Search results for: excretion pathways

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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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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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Milica Carević, Katarina Banjanac, Marija ĆOrović, Ana Milivojević, Nevena Prlainović, Aleksandar Marinković, Dejan Bezbradica

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Nowadays, considering the growing awareness of functional food beneficial effects on human health, due attention is dedicated to the research in the field of obtaining new prominent products exhibiting improved physiological and physicochemical characteristics. Therefore, different approaches to valuable bioactive compounds synthesis have been proposed. β-Galactosidase, for example, although mainly utilized as hydrolytic enzyme, proved to be a promising tool for these purposes. Namely, under the particular conditions, such as high lactose concentration, elevated temperatures and low water activities, reaction of galactose moiety transfer to free hydroxyl group of the alternative acceptor (e.g. different sugars, alcohols or aromatic compounds) can generate a wide range of potentially interesting products. Up to now, galacto-oligosaccharides and lactulose have attracted the most attention due to their inherent prebiotic properties. The goal of this study was to obtain a novel product sorbitol galactoside, using the similar reaction mechanism, namely transgalactosylation reaction catalyzed by β-galactosidase from Aspergillus oryzae. By using sugar alcohol (sorbitol) as alternative acceptor, a diverse mixture of potential prebiotics is produced, enabling its more favorable functional features. Nevertheless, an introduction of alternative acceptor into the reaction mixture contributed to the complexity of reaction scheme, since several potential reaction pathways were introduced. Therefore, the thorough optimization using response surface method (RSM), in order to get an insight into different parameter (lactose concentration, sorbitol to lactose molar ratio, enzyme concentration, NaCl concentration and reaction time) influences, as well as their mutual interactions on product yield and productivity, was performed. In view of product yield maximization, the obtained model predicted optimal lactose concentration 500 mM, the molar ratio of sobitol to lactose 9, enzyme concentration 0.76 mg/ml, concentration of NaCl 0.8M, and the reaction time 7h. From the aspect of productivity, the optimum substrate molar ratio was found to be 1, while the values for other factors coincide. In order to additionally, improve enzyme efficiency and enable its reuse and potential continual application, immobilization of β-galactosidase onto tailored silica nanoparticles was performed. These non-porous fumed silica nanoparticles (FNS)were chosen on the basis of their biocompatibility and non-toxicity, as well as their advantageous mechanical and hydrodinamical properties. However, in order to achieve better compatibility between enzymes and the carrier, modifications of the silica surface using amino functional organosilane (3-aminopropyltrimethoxysilane, APTMS) were made. Obtained support with amino functional groups (AFNS) enabled high enzyme loadings and, more importantly, extremely high expressed activities, approximately 230 mg proteins/g and 2100 IU/g, respectively. Moreover, this immobilized preparation showed high affinity towards sorbitol galactoside synthesis. Therefore, the findings of this study could provided a valuable contribution to the efficient production of physiologically active galactosides in immobilized enzyme reactors.

Keywords: β-galactosidase, immobilization, silica nanoparticles, transgalactosylation

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Authors: Shanaka Gunasekara, Maleen Jayasuriya, Nalin Harischandra, Lilantha Samaranayake, Gamini Dissanayake

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One serious facet of the worsening Human-Elephant conflict (HEC) in nations such as Sri Lanka involves elephant-train collisions. Endangered Asian elephants are maimed or killed during such accidents, which also often result in orphaned or disabled elephants, contributing to the phenomenon of lone elephants. These lone elephants are found to be more likely to attack villages and showcase aggressive behaviour, which further exacerbates the overall HEC. Furthermore, Railway Services incur significant financial losses and disruptions to services annually due to such accidents. Most elephant-train collisions occur due to a lack of adequate reaction time. This is due to the significant stopping distance requirements of trains, as the full braking force needs to be avoided to minimise the risk of derailment. Thus, poor driver visibility at sharp turns, nighttime operation, and poor weather conditions are often contributing factors to this problem. Initial investigations also indicate that most collisions occur in localised “hotspots” where elephant pathways/corridors intersect with railway tracks that border grazing land and watering holes. Taking these factors into consideration, this work proposes the leveraging of recent developments in Convolutional Neural Network (CNN) technology to detect elephants using an RGB/infrared capable camera around known hotspots along the railway track. The CNN was trained using a curated dataset of elephants collected on field visits to elephant sanctuaries and wildlife parks in Sri Lanka. With this vision-based detection system at its core, a prototype unit of an early warning system was designed and tested. This weatherised and waterproofed unit consists of a Reolink security camera which provides a wide field of view and range, an Nvidia Jetson Xavier computing unit, a rechargeable battery, and a solar panel for self-sufficient functioning. The prototype unit was designed to be a low-cost, low-power and small footprint device that can be mounted on infrastructures such as poles or trees. If an elephant is detected, an early warning message is communicated to the train driver using the GSM network. A mobile app for this purpose was also designed to ensure that the warning is clearly communicated. A centralized control station manages and communicates all information through the train station network to ensure coordination among important stakeholders. Initial results indicate that detection accuracy is sufficient under varying lighting situations, provided comprehensive training datasets that represent a wide range of challenging conditions are available. The overall hardware prototype was shown to be robust and reliable. We envision a network of such units may help contribute to reducing the problem of elephant-train collisions and has the potential to act as an important surveillance mechanism in dealing with the broader issue of human-elephant conflicts.

Keywords: computer vision, deep learning, human-elephant conflict, wildlife early warning technology

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Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

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Authors: T. C. C. Soo, S. Bhassu

