and innovation, which are indirect determinants of well-being but fundamental to social and economic progress. The authors propose an index for classifying Italian Regions by utilizing indicators from the BES and the Agenda 2030 and employing hierarchical clustering analysis associated with an algorithm based on the P2 distance method.From a broader perspective, the work provides a robust tool that combines various measures into a single value. This offers a more comprehensive view of a complex situation and allows for the identification of general trends or changes over time. Furthermore, this enables a more targeted assessment of goal achievement than analysing isolated individual variables.The results show the goodness and robustness of the proposed index. Therefore, the proposed index is a valuable tool capable of providing a comprehensive view of the situation, identifying trends, regional or national patterns, and information essential for governments to formulate strategies.

Effectiveness of agricultural extension models in food crop production in Cross River State, Nigeria

This study assessed the effectiveness of agricultural extension models in food crop production in Cross River State. Specifically, the study described the socio-economic characteristics of the respondents, identified the level of extension model activities in crop production and analyzed the effectiveness of agricultural extension models in the study area. A multi-stage random sampling technique was used in selecting respondents for the study. Data were collected using a structured questionnaire. Descriptive statistics such as frequency distribution, mean scores, percentages and standard deviation were used for the study. The result showed that the respondents had a mean age of x ̅ = 5. Majority (77.00%) of the respondents were married. Furthermore, the result of the socio economic characteristics of the respondents also showed that a negligible proportion (17.20%) of the respondents had no formal education. About 16.10% had primary level of education. A fair proportion (45.00%) had secondary level of education. Also, about 21.70% of the respondents had tertiary level of education. These implied that the respondents were educated. Educational attainment would make the farmers more responsible and responsive to agricultural extension models, programs and policies. The result also indicated that 79.50% of the respondents were farmers. These implied that farming was the major means of livelihood in the area. The result of distribution of respondents based on extension models available in the area showed that “training and visit” extension model was ranked first with standard deviation of 1.65; this means that the “training and visit” model of extension had a high level of acceptability in ensuring food crop production. Contact farmer model was ranked 2nd, with standard deviation of 1.28. This means that farmers had contact with fellow farmers faster than extension officers. In the same vein, video-based extension model was ranked 8th with standard deviation of 0.64. The result of the effectiveness of extension model revealed that mean (x ̅) of 3.58, 3.35, 3.49, 3.20 affirmed that agricultural extension models populated by extension officers are effective in food crop production in the study area. Similarly, individual persons oriented model such as mass media model with mean of x ̅ = 3.21 was very effective in food crop production. These results implied that agricultural extension models were effective in food crop production. The study concluded that the agricultural extension models are very effective and positively related to food crop production. Key words: Agriculture, Cross River, Effectiveness, Extension models, Food crop, Production

Assessment of Hepatoprotective and Antioxidant Effect of Acioa barteri Extract (ABE) in Alloxan-Induced Diabetic Rats

This study aimed to investigate the effects of Acioa barteri extract (ABE) on hepatocellular enzyme activity, hepatic function, and antioxidant stress indices in diabetic rats induced with alloxan. The antidiabetic effect of ABE was evaluated in six experimental groups: normal controls, diabetics untreated, diabetics treated with 200mg/kg, 400mg/kg, or 800 mg/kg ABE, and diabetics treated with 3 mg/kg Glibenclamide. ABE was orally administered to induce diabetes, and alloxan-monohydrate was intraperitoneally administered. Diabetic untreated rats exhibited significantly elevated levels of alkaline phosphatase, aspartate, and alanine transaminase activities, as well as higher concentrations of total bilirubin, conjugated bilirubin, and malondialdehyde. They also showed decreased levels of total protein, albumin, globulin, and protein-bound iodine, along with reduced antioxidant enzyme activity. In contrast, diabetic rats administered ABE demonstrated reduced hepatocellular enzyme activity and improved hepatic function. These rats exhibited increased levels of total protein, globulin, and albumin, as well as higher levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase activities, compared to diabetic untreated rats. The findings suggest that ABE may help prevent oxidative stress and improve hepatic functions in diabetic rats. ABE treatment led to decreased hepatocellular enzyme activity and improved hepatic function, along with increased antioxidant enzyme activities. These results highlight the potential of ABE as a therapeutic option for diabetes-induced liver dysfunction. Further research is warranted to explore its mechanisms of action and potential clinical applications.

