Search results for: Adnil Edwin Nurdin
3 Inferring Influenza Epidemics in the Presence of Stratified Immunity
Authors: Hsiang-Yu Yuan, Marc Baguelin, Kin O. Kwok, Nimalan Arinaminpathy, Edwin Leeuwen, Steven Riley
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Traditional syndromic surveillance for influenza has substantial public health value in characterizing epidemics. Because the relationship between syndromic incidence and the true infection events can vary from one population to another and from one year to another, recent studies rely on combining serological test results with syndromic data from traditional surveillance into epidemic models to make inference on epidemiological processes of influenza. However, despite the widespread availability of serological data, epidemic models have thus far not explicitly represented antibody titre levels and their correspondence with immunity. Most studies use dichotomized data with a threshold (Typically, a titre of 1:40 was used) to define individuals as likely recently infected and likely immune and further estimate the cumulative incidence. Underestimation of Influenza attack rate could be resulted from the dichotomized data. In order to improve the use of serosurveillance data, here, a refinement of the concept of the stratified immunity within an epidemic model for influenza transmission was proposed, such that all individual antibody titre levels were enumerated explicitly and mapped onto a variable scale of susceptibility in different age groups. Haemagglutination inhibition titres from 523 individuals and 465 individuals during pre- and post-pandemic phase of the 2009 pandemic in Hong Kong were collected. The model was fitted to serological data in age-structured population using Bayesian framework and was able to reproduce key features of the epidemics. The effects of age-specific antibody boosting and protection were explored in greater detail. RB was defined to be the effective reproductive number in the presence of stratified immunity and its temporal dynamics was compared to the traditional epidemic model using use dichotomized seropositivity data. Deviance Information Criterion (DIC) was used to measure the fitness of the model to serological data with different mechanisms of the serological response. The results demonstrated that the differential antibody response with age was present (ΔDIC = -7.0). The age-specific mixing patterns with children specific transmissibility, rather than pre-existing immunity, was most likely to explain the high serological attack rates in children and low serological attack rates in elderly (ΔDIC = -38.5). Our results suggested that the disease dynamics and herd immunity of a population could be described more accurately for influenza when the distribution of immunity was explicitly represented, rather than relying only on the dichotomous states 'susceptible' and 'immune' defined by the threshold titre (1:40) (ΔDIC = -11.5). During the outbreak, RB declined slowly from 1.22[1.16-1.28] in the first four months after 1st May. RB dropped rapidly below to 1 during September and October, which was consistent to the observed epidemic peak time in the late September. One of the most important challenges for infectious disease control is to monitor disease transmissibility in real time with statistics such as the effective reproduction number. Once early estimates of antibody boosting and protection are obtained, disease dynamics can be reconstructed, which are valuable for infectious disease prevention and control.Keywords: effective reproductive number, epidemic model, influenza epidemic dynamics, stratified immunity
Procedia PDF Downloads 2602 Identification of the Target Genes to Increase the Immunotherapy Response in Bladder Cancer Patients using Computational and Experimental Approach
Authors: Sahar Nasr, Lin Li, Edwin Wang
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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics
Procedia PDF Downloads 1561 The BETA Module in Action: An Empirical Study on Enhancing Entrepreneurial Skills through Kearney's and Bloom's Guiding Principles
Authors: Yen Yen Tan, Lynn Lam, Cynthia Lam, Angela Koh, Edwin Seng
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Entrepreneurial education plays a crucial role in nurturing future innovators and change-makers. Over time, significant progress has been made in refining instructional approaches to develop the necessary skills among learners effectively. Two highly valuable frameworks, Kearney's "4 Principles of Entrepreneurial Pedagogy" and Bloom's "Three Domains of Learning," serve as guiding principles in entrepreneurial education. Kearney's principles align with experiential and student-centric learning, which are crucial for cultivating an entrepreneurial mindset. The potential synergies between these frameworks hold great promise for enhancing entrepreneurial acumen among students. However, despite this potential, their integration remains largely unexplored. This study aims to bridge this gap by building upon the Business Essentials through Action (BETA) module and investigating its contributions to nurturing the entrepreneurial mindset. This study employs a quasi-experimental mixed-methods approach, combining quantitative and qualitative elements to ensure comprehensive and insightful data. A cohort of 235 students participated, with 118 enrolled in the BETA module and 117 in a traditional curriculum. Their Personal Entrepreneurial Competencies (PECs) were assessed before admission (pre-Y1) and one year into the course (post-Y1) using a comprehensive 55-item PEC questionnaire, enabling measurement of critical traits such as opportunity-seeking, persistence, and risk-taking. Rigorous computations of individual entrepreneurial competencies and overall PEC scores were performed, including a correction factor to mitigate potential self-assessment bias. The orchestration of Kearney's principles and Bloom's domains within the BETA module necessitates a granular examination. Here, qualitative revelations surface, courtesy of structured interviews aligned with contemporary research methodologies. These interviews act as a portal, ushering us into the transformative journey undertaken by students. Meanwhile, the study pivots to explore the BETA module's influence on students' entrepreneurial competencies from the vantage point of faculty members. A symphony of insights emanates from intimate focus group discussions featuring six dedicated lecturers, who share their perceptions, experiences, and reflective narratives, illuminating the profound impact of pedagogical practices embedded within the BETA module. Preliminary findings from ongoing data analysis indicate promising results, showcasing a substantial improvement in entrepreneurial skills among students participating in the BETA module. This study promises not only to elevate students' entrepreneurial competencies but also to illuminate the broader canvas of applicability for Kearney's principles and Bloom's domains. The dynamic interplay of quantitative analyses, proffering precise competency metrics, and qualitative revelations, delving into the nuanced narratives of transformative journeys, engenders a holistic understanding of this educational endeavour. Through a rigorous quasi-experimental mixed-methods approach, this research aims to establish the BETA module's effectiveness in fostering entrepreneurial acumen among students at Singapore Polytechnic, thereby contributing valuable insights to the broader discourse on educational methodologies.Keywords: entrepreneurial education, experiential learning, pedagogical frameworks, innovative competencies
Procedia PDF Downloads 64