Search results for: Biomarker Discovery

Authors: Harumi Katayama, Mina Suzuki, Taeko Muramatsu, Yui Shimogawa, Yoshimi Mizushima, Mitsuo Hiramatsu, Kimitsugu Nakamura, Takeshi Suzue

Abstract:

Purpose: There are very often footbaths in the hot-spring area as culture from old days in Japan. This culture moderately supported mental and physical health among people. In Japanese hospitals, nurses provide footbath for severe patients to mental comfortable. However, there are only a few evidences effect of footbath for mental comfortable. In this presentation, we show the effect of stress relief of the footbath using biomarker among 35 college students in volunteer. Methods: The experiment was designed in two groups of the footbath group and the simple relaxation group randomly. As mental load, Kraepelin test was given to the students beforehand. Ultra-weak chemiluminescence (UCL) in saliva and self-administered liner scale measurable emotional state were measured on four times concurrently; there is before and after the mental load, after the stress relief, and 30 minutes after the stress relief. The scale that measured emotional state was consisted of 7 factors; there is excitement, relaxation, vigorous, fatigue, tension, calm, and sleepiness with 22 items. ANOVA was calculated effect of the footbath for stress relief. Results: The level of UCL (photons/100sec) was significantly increased in response on both groups after mental load. After the two types of stress relief, UCL (photons/100sec) of footbath group was significantly decreased compared to simple relaxation group. Score of sleepiness and relaxation were significantly increased after the stress relief in the footbath group than the simple relaxation group. However, score of excitement, vigorous, tension, and calm were exhibit the same degree of decrease after the stress relief on both group. Conclusion: It was suggested that salivary UCL may be a sensitive biomarker for mild stress relief as nursing care. In the future, we will measure using UCL to evaluate as stress relief for inpatients, outpatients, or general public as the subjects.

Keywords: bio-marker, footbath, Japan, stress relief

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, Bayesian, echocardiographic image, feature vector

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Authors: Alyona Cerfontyne, Levita D'Souza, Lefteris Patlamazoglou

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Unlike adoption and donor-assisted reproduction, misattributed paternity occurring within the context of spontaneous conception and outside of formally recognised practices of having a child remains largely an understudied phenomenon. In adulthood, to discover misattributed paternity, i.e., that the man you call your father is not related to you genetically, can have profound implications for everyone affected. Until the advent of direct-to-consumer DNA testing 20 years ago, such discoveries were relatively rare. Despite the growing number of individuals uncovering their biogenetic paternity through genetic testing, there is very limited research on misattributed paternity from the perspective of adult children affected by it. No research exists on how to support these individuals through counselling post-discovery. Framed as insider action research, this study aimed to explore the perceived psychosocial consequences of misattributed paternity discoveries and coping strategies used by individuals who discover their misattributed paternity status in adulthood. In total, 12 individuals with misattributed paternity participated in semi-structured interviews in July-August 2022. The collected data was analysed using reflexive thematic analysis. The study’s results indicate that discovering misattributed paternity in adulthood can be likened to a watershed moment forever changing the trajectory of one’s life. Psychological experiences consistent with trauma, as well as grief and loss, re-evaluation of close family relationships, reestablishment of one’s identity, as well as experiencing a profound need to belong are the key themes emerging from the analysis of psychosocial experiences. Post-discovery, individuals with misattributed paternity employ a wide range of emotional and problem-focused coping strategies, amongst which seeking connection with those who understand, searching for information on the new biogenetic family and finding new meanings to life are most prominent. The study contributes both to the academic and practical knowledge of experiences of misattributed paternity and highlights the importance of further research on the topic.

