Search results for: ethical progression

Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Zahid Ullah, Atlas Khan

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The rapid growth of data in various domains has created a pressing need for effective methods to transform this data into meaningful knowledge. In this era of big data, mathematical and statistical innovations play a crucial role in unlocking insights and facilitating informed decision-making in data analytics. This abstract aims to explore the transformative potential of these innovations and their impact on converting raw data into actionable knowledge. Drawing upon a comprehensive review of existing literature, this research investigates the cutting-edge mathematical and statistical techniques that enable the conversion of data into knowledge. By evaluating their underlying principles, strengths, and limitations, we aim to identify the most promising innovations in data analytics. To demonstrate the practical applications of these innovations, real-world datasets will be utilized through case studies or simulations. This empirical approach will showcase how mathematical and statistical innovations can extract patterns, trends, and insights from complex data, enabling evidence-based decision-making across diverse domains. Furthermore, a comparative analysis will be conducted to assess the performance, scalability, interpretability, and adaptability of different innovations. By benchmarking against established techniques, we aim to validate the effectiveness and superiority of the proposed mathematical and statistical innovations in data analytics. Ethical considerations surrounding data analytics, such as privacy, security, bias, and fairness, will be addressed throughout the research. Guidelines and best practices will be developed to ensure the responsible and ethical use of mathematical and statistical innovations in data analytics. The expected contributions of this research include advancements in mathematical and statistical sciences, improved data analysis techniques, enhanced decision-making processes, and practical implications for industries and policymakers. The outcomes will guide the adoption and implementation of mathematical and statistical innovations, empowering stakeholders to transform data into actionable knowledge and drive meaningful outcomes.

Keywords: data analytics, mathematical innovations, knowledge extraction, decision-making

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Authors: Liang Wang, Wei Zhang

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Nowadays, sustainable development has increasingly become an important research topic of engineering education. Existing research on Engineering Education for Sustainable Development (EESD) has highlighted the importance of perceptions for ethical responsibility to address sustainable development in practice. However, whether and how the professional engineering experience affects those perceptions has not been proved, especially in a Chinese context. Our study fills this gap by investigating the perceptions bias of EESD between experienced engineers and engineering students. We specifically examined what EESD means for experienced engineers and engineering students using a triple-dimensional model to understand if there are obvious differences between the two groups. Our goal is to make the benefits of these experiences more accessible in school context. The data (n=438) came from a questionnaire created and adapted from previously published studies containing 288 students from mechanical or civil engineering and 150 civil engineers with rich working experience, and the questionnaire was distributed during Fall 2020. T-test was used to find the difference in different dimensions between the two groups. The statistical results show that there is a significant difference in the perceptions of EESD between experienced engineers and inexperienced engineering students in China. Experienced engineers tend to consider sustainable development from ecological, economic, and social perspectives, while engineering students' answers focus more on ecology and ignore economic and social dimensions to some extend. The findings provide empirical evidence that professional experience is helpful to cultivate the cognition and ability of sustainable development in engineering education. The results of this work indicate that more practical content should be added to engineering education to promote sustainable development. In addition, for the design of engineering courses and professional practice systems for sustainable development, we should not only pay attention to the ecological aspects but also emphasize the coordination of ecological, economic, and socially sustainable development (e.g., engineer's ethical responsibility).

Keywords: engineering education, sustainable development, experienced engineers, engineering students

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Christopher Restall

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field causing attraction between mixed charges of matter during charge exchanges with antimatter. This asymmetry is caused from none-trinary quark amount variation in matter and anti-matter during entropy progression. This document explains how a circularity critique exercise assessed scientific knowledge and develop a unified theory from the information collected. The circularity critique, creates greater intuition leaps than an individual would naturally, the information collected can be integrated and assessed thoroughly for correctness.

