Search results for: Automated drug delivery systems

Authors: Jorge Fernandes Teixeira Filho, André Oliveira Alcantara Fontenele, Érick Aragão Ribeiro

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The constant emergence of new technologies used in automated processes makes it necessary for teachers and traders to apply new technologies in their classes. This paper presents an application of a new technology that will be employed in a didactic plant, which represents an effluent treatment process located in a laboratory of a federal educational institution. At work were studied in the first place, all components to be placed on automation laboratory in order to determine ways to program, parameterize and organize the plant. New technologies that have been implemented to the process are basically an AS-i network and a Profinet network, a SCADA system, which represented a major innovation in the laboratory. The project makes it possible to carry out in the laboratory various practices of industrial networks and SCADA systems.

Keywords: automation, industrial networks, SCADA systems, lab automation

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Authors: Aminu Bashir Mohammad, Agwu Ezera, Abdulrazaq G. Habib, Garba Iliyasu

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Background: Drug resistance tuberculosis (DR-TB) continues to be a challenge in developing countries with poor resources. Routine screening for primary DR-TB before commencing treatment is not done in public hospitals in Nigeria, even with the large body of evidence that shows a high prevalence of primary DR-TB. Data on drug resistance and its genetic determinant among follow up TB patients is lacking in Nigeria. Hence the aim of this study was to determine the prevalence and genetic determinant of drug resistance among follow up TB patients in a tertiary hospital in Nigeria. Methods: This was a cross-sectional laboratory-based study conducted on 384 sputum samples collected from consented follow-up tuberculosis patients. Standard microbiology methods (Zeil-Nielsen staining and microscopy) and PCR (Line Probe Assay)] were used to analyze the samples collected. Person’s Chi-square was used to analyze the data generated. Results: Out of three hundred and eighty-four (384) sputum samples analyzed for mycobacterium tuberculosis (MTB) and DR-TB twenty-five 25 (6.5%) were found to be AFB positive. These samples were subjected to PCR (Line Probe Assay) out of which 18(72%) tested positive for DR-TB. Mutations conferring resistance to rifampicin (rpo B) and isoniazid (katG, and or inhA) were detected in 12/18(66.7%) and 6/18(33.3%), respectively. Transmission dynamic of DR-TB was not significantly (p>0.05) dependent on demographic characteristics. Conclusion: There is a need to strengthened the laboratory capacity for diagnosis of TB and drug resistance testing and make these services available, affordable, and accessible to the patients who need them.

Keywords: drug resistance tuberculosis, genetic determinant, intensive phase, Nigeria

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Authors: Karolina Wieczorek, Sophie Wiliams

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Introduction: Patient data is often collected in Electronic Health Record Systems (EHR) for purposes such as providing care as well as reporting data. This information can be re-used to validate data models in clinical trials or in epidemiological studies. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. Mentioning a disease in a discharge letter does not necessarily mean that a patient suffers from this disease. Many of them discuss a diagnostic process, different tests, or discuss whether a patient has a certain disease. The COVID-19 dataset in this study used natural language processing (NLP), an automated algorithm which extracts information related to COVID-19 symptoms, complications, and medications prescribed within the hospital. Free-text patient clinical patient notes are rich sources of information which contain patient data not captured in a structured form, hence the use of named entity recognition (NER) to capture additional information. Methods: Patient data (discharge summary letters) were exported and screened by an algorithm to pick up relevant terms related to COVID-19. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. A list of 124 Systematized Nomenclature of Medicine (SNOMED) Clinical Terms has been provided in Excel with corresponding IDs. Two independent medical student researchers were provided with a dictionary of SNOMED list of terms to refer to when screening the notes. They worked on two separate datasets called "A” and "B”, respectively. Notes were screened to check if the correct term had been picked-up by the algorithm to ensure that negated terms were not picked up. Results: Its implementation in the hospital began on March 31, 2020, and the first EHR-derived extract was generated for use in an audit study on June 04, 2020. The dataset has contributed to large, priority clinical trials (including International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) by bulk upload to REDcap research databases) and local research and audit studies. Successful sharing of EHR-extracted datasets requires communicating the provenance and quality, including completeness and accuracy of this data. The results of the validation of the algorithm were the following: precision (0.907), recall (0.416), and F-score test (0.570). Percentage enhancement with NLP extracted terms compared to regular data extraction alone was low (0.3%) for relatively well-documented data such as previous medical history but higher (16.6%, 29.53%, 30.3%, 45.1%) for complications, presenting illness, chronic procedures, acute procedures respectively. Conclusions: This automated NLP algorithm is shown to be useful in facilitating patient data analysis and has the potential to be used in more large-scale clinical trials to assess potential study exclusion criteria for participants in the development of vaccines.