Keywords: discovery of misattributed paternity, misattributed paternity, paternal discrepancy, psychosocial consequences, coping

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, bayesian, echocardiographic image, feature vector

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Authors: Tony Jehi, Sujatha Rajaram, Nader majzoub, Joan Sabate

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Aging significantly increases the incidence of various cardiometabolic diseases, including cardiovascular disease (CVD). To combat CVD and its associated risk factors, it is imperative to adopt a healthy dietary pattern that is rife with beneficial nutrient and non-nutrient compounds. Unsaturated fats, specifically n-3 polyunsaturated fatty acids (n-3 PUFA), have cardio-protective effects; the opposite is true for saturated fatty acids. What role, if any, does the biomarker of fatty acid intake (specific fatty acids in the erythrocyte) play in predicting cardiometabolic risk among the elderly, a population highly susceptible to increased mortality and morbidity from CVD risk factors, remains unclear. This was a secondary analysis of the Walnuts and Healthy Aging Study. Briefly, elderly (n=192, mean age 69 y) participants followed their usual diet and were randomized into two groups to either eat walnuts daily or abstain from eating walnuts for a period of 2 years. The purpose was to identify potential associations between erythrocyte membrane fatty acids and cardiometabolic risk factors (body weight, blood pressure, blood lipids, and fasting glucose). Erythrocyte n-3 PUFA were inversely associated with total cholesterol (ß = -3.83; p= 0.02), triglycerides (ß = -7.66; p= <0.01), and fasting glucose (ß = -0.19; p=0.03). Specifically, erythrocyte ALA (ß= -1.59; P = 0.04) and DPA (ß= -0.62; P=0.04) were inversely associated with diastolic blood pressure and fasting glucose, respectively. N-6 PUFAs were positively associated with systolic blood pressure (ß=1.10; P=0.02). Mono-unsaturated fatty acids were positively associated with TAG (ß = 4.16; P=0.03). Total saturated fatty acids were not associated with any cardiometabolic risk factors. No association was found between any erythrocyte fatty acid and body weight. In conclusion, erythrocyte n-3 PUFA may be used as a biomarker to predict the cardiometabolic risk among healthy elders, providing support for the American Heart Association guidelines for including n-3 PUFA for preventing CVD.

Keywords: cardiometabolic diseases, erythrocyte fatty acids, elderly, n-3 PUFA

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Authors: Hema Bhardwaj, D. Srinivasa Rao

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Technology for analysing, processing, and extracting meaningful data from enormous and complicated datasets can be termed as "big data." The technique of big data mining and big data analysis is extremely helpful for business movements such as making decisions, building organisational plans, researching the market efficiently, improving sales, etc., because typical management tools cannot handle such complicated datasets. Special computational and statistical issues, such as measurement errors, noise accumulation, spurious correlation, and storage and scalability limitations, are brought on by big data. These unique problems call for new computational and statistical paradigms. This research paper offers an overview of the literature on big data mining, its process, along with problems and difficulties, with a focus on the unique characteristics of big data. Organizations have several difficulties when undertaking data mining, which has an impact on their decision-making. Every day, terabytes of data are produced, yet only around 1% of that data is really analyzed. The idea of the mining and analysis of data and knowledge discovery techniques that have recently been created with practical application systems is presented in this study. This article's conclusion also includes a list of issues and difficulties for further research in the area. The report discusses the management's main big data and data mining challenges.

Keywords: big data, data mining, data analysis, knowledge discovery techniques, data mining challenges

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Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

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Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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Authors: Hwang Ahreum, Kang Taejoon, Kim Bongsoo

