Search results for: drug therapy problem

Authors: Ching-Shoei Chiang

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The Malfatti’s Problem is to ask for fitting 3 circles into a right triangle such that they are tangent to each other, and each circle is also tangent to a pair of the triangle’s side. This problem has been extended to any triangle (called general Malfatti’s Problem). Furthermore, the problem has been extended to have 1+2+…+n circles, we call it extended general Malfatti’s problem, these circles whose tangency graph, using the center of circles as vertices and the edge connect two circles center if these two circles tangent to each other, has the structure as Pascal’s triangle, and the exterior circles of these circles tangent to three sides of the triangle. In the extended general Malfatti’s problem, there are closed-form solutions for n=1, 2, and the problem becomes complex when n is greater than 2. In solving extended general Malfatti’s problem (n>2), we initially give values to the radii of all circles. From the tangency graph and current radii, we can compute angle value between two vectors. These vectors are from the center of the circle to the tangency points with surrounding elements, and these surrounding elements can be the boundary of the triangle or other circles. For each circle C, there are vectors from its center c to its tangency point with its neighbors (count clockwise) pi, i=0, 1,2,..,n. We add all angles between cpi to cp(i+1) mod (n+1), i=0,1,..,n, call it sumangle(C) for circle C. Using sumangle(C), we can reduce/enlarge the radii for all circles in next iteration, until sumangle(C) is equal to 2πfor all circles. With a similar idea, this paper proposed an algorithm to find the radii of circles whose tangency has the structure of Pascal’s triangle, and the exterior circles of these circles are tangent to the unit Realeaux Triangle.

Keywords: Malfatti’s problem, geometric constraint solver, computer-aided geometric design, circle packing, data visualization

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Authors: Marzieh Yassin, Azizeh Parandnia, Javad Sarrafzadeh, Reza Salehi

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Background: Myofascial trigger points (MTrPs) are one of the main causes of musculoskeletal pain syndromes and are associated with pain, tenderness, and limited range of motion (ROM). This study compared the effectiveness of high-intensity laser therapy (HILT) and dry needling (DN) on pain intensity, pain pressure threshold, cervical range of motion and disability in people with chronic neck pain. Method and Material: 30 patients with chronic neck pain were randomly divided into two groups: a HILT group (n=15) and a DN group (n=15). Treatment sessions were performed for three weeks, and all participants received related intervention twice a week (5 sessions). The pain level was measured using a Visual Analog Scale (VAS); the pain pressure threshold (PPT) was measured using a digital algometer; perceived disability was measured using the neck disability index (NDI); and cervical range of movements (CROMs) were measured using an iPhone app (lateral flexion) and a goniometer (Rotation). Results: In both the dry needling and high-intensity laser therapy groups, the pain and neck disability were significantly decreased (P < 0.05). Also, the pain pressure threshold and cervical range of motions were significantly increased in both groups. However, there was no significant difference between the two groups (P > 0.05). Conclusion: Both high-intensity laser therapy and dry needling can be used to treat chronic neck pain.

Keywords: chronic neck pain, dry needling, high intensity laser therapy (HILT), pain, pain pressure threshold

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Soad Ali Yehia, Mohamed Shafik El-Ridi, Mina Ibrahim Tadros, Nolwa Gamal El-Sherif

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Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 hours (Tmax) post-dose. The current work aimed to develop taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). FT-IR, DSC and XRD were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (crosscarmelose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting time, disintegration time and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant, sodium stearyl fumarate (Pruv®). The topography of the latter formula was examined via scanning electron microscopy (SEM). The in vivo estimation of FXD pharmacokinetics, relative to Allegra® tablets, was evaluated in healthy human volunteers. Based on the gustatory sensation test in healthy volunteers, FXD:CS (1:1) and FXD:ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties and showed short wetting and disintegration times. Drug release profiles of F23 and phenylalanine-containing Allegra® ODT were similar (f2 = 96) showing a complete release in two minutes. SEM micrographs revealed pores following camphor sublimation. Compared to Allegra® tablets, pharmacokinetic studies in healthy volunteers proved F23 ability to increase extent of FXD absorption (14%) and reduce Tmax to 1.83 h.

