Search results for: Navid Eghtedarpour

Authors: Ali Liaghat, Navid Tavanpour, Nima Tavanpour

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An increase in population and prevalence of urbanity have led plan makers and decision makers put effort into sustainable development of cities at national and local levels. One of the important issues in urban development is compliance with safety issues in cities. Despite natural disasters and unexpected events such as floods, earthquakes, hurricanes, fires, etc., urban development should be regarded as an axiom, or else any form of construction and development is not safe, because it will greatly harm economic growth and development and pose an obstacle to achieving sustainable development, plus a loss to lives and finances of people. Therefore, in line with urban development, it is necessary to identify particular environmental and local issues as determinants and pay attention to them at the top of everything, in that we can call it a good action and factor in urban sustainable developments. Physical structure of each city represents how it has developed or its development shaped and what incidents, changes, natural disasters it has undergone over time. Since any form of development plan should be in accordance with the previous situations of cities, disregarding it, unfortunately, can escalate into uncontrolled urban development, non-resistant and unstable construction against earthquake or invasion of river areas, destruction of agricultural lands or vegetation, periodic floods over time. It has been viewed as serious threats to developing cities, and typically caused destruction of bed and other urban facilities as well as damages to lives and finances. In addition, uncontrolled development has caused cities to look ugly in terms of urban façade, and off and on such unplanned measures caused the country to face countless losses, and it not only vitiates expenses incurred, but it will also impose additional costs of reconstruction, i.e. it is unsustainable development. Thus, in this paper, in addition to a discussion about necessity for a profound attitude toward this subject and making long-term plans, programs for organizing river and its surrounding area, creating open and green urban spaces, retrofitting and flood preventing are presented for sustainable safety and development of cities along with a critique of successful countries.

Keywords: flood, sustainable development, urbanisation, urban management

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Authors: Bahram Besharti, Hossein Navid, Hadi Karimi, Hossein Behfar, Iraj Eskandari

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Multiple or miss sowing by seed drills is a common problem on the farm. This problem causes overuse of seeds, wasting energy, rising crop treatment cost and reducing crop yield in harvesting. To be informed of mentioned faults and monitoring the performance of seed drills during sowing, developing a seed sensor for detecting seed mass flow rate and monitoring in a delivery tube is essential. In this research, an infrared seed sensor was developed to estimate seed mass flow rate in seed drills. The developed sensor comprised of a pair of spaced apart circuits one acting as an IR transmitter and the other acting as an IR receiver. Optical coverage in the sensing section was obtained by setting IR LEDs and photo-diodes directly on opposite sides. Passing seeds made interruption in radiation beams to the photo-diode which caused output voltages to change. The voltage difference of sensing units summed by a microcontroller and were converted to an analog value by DAC chip. The sensor was tested by using a roller seed metering device with three types of seeds consist of chickpea, wheat, and alfalfa (representing large, medium and fine seed, respectively). The results revealed a good fitting between voltage received from seed sensor and mass flow of seeds in the delivery tube. A linear trend line was set for three seeds collected data as a model of the mass flow of seeds. A final mass flow model was developed for various size seeds based on receiving voltages from the seed sensor, thousand seed weight and equivalent diameter of seeds. The developed infrared seed sensor, besides monitoring mass flow of seeds in field operations, can be used for the assessment of mechanical planter seed metering unit performance in the laboratory and provide an easy calibrating method for seed drills before planting in the field.

Keywords: seed flow, infrared, seed sensor, seed drills

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Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar

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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure

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Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

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Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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Authors: Jessica Chorostecki, Aashka Shah, Fen Bao, Ginny Bao, Edwin George, Navid Seraji-Bozorgzad, Veronica Gorden, Christina Caon, Elliot Frohman

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Background: Parkinson’s Disease (PD) is a neuro degenerative disorder associated with the loss of dopaminergic cells and the presence α-synuclein (AS) aggregation in of Lewy bodies. Both dopaminergic cells and AS are found in the retina. Optical coherence tomography (OCT) allows high-resolution in-vivo examination of retinal structure injury in neuro degenerative disorders including PD. Methods: We performed a cross-section OCT study in patients with definite PD and healthy controls (HC) using Spectral Domain SD-OCT platform to measure the peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). We performed intra-retinal segmentation with fully automated segmentation software to measure the volume of the RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and the outer nuclear layer (ONL). Segmentation was performed blinded to the clinical status of the study participants. Results: 101 eyes from 52 PD patients (mean age 65.8 years) and 46 eyes from 24 HC subjects (mean age 64.1 years) were included in the study. The mean pRNFL thickness was not significantly different (96.95 μm vs 94.42 μm, p=0.07) but the TMV was significantly lower in PD compared to HC (8.33 mm3 vs 8.58 mm3 p=0.0002). Intra-retinal segmentation showed no significant difference in the RNFL volume between the PD and HC groups (0.95 mm3 vs 0.92 mm3 p=0.454). However, GCL, IPL, INL, and ONL volumes were significantly reduced in PD compared to HC. In contrast, the volume of OPL was significantly increased in PD compared to HC. Conclusions: Our finding of the enlarged OPL corresponds with mRNA expression studies showing localization of AS in the OPL across vertebrate species and autopsy studies demonstrating AS aggregation in the deeper layers of retina in PD. We propose that the enlargement of the OPL may represent a potential biomarker of AS aggregation in PD. Longitudinal studies in larger cohorts are warranted to confirm our observations that may have significant implications in disease monitoring and therapeutic development.