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Unlike the common presence of both innate and adaptive immunity in vertebrates, crustaceans, in particular, shrimps, have been discovered to possess only innate immunity. This further emphasizes the importance of innate immunity within shrimps in pathogenic resistance. Under the study of pathogenic immune challenge, different shrimp species actually exhibit varying degrees of immune resistance towards the same pathogen. Furthermore, even within the same shrimp species, different batches of challenged shrimps can have different strengths of immune defence. Several important pathways are activated within shrimps during pathogenic infection. One of them is JAK-STAT pathway that is activated during bacterial, viral and fungal infections by which STAT(Signal Transducer and Activator of Transcription) gene is the core element of the pathway. Based on theory of Central Dogma, the genomic information is transmitted in the order of DNA, RNA and protein. This study is focused in uncovering the important evolutionary patterns present within the DNA (non-coding region) and RNA (coding region). The three shrimp species involved are Macrobrachium rosenbergii, Penaeus monodon and Litopenaeus vannamei which all possess commercial significance. The shrimp species were challenged with a famous penaeid shrimp virus called white spot syndrome virus (WSSV) which can cause serious lethality. Tissue samples were collected during time intervals of 0h, 3h, 6h, 12h, 24h, 36h and 48h. The DNA and RNA samples were then extracted using conventional kits from the hepatopancreas tissue samples. PCR technique together with designed STAT gene conserved primers were utilized for identification of the STAT coding sequences using RNA-converted cDNA samples and subsequent characterization using various bioinformatics approaches including Ramachandran plot, ProtParam and SWISS-MODEL. The varying levels of immune STAT gene activation for the three shrimp species during WSSV infection were confirmed using qRT-PCR technique. For one sample, three biological replicates with three technical replicates each were used for qRT-PCR. On the other hand, DNA samples were important for uncovering the structural variations within the genomic region of STAT gene which would greatly assist in understanding the STAT protein functional variations. The partially-overlapping primers technique was used for the genomic region sequencing. The evolutionary inferences and event predictions were then conducted through the Bayesian Inference method using all the acquired coding and non-coding sequences. This was supplemented by the construction of conventional phylogenetic trees using Maximum likelihood method. The results showed that adaptive evolution caused STAT gene sequence mutations between different shrimp species which led to evolutionary divergence event. Subsequently, the divergent sites were correlated to the differing expressions of STAT gene. Ultimately, this study assists in knowing the shrimp species innate immune variability and selection of disease resistant shrimps for breeding purpose. The deeper understanding of STAT gene evolution from the perspective of both purifying and adaptive approaches not only can provide better immunological insight among shrimp species, but also can be used as a good reference for immunological studies in humans or other model organisms.

Keywords: gene evolution, JAK-STAT pathway, immunology, STAT gene

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Authors: Yumei Han, Ling Li, Naiqing Song, Xiaoping Yang, Yuping Han

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Educational think tank is agreeably regarded as significant part of a nation’s soft power to promote the scientific and democratic level of educational policy making, and it plays critical role of bridging educational research in higher institutions and educational policy making. This study explores the concept, functions and significance of educational think tank in China, and conceptualizes a three dimensional framework to analyze the approaches of transforming research-based higher institutions into effective educational think tanks to serve educational policy making in the nation wide. Since 2014, the Ministry of Education P.R. China has been promoting the strategy of developing new type of educational think tanks in higher institutions, and such a strategy has been put into the agenda for the 13th Five Year Plan for National Education Development released in 2017.In such context, increasing scholars conduct studies to put forth strategies of promoting the development and transformation of new educational think tanks to serve educational policy making process. Based on literature synthesis, policy text analysis, and analysis of theories about policy making process and relationship between educational research and policy-making, this study constructed a three dimensional conceptual framework to address the following questions: (a) what are the new features of educational think tanks in the new era comparing traditional think tanks, (b) what are the functional objectives of the new educational think tanks, (c) what are the organizational patterns and mechanism of the new educational think tanks, (d) in what approaches traditional research-based higher institutions can be developed or transformed into think tanks to effectively serve the educational policy making process. The authors adopted case study approach on five influential education policy study centers affiliated with top higher institutions in China and applied the three dimensional conceptual framework to analyze their functional objectives, organizational patterns as well as their academic pathways that researchers use to contribute to the development of think tanks to serve education policy making process.Data was mainly collected through interviews with center administrators, leading researchers and academic leaders in the institutions. Findings show that: (a) higher institution based think tanks mainly function for multi-level objectives, providing evidence, theoretical foundations, strategies, or evaluation feedbacks for critical problem solving or policy-making on the national, provincial, and city/county level; (b) higher institution based think tanks organize various types of research programs for different time spans to serve different phases of policy planning, decision making, and policy implementation; (c) in order to transform research-based higher institutions into educational think tanks, the institutions must promote paradigm shift that promotes issue-oriented field studies, large data mining and analysis, empirical studies, and trans-disciplinary research collaborations; and (d) the five cases showed distinguished features in their way of constructing think tanks, and yet they also exposed obstacles and challenges such as independency of the think tanks, the discourse shift from academic papers to consultancy report for policy makers, weakness in empirical research methods, lack of experience in trans-disciplinary collaboration. The authors finally put forth implications for think tank construction in China and abroad.

Keywords: education policy-making, educational research, educational think tank, higher institution

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Authors: Saul Ngarava, Leocadia Zhou, Nomakhaya Monde

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Water crises have the fourth most significant societal impact after weapons of mass destruction, climate change, and extreme weather conditions, ahead of natural disasters. Intricacies between women and water are central to achieving the 2030 Sustainable Development Goals (SDGs). The majority of the 1.2 billion poor people worldwide, with two-thirds being women, and mostly located in Sub Sahara Africa (SSA) and South Asia, do not have access to safe and reliable sources of water. There exist gendered differences in water security based on the division of labour associating women with water. Globally, women and girls are responsible for water collection in 80% of the households which have no water on their premises. Women spend 16 million hours a day collecting water, while men and children spend 6 million and 4 million per day, respectively, which is time foregone in the pursuit of other livelihood activities. Due to their proximity and activities concerning water, women are vulnerable to water insecurity through exposures to water-borne diseases, fatigue from physically carrying water, and exposure to sexual and physical harassment, amongst others. Proximity to treated water and their wellbeing also has an effect on their sensitivity and adaptive capacity to water insecurity. The great distances, difficult terrain and heavy lifting expose women to vulnerabilities of water insecurity. However, few studies have quantified the vulnerabilities and burdens on women, with a few taking a phenomenological qualitative approach. Vulnerability studies have also been scanty in the water security realm, with most studies taking linear forms of either quantifying exposures, sensitivities or adaptive capacities in climate change studies. The current study argues for the need for a water insecurity vulnerability assessment, especially for women into research agendas as well as policy interventions, monitoring, and evaluation. The study sought to identify and provide pathways through which female-headed households were water insecure in South Africa, the 30th driest country in the world. This was through linking the drinking water decision as well as the vulnerability frameworks. Secondary data collected during the 2016 General Household Survey (GHS) was utilised, with a sample of 5928 female-headed households. Principal Component Analysis and Structural Equation Modelling were used to analyse the data. The results show dynamic relationships between water characteristics and water treatment. There were also associations between water access and wealth status of the female-headed households. Association was also found between water access and water treatment as well as between wealth status and water treatment. The study concludes that there are dynamic relationships in water insecurity (exposure, sensitivity, and adaptive capacity) for female-headed households in South Africa. The study recommends that a multi-prong approach is required in tackling exposures, sensitivities, and adaptive capacities to water insecurity. This should include capacitating and empowering women for wealth generation, improve access to water treatment equipment as well as prioritising the improvement of infrastructure that brings piped and safe water to female-headed households.