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

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Authors: I. Tulay Cagatay

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Blue-green microalgae cyanobacteria, which are important photosynthetic organisms of aquatic ecosystems, are the primary sources of many bioactive compounds such as proteins, carbohydrates, lipids, vitamins and enzymes that can be used as antimicrobial and antiviral agents. Some of these organisms are nowadays used directly in the food, cosmetic and pharmaceutical industry, or in aquaculture and biotechnological approaches like biofuel or drug therapy. Finding the effective, environmental friendly chemotropic and antimicrobial agents to control fish pathogens are crucial in a country like Turkey which has a production capacity of about 240 thousand tons of cultured fish and has 2377 production farms and which is the second biggest producer in Europe. In our study, we tested the antimicrobial activity of cyanobacterium spp. against some fish pathogens Aeromonas hydrophila and Yersinia ruckeri that are important pathogens for rainbow trout farms. Agar disk diffusion test method was used for studying antimicrobial activity on pathogens. Both tested microorganisms have shown antimicrobial activity positively as the inhibition zones were 0.45 mm and 0.40 mm respectively.

Keywords: fish pathogen, cyanobacteria, antimicrobial activity, trout

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Authors: Felipe Azocar Simonet, Luis Acosta Espejo

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In this article, we will try to find an efficient boundary approximation for the bi-objective location problem with coherent coverage for two levels of hierarchy (CCLP). We present the mathematical formulation of the model used. Supported efficient solutions and unsupported efficient solutions are obtained by solving the bi-objective combinatorial problem through the weights method using a Lagrangean heuristic. Subsequently, the results are validated through the DEA analysis with the GEM index (Global efficiency measurement).

Keywords: coherent covering location problem, efficient frontier, lagragian relaxation, data envelopment analysis

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Authors: Hessam Mortezaei, Saeid Joudakian

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In this paper, the wear problem on rider rings of boil off gas compressor has been studied. This kind of oil free double acting compressor has free floating piston (FFP) technology and as a result of that it should have the lowest possible wear on its rider rings. But a design problem had caused a complete wear of rider rings after one month of continuous operation. In this case study, the source of this problem was recognized and solved.

Keywords: piston rider, rings, gas distribution, pressure wear

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Authors: Lydia Wahid, Mona F. Ahmed, Nevin Darwish

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The vehicle routing problem (VRP) consists of a group of customers that needs to be served. Each customer has a certain demand of goods. A central depot having a fleet of vehicles is responsible for supplying the customers with their demands. The problem is composed of two subproblems: The first subproblem is an assignment problem where the number of vehicles that will be used as well as the customers assigned to each vehicle are determined. The second subproblem is the routing problem in which for each vehicle having a number of customers assigned to it, the order of visits of the customers is determined. Optimal number of vehicles, as well as optimal total distance, should be achieved. In this paper, an approach for solving the first subproblem (the assignment problem) is presented. In the approach, a clustering algorithm is proposed for finding the optimal number of vehicles by grouping the customers into clusters where each cluster is visited by one vehicle. Finding the optimal number of clusters is NP-hard. This work presents a polynomial time clustering algorithm for finding the optimal number of clusters and solving the assignment problem.

Keywords: vehicle routing problems, clustering algorithms, Clarke and Wright Saving Method, agglomerative hierarchical clustering

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Authors: Filipe Cardoso de Oliveira, Lino Marcos da Silva, Ademar Nogueira do Nascimento, Cristiano Hora de Oliveira Fontes

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This article presents a mathematical formulation for the production Break-Even Point problem in a non-homogeneous system. The optimization problem aims to obtain the composition of the best product mix in a non-homogeneous industrial plant, with the lowest cost until the breakeven point is reached. The problem constraints represent real limitations of a generic non-homogeneous industrial plant for n different products. The proposed model is able to solve the equilibrium point problem simultaneously for all products, unlike the existing approaches that propose a resolution in a sequential way, considering each product in isolation and providing a sub-optimal solution to the problem. The results indicate that the product mix found through the proposed model has economical advantages over the traditional approach used.

