Search results for: drug synergy
2197 Graph Clustering Unveiled: ClusterSyn - A Machine Learning Framework for Predicting Anti-Cancer Drug Synergy Scores
Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi
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In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.Keywords: drug synergy, clustering, prediction, machine learning., deep learning
Procedia PDF Downloads 782196 Synergy Effect of Energy and Water Saving in China's Energy Sectors: A Multi-Objective Optimization Analysis
Authors: Yi Jin, Xu Tang, Cuiyang Feng
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The ‘11th five-year’ and ‘12th five-year’ plans have clearly put forward to strictly control the total amount and intensity of energy and water consumption. The synergy effect of energy and water has rarely been considered in the process of energy and water saving in China, where its contribution cannot be maximized. Energy sectors consume large amounts of energy and water when producing massive energy, which makes them both energy and water intensive. Therefore, the synergy effect in these sectors is significant. This paper assesses and optimizes the synergy effect in three energy sectors under the background of promoting energy and water saving. Results show that: From the perspective of critical path, chemical industry, mining and processing of non-metal ores and smelting and pressing of metals are coupling points in the process of energy and water flowing to energy sectors, in which the implementation of energy and water saving policies can bring significant synergy effect. Multi-objective optimization shows that increasing efforts on input restructuring can effectively improve synergy effects; relatively large synergetic energy saving and little water saving are obtained after solely reducing the energy and water intensity of coupling sectors. By optimizing the input structure of sectors, especially the coupling sectors, the synergy effect of energy and water saving can be improved in energy sectors under the premise of keeping economy running stably.Keywords: critical path, energy sector, multi-objective optimization, synergy effect, water
Procedia PDF Downloads 3592195 Existence of Financial Service Authority Prior to 2045
Authors: Syafril Hendrik Hutabarat, Hartiwiningsih, Pujiyono Suwadi
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The Financial Service Authority (FSA) was formed as a response to the 1997 monetary crisis and the 2008 financial crisis so that it was more defensive in nature while developments in information and communication technology have required state policies to be more offensive to keep up with times. Reconstruction of Authorities of the FSA's Investigator is intended to keep the agency worthy to be part of an integrated criminal justice system in Indonesia which has implications for expanding its authority in line with efforts to protect and increase the welfare of the people. The results show that internal synergy between sub-sectors in the financial services sector is not optimised, some are even left behind so that the FSA is not truly an authority in the financial services sector. This research method is empirical. The goal of synergy must begin with internal synergy which has its moment when Indonesia gets a demographic bonus in the 2030s and becomes an international logistics hub supported by the national financial services sector.Keywords: reconstruction, authorities, FSA investigators, synergy, demography
Procedia PDF Downloads 752194 Synergy and Complementarity in Technology-Intensive Manufacturing Networks
Authors: Daidai Shen, Jean Claude Thill, Wenjia Zhang
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This study explores the dynamics of synergy and complementarity within city networks, specifically focusing on the headquarters-subsidiary relations of firms. We begin by defining these two types of networks and establishing their pivotal roles in shaping city network structures. Utilizing the mesoscale analytic approach of weighted stochastic block modeling, we discern relational patterns between city pairs and determine connection strengths through statistical inference. Furthermore, we introduce a community detection approach to uncover the underlying structure of these networks using advanced statistical methods. Our analysis, based on comprehensive network data up to 2017, reveals the coexistence of both complementarity and synergy networks within China’s technology-intensive manufacturing cities. Notably, firms in technology hardware and office & computing machinery predominantly contribute to the complementarity city networks. In contrast, a distinct synergy city network, underpinned by the cities of Suzhou and Dongguan, emerges amidst the expansive complementarity structures in technology hardware and equipment. These findings provide new insights into the relational dynamics and structural configurations of city networks in the context of technology-intensive manufacturing, highlighting the nuanced interplay between synergy and complementarity.Keywords: city system, complementarity, synergy network, higher-order network
