Search results for: human and computer resources

Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Obada Ahmad Al Jayyousi, Ihdaa Mahmoud Bani Khalaf, Eman E. Alshial

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Background: Bipolar disorder, formerly known as manic depression, is a mental health status that leads to extreme mood swings that include emotional lows (depression) and highs (mania or hypomania). This systematic review and meta-analysis aimed to assess the safety and efficacy of lithium versus valproate among bipolar patients. Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until June 2022. Studies comparing lithium versus valproate among bipolar patients were selected for the analysis, and all relevant outcomes were pooled in the meta-analysis using Review Manager Software. Results: 11 Randomized Clinical Trials were included in this meta-analysis with a total of 4159 patients. Our meta showed that lithium was superior to valproate in terms of Young Mania Rating Scale (YMRS) (MD = 0.00 with 95% CI, (-0.55 – 0.55; I2 = 0%), P = 1.00). The results of the Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored the valproate treated group (MD = 1.41 with 95% CI, (-0.15 – 2.67; I2 = 0%), P = 0.03). Concerning the results of the Montgomery-Asberg Depression Rating Scale (MADRS), the results showed that the lithium was superior to valproate (MD = 0.03 with 95% CI, (-0.80 to 0.87; I2 = 40%), P = 0.94). In terms of the sexual side effect, we found that the valproate was superior to lithium (RR 1.19 with 95% CI, (0.74 to 1.91; I2 = 0%), P = 0.47). The lithium-treated group was superior in comparison to valproate treated group in terms of Abnormal Involuntary Movement Scale (AIMS) (MD = -0.03 with 95% CI (-0.38 to 0.32; I2 = 0%), P = 0.87). The lithium was more favorable in terms of Simpson-Agnes scale (MD = -0.40 with 95% CI, (-0.86 to 0.06; I2 = 0%), P = 0.09). The results of the Barnes akathisia scale showed that the overall effect of the valproate was more favorable in comparison to lithium (MD = 0.05 with 95% CI, (-0.12 to 0.22; I2 = 0%), P = 0.57). Conclusion: Our study revealed that on the scales of efficacy Lithium treated group surpassed Valproate treated group in terms of Young Mania Rating Scale (YMRS), Abnormal Involuntary Movement Scale (AIMS) and Simpson-Agnes scale, but valproate surpassed it in Barnes Akathisia scale. Furthermore, on the scales of depression Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored Valproate treated group, but Lithium surpassed valproate in terms of Montgomery-Asberg Depression Rating Scale (MADRS). Valproate surpassed Lithium in terms of sexual side effects.

Keywords: bipolar, mania, bipolar-depression, sexual dysfunction, sexual side effects, treatment

Procedia PDF Downloads 131

Authors: Sarah Faulkner, Patrick Faulkner, Caroline Ellison

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Improved mental and physical health, community connection, and increased life satisfaction has been strongly associated with bike riding for those with and without a disability. However, much evidence suggests that people living with a disability face increased barriers to engaging in cycling compared to members of the general population. People with an intellectual disability often live more sedentary and socially isolated lives that negatively impact their mental and physical health, as well as life satisfaction. This paper is based on preliminary findings from a three-year intervention cycling project funded by the South Australian Government. The cycling project was developed in partnership with community stakeholders that provided weekly instruction, training, and support to individuals living with intellectual disabilities to increase their capacity in cycling. This project aimed to support people living with intellectual disabilities to foster and facilitate improved physical and mental health, confidence, and independence and enhance social networking through their engagement in community cycling. The program applied principles of social role valorisation (SRV) theory as its guiding framework. Preliminary data collected is based on qualitative interviews with over 50 program participants, results from two participant wellness questionnaires, as well as a perceptually regulated exercise test administered throughout the project implementation. Preliminary findings are further supplemented with ethnographic analyses by the researchers who took a phenology of life experience approach. Preliminary findings of the program suggest a variety of social motivations behind participants' desire to learn cycling that acknowledges previous barriers to engagement and cycling’s role to address feelings of loneliness and social isolation. Meaningful health benefits can be achieved as demonstrated by increases in predicted V02 max measures, suggesting that physical intervention can not only improve physical health outcomes but also provide a variety of other social benefits. Initial engagement in the project has demonstrated an increase in participants' sense of confidence, well-being, and physical fitness. Implementation of the project in partnership with a variety of community stakeholders has identified a number of critical factors and processes necessary for future service replication, sustainability, and success. Findings from this intervention study contribute to the development of a knowledge base on how best to support individuals living with an intellectual disability to partake in bike riding and increase positive outcomes associated with their capacity building, social interaction, increased physical activity, physical health, and mental well-being. The initial findings of this study provide critical academic insights into the social and physical benefits of cycling for people living with a disability, as well as practical advice for future human service applications.

Keywords: cycling, disability, social inclusion, capacity building

Procedia PDF Downloads 49

Authors: Jingjing Yan, Gengen He, Anahid Basiri

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The design of an indoor navigation system for fire evacuation support requires not only physical feasibility but also a relatively thorough consideration of the human factors. This study has taken a survey to investigate the fire response performances (FRP) of the indoor occupants in age of 20s, virtually in an environment for their routine life, focusing on the aspects of indoor familiarity (spatial cognition), psychological stress and decision makings. For indoor familiarity, it is interested in three factors, i.e., the familiarity to exits and risky places as well as the satisfaction degree of the current indoor sign installation. According to the results, males have a higher average familiarity with the indoor exits while both genders have a relatively low level of risky place awareness. These two factors are positively correlated with the satisfaction degree of the current installation of the indoor signs, and this correlation is more evident for the exit familiarity. The integration of the height factor with the other two indoor familiarity factors can improve the degree of indoor sign satisfaction. For psychological stress, this study concentrates on the situated cognition of moving difficulty, nervousness, and speed reduction when using a bending posture during the fire evacuation to avoid smoke inhalation. The results have shown that both genders have a similar mid-level of hardness sensation. The females have a higher average level of nervousness, while males have a higher average level of speed reduction sensation. This study has assumed that the growing indoor spatial cognition can help ease the psychological hardness and nervousness. However, it only seems to be true after reaching a certain level. When integrating the effects from indoor familiarity and the other two psychological factors, the correlation to the sensation of speed change can be strengthened, based on a stronger positive correlation with the integrated factors. This study has also investigated the participants’ attitude to the navigation support during evacuation, and the majority of the participants have shown positive attitudes. For following the guidance under some extreme cases, i.e., changing to a longer path and to an alternative exit, the majority of the participants has shown the confidence of keeping trusting the guidance service. These decisions are affected by the combined influences from indoor familiarity, psychological stress, and attitude of using navigation service. For the decision time of the selected extreme cases, it costs more time in average for deciding to use a longer route than to use an alternative exit, and this situation is more evident for the female participants. This requires further considerations when designing a personalized smartphone-based navigation app. This study has also investigated the calming factors for people being trapped during evacuation. The top consideration is the distance to the nearest firefighters, and the following considerations are the current fire conditions in the surrounding environment and the locations of all firefighters. The ranking of the latter two considerations is very gender-dependent according to the results.