Keywords: branch and bound, break-even point, non-homogeneous production system, integer linear programming, management accounting

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Authors: Jungbin Lim, Bohee Kang, Heelim Lee, Sunjin Kim, GeumHee Choi, Jae-Suk Jung, Suk Ji

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Nonsurgical periodontal therapies have, for several decades, been the basis of periodontal treatment concepts. The aim of this paper is to investigate the effectiveness of non-surgical periodontal therapy according to the severity of periodontitis disease. Methods: Retrospective data of patients who visited Department of periodontics in Ajou University Medical Center from 2016 to 2022 were collected. Among the patients, those who took full mouth examination of clinical parameters and non-surgical periodontal therapy were chosen for this study. Selected patients were divided into initial, moderate, and severe periodontitis based on severity and complexity of management (2018 World Workshop EFP/AAP consensus). Recall visits with clinical periodontal examination were scheduled for 1,2,3 months or 1,3,6 months after the treatment. The results were evaluated by recordings of mean probing pocket depth (mean PD), mean clinical attachment levels (mean CAL), bleeding on probing (BOP%), mean gingival index (mean GI), mean regression, mean sulcus bleeding index (mean SBI), mean plaque scores (mean PI). All statistical analyses were performed with R software, version 4.3.0. A level of significance, P<0.05, was considered to be statistically significant. Results: A total of 92 patients were included in this study. 15 patients were diagnosed as initial periodontitis, 14 moderate periodontitis, and 63 severe periodontitis. The all parameters except for mean recession decreased over time in all groups. The amount of mean PD decreased were the greatest in severe periodontitis group followed by moderate and initial, which was found to be statistically significant. The changes of mean PD were 0.15±0.05 mm, 0.37±0.06 mm, and 1.01±0.07 mm (initial, moderate, and severe, respectively, P<0.001). When comparing before and after treatment, the reductions in BOP(%), mean GI, mean SBI, and mean PI were statistically significant. Conclusion: All patients who received non-surgical periodontal therapy showed periodontal healing in terms of improvements in clinical parameters, and it was greater in the severe group.

Keywords: periodontology, clinical periodontology, oral treatment, comprehensive preventive dentistry, non-surgical periodontal therapy

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Authors: Mahdi Akhbardeh

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St John's wort plant can help to treat depression disease through decreasing this disease symptom, due to having some similar features of Prozac (Fluoxetine Hcl) pill. People suffering from slight depression who have fear of using antidepressants side effects can use St John's wort drops under doctor observation. This method of treatment is proposed specially to those women who are spending menopause or depression resulted from this period. St John's wort plant have proposed traditional and plant medicine as newest researches in treating mood disorders compared to Prozac (Fluoxetine Hcl) drug in treating depression disease which is being administrated in clinic research center of Washington. Objective: the aim of this study is to find an alternative treatment method in people suffering from depression which are treated with Prozac (Fluoxetine Hcl). Almost 70 percent of treatment failures with Prozac (Fluoxetine Hcl) drug in patients suffering from slight to normal depression is due to intensive side effects including: decrease in blood pressure, reduce in sexual desire and 30 percent of it is due to this drug affectless in treatment procedure which leads to leaving treatment. Results of Hypercuim plant function are exactly similar to antidepressants. Increase in serotonin amount in brain synopsis terminal end causes increase in existence time of this material in this part. In fact these two drugs have similar function. Though side effects of Hypercuim plant(St John's wort) including headache and slight nausea tolerable. Results: St John's wort plant can be used lonely in slight to normal depressions in which patients are avoiding Prozac (Fluoxetine Hcl) drug due to it's side effects. In intensive depressions through which general patients don’t indicate positive response to drug, it is probably expected relative or even complete treatment through combining antidepressants drugs with this plant. This treatment method has been investigated and confirmed in clinical tests and researches.

Keywords: depression, St John's wort, Prozac, antidepressant

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Authors: Said Abdirasak Abidrahman, Ibrahim Mohamed