Keywords: gender, principal component analysis, structural equation modelling, vulnerability, water insecurity

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Authors: Dmitriy Chernov, Maria Karavassilis, Suhyoun Youn, Amna Izhar, Devasenan Devendra

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Introduction and Background: A well-structured and comprehensive departmental induction improves patient safety and job satisfaction amongst doctors. The aims of our Project were as follows: 1. Assess the perceived preparedness of junior doctors starting their rotation in Acute Medicine at Watford General Hospital. 2. Develop a supplemental Induction Guide and Pocket reference in the form of an iOS mobile application. 3. To collect feedback after implementing the mobile application following a trial period of 8 weeks with a small cohort of junior doctors. Materials and Methods: A questionnaire was distributed to all new junior trainees starting in the department of Acute Medicine to assess their experience of current induction. A mobile Induction application was developed and trialled over a period of 8 weeks, distributed in addition to the existing didactic induction session. After the trial period, the same questionnaire was distributed to assess improvement in induction experience. Analytics data were collected with users’ consent to gauge user engagement and identify areas of improvement of the application. A feedback survey about the app was also distributed. Results: A total of 32 doctors used the application during the 8-week trial period. The application was accessed 7259 times in total, with the average user spending a cumulative of 37 minutes 22 seconds on the app. The most used section was Clinical Guidelines, accessed 1490 times. The App Feedback survey revealed positive reviews: 100% of participants (n=15/15) responded that the app improved their overall induction experience compared to other placements; 93% (n=14/15) responded that the app improved overall efficiency in completing daily ward jobs compared to previous rotations; and 93% (n=14/15) responded that the app improved patient safety overall. In the Pre-App and Post-App Induction Surveys, participants reported: a 48% improvement in awareness of practical aspects of the job; a 26% improvement of awareness on locating pathways and clinical guidelines; a 40% reduction of feelings of overwhelmingness. Conclusions and recommendations: This study demonstrates the importance of technology in Medical Education and Clinical Induction. The mobile application average engagement time equates to over 20 cumulative hours of on-the-job training delivered to each user, within an 8-week period. The most used and referred to section was clinical guidelines. This shows that there is high demand for an accessible pocket guide for this type of material. This simple mobile application resulted in a significant improvement in feedback about induction in our Department of Acute Medicine, and will likely impact workplace satisfaction. Limitations of the application include: post-app surveys had a small number of participants; the app is currently only available for iPhone users; some useful sections are nested deep within the app, lacks deep search functionality across all sections; lacks real time user feedback; and requires regular review and updates. Future steps for the app include: developing a web app, with an admin dashboard to simplify uploading and editing content; a comprehensive search functionality; and a user feedback and peer ratings system.

Keywords: mobile app, doctor induction, medical education, acute medicine

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Chiara Cosentino, Carlo Pruneti, Carla Merisio, Domenico Sgromo

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Introduction – Psychoneuroimmunology as approach clearly showed how psychological features can influence health through specific physiological pathways linked to the stress reaction. This can be true also in cancer, in its latter conceptualization seen as a chronic disease. Therefore, it is still not clear how the psychological features can combine with a physiological specific path, for a better adjustment to cancer. The aim of this study is identifying how in Italian survivors, perceived social support, body image, coping and quality of life correlate with or influence Heart Rate Variability (HRV), the physiological parameter that can mirror a condition of chronic stress or a good relaxing capability. Method - The study had an exploratory transversal design. The final sample was made of 38 ovarian cancer survivors aged from 29 to 80 (M= 56,08; SD=12,76) following a program for Ovarian Cancer at the Oncological Clinic, University Hospital of Parma, Italy. Participants were asked to fill: Multidimensional Scale of Perceived Social Support (MSPSS); Derridford Appearance Scale-59 (DAS-59); Mental Adjustment to Cancer (MAC); Quality of Life Questionnaire (EORTC). For each participant was recorded Short-Term HRV (5 minutes) using emWavePro. Results– Data showed many interesting correlations within the psychological features. EORTC scores have a significant correlation with DAS-59 (r =-.327 p <.05), MSPSS (r =.411 p<.05), and MAC scores, in particular with the strategy Fatalism (r =.364 p<.05). A good social support improves HRV (F(1,33)= 4.27 p<.05). Perceiving themselves as effective in their environment, preserving a good role functioning (EORTC), positively affects HRV (F(1,33)=9.810 p<.001). Women admitting concerns towards body image seem prone to emotive disclosure, reducing emotional distress and improving HRV (β=.453); emotional avoidance worsens HRV (β=-.391). Discussion and conclusion - Results showed a strong relationship between body image and Quality of Life. These data suggest that higher concerns on body image, in particular, the negative self-concept linked to appearance, was linked to the worst functioning in everyday life. The relation between the negative self-concept and a reduction in emotional functioning is understandable in terms of possible distress deriving from the perception of body appearance. The relationship between a high perceived social support and a better functioning in everyday life was also confirmed. In this sample fatalism, was associated with a better physical, role and emotional functioning. In these women, the presence of a good support may activate the physiological Social Engagement System improving their HRV. Perceiving themselves effective in their environment, preserving a good role functioning, also positively affects HRV, probably following the same physiological pathway. A higher presence of concerns about appearance contributes to a higher HRV. Probably women admitting more body concerns are prone to a better emotive disclosure. This could reduce emotional distress improving HRV and global health. This study reached preliminary demonstration of an ‘Integrated Model of Defense’ in these cancer survivors. In these model, psychological features interact building a better quality of life and a condition of psychological well-being that is associated and influence HRV, then the physiological condition.

