Search results for: cancer risks
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3854

Search results for: cancer risks

1994 South African Breast Cancer Mutation Spectrum: Pitfalls to Copy Number Variation Detection Using Internationally Designed Multiplex Ligation-Dependent Probe Amplification and Next Generation Sequencing Panels

Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

Abstract:

The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

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1993 New Method for the Synthesis of Different Pyrroloquinazolinoquinolin Alkaloids

Authors: Abdulkareem M. Hamid, Yaseen Elhebshi, Adam Daïch

Abstract:

Luotonins and its derivatives (Isoluotonins) are alkaloids from the aerial parts of Peganum nigellastrum Bunge that display three major skeleton types. Luotonins A, B, and E are pyrroloquinazolinoquinoline alkaloids. A few methods were known for the sysnthesis of Isoluotonin. All luotonins have shown promising cytotoxicities towards selected human cancer cell lines, especially against leukemia P-388 cells. Luotonin A is the most active one, with its activity stemming from topoisomerase I-dependent DNA-cleavage. Such intriguing biological activities and unique structures have led not only to the development of synthetic methods for the efficient synthesis of these compounds, but also to interest in structural modifications for improving the biological properties. Recent progress in the study of luotonins is covered.

Keywords: luotonin A, isoluotonin, pyrroloquiolines, alkaloids

Procedia PDF Downloads 420
1992 A Security Study for Smart Metering Systems

Authors: Musaab Hasan, Farkhund Iqbal, Patrick C. K. Hung, Benjamin C. M. Fung, Laura Rafferty

Abstract:

In modern societies, the smart cities concept raised simultaneously with the projection towards adopting smart devices. A smart grid is an essential part of any smart city as both consumers and power utility companies benefit from the features provided by the power grid. In addition to advanced features presented by smart grids, there may also be a risk when the grids are exposed to malicious acts such as security attacks performed by terrorists. Considering advanced security measures in the design of smart meters could reduce these risks. This paper presents a security study for smart metering systems with a prototype implementation of the user interfaces for future works.

Keywords: security design, smart city, smart meter, smart grid, smart metering system

Procedia PDF Downloads 340
1991 Intellectual Property Risk Assessment in Planning Market Entry to China

Authors: Qing Cao

Abstract:

Generally speaking, China has a relatively high level of intellectual property (IP) infringement. Risk assessment is indispensable in the strategic planning process. To complement the current literature in international business, the paper sheds the light on how to assess IP risk for foreign companies in planning market entry to China. Evaluating internal and external IP environment, proposed in the paper, consists of external analysis, internal analysis and further internal analysis. Through position the company’s IP environment, the risk assessment approach enables the foreign companies to either build the corresponding IP strategies or abort the entry plan beforehand to minimize the IP risks.

Keywords: intellectual property, IP environment, risk assessment

Procedia PDF Downloads 564
1990 Evaluation of Aggregate Risks in Sustainable Manufacturing Using Fuzzy Multiple Attribute Decision Making

Authors: Gopinath Rathod, Vinod Puranik

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Sustainability is regarded as a key concept for survival in the competitive scenario. Industrial risk and diversification of risk type’s increases with industrial developments. In the context of sustainable manufacturing, the evaluation of risk is difficult because of the incomplete information and multiple indicators. Fuzzy Multiple Attribute Decision Method (FMADM) has been used with a three level hierarchical decision making model to evaluate aggregate risk for sustainable manufacturing projects. A case study has been presented to reflect the risk characteristics in sustainable manufacturing projects.

Keywords: sustainable manufacturing, decision making, aggregate risk, fuzzy logic, fuzzy multiple attribute decision method

Procedia PDF Downloads 523
1989 Risks in Forestry Operations, Analysis of Fatal Accidents

Authors: Rino Gubiani, Gianfranco Pergher

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The work focused on the statistical analysis of accidents in the forestry sector (2000-2020) in Friuli-Venezia Giulia region, located in the North-East of Italy. The aim of the work was to analyse the evolution of the casualties throughout time and to evaluate possible improvements in the sector. It was shown that even nowadays the rate of accidents in forestry work is higher compared with all the other sectors, including agriculture; moreover, it was highlighted that some accidents remained present throughout the whole analysed range, such as slipping on the soil, being hit by trees and falling down from the plants. The results showed that an increase in forestry exploitation could even increase the total number of accidents, if advanced technological machines, such as cable cranes, would not implemented, given the fact that there is also a significant number of old people (above 50 years old) working in the sector.

