Search results for: specificity

Authors: Maria Ashitko

Abstract:

The Constitution of the Republic of Belarus is based on the principle of the unity of rights and obligations, including those of the child. The constitutional status of the child is aspecific system of constitutional elements established and guaranteed by the state through the current legislation and regulatory acts that ensure the special legal status of the child, his or her constitutional legal capacity, implementation of the principles of the constitutional and legal status of the child, constitutional rights of the child and their safeguards. Under the principles of the constitutional status of the child, we consider the general, normative, social-volitional rules of behavior established by the Constitution of the Republic of Belarus, laws and other regulatory acts that determine the content and social purpose of the legal status of the child. The constitutional and legal status of the child is characterized by the following special principles, which form a feature of the state legal system:1) Ensuring the interests of the child means providing for the child in accordance with his or her age, state of health, characteristics of development, life experience, family life, cultural traditions, ethnicity. 2) The principle of equal responsibility of both parents or their substitutes characterized by caring for the next generation as one of the priority tasks of the state and society, and all issues related to the implementation of children’s rights should be addressed at the constitutional level. 3) We would like to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child. It is also worth noting that in legal studies, there is no relationship between safety and constitutional rights as general safeguards of individual rights and freedoms, and as special safeguards for the right to life. 4) The principle of justice is expressed by the fact that in modern conditions, the quality of life is determined not only by material wealth but also by the ability of the state to ensure the harmonization of social relations and social harmony on the basis of humanism and justice. Thus, the specificity of the constitutional status of the child is the age boundary between adulthood and minority; therefore, we propose to highlight the age characteristics of the child as an additional element. It is advisable to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child.

Keywords: children’s rights, constitutional status, constitutional principles, constitutional rights

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Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris

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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.

Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size

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Authors: Ergün Şakalar, Şeyma Özçirak Ergün, Emrah Yalazi̇, Emine Altinkaya, Cengiz Ataşoğlu

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In recent years, food allergies which cause serious health problems affect to public health around the world. Foodstuffs which contain allergens are either intentionally used as ingredients or are encased as contaminant in food products. The prevalence of clinical allergy to peanuts and nuts is estimated at about 0.4%-1.1% of the adult population, representing the allergy to pistachio the 7% of the cases of tree nut causing allergic reactions. In order to protect public health and enforce the legislation, methods for sensitive analysis of pistachio and peanut contents in food are required. Pea, pistachio and peanut are used together, to reduce the cost in food production such as baklava, snack foods.DNA technology-based methods in food analysis are well-established and well-roundedtools for species differentiation, allergen detection. Especially, the probe-based TaqMan real-time PCR assay can amplify target DNA with efficiency, specificity, and sensitivity.In this study, pistachio, peanut and pea were finely ground and three separate series of triplet mixtures containing 0.1, 1, 10, 100, 1000, 10,000 and 100,000 mg kg-1 of each sample were prepared for each series, to a final weight of 100 g. DNA from reference samples and industrial products was successfully extracted with the GIDAGEN® Multi-Fast DNA Isolation Kit. TaqMan probes were designed for triplex determination of ITS, Ara h 3 and pea lectin genes which are specific regions for identification pistachio, peanut and pea, respectively.The real-time PCR as quantitative detected pistachio, peanut and pea in these mixtures down to the lowest investigated level of 0.1, 0.1 and 1 mg kg-1, respectively. Also, the methods reported here are capable of detecting of as little as 0.001% level of peanut DNA, 0,000001% level of pistachio DNA and 0.000001% level of pea DNA. We accomplish that the quantitative triplex real-time PCR method developed in this study canbe applied to detect pistachio, peanut and peatraces for three allergens at once in commercial food products.

Keywords: allergens, DNA, real-time PCR, TaqMan probe

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Authors: Heri Hermansyah, Annisa Kurnia, A. Vania Anisya, Adi Surjosatyo, Yopi Sunarya, Rita Arbianti, Tania Surya Utami

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Lipase is one of biocatalyst which is applied commercially for the process in industries, such as bioenergy, food, and pharmaceutical industry. Nowadays, biocatalysts are preferred in industries because they work in mild condition, high specificity, and reduce energy consumption (high pressure and temperature). But, the usage of lipase for industry scale is limited by economic reason due to the high price of lipase and difficulty of the separation system. Immobilization of lipase is one of the solutions to maintain the activity of lipase and reduce separation system in the process. Therefore, we conduct a study about lipase immobilization with the adsorption-cross linking method using glutaraldehyde because this method produces high enzyme loading and stability. Lipase is immobilized on different kind of resin with the various functional group. Highest enzyme loading (76.69%) was achieved by lipase immobilized on anion macroporous which have anion functional group (OH^‑). However, highest activity (24,69 U/g support) through olive oil emulsion method was achieved by lipase immobilized on anion macroporous-chitosan which have amino (NH₂) and anion (OH^-) functional group. In addition, it also success to produce biodiesel until reach yield 50,6% through interesterification reaction and after 4 cycles stable 63.9% relative with initial yield. While for Aspergillus, niger lipase immobilized on anion macroporous-kitosan have unit activity 22,84 U/g resin and yield biodiesel higher than commercial lipase (69,1%) and after 4 cycles stable reach 70.6% relative from initial yield. This shows that optimum functional group on support for immobilization with adsorption-cross linking is the support that contains amino (NH₂) and anion (OH^-) functional group because they can react with glutaraldehyde and binding with enzyme prevent desorption of lipase from support through binding lipase with a functional group on support.