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Nanosensors for high sensitive detection of diseases have been widely studied to improve the quality of life. Here, we suggest robust nano-plasmonic diagnostic sensor using cysteine tagged protein G (Cys3-protein G) and ultraflat, ultraclean and single-crystalline Au nanoplates. Protein G formed on an ultraflat Au surface provides ideal background for dense and uniform immobilization of antibodies. The Au is highly stable in diverse biochemical environment and can immobilize antibodies easily through Au-S bonding, having been widely used for various biosensing applications. Especially, atomically smooth single-crystalline Au nanomaterials synthesized using chemical vapor transport (CVT) method are very suitable to fabricate reproducible sensitive sensors. As the C-reactive protein (CRP) is a nonspecific biomarker of inflammation and infection, it can be used as a predictive or prognostic marker for various cardiovascular diseases. Cys3-protein G immobilized uniformly on the Au nanoplate enable CRP antibody (anti-CRP) to be ordered in a correct orientation, making their binding capacity be maximized for CRP detection. Immobilization condition for the Cys3-protein G and anti-CRP on the Au nanoplate is optimized visually by AFM analysis. Au nanoparticle - Au nanoplate (NPs-on-Au nanoplate) assembly fabricated from sandwich immunoassay for CRP can reduce zero-signal extremely caused by nonspecific bindings, providing a distinct surface-enhanced Raman scattering (SERS) enhancement still in 10-18 M of CRP concentration. Moreover, the NP-on-Au nanoplate sensor shows an excellent selectivity against non-target proteins with high concentration. In addition, comparing with control experiments employing a Au film fabricated by e-beam assisted deposition and linker molecule, we validate clearly contribution of the Au nanoplate for the attomolar sensitive detection of CRP. We expect that the devised platform employing the complex of single-crystalline Au nanoplates and Cys3-protein G can be applied for detection of many other cancer biomarkers.

Keywords: Au nanoplate, biomarker, diagnostic sensor, protein G, SERS

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

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Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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Authors: Luís Antonio de Almeida Rodriguez, José Maria Parente de Oliveira, Ednelson Oliveira

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In the last two decades, the world’s aviation authorities have made several attempts to create consensus about a global and accepted approach for applying semantics to web services registry descriptions. This problem has led communities to face a fat and disorganized infrastructure to describe aeronautical web services. It is usual for developers to implement ad-hoc connections among consumers and providers and manually create non-standardized service compositions, which need some particular approach to compose and semantically discover a desired web service. Current practices are not precise and tend to focus on lightweight specifications of some parts of the OWL-S and embed them into syntactic descriptions (SOAP artifacts and OWL language). It is necessary to have the ability to manage the use of both technologies. This paper presents an implementation of the ontology OWL-S that describes a Brazilian Aeronautical Web Service Registry, which makes it able to publish, advertise, make multi-criteria semantic discovery aligned with the ideas of the System Wide Information Management (SWIM) Program, and invoke web services within the Air Traffic Management context. The proposal’s best finding is a generic approach to describe semantic web services. The paper also presents a set of functional requirements to guide the ontology development and to compare them to the results to validate the implementation of the OWL-S Ontology.

Keywords: aeronautical web services, OWL-S, semantic web services discovery, ontologies

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Authors: Bing Li, Zhi Li, Yilong Yang

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Web classification can promote the quality of service discovery and management in the service repository. It is widely used to locate developers desired services. Although traditional classification methods based on supervised learning models can achieve classification tasks, developers need to manually mark web services, and the quality of these tags may not be enough to establish an accurate classifier for service classification. With the doubling of the number of web services, the manual tagging method has become unrealistic. In recent years, the attention mechanism has made remarkable progress in the field of deep learning, and its huge potential has been fully demonstrated in various fields. This paper designs a multi-head attention graph convolutional network (MHAGCN) service classification method, which can assign different weights to the neighborhood nodes without complicated matrix operations or relying on understanding the entire graph structure. The framework combines the advantages of the attention mechanism and graph convolutional neural network. It can classify web services through automatic feature extraction. The comprehensive experimental results on a real dataset not only show the superior performance of the proposed model over the existing models but also demonstrate its potentially good interpretability for graph analysis.

Keywords: attention mechanism, graph convolutional network, interpretability, service classification, service discovery

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Authors: Gwo-Hwa Wan, Tai-Ho Hung, Fen-Fang Chung, Wan-Ying Lee, Hui-Ching Yang