Keywords: safety, forestry work, accidents, risk analysis, casualties, statistical analysis

Procedia PDF Downloads 135
1988 Artificial Intelligence: Reimagining Education

Authors: Silvia Zanazzi

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Artificial intelligence (AI) has become an integral part of our world, transitioning from scientific exploration to practical applications that impact daily life. The emergence of generative AI is reshaping education, prompting new questions about the role of teachers, the nature of learning, and the overall purpose of schooling. While AI offers the potential for optimizing teaching and learning processes, concerns about discrimination and bias arising from training data and algorithmic decisions persist. There is a risk of a disconnect between the rapid development of AI and the goals of building inclusive educational environments. The prevailing discourse on AI in education often prioritizes efficiency and individual skill acquisition. This narrow focus can undermine the importance of collaborative learning and shared experiences. A growing body of research challenges this perspective, advocating for AI that enhances, rather than replaces, human interaction in education. This study aims to examine the relationship between AI and education critically. Reviewing existing research will identify both AI implementation’s potential benefits and risks. The goal is to develop a framework that supports the ethical and effective integration of AI into education, ensuring it serves the needs of all learners. The theoretical reflection will be developed based on a review of national and international scientific literature on artificial intelligence in education. The primary objective is to curate a selection of critical contributions from diverse disciplinary perspectives and/or an inter- and transdisciplinary viewpoint, providing a state-of-the-art overview and a critical analysis of potential future developments. Subsequently, the thematic analysis of these contributions will enable the creation of a framework for understanding and critically analyzing the role of artificial intelligence in schools and education, highlighting promising directions and potential pitfalls. The expected results are (1) a classification of the cognitive biases present in representations of AI in education and the associated risks and (2) a categorization of potentially beneficial interactions between AI applications and teaching and learning processes, including those already in use or under development. While not exhaustive, the proposed framework will serve as a guide for critically exploring the complexity of AI in education. It will help to reframe dystopian visions often associated with technology and facilitate discussions on fostering synergies that balance the ‘dream’ of quality education for all with the realities of AI implementation. The discourse on artificial intelligence in education, highlighting reductionist models rooted in fragmented and utilitarian views of knowledge, has the merit of stimulating the construction of alternative perspectives that can ‘return’ teaching and learning to education, human growth, and the well-being of individuals and communities.

Keywords: education, artificial intelligence, teaching, learning

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1987 Chatbots and the Future of Globalization: Implications of Businesses and Consumers