Keywords: Optical Coherence Tomography, biomarker, Parkinson's disease, alpha-synuclein, retina

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Authors: Navid Mirzaei Varzeghani, Mahmoud Saffarzadeh, Ali Naderan, Amirhossein Taheri

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Countries are progressing, and the world's busiest airports see year-on-year increases in travel demand. Passenger acceptability of an airport depends on the airport's appeals, which may include one of these routes between the city and the airport, as well as the facilities to reach them. One of the critical roles of transportation planners is to predict future transportation demand so that an integrated, multi-purpose system can be provided and diverse modes of transportation (rail, air, and land) can be delivered to a destination like an airport. In this study, 356 questionnaires were filled out in person over six days. First, the attraction of business and non-business trips was studied using data and a linear regression model. Lower travel costs, a range of ages more significant than 55, and other factors are essential for business trips. Non-business travelers, on the other hand, have prioritized using personal vehicles to get to the airport and ensuring convenient access to the airport. Business travelers are also less price-sensitive than non-business travelers regarding airport travel. Furthermore, carrying additional luggage (for example, more than one suitcase per person) undoubtedly decreases the attractiveness of public transit. Afterward, based on the manner and purpose of the trip, the locations with the highest trip generation to the airport were identified. The most famous district in Tehran was District 2, with 23 visits, while the most popular mode of transportation was an online taxi, with 12 trips from that location. Then, significant variables in separation and behavior of travel methods to access the airport were investigated for all systems. In this scenario, the most crucial factor is the time it takes to get to the airport, followed by the method's user-friendliness as a component of passenger preference. It has also been demonstrated that enhancing public transportation trip times reduces private transportation's market share, including taxicabs. Based on the responses of personal and semi-public vehicles, the desire of passengers to approach the airport via public transportation systems was explored to enhance present techniques and develop new strategies for providing the most efficient modes of transportation. Using the binary model, it was clear that business travelers and people who had already driven to the airport were the least likely to change.

Keywords: multimodal transportation, demand modeling, travel behavior, statistical models

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Authors: Navid P Roodaki, Rochelle Abila, Daisy Evangeline Garcia

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Background and Objective: Respiratory Distress Syndrome (RDS) among premature infants is a major causes of neonatal death. The use of Continuous Positive Airway Pressure (CPAP) has become a standard of care for preterm newborns with RDS hence cost-effective innovations are needed. This study compared a novel low-cost Bubble CPAP (bCPAP) device to ventilator driven CPAP in the treatment of RDS. Methods: This is a single-blind, randomized controlled trial done on May 2022 to October 2022 in a Level III Neonatal Intensive Care Unit in the Philippines. Preterm newborns (<36 weeks) with RDS were randomized to receive Vayu bCPAP device or Ventilator-derived CPAP. Arterial Blood Gases, Oxygen Saturation, administration of surfactant, and CPAP failure rates were measured. Results: Seventy preterm newborns were included. No differences were observed between the Ventilator driven CPAP and Vayu bCPAP on the PaO2 (97.51mmHg vs 97.37mmHg), So2 (97.08% vs 95.60%) levels, amount of surfactant administered between groups. There were no observed differences in CPAP failure rates between Vayu bPCAP (x̄ 3.23 days) and ventilator-driven CPAP (x̄ 2.98 days). However, a significant difference was noted on the CO2 level (40.32mmHg vs 50.70mmHg), which was higher among those hooked to Ventilator-driven CPAP (p 0.004). Conclusion: This study has shown that the novel low-cost bubble CPAP (Vayu bCPAP) can be used as an efficacious alternate non invasive oxygen therapy among preterm neonates with RDS, although the CO2 levels were higher among those hooked to ventilator driven CPAP, other outcome parameters measured showed that both devices are comparable. Recommendation: A multi-center or national study to account for geographic region, which may alter the outcomes of patients connected to different ventilatory support. Cost comparison between devices is also suggested. A mixed-method research assessing the experiences of health care professionals in assembling and utilizing the gadget is a second consideration.