Keywords: unified theory of everything, gravity, quantum gravity, standard model

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Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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Authors: Toby Gibbs, Glen Craigie, Suwaree Yordchim

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Using the Speexx Online Language Training Program with Thai students has allowed us to evaluate their learning comprehension and track their progression through the English language program. Speexx sets the standard for excellence and innovation in web-based language training and online coaching services. The program is designed to improve the business communication skills of language learners for Thai students. Speexx consists of English lessons, exercises, tests, web boards, and supplementary lessons to help students practice English. The sample groups are 191 Thai sophomores studying Business English with the department of Humanities and Social Science. The data was received by standard deviation (S.D.) value from questionnaires and samples provided from the Speexx training program. The results found that most Thai sophomores fail the Speexx training program due to their learning comprehension of the English language is below average. With persisted efforts on new training methods, the success of the Speexx Language Training Program can break through the cultural barriers and help future students adopt English as a second language. The Speexx results revealed four main factors affecting the success as follows: 1) Future English training should be pursued in applied Speexx development. 2) Thai students didn’t see the benefit of having an Online Language Training Program. 3) There is a great need to educate the next generation of learners on the benefits of Speexx within the community. 4) A great majority of Thai Sophomores didn't know what Speexx was. A guideline for self-reliance planning consisted of four aspects: 1) Development planning: by arranging groups to further improve English abilities with the Speexx Language Training program and encourage using Speexx every day. Local communities need to develop awareness of the usefulness of Speexx and share the value of using the program among family and friends. 2) Humanities and Social Science staff should develop skills using this Online Language Training Program to expand on the benefits of Speexx within their departments. 3) Further research should be pursued on the Thai Students progression with Speexx and how it helps them improve their language skills with Business English. 4) University’s and Language centers should focus on using Speexx to encourage learning for any language, not just English.

Keywords: ability, comprehension, sophomore, speexx

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Sangchul Kim, Dosaeng Park

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It is one of the important design issues to provide various levels of difficulty in order to suit the skillfulness of an individual. In this paper we propose an integer programming-based method for selecting a mixture of challenges for a racing game that meet a given degree of difficulty. The proposed method can also be used to dynamically adjust the difficulty of the game during the progression of playing. By experiments, it is shown that our method performs well enough to generate games with various degrees of difficulty that match the perception of players.

Keywords: level generation, level adjustment, racing game, ip

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Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

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Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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Authors: Zuliani Mahmood, Thirumulu Ponnuraj Kannan, Yean Yean Chan, Salahddin A. Al-Hudhairy

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Caries is the most common childhood disease which develops due to disturbances in the physiological equilibrium in the dental plaque resulting in demineralization of tooth structures. Plaque and dentine samples were collected from three different tooth surfaces representing caries progression (intact, over carious lesion and dentine) in children with early childhood caries (ECC, n=36). In caries free (CF) children, plaque samples were collected from sound tooth surfaces at baseline and after one year (n=12). The genomic DNA was extracted from all samples and subjected to 16S rRNA PCR amplification. The end products were cloned into pCR®2.1-TOPO® Vector. Five randomly selected positive clones collected from each surface were sent for sequencing. Identification of the bacterial clones was performed using BLAST against GenBank database. In the ECC group, the frequency of Lactobacillus sp. detected was significantly higher in the dentine surface (p = 0.031) than over the cavitated lesion. The highest frequency of bacteria detected in the intact surfaces was Fusobacterium nucleatum subsp. polymorphum (33.3%) while Streptococcus mutans was detected over the carious lesions and dentine surfaces at a frequency of 33.3% and 52.7% respectively. Fusobacterium nucleatum subsp. polymorphum was also found to be highest in the CF group (41.6%). Follow up at the end of one year showed that the frequency of Corynebacterium matruchotii detected was highest in those who remained caries free (16.6%), while Porphyromonas catoniae was highest in those who developed caries (25%). In conclusion, Streptococcus mutans and Porphyromonas catoniae are strongly associated with caries progression, while Lactobacillus sp. is restricted to deep carious lesions. Fusobacterium nucleatum subsp. polymorphum and Corynebacterium matruchotii may play a role in sustaining the healthy equilibrium in the dental plaque. These identified bacteria show promise as potential biomarkers in diagnosis which could help in the management of dental caries in children.