Keywords: automated, algorithm, NLP, COVID-19

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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Authors: Dovile Petkeviciute-Barysiene

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Legal technologies not only create new ways for accessing and providing legal services but also transform the role of legal practitioners. Both lawyers and users of legal services expect automated solutions to outperform people with objectivity and impartiality. Although fairness of the automated decisions is crucial, research on assessing various characteristics of automated processes related to the perceived fairness has only begun. One of the major obstacles to this research is the lack of comprehensive understanding of what legal actions are automated and could be meaningfully automated, and to what extent. Neither public nor legal practitioners oftentimes cannot envision technological input due to the lack of general without illustrative examples. The aim of this study is to map decision making stages and automation levels which are and/or could be achieved in legal actions related to pre-trial and trial processes. Major legal decisions and judgments are identified during the consultations with legal practitioners. The dual-process model of information processing is used to describe cognitive processes taking place while making legal decisions and judgments during pre-trial and trial action. Some of the existing legal technologies are incorporated into the analysis as well. Several published automation level taxonomies are considered because none of them fit well into the legal context, as they were all created for avionics, teleoperation, unmanned aerial vehicles, etc. From the information processing perspective, analysis of the legal decisions and judgments expose situations that are most sensitive to cognitive bias, among others, also help to identify areas that would benefit from the automation the most. Automation level analysis, in turn, provides a systematic approach to interaction and cooperation between humans and algorithms. Moreover, an integrated map of legal decisions and judgments, information processing characteristics, and automation levels all together provide some groundwork for the research of legal technology perceived fairness and acceptance. Acknowledgment: This project has received funding from European Social Fund (project No 09.3.3-LMT-K-712-19-0116) under grant agreement with the Research Council of Lithuania (LMTLT).

Keywords: automation levels, information processing, legal judgment and decision making, legal technology

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Authors: Mohamad Reza Khodabakhsh

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Drug use and addiction are major biological, psychological, and social problems. In drug abuse treatment, it is important to pay attention to personality problems and coping methods of patients. Today, the third-wave treatments in psychotherapy emphasize people's awareness and acceptance of feelings and emotions, cognitions, and behaviors instead of challenging cognitions. For this reason, this research was conducted with the aim of investigating the effectiveness of group therapy based on acceptance and commitment to self-criticism and coping strategies of people with drug use disorder. This research was a quasi-experimental type of research (pre-test-post-test design with an unequal control group), and the statistical population of this research included all men with drug use disorder in Mashhad, 174 of whom among the 75 people eligible for this research, 30 of them were selected by available sampling method and randomly assigned to two experimental and control groups. In this research, Gilbert's self-criticism scale was used to measure self-criticism, and Andler and Barker's coping strategies questionnaire was used to measure coping strategies. Therapeutic intervention (treatment based on acceptance and commitment) was performed on the experimental group for eight sessions of 90 minutes, and then post-tests were taken from both groups, and multivariate analysis of covariance (MANCOVA) was used to analyze the data. The results showed that treatment based on acceptance and commitment significantly reduced self-criticism and improved coping strategies used by patients with drug use disorder (p>0.01). Therefore, treatment based on acceptance and commitment has been effective in reducing self-criticism and improving the coping strategies of patients with drug use disorder due to teaching clients to accept thoughts and conditions.

Keywords: treatment based on acceptance and commitment, self-criticism, coping strategies, addiction

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Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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Authors: Peeranan Wisanskoonwong, Sumitta Sawangtook