Keywords: cancer survivors, heart rate variability, ovarian cancer, psychophysiological adjustment

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Authors: Sahar Yousef, Chantelle Niblock, Gul Kacmaz

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Salt City, in the context of Jordan’s heritage landscape, is a significant case to explore when it comes to the interaction between tangible and intangible qualities of liveable cities. Most city centers, including Jerash, Salt, Irbid, and Amman, are historical locations. Six of these extraordinary sites were designated UNESCO World Heritage Sites. Jordan is widely acknowledged as a developing country characterized by swift urbanization and unrestrained expansion that exacerbate the challenges associated with the preservation of historic urban areas. The aim of this study is to conduct an examination and analysis of the existing condition of heritage connectivity within heritage city centers. This includes outdoor staircases, pedestrian pathways, footpaths, and other public spaces. Case study-style analysis of the urban core of As-Salt is the focus of this investigation. Salt City is widely acknowledged for its substantial tangible and intangible cultural heritage and has been designated as ‘The Place of Tolerance and Urban Hospitality’ by UNESCO since 2021. Liveability in urban heritage, particularly in historic city centers, incorporates several factors that affect our well-being; its enhancement is a critical issue in contemporary society. The dynamic interaction between humans and historical materials, which serves as a vehicle for the expression of their identity and historical narrative, constitutes preservation that transcends simple conservation. This form of engagement enables people to appreciate the diversity of their heritage recognising their previous and planned futures. Heritage preservation is inextricably linked to a larger physical and emotional context; therefore, it is difficult to examine it in isolation. Urban environments, including roads, structures, and other infrastructure, are undergoing unprecedented physical design and construction requirements. Concurrently, heritage reinforces a sense of affiliation with a particular location or space and unifies individuals with their ancestry, thereby defining their identity. However, a considerable body of research has focused on the conservation of heritage buildings in a fragmented manner without considering their integration within a holistic urban context. Insufficient attention is given to the significance of the physical and social roles played by the heritage staircases and baths that serve as connectors between these valued historical buildings. In doing so, the research uses a methodology that is based on consensus. Given that liveability is considered a complex matter with several dimensions. The discussion starts by making initial observations on the physical context and societal norms inside the urban center while simultaneously establishing the definitions of liveability and connectivity and examining the key criteria associated with these concepts. Then, identify the key elements that contribute to liveable connectivity within the framework of urban heritage in Jordanian city centers. Some of the outcomes that will be discussed in the presentation are: (1) There is not enough connectivity between heritage buildings as can be seen, for example, between buildings in Jada and Qala'. (2) Most of the outdoor spaces suffer from physical issues that hinder their use by the public, like in Salalem. (3) Existing activities in the city center are not well attended because of lack of communication between the organisers and the citizens.

Keywords: connectivity, Jordan, liveability, salt city, tangible and intangible heritage, urban heritage

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Authors: Ndumbe Eric Esongami, Manga Veronica Ebot, Foba Josepha Tendo, Yengong Fabrice Lamfu, Tiku David Tambe

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The prevalence and unpleasant nature of plastics pollution constantly observed on beach shore on stormy events has prompt researchers worldwide to thesis on sustainable economic and environmental designs on plastics, especially in Cameroon, a major touristic destination in the Central Africa Region. The inconsistent protocols develop by researchers has added to this burden, thus the morphological nature of microplastic remediation is a call for concerns. The prime aim of the study is to morphologically identify, quantify and forensically understands the distribution of each plastics polymer composition. Duplicates of 2×2 m (4m2) quadrants were sampled in each beach/month over 8 months period across five purposive beaches along the Limbe – Idenau coastline, Cameroon. Collected plastic samples were thoroughly washed and separation done using a 2 mm sieve. Only particles of size, < 2 mm, were considered and forward follow the microplastics laboratory analytical processes. Established step by step methodological procedures of particle filtration, organic matter digestion, density separation, particle extraction and polymer identification including microscope and were applied for the beach microplastics samples. Microplastics were observed in each sample/beach/month with an overall abundance of 241 particles/number weighs 89.15 g in total and with a mean abundance of 2 particles/m2 (0.69 g/m2) and 6 particles/month (2.0 g/m2). The accumulation of beach shoreline MPs rose dramatically towards decreasing size with microbeads and fiber only found in the < 1 mm size fraction. Approximately 75% of beach MPs contamination were found in LDB 2, LDB 1 and IDN beaches/average particles/number while the most dominant polymer type frequently observed also were PP, PE, and PS in all morphologically parameters analysed. Beach MPs accumulation significantly varied temporally and spatially at p = 0.05. ANOVA and Spearman’s rank correlation used shows linear relationships between the sizes categories considered in this study. In terms of polymer MPs analysis, the colour class recorded that white coloured MPs was dominant, 50 particles/number (22.25 g) with recorded abundance/number in PP (25), PE (15) and PS (5). The shape class also revealed that irregularly shaped MPs was dominant, 98 particles/number (30.5 g) with higher abundance/number in PP (39), PE (33), and PS (11). Similarly, MPs type class shows that fragmented MPs type was also dominant, 80 particles/number (25.25 g) with higher abundance/number in PP (30), PE (28) and PS (15). Equally, the sized class forward revealed that 1.5 – 1.99 mm sized ranged MPs had the highest abundance of 102 particles/number (51.77 g) with higher concentration observed in PP (47), PE (41), and PS (7) as well and finally, the weight class also show that 0.01 g weighs MPs was dominated by 98 particles/number (56.57 g) with varied numeric abundance seen in PP (49), PE (29) and PS (13). The forensic investigation of the pollution indicated that majority of the beach microplastic is sourced from the site/nearby area. The investigation could draw useful conclusions regarding the pathways of pollution. The fragmented microplastic, a significant component in the sample, was found to be sourced from recreational activities and partly from fishing boat installations and repairs activities carried out close to the shore.

Keywords: forensic analysis, beach MPs, particle/number, polymer composition, cameroon

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Authors: Yana Snegireva

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Carbonate reservoirs are known for their heterogeneity, resulting from various geological processes such as diagenesis and fracturing. These complexities may cause great challenges in understanding fluid flow behavior and predicting the production performance of naturally fractured reservoirs. The investigation of carbonate reservoirs is crucial, as many petroleum reservoirs are naturally fractured, which can be difficult due to the complexity of their fracture networks. This can lead to geological uncertainties, which are important for global petroleum reserves. The problem outlines the key challenges in carbonate reservoir modeling, including the accurate representation of fractures and their connectivity, as well as capturing the impact of fractures on fluid flow and production. Traditional reservoir modeling techniques often oversimplify fracture networks, leading to inaccurate predictions. Therefore, there is a need for a modern approach that can capture the complexities of carbonate reservoirs and provide reliable predictions for effective reservoir management and production optimization. The modern approach to carbonate reservoir modeling involves the utilization of the hybrid fracture modeling approach, including the discrete fracture network (DFN) method and implicit fracture network, which offer enhanced accuracy and reliability in characterizing complex fracture systems within these reservoirs. This study focuses on the application of the hybrid method in the Nepsko-Botuobinskaya anticline of the Eastern Siberia field, aiming to prove the appropriateness of this method in these geological conditions. The DFN method is adopted to model the fracture network within the carbonate reservoir. This method considers fractures as discrete entities, capturing their geometry, orientation, and connectivity. But the method has significant disadvantages since the number of fractures in the field can be very high. Due to limitations in the amount of main memory, it is very difficult to represent these fractures explicitly. By integrating data from image logs (formation micro imager), core data, and fracture density logs, a discrete fracture network (DFN) model can be constructed to represent fracture characteristics for hydraulically relevant fractures. The results obtained from the DFN modeling approaches provide valuable insights into the East Siberia field's carbonate reservoir behavior. The DFN model accurately captures the fracture system, allowing for a better understanding of fluid flow pathways, connectivity, and potential production zones. The analysis of simulation results enables the identification of zones of increased fracturing and optimization opportunities for reservoir development with the potential application of enhanced oil recovery techniques, which were considered in further simulations on the dual porosity and dual permeability models. This approach considers fractures as separate, interconnected flow paths within the reservoir matrix, allowing for the characterization of dual-porosity media. The case study of the East Siberia field demonstrates the effectiveness of the hybrid model method in accurately representing fracture systems and predicting reservoir behavior. The findings from this study contribute to improved reservoir management and production optimization in carbonate reservoirs with the use of enhanced and improved oil recovery methods.