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Air pollutant exposure results in elevated concentrations of oxidative stress and inflammatory biomarkers in general populations. Increased concentrations of inflammatory biomarkers in pregnant women would be associated with preterm labor and low birth weight. To our best knowledge, the associations between air pollutants exposure and inflammation in pregnant women and fetuses are unknown, as well as their effects on fetal growth. This study aimed to evaluate the influences of outdoor air pollutants in northern Taiwan areas on the inflammatory biomarker (high sensitivity C-reactive protein, hs-CRP) concentration in the blood of healthy pregnant women and how the biomarker impacts fetal growth. In this study, 38 healthy pregnant women who are in their first trimester and live in northern Taiwan area were recruited from the Taipei Chang Gung Memorial Hospital. Personal characteristics and prenatal examination data (e.g., blood pressure) were obtained from recruited subjects. The concentrations of inflammatory mediators, hs-CRP, in the blood of healthy pregnant women were analyzed. Additionally, hourly data of air pollutants (PM10, SO2, NO2, O3, CO) concentrations were obtained from air quality monitoring stations in Taipei area, established by the Taiwan Environmental Protection Administration. The definition of lag 0 and lag 01 are the exposure to air pollutants on the day of blood withdrawal, and the average exposure to air pollutants one day before and on the day of blood withdrawal, respectively. The statistical analyses were conducted using SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). This analytical result indicates that the healthy pregnant women aged between 28 and 42 years old. The body mass index before pregnancy averaged 21.51 (sd = 2.51) kg/m2. Around 90% of the pregnant women had never smoking habit, and 28.95% of them had allergic diseases. Approximately around 84% and 5.26% of the pregnant women worked at indoor and outdoor environments, respectively. The mean hematocrit level of the pregnant women was 37.10%, and the hemoglobin levels were ranged between 10.1 and 14.7 g/dL with 12.47 g/dL of mean value. The blood hs-CRP concentrations of healthy pregnant women in the first trimester ranged between 0.32 and 32.5 mg/L with 2.83 (sd = 5.69) mg/L of mean value. The blood hs-CRP concentrations were positively associated with ozone concentrations at lag 0-14 (r = 0.481, p = 0.017) in healthy pregnant women. Significant lag effects were identified in ozone at lag 0-14 with a positive excess concentration of blood hs-CRP.

Keywords: air pollutant, hs-CRP, pregnant woman, ozone, first trimester

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Authors: Getachew Belay Kassahun

Abstract:

Background: Aspartate aminotransferase to Platelet Ratio Index (APRI) currently becomes a biomarker for screening liver fibrosis since liver biopsy procedure is invasive and variation in pathological interpretation. Clinical Laboratory Standard Institute recommends establishing age, sex and environment specific reference interval for biomarkers in a homogenous population. The current study was aimed to derive community based reference interval of APRI aged between 12 and 60 years old in Mekelle city Tigrai, Northern Ethiopia. Method: Six hundred eighty eight study participants were collected from three districts in Mekelle city. The 3 districts were selected through random sampling technique and sample size to kebelles (small administration) were distributed proportional to household number in each district. Lottery method was used at household level if more than 2 study participants to each age partition were found. A community based cross sectional in a total of 534 study participants, 264 male and 270 females, were included in the final laboratory and data analysis but around 154 study participants were excluded through exclusion criteria. Aspartate aminotransferase was analyzed through Biosystem chemistry analyzer and Sysmix machine was used to analyze platelet. Man Whitney U test non parametric stastical tool was used to appreciate stastical difference among gender after excluding the outliers through Box and Whisker. Result: The study appreciated stastical difference among gender for APRI reference interval. The combined, male and female reference interval in the current study was 0.098-0.390, 0.133-0.428 and 0.090-0.319 respectively. The upper and lower reference interval of males was higher than females in all age partition and there was no stastical difference (p-value (<0.05)) between age partition. Conclusion: The current study showed using sex specific reference interval is significant to APRI biomarker in clinical practice for result interpretation.