How Citizens Meet the State: Police Contact, Trust, and Civic Engagement

This paper investigates the relationship between the police, the most visible street-level bureaucrat of local city governments, and citizen political attitudes and behaviors toward local city institutions. We introduce a holistic conceptualization of police-citizen contact and examine how each type impacts citizen trust toward and participation in political institutions. Leveraging an original survey targeting the city of South Bend and spatial data from the city government, results demonstrate that greater day-to-day contact with police has a positive impact on trust in state agencies while citizens who seek service from the police but are left unsatisfied result in lower trust in state apparatus. Most importantly, indirect exposure to police coercion has a negative impact on trust while direct and proximal contact with police predicts higher level of civic activism. This study demonstrates the fragility and challenge of building trust in police-citizen relationships, and how extreme encounters with the police can, in the right circumstances, spur citizen activism.

Abstract CT035: Proof-of-concept and preliminary efficacy of triple IAP blockade to maximize immunogenic cell death and induce efficient adaptive immune response: First report on the ASTEROID phase 1 trial

Abstract Background: Dying cells play an important role in CD8+ T cell-mediated immunity. While apoptosis is mainly immunologically silent, necroptosis is immunogenic and can more efficiently initiate an adaptive immune response that could be augmented by immune checkpoint inhibition (ICI). Inhibitor of Apoptosis (IAP) proteins are key gatekeepers of how a cell dies, and frequently overexpressed in cancer. ASTX660 (tolinapant) is a triple blocker of cIAP1/2 and XIAP, sensitizing cancer cells to death ligands through ripoptosome formation, activating ‘danger’ co-stimulatory signals and dendritic cell (DC) maturation required to prime a potent antitumor response. Methods: We assessed the safety, pharmacodynamic (PD), and clinical activity of 7 days of oral ASTX660 given prior to pembrolizumab 200 mg (Q3W), in patients (pts) refractory to standard therapy. TITE-CRM was used to explore ASTX660 doses 90-180 mg. Serial paired blood and tumor samples were analyzed to interrogate the effect of ASTX660 on cell death, tumor microenvironment and host immune system. Results: 22 pts have been enrolled; median age 55 years (range 38-81); male:female 5:17; all ECOG PS ≤1; median 4.5 prior therapies. Tumor types included breast, head and neck (HN), hepatocellular, cervical, pancreatic and cholangiocarcinoma. Combination ASTX660-pembrolizumab is currently recruiting at highest dose 180 mg without any dose limiting toxicities (DLT) seen within the 6-week DLT observation period. Most common adverse events (AE) were G1-2 rash, nausea, and asymptomatic increases in amylase, lipase and transaminases; all reversible and easily manageable. Four iRECIST confirmed partial responses were seen in 10 efficacy evaluable pts treated at biologically active dose levels 120 and 150 mg (Overall response rate 40%), including 2 pts with ER+ HER2- breast cancer, 1 cervical adenocarcinoma pt (exceptional response following initial pseudoprogression) and a HN cancer pt refractory to ICI monotherapy. 3/4 responders are ongoing. Efficacy data from pts treated at highest dose level 180 mg is pending. FACS of paired blood samples from responders shows a significant rise in %CD57+/CD3+ cytotoxic effector T cells [mean 11.90% (pre-) vs 14.25% (post-ASTX660); p=.0176]. These changes were not seen in the non-responders group. Full PD from paired blood and tumour sampling will be shared at the meeting. Conclusion: ASTX660-pembrolizumab is is well-tolerated with durable antitumor responses in pts with immunologically cold tumors, providing the first clinical proof-of-concept of immunogenic cell death induction leading to effective adaptive immune response when combined with ICI. Recommended Phase 2 dose optimization and expansion cohorts in immunologically cold cancers are ongoing. Citation Format: Crescens Tiu, Wing Yau, Victoria Sanchez-Perez, Giovanni Codacci-Pisanelli, Ching Leung, Eden S. Andrews, Bristi Basu, Anna Zachariou, Toby Prout, Mona Parmar, Alison Turner, Xiaoran Lai, Zhulin Yin, Karen E. Swales, Syed Haider, Thomas Lund, Diego C. Dos Reis, Tatiany L. Silveira, Alan S. Dunlop, Ann-Marie Baker, Bora Gurel, Ana Ferreira, Claudia Bertan, Nina Tunariu, Edward W. Johnston, Alistair Ring, Tencho Tenev, Tomoko Smyth, Simone Jueliger, Udai Banerji, Johann S. de Bono, Alec Paschalis, Adam Sharp, Anna Minchom, Christina Yap, Pascal Meier, Juanita S. Lopez. Proof-of-concept and preliminary efficacy of triple IAP blockade to maximize immunogenic cell death and induce efficient adaptive immune response: First report on the ASTEROID phase 1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT035.