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Practicum in Midwifery II is the subject that affects most students to be stressed and anxious because they lack of experiences and self-confidence in delivery baby. This study is a qualitative research. That research objectives were (1) to study learning through reflective practice of nursing students (2) to explain the effects of learning through reflective practice of nursing students in the delivery room. The selected key informant method was criterion-based selection. Thirty-two of fourth-year nursing students in Kuakarun Faculty of nursing who practiced in Delivery room at Taksin Hospital in academic year 2014 were selected. Data collection was data triangulation which consisted of in-depth interview, group discussion and reading students’ reflective practice journal. The research instruments were students’ reflective practice journal, semi-structured questionnaires for in-depth interview, group discussion. Data analysis was thematic analysis. The research result found that: The learning method through reflective practice of nursing students in the delivery room were (1) reflective practice journal (2) dialogue (3) critical thinking and problem solving (4) incident analysis (5) self-criticism (6) observation and evaluation of practice. There were eight issues that students learned through their reflective practice were that (1) students' ethics and morality. (2) students' knowledge and comprehension (3) creative thinking of students (4) communications and collaboration (5) experiential learning of students (6) students’memories and impressions (7) students’experience in delivery baby (8) self-learning of students. Learning through reflective practice supported students’ awareness in improving knowledge and learning continuously and systematically. It helped to adjust the attitude to learning and leadership to be careful which help develop their skills, including critical thinking and understand themselves and understand others. Recommendation for applying research results: midwifery and nursing lecturers can apply these results to be a guide for development their clinical teaching in delivery rooms and other wards.

Keywords: learning, reflection, birth, qualitative research

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Authors: Gayathri Vijayakumar, Preethi Baskaran

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The effluents that are let down by the industries mix with the water bodies and drastically affect the aquatic life, which leads to pollution and bio magnifications. Effluents mostly contain chemicals, heavy metals etc., and cause toxicity to the environment. The pharmaceutical industries too contribute. The by-products and other unwanted waste are discharged without any treatment; these causes DNA damage and affect behavior of aquatic life. The study was conducted on koi carp (Cyprinus carpio) the ornamental variety of common carp. A two week long study was conducted on them using common anti-depressant drug (Diazepam) in various concentrations. These drugs are known to cause behavioral damage and organ malfunctions (muscle twitch). The histopathological study conducted showed permanent muscle twitching and lesions in the fish samples studied. The sociability was also affected in the span of 14 days. Higher concentrations of this drug showed severe damage in the muscle structures. Thus, this drug can cause adverse effects on marine ecosystem and eventually cause bio magnification of drug by running through the food chain.

Keywords: pollution, toxicity, bio-magnifications, koi carp, muscle twitch, diazepam, histopathology

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Authors: Nagat M. Saeed, Mabruka S. Elashheb, Fatma M. Ben Rabaha, Aisha M Edrah

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The aim of the study was to determine the type and pattern of antibiotic susceptibility of the pathogenic microorganisms causing chronic suppurative otitis media (CSOM), which could lead to better therapeutic decisions and consequently avoidance of appearance of resistance to specific antibiotics. Most frequently isolated agents were Pseudomonas aeruginosa 28.5%; followed by Staphylococcus aureus 18.2%; proteus mirabilis 13.9%; Providencia stuartti 6.7%; Bacteroides melaninogenicus, Aspergillus sp., candida sp., 4.2% each; and other microorganisms were represented in 3-0.2%. Drug sensitivities pattern of Pseudomonas aeruginosa showed that ciprofloxacin was active against the majority of isolates (93.9%) followed by ceftazidime 86.2%, amikacin 76.2% and gentamicin 40.8%. However, Staphylococcus aureus isolates were resistant to penicillin 72.7%, erythromycin 28.6%, cephalothin 18.2%, cloxacillin 8.3% and ciprofloxacin was active against 96.2% of isolates. The resistance pattern of proteus mirabilis was 55.6% to ampicillin, 47.1% to carbencillin, 29.4% to cephalothin, 14.3% to gentamicin and 4.8% to amikacin while 100% were sensitive to ciprofloxacin. We conclude that ciprofloxacin is the best drug of choice in the treatment of CSOM caused by the common microorganisms.

Keywords: otitis media, chronic suppurative otitis media (CSOM), microorganisms, drug sensitivity

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Authors: Kh. Alaa, Sh. Sarah, J. Khowlah, S. Liyakathunsia

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Education has become very important nowadays and with the rapidly increasing number of student, taking the attendance manually is getting very difficult and time wasting. In order to solve this problem, an automated solution is required. An effective automated system can be implemented to manage student attendance in different ways. This research will discuss a unique class attendance system which integrates both Face Recognition and RFID technique. This system focuses on reducing the time spent on submitting of the lecture and the wastage of time on submitting and getting approval for the absence excuse and sick leaves. As a result, the suggested solution will enhance not only the time, also it will also be helpful in eliminating fake attendance.