Authors: Shoury Gupta

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Chatbots are a rapidly growing technological trend that has revolutionized the way businesses interact with their customers. With the advancements in artificial intelligence, chatbots can now mimic human-like conversations and provide instant and efficient responses to customer inquiries. In this research paper, we aim to explore the implications of chatbots on the future of globalization for both businesses and consumers. The paper begins by providing an overview of the current state of chatbots in the global market and their growth potential in the future. The focus is on how chatbots have become a valuable tool for businesses looking to expand their global reach, especially in areas with high population density and language barriers. With chatbots, businesses can engage with customers in different languages and provide 24/7 customer service support, creating a more accessible and convenient customer experience. The paper then examines the impact of chatbots on cross-cultural communication and how they can help bridge communication gaps between businesses and consumers from different cultural backgrounds. Chatbots can potentially facilitate cross-cultural communication by offering real-time translations, voice recognition, and other innovative features that can help users communicate effectively across different languages and cultures. By providing more accessible and inclusive communication channels, chatbots can help businesses reach new markets and expand their customer base, making them more competitive in the global market. However, the paper also acknowledges that there are potential drawbacks associated with chatbots. For instance, chatbots may not be able to address complex customer inquiries that require human input. Additionally, chatbots may perpetuate biases if they are programmed with certain stereotypes or assumptions about different cultures. These drawbacks may have significant implications for businesses and consumers alike. To explore the implications of chatbots on the future of globalization in greater detail, the paper provides a thorough review of existing literature and case studies. The review covers topics such as the benefits of chatbots for businesses and consumers, the potential drawbacks of chatbots, and how businesses can mitigate any risks associated with chatbot use. The paper also discusses the ethical considerations associated with chatbot use, such as privacy concerns and the need to ensure that chatbots do not discriminate against certain groups of people. The ethical implications of chatbots are particularly important given the potential for chatbots to be used in sensitive areas such as healthcare and financial services. Overall, this research paper provides a comprehensive analysis of chatbots and their implications for the future of globalization. By exploring both the potential benefits and drawbacks of chatbot use, the paper aims to provide insights into how businesses and consumers can leverage this technology to achieve greater global reach and improve cross-cultural communication. Ultimately, the paper concludes that chatbots have the potential to be a powerful tool for businesses looking to expand their global footprint and improve their customer experience, but that care must be taken to mitigate any risks associated with their use.

Keywords: chatbots, conversational AI, globalization, businesses

Procedia PDF Downloads 102
1986 Normal Hematopoietic Stem Cell and the Toxic Effect of Parthenolide

Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

Abstract:

Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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1985 Molecular Alterations Shed Light on Alteration of Methionine Metabolism in Gastric Intestinal Metaplesia; Insight for Treatment Approach

Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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1984 Immigration Solutions for the United States

Authors: Philip Robert Alldritt

Abstract:

The continuing increase in human migration is at crisis levels in all areas of the planet. The causes are varied, and the risks are high for the migrants. Migration has been ongoing since the beginning of human emergence on the planet, but for the first time in our historic memory has the, migration reached this level of critical mass. The causes are many. Climate collapse, economic opportunity, drug cartel activity, political upheaval, and gang wars. Many locations are seemingly “within reach” of the migrants, and the push factors are so loaded with hopelessness that almost anyone would be willing to risk anything to improve their conditions. There is no argument about that mass migrations are occurring and will increase in the future. The solutions to this increase are complex. This paper will examine the causes of migration and attempt to provide some reasonable solutions to mitigate the migrations with equitable outcomes that may guide immigration policy in impacted areas.

Keywords: immigration, crisis, climate, cartels

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1983 The Current Home Hemodialysis Practices and Patients’ Safety Related Factors: A Case Study from Germany

Authors: Ilyas Khan. Liliane Pintelon, Harry Martin, Michael Shömig

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The increasing costs of healthcare on one hand, and the rise in aging population and associated chronic disease, on the other hand, are putting increasing burden on the current health care system in many Western countries. For instance, chronic kidney disease (CKD) is a common disease and in Europe, the cost of renal replacement therapy (RRT) is very significant to the total health care cost. However, the recent advancement in healthcare technology, provide the opportunity to treat patients at home in their own comfort. It is evident that home healthcare offers numerous advantages apparently, low costs and high patients’ quality of life. Despite these advantages, the intake of home hemodialysis (HHD) therapy is still low in particular in Germany. Many factors are accounted for the low number of HHD intake. However, this paper is focusing on patients’ safety-related factors of current HHD practices in Germany. The aim of this paper is to analyze the current HHD practices in Germany and to identify risks related factors if any exist. A case study has been conducted in a dialysis center which consists of four dialysis centers in the south of Germany. In total, these dialysis centers have 350 chronic dialysis patients, of which, four patients are on HHD. The centers have 126 staff which includes six nephrologists and 120 other staff i.e. nurses and administration. The results of the study revealed several risk-related factors. Most importantly, these centers do not offer allied health services at the pre-dialysis stage, the HHD training did not have an established curriculum; however, they have just recently developed the first version. Only a soft copy of the machine manual is offered to patients. Surprisingly, the management was not aware of any standard available for home assessment and installation. The home assessment is done by a third party (i.e. the machines and equipment provider) and they may not consider the hygienic quality of the patient’s home. The type of machine provided to patients at home is similar to the one in the center. The model may not be suitable at home because of its size and complexity. Even though portable hemodialysis machines, which are specially designed for home use, are available in the market such as the NxStage series. Besides the type of machine, no assistance is offered for space management at home in particular for placing the machine. Moreover, the centers do not offer remote assistance to patients and their carer at home. However, telephonic assistance is available. Furthermore, no alternative is offered if a carer is not available. In addition, the centers are lacking medical staff including nephrologists and renal nurses.