Keywords: adsorption-cross linking, immobilization, lipase, resin

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Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie

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Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.

Keywords: antibody engineering, biosensor, phage display, unnatural amino acids

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Authors: Binh T. T. Nguyen, Zhenyu Li, Eric Yap, Yi Zhang, Ai-Qun Liu

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Silicon-photonic-sensor system is an emerging class of analytical technologies that use evanescent field wave to sensitively measure the slight difference in the surrounding environment. The wavelength shift induced by local refractive index change is used as an indicator in the system. These devices can be served as sensors for a wide variety of chemical or biomolecular detection in clinical and environmental fields. In our study, a system including a silicon-based micro-ring resonator, microfluidic channel, and optical processing is designed, fabricated for biomolecule detection. The system is demonstrated to detect Clostridium botulinum type A neurotoxin (BoNT) in different water sources. BoNT is one of the most toxic substances known and relatively easily obtained from a cultured bacteria source. The toxin is extremely lethal with LD50 of about 0.1µg/70kg intravenously, 1µg/ 70 kg by inhalation, and 70µg/kg orally. These factors make botulinum neurotoxins primary candidates as bioterrorism or biothreat agents. It is required to have a sensing system which can detect BoNT in a short time, high sensitive and automatic. For BoNT detection, silicon-based micro-ring resonator is modified with a linker for the immobilization of the anti-botulinum capture antibody. The enzymatic reaction is employed to increase the signal hence gains sensitivity. As a result, a detection limit to 30 pg/mL is achieved by our silicon-photonic sensor within a short period of 80 min. The sensor also shows high specificity versus the other type of botulinum. In the future, by designing the multifunctional waveguide array with fully automatic control system, it is simple to simultaneously detect multi-biomaterials at a low concentration within a short period. The system has a great potential to apply for online, real-time and high sensitivity for the label-free bimolecular rapid detection.

Keywords: biotoxin, photonic, ring resonator, sensor

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Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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Authors: Mariam Vardiashvili

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The economic value of the asset impairment process is quite large. Impairment reflects the reduction of future economic benefits or service potentials itemized in the asset. The assets owned by public sector entities bring economic benefits or are used for delivery of the free-of-charge services. Consequently, they are classified as cash-generating and non-cash-generating assets. IPSAS 21 - Impairment of non-cash-generating assets, and IPSAS 26 - Impairment of cash-generating assets, have been designed considering this specificity.  When measuring impairment of assets, it is important to select the relevant methods. For measurement of the impaired Non-Cash-Generating Assets, IPSAS 21 recommends three methods: Depreciated Replacement Cost Approach, Restoration Cost Approach, and  Service Units Approach. Impairment of Value in Use of Cash-Generating Assets (according to IPSAS 26) is measured by discounted value of the money sources to be received in future. Value in use of the cash-generating asserts (as per IPSAS 26) is measured by the discounted value of the money sources to be received in the future. The article provides classification of the assets in the public sector  as non-cash-generating assets and cash-generating assets and, deals also with the factors which should be considered when evaluating  impairment of assets. An essence of impairment of the non-financial assets and the methods of measurement thereof evaluation are formulated according to IPSAS 21 and IPSAS 26. The main emphasis is put on different methods of measurement of the value in use of the impaired Cash-Generating Assets and Non-Cash-Generation Assets and the methods of their selection. The traditional and the expected cash flow approaches for calculation of the discounted value are reviewed. The article also discusses the issues of recognition of impairment loss and its reflection in the financial reporting. The article concludes that despite a functional purpose of the impaired asset, whichever method is used for measuring the asset, presentation of realistic information regarding the value of the assets should be ensured in the financial reporting. In the theoretical development of the issue, the methods of scientific abstraction, analysis and synthesis were used. The research was carried out with a systemic approach. The research process uses international standards of accounting, theoretical researches and publications of Georgian and foreign scientists.

