Search results for: injection drug users

Authors: Kaowen Grace Chang

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Urban green spaces play an important role in promoting wellbeing through the sense of relaxation for urban residents. Among many designing factors, what the principal ones that could effectively influence people’s sense of relaxation? And, what are the relationship between the sense of relaxation and those factors? Regarding those questions, there is still little evidence for sufficient support. Therefore, the purpose of this study, based on individual responses to environmental information, is to investigate the landscape factors that relate to well-being through the sense of relaxation in mixed-use urban environments. We conducted the experimental design and model construction utilizing choice-based conjoint analysis to test the factors of plant arrangement pattern, plant trimming condition, the distance to visible automobile, the number of landmark objects, and the depth of view. Through the operation of balanced fractional orthogonal design, the goal is to know the relationship between the sense of relaxation and different designs. In a result, the three factors of plant trimming condition, the distance to visible automobile, and the depth of view shed are significantly effective to the sense of relaxation. The stronger magnitude of maintenance and trimming, the further distance to visible automobiles, and deeper view shed that allow the users to see further scenes could significantly promote green space users’ sense of relaxation in urban green spaces.

Keywords: urban green space, landscape planning and design, sense of relaxation, choice model

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Authors: Xuan Pang, Alvin L. Lee, Peggy Glatthaar

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Libraries across the world have been an innovation engine of creativity and opportunityin many decades. The on-going global epidemiology outbreak and health crisis experience illuminates potential reforms, rethinking beyond traditional library operations and services. Controlled Digital Lending (CDL) is one of the emerging technologies libraries used to deliver information digitally in support of online learning and teachingand make educational materials more affordable and more accessible. CDL became a popular term in the United States of America (USA) as a result of a white paper authored by Kyle K. Courtney (Harvard University) and David Hansen (Duke University). The paper gave the legal groundwork to explore CDL: Fair Use, First Sale Doctrine, and Supreme Court rulings. Library professionals implemented this new technology to fulfill their users’ needs. Three libraries in the state of Florida (University of Florida, Florida Gulf Coast University, and Florida A&M University) started a conversation about how to develop strategies to make CDL work possible at each institution. This paper shares the stories of piloting and initiating a CDL program to ensure students have reliable, affordable access to course materials they need to be successful. Additionally, this paper offers an overview of the emerging trends of Controlled Digital Lending in the USA and demonstrates the development of the CDL platforms, policies, and implementation plans. The paper further discusses challenges and lessons learned and how each institution plans to sustain the program into future library services. The fundamental mission of the library is providing users unrestricted access to library resources regardless of their physical location, disability, health status, or other circumstances. The professional due diligence of librarians, as information professionals, is to makeeducational resources more affordable and accessible.CDL opens a new frontier of library services as a mechanism for library practice to enhance user’s experience of using libraries’ services. Libraries should consider exploring this tool to distribute library resources in an effective and equitable way. This new methodology has potential benefits to libraries and end users.

Keywords: controlled digital lending, emerging technologies, equitable access, collaborations

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Authors: Qin Zhu

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Under the development concept of Park City, Tianfu Greenway system, as the basic and pre-configuration element of Chengdu Global Park construction, connects urban open space with linear and circular structures and undertakes and exerts the ecological, cultural and recreational functions of the park system. Chengdu greenway construction is in full swing. In the process of greenway planning and construction, the landscape effect of greenway on urban quality improvement is more valued, and the long-term impact of crowd experience on the sustainable development of greenway is often ignored. Therefore, it is very important to test the effectiveness of greenway construction from the perspective of users. Taking Jincheng Greenway in Chengdu as an example, this paper attempts to introduce multi-source data to construct a post-occupancy evaluation model of greenway and adopts behavior mapping method, questionnaire survey method, web text analysis and IPA analysis method to comprehensively evaluate the user 's behavior characteristics and satisfaction. According to the evaluation results, we can grasp the actual behavior rules and comprehensive needs of users so that the experience of building greenways can be fed back in time and provide guidance for the optimization and improvement of built greenways and the planning and construction of future greenways.