Keywords: home hemodialysis, home hemodialysis practices, patients’ related risks in the current home hemodialysis practices, patient safety in home hemodialysis

Procedia PDF Downloads 120
1982 A Prediction Model of Tornado and Its Impact on Architecture Design

Authors: Jialin Wu, Zhiwei Lian, Jieyu Tang, Jingyun Shen

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Tornado is a serious and unpredictable natural disaster, which has an important impact on people's production and life. The probability of being hit by tornadoes in China was analyzed considering the principles of tornado formation. Then some suggestions on layout and shapes for newly-built buildings were provided combined with the characteristics of tornado wind fields. Fuzzy clustering and inverse closeness methods were used to evaluate the probability levels of tornado risks in various provinces based on classification and ranking. GIS was adopted to display the results. Finally, wind field single-vortex tornado was studied to discuss the optimized design of rural low-rise houses in Yancheng, Jiangsu as an example. This paper may provide enough data to support building and urban design in some specific regions.

Keywords: tornado probability, computational fluid dynamics, fuzzy mathematics, optimal design

Procedia PDF Downloads 140
1981 Quantifying Multivariate Spatiotemporal Dynamics of Malaria Risk Using Graph-Based Optimization in Southern Ethiopia

Authors: Yonas Shuke Kitawa

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Background: Although malaria incidence has substantially fallen sharply over the past few years, the rate of decline varies by district, time, and malaria type. Despite this turn-down, malaria remains a major public health threat in various districts of Ethiopia. Consequently, the present study is aimed at developing a predictive model that helps to identify the spatio-temporal variation in malaria risk by multiple plasmodium species. Methods: We propose a multivariate spatio-temporal Bayesian model to obtain a more coherent picture of the temporally varying spatial variation in disease risk. The spatial autocorrelation in such a data set is typically modeled by a set of random effects that assign a conditional autoregressive prior distribution. However, the autocorrelation considered in such cases depends on a binary neighborhood matrix specified through the border-sharing rule. Over here, we propose a graph-based optimization algorithm for estimating the neighborhood matrix that merely represents the spatial correlation by exploring the areal units as the vertices of a graph and the neighbor relations as the series of edges. Furthermore, we used aggregated malaria count in southern Ethiopia from August 2013 to May 2019. Results: We recognized that precipitation, temperature, and humidity are positively associated with the malaria threat in the area. On the other hand, enhanced vegetation index, nighttime light (NTL), and distance from coastal areas are negatively associated. Moreover, nonlinear relationships were observed between malaria incidence and precipitation, temperature, and NTL. Additionally, lagged effects of temperature and humidity have a significant effect on malaria risk by either species. More elevated risk of P. falciparum was observed following the rainy season, and unstable transmission of P. vivax was observed in the area. Finally, P. vivax risks are less sensitive to environmental factors than those of P. falciparum. Conclusion: The improved inference was gained by employing the proposed approach in comparison to the commonly used border-sharing rule. Additionally, different covariates are identified, including delayed effects, and elevated risks of either of the cases were observed in districts found in the central and western regions. As malaria transmission operates in a spatially continuous manner, a spatially continuous model should be employed when it is computationally feasible.