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Background: Urinary Tract Infections (UTIs) are the commonest infections described among diabetes mellitus patients. More often, empirical antimicrobial therapy is initiated before the laboratory results are made available with minimal treatment success. The knowledge of the etiology and antibiotic susceptibility patterns of the organisms causing urinary tract infections among diabetes mellitus patients remains scarce, despite its vitality. This study sought to determine the prevalence, bacteria species, and drug susceptibility patterns of common causes of urinary tract infections among diabetes mellitus patients attending Bosaso health centers. Materials and methods: We conducted a cross-sectional study involving adult diabetic patients at Bosaso health centers between the months of May and July 2020. Laboratory assay of mid-stream urine samples was done to isolate bacteria causes of UTIs. These were biochemically identified using Gram stain, Kligler iron agar (KIA), Indole test, citrate, urea, coagulase, catalase, motility agar, and lysine iron agar. Their antibiotic susceptibility pattern for the isolated organisms was made for Ampicillin 10μg, Ciprofloxacin 5μg, Cotrimoxazole 25μg, Gentamycin 10μg, Ceftriaxone 10μg, and determined using the Kirby Bauer Disc Diffusion method. Results: Of 177 participants, 69 (39.0%) were males and 108 (61.0%) were females. Their mean age was 33.1 years (range; 18-67 years). Of these, 14.7% (26/177) of the samples revealed significant growth (>= 105 CFU/mL) giving a prevalence of 14.9 % (95% CI: 10.6 to 16.3). The organisms isolated were Escherichia coli -50% (N=13), Klebsiella pneumonia 30.8% (N=8), Staphylococcus aureus 15.4% (N=4), and unidentified organism 3.8% (N=1), and these were associated with such socio-demographic factors like history of catheterization and sexual activity. Antibiotic susceptibility to the commonly used agents for treating UTIs indicated higher sensitivity to Gentamicin and Ceftriaxone.

Keywords: antimicrobials, bacteria, urinary tract infections, diabetes

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. There is very few data on changes of the musculoskeletal manifestations (artritis, arthralgia, muscle weakness, etc.) in systemic sclerosis (SSc) on rituximab (RTX) therapy. The aim of our study was to assess the severity of the musculoskeletal involvement in SSc patients (pts) and its changes during RTX therapy. Methods. Our study included 103 pts with SSc. The mean followup period was 12.6±10.7 months. The mean age was 47±12.9 years, female-87 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had interstitial lung disease (ILD) and were positive for ANA, 67% of them were positive for antitopoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. Arthritis was observed in 22 pts (21%), arthralgias in 47 pts (46%). Muscle weakness was observed in 17 pts (17%). Tendon friction rubs was established in 7 pts (7%). The results at baseline and at the end of the follow up are presented in the form of mean values. Results. There was an improvement of all outcome parameters and musculoskeletal manifestations on RTX therapy. There was a decrease in the number of pts with arthritis from 22 (21%) to 10 (9%), a decrease in the number of pts with arthralgias from 47 (46%) to 31 (30%). The number of pts with muscle weakness decreased from 17 (17%) to 7 (7%). The number of pts with tendon friction rubs decreased from 7 (7%) to 3 (3%). The creatine phosphokinase decreased from 365.5±186 to 70.8±50.4 (p=0.00006). The C-reactive protein (CRP) decreased from 23.2±31.3 to 8.62±7.4 (p=0.001). The dose of prednisolone was reduced from 11.3±4.5 to 9.8±3.5 mg/day (p=0.0004). Conclusion. In our study, musculoskeletal involvement was detected in almost half of the patients with SSc-ILD. There was an improvement of musculoskeletal manifestations despite a small cumulative dose of RTX. We also managed to reduce the dose of glucocorticosteroids. The improvement of musculoskeletal manifestations was accompanied by a decrease in laboratory parameters - creatine phosphokinase and CRP. RTX is effective option for treatment of musculoskeletal manifestations in SSc.

Keywords: arthritis, musculoskeletal involvement, systemic sclerosis, rituximab

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Authors: Tarek Aboueldahab, Hanan Farag

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Cost minimization of Multiple Vehicle Routing Problem becomes a critical issue in the field of transportation because it is NP-hard optimization problem and the search space is complex. Many researches use the hybridization of artificial intelligence (AI) models to solve this problem; however, it can not guarantee to reach the best solution due to the difficulty of searching the whole search space. To overcome this problem, we introduce the hybrid model of Discrete Particle Swarm Optimization (DPSO) with a passive congregation which enable searching the whole search space to compromise between both local and global search. The practical experiment shows that our model obviously outperforms other hybrid models in cost minimization.

Keywords: cost minimization, multi-vehicle routing problem, passive congregation, discrete swarm, passive congregation

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Rosa L. Figueroa, Joselyn A. Hernández

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During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF, and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

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The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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Authors: M. G. Gopisankar, A. Surendiran, M. Hemachandren

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The dose requirement of warfarin to achieve target INR range varies in patients with prosthetic heart valve. This variation in is affected by both genetic and non-genetic factors. Earlier studies have identified role of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement. Warfarin being a substrate for drug transporter, P-glycoprotein coded by ABCB1 gene, may also be influenced by its genetic polymorphisms. This study was aimed to study the effect of single nucleotide polymorphism (SNP), ABCB1 2677G > T on warfarin maintenance dose requirement in patients with steady-state International Normalized Ratio (INR). The median dose requirement was significantly different between the genotype groups GG vs. GT (35 ± 20; 42.5 ± 18, p < 0.05), GG vs. TT (35 ± 20; 41.25 ± 25, p<0.05). There was no significant difference between GT vs. TT. In conclusion, patients with variant allele require a higher weekly maintenance dose of warfarin compared to patients without variant allele.