Keywords: fire response performances, indoor spatial cognition, situated cognition, survey analysis

Procedia PDF Downloads 119

Authors: Niamh Herlihy, Helen Fischer, Rainer Sauerborn, Anneliese Depoux, Avner Bar-Hen, Antoine Flauhault, Stefanie Schütte

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In the recent decades, there has been an increase in the number of publications both in the scientific and grey literature on the potential health risks associated with climate change. Though interest in climate change and health is growing, there are still many gaps to adequately assess our future health needs in a warmer world. Generating a greater understanding of the health impacts of climate change could be a key step in inciting the changes necessary to decelerate global warming and to target new strategies to mitigate the consequences on health systems. A long term and broad overview of existing scientific literature in the field of climate change and health is currently missing in order to ensure that all priority areas are being adequately addressed. We conducted a scoping review of published peer-reviewed literature on climate change and health from two large databases, PubMed and Web of Science, between 1990 and 2015. A scoping review allowed for a broad analysis of this complex topic on a meta-level as opposed to a thematically refined literature review. A detailed search strategy including specific climate and health terminology was used to search the two databases. Inclusion and exclusion criteria were applied in order to capture the most relevant literature on the human health impact of climate change within the chosen timeframe. Two reviewers screened the papers independently and any differences arising were resolved by a third party. Data was extracted, categorized and coded both manually and using R software. Analytics and infographics were developed from results. There were 7269 articles identified between the two databases following the removal of duplicates. After screening of the articles by both reviewers 3751 were included. As expected, preliminary results indicate that the number of publications on the topic has increased over time. Geographically, the majority of publications address the impact of climate change and health in Europe and North America, This is particularly alarming given that countries in the Global South will bear the greatest health burden. Concerning health outcomes, infectious diseases, particularly dengue fever and other mosquito transmitted infections are the most frequently cited. We highlight research gaps in certain areas e.g climate migration and mental health issues. We are developing a database of the identified climate change and health publications and are compiling a report for publication and dissemination of the findings. As health is a major co-beneficiary to climate change mitigation strategies, our results may serve as a useful source of information for research funders and investors when considering future research needs as well as the cost-effectiveness of climate change strategies. This study is part of an interdisciplinary project called 4CHealth that confronts results of the research done on scientific, political and press literature to better understand how the knowledge on climate change and health circulates within those different fields and whether and how it is translated to real world change.

Keywords: climate change, health, review, mapping

Procedia PDF Downloads 299

Authors: L. Raczynski, P. Moskal, P. Kowalski, W. Wislicki, T. Bednarski, P. Bialas, E. Czerwinski, A. Gajos, L. Kaplon, A. Kochanowski, G. Korcyl, J. Kowal, T. Kozik, W. Krzemien, E. Kubicz, Sz. Niedzwiecki, M. Palka, Z. Rudy, O. Rundel, P. Salabura, N.G. Sharma, M. Silarski, A. Slomski, J. Smyrski, A. Strzelecki, A. Wieczorek, M. Zielinski, N. Zon

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The J-PET scanner, which allows for single bed imaging of the whole human body, is currently under development at the Jagiellonian University. The J-PET detector improves the TOF resolution due to the use of fast plastic scintillators. Since registration of the waveform of signals with duration times of few nanoseconds is not feasible, a novel front-end electronics allowing for sampling in a voltage domain at four thresholds was developed. To take fully advantage of these fast signals a novel scheme of recovery of the waveform of the signal, based on ideas from the Tikhonov regularization (TR) and Compressive Sensing methods, is presented. The prior distribution of sparse representation is evaluated based on the linear transformation of the training set of waveform of the signals by using the Principal Component Analysis (PCA) decomposition. Beside the advantage of including the additional information from training signals, a further benefit of the TR approach is that the problem of signal recovery has an optimal solution which can be determined explicitly. Moreover, from the Bayes theory the properties of regularized solution, especially its covariance matrix, may be easily derived. This step is crucial to introduce and prove the formula for calculations of the signal recovery error. It has been proven that an average recovery error is approximately inversely proportional to the number of samples at voltage levels. The method is tested using signals registered by means of the single detection module of the J-PET detector built out from the 30 cm long BC-420 plastic scintillator strip. It is demonstrated that the experimental and theoretical functions describing the recovery errors in the J-PET scenario are largely consistent. The specificity and limitations of the signal recovery method in this application are discussed. It is shown that the PCA basis offers high level of information compression and an accurate recovery with just eight samples, from four voltage levels, for each signal waveform. Moreover, it is demonstrated that using the recovered waveform of the signals, instead of samples at four voltage levels alone, improves the spatial resolution of the hit position reconstruction. The experiment shows that spatial resolution evaluated based on information from four voltage levels, without a recovery of the waveform of the signal, is equal to 1.05 cm. After the application of an information from four voltage levels to the recovery of the signal waveform, the spatial resolution is improved to 0.94 cm. Moreover, the obtained result is only slightly worse than the one evaluated using the original raw-signal. The spatial resolution calculated under these conditions is equal to 0.93 cm. It is very important information since, limiting the number of threshold levels in the electronic devices to four, leads to significant reduction of the overall cost of the scanner. The developed recovery scheme is general and may be incorporated in any other investigation where a prior knowledge about the signals of interest may be utilized.

Keywords: plastic scintillators, positron emission tomography, statistical analysis, tikhonov regularization

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Authors: Abdul Ganiyu Iddrisu, Bei Chen

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Digitization is the process of transforming analog material into digital form, especially for storage and use in a computer. Significant development of information and communication technology (ICT) over the past years has encouraged many researchers to investigate its contribution to promoting economic growth and reducing poverty. Yet the compelling empirical evidence on the effects of digitization on economic growth remains weak, particularly in Africa. This is because extant studies that explicitly evaluate digitization and economic growth nexus are mostly reports and desk reviews. This points out an empirical knowledge gap in the literature. Hypothetically, digitization influences financial sector development which in turn influences economic growth. Digitization has changed the financial sector and its operating environment. Obstacles to access to financing, for instance, physical distance, minimum balance requirements, and low-income flows, among others can be circumvented. Savings have increased, micro-savers have opened bank accounts, and banks are now able to price short-term loans. This has the potential to develop the financial sector. However, empirical evidence on the digitization-financial development nexus is dearth. On the other hand, a number of studies maintained that financial sector development greatly influences growth of economies. We, therefore, argue that financial sector development is one of the transmission mechanisms through which digitization affects economic growth. Employing macro-country-level data from African countries and using fixed effects, random effects and Hausman-Taylor estimation approaches, this paper contributes to the literature by analysing economic growth in Africa, focusing on the role of digitization and financial sector development. First, we assess how digitization influences financial sector development in Africa. From an economic policy perspective, it is important to identify digitization determinants of financial sector development so that action can be taken to reduce the economic shocks associated with financial sector distortions. This nexus is rarely examined empirically in the literature. Secondly, we examine the effect of domestic credit to the private sector and stock market capitalization as a percentage of GDP as used to proxy for financial sector development on economic growth. Digitization is represented by the volume of digital/ICT equipment imported and GDP growth is used to proxy economic growth. Finally, we examine the effect of digitization on economic growth in the light of financial sector development. The following key results were found; first, digitalization propels financial sector development in Africa. Second, financial sector development enhances economic growth. Finally, contrary to our expectation, the results also indicate that digitalization conditioned on financial sector development tends to reduce economic growth in Africa. However, results of the net effects suggest that digitalization, overall, improve economic growth in Africa. We, therefore, conclude that, digitalization in Africa does not only develop the financial sector but unconditionally contributes the growth of the continent’s economies.