Keywords: multi-source data, greenway, IPA analysis, post -occupancy evaluation (POE)

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Authors: Famurewa Olumide Joseph, Akinsulore Adesanmi

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The current study investigated aggressive behaviour and its association with substance use disorder among senior secondary school students in Ilesha, Nigeria. Participants were three hundred and seventy-five (375) comprising (212) females and (163) males of senior secondary school students in Ilesa East and Ilesa West; who were randomly selected among the population of students from the schools. The mean age of the respondents was 14.61 years (S.D = 1.16), with 311 (82.9%) between 14 – 16 years. Female respondents were 212 (56.5%), while male respondents were 163 (43.5%). A cross sectional design was adopted. Three instruments were used for data collection. Buss Perry Aggression Questionnaire, Alcohol Use Disorder Identification Test (AUDIT) and Drug Abuse Screening Test (DAST). It was hypothesized that aggressive behaviour will be associated with substance use disorder among senior secondary school students in Ilesa East and Ilesa West. The result indicated that the overall prevalence of substance use disorder was 16.0%. Chi-Square test exploring the association between aggressive behaviour and substance use disorder shows that there is a significant association between aggressive behaviour and substance use disorder (χ2 =8.55, p =0.014). Results also showed that emotional problem (χ2 (2) =13.0; p = 0.001) was statistically significant while current medications intake (χ2 (2) =2.03; p =0.362) and overall wellbeing (χ2 (4) =2.49; p =0.646) were not statistically significant. There is an inverse association between prosocial behaviour and aggressive behaviour (r= -0.037, p>0.05). This indicates that as the level of prosocial behaviour increases, the level of aggressive behaviour among respondents decreases. However, alcohol use had no correlation with aggressive behaviour (r=0.070, p>0.05). Among the implications stated is that factors such as emotional symptoms, conduct problems, hyperactivity, peer problem and drug use contributed to the prevalence of aggressive behaviour among students. Suggestions for further studies were equally made.

Keywords: aggressive behaviour, alcohol, prevalence, students, substance use disorder (SUD)

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Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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Authors: Aarnav Singh, Jatin Moolchandani

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The proposed research work aims to build a query-based AI chatbot that can answer any question related to any topic. A chatbot is software that converses with users via text messages. In the proposed system, we aim to build a chatbot that generates a response based on the user’s query. For this, we use natural language processing to analyze the query and some set of texts to form a concise answer. The texts are obtained through web-scrapping and filtering all the credible sources from a web search. The objective of this project is to provide a chatbot that is able to provide simple and accurate answers without the user having to read through a large number of articles and websites. Creating an AI chatbot that can answer a variety of user questions on a variety of topics is the goal of the proposed research project. This chatbot uses natural language processing to comprehend user inquiries and provides succinct responses by examining a collection of writings that were scraped from the internet. The texts are carefully selected from reliable websites that are found via internet searches. This project aims to provide users with a chatbot that provides clear and precise responses, removing the need to go through several articles and web pages in great detail. In addition to exploring the reasons for their broad acceptance and their usefulness across many industries, this article offers an overview of the interest in chatbots throughout the world.

Keywords: Chatbot, Artificial Intelligence, natural language processing, web scrapping

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Authors: Abbas Jafarizad, Duygu Ekinci

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In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