Procedia PDF Downloads 432193 Optimization Analysis of a Concentric Tube Heat Exchanger with Field Synergy Principle
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The paper investigates the optimization analysis to the heat exchanger design, mainly with response surface method and genetic algorithm to explore the relationship between optimal fluid flow velocity and temperature of the heat exchanger using field synergy principle. First, finite volume method is proposed to calculate the flow temperature and flow rate distribution for numerical analysis. We identify the most suitable simulation equations by response surface methodology. Furthermore, a genetic algorithm approach is applied to optimize the relationship between fluid flow velocity and flow temperature of the heat exchanger. The results show that the field synergy angle plays vital role in the performance of a true heat exchanger.Keywords: optimization analysis, field synergy, heat exchanger, genetic algorithm
Procedia PDF Downloads 3072192 Strategic Alliances and Creative Synergy within European Union: A Theoretical Perspective
Authors: Maha Tichetti, Barzi Redouane, Selim Kanat
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In the European Union (EU), where economic, political, and cultural ties converge, strategic alliances play a pivotal role in shaping the collaborative landscape. This paper embarks on a journey into the EuroSphere, offering a comprehensive analysis review that unravels the dynamics of these alliances within the European context. The focus is specifically directed towards understanding their profound impact on creative synergy and innovation among teams. In our analysis, we provide theoretical explanations for key terms such as "creative synergy" and "strategic alliances." We outline various types of competitive strategies, delve into the motivations prompting the formation of strategic alliances, and critically examine the success and failure factors in these kinds of collaboration. Additionally, we explore the goals achievable through strategic alliances, especially in the context of external growth. A central focus of this paper focus on how strategic alliances can significantly impact creative synergy within the European landscape. Through a theoretical lens, we explore the interplay between collaborative strategies and the enhancement of creative thinking within teams engaged in strategic alliances. The article goes beyond theoretical frameworks to present a tangible example of a strategic alliance emerging in the European market. This case study illuminates how such alliances have empowered European companies to enhance their competitive positions on the global stage while concurrently fostering creative synergy among their teams. This comprehensive review not only contributes to the theoretical understanding of strategic alliances and creative synergy but also offers practical insights for businesses navigating the collaborative landscape within the EuroSphere. As we unravel the complexities of these alliances, we uncover valuable lessons and opportunities for future research, providing a roadmap for those seeking to harness the full potential of strategic collaborations in the dynamic European context.Keywords: European Union, strategic alliances, creative synergy, competitiveness
Procedia PDF Downloads 642191 Transgenerational Entrepreneurship in Chinese Family Businesses: Proposal for a Model of Work-Life Synergy
Authors: Jenny Oliveros Lao Phillips, Arturo E. Osorio, José Alves
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Family business are the dominant form of business in the world, and Chinese family business (CFB) is a unique type of family business that relies on collective action to survive. This paper argues that in CFBs, entrepreneurial actions are transgenerational collective endeavors, and successors are groomed as stewards of the family legacy. Work-life relationship in CFBs is about synergy and not balance because the family identity is the business identity, and vice-versa. Using five in-depth case studies, this research introduces an alternative understanding of CFBs and proposes a model of work-life synergy in transgenerational entrepreneurship based on discussion of five theory-based propositions. This model explains that through emphasizing on the business family’s shared value and entrepreneurial legacy, elements of trust, shared identity and stewardship of family members are enhanced which leads to collective action and goal of the business family, resulting in transgenerational entrepreneurship. Limitations and future research are presented.Keywords: Chinese family business, family legacy, stewardship, transgenerational entrepreneurship, work-life synergy