Keywords: disease mapping, MSTCAR, graph-based optimization algorithm, P. falciparum, P. vivax, waiting matrix

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1980 Ethical Artificial Intelligence: An Exploratory Study of Guidelines

Authors: Ahmad Haidar

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The rapid adoption of Artificial Intelligence (AI) technology holds unforeseen risks like privacy violation, unemployment, and algorithmic bias, triggering research institutions, governments, and companies to develop principles of AI ethics. The extensive and diverse literature on AI lacks an analysis of the evolution of principles developed in recent years. There are two fundamental purposes of this paper. The first is to provide insights into how the principles of AI ethics have been changed recently, including concepts like risk management and public participation. In doing so, a NOISE (Needs, Opportunities, Improvements, Strengths, & Exceptions) analysis will be presented. Second, offering a framework for building Ethical AI linked to sustainability. This research adopts an explorative approach, more specifically, an inductive approach to address the theoretical gap. Consequently, this paper tracks the different efforts to have “trustworthy AI” and “ethical AI,” concluding a list of 12 documents released from 2017 to 2022. The analysis of this list unifies the different approaches toward trustworthy AI in two steps. First, splitting the principles into two categories, technical and net benefit, and second, testing the frequency of each principle, providing the different technical principles that may be useful for stakeholders considering the lifecycle of AI, or what is known as sustainable AI. Sustainable AI is the third wave of AI ethics and a movement to drive change throughout the entire lifecycle of AI products (i.e., idea generation, training, re-tuning, implementation, and governance) in the direction of greater ecological integrity and social fairness. In this vein, results suggest transparency, privacy, fairness, safety, autonomy, and accountability as recommended technical principles to include in the lifecycle of AI. Another contribution is to capture the different basis that aid the process of AI for sustainability (e.g., towards sustainable development goals). The results indicate data governance, do no harm, human well-being, and risk management as crucial AI for sustainability principles. This study’s last contribution clarifies how the principles evolved. To illustrate, in 2018, the Montreal declaration mentioned eight principles well-being, autonomy, privacy, solidarity, democratic participation, equity, and diversity. In 2021, notions emerged from the European Commission proposal, including public trust, public participation, scientific integrity, risk assessment, flexibility, benefit and cost, and interagency coordination. The study design will strengthen the validity of previous studies. Yet, we advance knowledge in trustworthy AI by considering recent documents, linking principles with sustainable AI and AI for sustainability, and shedding light on the evolution of guidelines over time.

Keywords: artificial intelligence, AI for sustainability, declarations, framework, regulations, risks, sustainable AI

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1979 Realistic Modeling of the Preclinical Small Animal Using Commercial Software

Authors: Su Chul Han, Seungwoo Park

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As the increasing incidence of cancer, the technology and modality of radiotherapy have advanced and the importance of preclinical model is increasing in the cancer research. Furthermore, the small animal dosimetry is an essential part of the evaluation of the relationship between the absorbed dose in preclinical small animal and biological effect in preclinical study. In this study, we carried out realistic modeling of the preclinical small animal phantom possible to verify irradiated dose using commercial software. The small animal phantom was modeling from 4D Digital Mouse whole body phantom. To manipulate Moby phantom in commercial software (Mimics, Materialise, Leuven, Belgium), we converted Moby phantom to DICOM image file of CT by Matlab and two- dimensional of CT images were converted to the three-dimensional image and it is possible to segment and crop CT image in Sagittal, Coronal and axial view). The CT images of small animals were modeling following process. Based on the profile line value, the thresholding was carried out to make a mask that was connection of all the regions of the equal threshold range. Using thresholding method, we segmented into three part (bone, body (tissue). lung), to separate neighboring pixels between lung and body (tissue), we used region growing function of Mimics software. We acquired 3D object by 3D calculation in the segmented images. The generated 3D object was smoothing by remeshing operation and smoothing operation factor was 0.4, iteration value was 5. The edge mode was selected to perform triangle reduction. The parameters were that tolerance (0.1mm), edge angle (15 degrees) and the number of iteration (5). The image processing 3D object file was converted to an STL file to output with 3D printer. We modified 3D small animal file using 3- Matic research (Materialise, Leuven, Belgium) to make space for radiation dosimetry chips. We acquired 3D object of realistic small animal phantom. The width of small animal phantom was 2.631 cm, thickness was 2.361 cm, and length was 10.817. Mimics software supported efficiency about 3D object generation and usability of conversion to STL file for user. The development of small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Keywords: mimics, preclinical small animal, segmentation, 3D printer