Keywords: digitalization, financial sector development, Africa, economic growth

Procedia PDF Downloads 118

Authors: Andrzej Wałęga, Marta Cebulska, Agnieszka Ziernicka-Wojtaszek, Wojciech Młocek, Agnieszka Wałęga, Tommaso Caloiero

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Drought is one of the natural phenomena influencing many aspects of human activities like food production, agriculture, industry, and the ecological conditions of the environment. In the area of the Polish Carpathians, there are periods with a deficit of rainwater and an increasing frequency in dry months, especially in the cold half of the year. The aim of this work is a spatial and temporal analysis of drought, expressed as SPI in a heterogenous area of the Polish Carpathian and of the highland Region in the Central part of Europe based on long-term precipitation data. Also, to our best knowledge, for the first time in this work, drought characteristics analyzed via the SPI were discussed based on the atmospheric circulation calendar. The study region is the Upper Vistula Basin, located in the southern and south-eastern part of Poland. In this work, monthly precipitation from 56 rainfall stations was analysed from 1961 to 2022. The 3-, 6-, 9-, and 12-month Standardized Precipitation Index (SPI) were used as indicators of meteorological drought. For the 3-month SPI, the main climatic mechanisms determining extreme droughts were defined based on the calendar of synoptic circulations. The Mann-Kendall test was used to detect the trend of extreme droughts. Statistically significant trends of SPI were observed on 52.7% of all analyzed stations, and in most cases, a positive trend was observed. Statistically significant trends were more frequently observed in stations located in the western part of the analyzed region. Long-term droughts, represented by the 12-month SPI, occurred in all stations but not in all years. Short-term droughts (3-month SPI) were most frequent in the winter season, 6 and 9-month SPI in winter and spring, and 12-month SPI in winter and autumn, respectively. The spatial distribution of drought was highly diverse. The most intensive drought occurred in 1984, with the 6-month SPI covering 98% of the analyzed region and the 9 and 12-month SPI covering 90% of the entire region. Droughts exhibit a seasonal pattern, with a dominant 10-year periodicity for all analyzed variants of SPI. Additionally, Fourier analysis revealed a 2-year periodicity for the 3-, 6-, and 9-month SPI and a 31-year periodicity for the 12-month SPI. The results provide insights into the typical climatic conditions in Poland, with strong seasonality in precipitation. The study highlighted that short-term extreme droughts, represented by the 3-month SPI, are often caused by anticyclonic situations with high-pressure wedges Ka and Wa, and anticyclonic West as observed in 52.3% of cases. These findings are crucial for understanding the spatial and temporal variability of short and long-term extreme droughts in Central Europe, particularly for the agriculture sector dominant in the northern part of the analyzed region, where drought frequency is highest.

Keywords: atmospheric circulation, drought, precipitation, SPI, the Upper Vistula Basin

Procedia PDF Downloads 53

Authors: Eunsu Jang, Kang Park

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In developing an armored ground combat vehicle (AGCV), it is a very important step to analyze the vulnerability (or the survivability) of the AGCV against enemy’s attack. In the vulnerability analysis, the penetration equations are usually used to get the penetration depth and check whether a bullet can penetrate the armor of the AGCV, which causes the damage of internal components or crews. The penetration equations are derived from penetration experiments which require long time and great efforts. However, they usually hold only for the specific material of the target and the specific type of the bullet used in experiments. Thus, penetration simulation using ANSYS can be another option to calculate penetration depth. However, it is very important to model the targets and select the input parameters in order to get an accurate penetration depth. This paper performed a sensitivity analysis of input parameters of ANSYS on the accuracy of the calculated penetration depth. Two conflicting objectives need to be achieved in adopting ANSYS in penetration analysis: maximizing the accuracy of calculation and minimizing the calculation time. To maximize the calculation accuracy, the sensitivity analysis of the input parameters for ANSYS was performed and calculated the RMS error with the experimental data. The input parameters include mesh size, boundary condition, material properties, target diameter are tested and selected to minimize the error between the calculated result from simulation and the experiment data from the papers on the penetration equation. To minimize the calculation time, the parameter values obtained from accuracy analysis are adjusted to get optimized overall performance. As result of analysis, the followings were found: 1) As the mesh size gradually decreases from 0.9 mm to 0.5 mm, both the penetration depth and calculation time increase. 2) As diameters of the target decrease from 250mm to 60 mm, both the penetration depth and calculation time decrease. 3) As the yield stress which is one of the material property of the target decreases, the penetration depth increases. 4) The boundary condition with the fixed side surface of the target gives more penetration depth than that with the fixed side and rear surfaces. By using above finding, the input parameters can be tuned to minimize the error between simulation and experiments. By using simulation tool, ANSYS, with delicately tuned input parameters, penetration analysis can be done on computer without actual experiments. The data of penetration experiments are usually hard to get because of security reasons and only published papers provide them in the limited target material. The next step of this research is to generalize this approach to anticipate the penetration depth by interpolating the known penetration experiments. This result may not be accurate enough to be used to replace the penetration experiments, but those simulations can be used in the early stage of the design process of AGCV in modelling and simulation stage.

Keywords: ANSYS, input parameters, penetration depth, sensitivity analysis

Procedia PDF Downloads 374

Authors: Mohammad Ashraful Alam, Biro Judit

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Fear of gender-based crime and fear of crime victimization for women is a major concern in the urban areas of Bangladesh. Based on the recent data from various human rights organizations and international literature the study found that gender-based crime especially sexual assault and rape are increasing in Bangladesh at a significant rate in comparison to other countries. The major focus of the study was to identify the relationship between fear of gender-based crime and women empowerment. To explore the fact the study followed the mixed methodological approach comprising with quantitative and qualitative methods and used secondary information from national and international sources. Corresponding global pictures the present study found that gender, age, complexion, social position, and ethnicity were more common factors of sexual assault and victimization in Bangladesh which lead to women become more fearful about crime victimization than men. Fear of gender-based crime traumatizes women which leads to withdrawal of their non-essential everyday works and some time from the essential works based on their social position, financial status, and social honor in the society. The increasing crime rate also increases the propensity to fear of criminal victimization, traumatization, and feeling of helplessness which make them vulnerable. The patriarchal culture and practices in Bangladesh based on religious culture and established social norms women always feel defenseless therefore they withdraw themselves from various social activities and own interest. Women who have already victimized feel more fear and become traumatized, and who do not victimize yet but know the severity of victimization from the media and others’ have the feeling of fear of crime. Women who find themselves as weak bonding and low networks with their neighbors and living for a short duration have a feeling of more fear and avoid visiting a certain place in a certain time and avoid some social activities. The study found the young women have more possibilities to become victimized through the feeling of fear of crime is higher among elderly women than young. Though women feel fear of all kinds of crime but usually all aged women are more fearful of sexual assault and rape than other violent crimes. Therefore, elderly women and another person in the family does not allow younger girls to go and involve outside activities to secure their family status. On the other hand, fear of crime in public transport is more common to all aged women at a higher level and sometimes they compromise their freedom, independence, financial opportunities, the job only to avoid the perceived threat, and save their social and cultural honor. The study also explores that fear of crime does not always depend on crime rate but the crime news, the severity of the crime, delay justice, the ineffectiveness of police, bail of criminals, corruption and political favoritism, etc. Finally, the study shows that the fear of gender-based crime and violence is working as a potential barrier to ensuring women's empowerment in Bangladesh.

Keywords: compromise personal freedom, fear of crime, fear of gender-based crime, fear of violent crime victimization, rape, sexual assaults, withdrawal from regular activities, women empowerment