Keywords: carbonate reservoir, discrete fracture network, fracture modeling, dual porosity, enhanced oil recovery, implicit fracture model, hybrid fracture model

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Authors: Kuo Chieh Chao, Thishani Amarathunga, Sangam Shrestha

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Rainfall induced slope failures are one of the most damaging and disastrous natural hazards which occur frequently in the world. This type of sliding mainly occurs in the zone above the groundwater level in silty/sandy soils. When the rainwater begins to infiltrate into the vadose zone of the soil, the negative pore-water pressure tends to decrease and reduce the shear strength of soil material. Climate change has resulted in excessive and unpredictable rainfall in all around the world, resulting in landslides with dire consequences to human lives and infrastructure. Such problems could be overcome by examining in detail the causes for such slope failures and recommending effective repair plans for vulnerable locations by considering future climatic change. The selected area for this study is located in the road rehabilitation section from Maubara to Mota Ain road in Timor-Leste. Slope failures and cracks have occurred in 2013 and after repairs reoccurred again in 2017 subsequent to heavy rains. Both observed and future predicted climate data analyses were conducted to understand the severe precipitation conditions in past and future. Observed climate data were collected from NOAA global climate data portal. CORDEX data portal was used to collect Regional Climate Model (RCM) future predicted climate data. Both observed and RCM data were extracted to location-based data using ArcGIS Software. Linear scaling method was used for the bias correction of future data and bias corrected climate data were assigned to GeoStudio Software. Precipitations of wet seasons (December to March ) in 2007 to 2013 is higher than 2001-2006 period and it is more than nearly 40% higher precipitation than usual monthly average precipitation of 160mm.The results of seepage analyses which were carried out using SEEP/W model with observed climate, clearly demonstrated that the pore water pressure within the fill slope was significantly increased due to the increase of the infiltration during the wet season of 2013.One main Regional Climate Models (RCM) was analyzed in order to predict future climate variation under two Representative Concentration Pathways (RCPs).In the projected period of 76 years ahead from 2014, shows that the amount of precipitation is considerably getting higher in the future in both RCP 4.5 and RCP 8.5 emission scenarios. Critical pore water pressure conditions during 2014-2090 were used in order to recommend appropriate remediation methods. Results of slope stability analyses indicated that the factor of safety of the fill slopes was reduced from 1.226 to 0.793 during the dry season to wet season in 2013.Results of future slope stability which were obtained using SLOPE/W model for the RCP emissions scenarios depict that, the use of tieback anchors and geogrids in slope protection could be effective in increasing the stability of slopes to an acceptable level during the wet seasons. Moreover, methods and procedures like monitoring of slopes showing signs or susceptible for movement and installing surface protections could be used to increase the stability of slopes.

Keywords: climate change, precipitation, SEEP/W, SLOPE/W, unsaturated soil

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Authors: Juergen Junk, Franz Ronellenfitsch, Michael Eickermann

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An appropriate weed management in autumn is a prerequisite for an economically successful harvest in the following year. In Luxembourg oilseed rape, wheat and barley is sown from August until October, accompanied by a chemical weed control with soil active herbicides, depending on the state of the weeds and the meteorological conditions. Based on regular ground and surface water-analysis, high levels of contamination by transformation products of respective herbicide compounds have been found in Luxembourg. The most ideal conditions for incorporating soil active herbicides are single rain events. Weed control may be reduced if application is made when weeds are under drought stress or if repeated light rain events followed by dry spells, because the herbicides tend to bind tightly to the soil particles. These effects have been frequently reported for Luxembourg throughout the last years. In the framework of a multisite long-term field experiment (EFFO) weed monitoring, plants observations and corresponding meteorological measurements were conducted. Long-term time series (1947-2016) from the SYNOP station Findel-Airport (WMO ID = 06590) showed a decrease in the number of days with precipitation. As the total precipitation amount has not significantly changed, this indicates a trend towards rain events with higher intensity. All analyses are based on decades (10-day periods) for September and October of each individual year. To assess the future meteorological conditions for Luxembourg, two different approaches were applied. First, multi-model ensembles from the CORDEX experiments (spatial resolution ~12.5 km; transient projections until 2100) were analysed for two different Representative Concentration Pathways (RCP8.5 and RCP4.5), covering the time span from 2005 until 2100. The multi-model ensemble approach allows for the quantification of the uncertainties and also to assess the differences between the two emission scenarios. Second, to assess smaller scale differences within the country a high resolution model projection using the COSMO-LM model was used (spatial resolution 1.3 km). To account for the higher computational demands, caused by the increased spatial resolution, only 10-year time slices have been simulated (reference period 1991-2000; near future 2041-2050 and far future 2091-2100). Statistically significant trends towards higher air temperatures, +1.6 K for September (+5.3 K far future) and +1.3 K for October (+4.3 K), were predicted for the near future compared to the reference period. Precipitation simultaneously decreased by 9.4 mm (September) and 5.0 mm (October) for the near future and -49 mm (September) and -10 mm (October) in the far future. Beside the monthly values also decades were analyzed for the two future time periods of the CLM model. For all decades of September and October the number of days with precipitation decreased for the projected near and far future. Changes in meteorological variables such as air temperature and precipitation did already induce transformations in weed societies (composition, late-emerging etc.) of arable ecosystems in Europe. Therefore, adaptations of agronomic practices as well as effective weed control strategies must be developed to maintain crop yield.