Procedia PDF Downloads 2982190 In Silico Studies on Selected Drug Targets for Combating Drug Resistance in Plasmodium Falcifarum
Authors: Deepika Bhaskar, Neena Wadehra, Megha Gulati, Aruna Narula, R. Vishnu, Gunjan Katyal
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With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.Keywords: plasmodium, malaria, drug targets, in silico studies
Procedia PDF Downloads 4452189 Potential Drug-Drug Interactions at a Referral Hematology-Oncology Ward in Iran: A Cross-Sectional Study
Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh
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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies
Procedia PDF Downloads 4522188 Drug Use Knowledge and Antimicrobial Drug Use Behavior
Authors: Pimporn Thongmuang
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The import value of antimicrobial drugs reached approximately fifteen million Baht in 2010, considered as the highest import value of all modern drugs, and this value is rising every year. Antimicrobials are considered the hazardous drugs by the Ministry of Public Health. This research was conducted in order to investigate the past knowledge of drug use and Antimicrobial drug use behavior. A total of 757 students were selected as the samples out of a population of 1,800 students. This selected students had the experience of Antimicrobial drugs use a year ago. A questionnaire was utilized in this research. The findings put on the view that knowledge gained by the students about proper use of antimicrobial drugs was not brought into practice. This suggests that the education procedure regarding drug use needs adjustment. And therefore the findings of this research are expected to be utilized as guidelines for educating people about the proper use of antimicrobial drugs. At a broader perspective, correct drug use behavior of the public may potentially reduce drug cost of the Ministry of Public Health of Thailand.Keywords: drug use knowledge, antimicrobial drugs, drug use behavior, drug
Procedia PDF Downloads 2792187 Drug-Drug Interaction Prediction in Diabetes Mellitus
Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe
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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects
Procedia PDF Downloads 992186 Spray-Dried, Biodegradable, Drug-Loaded Microspheres for Use in the Treatment of Lung Diseases
Authors: Mazen AlGharsan
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Objective: The Carbopol Microsphere of Linezolid, a drug used to treat lung disease (pulmonary disease), was prepared using Buchi B-90 nano spray-drier. Methods: Production yield, drug content, external morphology, particle size, and in vitro release pattern were performed. Results: The work was 79.35%, and the drug content was 66.84%. The surface of the particles was shriveled in shape, with particle size distribution with a mean diameter of 9.6 µm; the drug was released in a biphasic manner with an initial release of 25.2 ± 5.7% at 60 minutes. It later prolonged the release by 95.5 ± 2.5% up to 12 hours. Differential scanning calorimetry (DSC) revealed no change in the melting point of the formulation. Fourier-transform infrared (FT-IR) studies showed no polymer-drug interaction in the prepared nanoparticles.Keywords: nanotechnology, drug delivery, Linezolid, lung disease
Procedia PDF Downloads 122185 Role of Social Support in Drug Cessation among Male Addicts in the West of Iran
Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh, Fazel Zinat Motlagh
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Social support is an important benchmark of health for people in avoidance conditions. The main goal of this study was to determine the three kinds of social support (family, friend and other significant) to drug cessation among male addicts, in Kermanshah, the west of Iran. This cross-sectional study was conducted among 132 addicts, randomly selected to participate voluntarily in the study. Data were collected from conduct interviews based on standard questionnaire and analyzed by using SPSS-18 at 95% significance level. The majority of addicts were young (Mean: 30.4 years), and with little education. Opium (36.4%), Crack (21.2%), and Methamphetamine (12.9%) were the predominant drugs. Inabilities to reject the offer and having addict friends are the most often reasons for drug usage. Almost, 18.9% reported history of drug injection. 43.2% of the participants already did drug cessation at least once. Logistic regression showed the family support (OR = 1.110), age (OR = 1.106) and drug use initiation age (OR = 0.918) was predicting drug cessation. Our result showed; family support is a more important effect among types of social support in drug cessation. It seems that providing educational program to addict’s families for more support of patients at drug cessation can be beneficial.Keywords: drug cessation, family support, drug use, initiation age