Procedia PDF Downloads 116

Authors: Michael Mertel, Lars Friedrich, Kai-Ingo Voigt

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Based on principle-agent theory, an information asymmetry exists in the traditional donation process. Consumers cannot comprehend whether nonprofit organizations (NPOs) use raised funds according to the designated cause after the transaction took place (hidden action). Therefore, charity organizations have tried to appear transparent and gain trust by using the same marketing instruments for decades (e.g., releasing project success reports). However, none of these measures can guarantee consumers that charities will use their donations for the purpose. With awareness of misuse of donations rising due to the Ukraine conflict (e.g., funding crime), consumers are increasingly concerned about the destination of their charitable purposes. Therefore, innovative charities like the Human Rights Foundation have started to offer donations via blockchain. Blockchain technology has the potential to establish profound trust and transparency in the donation process: Consumers can publicly track the progress of their donation at any time after deciding to donate. This ensures that the charity is not using donations against its original intent. Hence, the aim is to investigate the effect of blockchain-enabled transactions on the willingness to donate. Sample and Design: To investigate consumers' behavior, we use a scenario-based experiment. After removing participants (e.g., due to failed attention checks), 3192 potential donors participated (47.9% female, 62.4% bachelor or above). Procedure: We randomly assigned the participants to one of two scenarios. In all conditions, the participants read a scenario about a fictive charity organization called "Helper NPO." Afterward, the participants answered questions regarding their perception of the charity. Manipulation: The first scenario (n = 1405) represents a typical donation process, where consumers donate money without any option to track and trace. The second scenario (n = 1787) represents a donation process via blockchain, where consumers can track and trace their donations respectively. Using t-statistics, the findings demonstrate a positive effect of donating via blockchain on participants’ willingness to donate (mean difference = 0.667, p < .001, Cohen’s d effect size = 0.482). A mediation analysis shows significant effects for the mediation of transparency (Estimate = 0.199, p < .001), trust (Estimate = 0.144, p < .001), and transparency and trust (Estimate = 0.158, p < .001). The total effect of blockchain usage on participants’ willingness to donate (Estimate = 0.690, p < .001) consists of the direct effect (Estimate = 0.189, p < .001) and the indirect effects of transparency and trust (Estimate = 0.501, p < .001). Furthermore, consumers' affinity for technology moderates the direct effect of blockchain usage on participants' willingness to donate (Estimate = 0.150, p < .001). Donating via blockchain is a promising way for charities to engage consumers for several reasons: (1) Charities can emphasize trust and transparency in their advertising campaigns. (2) Established charities can target new customer segments by specifically engaging technology-affine consumers in the future. (3) Charities can raise international funds without previous barriers (e.g., setting up bank accounts). Nevertheless, increased transparency can also backfire (e.g., disclosure of costs). Such cases require further research.

Keywords: blockchain, social sector, transparency, trust

Procedia PDF Downloads 76

Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

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The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

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Authors: Rawan Ashraf, Ahmed E. Gomaa, Gehan Safwat, Ayman Diab

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Background: Three-dimensional (3D) bio-printing has become a versatile and powerful method for generating a variety of biological constructs, including bone or extracellular matrix scaffolds endo- or epithelial, muscle tissue, as well as organoids. Aim of the study: Fabricate a low cost DIY 3D bio-printer to produce 3D bio-printed products such as anti-microbial packaging or multi-organs on chips. We demonstrate the alignment between two types of 3D printer technology (3D Bio-printer and DLP) on Multi-organ-on-a-chip (multi-OoC) devices fabrication. Methods: First, Design and Fabrication of the Syringe Unit for Modification of an Off-the-Shelf 3D Printer, then Preparation of Hydrogel based on natural polymers Sodium Alginate and Gelatin, followed by acquisition of the cell suspension, then modeling the desired 3D structure. Preparation for 3D printing, then Cell-free and cell-laden hydrogels went through the printing process at room temperature under sterile conditions and finally post printing curing process and studying the printed structure regards physical and chemical characteristics. The hard scaffold of the Organ on chip devices was designed and fabricated using the DLP-3D printer, following similar approaches as the Microfluidics system fabrication. Results: The fabricated Bio-Ink was based onHydrogel polymer mix of sodium alginate and gelatin 15% to 0.5%, respectively. Later the 3D printing process was conducted using a higher percentage of alginate-based hydrogels because of it viscosity and the controllable crosslinking, unlike the thermal crosslinking of Gelatin. The hydrogels were colored to simulate the representation of two types of cells. The adaption of the hard scaffold, whether for the Microfluidics system or the hard-tissues, has been acquired by the DLP 3D printers with fabricated natural bioactive essential oils that contain antimicrobial activity, followed by printing in Situ three complex layers of soft-hydrogel as a cell-free Bio-Ink to simulate the real-life tissue engineering process. The final product was a proof of concept for a rapid 3D cell culturing approaches that uses an engineered hard scaffold along with soft-tissues, thus, several applications were offered as products of the current prototype, including the Organ-On-Chip as a successful integration between DLP and 3D bioprinter. Conclusion: Multiple designs for the organ-on-a-chip (multi-OoC) devices have been acquired in our study with main focus on the low cost fabrication of such technology and the potential to revolutionize human health research and development. We describe circumstances in which multi-organ models are useful after briefly examining the requirement for full multi-organ models with a systemic component. Following that, we took a look at the current multi-OoC platforms, such as integrated body-on-a-chip devices and modular techniques that use linked organ-specific modules.

Keywords: 3d bio-printer, hydrogel, multi-organ on chip, bio-inks

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Authors: Lan Cheng, Harry Qin, Yang Wang

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Background: COVID-19 has induced the largest digital learning experiment in history. There is also emerging research evidence that students have paid a high cost of learning loss from virtual learning. University-wide survey results demonstrate that digital learning remains difficult for students who struggle with learning challenges, isolation, or a lack of resources. Large-scale efforts are therefore increasingly utilized for digital education. To better prepare students in higher education for this grand scientific and technological transformation, STEM education has been prioritized and promoted as a strategic imperative in the ongoing curriculum reform essential for unfinished learning needs and whole-person development. Building upon five key elements identified in the STEM education literature: Problem-based Learning, Community and Belonging, Technology Skills, Personalization of Learning, Connection to the External Community, this case study explores the potential of pedagogical innovation that integrates computational and experimental methodologies to support, enrich, and navigate STEM education. Objectives: The goal of this case study is to create a high-fidelity prototype design for STEM education with knowledge transfer technology that contains a Cooperative Multi-Agent System (CMAS), which has the objectives of (1) conduct assessment to reveal a virtual learning mechanism and establish strategies to facilitate scientific learning engagement, accessibility, and connection within and beyond university setting, (2) explore and validate an interactional co-creation approach embedded in project-based learning activities under the STEM learning context, which is being transformed by both digital technology and student behavior change,(3) formulate and implement the STEM-oriented campaign to guide learning network mapping, mitigate the loss of learning, enhance the learning experience, scale-up inclusive participation. Methods: This study applied a case study strategy and a methodology informed by Social Network Analysis Theory within a cross-disciplinary communication paradigm (students, peers, educators). Knowledge transfer technology is introduced to address learning challenges and to increase the efficiency of Reinforcement Learning (RL) algorithms. A co-creation learning framework was identified and investigated in a context-specific way with a learning analytic tool designed in this study. Findings: The result shows that (1) CMAS-empowered learning support reduced students’ confusion, difficulties, and gaps during problem-solving scenarios while increasing learner capacity empowerment, (2) The co-creation learning phenomenon have examined through the lens of the campaign and reveals that an interactive virtual learning environment fosters students to navigate scientific challenge independently and collaboratively, (3) The deliverables brought from the STEM educational campaign provide a methodological framework both within the context of the curriculum design and external community engagement application. Conclusion: This study brings a holistic and coherent pedagogy to cultivates students’ interest in STEM and develop them a knowledge base to integrate and apply knowledge across different STEM disciplines. Through the co-designing and cross-disciplinary educational content and campaign promotion, findings suggest factors to empower evidence-based learning practice while also piloting and tracking the impact of the scholastic value of co-creation under the dynamic learning environment. The data nested under the knowledge transfer technology situates learners’ scientific journey and could pave the way for theoretical advancement and broader scientific enervators within larger datasets, projects, and communities.