Keywords: CORDEX projections, dry spells, ensembles, weed management

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Authors: Ashlie Latiolais

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Architecture, as a discipline, is on a trajectory of extension beyond the boundaries of buildings and, more increasingly, is coupled with research that connects to alternative and typically disjointed disciplines. A “both/and” approach and (expanded) definition of architecture, as depicted here, expands the margins that contain the profession. Figuratively, architecture is a series of edges, events, and occurrences that establishes a choreography or stage by which humanity exists. The way in which architecture controls and suggests the movement through these spaces, being within a landscape, city, or building, can be viewed as a datum by which the “dance” of everyday life occurs. This submission views the realm of architecture through the lens of movement and dance as a cross-fertilizer of collaboration, tectonic, and spatial geometry investigations. “Designing on digital programs puts architects at a distance from the spaces they imagine. While this has obvious advantages, it also means that they lose the lived, embodied experience of feeling what is needed in space—meaning that some design ideas that work in theory ultimately fail in practice.” By studying the body in motion through real-time performance, a more holistic understanding of architectural space surfaces and new prospects for theoretical teaching pedagogies emerge. The atypical intersection rethinks how architecture is considered, created, and tested, similar to how “dance artists often do this by thinking through the body, opening pathways and possibilities that might not otherwise be accessible” –this is the essence of this poster submission as explained through unFOLDED, a creative performance work. A new languageismaterialized through unFOLDED, a dynamic occupiable installation by which architecture is investigated through dance, movement, and body analysis. The entry unfolds a collaboration of an architect, dance choreographer, musicians, video artist, and lighting designers to re-create one of the first documented avant-garde performing arts collaborations (Matisse, Satie, Massine, Picasso) from the Ballet Russes in 1917, entitled Parade. Architecturally, this interdisciplinary project orients and suggests motion through structure, tectonic, lightness, darkness, and shadow as it questions the navigation of the dark space (stage) surrounding the installation. Artificial light via theatrical lighting and video graphics brought the blank canvas to life – where the sensitive mix of musicality coordinated with the structure’s movement sequencing was certainly a challenge. The upstage light from the video projections created both flickered contextual imagery and shadowed figures. When the dancers were either upstage or downstage of the structure, both silhouetted figures and revealed bodies are experienced as dancer-controlled installation manipulations occurred throughout the performance. The experimental performance, through structure, prompted moving (dancing) bodies in space, where the architecture served as a key component to the choreography itself. The tectonic of the delicate steel structure allowed for the dancers to interact with the installation, which created a variety of spatial conditions – the contained box of three-dimensional space, to a wall, and various abstracted geometries in between. The development of this research unveils the new role of an Architect as a Choreographer of the built environment.

Keywords: dance, architecture, choreography, installation, architect, choreographer, space

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Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony

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Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.

Keywords: androgenesis, chloroplast, metabolism, temperature stress

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Authors: Jawaad Saleem, Hannah Wright, Peter Sommerville, Adrian Hopper

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Introduction: Inpatient falls are the most commonly reported patient safety incidents, and carry a significant burden on resources, morbidity, and mortality. Ensuring adequate post falls management of patients by staff is therefore paramount to maintaining patient safety especially in out of hours and resource stretched settings. Aims: This quality improvement project aims to improve the current practice of falls management at Guys St Thomas Hospital, London as compared to our 2016 Quality Improvement Project findings. Furthermore, it looks to increase current junior doctors confidence in managing falls and their use of new guidance protocols. Methods: Multifaceted Interventions implemented included: the development of new trust wide guidelines detailing management pathways for patients post falls, available for intranet access. Furthermore, the production of 2000 lanyard cards distributed amongst junior doctors and staff which summarised these guidelines. Additionally, a ‘safety signal’ email was sent from the Trust chief medical officer to all staff raising awareness of falls and the guidelines. Formal falls teaching was also implemented for new doctors at induction. Using an established incident database, 189 consecutive falls in 2017were retrospectively analysed electronically to assess and compared to the variables measured in 2016 post interventions. A separate serious incident database was used to analyse 50 falls from May 2015 to March 2018 to ascertain the statistical significance of the impact of our interventions on serious incidents. A similar questionnaire for the 2017 cohort of foundation year one (FY1) doctors was performed and compared to 2016 results. Results: Questionnaire data demonstrated improved awareness and utility of guidelines and increased confidence as well as an increase in training. 97% of FY1 trainees felt that the interventions had increased their awareness of the impact of falls on patients in the trust. Data from the incident database demonstrated the time to review patients post fall had decreased from an average of 130 to 86 minutes. Improvement was also demonstrated in the reduced time to order and schedule X-ray and CT imaging, 3 and 5 hours respectively. Data from the serious incident database show that ‘the time from fall until harm was detected’ was statistically significantly lower (P = 0.044) post intervention. We also showed the incidence of significant delays in detecting harm ( > 10 hours) reduced post intervention. Conclusions: Our interventions have helped to significantly reduce the average time to assess, order and schedule appropriate imaging post falls. Delays of over ten hours to detect serious injuries after falls were commonplace; since the intervention, their frequency has markedly reduced. We suggest this will lead to identifying patient harm sooner, reduced clinical incidents relating to falls and thus improve overall patient safety. Our interventions have also helped increase clinical staff confidence, management, and awareness of falls in the trust. Next steps include expanding teaching sessions, improving multidisciplinary team involvement to aid this improvement.

Keywords: patient safety, quality improvement, serious incidents, falls, clinical care

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Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

Procedia PDF Downloads 135

Authors: Miguel A. Figueroa, José A. Lara-Ramos, Miguel A. Mueses

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Pharmaceutical residues are a section of emerging contaminants of anthropogenic origin that are present in a myriad of waters with which human beings interact daily and are starting to affect the ecosystem directly. Conventional waste-water treatment systems are not capable of degrading these pharmaceutical effluents because their designs cannot handle the intermediate products and biological effects occurring during its treatment. That is why it is necessary to hybridize conventional waste-water systems with non-conventional processes. In the specific case of an ozonation process, its efficiency highly depends on a perfect dispersion of ozone, long times of interaction of the gas-liquid phases and the size of the ozone bubbles formed through-out the reaction system. In order to increase the efficiency of these parameters, the use of a modified flotation cell has been proposed recently as a reactive system, which is used at an industrial level to facilitate the suspension of particles and spreading gas bubbles through the reactor volume at a high rate. The objective of the present work is the development of a mathematical model that can closely predict the kinetic rates of reactions taking place in the flotation cell at an experimental scale by means of identifying proper reaction mechanisms that take into account the modified chemical and hydrodynamic factors in the FeO-catalyzed Ozonation of Diclofenac aqueous solutions in a flotation cell. The methodology is comprised of three steps: an experimental phase where a modified flotation cell reactor is used to analyze the effects of ozone concentration and loading catalyst over the degradation of Diclofenac aqueous solutions. The performance is evaluated through an index of utilized ozone, which relates the amount of ozone supplied to the system per milligram of degraded pollutant. Next, a theoretical phase where the reaction mechanisms taking place during the experiments must be identified and proposed that details the multiple direct and indirect reactions the system goes through. Finally, a kinetic model is obtained that can mathematically represent the reaction mechanisms with adjustable parameters that can be fitted to the experimental results and give the model a proper physical meaning. The expected results are a robust reaction rate law that can simulate the improved results of Diclofenac mineralization on water using the modified flotation cell reactor. By means of this methodology, the following results were obtained: A robust reaction pathways mechanism showcasing the intermediates, free-radicals and products of the reaction, Optimal values of reaction rate constants that simulated Hatta numbers lower than 3 for the system modeled, degradation percentages of 100%, TOC (Total organic carbon) removal percentage of 69.9 only requiring an optimal value of FeO catalyst of 0.3 g/L. These results showed that a flotation cell could be used as a reactor in ozonation, catalytic ozonation and photocatalytic ozonation processes, since it produces high reaction rate constants and reduces mass transfer limitations (Ha > 3) by producing microbubbles and maintaining a good catalyst distribution.