Procedia PDF Downloads 5492184 Functionalized Nanoparticles for Drug Delivery Applications
Authors: Temesgen Geremew
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Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.Keywords: nanoparticles, drug, nanomaterials, applications
Procedia PDF Downloads 662183 Pharmaceutical Science and Development in Drug Research
Authors: Adegoke Yinka Adebayo
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An understanding of the critical product attributes that impact on in vivo performance is key to the production of safe and effective medicines. Thus, a key driver for our research is the development of new basic science and technology underpinning the development of new pharmaceutical products. Research includes the structure and properties of drugs and excipients, biopharmaceutical characterisation, pharmaceutical processing and technology and formulation and analysis.Keywords: drug discovery, drug development, drug delivery
Procedia PDF Downloads 4932182 Hybrid-Nanoengineering™: A New Platform for Nanomedicine
Authors: Mewa Singh
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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals
Procedia PDF Downloads 4842181 Spatial Relationship of Drug Smuggling Based on Geographic Information System Knowledge Discovery Using Decision Tree Algorithm
Authors: S. Niamkaeo, O. Robert, O. Chaowalit
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In this investigation, we focus on discovering spatial relationship of drug smuggling along the northern border of Thailand. Thailand is no longer a drug production site, but Thailand is still one of the major drug trafficking hubs due to its topographic characteristics facilitating drug smuggling from neighboring countries. Our study areas cover three districts (Mae-jan, Mae-fahluang, and Mae-sai) in Chiangrai city and four districts (Chiangdao, Mae-eye, Chaiprakarn, and Wienghang) in Chiangmai city where drug smuggling of methamphetamine crystal and amphetamine occurs mostly. The data on drug smuggling incidents from 2011 to 2017 was collected from several national and local published news. Geo-spatial drug smuggling database was prepared. Decision tree algorithm was applied in order to discover the spatial relationship of factors related to drug smuggling, which was converted into rules using rule-based system. The factors including land use type, smuggling route, season and distance within 500 meters from check points were found that they were related to drug smuggling in terms of rules-based relationship. It was illustrated that drug smuggling was occurred mostly in forest area in winter. Drug smuggling exhibited was discovered mainly along topographic road where check points were not reachable. This spatial relationship of drug smuggling could support the Thai Office of Narcotics Control Board in surveillance drug smuggling.Keywords: decision tree, drug smuggling, Geographic Information System, GIS knowledge discovery, rule-based system
Procedia PDF Downloads 1682180 Functionalized DOX Nanocapsules by Iron Oxide Nanoparticles for Targeted Drug Delivery
Authors: Afsaneh Ghorbanzadeh, Afshin Farahbakhsh, Zakieh Bayat
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The drug capsulation was used for release and targeted delivery in determined time, place and temperature or pH. The DOX nanocapsules were used to reduce and to minimize the unwanted side effects of drug. In this paper, the encapsulation methods of doxorubicin (DOX) and the labeling it by the magnetic core of iron (Fe3O4) has been studied. The Fe3O4 was conjugated with DOX via hydrazine bond. The solution was capsuled by the sensitive polymer of heat or pH such as chitosan-g-poly (N-isopropylacrylamide-co-N,N-dimethylacrylamide), dextran-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and mPEG-G2.5 PAMAM by hydrazine bond. The drug release was very slow at temperatures lower than 380°C. There was a rapid and controlled drug release at temperatures higher than 380°C. According to experiments, the use mPEG-G2.5PAMAM is the best method of DOX nanocapsules synthesis, because in this method, the drug delivery time to certain place is lower than other methods and the percentage of released drug is higher. The synthesized magnetic carrier system has potential applications in magnetic drug-targeting delivery and magnetic resonance imaging.Keywords: drug carrier, drug release, doxorubicin, iron oxide NPs