Keywords: attendance system, face recognition, RFID, process model, cost, time

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Authors: Anisur Rahman, Sabyasachi Behera, Pawan Pathak, Benazir Patil, Rajesh Khanna

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Background: Nearly half of India’s population is expected to reside in urban areas by 2030. The extent to which India's health system can provide for this large and growing city-based population will determine the country's success in achieving universal health coverage and improved national health indices. National Urban Health Mission (NUHM) strive for improving access to primary health care in urban areas. Implementation of NUHM solicits sensitive, effective and sustainable strategies to strengthen the service delivery mechanisms. The Challenge Initiative for Healthy Cities (TCIHC) is working with the Government of India and three provincial states to develop effective service delivery mechanisms for reproductive, maternal, newborn and child health (RMNCH) through a health systems approach for the urban poor. Method: A rapid assessment study was conceptualized and executed to generate evidence in order to address the challenges impeding in functioning of urban health facilities to deliver effective, efficient and equitable health care services in 7 cities spread across two project States viz. Madhya Pradesh and Odisha. Results: The findings of the assessment reflect: 1. The overall ecosystem pertaining to planning and management of public health interventions is not conducive. 2. The challenges regarding population dynamics like migration keeps on influencing the demand-supply-enabling environment triangle for both public and private service providers. 3. Lack of norms for planning and benchmark for service delivery further impedes urban health system as a whole. 4. Operationalization of primary level services have enough potential to meet the demand of slum dwellers at large. 5. Lack of policy driven strategies on how to integrate the NUHM with other thematic areas of Maternal, Newborn & Child Health (MNCH) and Family Planning (FP). 5. The inappropriate capacity building and acute shortage of Human Resources has huge implication on service provisioning and adherence to the service delivery protocols. Conclusion: The findings from rapid assessment are aimed to inform pertinent stakeholders to develop a multiyear city health action plan to strengthen the health systems in order to improve the efficacy of service delivery mechanism in urban settings.

Keywords: city health plan, health system, rapid assessment, urban mission

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Authors: Arianna Zhu, Thomas Bakupog

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Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

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Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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Authors: Paresh Patel, Harshit Patel

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Superficial fungal skin infection is among the most common skin disease. The drug administration through skin has received attention due to several advantages: Avoidance of significant pre-systemic metabolism, drug levels within the therapeutic window, drugs with short biological half-lives, decreased side effects, the non-invasive character, and very high acceptance.

Keywords: transdermal spray, ketoconazole, Eudragit® RLPO, therapeutic window

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Authors: Yuan Yang, Mickey Lam

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Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

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Authors: Nadia A. Mohamed, Zakaria El-Khayat, Wagdy K. B. Khalil, Mehrez E. El-Naggar

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Drug nephrotoxicity is still a problem for patients who have taken drugs for elongated periods or permanently. Ultrasound-assisted sol−gel method was used to prepare hollow structured poroussilica nanoemulsion loaded with sodium salicylate as a model drug. The work was extended to achieve the target of the current work via investigating the protective role of this nanoemulsion model as anti-inflammatory drug or ginger for its antioxidant effect against cisplatin-induced nephrotoxicity in male albino rats. The results clarify that the nanoemulsion model was synthesized using ultrasonic assisted with small size and well stabilization as proved by TEM and DLS analysis. Additionally, blood urea nitrogen (BUN), Serum creatinine (SC) and Urinary total protein (UTP) were increased, and the level of creatinine clearance (Crcl) was decreased. All those were met with disorders in oxidative stress and downregulation in the expression of the nephrin gene. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with silica nanoparticles loaded sodium salicylate (Si-Sc-NPs), ginger or both. Conclusions oil/water nanoemulsion of (Si-Sc NPs) and ginger showed a protective and promising preventive strategy against nephrotoxicity due to their antioxidant and anti-inflammatory effects, and that offers a new approach in attenuating drug induced nephrotoxicity.