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Authors: Emre Bayamlıoğlu

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This paper aims to provide an account of the legal and the regulative aspects of the algorithmic reputation systems with a special emphasis on the sharing economy (i.e., Uber, Airbnb, Lyft) business model. The first section starts with an analysis of the legal and commercial nature of the tripartite relationship among the parties, namely, the host platform, individual sharers/service providers and the consumers/users. The section further examines to what extent an algorithmic system of reputational information could serve as an alternative to legal regulation. Shortcomings are explained and analyzed with specific examples from Airbnb Platform which is a pioneering success in the sharing economy. The following section focuses on the issue of governance and control of the reputational information. The section first analyzes the legal consequences of algorithmic filtering systems to detect undesired comments and how a delicate balance could be struck between the competing interests such as freedom of speech, privacy and the integrity of the commercial reputation. The third section deals with the problem of manipulation by users. Indeed many sharing economy businesses employ certain techniques of data mining and natural language processing to verify consistency of the feedback. Software agents referred as "bots" are employed by the users to "produce" fake reputation values. Such automated techniques are deceptive with significant negative effects for undermining the trust upon which the reputational system is built. The third section is devoted to explore the concerns with regard to data mobility, data ownership, and the privacy. Reputational information provided by the consumers in the form of textual comment may be regarded as a writing which is eligible to copyright protection. Algorithmic reputational systems also contain personal data pertaining both the individual entrepreneurs and the consumers. The final section starts with an overview of the notion of reputation as a communitarian and collective form of referential trust and further provides an evaluation of the above legal arguments from the perspective of public interest in the integrity of reputational information. The paper concludes with certain guidelines and design principles for algorithmic reputation systems, to address the above raised legal implications.

Keywords: sharing economy, design principles of algorithmic regulation, reputational systems, personal data protection, privacy

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Authors: Nashed Atef Nashed Farag

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Introduction: Reporting adverse events following vaccination remains a challenge. WHO has mandated pharmacovigilance centers around the world to submit Adverse Events Following Immunization (AEFI) reports from different countries to a large electronic database of adverse drug event data called Vigibase. Despite sufficient information about AEFIs on Vigibase, they are not available to the general public. However, the WHO has an alternative website called VigiAccess, an open-access website that serves as an archive for reported adverse reactions and AEFIs. The aim of the study was to establish a reporting model for a number of commonly used vaccines in the VigiAccess system. Methods: On February 5, 2018, VigiAccess comprehensively searched for ESSI reports on the measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine, and tuberculosis vaccine (BCG). These are reports from all pharmacovigilance centers around the world since they joined the WHO Drug Monitoring Program. Results: After an extensive search, VigiAccess found 9,062 AEFIs from the measles vaccine, 185,829 AEFIs from the OPV vaccine, 24,577 AEFIs from the yellow fever vaccine, 317,208 AEFIs from the pneumococcal vaccine, 73,513 AEFIs from the rotavirus vaccine, and 145,447 AEFIs from meningococcal cal vaccine, 22,781 EI FI vaccines against tetanus and 35,556 BCG vaccines against AEFI. Conclusion: The study found that among the eight vaccines examined, pneumococcal vaccines were associated with the highest number of AEFIs, while measles vaccines were associated with the fewest AEFIs.

Keywords: surgical approach, anatomical approach, decompression, axillary nerve, quadrangular space adverse events following immunization, cameroon, COVID-19 vaccines, nOPV, ODK vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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Authors: Florian Engel

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Only with a radical change to an intrinsically motivated project team, through giving the employees the freedom for autonomy, mastery and purpose, it is then possible to develop excellent products. With these changes, combined with using a rapid application development approach, the group of users serves as an important indicator to test the market needs, rather than only as the stakeholders for requirements.

Keywords: intrinsic motivation, requirements elicitation, self-directed work, stakeholder participation

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Authors: David Bakker, Nikki Rickard