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1978 Prayer Therapy in a Case of Acute Myeloid Leukemia: The Good, the Bad and the Ugly

Authors: Rubai M. Ochieng

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Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

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1977 Efficient Reuse of Exome Sequencing Data for Copy Number Variation Callings

Authors: Chen Wang, Jared Evans, Yan Asmann

Abstract:

With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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1976 Using the Structural Equation Model to Explain the Effect of Supervisory Practices on Regulatory Density

Authors: Jill Round

Abstract:

In the economic system, the financial sector plays a crucial role as an intermediary between market participants, other financial institutions, and customers. Financial institutions such as banks have to make decisions to satisfy the demands of all the participants by keeping abreast of regulatory change. In recent years, progress has been made regarding frameworks, development of rules, standards, and processes to manage risks in the banking sector. The increasing focus of regulators and policymakers placed on risk management, corporate governance, and the organization’s culture is of special interest as it requires a well-resourced risk controlling function, compliance function, and internal audit function. In the past years, the relevance of these functions that make up the so-called Three Lines of Defense has moved from the backroom to the boardroom. The approach of the model can vary based on the various organizational characteristics. Due to the intense regulatory requirements, organizations operating in the financial sector have more mature models. In less regulated industries there is more cloudiness about what tasks are allocated where. All parties strive to achieve their objectives through the effective management of risks and serve the identical stakeholders. Today, the Three Lines of Defense model is used throughout the world. The research looks at trends and emerging issues in the professions of the Three Lines of Defense within the banking sector. The answers are believed to helping to explain the increasing regulatory requirements for the banking sector. While the number of supervisory practices increases the risk management requirements intensify and demand more regulatory compliance at the same time. The Structural Equation Modeling (SEM) is applied by making use of conducted surveys in the research field. It aims to describe (i) the theoretical model regarding the applicable linearity relationships, (ii) the causal relationship between multiple predictors (exogenous) and multiple dependent variables (endogenous), (iii) taking into consideration the unobservable variables and (iv) the measurement errors. The surveys conducted on the research field suggest that the observable variables are caused by various latent variables. The SEM consists of the 1) measurement model and the 2) structural model. There is a detectable correlation regarding the cause-effect relationship among the performed supervisory practices and the increasing scope of regulation. Supervisory practices reinforce the regulatory density. In the past, controls were placed after supervisory practices were conducted or incidents occurred. In further research, it is of interest to examine, whether risk management is proactive, reactive to incidents and supervisory practices or can be both at the same time.

Keywords: risk management, structural equation model, supervisory practice, three lines of defense

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1975 Agile Succession Planning in the Post-Covid World

Authors: Ashneel Kumar Singh

Abstract:

The COVID-19 pandemic has dramatically transformed the global workforce, leading to significant challenges in staffing and employment. The shift to remote work, the health risks posed by the virus, and the phenomenon known as ‘The Great Termination’ have all contributed to the disruption of traditional succession planning methods. This paper explores how agile succession planning can be effectively implemented in the post-COVID world to retain top talent and ensure organizational resilience. Through a review of the literature and practical examples, the paper discusses the difficulties of succession planning in the current environment and the importance of adopting an agile approach and offers recommendations for businesses to navigate the complexities of succession planning in a rapidly changing landscape.