Keywords: early childhood caries, genotypic identification, oral bacteria, 16S rRNA

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Authors: Pippa Sipanoun, Jo Wray, Kate Oulton, Faith Gibson

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Background: With rapidly evolving digital health innovation, there is a need for digital health transformation that is accessible and sustainable, that demonstrates utility for all stakeholders while maintaining data safety. Great Ormond Street Hospital for Children aimed to future-proof the hospital by transitioning to an electronic patient record (EPR) system with a tethered patient portal (MyGOSH) in April 2019. MyGOSH patient portal enables patients 12 years or older (with their parent's consent) to access their digital health data. This includes access to results, documentation, and appointments that facilitate communication with their care team. As part of the Going Digital Study conducted between 2018-2021, data were collected from a sample of all relevant stakeholders before and after EPR and MyGOSH implementation. Data collection reach was wide and included the hospital legal and ethics teams. Aims: This study aims to understand the ethical and legal implications of young people and their parents accessing their digital health data. Methods: A focus group was conducted. Recruited participants were members of the Great Ormond Street Hospital Paediatric Bioethics Centre. Participants included expert and lay members from the Committee from a variety of professional or academic disciplines. Written informed consent was provided by all participants (n=7). The focus group was recorded, transcribed verbatim, and analyzed using thematic analysis. Results: Six themes were identified: access, competence and capacity - granting access to the system; inequalities in access resulting in inequities; burden, uncertainty and responding to change - managing expectations; documenting, risks and data safety; engagement, empowerment and understanding – how to use and manage personal information; legal considerations and obligations. Discussion: If healthcare professionals are to empower young people to be more engaged in their care, the importance of including them in decisions about their health is paramount, especially when they are approaching the age of becoming the consenter for treatment. Complexities exist in assessing competence or capacity when granting system access, when disclosing sensitive information, and maintaining confidentiality. Difficulties are also present in managing clinician burden, managing user expectations whilst providing an equitable service, and data management that meets professional and legal requirements. Conclusion: EPR and tethered-portal implementation at Great Ormond Street Hospital for Children was not only timely, due to the need for a rapid transition to remote consultations during the COVID-19 pandemic, which would not have been possible had EPR/MyGOSH not been implemented, but also integral to the digital health revolution required in healthcare today. This study is highly relevant in understanding the complexities around young people and their parents accessing their digital health data and, although the focus of this research related to portal use and access, the findings translate to young people in the wider digital health context. Ongoing support is required for all relevant stakeholders following MyGOSH patient portal implementation to navigate the ethical and legal complexities. Continued commitment is needed to balance the benefits and burdens, promote inclusion and equity, and ensure portal utility for patient benefit, whilst maintaining an individualized approach to care.

Keywords: patient portal, young people and their parents, ethical, legal

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Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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Authors: Bahram Soltani, Louai Ghazieh

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The responsibility has a big importance further to the financial crisis and the various pressures, which companies face their duties. The main objective of this study is to explain the variation of mechanisms of the responsibility of the manager in the company among the advanced capitalist economies. Then we study the impact of these mechanisms on the performance and the value creation in European companies. To reach our goal, we established a final sample composed on average of 284 French, British and German companies quoted in stock exchanges with 2272 annual reports examined during the period from 2005 to 2012. We examined at first the link of causalities between the determining-mechanisms bound to the company such as the characteristics of the board of directors, the composition of the shareholding and the ethics of the company on one side and the profitability of the company on the other side. The results show that the smooth running of the board of directors and its specialist committees are very important determinants of the responsibility of the managers who impact positively the performance and the value creation in the company. Furthermore, our results confirm that the presence of a solid ethical environment within the company will be effective to increase the probability that the managers realize ethical choices in the organizational decision-making. At the second time, we studied the impact of the determining mechanisms bound to the function and to the profile of manager to know its relational links, his remuneration, his training, his age and his experiences about the performance and the value creation in the company. Our results highlight the existence of a negative relation between the relational links of the manager, his very high remuneration and the general profitability of the company. This study is a contribution to the literature on the determining mechanisms of company director's responsibility (Accountability). It establishes an empirical and comparative analysis between three influential countries of Europe, to know France, the United Kingdom and Germany.