Keywords: co-creation, cross-disciplinary, knowledge transfer, STEM education, social network analysis

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Authors: Lolwa Alansari, Abdelhamid Azhaghdani, Sufia Athar, Hanen Mrabet, Annaliza Cruz, Tamara Alshadafat, Almunzer Zakaria

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Introduction: Improving the patient experience is a fundamental pillar of healthcare's quadruple aims. Recognizing the importance of patient experiences and perceptions in healthcare interactions is pivotal for driving quality improvement. This abstract centers around the Patient Experience Program, an endeavor crafted with the purpose of comprehending and elevating the experiences of patients in the Obstetrics & Gynecology Emergency Department (OB/GYN ED). Methodology: This comprehensive endeavor unfolded through a structured sequence of phases following Plan-Do-Study-Act (PDSA) model, spanning over 12 months, focused on enhancing patient experiences in the Obstetrics & Gynecology Emergency Department (OB/GYN ED). The study meticulously examined the journeys of patients with acute obstetrics and gynecological conditions, collecting data from over 100 participants monthly. The inclusive approach covered patients of different priority levels (1-5) admitted for acute conditions, with no exclusions. Historical data from March and April 2022 serves as a benchmark for comparison, strengthening causality claims by providing a baseline understanding of OB/GYN ED performance before interventions. Additionally, the methodology includes the incorporation of staff engagement surveys to comprehensively understand the experiences of healthcare professionals with the implemented improvements. Data extraction involved administering open-ended questions and comment sections to gather rich qualitative insights. The survey covered various aspects of the patient journey, including communication, emotional support, timely access to care, care coordination, and patient-centered decision-making. The project's data analysis utilized a mixed-methods approach, combining qualitative techniques to identify recurring themes and extract actionable insights and quantitative methods to assess patient satisfaction scores and relevant metrics over time, facilitating the measurement of intervention impact and longitudinal tracking of changes. From the themes we discovered in both the online and in-person patient experience surveys, several key findings emerged that guided us in initiating improvements, including effective communication and information sharing, providing emotional support and empathy, ensuring timely access to care, fostering care coordination and continuity, and promoting patient-centered decision-making. Results: The project yielded substantial positive outcomes, significantly improving patient experiences in the OB/GYN ED. Patient satisfaction levels rose from 62% to a consistent 98%, with notable improvements in satisfaction with care plan information and physician care. Waiting time satisfaction increased from 68% to a steady 97%. The project positively impacted nurses' and midwives' job satisfaction, increasing from 64% to an impressive 94%. Operational metrics displayed positive trends, including a decrease in the "left without being seen" rate from 3% to 1%, the discharge against medical advice rate dropping from 8% to 1%, and the absconded rate reducing from 3% to 0%. These outcomes underscore the project's effectiveness in enhancing both patient and staff experiences in the healthcare setting. Conclusion: The use of a patient experience questionnaire has been substantiated by evidence-based research as an effective tool for improving the patient experience, guiding interventions, and enhancing overall healthcare quality in the OB/GYN ED. The project's interventions have resulted in a more efficient allocation of resources, reduced hospital stays, and minimized unnecessary resource utilization. This, in turn, contributes to cost savings for the healthcare facility.

Keywords: patient experience, patient survey, person centered care, quality initiatives

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Authors: Gizem Kayar, Ramazan Bakir, M. Ilkay Koşar, Ceren U. Gencer, Alperen Ayyildiz

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Anatomy classes are crucial for general education of medical students, whereas learning anatomy is quite challenging and requires memorization of thousands of structures. In traditional teaching methods, learning materials are still based on books, anatomy mannequins, or videos. This results in forgetting many important structures after several years. However, more interactive teaching methods like virtual reality, augmented reality, gamification, and motion sensors are becoming more popular since such methods ease the way we learn and keep the data in mind for longer terms. During our study, we designed a virtual reality based digital head anatomy platform to investigate whether a fully interactive anatomy platform is effective to learn anatomy and to understand the level of teaching and learning optimization. The Head is one of the most complicated human anatomy structures, with thousands of tiny, unique structures. This makes the head anatomy one of the most difficult parts to understand during class sessions. Therefore, we developed a fully interactive digital tool with 3D model marking, quiz structures, 2D/3D puzzle structures, and VR support so as to integrate the power of VR and gamification. The project has been developed in Unity game engine with HTC Vive Cosmos VR headset. The head anatomy 3D model has been selected with full skeletal, muscular, integumentary, head, teeth, lymph, and vein system. The biggest issue during the development was the complexity of our model and the marking of it in the 3D world system. 3D model marking requires to access to each unique structure in the counted subsystems which means hundreds of marking needs to be done. Some parts of our 3D head model were monolithic. This is why we worked on dividing such parts to subparts which is very time-consuming. In order to subdivide monolithic parts, one must use an external modeling tool. However, such tools generally come with high learning curves, and seamless division is not ensured. Second option was to integrate tiny colliders to all unique items for mouse interaction. However, outside colliders which cover inner trigger colliders cause overlapping, and these colliders repel each other. Third option is using raycasting. However, due to its own view-based nature, raycasting has some inherent problems. As the model rotate, view direction changes very frequently, and directional computations become even harder. This is why, finally, we studied on the local coordinate system. By taking the pivot point of the model into consideration (back of the nose), each sub-structure is marked with its own local coordinate with respect to the pivot. After converting the mouse position to the world position and checking its relation with the corresponding structure’s local coordinate, we were able to mark all points correctly. The advantage of this method is its applicability and accuracy for all types of monolithic anatomical structures.

Keywords: anatomy, e-learning, virtual reality, 3D model marking

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Authors: Debraj Gangopadhyay, Moumita Das, Ranjan K. Singh, Poonam Tandon

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Creatinine is a toxic chemical waste generated from muscle metabolism. Abnormally high levels of creatinine in the body fluid indicate possible malfunction or failure of the kidneys. This leads to a condition termed as creatinine induced nephrotoxicity. N-acetylcysteine is an antioxidant drug which is capable of preventing creatinine induced nephrotoxicity and is helpful to treat renal failure in its early stages. Taurine is another antioxidant drug which serves similar purpose. The kidneys have a natural power that whenever reactive oxygen species radicals increase in the human body, the kidneys make an antioxidant shell so that these radicals cannot harm the kidney function. Taurine plays a vital role in increasing the power of that shell such that the glomerular filtration rate can remain in its normal level. Thus taurine protects the kidneys against several diseases. However, taurine also has some negative effects on the body as its chloramine derivative is a weak oxidant by nature. N-acetylcysteine is capable of inhibiting the residual oxidative property of taurine chloramine. Therefore, N-acetylcysteine is given to a patient along with taurine and this combination is capable of suppressing the negative effect of taurine. Both N-acetylcysteine and taurine being affordable, safe, and widely available medicines, knowledge of the mechanism of their combined effect on creatinine, the favored route of administration, and the proper dose may be highly useful in their use for treating renal patients. Raman spectroscopy is a precise technique to observe minor structural changes taking place when two or more molecules interact. The possibility of formation of a complex between a drug molecule and an analyte molecule in solution can be explored by analyzing the changes in the Raman spectra. The formation of a stable complex of creatinine with N-acetylcysteinein vitroin aqueous solution has been observed with the help of Raman spectroscopic technique. From the Raman spectra of the mixtures of aqueous solutions of creatinine and N-acetylcysteinein different molar ratios, it is observed that the most stable complex is formed at 1:1 ratio of creatinine andN-acetylcysteine. Upon drying, the complex obtained is gel-like in appearance and reddish yellow in color. The complex is hygroscopic and has much better water solubility compared to creatinine. This highlights that N-acetylcysteineplays an effective role in reducing the toxic effect of creatinine by forming this water soluble complex which can be removed through urine. Since the drug taurine is also known to be useful in reducing nephrotoxicity caused by creatinine, the aqueous solution of taurine with those of creatinine and N-acetylcysteinewere mixed in different molar ratios and were investigated by Raman spectroscopic technique. It is understood that taurine itself does not undergo complexation with creatinine as no additional changes are observed in the Raman spectra of creatinine when it is mixed with taurine. However, when creatinine, N-acetylcysteine and taurine are mixed in aqueous solution in molar ratio 1:1:3, several changes occurring in the Raman spectra of creatinine suggest the diminishing toxic effect of creatinine in the presence ofantioxidant drugs N-acetylcysteine and taurine.