Procedia PDF Downloads 4162179 Prevalence of Drug Injection among Male Prisoners in the West of Iran
Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh
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Background: Substance addiction is one of the major worldwide problems that destroys economy, familial relationships, and the abuser’s career and has several side effects; in the meantime drug injection due to the possibility of shared use of syringes among drug users could have multiple complications to be followed. The purpose of this study was to determine the prevalence of drug injection among male prisoners in Kermanshah city, the west of Iran. Methods: In this cross-sectional study 615 male prisoners were randomly selected to participate voluntarily in the study. Participants filled out a writing self-report questionnaire. Data were analyzed by the SPSS software (ver. 21.0) at 95% significant level. Results: The mean age of respondents was 31.13 years [SD: 7.76]. Mean initiation age for drug use was 14.36 years (range, 9-34 years). Almost, 39.4 % reported a history of drug use before prison. Opium (33.2%) and crystal (27.1%) was the most used drug among prisoners. Furthermore, 9.3 % had a history of injection addiction. There was a significant correlation between age, crime type, marital status, economic status, unprotected sex and drug injection (P < 0.05). Conclusion: The low age of drug abuse and the prevalence of drug injection among offenders can be as a warning for responsible; in this regard, implementation of prevention programs to risky behavior and harm reduction among high-risk groups can follow useful results.Keywords: substance abuse, drug injection, prison, Iran
Procedia PDF Downloads 4832178 Modeling Optimal Lipophilicity and Drug Performance in Ligand-Receptor Interactions: A Machine Learning Approach to Drug Discovery
Authors: Jay Ananth
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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development
Procedia PDF Downloads 1102177 Proposing an Architecture for Drug Response Prediction by Integrating Multiomics Data and Utilizing Graph Transformers
Authors: Nishank Raisinghani
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Efficiently predicting drug response remains a challenge in the realm of drug discovery. To address this issue, we propose four model architectures that combine graphical representation with varying positions of multiheaded self-attention mechanisms. By leveraging two types of multi-omics data, transcriptomics and genomics, we create a comprehensive representation of target cells and enable drug response prediction in precision medicine. A majority of our architectures utilize multiple transformer models, one with a graph attention mechanism and the other with a multiheaded self-attention mechanism, to generate latent representations of both drug and omics data, respectively. Our model architectures apply an attention mechanism to both drug and multiomics data, with the goal of procuring more comprehensive latent representations. The latent representations are then concatenated and input into a fully connected network to predict the IC-50 score, a measure of cell drug response. We experiment with all four of these architectures and extract results from all of them. Our study greatly contributes to the future of drug discovery and precision medicine by looking to optimize the time and accuracy of drug response prediction.Keywords: drug discovery, transformers, graph neural networks, multiomics
Procedia PDF Downloads 1522176 Detection of Important Biological Elements in Drug-Drug Interaction Occurrence
Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi
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Drug-drug interactions (DDIs) are main cause of the adverse drug reactions and nature of the functional and molecular complexity of drugs behavior in human body make them hard to prevent and treat. With the aid of new technologies derived from mathematical and computational science the DDIs problems can be addressed with minimum cost and efforts. Market basket analysis is known as powerful method to identify co-occurrence of thing to discover patterns and frequency of the elements. In this research, we used market basket analysis to identify important bio-elements in DDIs occurrence. For this, we collected all known DDIs from DrugBank. The obtained data were analyzed by market basket analysis method. We investigated all drug-enzyme, drug-carrier, drug-transporter and drug-target associations. To determine the importance of the extracted bio-elements, extracted rules were evaluated in terms of confidence and support. Market basket analysis of the over 45,000 known DDIs reveals more than 300 important rules that can be used to identify DDIs, CYP 450 family were the most frequent shared bio-elements. We applied extracted rules over 2,000,000 unknown drug pairs that lead to discovery of more than 200,000 potential DDIs. Analysis of the underlying reason behind the DDI phenomena can help to predict and prevent DDI occurrence. Ranking of the extracted rules based on strangeness of them can be a supportive tool to predict the outcome of an unknown DDI.Keywords: drug-drug interaction, market basket analysis, rule discovery, important bio-elements