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Smartphone apps hold immense potential as mental health and wellbeing tools. Support can be made easily accessible and can be used in real-time while users are experiencing distress. Furthermore, data can be collected to enable machine learning and automated tailoring of support to users. While many apps have been developed for mental health purposes, few have adhered to evidence-based recommendations and even fewer have pursued experimental validation. This paper details the development and experimental evaluation of an app, MoodMission, that aims to provide support for low moods and anxiety, help prevent clinical depression and anxiety disorders, and serve as an adjunct to professional clinical supports. MoodMission was designed to deliver cognitive behavioural therapy for specifically reported problems in real-time, momentary interactions. Users report their low moods or anxious feelings to the app along with a subjective units of distress scale (SUDS) rating. MoodMission then provides a choice of 5-10 short, evidence-based mental health strategies called Missions. Users choose a Mission, complete it, and report their distress again. Automated tailoring, gamification, and in-built data collection for analysis of effectiveness was also included in the app’s design. The development process involved construction of an evidence-based behavioural plan, designing of the app, building and testing procedures, feedback-informed changes, and a public launch. A randomized controlled trial (RCT) was conducted comparing MoodMission to two other apps and a waitlist control condition. Participants completed measures of anxiety, depression, well-being, emotional self-awareness, coping self-efficacy and mental health literacy at the start of their app use and 30 days later. At the time of submission (November 2016) over 300 participants have participated in the RCT. Data analysis will begin in January 2017. At the time of this submission, MoodMission has over 4000 users. A repeated-measures ANOVA of 1390 completed Missions reveals that SUDS (0-10) ratings were significantly reduced between pre-Mission ratings (M=6.20, SD=2.39) and post-Mission ratings (M=4.93, SD=2.25), F(1,1389)=585.86, p < .001, np2=.30. This effect was consistent across both low moods and anxiety. Preliminary analyses of the data from the outcome measures surveys reveal improvements across mental health and wellbeing measures as a result of using the app over 30 days. This includes a significant increase in coping self-efficacy, F(1,22)=5.91, p=.024, np2=.21. Complete results from the RCT in which MoodMission was evaluated will be presented. Results will also be presented from the continuous outcome data being recorded by MoodMission. MoodMission was successfully developed and launched, and preliminary analysis suggest that it is an effective mental health and wellbeing tool. In addition to the clinical applications of MoodMission, the app holds promise as a research tool to conduct component analysis of psychological therapies and overcome restraints of laboratory based studies. The support provided by the app is discrete, tailored, evidence-based, and transcends barriers of stigma, geographic isolation, financial limitations, and low health literacy.

Keywords: anxiety, app, CBT, cognitive behavioural therapy, depression, eHealth, mission, mobile, mood, MoodMission

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Authors: Kobauri Sophio, Kantaria Tengiz, Tugushi David, Puiggali Jordi, Katsarava Ramaz

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Biodegradable biomaterials (BB) are of high interest for numerous applications in modern medicine as resorbable surgical materials and drug delivery systems. This kind of materials can be cleared from the body after the fulfillment of their function that excludes a surgical intervention for their removal. One of the most promising BBare amino acids based biodegradable poly(ester amide)s (PEAs) which are composed of naturally occurring (α-amino acids) and non-toxic building blocks such as fatty diols and dicarboxylic acids. Key bis-nucleophilic monomers for synthesizing the PEAs are diamine-diesters-di-p-toluenesulfonic acid salts of bis-(α-amino acid)-alkylenediesters (TAADs) which form the PEAs after step-growth polymerization (polycondensation) with bis-electrophilic counter-partners - activated diesters of dicarboxylic acids. The PEAs combine all advantages of the 'parent polymers' – polyesters (PEs) and polyamides (PAs): Ability of biodegradation (PEs), a high affinity with tissues and a wide range of desired mechanical properties (PAs). The scopes of applications of thePEAs can substantially be expanded by their functionalization, e.g. through the incorporation of hydrophobic fragments into the polymeric backbones. Hydrophobically modified PEAs can form non-covalent adducts with various compounds that make them attractive as drug carriers. For hydrophobic modification of the PEAs, we selected so-called 'Azlactone Method' based on the application of p-phenylene-bis-oxazolinons (bis-azlactones, BALs) as active bis-electrophilic monomers in step-growth polymerization with TAADs. Interaction of BALs with TAADs resulted in the PEAs with low MWs (Mw2,800-19,600 Da) and poor material properties. The high-molecular-weight PEAs (Mw up to 100,000) with desirable material properties were synthesized after replacement of a part of BALs with activated diester - di-p-nitrophenylsebacate, or a part of TAAD with alkylenediamine – 1,6-hexamethylenediamine. The new hydrophobically modified PEAs were characterized by FTIR, NMR, GPC, and DSC. It was shown that after the hydrophobic modification the PEAs retain the biodegradability (in vitro study catalyzed by α-chymptrypsin and lipase), and are of interest for constructing resorbable surgical and pharmaceutical devices including drug delivering containers such as microspheres. The new PEAs are insoluble in hydrophobic organic solvents such as chloroform or dichloromethane (swell only) that allowed elaborating a new technology of fabricating microspheres.