Keywords: agile succession planning, adopt a culture of continuous learning, create a multi-successor planning approach, the great termination

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1974 Justitium: Endangered Species and Humanitarian Interventions in the Anthropocene Era

Authors: Eleni Panagiotarakou

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This paper argues that humans have a collective moral responsibility to help wild animals during the Anthropocene era. Seen from the perspective of deontic logic, this moral responsibility did not exist in the Holocene era (ca. 11,700 BC-1945 AD) on account of humanity’s limited impact on the natural environment. By contrast in the Anthropocene, human activities are causing significant disturbances to planetary ecosystems and by inference to wildlife communities. Under these circumstances controversial and deeply regrettable interventional methods such as Managed Relocations (MR) and synthetic biology should be expanded and become policy measures despite their known and unknown risks. The main rationale for the above stems from the fact that traditional management strategies are simply insufficient in the Anthropocene. If the same anthropogenic activities continue unabated they risk triggering a sixth mass species extinction.

Keywords: anthropocene, humanitarian interventions, managed relocations, species extinctions, synthetic biology

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1973 Safety Status of Stations and Tunnels of Tehran Line 4 Urban and Suburb Railways (Subway) Against Fire Risks

Authors: Yousefi Aryian, Ghanbaripour Amir naser

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Record of 2 million trips during a day by subway makes it the most application and the most efficient branch of public transportation. Great safety, energy consumption reduction, appropriate speed, and lower prices for passengers in comparison with private cars or buses, are some reasons for this remarkable statics. This increasing popularity compels the author to evaluate the safety of subway stations and tunnels against fire and fire extinguishing systems in Tehran subway network and then compare some of its safety parameters to other countries. This paper assessed the methods and systems used in different parts of Tehran subway and then by comparing the facilities and equipment necessary to declare and extinguish the fire, the solutions and world standards (NFPA) are explored.

Keywords: subway station, tunnel, fire alarm, extinguishing fire, NFPA standards

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1972 Synthesis of Monocyclic, Bicyclic, and Benzocyclobutene Amino Endoperoxides through Visible Light Catalysis

Authors: Enoch Kudoahor, Nan Zheng

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We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.

Keywords: catalysis, endoperoxides, titanium dioxide, visible light

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1971 A Model of Preventing Global Financial Crisis: Gauss Law Model Proposal Used in Electrical Field Calculations

Authors: Arzu K. Kamberli

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This article examines the relationship between economics and physics, starting with Adam Smith, with a new econophysics approach in Economics-Physics with the Gauss Law model proposal using for the Electric Field calculation, which will allow us to anticipate the Global Financial Crisis. For this purpose, the similarities between the Gauss Law using the electric field calculations and the global financial crisis have been explained on the formula, and a model has been suggested to predict the risks of the financial systems from the electricity field calculations. Thus, this study is expected to help for preventing the Global Financial Crisis with the contribution of the science of economics and physics from the aspect of econophysics.

Keywords: econophysics, electric field, financial system, Gauss law, global financial crisis

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1970 Menopause Hormone Therapy: An Insight into Knowledge and Attitudes of Obstetricians and Gynecologists in Singapore

Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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1969 The Impact of Artificial Intelligence on Food Industry

Authors: George Hanna Abdelmelek Henien

Abstract:

Quality and safety issues are common in Ethiopia's food processing industry, which can negatively impact consumers' health and livelihoods. The country is known for its various agricultural products that are important to the economy. However, food quality and safety policies and management practices in the food processing industry have led to many health problems, foodborne illnesses and economic losses. This article aims to show the causes and consequences of food safety and quality problems in the food processing industry in Ethiopia and discuss possible solutions to solve them. One of the main reasons for food quality and safety in Ethiopia's food processing industry is the lack of adequate regulation and enforcement mechanisms. Inadequate food safety and quality policies have led to inefficiencies in food production. Additionally, the failure to monitor and enforce existing regulations has created a good opportunity for unscrupulous companies to engage in harmful practices that endanger the lives of citizens. The impact on food quality and safety is significant due to loss of life, high medical costs, and loss of consumer confidence in the food processing industry. Foodborne diseases such as diarrhoea, typhoid and cholera are common in Ethiopia, and food quality and safety play an important role in . Additionally, food recalls due to contamination or contamination often cause significant economic losses in the food processing industry. To solve these problems, the Ethiopian government began taking measures to improve food quality and safety in the food processing industry. One of the most prominent initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to monitor and control the quality and safety of food and beverage products in the country. EFDA has implemented many measures to improve food safety, such as carrying out routine inspections, monitoring the import of food products and implementing labeling requirements. Another solution that can improve food quality and safety in the food processing industry in Ethiopia is the implementation of food safety management system (FSMS). FSMS is a set of procedures and policies designed to identify, assess and control food safety risks during food processing. Implementing a FSMS can help companies in the food processing industry identify and address potential risks before they harm consumers. Additionally, implementing an FSMS can help companies comply with current safety and security regulations. Consequently, improving food safety policy and management system in Ethiopia's food processing industry is important to protect people's health and improve the country's economy. . Addressing the root causes of food quality and safety and implementing practical solutions that can help improve the overall food safety and quality in the country, such as establishing regulatory bodies and implementing food management systems.