Keywords: reference interval, aspartate aminotransferase to platelet ratio Index, Ethiopia, tigray

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Authors: Kan Yu, Khui Hung Lee, Eben Afrifa-Yamoah, Jing Guo, Katrina Harrison, Jack Goldblatt, Nicholas Pachter, Jitian Xiao, Guicheng Brad Zhang

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Background and Significance of the Study: Congenital Heart Defects (CHDs) are the most common malformation at birth and one of the leading causes of infant death. Although the exact etiology remains a significant challenge, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of congenital heart defects. At present, no existing DNA methylation biomarkers are used for early detection of CHDs. The existing CHD diagnostic techniques are time-consuming and costly and can only be used to diagnose CHDs after an infant was born. The present study employed a machine learning technique to analyse genome-wide methylation data in children with and without CHDs with the aim to find methylation biomarkers for CHDs. Methods: The Illumina Human Methylation EPIC BeadChip was used to screen the genome‐wide DNA methylation profiles of 24 infants diagnosed with congenital heart defects and 24 healthy infants without congenital heart defects. Primary pre-processing was conducted by using RnBeads and limma packages. The methylation levels of top 600 genes with the lowest p-value were selected and further investigated by using a random forest approach. ROC curves were used to analyse the sensitivity and specificity of each biomarker in both training and test sample sets. The functionalities of selected genes with high sensitivity and specificity were then assessed in molecular processes. Major Findings of the Study: Three genes (MIR663, FGF3, and FAM64A) were identified from both training and validating data by random forests with an average sensitivity and specificity of 85% and 95%. GO analyses for the top 600 genes showed that these putative differentially methylated genes were primarily associated with regulation of lipid metabolic process, protein-containing complex localization, and Notch signalling pathway. The present findings highlight that aberrant DNA methylation may play a significant role in the pathogenesis of congenital heart defects.

Keywords: biomarker, congenital heart defects, DNA methylation, random forest

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Authors: Olanrewaju B. Lasisi

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The position of Ijebu-Ode, the historical capital of the Ijebu Kingdom, at the center of gravity of Ijebu land is enclosed by the 180-km-long earthwork and suggests a centrally controlled project. This paper reflects on the first stratigraphic drawing of the banks and ditches of this earthwork, and place its construction mechanism in a chronological framework. Nine radiocarbon dates obtained at the site suggest that the earthwork was built in the late 14th or early 15th century. This suggests a relationship with the Ijebu Kingdom, which pre-existed the opening of the Atlantic trade but first became visible only in the Portuguese records in the 1480s. In June 2017, more earthworks were found but within the core of Ijebu Land. This most recent finding points to an extension of territory from the center to the outlying villages. One central question about this discovery of monumental architectures that was functional around the 14th century or before is in its mode of construction. Apparently, iron tools must have been used in the construction of ‘a 20m deep ditch that runs 180km in circumference.’ Thus, the discovery of iron-working sites around the vicinity of the earthwork is a pointer to this building process that is up till now shrouded in mystery. By comparing the chronology of Ijebu earthworks with the evidence of Iron working in south western Nigeria around the first half of the first millennium AD, it can be thought that the rise in polity triggered the knowledge of metallurgy in the region.

Keywords: archaeology, earthworks, Ijebu, metallurgy

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Surajit Bhattacharya, Daniel Veltri, Atit A. Patel, Daniel N. Cox

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miRNAs have emerged as key post-transcriptional regulators of gene expression, however identification of biologically-relevant target genes for this epigenetic regulatory mechanism remains a significant challenge. To address this knowledge gap, we have developed a novel tool in R, Intra-miR-ExploreR, that facilitates integrated discovery of miRNA targets by incorporating target databases and novel target prediction algorithms, using statistical methods including Pearson and Distance Correlation on microarray data, to arrive at high confidence intragenic miRNA target predictions. We have explored the efficacy of this tool using Drosophila melanogaster as a model organism for bioinformatics analyses and functional validation. A number of putative targets were obtained which were also validated using qRT-PCR analysis. Additional features of the tool include downloadable text files containing GO analysis from DAVID and Pubmed links of literature related to gene sets. Moreover, we are constructing interaction maps of intragenic miRNAs, using both micro array and RNA-seq data, focusing on neural tissues to uncover regulatory codes via which these molecules regulate gene expression to direct cellular development.