Keywords: leaders, company’s performance, accountability mechanisms, corporate governance, value creation of firm, financial crisis

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Authors: Stephen Acheampong Amoafoh

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In today's dynamic economic landscape, businesses face multifaceted challenges that demand strategic foresight and informed decision-making. This abstract explores the pivotal role of financial analytics in driving business performance amidst evolving market conditions. By integrating accounting principles with economic insights, organizations can harness the power of data-driven strategies to optimize resource allocation, mitigate risks, and capitalize on emerging opportunities. This presentation will delve into the practical applications of financial analytics across various sectors, highlighting case studies and empirical evidence to underscore its efficacy in enhancing operational efficiency and fostering sustainable growth. From predictive modeling to performance benchmarking, attendees will gain invaluable insights into leveraging advanced analytics tools to drive profitability, streamline processes, and adapt to changing market dynamics. Moreover, this abstract will address the ethical considerations inherent in financial analytics, emphasizing the importance of transparency, integrity, and accountability in data-driven decision-making. By fostering a culture of ethical conduct and responsible stewardship, organizations can build trust with stakeholders and safeguard their long-term viability in an increasingly interconnected global economy. Ultimately, this abstract aims to stimulate dialogue and collaboration among scholars, practitioners, and policymakers, fostering knowledge exchange and innovation in the realms of accounting, business, and economics. Through interdisciplinary insights and actionable recommendations, participants will be equipped to navigate the complexities of today's business environment and seize opportunities for sustainable success.

Keywords: financial analytics, business performance, data-driven strategies, sustainable growth

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Authors: Nicholas Fieseler

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The nature of religion implicit in popular culture is relevant both in and out of the university. The traditional rules-based conception of religion and the ethical systems that emerge from them do not necessarily convey the behavior of daily life as it exists apart from spaces deemed sacred. This paper proposes to examine the religion implicit in the popular culture phenomenon of professional wrestling and how that affects the understanding of popular religion. Pro wrestling, while frequently dismissed, offers a unique manner through which to re-examine religion in popular culture. A global phenomenon, pro wrestling occupies a distinct space in numerous countries and presents a legitimate reflection of human behavior cross-culturally on a scale few other phenomena can equal. Given its global viewership of millions, it should be recognized as a significant means of interpreting the human attraction to violence and its association with religion in general. Hans Urs von Balthasar’s theory of Theodrama will be used to interrogate the inchoate religion within pro wrestling. While Balthasar developed theodrama within the confines of Christian theology; theodrama contains remarkable versatility in its potential utility. Since theodrama re-envisions reality as drama, the actions of every human actor on the stage contributes to the play’s development, and all action contains some transcendent value. It is in this sense that even the “low brow” activity of pro wrestling may be understood in religious terms. Moreover, a pro wrestling storyline acts as a play within a play: the struggles in a pro wrestling match reflect the human attitudes toward life as it exists in the sacred and profane realms. The indistinct lines separating traditionally good (face) from traditionally bad (heel)wrestlers mirror the moral ambiguity in which many people interpret life. This blurred distinction between good and bad, and large segments of an audience’s embrace of the heel wrestlers, reveal ethical constraints that guide the everyday values of pro wrestling spectators, a moral ambivalence that is often overlooked by traditional religious systems, and which has hitherto been neglected in the academic literature on pro wrestling. The significance of interpreting the religion implicit in pro wrestling through a the dramatic lens extends beyond pro wrestling specifically and can examine the religion implicit in popular culture in general. The use of theodrama mitigates the rigid separation often ascribed to areas deemed sacred/ profane, ortranscendent / immanent, enabling a re-evaluation of religion and ethical systems as practiced in popular culture. The use of theodrama will be expressed by utilizing the pro wrestling match as a literary text that reflects the society from which it emerges. This analysis will also reveal the complex nature of religion in popular culture and provides new directions for the academic study of religion. This project consciously bridges the academic and popular realms. The goal of the research is not to add only to the academic literature on implicit religion in popular culture but to publish it in a form which speaks to those outside the standard academic audiences for such work.