Keywords: warfarin pharamcogenetics, pharmacogenomics of warfarin, ABCB1 and warfarin, pglycoprotein and warfarin

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Authors: Temitayo Ogunsanwo

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Problem-solving is an important way of learning way of learning because it propels children to use previous experiences to deal with new situations. The purpose of this study is to find out the attitude of pre-service teachers to problem-solving as a strategy for promoting early mathematics learning in children. This qualitative study employed a descriptive design to investigate the experiences of twenty second-year undergraduate early childhood education Pre-service teachers in a teaching practice and their attitude towards five-year-old children’s problem-solving strategies in mathematics. Pre-service teachers were exposed to different strategies for teaching children how to solve problems in mathematics. They were taken through a micro teaching in class using different strategies to teach problem-solving in different topics in the five-year-old mathematics curriculum. The students were then made to teach five-year-olds in neighbouring schools for three weeks, working in pairs, observing and recording children’s problem-solving activities and strategies. After the three weeks exercise, their experiences and attitude towards children’s problem-solving strategies were collected using open-ended questions and analysed in themes. Findings were discussed.

Keywords: attitude, early mathematics learning, experience, pre-service teachers, problem-solving, strategies

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Authors: Kyou Hee Shim, Hwa Sung Shin

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When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Bill D. Geis

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Even with significantly increased spending, suicide rates continue to climb—with alarming increases among traditionally low-risk groups. This has caused clinicians and researchers to call for a complete rethinking of all assumptions about suicide prevention, assessment, and intervention. A form of therapy--Internal Family Systems Therapy--affords tremendous promise in sustained diminishment of lethal suicide risk. Though a form of therapy that is most familiar to trauma therapists, Internal Family Systems Therapy, involving direct work with suicidal parts, is a promising therapy for meaningful and sustained reduction in suicide deaths. Developed by Richard Schwartz, Internal Family Systems Therapy proposes that we are all influenced greatly by internal parts, frozen by development adversities, and these often-contradictory parts contribute invisibly to mood, distress, and behavior. In making research videos of patients from our database and discussing their suicide attempts, it is clear that many persons who attempt suicide are in altered states at the time of their attempt and influenced by factors other than conscious intent. Suicide intervention using this therapy involves direct work with suicidal parts and other interacting parts that generate distress and despair. Internal Family Systems theory posits that deep experiences of pain, fear, aloneness, and distress are defended by a range of different parts that attempt to contain these experiences of pain through various internal activities that unwittingly push forward inhibition, fear, self-doubt, hopelessness, desires to cut and engage in destructive behavior, addictive behavior, and even suicidal actions. These suicidal parts are often created (and “frozen”) at young ages, and these very young parts do not understand the consequences of this influence. Experience suggests that suicidal parts can create impulsive risk behind the scenes when pain is high and emotional support reduced—with significant crisis potential. This understanding of latent suicide risk is consistent with many of our video accounts of serious suicidal acts—compiled in a database of 1104 subjects. Since 2016, consent has been obtained and records kept of 23 highly suicidal patients, with initial Intention-to-Die ratings (0= no intent, 10 = conviction to die) between 5 and 10. In 67% of these cases using IFST parts-work intervention, these highly suicidal patients’ risk was reduced to 0-1, and 83% of cases were reduced to 4 or lower. There were no suicide deaths. Case illustrations will be offered.