Keywords: food quality, food safety, policy, management system, food processing industry food traceability, industry 4.0, internet of things, block chain, best worst method, marcos

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1968 Full Mini Nutritional Assessment Questionnaire and the Risk of Malnutrition and Mortality in Elderly, Hospitalized Patients: A Cross-Sectional Study

Authors: Christos E. Lampropoulos, Maria Konsta, Tamta Sirbilatze, Ifigenia Apostolou, Vicky Dradaki, Konstantina Panouria, Irini Dri, Christina Kordali, Vaggelis Lambas, Georgios Mavras

Abstract:

Objectives: Full Mini Nutritional Assessment (MNA) questionnaire is one of the most useful tools in diagnosis of malnutrition in hospitalized patients, which is related to increased morbidity and mortality. The purpose of our study was to assess the nutritional status of elderly, hospitalized patients and examine the hypothesis that MNA may predict mortality and extension of hospitalization. Methods: One hundred fifty patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. The following data were taken into account in analysis: anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission. The latter was compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and extended hospitalization respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 20% per each unit increase of full MNA score (OR=0.8, 95% CI 0.74-0.89, p < 0.0001). Patients who admitted due to cancer were 23 times more likely to die, compared to those with infection (OR=23, 95% CI 3.8-141.6, p=0.001). Similarly, patients who admitted due to stroke were 7 times more likely to die (OR=7, 95% CI 1.4-34.5, p=0.02), while these with all other causes of admission were less likely (OR=0.2, 95% CI 0.06-0.8, p=0.03), compared to patients with infection. According to multivariate linear regression analysis, each increase of unit of full MNA, decreased the admission duration on average 0.3 days (b:-0.3, 95% CI -0.45 - -0.15, p < 0.0001). Patients admitted due to cancer had on average 6.8 days higher extension of hospitalization, compared to those admitted for infection (b:6.8, 95% CI 3.2-10.3, p < 0.0001). Conclusion: Mortality and extension of hospitalization is significantly increased in elderly, malnourished patients. Full MNA score is a useful diagnostic tool of malnutrition.

Keywords: duration of admission, malnutrition, mini nutritional assessment score, prognostic factors for mortality

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1967 Machine Learning Development Audit Framework: Assessment and Inspection of Risk and Quality of Data, Model and Development Process

Authors: Jan Stodt, Christoph Reich

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The usage of machine learning models for prediction is growing rapidly and proof that the intended requirements are met is essential. Audits are a proven method to determine whether requirements or guidelines are met. However, machine learning models have intrinsic characteristics, such as the quality of training data, that make it difficult to demonstrate the required behavior and make audits more challenging. This paper describes an ML audit framework that evaluates and reviews the risks of machine learning applications, the quality of the training data, and the machine learning model. We evaluate and demonstrate the functionality of the proposed framework by auditing an steel plate fault prediction model.

Keywords: audit, machine learning, assessment, metrics

Procedia PDF Downloads 274
1966 Magnesium Nanoparticles for Photothermal Therapy

Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

Abstract:

Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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1965 Oncolytic Efficacy of Thymidine Kinase-Deleted Vaccinia Virus Strain Tiantan (oncoVV-TT) in Glioma

Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

Abstract:

Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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