Keywords: creatinine, creatinine induced nephrotoxicity, N-acetylcysteine, taurine

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Authors: Jennifer Zelmer

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The debate regarding the morality, and therefore legality, of abortion has many social, political, and medical ramifications worldwide. In a developing country like Bolivia, carrying a pregnancy to delivery is incredibly risky. Given the very high maternal mortality rate in Bolivia, greater consideration has been given to the (de)criminalization of abortion – a contributing cause of maternal death. In the spring of 2017, the Bolivian government proposed to loosen restrictions on women’s access to receiving a safe abortion, which was met with harsh criticism from 'pro-vida' (pro-life) factions. Although the current Bolivian government Movimiento al Socialismo (Movement Toward Socialism) portrays an agenda of decolonization, or to seek a 'traditionally-modern' society, nevertheless, Bolivia still has one of the highest maternal mortality rates in the Americas, because of centuries of colonial and patriarchal order. Applying a feminist critique and using the abortion debate as the central point, this paper argues that the 'traditionally-modern' society Bolivia strives towards is a paradox, and in fact only contributes to the reciprocal process of the death of 'mother tongues' and the unnecessary death of women. This claim is supported by a critical analysis of historical texts about Spanish Colonialism in Bolivia; the linguistic reality of reproductive educational strategies, and the philosophical framework which the Bolivian government and its citizens implement. This analysis is demonstrated in the current state of women’s access to reproductive healthcare in Cochabamba, Bolivia based on recent fieldwork which included audits of clinics and hospitals, interviews, and participant observation. This paper has two major findings: 1) the language used by opponents of abortion in Bolivia is not consistent with the claim of being 'pro-life' but more accurately with being 'pro-potential'; 2) when the topic of reproductive health appears in Cochabamba, Bolivia, it is often found written in the Spanish language, and does not cater to the many indigenous communities that inhabit or visit this city. Finally, this paper considers the crucial role of public health documentation to better inform the abortion debate, as well as the necessity of expanding reproductive health information to more than text-based materials in Cochabamba. This may include more culturally appropriate messages and mediums that cater to the oral tradition of the indigenous communities, who historically and currently have some of the highest fertility rates. If the objective of one who opposes abortion is to save human lives, then preventing the death of women should equally be of paramount importance. But rather, the 'pro-life' movement in Bolivia is willing to risk the lives of to-be mothers, by judicial punishment or death, for the chance of a potential baby. Until abortion is fully legal, safe, and accessible, there will always be the vestiges of colonial and patriarchal order in Bolivia which only perpetuates the needless death of women.

Keywords: abortion, feminist theory, Quechua, reproductive health education

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Authors: Andrey Davydov, Konstantin Sveshnikov, Yulia Voronina

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There is now a lot of interest to the non-perturbative QED-effects, caused by diving of discrete levels into the negative continuum in the supercritical static or adiabatically slowly varying Coulomb fields, that are created by the localized extended sources with Z > Z_cr. Such effects have attracted a considerable amount of theoretical and experimental activity, since in 3+1 QED for Z > Z_cr,1 ≈ 170 a non-perturbative reconstruction of the vacuum state is predicted, which should be accompanied by a number of nontrivial effects, including the vacuum positron emission. Similar in essence effects should be expected also in both 2+1 D (planar graphene-based hetero-structures) and 1+1 D (one-dimensional ‘hydrogen ion’). This report is devoted to the study of such essentially non-perturbative vacuum effects for the supercritical Dirac-Coulomb systems in 1+1D and 2+1D, with the main attention drawn to the vacuum polarization energy. Although the most of works considers the vacuum charge density as the main polarization observable, vacuum energy turns out to be not less informative and in many respects complementary to the vacuum density. Moreover, the main non-perturbative effects, which appear in vacuum polarization for supercritical fields due to the levels diving into the lower continuum, show up in the behavior of vacuum energy even more clear, demonstrating explicitly their possible role in the supercritical region. Both in 1+1D and 2+1D, we explore firstly the renormalized vacuum density in the supercritical region using the Wichmann-Kroll method. Thereafter, taking into account the results for the vacuum density, we formulate the renormalization procedure for the vacuum energy. To evaluate the latter explicitly, an original technique, based on a special combination of analytical methods, computer algebra tools and numerical calculations, is applied. It is shown that, for a wide range of the external source parameters (the charge Z and size R), in the supercritical region the renormalized vacuum energy could significantly deviate from the perturbative quadratic growth up to pronouncedly decreasing behavior with jumps by (-2 x mc^2), which occur each time, when the next discrete level dives into the negative continuum. In the considered range of variation of Z and R, the vacuum energy behaves like ~ -Z^2/R in 1+1D and ~ -Z^3/R in 2+1D, exceeding deeply negative values. Such behavior confirms the assumption of the neutral vacuum transmutation into the charged one, and thereby of the spontaneous positron emission, accompanying the emergence of the next vacuum shell due to the total charge conservation. To the end, we also note that the methods, developed for the vacuum energy evaluation in 2+1 D, with minimal complements could be carried over to the three-dimensional case, where the vacuum energy is expected to be ~ -Z^4/R and so could be competitive with the classical electrostatic energy of the Coulomb source.

Keywords: non-perturbative QED-effects, one- and two-dimensional Dirac-Coulomb systems, supercritical fields, vacuum polarization

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Authors: Avi Shrivastava

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Our world continues to grapple with a lot of social issues. Economic growth and scientific advancements have not completely eradicated poverty, homelessness, discrimination and bias, gender inequality, health issues, mental illness, addiction, and other social issues. So, how do we improve the human condition in a world driven by advanced technology? The answer is simple: we will have to leverage technology to address some of the most important social challenges of the day. AI, or artificial intelligence, has emerged as a critical tool in the battle against issues that deprive marginalized and disadvantaged groups of the right to enjoy benefits that a society offers. Social work professionals can transform their lives by harnessing it. The lack of reliable data is one of the reasons why a lot of social work projects fail. Social work professionals continue to rely on expensive and time-consuming primary data collection methods, such as observation, surveys, questionnaires, and interviews, instead of tapping into AI-based technology to generate useful, real-time data and necessary insights. By leveraging AI’s data-mining ability, we can gain a deeper understanding of how to solve complex social problems and change lives of people. We can do the right work for the right people and at the right time. For example, AI can enable social work professionals to focus their humanitarian efforts on some of the world’s poorest regions, where there is extreme poverty. An interdisciplinary team of Stanford scientists, Marshall Burke, Stefano Ermon, David Lobell, Michael Xie, and Neal Jean, used AI to spot global poverty zones – identifying such zones is a key step in the fight against poverty. The scientists combined daytime and nighttime satellite imagery with machine learning algorithms to predict poverty in Nigeria, Uganda, Tanzania, Rwanda, and Malawi. In an article published by Stanford News, Stanford researchers use dark of night and machine learning, Ermon explained that they provided the machine-learning system, an application of AI, with the high-resolution satellite images and asked it to predict poverty in the African region. “The system essentially learned how to solve the problem by comparing those two sets of images [daytime and nighttime].” This is one example of how AI can be used by social work professionals to reach regions that need their aid the most. It can also help identify sources of inequality and conflict, which could reduce inequalities, according to Nature’s study, titled The role of artificial intelligence in achieving the Sustainable Development Goals, published in 2020. The report also notes that AI can help achieve 79 percent of the United Nation’s (UN) Sustainable Development Goals (SDG). AI is impacting our everyday lives in multiple amazing ways, yet some people do not know much about it. If someone is not familiar with this technology, they may be reluctant to use it to solve social issues. So, before we talk more about the use of AI to accomplish social work objectives, let’s put the spotlight on how AI and social work can complement each other.