Keywords: ethics, popular religion, professional wrestling, theodrama

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Authors: Muhammed Shahriar Haque

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As an offshoot of journalistic discourse, the documentary should be objective in nature without harbouring any preconceived notion to foster ulterior motifs. When it comes to a social issue like rape in South Asian countries, as media in recent times is inundated with this violent act in India, Pakistan, Myanmar, Bangladesh, how does one document it in terms of objectivity and subjectivity? The objective of this study is twofold: to document the history of documentaries, and to critically analyze South Asian rape/flesh trade-documentaries. The overall goal is to trace the (re/de)construction of objectivity-subjectivity in documentaries. This paper adopts a qualitative approach to documentarist discourse through the lens of critical discourse analysis (CDA). Data was gathered for 10 documentaries on the theme of rape and/or flesh trade from eight South Asian countries, predominantly the South Asian Association of Regional Cooperation (SAARC) region. The documentaries were primarily categorised by using three frameworks based on six modes, six subgenres, and four basic approaches of documentary. Subsequently, the findings were critiqued from CDA perspective. The outcome suggests that there a two schools of thoughts regarding documentaries. According to journalistic ethics, news and/or documentaries should be objective in orientation and focus on informing the audience and/common people. The empirical findings tend to challenge ethical parameters of objectivity. At times, it seems that journalistic discourse is discursively (re)constructed to give an augmented simulation of objectivity. Based on the findings it may be recommended that if documentaries steer away from empirical facts and indulge in poetic naivety, their credibility could be questioned. A research of this nature is significant as it raises questions with regard to ethical and moral conscience of documentary filmmakers. Furthermore, it looks at whether they uphold journalistic integrity or succumb to their bias, and thereby depict subjective views, which could be tainted with political and/or propagandist ulterior motifs.

Keywords: discursive (re/de)construction, documentaries, journalistic integrity, rape/flesh trade

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Authors: Netanel Stern

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Artificial intelligence (AI) algorithms have emerged as powerful tools in the field of psychiatry, offering new possibilities for enhancing diagnosis and treatment outcomes. This article explores the utilization of AI algorithms in psychiatry, highlighting their potential to revolutionize patient care. Various AI algorithms, including machine learning, natural language processing (NLP), reinforcement learning, clustering, and Bayesian networks, are discussed in detail. Moreover, ethical considerations and future directions for research and implementation are addressed.

Keywords: AI, software engineering, psychiatry, neuroimaging

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Authors: Shideh Mohseni Movahed, Mansoureh Safari

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Intelligent drug delivery systems (IDDS) are innovative technological innovations and clinical way to advance current treatments. These systems differ in technique of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require different pharmacological therapies. IDDS capable of releasing an active molecule at the proper site and at a amount that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism is particularly appealing. In this paper, we describe the most recent advances in the development of intelligent drug delivery systems.