An Analysis of the Relationship between Business Confidence and Macroeconomic Factors: Türkiye Case

Investor sentiment plays an important role in the all level of economic activities. Confidence as an indicator of investor sentiment has become an important and interesting concept in recent years. Confidence indicators are a way in assessing economic developments in the short term. The aim of this study is to analyze the long and short term relationship between the Real Sector Confidence Index and macroeconomic/financial variables for the period of January 2007 – December 2021. The Johansen Cointegration Test results prove a long-term cointegration relationship. Vector Error Correction Models for both macroeconomic and financial variables are statistically significant at the 5% level. In the short run, Manufacturing Capacity Utilization Ratio, Official Reserves, Domestic Debt Stocks, Real Exchance Rate, US Dollar/TRL Buying Rate, Non-Residents’ Stock Portfolio and Volatility Index have a statistically significant effect on the changes in Real Sector Confidence Index. Thus, this study informs investors to predict the effects of changes in the confidence index on financial instruments bilaterally and contribute to their investment decision.

A split single-stranded DNA activator-based Cas12a fluorescence biosensor for specific H1N1 detection

We developed a novel CRISPR/Cas12a fluorescence biosensor to specifically detect the H1N1 virus based on splitting single-stranded DNA (ssDNA) activators. Specifically, activators 1 and 2 were generated from dual target nucleic acid sites to induce a three-way junction (3WJ) isothermal amplification process. Two specific H1N1 RNA nucleic acid sites were bound to a set of probes to form a 3WJ, which facilitated repeated extension and nicking reactions to produce high levels of split ssDNA activators via DNA polymerase and nicking endonuclease activity. Amplified activators 1 and 2 fully assembled with Cas12a/crRNA to form complexes. Activated Cas12a trans-cleaved ssDNA reporter molecules to generate fluorescence signals. Under optimal conditions, biosensor dynamic detection range was 1 pM–10 nM, and the detection limit was 205 fM. Thus, our biosensor showed high specificity, reliability, and robustness, which highlights its potential use for H1N1 diagnostics.

The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial

Background and AimFrequent administration of blood in β- thalassemia patients can lead to over-loaded iron, a reduction in the levels of antioxidant activities in the body, and oxidative stress. This study was done to evaluate the antioxidant and protective effect of aqueous oak (Quercus brantii) extract supplementation on these patients. MethodsThis clinical trial was performed on 60 major β thalassemia patients dividing them into intervention and control groups. In addition to taking desferrioxamine (DFO), the control and intervention groups received respectively placebo capsule supplementation and aqueous Quercus extract capsules (300 mg/day) for 3 months. Serum lipid profiles (LDL-c, HDL-c, triglyceride), Total Antioxidant Capacity (TAC), Glucose, Uric acid, urea nitrogen (BUN), Creatinine, LFT (Liver Function Tests) such as SGOT, SGPT, ALP, Total bilirubin, Direct bilirubin, ferritin, MDA and carbonyl protein (CO) levels were measured before and after the period. In addition, the activity of catalase (CAT), and superoxide dismutase (SOD) was measured in the red blood cell. Furthermore, antioxidant activity and total phenolic content of aqueous Quercus were recorded to standardize capsule formulation. ResultsMean serum MDA, and protein CO, significantly decreased in the intervention group with β-TM after 3 months of treatment with Quercus extract. In addition, the superoxide dismutase (SOD) enzyme and Total antioxidant capacity (TAC) significantly increased in comparison with the control group. Changes in serum creatinine, BUN, and alanine transferase were not significant. In the study, Quercus extract capsules contain 48/56 mg gallic acid / g (dry extract) total phenol, 58/6 mg / g (dry extract), and flavonoids of 63/8 μg/ml antioxidant power which by GC/MS analysis has been measured. At the end of the study, serum MDA decreased from 48.65 ± 8.74 to 43.94 ± 10.39 μ mol/l after administration of oak extract and protein CO dropped from 2.44 ± 0.38 to 1.2 ± 0.31 nmol DNPH/mg protein after administration of the oak extract. At the end of the study serum, TAC increased in patients interventional group from 907 ± 319 to 977 ± 327μmol FeSO4/l compared to the control group 916 ± 275 to 905.233 ± 233 μmol FeSO4/l with placebo, and SOD increased from 1577 ±325 to 2079 ±554 U/l (compared to 1687 ± 323 U/l with placebo). The treatment effect of Quercus was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and SOD, with significant effects being demonstrated for each laboratory parameter (P=0.15, P=0.001, P=0.02, and P < 0.003, respectively). ConclusionsAqueous Quercus extract, due to its high antioxidant potential, reduced MDA, serum carbonyl protein, and increased superoxide dismutase activity effectively decreased serum OS and enhanced serum antioxidant capacity in patients with β-thalassemia major. oak given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients. Registration informationThis study was submitted, evaluated, and approved by the Iranian Registry of Clinical Trials (IRCT: http://www.irct.ir; IRCT2015101411819N4), which was established for national medical schools in Iran.