Keywords: sodium salicylate nanoencapsulation, nephrin mRNA, drug nephrotoxicity, cisplatin, experimental rats

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Authors: Sabine Pau, Sophia Volz, Emanuel Bauer, Amelie De Gregorio, Frank Reister, Wolfgang Janni, Florian Ebner

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Purpose: The umbilical cord pH is a well evaluated contributor for prediction of neonatal outcome. This study correlates nenonatal umbilical cord pH with the weekday of delivery, the time of birth as well as the staff hand over times (midwifes and doctors). Material and Methods: This retrospective study included all deliveries of a 20 year period (1994-2014) at our primary obstetric center. All deliveries with a newborn cord pH under 7,20 were included in this analysis (6929 of 48974 deliveries (14,4%)). Further subgroups were formed according to the pH (< 7,05; 7,05 – 7,09; 7,10 – 7,14; 7,15 – 7,19). The data were then separated in day- and night time (8am-8pm/8pm-8am) for a first analysis. Finally, handover times were defined at 6 am – 6.30 am, 2 pm -2.30 pm, 10 pm- 10.30 pm (midwives) and for the doctors 8-8.30 am, 4 – 4.30 pm (Monday- Thursday); 2 pm -2.30 pm (Friday) and 9 am – 9.30 am (weekend). Routinely a shift consists of at least three doctors as well as three midwives. Results: During the last 20 years, 6929 neonates were born with an umbilical cord ph < 7,20 ( < 7,05 : 7,1%; 7,05 – 7,09 : 10,9%; 7,10 – 7,14 : 30,2%; 7,15 – 7,19:51,8%). There was no significant difference between either night/day delivery (p = 0.408), delivery on different weekdays (p = 0.253), delivery between Monday to Thursday, Friday and the weekend (p = 0.496 ) or delivery during the handover times of the doctors as well as the midwives (p = 0.221). Even the standard deviation showed no differences between the groups. Conclusion: Despite an increased workload over the last 20 years, the standard of care remains high even during the handover times and night shifts. This applies for midwives and doctors. As the neonatal outcome depends on various factors, further studies are necessary to take more factors influencing the fetal outcome into consideration. In order to maintain this high standard of care, an adaption of work-load and changing conditions is necessary.

Keywords: delivery, fetal umbilical cord pH, day time, hand over times

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: Shayma Mohammed, Adel Trabelsi

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Radiopharmacy is the art of preparing high-quality, radioactive, medicinal products for use in diagnosis and therapy. Radiopharmaceuticals unlike normal medicines, this dual aspect (radioactive, medical) makes their management highly critical. One of the most convincing applications of modern technologies is the ability to delegate the execution of repetitive tasks to programming scripts. Automation has found its way to the most skilled jobs, to improve the company's overall performance by allowing human workers to focus on more important tasks than document filling. This project aims to contribute to implement a comprehensive system to insure rigorous management of radiopharmaceuticals through the use of a platform that links the Nuclear Medicine Service Management System to the Nuclear Radio-pharmacy Management System in accordance with the recommendations of World Health Organization (WHO) and International Atomic Energy Agency (IAEA). In this project we attempt to build a web application that targets radiopharmacies, the platform is built atop the inherently compatible web stack which allows it to work in virtually any environment. Different technologies are used in this project (PHP, Symfony, MySQL Workbench, Bootstrap, Angular 7, Visual Studio Code and TypeScript). The operating principle of the platform is mainly based on two parts: Radiopharmaceutical Backoffice for the Radiopharmacian, who is responsible for the realization of radiopharmaceutical preparations and their delivery and Medical Backoffice for the Doctor, who holds the authorization for the possession and use of radionuclides and he/she is responsible for ordering radioactive products. The application consists of sven modules: Production, Quality Control/Quality Assurance, Release, General Management, References, Transport and Stock Management. It allows 8 classes of users: The Production Manager (PM), Quality Control Manager (QCM), Stock Manager (SM), General Manager (GM), Client (Doctor), Parking and Transport Manager (PTM), Qualified Person (QP) and Technical and Production Staff. Digital platform bringing together all players involved in the use of radiopharmaceuticals and integrating the stages of preparation, production and distribution, Web technologies, in particular, promise to offer all the benefits of automation while requiring no more than a web browser to act as a user client, which is a strength because the web stack is by nature multi-platform. This platform will provide a traceability system for radiopharmaceuticals products to ensure the safety and radioprotection of actors and of patients. The new integrated platform is an alternative to write all the boilerplate paperwork manually, which is a tedious and error-prone task. It would minimize manual human manipulation, which has proven to be the main source of error in nuclear medicine. A codified electronic transfer of information from radiopharmaceutical preparation to delivery will further reduce the risk of maladministration.