Keywords: miRNA, miRNA:mRNA target prediction, statistical methods, miRNA:mRNA interaction network

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Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi

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Drug-drug interactions (DDIs) are main cause of the adverse drug reactions and nature of the functional and molecular complexity of drugs behavior in human body make them hard to prevent and treat. With the aid of new technologies derived from mathematical and computational science the DDIs problems can be addressed with minimum cost and efforts. Market basket analysis is known as powerful method to identify co-occurrence of thing to discover patterns and frequency of the elements. In this research, we used market basket analysis to identify important bio-elements in DDIs occurrence. For this, we collected all known DDIs from DrugBank. The obtained data were analyzed by market basket analysis method. We investigated all drug-enzyme, drug-carrier, drug-transporter and drug-target associations. To determine the importance of the extracted bio-elements, extracted rules were evaluated in terms of confidence and support. Market basket analysis of the over 45,000 known DDIs reveals more than 300 important rules that can be used to identify DDIs, CYP 450 family were the most frequent shared bio-elements. We applied extracted rules over 2,000,000 unknown drug pairs that lead to discovery of more than 200,000 potential DDIs. Analysis of the underlying reason behind the DDI phenomena can help to predict and prevent DDI occurrence. Ranking of the extracted rules based on strangeness of them can be a supportive tool to predict the outcome of an unknown DDI.

Keywords: drug-drug interaction, market basket analysis, rule discovery, important bio-elements

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Gabriela V. Angeles Perez, Jose Castillejos Lopez, Araceli L. Reyes Cabello, Emilio Bravo Grajales, Adriana Perez Espinosa, Jose L. Quiroz Fabian

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Road traffic accidents are among the principal causes of traffic congestion, causing human losses, damages to health and the environment, economic losses and material damages. Studies about traditional road traffic accidents in urban zones represents very high inversion of time and money, additionally, the result are not current. However, nowadays in many countries, the crowdsourced GPS based traffic and navigation apps have emerged as an important source of information to low cost to studies of road traffic accidents and urban congestion caused by them. In this article we identified the zones, roads and specific time in the CDMX in which the largest number of road traffic accidents are concentrated during 2016. We built a database compiling information obtained from the social network known as Waze. The methodology employed was Discovery of knowledge in the database (KDD) for the discovery of patterns in the accidents reports. Furthermore, using data mining techniques with the help of Weka. The selected algorithms was the Maximization of Expectations (EM) to obtain the number ideal of clusters for the data and k-means as a grouping method. Finally, the results were visualized with the Geographic Information System QGIS.

Keywords: data mining, k-means, road traffic accidents, Waze, Weka

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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Authors: Paolo Fantozzi, Luigi Laura, Umberto Nanni

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The problem of Entity relation discovery in structured data, a well covered topic in literature, consists in searching within unstructured sources (typically, text) in order to find connections among entities. These can be a whole dictionary, or a specific collection of named items. In many cases machine learning and/or text mining techniques are used for this goal. These approaches might be unfeasible in computationally challenging problems, such as processing massive data streams. A faster approach consists in collecting the cooccurrences of any two words (entities) in order to create a graph of relations - a cooccurrence graph. Indeed each cooccurrence highlights some grade of semantic correlation between the words because it is more common to have related words close each other than having them in the opposite sides of the text. Some authors have used sliding windows for such problem: they count all the occurrences within a sliding windows running over the whole text. In this paper we generalise such technique, coming up to a Weighted-Distance Sliding Window, where each occurrence of two named items within the window is accounted with a weight depending on the distance between items: a closer distance implies a stronger evidence of a relationship. We develop an experiment in order to support this intuition, by applying this technique to a data set consisting in the text of the Bible, split into verses.

Keywords: cooccurrence graph, entity relation graph, unstructured text, weighted distance

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Authors: Iván Castelló, Georgiana Stoica, Emilio Palomares, Fernando Bravo

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We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. The system proved to be a faster (minutes) method, with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis (CF), allowing the quantification of trypsin concentrations in a wide range (0-350 mg/L). Furthermore, as trypsin is directly related to the development of cystic fibrosis, different human genotypes, i.e. healthy homozygotic (> 80 mg/L), CF homozygotic (< 50 mg/L), and heterozygotic (> 50 mg/L), respectively, can be determined using our 2nanoSi nanospheres.