Keywords: drug delivery systems, IDDS, medicine, health

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Mamunur Rashid, Jialin Yan

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The current years have witnessed a rapid evolution and integration of artificial intelligence (AI) in various fields, prominently influencing the education industry. Acknowledging this transformative wave, AI tools like ChatGPT and Grammarly have undeniably introduced perspectives and skills, enriching the educational experiences of higher education students. The prevalence of AI utilization in higher education also drives an increasing number of researchers' attention in various dimensions. Departments, offices, and professors in universities also designed and released a set of policies and guidelines on using AI effectively. In regard to this, the study targets exploring and analyzing graduate students' perspectives regarding AI guidelines set by teachers. A mixed-methods study will be mainly conducted in this study, employing in-depth interviews and focus groups to investigate and collect students' perspectives. Relevant materials, such as syllabi and course instructions, will also be analyzed through the documentary analysis to facilitate understanding of the study. Surveys will also be used for data collection and students' background statistics. The integration of both interviews and surveys will provide a comprehensive array of student perspectives across various academic disciplines. The study is anchored in the theoretical framework of self-determination theory (SDT), which emphasizes and explains the students' perspective under the AI guidelines through three core needs: autonomy, competence, and relatedness. This framework is instrumental in understanding how AI guidelines influence students' intrinsic motivation and sense of empowerment in their learning environments. Through qualitative analysis, the study reveals a sense of confusion and uncertainty among students regarding the appropriate application and ethical considerations of AI tools, indicating potential challenges in meeting their needs for competence and autonomy. The quantitative data further elucidates these findings, highlighting a significant communication gap between students and educators in the formulation and implementation of AI guidelines. The critical findings of this study mainly come from two aspects: First, the majority of graduate students are uncertain and confused about relevant AI guidelines given by teachers. Second, this study also demonstrates that the design and effectiveness of course materials, such as the syllabi and instructions, also need to adapt in regard to AI policies. It indicates that certain of the existing guidelines provided by teachers lack consideration of students' perspectives, leading to a misalignment with students' needs for autonomy, competence, and relatedness. More emphasize and efforts need to be dedicated to both teacher and student training on AI policies and ethical considerations. To conclude, in this study, graduate students' perspectives on teacher-provided AI guidelines are explored and reflected upon, calling for additional training and strategies to improve how these guidelines can be better disseminated for their effective integration and adoption. Although AI guidelines provided by teachers may be helpful and provide new insights for students, educational institutions should take a more anchoring role to foster a motivating, empowering, and student-centered learning environment. The study also provides some relevant recommendations, including guidance for students on the ethical use of AI and AI policy training for teachers in higher education.

Keywords: higher education policy, graduate students’ perspectives, higher education teacher, AI guidelines, AI in education

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Authors: dr. Bendes Ákos

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Digital skepticism, a critical stance towards digital technology and its pervasive influence on society, presents significant challenges when analyzed from a legal philosophical perspective. This abstract aims to explore the intersection of digital skepticism and legal philosophy, emphasizing the implications for justice, rights, and the rule of law in the digital age. Digital skepticism arises from concerns about privacy, security, and the ethical implications of digital technology. It questions the extent to which digital advancements enhance or undermine fundamental human values. Legal philosophy, which interrogates the foundations and purposes of law, provides a framework for examining these concerns critically. One key area where digital skepticism and legal philosophy intersect is in the realm of privacy. Digital technologies, particularly data collection and surveillance mechanisms, pose substantial threats to individual privacy. Legal philosophers must grapple with questions about the limits of state power and the protection of personal autonomy. They must consider how traditional legal principles, such as the right to privacy, can be adapted or reinterpreted in light of new technological realities. Security is another critical concern. Digital skepticism highlights vulnerabilities in cybersecurity and the potential for malicious activities, such as hacking and cybercrime, to disrupt legal systems and societal order. Legal philosophy must address how laws can evolve to protect against these new forms of threats while balancing security with civil liberties. Ethics plays a central role in this discourse. Digital technologies raise ethical dilemmas, such as the development and use of artificial intelligence and machine learning algorithms that may perpetuate biases or make decisions without human oversight. Legal philosophers must evaluate the moral responsibilities of those who design and implement these technologies and consider the implications for justice and fairness. Furthermore, digital skepticism prompts a reevaluation of the concept of the rule of law. In an increasingly digital world, maintaining transparency, accountability, and fairness becomes more complex. Legal philosophers must explore how legal frameworks can ensure that digital technologies serve the public good and do not entrench power imbalances or erode democratic principles. Finally, the intersection of digital skepticism and legal philosophy has practical implications for policy-making. Legal scholars and practitioners must work collaboratively to develop regulations and guidelines that address the challenges posed by digital technology. This includes crafting laws that protect individual rights, ensure security, and promote ethical standards in technology development and deployment. In conclusion, digital skepticism provides a crucial lens for examining the impact of digital technology on law and society. A legal philosophical approach offers valuable insights into how legal systems can adapt to protect fundamental values in the digital age. By addressing privacy, security, ethics, and the rule of law, legal philosophers can help shape a future where digital advancements enhance, rather than undermine, justice and human dignity.