Procedia PDF Downloads 3082175 Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin
Authors: Arpa Petchsomrit, Namfa Sermkaew, Ruedeekorn Wiwattanapatapee
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Oil entrapped floating alginate beads of curcumin were developed and characterized. Cremophor EL, Cremophor RH and Tween 80 were utilized to improve the solubility of the drug. The oil-loaded floating gel beads prepared by emulsion gelation method contained sodium alginate, mineral oil and surfactant. The drug content and % encapsulation declined as the ratio of surfactant was increased. The release of curcumin from 1% alginate beads was significantly more than for the 2% alginate beads. The drug released from the beads containing 25% of tween 80 was about 70% while a higher drug release was observed with the beads containing Cremophor EL or Cremohor RH (approximately 90%). The developed floating beads of curcumin powder with surfactant provided a superior drug release than those without surfactant. Floating beads based on oil entrapment containing the drug solubilized in surfactants is a new delivery system to enhance the dissolution of poorly soluble drugs.Keywords: alginate, curcumin, floating drug delivery, oil entrapped bead
Procedia PDF Downloads 3842174 An In-silico Pharmacophore-Based Anti-Viral Drug Development for Hepatitis C Virus
Authors: Romasa Qasim, G. M. Sayedur Rahman, Nahid Hasan, M. Shazzad Hosain
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Millions of people worldwide suffer from Hepatitis C, one of the fatal diseases. Interferon (IFN) and ribavirin are the available treatments for patients with Hepatitis C, but these treatments have their own side-effects. Our research focused on the development of an orally taken small molecule drug targeting the proteins in Hepatitis C Virus (HCV), which has lesser side effects. Our current study aims to the Pharmacophore based drug development of a specific small molecule anti-viral drug for Hepatitis C Virus (HCV). Drug designing using lab experimentation is not only costly but also it takes a lot of time to conduct such experimentation. Instead in this in silico study, we have used computer-aided techniques to propose a Pharmacophore-based anti-viral drug specific for the protein domains of the polyprotein present in the Hepatitis C Virus. This study has used homology modeling and ab initio modeling for protein 3D structure generation followed by pocket identification in the proteins. Drug-able ligands for the pockets were designed using de novo drug design method. For ligand design, pocket geometry is taken into account. Out of several generated ligands, a new Pharmacophore is proposed, specific for each of the protein domains of HCV.Keywords: pharmacophore-based drug design, anti-viral drug, in-silico drug design, Hepatitis C virus (HCV)
Procedia PDF Downloads 2702173 Development of pH Responsive Nanoparticles for Colon Targeted Drug Delivery System
Authors: V. Balamuralidhara
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The aim of the present work was to develop Paclitaxel loaded polyacrylamide grafted guar gum nanoparticles as pH responsive nanoparticle systems for targeting colon. The pH sensitive nanoparticles were prepared by modified ionotropic gelation technique. The prepared nanoparticles showed mean diameters in the range of 264±0.676 nm to 726±0.671nm, and a negative net charge 10.8 mV to 35.4mV. Fourier Transformed Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) studies suggested that there was no chemical interaction between drug and polymers. The encapsulation efficiency of the drug was found to be 40.92% to 48.14%. The suitability of the polyacrylamide grafted guar gum ERN’s for the release of Paclitaxel was studied by in vitro release at pH 1.2 and 7.4. It was observed that, there was no significant amount of drug release at gastric pH and 97.63% of drug release at pH 7.4 was obtained for optimized formulation F3 at the end of 12 hrs. In vivo drug targeting performance for the prepared optimized formulation (F3) and pure drug Paclitaxel was evaluated by HPLC. It was observed that the polyacrylamide grafted guar gum can be used to prepare nanoparticles for targeting the drug to the colon. The release performance was greatly affected by the materials used in ERN’s preparation, which allows maximum release at colon’s pH. It may be concluded that polyacrylamide grafted guar gum nanoparticles loaded with paclitaxel have desirable release responsive to specific pH. Hence it is a unique approach for colonic delivery of drug having appropriate site specificity and feasibility and controlled release of drug.Keywords: colon targeting, polyacrylamide grafted guar gum nanoparticles, paclitaxel, nanoparticles