Keywords: bubble CPAP, ventilator-derived CPAP; infant, premature, respiratory distress syndrome

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Authors: Navid Nasrolah Mazandarani, Faezeh Mohammadi Tahrodi, Jr., Norshida Ujang, Richard Jan Pech

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Human evolution has designed us to be dependent on social and natural settings, but designed of our modern cities often ignore this fact. It is evident that high-rise buildings dominate most metropolitan city centers. As a result urban parks are very limited and in many cases are not socially responsive to our social needs in these urban ‘jungles’. This paper emphasizes the functions of urban morphology in supporting socialization in Lake Garden, one of the main urban parks in Kuala Lumpur, Malaysia. It discusses two relevant theories; first the concept of users’ experience coined by Kevin Lynch (1960) which states that way-finding is related to the process of forming mental maps of environmental surroundings. Second, the concept of social activity coined by Jan Gehl (1987) which holds that urban public spaces can be more attractive when they provide welcoming places in which people can walk around and spend time. Until recently, research on socio-spatial behavior mainly focused on social ties, place attachment and human well-being; with less focus on the spatial dimension of social behavior. This paper examines the socio-spatial behavior within the spatial structure of the urban park by exploring the relationship between way-finding and social activity. The urban structures defined by the paths and nodes were analyzed as the fundamental topological structure of space to understand their effects on the social engagement pattern. The study uses a photo questionnaire survey to inspect the spatial dimension in relation to the social activities within paths and nodes. To understand the legibility of the park, spatial cognition was evaluated using sketch maps produced by 30 participants who visited the park. The results of the sketch mapping indicated that a spatial image has a strong interrelation with socio-spatial behavior. Moreover, an integrated spatial structure of the park generated integrated use and social activity. It was found that people recognized and remembered the spaces where they engaged in social activities. They could experience the park more thoroughly, when they found their way continuously through an integrated park structure. Therefore, the benefits of both perceptual and social dimensions of planning and design happened simultaneously. The findings can assist urban planners and designers to redevelop urban parks by considering the social quality design that contributes to clear mental images of these places.

Keywords: spatial structure, social activities, sketch map, urban park, way-finding

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Authors: Navid Kaboudi, Ali Shayanfar

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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.

Keywords: logistic regression, breastfeeding, descriptors, penetration

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Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

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Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: Navid Ebrahmi Madiseh, Sina Esfandiarpour-Broujeni, Rahil Razeghi

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Introduction: Quantitative analysis of game-related statistical parameters is widely used to evaluate basketball performance at both individual and team levels. Non-free throw shooting plays a crucial role as the primary scoring method, holding significant importance in the game's technical aspect. It has been explored the predictive value of game-related statistics in relation to various contextual and situational variables. Many similarities and differences also have been found between different age groups and levels of competition. For instance, in the World Basketball Championships after the 2010 rule change, 2-point field goals distinguished winners from losers in women's games but not in men's games, and the impact of successful 3-point field goals on women's games was minimal. The study aimed to identify and compare discriminant shooting-related statistics between winning and losing teams in men’s and women’s FIBA-U19-Basketball-World-Cup-2023 tournaments. Method: Data from 112 observations (2 per game) of 16 teams (for each gender) in the FIBA-U19-Basketball-World-Cup-2023 were selected as samples. The data were obtained from the official FIBA website using Python. Specific information was extracted, organized into a DataFrame, and consisted of twelve variables, including shooting percentages, attempts, and scoring ratio for 3-pointers, mid-range shots, paint shots, and free throws. Made% = scoring type successful attempts/scoring type total attempts¬ (1)Free-throw-pts% (free throw score ratio) = (free throw score/total score) ×100 (2)Mid-pts% (mid-range score ratio) = (mid-range score/total score) ×100 (3) Paint-pts% (paint score ratio) = (Paint score/total score) ×100 (4) 3p_pts% (three-point score ratio) = (three-point score/total score) ×100 (5) Independent t-tests were used to examine significant differences in shooting-related statistical parameters between winning and losing teams for both genders. Statistical significance was p < 0.05. All statistical analyses were completed with SPSS, Version 18. Results: The results showed that 3p-made%, mid-pts%, paint-made%, paint-pts%, mid-attempts, and paint-attempts were significantly different between winners and losers in men (t=-3.465, P<0.05; t=3.681, P<0.05; t=-5.884, P<0.05; t=-3.007, P<0.05; t=2.549, p<0.05; t=-3.921, P<0.05). For women, significant differences between winners and losers were found for 3p-made%, 3p-pts%, paint-made%, and paint-attempt (t=-6.429, P<0.05; t=-1.993, P<0.05; t=-1.993, P<0.05; t=-4.115, P<0.05; t=02.451, P<0.05). Discussion: The research aimed to compare shooting-related statistics between winners and losers in men's and women's teams at the FIBA-U19-Basketball-World-Cup-2023. Results indicated that men's winners excelled in 3p-made%, paint-made%, paint-pts%, paint-attempts, and mid-attempt, consistent with previous studies. This study found that losers in men’s teams had higher mid-pts% than winners, which was inconsistent with previous findings. It has been indicated that winners tend to prioritize statistically efficient shots while forcing the opponent to take mid-range shots. In women's games, significant differences in 3p-made%, 3p-pts%, paint-made%, and paint-attempts were observed, indicating that winners relied on riskier outside scoring strategies. Overall, winners exhibited higher accuracy in paint and 3P shooting than losers, but they also relied more on outside offensive strategies. Additionally, winners acquired a higher ratio of their points from 3P shots, which demonstrates their confidence in their skills and willingness to take risks at this competitive level.

Keywords: gender, losers, shoot-statistic, U19, winners

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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