Keywords: legal philosophy, privacy, security, ethics, digital skepticism

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Authors: Randall E. Osborne

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A four-step ‘humanities’ thought model has been used in an interdisciplinary course for almost two decades and has been proven to aid in student abilities to become more inclusive in their world view. Lack of tolerance for ambiguity can interfere with this progression so we developed an assignment that seems to have assisted students in developing more tolerance for ambiguity and, therefore, opened them up to make more progress on the critical thought model. A four-step critical thought model (built from a humanities education approach) is used in an interdisciplinary course on prejudice, discrimination, and hate in an effort to minimize egocentrism and promote sociocentrism in college students. A fundamental barrier to this progression is a lack of tolerance for ambiguity. The approach to the course is built on the assumption that Tolerance for Ambiguity (characterized by a dislike of uncertain, ambiguous or situations in which expected behaviors are uncertain, will like serve as a barrier (if tolerance is low) or facilitator (if tolerance is high) of active ‘engagement’ with assignments. Given that active engagement with course assignments would be necessary to promote an increase in critical thought and the degree of multicultural attitude change, tolerance for ambiguity inhibits critical thinking and, ultimately multicultural attitude change. As expected, those students showing the least amount of decrease (or even an increase) in intolerance across the semester, earned lower grades in the course than those students who showed a significant decrease in intolerance, t(1,19) = 4.659, p < .001. Students who demonstrated the most change in their Tolerance for Ambiguity (showed an increasing ability to tolerate ambiguity) earned the highest grades in the course. This is, especially, significant because faculty did not know student scores on this measure until after all assignments had been graded and course grades assigned. An assignment designed to assist students in making their assumption and inferences processes visible so they could be explored, was implemented with the goal of this exploration then promoting more tolerance for ambiguity, which, as already outlined, promotes critical thought. The assignment offers students two options and then requires them to explore what they have learned about inferences and/or assumptions This presentation outlines the assignment and demonstrates the humanities model, what students learn from particular assignments and how it fosters a change in Tolerance for Ambiguity which, serves as the foundational component of critical thinking.

Keywords: critical thinking, humanities education, sociocentrism, tolerance for ambiguity

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Thorsten Auer, Sumaya Islam, Sabrina Plaß, Colin Wooldridge

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Whether individuals are more likely to forgo some ethical values if it is for a “great” social mission remains questionable. Research interest in the mechanism of moral disengagement has risen sharply in the organizational context over the last decades. Moral disengagement provides an explanatory approach to why individuals decide against their moral intent and describes the tendency to make unethical decisions due to a lack of self-regulation given various actions and their consequences. In our study, we examine the differences between individual decision-making given a commercial and social entrepreneurial context. Thereby, we investigate whether individuals in a social entrepreneurial context, characterized by pro-social goals and purpose beyond profit maximization, tend to make more or less “unethical” decisions in trade-off situations than those given a profit-focused commercial, entrepreneurial context. While a general priming effect may explain the tendency for individuals to make less unethical decisions given a social context, it remains unclear how individuals decide given a trade-off in that specific context. The trade-off in our study is characterized by the option to decide (un-) ethically to enhance the business purpose (in the social context, a social purpose, in the commercial context, a profit-maximization purpose). To investigate which characteristics of the context –and specifically of a trade-off – lead individuals to disregard and override their ethical values for a “greater good”, we design a conjoint analysis. This approach allows us to vary the attributes and scenarios and to test which attributes of a trade-off increase the probability of making an unethical choice. We add survey data to examine the individual propensity to morally disengage as an influencing factor to prefer certain attributes. Currently, we are in the final process of designing the conjoint analysis and plan to conduct the study by December 2022. We contribute to a better understanding of the role of moral disengagement in individual decision-making in a (social) entrepreneurial trade-off.

Keywords: moral disengagement, social entrepreneurship, unethical decision, conjoint analysis

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Authors: Chris Preston

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As we devise ever more sophisticated methods of on-line marketing, devising systems that are able to reach into the everyday lives of consumers, we are confronted by a generation of children who face unprecedented intervention by commercial organisations into young minds, via electronic devices, and whether by computer, tablet or phone, such children have been somehow reduced to the status of their devices, with little regard for their well being as individuals. This discussion paper seeks to draw attention to such practice and questions the ethics of digital marketing methods.