Procedia PDF Downloads 3512172 'When 2 + 2 = 5: Synergistic Effects of HRM Practices on the Organizational Performance'
Authors: Qura-tul-aain Khair, Mohtsham Saeed
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Synergy is a main characteristic of human resource management (HRM) system. It highlights the hidden characteristics of HRM system. This research paper has empirically tested that internally consistent and complementary HR practices/components in the HR system are more able to predict and enhance the organizational performance than the sum of individual practice. The data was collected from the sample of 109 firm respondents of service industry through convenience sampling technique. The major finding of this research highlighted that configurational approach to synergy or the HRM system as a whole has an ability to enhance the organizational performance more than by the sum of individual HRM practices of HRM system. Hence, confirming that the whole is greater than the sum of individual parts.Keywords: internally consistant HRM practices, synergistic effects, horizontal fit, vertical fit
Procedia PDF Downloads 3532171 Assessment of Drug Delivery Systems from Molecular Dynamic Perspective
Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah
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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier
Procedia PDF Downloads 3392170 Preparation and Evaluation of Zidovudine Nanoparticles
Authors: D. R. Rama Brahma Reddy, A. Vijaya Sarada Reddy
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Nanoparticles represent a promising drug delivery system of controlled and targeted drug release. They are specially designed to release the drug in the vicinity of target tissue. The aim of this study was to prepare and evaluate polymethacrylic acid nanoparticles containing Zidovudine in different drug to polymer ratio by nanoprecipitation method. SEM indicated that nanoparticles have a discrete spherical structure without aggregation. The average particle size was found to be 120 ± 0.02 - 420 ± 0.05 nm. The particle size of the nanoparticles was gradually increased with increase in the proportion of polymethacrylic acid polymer. The drug content of the nanoparticles was increasing on increasing polymer concentration up to a particular concentration. No appreciable difference was observed in the extent of degradation of product during 60 days in which, nanoparticles were stored at various temperatures. FT-IR studies indicated that there was no chemical interaction between drug and polymer and stability of drug. The in-vitro release behavior from all the drug loaded batches was found to be zero order and provided sustained release over a period of 24 h. The developed formulation overcome and alleviates the drawbacks and limitations of Zidovudine sustained release formulations and could possibility be advantageous in terms of increased bio availability of Zidovudine.Keywords: nanoparticles, zidovudine, biodegradable, polymethacrylic acid
Procedia PDF Downloads 6222169 When and How Do Individuals Transition from Regular Drug Use to Injection Drug Use in Uganda? Findings from a Rapid Assessment
Authors: Stanely Nsubuga
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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.Keywords: People who Use Drugs, transition, injection drug use, Uganda
Procedia PDF Downloads 1292168 The Effect of Backing Layer on Adhesion Properties of Single Layer Ketoprofen Transdermal Drug Delivery System
Authors: Maryam Hamedanlou, Shahla Hajializadeh
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The transdermal drug delivery system is one of the types of novel drug delivery system that the drug is absorbed into the skin. The major considerations for designing and producing transdermal patch are small size, suitable drug release and good adhering. In this study, drug-in-adhesive transdermal patch contained non-steroidal anti-inflammatory ketoprofen is prepared. Also, the effect of non-woven fabric and plastic backing layers on adhesion properties is assessed. The results of the test, demonstrated the use of plastic backing layer increases tack and peel rather than non-woven fabric type. The balance tack with plastic backing layer patch is 6.7 (N/mm2), and the fabric one is 3.8 (N/mm2), and their peel is 9.2 (N/25mm) and 8.3 (N/25mm) by arrangement.Keywords: transdermal drug delivery system, single layer patch of ketoprofen, plastic layer, fabric backing layer
Procedia PDF Downloads 251