Keywords: social work, artificial intelligence, AI based social work, machine learning, technology

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Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

Procedia PDF Downloads 275

Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: C. Silveira, A. Ascenso, J. Ferreira, A. I. Miranda, P. Tuccella, G. Curci

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Poor air quality is one of the main environmental causes of premature deaths worldwide, and mainly in cities, where the majority of the population lives. It is a consequence of successive land cover (LC) and use changes, as a result of the intensification of human activities. Knowing these landscape modifications in a comprehensive spatiotemporal dimension is, therefore, essential for understanding variations in air pollutant concentrations. In this sense, the use of air quality models is very useful to simulate the physical and chemical processes that affect the dispersion and reaction of chemical species into the atmosphere. However, the modelling performance should always be evaluated since the resolution of the input datasets largely dictates the reliability of the air quality outcomes. Among these data, the updated LC is an important parameter to be considered in atmospheric models, since it takes into account the Earth’s surface changes due to natural and anthropic actions, and regulates the exchanges of fluxes (emissions, heat, moisture, etc.) between the soil and the air. This work aims to evaluate the performance of the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), when different LC classifications are used as an input. The influence of two LC classifications was tested: i) the 24-classes USGS (United States Geological Survey) LC database included by default in the model, and the ii) CLC (Corine Land Cover) and specific high-resolution LC data for Portugal, reclassified according to the new USGS nomenclature (33-classes). Two distinct WRF-Chem simulations were carried out to assess the influence of the LC on air quality over Europe and Portugal, as a case study, for the year 2015, using the nesting technique over three simulation domains (25 km², 5 km² and 1 km² horizontal resolution). Based on the 33-classes LC approach, particular emphasis was attributed to Portugal, given the detail and higher LC spatial resolution (100 m x 100 m) than the CLC data (5000 m x 5000 m). As regards to the air quality, only the LC impacts on tropospheric ozone concentrations were evaluated, because ozone pollution episodes typically occur in Portugal, in particular during the spring/summer, and there are few research works relating to this pollutant with LC changes. The WRF-Chem results were validated by season and station typology using background measurements from the Portuguese air quality monitoring network. As expected, a better model performance was achieved in rural stations: moderate correlation (0.4 – 0.7), BIAS (10 – 21µg.m^-3) and RMSE (20 – 30 µg.m^-3), and where higher average ozone concentrations were estimated. Comparing both simulations, small differences grounded on the Leaf Area Index and air temperature values were found, although the high-resolution LC approach shows a slight enhancement in the model evaluation. This highlights the role of the LC on the exchange of atmospheric fluxes, and stresses the need to consider a high-resolution LC characterization combined with other detailed model inputs, such as the emission inventory, to improve air quality assessment.

Keywords: land use, spatial resolution, WRF-Chem, air quality assessment

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Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

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In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Gertraud Koch, Teresa Stumpf, Alejandra Tijerina García

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Discourse analysis research approaches belong to the central research strategies applied throughout the humanities; they focus on the countless forms and ways digital texts and images shape present-day notions of the world. Despite the constantly growing number of relevant digital, multimodal discourse resources, digital humanities (DH) methods are thus far not systematically developed and accessible for discourse analysis approaches. Specifically, the significance of multimodality and meaning plurality modelling are yet to be sufficiently addressed. In order to address this research gap, the D-WISE project aims to develop a prototypical working environment as digital support for the sociology of knowledge approach to discourse analysis and new IT-analysis approaches for the use of context-oriented embedding representations. Playing an essential role throughout our research endeavor is the constant optimization of hermeneutical methodology in the use of (semi)automated processes and their corresponding epistemological reflection. Among the discourse analyses, the sociology of knowledge approach to discourse analysis is characterised by the reconstructive and accompanying research into the formation of knowledge systems in social negotiation processes. The approach analyses how dominant understandings of a phenomenon develop, i.e., the way they are expressed and consolidated by various actors in specific arenas of discourse until a specific understanding of the phenomenon and its socially accepted structure are established. This article presents insights and initial findings from D-WISE, a joint research project running since 2021 between the Institute of Anthropological Studies in Culture and History and the Language Technology Group of the Department of Informatics at the University of Hamburg. As an interdisciplinary team, we develop central innovations with regard to the availability of relevant DH applications by building up a uniform working environment, which supports the procedure of the sociology of knowledge approach to discourse analysis within open corpora and heterogeneous, multimodal data sources for researchers in the humanities. We are hereby expanding the existing range of DH methods by developing contextualized embeddings for improved modelling of the plurality of meaning and the integrated processing of multimodal data. The alignment of this methodological and technical innovation is based on the epistemological working methods according to grounded theory as a hermeneutic methodology. In order to systematically relate, compare, and reflect the approaches of structural-IT and hermeneutic-interpretative analysis, the discourse analysis is carried out both manually and digitally. Using the example of current discourses on digitization in the healthcare sector and the associated issues regarding data protection, we have manually built an initial data corpus of which the relevant actors and discourse positions are analysed in conventional qualitative discourse analysis. At the same time, we are building an extensive digital corpus on the same topic based on the use and further development of entity-centered research tools such as topic crawlers and automated newsreaders. In addition to the text material, this consists of multimodal sources such as images, video sequences, and apps. In a blended reading process, the data material is filtered, annotated, and finally coded with the help of NLP tools such as dependency parsing, named entity recognition, co-reference resolution, entity linking, sentiment analysis, and other project-specific tools that are being adapted and developed. The coding process is carried out (semi-)automated by programs that propose coding paradigms based on the calculated entities and their relationships. Simultaneously, these can be specifically trained by manual coding in a closed reading process and specified according to the content issues. Overall, this approach enables purely qualitative, fully automated, and semi-automated analyses to be compared and reflected upon.

Keywords: entanglement of structural IT and hermeneutic-interpretative analysis, multimodality, plurality of meaning, sociology of knowledge approach to discourse analysis

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Authors: Jonathan Turner, Julie Doyle, Laura O’Philbin, Dympna O’Sullivan

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People living with dementia should be at the centre of decision-making regarding goals for daily living. These goals include basic activities (dressing, hygiene, and mobility), advanced activities (finances, transportation, and shopping), and meaningful activities that promote well-being (pastimes and intellectual pursuits). However, there is limited involvement of people living with dementia in the design of technology to support their goals. A project is described that is co-designing intelligent computer-based support for, and with, people affected by dementia and their carers. The technology will support self-management, empower participation in shared decision-making with carers and help people living with dementia remain healthy and independent in their homes for longer. It includes information from the patient’s care plan, which documents medications, contacts, and the patient's wishes on end-of-life care. Importantly for this work, the plan can outline activities that should be maintained or worked towards, such as exercise or social contact. The authors discuss how to integrate care goal information from such a care plan with data collected from passive sensors in the patient’s home in order to deliver individualized planning and interventions for persons with dementia. A number of scientific challenges are addressed: First, to co-design with dementia patients and their carers computerized support for shared decision-making about their care while allowing the patient to share the care plan. Second, to develop a new and open monitoring framework with which to configure sensor technologies to collect data about whether goals and actions specified for a person in their care plan are being achieved. This is developed top-down by associating care quality types and metrics elicited from the co-design activities with types of data that can be collected within the home, from passive and active sensors, and from the patient’s feedback collected through a simple co-designed interface. These activities and data will be mapped to appropriate sensors and technological infrastructure with which to collect the data. Third, the application of machine learning models to analyze data collected via the sensing devices in order to investigate whether and to what extent activities outlined via the care plan are being achieved. The models will capture longitudinal data to track disease progression over time; as the disease progresses and captured data show that activities outlined in the care plan are not being achieved, the care plan may recommend alternative activities. Disease progression may also require care changes, and a data-driven approach can capture changes in a condition more quickly and allow care plans to evolve and be updated.