Keywords: online marketing to children, online research of children, online targeting of children, consumer rights, ethics

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Authors: Mehwish Durrani, Rubina Nazli, Muhammad Abubakr, Muhammad Shafiq

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Objectives: To evaluate the high socio-economic status, urbanization, and decrease ambulation can lead to early osteoporosis in women reporting from Peshawar region. Study Design: Descriptive cross-sectional study was done. Sample size was 100 subjects, using 30% proportion of osteoporosis, 95% confidence level, and 9% margin of error under WHO software for sample size determination. Place and Duration of study: This study was carried out in the tertiary referral health care facilities of Peshawar viz PGMI Hayatabad Medical Complex, Peshawar, Khyber Pakhtunkhwa Province, Pakistan. Ethical approval for the study was taken from the Institutional Ethical Research board (IERD) at Post Graduate Medical Institute, Hayatabad Medical Complex, and Peshawar.The study was done in six months time period. Patients and Methods: Levels of CTX1 as a marker of bone degradation in radiographically assessed perimenopausal women was determined. These females were randomly selected and screened for osteoporosis. Hemoglobin in gm/dl, ESR by Westergren method as millimeter in 1 hour, Serum Ca mg/dl, Serum alkaline Phosphatase international units per liter radiographic grade of osteoporosis according to Singh index as 1-6 and CTX 1 level in pg/ml. Results: High levels of CTX1 was observed in perimenopausal osteoporotic women which were radiographically diagnosed as osteoporotic patients. The High socio-economic class also predispose to osteoporosis. Decrease ambulation another risk factor showed significant association with the increased levels of CTX1. Conclusion: The results of this study propose that minimum ambulation and high socioeconomic class both had significance association with the increase levels of serum CTX1, which in turn will lead to osteoporosis and to its complications.

Keywords: osteoporosis, CTX1, perimenopausal women, Hayatabad Medical Complex, Khyberpuktoonkhwa

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Authors: Shem Ikoojo Ayegba, Ye Qi

Abstract:

Public-private partnerships (PPPs) can potentially be a transformative mechanism for advancing affordable housing in Nigeria., considering the current housing deficit between 17 – 24 million. Nevertheless, their effectiveness is marred by persistent unethical practices such as corruption and the utilization of subpar materials. Through a comprehensive mixed-methods approach, this study delves into the ethical quandaries within Nigerian housing construction and their cascading effects on the success of PPPs. Semi-structured interviews encompassing seasoned construction professionals and an in-depth content analysis of ongoing housing policies and projects in Nigeria reveal a culture of corruption across the value chain. This malaise is exacerbated by glaring deficiencies in oversight and a lack of transparent practices. A robust statistical survey involving diverse professionals, including engineers, architects, and project managers, echoes these findings, emphasizing that a frail institutional framework facilitates the persistence of substandard material use, professional negligence, and rampant bribery. Such compromised construction standards place residents in potential jeopardy and impede the achievement of broader sustainability objectives. This study propounds a suite of policy interventions to pave the way for thriving affordable housing PPPs: initiating transparent bidding processes, establishing non-negotiable quality benchmarks for construction materials, and incorporating independent third-party audits throughout the building phase. Furthermore, cultivating a culture of professional integrity through targeted ethics training for all construction personnel is imperative. This research furnishes pragmatic strategies that can radically enhance the potency of housing PPPs, thereby ensuring safe, durable, and affordable housing solutions for Nigeria's underserved populace.

Keywords: public-private partnerships, affordable housing, unethical practicies, housing policies, construction ethics

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Authors: Austin Oduor Otieno

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There is an ingrained belief that the use of performance-enhancing drugs by athletes enable them to perform better. While this has been found to be truth, it also raises ethical and health issues. This paper analyzes the health hazards associated with performance enhancing drugs. It seeks to achieve this through the analysis of different academic journals as well as publications on the relationship between doping in sports and health. It concludes that there are inherent health hazards associated with the use of performance-enhancing drugs as they affect the physical and psychological health and wellbeing of a user (athlete).

Keywords: doping, health hazards, athletes, drugs

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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