Keywords: amino acids, biodegradable polymers, bis-azlactones, microspheres

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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Authors: Rujijan Vichivanives

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This research aims to create a knowledge-based system as a database for self-healthcare analysis, diagnosis of simple illnesses, and the use of Thai herbs instead of modern medicine by using principles of Thai traditional medication theory. These were disseminated by website network programs within Suan Sunandha Rajabhat University. The population used in this study was divided into two groups: the first group consisted of four experts of Thai traditional medication and the second group was 300 website users. The methods used for collecting data were paper questionnaires and poll questionnaires on the website. The statistics used for analyzing data was at an average level. The results were divided into three parts: the first part was the development of a knowledge-based system and the second part was applied programs on website. Both parts could be fulfilled and achieved according to the set goal. The third part was the evaluation of the study: The evaluation of the viewpoints of the experts towards website designs were evaluated at a good level of 4.20. The satisfaction evaluation of the users was found at a good level of average satisfactory level at 4.24. It was found that the young population of those under the age of 16 had less cares about their health than the population of other teenagers, working age adults and those of older age. The research findings should be extended in order to encourage the lifestyle modifications to people of all ages by using the self-healthcare principles.

Keywords: developing, herbs, knowledge-based system, medical treatment

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Angelica S. Valeriani, Lorenzo Biasiolo

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In recent years, the scale of the impact of climate change and its related side effects has become ever more massive and devastating. Sustainable Development Goals (SDGs), promoted by United Nations, aim to front issues related to climate change, among others. In particular, the project CROWD4SDG focuses on a bunch of SDGs since it promotes environmental activities and climate-related issues. In this context, we developed a prototype of an application, under advanced development considering web design, that focuses on SDG 13 (SDG on climate action) by providing users with useful instruments to face environmental crises and climate-related disasters. Our prototype is thought and structured for both web and mobile development. The main goal of the application, POLI4SDG, is to help users to get through emergency services. To this extent, an organized overview and classification prove to be very effective and helpful to people in need. A careful analysis of data related to environmental crises prompted us to integrate the user contribution, i.e., exploiting a core principle of Citizen Science, into the realization of a public catalog, available for consulting and organized according to typology and specific features. In addition, gender equality and opportunity features are considered in the prototype in order to allow women, often the most vulnerable category, to have direct support. The overall description of the application functionalities is detailed. Moreover, the implementation features and properties of the prototype are discussed.

Keywords: crowdsourcing, social media, SDG, climate change, natural disasters, gender equality

Procedia PDF Downloads 94

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

Abstract:

A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

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Authors: Shweta Verma

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Background: Epilepsy is a chronic non-communicable central nervous system (CNS) disorder which affects a large population of all ages. Different classes of drugs are used for the treatment of this neurological disorder, but due to augmented drug resistance and side effects, these drugs become incompetent. Therefore, we design the synthesis of ten new derivatives of Phenytoin. The moiety of Phenytoin was hybridized with different phenols by using three step approach. The synthesized molecules were then investigated for different physicochemical parameters, such as Log P values using diverse software programs and to predict the potential to cross the blood-brain barrier. Objective: The Phenytoin derivatives were designed, synthesized, and characterized to meet the structural necessities indispensable for antiepileptic activity. Method: Firstly, the chloroacetylation of the 5,5-diphenyl hydantoin was carried out, and then various substituted phenols were added to it. The synthesized compounds were characterized and evaluated for antianxiety activity by elevated plus maze method and antiepileptic activity by using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) models and neurotoxicity. Result: The number of derivatives of 5,5-diphenyl hydantoin was developed and optimized. The number of parameters was optimized which reveal that the compound containing chloro group such as C3 and C6 showed imperative potential when compared with the standard drug Diazepam. Other compounds containing nitro and methyl group were also found to possess activity. Conclusion: It was summarized that the new compounds of 5,5-diphenyl hydantoin derivatives were synthesized. The results of the data show that the compound containing chloro group is more potent for CNS activity. The new compounds have the probability of being optimized further to engender new scaffolds to treat various CNS disorders.

Keywords: phenytoin, parameters, CNS activity, blood-brain barrier, Log P, CNS active

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Authors: G. S. Thyagaraju, U. P. Kulkarni

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Context-aware computing refers to a general class of computing systems that can sense their physical environment, and adapt their behaviour accordingly. Context aware computing makes systems aware of situations of interest, enhances services to users, automates systems and personalizes applications. Context-aware services have been introduced into mobile devices, such as PDA and mobile phones. In this paper we are presenting a novel approaches used to realize the context aware mobile. The context aware mobile phone (CAMP) proposed in this paper senses the users situation automatically and provides user context required services. The proposed system is developed by using artificial intelligence techniques like Bayesian Network, fuzzy logic and rough sets theory based decision table. Bayesian Network to classify the incoming call (high priority call, low priority call and unknown calls), fuzzy linguistic variables and membership degrees to define the context situations, the decision table based rules for service recommendation. To exemplify and demonstrate the effectiveness of the proposed methods, the context aware mobile phone is tested for college campus scenario including different locations like library, class room, meeting room, administrative building and college canteen.

Keywords: context aware mobile, fuzzy logic, decision table, Bayesian probability

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Authors: Teo Hao Jing, Shane Ho Ken Wae, Lee Jin Yu, Burra Venkata Durga Kumar

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Current distributed healthcare systems face the challenge of interoperability of health data. Storing electronic health records (EHR) in local databases causes them to be fragmented. This problem is aggravated as patients visit multiple healthcare providers in their lifetime. Existing solutions are unable to solve this issue and have caused burdens to healthcare specialists and patients alike. Blockchain technology was found to be able to increase the interoperability of health data by implementing digital access rules, enabling uniformed patient identity, and providing data aggregation. Consortium blockchain was found to have high read throughputs, is more trustworthy, more secure against external disruptions and accommodates transactions without fees. Therefore, this paper proposes a blockchain-based model for data management applications. In this model, a consortium blockchain is implemented by using a delegated proof of stake (DPoS) as its consensus mechanism. This blockchain allows collaboration between users from different organizations such as hospitals and medical bureaus. Patients serve as the owner of their information, where users from other parties require authorization from the patient to view their information. Hospitals upload the hash value of patients’ generated data to the blockchain, whereas the encrypted information is stored in a distributed cloud storage.

Keywords: blockchain technology, data management applications, healthcare, interoperability, delegated proof of stake

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Authors: Bi Zhao

Abstract:

Neural network technology has greatly improved the output of machine translation in terms of both fluency and accuracy, which greatly increases its appeal for young users. The present exploratory study aims to find out how the Chinese undergraduates perceive and use machine translation in their daily life. A survey is conducted to collect data from 100 undergraduate students from multiple Chinese universities and with varied academic backgrounds, including arts, business, science, engineering, and medicine. The survey questions inquire about their use (including frequency, scenarios, purposes, and preferences) of and attitudes (including trust, quality assessment, justifications, and ethics) toward machine translation. Interviews and tasks of evaluating machine translation output are also employed in combination with the survey on a sample of selected respondents. The results indicate that Chinese undergraduate students use machine translation on a daily basis for a wide range of purposes in academic, communicative, and entertainment scenarios. Most of them have preferred machine translation tools, but the availability of machine translation tools within a certain scenario, such as the embedded machine translation tool on the webpage, is also the determining factor in their choice. The results also reveal that despite the reportedly limited trust in the accuracy of machine translation output, most students lack the ability to critically analyze and evaluate such output. Furthermore, the evidence is revealed of the inadequate awareness of ethical responsibility as machine translation users among Chinese undergraduate students.

Keywords: Chinese undergraduates, machine translation, trust, usage

Procedia PDF Downloads 116

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Pimpak Phumat, Sakornrat Khongkhunthian, Thomas Rades, Anette Müllertz, Siriporn Okonogi

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Self-nanoemulsifying drug delivery systems (SNEDDS) containing 4-allylpyrocatechol (AP) extracted from Piper betle were developed to enhance water solubility of AP by using modeling and design (MODDE) program. The amount of AP in each SNEDDS formulation was determined by using high-performance liquid chromatography. The formulation consisted of 20% Miglyol®812N, 40 % Kolliphor®RH40, 30 % Maisine®35-1 and 10 % ethanol was found to be the best SNEDDS that provided the highest loading capacity of AP. (141.48±15.64 mg/g SNEDDS). The system also showed miscibility with water. The particle shape and size of the AP-SNEDDS after dispersing in water was investigated by using a transmission electron microscope and photon correlation spectrophotometer, respectively. The results showed that they were a spherical shape, having a particle size of 34.27 ± 1.14 nm with a narrow size distribution of 0.17 ± 0.04. The particles showed negative zeta potential with a value of -21.66 ± 2.09 mV. Antibacterial activity of AP-SNEDDS containing 1.5 mg/mL of AP was investigated against Streptococcus intermedius. The effect of this system on S. intermedius cells was observed by a scanning electron microscope (SEM). The results from SEM revealed that the bacterial cells were obviously destroyed. Killing kinetic study of AP-SNEDDS was carried out. It was found that the killing rate of AP-SNEDDS against S. intermedius was dose-dependent and the bacterial reduction was 79.86 ± 0.45 % within 30 min. In comparison with chlorhexidine (CHX), AP-SNEDDS showed similar antibacterial effects against S. intermedius. It is concluded that SNEDDS is a potential system for enhancing water solubility of AP. The antibacterial study reveals that AP-SNEDDS can be a promising system to treat bacterial infection caused by S. intermedius.

Keywords: SNEDDS, 4-allylpyrocathecol, solubility, antibacterial activity, Streptococcus intermedius