Keywords: care goals, decision-making, dementia, self-care, sensors

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Authors: Sadi Ali, Yaser Kishawi

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As part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely cover the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is to find non-conventional water resource from treated wastewater to irrigate 1500 hectares and serves over 100,000 inhabitants. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line & 9 infiltration basins - IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme – RRS – to capture the spreading plume). Currently, phase A is functioning since Apr 2009. Since Apr 2009, a monitoring plan is conducted to monitor the infiltration rate (I.R.) of the 9 basins. Nearly 23 million m3 of partially treated wastewater were infiltrated up to Jun 2014. It is important to maintain an acceptable rate to allow the basins to handle the coming quantities (currently 10,000 m3 are pumped an infiltrated daily). The methodology applied was to review and analysis the collected data including the I.R.s, the WW quality and the drying-wetting schedule of the basins. One of the main findings is the relation between the Total Suspended Solids (TSS) at BLWWTP and the I.R. at the basins. Since April 2009, the basins scored an average I.R. of about 2.5 m/day. Since then the records showed a decreasing pattern of the average rate until it reached the lower value of 0.42 m/day in Jun 2013. This was accompanied with an increase of TSS (mg/L) concentration at the source reaching above 200 mg/L. The reducing of TSS concentration directly improved the I.R. (by cleaning the WW source ponds at Biet Lahia WWTP site). This was reflected in an improvement in I.R. in last 6 months from 0.42 m/day to 0.66 m/day then to nearly 1.0 m/day as the average of the last 3 months of 2013. The wetting-drying scheme of the basins was observed (3 days wetting and 7 days drying) besides the rainfall rates. Despite the difficulty to apply this scheme accurately a control of flow to each basin was applied to improve the I.R. The drying-wetting system affected the I.R. of individual basins, thus affected the overall system rate which was recorded and assessed. Also the ploughing activities at the infiltration basins as well were recommended at certain times to retain a certain infiltration level. This breaks the confined clogging layer which prevents the infiltration. It is recommended to maintain proper quality of WW infiltrated to ensure an acceptable performance of IBs. The continual maintenance of settling ponds at BLWWTP, continual ploughing of basins and applying soil treatment techniques at the IBs will improve the I.R.s. When the new WWTP functions a high standard effluent quality (TSS 20mg, BOD 20 mg/l and TN 15 mg/l) will be infiltrated, thus will enhance I.R.s of IBs due to lower organic load.

Keywords: SAT, wastewater quality, soil remediation, North Gaza

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Authors: Jong H. Kim, Kathleen L. Chan, Luisa W. Cheng

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Control of fungal pathogens, such as foodborne mycotoxin producers, is problematic as effective antimycotic agents are often very limited. Mycotoxin contamination significantly interferes with the safe production of foods or crops worldwide. Moreover, expansion of fungal resistance to commercial drugs or fungicides is a global human health concern. Therefore, there is a persistent need to enhance the efficacy of commercial antimycotic agents or to develop new intervention strategies. Disruption of the cellular antioxidant system should be an effective method for pathogen control. Such disruption can be achieved with safe, redox-active compounds. Natural phenolic derivatives are potent redox cyclers that inhibit fungal growth through destabilization of the cellular antioxidant system. The goal of this study is to identify novel, redox-active compounds that disrupt the fungal antioxidant system. The identified compounds could also function as sensitizing agents to conventional antimycotics (i.e., chemosensitization) to improve antifungal efficacy. Various benzo derivatives were tested against fungal pathogens. Gene deletion mutants of the yeast Saccharomyces cerevisiae were used as model systems for identifying molecular targets of benzo analogs. The efficacy of identified compounds as potent antifungal agents or as chemosensitizing agents to commercial drugs or fungicides was examined with methods outlined by the Clinical Laboratory Standards Institute or the European Committee on Antimicrobial Susceptibility Testing. Selected benzo derivatives possessed potent antifungal or antimycotoxigenic activity. Molecular analyses by using S. cerevisiae mutants indicated antifungal activity of benzo derivatives was through disruption of cellular antioxidant or cell wall integrity system. Certain benzo analogs screened overcame tolerance of Aspergillus signaling mutants, namely mitogen-activated protein kinase mutants, to fludioxonil fungicide. Synergistic antifungal chemosensitization greatly lowered minimum inhibitory or fungicidal concentrations of test compounds, including inhibitors of mitochondrial respiration. Of note, salicylaldehyde is a potent antimycotic volatile that has some practical application as a fumigant. Altogether, benzo derivatives targeting cellular antioxidant system of fungi (along with cell wall integrity system) effectively suppress fungal growth. Candidate compounds possess the antifungal, antimycotoxigenic or chemosensitizing capacity to augment the efficacy of commercial antifungals. Therefore, chemogenetic approaches can lead to the development of novel antifungal intervention strategies, which enhance the efficacy of established microbe intervention practices and overcome drug/fungicide resistance. Chemosensitization further reduces costs and alleviates negative side effects associated with current antifungal treatments.

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: Radik D. Aglyamov, Alexander K. Naumov, Alexey A. Shavelev, Oleg A. Morozov, Arsenij D. Shishkin, Yury P.Brodnikovsky, Alexander A.Karabutov, Alexander A. Oraevsky, Vadim V. Semashko

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The development of medical optoacoustic tomography with the using human blood as endogenic contrast agent is constrained by the lack of reliable, easy-to-use and inexpensive sources of high-power pulsed laser radiation in the spectral region of 750-900 nm [1-2]. Currently used titanium-sapphire, alexandrite lasers or optical parametric light oscillators do not provide the required and stable output characteristics, they are structurally complex, and their cost is up to half the price of diagnostic optoacoustic systems. Here we are developing the lasers based on Cr:LiCaAlF6 crystals which are free of abovementioned disadvantages and provides intensive ten’s ns-range tunable laser radiation at specific absorption bands of oxy- (~840 nm) and -deoxyhemoglobin (~757 nm) in the blood. Cr:LiCAF (с=3 at.%) crystals were grown in Kazan Federal University by the vertical directional crystallization (Bridgman technique) in graphite crucibles in a fluorinating atmosphere at argon overpressure (P=1500 hPa) [3]. The laser elements have cylinder shape with the diameter of 8 mm and 90 mm in length. The direction of the optical axis of the crystal was normal to the cylinder generatrix, which provides the π-polarized laser action correspondent to maximal stimulated emission cross-section. The flat working surfaces of the active elements were polished and parallel to each other with an error less than 10”. No any antireflection coating was applied. The Q-switched master oscillator-power amplifiers laser system (MOPA) with the dual-Xenon flashlamp pumping scheme in diffuse-reflectivity close-coupled head were realized. A specially designed laser cavity, consisting of dielectric highly reflective reflectors with a 2 m-curvature radius, a flat output mirror, a polarizer and Q-switch sell, makes it possible to operate sequentially in a circle (50 ns - laser one pulse after another) at wavelengths of 757 and 840 nm. The programmable pumping system from Tomowave Laser LLC (Russia) provided independent to each pulses (up to 250 J at 180 μs) pumping to equalize the laser radiation intensity at these wavelengths. The MOPA laser operates at 10 Hz pulse repetition rate with the output energy up to 210 mJ. Taking into account the limitations associated with physiological movements and other characteristics of patient tissues, the duration of laser pulses and their energy allows molecular and functional high-contrast imaging to depths of 5-6 cm with a spatial resolution of at least 1 mm. Highly likely the further comprehensive design of laser allows improving the output properties and realizing better spatial resolution of medical multispectral optoacoustic tomography systems.

Keywords: medical optoacoustic, endogenic contrast agent, multiwavelength tunable pulse lasers, MOPA laser system

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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