Keywords: cystic fibrosis, trypsin, quantum dots, biomarker, homozygote, heterozygote

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Authors: Abdullah M. Algarni, Yashwant K. Malaiya

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Some of the key aspects of vulnerability-discovery, dissemination, and disclosure-have received some attention recently. However, the role of interaction among the vulnerability discoverers and vulnerability acquirers has not yet been adequately addressed. Our study suggests that a major percentage of discoverers, a majority in some cases, are unaffiliated with the software developers and thus are free to disseminate the vulnerabilities they discover in any way they like. As a result, multiple vulnerability markets have emerged. In some of these markets, the exchange is regulated, but in others, there is little or no regulation. In recent vulnerability discovery literature, the vulnerability discoverers have remained anonymous individuals. Although there has been an attempt to model the level of their efforts, information regarding their identities, modes of operation, and what they are doing with the discovered vulnerabilities has not been explored. Reports of buying and selling of the vulnerabilities are now appearing in the press; however, the existence of such markets requires validation, and the natures of the markets need to be analysed. To address this need, we have attempted to collect detailed information. We have identified the most prolific vulnerability discoverers throughout the past decade and examined their motivation and methods. A large percentage of these discoverers are located in Eastern and Western Europe and in the Far East. We have contacted several of them in order to collect first-hand information regarding their techniques, motivations, and involvement in the vulnerability markets. We examine why many of the discoverers appear to retire after a highly successful vulnerability-finding career. The paper identifies the actual vulnerability markets, rather than the hypothetical ideal markets that are often examined. The emergence of worldwide government agencies as vulnerability buyers has significant implications. We discuss potential factors that can impact the risk to society and the need for detailed exploration.

Keywords: risk management, software security, vulnerability discoverers, vulnerability markets

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Authors: Sayani Chatterjee, Kusum Lata Pangtey, Sarita Singh, Harvir Singh

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Biodegradation leads to a systematic alteration of the chemical and physical properties of crude oil showing sequential depletion of n-alkane, cycloalkanes, aromatic which increases its specific gravity, viscosity and the abundance of heteroatom-containing compounds. The biodegradation leads to a change in the molecular fingerprints and geochemical parameters of degraded oils, thus make source and maturity identification inconclusive or ambiguous. Asphaltene is equivalent to the most labile part of the respective kerogen and generally has high molecular weight. Its complex chemical structure with substantial microporous units makes it suitable to occlude the hydrocarbon expelled from the source. The occluded molecules are well preserved by the macromolecular structure and thus prevented from secondary alterations. They retain primary organic geochemical information over the geological time. The present study involves the extraction of this occluded hydrocarbon from the asphaltene cage through mild oxidative degradation using mild oxidative reagents like Hydrogen Peroxide (H₂O₂) and Acetic Acid (CH₃COOH) on purified asphaltene of the biodegraded oils of Mansa, Lanwa and Santhal fields in Cambay Basin. The study of these extracted occluded hydrocarbons was carried out for establishing oil to oil and oil to source correlation in the Mehsana block of Cambay Basin. The n-alkane and biomarker analysis through GC and GC-MS of these occluded hydrocarbons show similar biomarker imprint as the normal oil in the area and hence correlatable with them. The abundance of C29 steranes, presence of Oleanane, Gammacerane and 4-Methyl sterane depicts that the oils are derived from terrestrial organic matter deposited in the stratified saline water column in the marine environment with moderate maturity (VRc 0.6-0.8). The oil source correlation study suggests that the oils are derived from Jotana-Warosan Low area. The developed geochemical technique to extract the occluded hydrocarbon has effectively resolved the ambiguity that resulted from the inconclusive fingerprint of the biodegraded oil and the method can be also applied in other biodegraded oils as well.

Keywords: asphaltene, biomarkers, correlation, mild oxidation, occluded hydrocarbon

Procedia PDF Downloads 158