Keywords: advanced oxidation technologies, iron oxide, emergent contaminants, AOTS intensification

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: F. Uriel, M. M. Fernandez Liporace

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In the last decade, academic achievement in higher education has become a topic of agenda in Argentina, regarding the high figures of adjustment problems, academic failure and dropout, and the low graduation rates in the context of massive classes and traditional teaching methods. Psychological variables, such as perceived social support, academic motivation and learning styles and strategies have much to offer since their measurement by tests allows a proper diagnose of their influence on academic achievement. Framed in a major research, several studies analysed multiple samples, totalizing 5135 students attending Argentinean public universities. The first goal was aimed at the identification of statistically significant differences in psychological variables -perceived social support, learning styles, learning strategies, and academic motivation- by age, gender, and degree of academic advance (freshmen versus sophomores). Thus, an inferential group differences study for each psychological dependent variable was developed by means of student’s T tests, given the features of data distribution. The second goal, aimed at examining associations between the four psychological variables on the one hand, and academic achievement on the other, was responded by correlational studies, calculating Pearson’s coefficients, employing grades as the quantitative indicator of academic achievement. The positive and significant results that were obtained led to the formulation of different predictive models of academic achievement which had to be tested in terms of adjustment and predictive power. These models took the four psychological variables above mentioned as predictors, using regression equations, examining predictors individually, in groups of two, and together, analysing indirect effects as well, and adding the degree of academic advance and gender, which had shown their importance within the first goal’s findings. The most relevant results were: first, gender showed no influence on any dependent variable. Second, only good achievers perceived high social support from teachers, and male students were prone to perceive less social support. Third, freshmen exhibited a pragmatic learning style, preferring unstructured environments, the use of examples and simultaneous-visual processing in learning, whereas sophomores manifest an assimilative learning style, choosing sequential and analytic processing modes. Despite these features, freshmen have to deal with abstract contents and sophomores, with practical learning situations due to study programs in force. Fifth, no differences in academic motivation were found between freshmen and sophomores. However, the latter employ a higher number of more efficient learning strategies. Sixth, freshmen low achievers lack intrinsic motivation. Seventh, models testing showed that social support, learning styles and academic motivation influence learning strategies, which affect academic achievement in freshmen, particularly males; only learning styles influence achievement in sophomores of both genders with direct effects. These findings led to conclude that educational psychologists, education specialists, teachers, and universities must plan urgent and major changes. These must be applied in renewed and better study programs, syllabi and classes, as well as tutoring and training systems. Such developments should be targeted to the support and empowerment of students in their academic pathways, and therefore to the upgrade of learning quality, especially in the case of freshmen, male freshmen, and low achievers.

Keywords: academic achievement, academic motivation, coping, learning strategies, learning styles, perceived social support

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Authors: Xiaoqing Peng, Aijing Luo, Yang Chen

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Background: Cyberchondria, as an "emerging risk" accompanied by the information era, is a new abnormal pattern characterized by excessive or repeated online searches for health-related information and escalating health anxiety, which endangers people's physical and mental health and poses a huge threat to public health. Objective: To explore and discuss the research status, hotspots and trends of Cyberchondria. Methods: Based on a total of 77 articles regarding "Cyberchondria" extracted from Web of Science from the beginning till October 2019, the literature trends, countries, institutions, hotspots are analyzed by bibliometric analysis, the concept definition of Cyberchondria, instruments, relevant factors, treatment and intervention are discussed as well. Results: Since "Cyberchondria" was put forward for the first time in 2001, the last two decades witnessed a noticeable increase in the amount of literature, especially during 2014-2019, it quadrupled dramatically at 62 compared with that before 2014 only at 15, which shows that Cyberchondria has become a new theme and hot topic in recent years. The United States was the most active contributor with the largest publication (23), followed by England (11) and Australia (11), while the leading institutions were Baylor University(7) and University of Sydney(7), followed by Florida State University(4) and University of Manchester(4). The WoS categories "Psychiatry/Psychology " and "Computer/ Information Science "were the areas of greatest influence. The concept definition of Cyberchondria is not completely unified in the world, but it is generally considered as an abnormal behavioral pattern and emotional state and has been invoked to refer to the anxiety-amplifying effects of online health-related searches. The first and the most frequently cited scale for measuring the severity of Cyberchondria called “The Cyberchondria Severity Scale (CSS) ”was developed in 2014, which conceptualized Cyberchondria as a multidimensional construct consisting of compulsion, distress, excessiveness, reassurance, and mistrust of medical professionals which was proved to be not necessary for this construct later. Since then, the Brazilian, German, Turkish, Polish and Chinese versions were subsequently developed, improved and culturally adjusted, while CSS was optimized to a simplified version (CSS-12) in 2019, all of which should be worthy of further verification. The hotspots of Cyberchondria mainly focuses on relevant factors as follows: intolerance of uncertainty, anxiety sensitivity, obsessive-compulsive disorder, internet addition, abnormal illness behavior, Whiteley index, problematic internet use, trying to make clear the role played by “associated factors” and “anxiety-amplifying factors” in the development of Cyberchondria, to better understand the aetiological links and pathways in the relationships between hypochondriasis, health anxiety and online health-related searches. Although the treatment and intervention of Cyberchondria are still in the initial stage of exploration, there are kinds of meaningful attempts to seek effective strategies from different aspects such as online psychological treatment, network technology management, health information literacy improvement and public health service. Conclusion: Research on Cyberchondria is in its infancy but should be deserved more attention. A conceptual consensus on Cyberchondria, a refined assessment tool, prospective studies conducted in various populations, targeted treatments for it would be the main research direction in the near future.