Keywords: automated system, management, radiopharmacy, technical papers

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: Arne Hitzmann, Philipp Wentscher, Alexander Gabel, Reinhard Gerndt

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Autonomous mobile robots can be found in a wide field of applications. Their types range from household robots over workshop robots to autonomous cars and many more. All of them undergo a number of testing steps during development, production and maintenance. This paper describes an approach to improve testing of robot behavior. It was inspired by the RoboCup @work competition that itself reflects a robotics benchmark for industrial robotics. There, scaled down versions of mobile industrial robots have to navigate through a workshop-like environment or operation area and have to perform tasks of manipulating and transporting work pieces. This paper will introduce an approach of automated vision-based testing of the behavior of the so called youBot robot, which is the most widely used robot platform in the RoboCup @work competition. The proposed system allows automated testing of multiple tries of the robot to perform a specific missions and it allows for the flexibility of the robot, e.g. selecting different paths between two tasks within a mission. The approach is based on a multi-camera setup using, off the shelf cameras and optical markers. It has been applied for test-driven development (TDD) and maintenance-like verification of the robot behavior and performance.

Keywords: supervisory control, testing, markers, mono vision, automation

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Authors: Hoyeon Park, Yunhwan Keon, Kyoung-Jae Kim

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Location Based Social Network services (LBSNs) is a new term that combines location based service and social network service (SNS). Unlike traditional SNS, LBSNs emphasizes empirical elements in the user's actual physical location. Point-of-Interest (POI) is the most important factor to implement LBSNs recommendation system. POI information is the most popular spot in the area. In this study, we would like to recommend POI to users in a specific area through recommendation system using collaborative filtering. The process is as follows: first, we will use different data sets based on Seoul and New York to find interesting results on human behavior. Secondly, based on the location-based activity information obtained from the personalized LBSNs, we have devised a new rating that defines the user's preference for the area. Finally, we have developed an automated rating algorithm from massive raw data using distributed systems to reduce advertising costs of LBSNs.

Keywords: location-based social network services, point-of-interest, recommender systems, business analytics

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Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

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Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

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Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

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Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

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Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

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Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

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Authors: Felix E. Gbenoba, Opeyemi Dahunsi

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Self-instructional materials are at the heart of instructional delivery in Open and Distance Learning (ODL). The success of any ODL institution depends on the availability of instructional materials in quality and quantity. An ODL study material is expected to fully play the teacher plays in the face-to-face learning environment. In Nigeria, efforts to deliver ODL learning materials have been peculiarly challenging. Although researchers are unrelenting in hewing out ways to make ODL delivery in Africa generally and Nigeria in particular, meet the learners’ needs and acceptable global practices, the prospects of integrating instructional media into distance learning courses are largely unexplored. In the present study, we critically examine the prospects of integration of instructional media into ODL courses for pedagogic and other benefits it portends for delivery via the distance learning mode. Although efforts to integrate media in ODL have been recorded before now, the reality has not matched the expectation so far in Nigeria. This does not mean that the existing instructional materials have not produced any significant positive results in improving the overall learning (and teaching) experience in its institutions; it implies that increased integration as suggested here will further improve the experience as well as bring up the new challenges. Obstacles and problems of instructional materials and media development that could have affected the open educational resource initiatives are well established. The first aspect of this paper recalls the revolutionary strides that ODL brought to delivery of education in Nigeria particularly. The other aspect is on what instructional media are, their role, prospects and challenges for ODL in Nigeria; these are examined vis a vis the challenges of development, production and distribution of print instructional materials as the major format of instructional delivery at Nigeria’s only single mode ODL institution, NOUN. In the third aspect, we justify the need and benefits of integrating instructional media into the courses and make recommendations.

Keywords: instructional delivery, instructional media, ODL, media integration, Nigeria, self-instructional materials

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Authors: Timur R. Azizov, Eugenia F. Shaykhutdinova, Ayrat G. Sitdikov

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In this article, we consider problems of automatic research result analysis and current monitoring of cultural legacy objects in island-city Sviyazhsk. We make basic concept of creating Automatic system, including developing the knowledge library with all conditions of three historical objects. In addition, we made described process of developing Automatic system of research result analysis of cultural legacy objects in island-city Sviyazhsk.

Keywords: automated system, record, results of research, unity3D, ASP .NET

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