Procedia PDF Downloads 101

Authors: Shanhua Hu

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Social media as a critical propagandizing form of film, video games, and digital products has received substantial research attention, but there exists several critical barriers such as: (1) few studies exploring the internal and external connections of a product as part of the multimodal context that gives rise to readability and commercial return; (2) the lack of study of multimodal analysis in product’s official account of game publishers and its impact on users’ behaviors including purchase intention, social media engagement, and playing time; (3) no standardized ecologically-valid, game type-varying data can be used to study the complexity of official account’s postings within a time period. This proposed research helps to tackle these limitations in order to develop a model of readability study that is more ecologically valid, robust, and thorough. To accomplish this objective, this paper provides a more diverse dataset comprising different visual elements and messages collected from the official Twitter accounts of the Top 20 best-selling games of 2021. Video game companies target potential users through social media, a popular approach is to set up an official account to maintain exposure. Typically, major game publishers would create an official account on Twitter months before the game's release date to update on the game's development, announce collaborations, and reveal spoilers. Analyses of tweets from those official Twitter accounts would assist publishers and marketers in identifying how to efficiently and precisely deploy advertising to increase game sales. The purpose of this research is to determine how official game accounts use Twitter to attract new customers, specifically which types of messages are most effective at increasing sales. The dataset includes the number of days until the actual release date on Twitter posts, the readability of the post (Flesch Reading Ease Score, FRES), the number of emojis used, the number of hashtags, the number of followers of the mentioned users, the categorization of the posts (i.e., spoilers, collaborations, promotions), and the number of video views. The timeline of Twitter postings from official accounts will be compared to the history of pre-orders and sales figures to determine the potential impact of social media posts. This study aims to determine how the above-mentioned characteristics of official accounts' Twitter postings influence the sales of the game and to examine the possible causes of this influence. The outcome will provide researchers with a list of potential aspects that could influence people's judgments in limited-word posts. With the increased average online time, users would adapt more quickly than before in online information exchange and readings, such as the word to use sentence length, and the use of emojis or hashtags. The study on the promotion of official game accounts will not only enable publishers to create more effective promotion techniques in the future but also provide ideas for future research on the influence of social media posts with a limited number of words on consumers' purchasing decisions. Future research can focus on more specific linguistic aspects, such as precise word choice in advertising.

Keywords: engagement, official account, promotion, twitter, video game

Procedia PDF Downloads 62

Authors: Alessandro Evangelista, Vito M. Manghisi, Michele Gattullo, Enricoandrea Laviola

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In this work, we propose a custom visualization technique for Out-Of-View-Objects in Virtual and Augmented Reality applications using Head Mounted Displays. In the last two decades, Augmented Reality (AR) and Virtual Reality (VR) technologies experienced a remarkable growth of applications for navigation, interaction, and collaboration in different types of environments, real or virtual. Both environments can be potentially very complex, as they can include many virtual objects located in different places. Given the natural limitation of the human Field of View (about 210° horizontal and 150° vertical), humans cannot perceive objects outside this angular range. Moreover, despite recent technological advances in AR e VR Head-Mounted Displays (HMDs), these devices still suffer from a limited Field of View, especially regarding Optical See-Through displays, thus greatly amplifying the challenge of visualizing out-of-view objects. This problem is not negligible when the user needs to be aware of the number and the position of the out-of-view objects in the environment. For instance, during a maintenance operation on a construction site where virtual objects serve to improve the dangers' awareness. Providing such information can enhance the comprehension of the scene, enable fast navigation and focused search, and improve users' safety. In our research, we investigated how to represent out-of-view-objects in HMD User Interfaces (UI). Inspired by commercial video games such as Call of Duty Modern Warfare, we designed a customized Compass. By exploiting the Unity 3D graphics engine, we implemented our custom solution that can be used both in AR and VR environments. The Compass Bar consists of a graduated bar (in degrees) at the top center of the UI. The values of the bar range from -180 (far left) to +180 (far right), the zero is placed in front of the user. Two vertical lines on the bar show the amplitude of the user's field of view. Every virtual object within the scene is represented onto the compass bar as a specific color-coded proxy icon (a circular ring with a colored dot at its center). To provide the user with information about the distance, we implemented a specific algorithm that increases the size of the inner dot as the user approaches the virtual object (i.e., when the user reaches the object, the dot fills the ring). This visualization technique for out-of-view objects has some advantages. It allows users to be quickly aware of the number and the position of the virtual objects in the environment. For instance, if the compass bar displays the proxy icon at about +90, users will immediately know that the virtual object is to their right and so on. Furthermore, by having qualitative information about the distance, users can optimize their speed, thus gaining effectiveness in their work. Given the small size and position of the Compass Bar, our solution also helps lessening the occlusion problem thus increasing user acceptance and engagement. As soon as the lockdown measures will allow, we will carry out user-tests comparing this solution with other state-of-the-art existing ones such as 3D Radar, SidebARs and EyeSee360.

Keywords: augmented reality, situation awareness, virtual reality, visualization design

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

Procedia PDF Downloads 127