Keywords: cyberchondria, hypochondriasis, health anxiety, online health-related searches

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Authors: Lauren B. Birney

Abstract:

The BOP-CCERS (Billion Oyster Project- Curriculum and Community Enterprise for Restoration Science) Near-Peer Mentoring Program provides the long-term (five-year) support network to motivate and guide students toward restoration science-based CTE pathways. Students are selected from middle schools with actively participating BOP-CCERS teachers. Teachers will nominate students from grades 6-8 to join cohorts of between 10 and 15 students each. Cohorts are comprised primarily of students from the same school in order to facilitate mentors' travel logistics as well as to sustain connections with students and their families. Each cohort is matched with an exceptional undergraduate or graduate student, either a BOP research associate or STEM mentor recruited from collaborating City University of New York (CUNY) partner programs. In rare cases, an exceptional high school junior or senior may be matched with a cohort in addition to a research associate or graduate student. In no case is a high school student or minor be placed individually with a cohort. Mentors meet with students at least once per month and provide at least one offsite field visit per month, either to a local STEM Hub or research lab. Keeping with its five-year trajectory, the near-peer mentoring program will seek to retain students in the same cohort with the same mentor for the full duration of middle school and for at least two additional years of high school. Upon reaching the final quarter of 8th grade, the mentor will develop a meeting plan for each individual mentee. The mentee and the mentor will be required to meet individually or in small groups once per month. Once per quarter, individual meetings will be substituted for full cohort professional outings. The mentor will organize the entire cohort on a field visit or educational workshop with a museum or aquarium partner. In addition to the mentor-mentee relationship, each participating student will also be asked to conduct and present his or her own BOP field research. This research is ideally carried out with the support of the students’ regular high school STEM subject teacher; however, in cases where the teacher or school does not permit independent study, the student will be asked to conduct the research on an extracurricular basis. Near-peer mentoring affects students’ social identities and helps them to connect to role models from similar groups, ultimately giving them a sense of belonging. Qualitative and quantitative analytics were performed throughout the study. Interviews and focus groups also ensued. Additionally, an external evaluator was utilized to ensure project efficacy, efficiency, and effectiveness throughout the entire project. The BOP-CCERS Near Peer Mentoring program is a peer support network in which high school students with interest or experience in BOP (Billion Oyster Project) topics and activities (such as classroom oyster tanks, STEM Hubs, or digital platform research) provide mentorship and support for middle school or high school freshmen mentees. Peer mentoring not only empowers those students being taught but also increases the content knowledge and engagement of mentors. This support provides the necessary resources, structure, and tools to assist students in finding success.

Keywords: STEM education, environmental science, citizen science, near peer mentoring

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Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

Abstract:

The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Elvin P. Chizenga, Heidi Abrahamse

Abstract:

Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Mazaher Yarmohamadi-Vasel, Ali Reza Modarresi-Alama, Sahar Shabzendedara

Abstract:

Purpose/Objectives: The first purpose was synthesize Poly(N-(sulfophenyl)aniline) nanoflowers (PSANFLs) and Poly(N-(sulfophenyl)aniline) nanofibers/titanium dioxide nanoparticles ((PSANFs/TiO2NPs) by a solid-state mechano-chemical reaction and template-free method and use them in hybrid solar cell. Also, our second aim was to increase the solubility and the processability of conjugated nanomaterials in water through polar functionalized materials. poly[N-(4-sulfophenyl)aniline] is easily soluble in water because of the presence of polar groups of sulfonic acid in the polymer chain. Materials/Methods: Iron (III) chloride hexahydrate (FeCl3∙6H2O) were bought from Merck Millipore Company. Titanium oxide nanoparticles (TiO2, <20 nm, anatase) and Sodium diphenylamine-4-sulfonate (99%) were bought from Sigma-Aldrich Company. Titanium dioxide nanoparticles paste (PST-20T) was prepared from Sharifsolar Co. Conductive glasses coated with indium tin oxide (ITO) were bought from Xinyan Technology Co (China). For the first time we used the solid-state mechano-chemical reaction and template-free method to synthesize Poly(N-(sulfophenyl)aniline) nanoflowers. Moreover, for the first time we used the same technique to synthesize nanocomposite of Poly(N-(sulfophenyl)aniline) nanofibers and titanium dioxide nanoparticles (PSANFs/TiO2NPs) also for the first time this nanocomposite was synthesized. Examining the results of electrochemical calculations energy gap obtained by CV curves and UV–vis spectra demonstrate that PSANFs/TiO2NPs nanocomposite is a p-n type material that can be used in photovoltaic cells. Doctor blade method was used to creat films for three kinds of hybrid solar cells in terms of different patterns like ITO│TiO2NPs│Semiconductor sample│Al. In the following, hybrid photovoltaic cells in bilayer and bulk heterojunction structures were fabricated as ITO│TiO2NPs│PSANFLs│Al and ITO│TiO2NPs│PSANFs /TiO2NPs│Al, respectively. Fourier-transform infrared spectra, field emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectra, cyclic voltammetry (CV) and electrical conductivity were the analysis that used to characterize the synthesized samples. Results and Conclusions: FE-SEM images clearly demonstrate that the morphology of the synthesized samples are nanostructured (nanoflowers and nanofibers). Electrochemical calculations of band gap from CV curves demonstrated that the forbidden band gap of the PSANFLs and PSANFs/TiO2NPs nanocomposite are 2.95 and 2.23 eV, respectively. I–V characteristics of hybrid solar cells and their power conversion efficiency (PCE) under 100 mWcm−2 irradiation (AM 1.5 global conditions) were measured that The PCE of the samples were 0.30 and 0.62%, respectively. At the end, all the results of solar cell analysis were discussed. To sum up, PSANFLs and PSANFLs/TiO2NPs were successfully synthesized by an affordable and straightforward mechanochemical reaction in solid-state under the green condition. The solubility and processability of the synthesized compounds have been improved compared to the previous work. We successfully fabricated hybrid photovoltaic cells of synthesized semiconductor nanostructured polymers and TiO2NPs as different architectures. We believe that the synthesized compounds can open inventive pathways for the development of other Poly(N-(sulfophenyl)aniline based hybrid materials (nanocomposites) proper for preparing new generation solar cells.

Keywords: mechanochemical synthesis, PSANFLs, PSANFs/TiO2NPs, solar cell

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