Keywords: suicide, internal family systems therapy, crisis management, suicide prevention

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

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Authors: Lucas Derks, Christine Beenhakker, Michiel Brandt, Gert Arts, Ruud van Langeveld

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Background: The method Depression in Awareness Space (DAS) is a psychotherapeutic intervention technique based on the principles of spatial cognition and imagination therapy with spatial components. The basic assumptions are: mental space is the primary organizing principle in the mind, and all psychological issues can be treated by first locating and by next relocating the conceptualizations involved. The most clinical experience was gathered over the last 20 years in the area of social issues (with the social panorama model). The latter work led to the conclusion that a mental object (image) gains emotional impact when it is placed more central, closer and higher in the visual field – and vice versa. Changing the locations of mental objects in space thus alters the (socio-) emotional meaning of the relationships. The experience of depression seems always associated with darkness. Psychologists tend to see the link between depression and darkness as a metaphor. However, clinical practice hints to the existence of more literal forms of darkness. Aims: The aim of the method Depression in Awareness Space is to reduce the distress of clients with depression in the clinical counseling practice, as a reliable alternative method of psychological therapy for the treatment of depression. The method Depression in Awareness Space aims at making dark areas smaller, lighter and more transparent in order to identify the problem or the cause of the depression which lies behind the darkness. It was hypothesized that the darkness is a subjective side-effect of the neurological process of repression. After reducing the dark clouds the real problem behind the depression becomes more visible, allowing the client to work on it and in that way reduce their feelings of depression. This makes repression of the issue obsolete. Results: Clients could easily get into their 'sadness' when asked to do so and finding the location of the dark zones proved pretty easy as well. In a recent pilot study with five participants with mild depressive symptoms (measured on two different scales and tested against an untreated control group with similar symptoms), the first results were also very promising. If the mental spatial approach to depression can be proven to be really effective, this would be very good news. The Society of Mental Space Psychology is now looking for sponsoring of an up scaled experiment. Conclusions: For spatial cognition and the research into spatial psychological phenomena, the discovery of dark areas can be a step forward. Beside out of pure scientific interest, it is great to know that this discovery has a clinical implication: when darkness can be connected to depression. Also, darkness seems to be more than metaphorical expression. Progress can be monitored over measurement tools that quantify the level of depressive symptoms and by reviewing the areas of darkness.

Keywords: depression, spatial cognition, spatial imagery, social panorama

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Authors: Rachid Ziteuni, Selt Omar

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In this paper, we propose a new polynomial metaheuristic elaboration (tabu search) for solving scheduling problems. This method allows us to solve the scheduling problem of n tasks on m identical parallel machines with unavailability periods. This problem is NP-complete in the strong sens and finding an optimal solution appears unlikely. Note that all data in this problem are integer and deterministic. The performance criterion to optimize in this problem which we denote Pm/N-c/summs of (wjCj) is the weighted sum of the end dates of tasks.

Keywords: scheduling, parallel identical machines, unavailability periods, metaheuristic, tabu search

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Authors: Rasha Ahmadi

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In December 2019, a coronavirus, currently identified as SARS-CoV-2, produced a series of acute atypical respiratory illnesses in Wuhan, Hubei Province, China. The sickness induced by this virus was named COVID-19. The virus is transmittable between humans and has caused pandemics worldwide. The number of death tolls continues to climb and a huge number of countries have been obliged to perform social isolation and lockdown. Lack of focused therapy continues to be a problem. Epidemiological research showed that senior patients were more susceptible to severe diseases, whereas children tend to have milder symptoms. In this study, we focus on other possible side effects of COVID-19 and more detailed treatment strategies. Using bioinformatics analysis, we first isolated the gene expression profile of patients with severe COVID-19 from the GEO database. Patients' blood samples were used in the GSE183071 dataset. We then categorized the genes with high and low expression. In the next step, we uploaded the genes separately to the Enrichr database and evaluated our data for signs and symptoms as well as related medication regimens. The results showed that 138 genes with high expression and 108 genes with low expression were observed differentially in the severe COVID-19 VS control group. Symptoms and diseases such as embolism and thrombosis of the abdominal aorta, ankylosing spondylitis, suicidal ideation or attempt, regional enteritis were observed in genes with high expression and in genes with low expression of acute and subacute forms of ischemic heart, CNS infection and poliomyelitis, synovitis and tenosynovitis. Following the detection of diseases and possible signs and symptoms, Carmustine, Bithionol, Leflunomide were evaluated more significantly for high-expression genes and Chlorambucil, Ifosfamide, Hydroxyurea, Bisphenol for low-expression genes. In general, examining the different and invisible aspects of COVID-19 and identifying possible treatments can help us significantly in the emergency and hospitalization of patients.

Keywords: phenotypes, drug regimens, gene expression profiles, bioinformatics analysis, severe COVID-19

Procedia PDF Downloads 127