Keywords: cash-generating assets, non-cash-generating assets, recoverable (usable restorative) value, value of use

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Authors: Oktavian Prasetia Wardana, Martono Tri Utomo, Risa Etika, Kartika Darma Handayani, Dina Angelika, Wurry Ayuningtyas

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Background: Critically ill neonates are newborn babies with high-risk factors that potentially cause disability and/or death. Scoring systems for determining the severity of the disease have been widely developed as well as some designs for use in neonates. The SNAPPE-II method, which has been used as a mortality predictor scoring system in several referral centers, was found to be slow in assessing the outcome of critically ill neonates in the Neonatal Intensive Care Unit (NICU). Objective: To analyze the predictive value of MSNS on the outcome of critically ill neonates at the time of arrival up to 24 hours after being admitted to the NICU. Methods: A longitudinal observational analytic study based on medical record data was conducted from January to August 2022. Each sample was recorded from medical record data, including data on gestational age, mode of delivery, APGAR score at birth, resuscitation measures at birth, duration of resuscitation, post-resuscitation ventilation, physical examination at birth (including vital signs and any congenital abnormalities), the results of routine laboratory examinations, as well as the neonatal outcomes. Results: This study involved 105 critically ill neonates who were admitted to the NICU. The outcome of critically ill neonates was 50 (47.6%) neonates died, and 55 (52.4%) neonates lived. There were more males than females (61% vs. 39%). The mean gestational age of the subjects in this study was 33.8 ± 4.28 weeks, with the mean birth weight of the subjects being 1820.31 ± 33.18 g. The mean MSNS score of neonates with a deadly outcome was lower than that of the lived outcome. ROC curve with a cut point MSNS score <10.5 obtained an AUC of 93.5% (95% CI: 88.3-98.6) with a sensitivity value of 84% (95% CI: 80.5-94.9), specificity 80 % (CI 95%: 88.3-98.6), Positive Predictive Value (PPV) 79.2%, Negative Predictive Value (NPV) 84.6%, Risk Ratio (RR) 5.14 with Hosmer & Lemeshow test results p>0.05. Conclusion: The MSNS score has a good predictive value and good calibration of the outcomes of critically ill neonates admitted to the NICU.

Keywords: critically ill neonate, outcome, MSNS, NICU, predictive value

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Authors: Reza Safdari, Goli Arji, Robab Abdolkhani Maryam zahmatkeshan

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Background and purpose: Cardiovascular diseases are among the most common diseases in all societies. The most important step in minimizing myocardial infarction and its complications is to minimize its risk factors. The amount of medical data is increasingly growing. Medical data mining has a great potential for transforming these data into information. Using data mining techniques to generate predictive models for identifying those at risk for reducing the effects of the disease is very helpful. The present study aimed to collect data related to risk factors of heart infarction from patients’ medical record and developed predicting models using data mining algorithm. Methods: The present work was an analytical study conducted on a database containing 350 records. Data were related to patients admitted to Shahid Rajaei specialized cardiovascular hospital, Iran, in 2011. Data were collected using a four-sectioned data collection form. Data analysis was performed using SPSS and Clementine version 12. Seven predictive algorithms and one algorithm-based model for predicting association rules were applied to the data. Accuracy, precision, sensitivity, specificity, as well as positive and negative predictive values were determined and the final model was obtained. Results: five parameters, including hypertension, DLP, tobacco smoking, diabetes, and A+ blood group, were the most critical risk factors of myocardial infarction. Among the models, the neural network model was found to have the highest sensitivity, indicating its ability to successfully diagnose the disease. Conclusion: Risk prediction models have great potentials in facilitating the management of a patient with a specific disease. Therefore, health interventions or change in their life style can be conducted based on these models for improving the health conditions of the individuals at risk.

Keywords: decision trees, neural network, myocardial infarction, Data Mining

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Authors: Joseph L. Mathew, Shourjendra N. Banerjee, R. K. Ratho, Sourabh Dutta, Vanita Suri

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Background: In India and many other developing countries, a single dose of measles vaccine is administered to infants at 9 months of age. This is based on the assumption that maternal transplacentally transferred antibodies will protect infants until that age. However, our previous data showed that most infants lose maternal anti-measles antibodies before 6 months of age, making them susceptible to measles before vaccination at 9 months. Objective: This prospective study was designed to compare susceptibility in pre-term vs term infants, at different time points. Material and Methods: Following Institutional Ethics Committee approval and a formal informed consent process, venous blood was drawn from a cohort of 45 consecutive term infants and 45 consecutive pre-term infants (both groups delivered by the vaginal route); at birth, 3 months, 6 months and 9 months (prior to measles vaccination). Serum was separated and anti-measles IgG antibody levels were measured by quantitative ELISA kits (with sensitivity and specificity > 95%). Susceptibility to measles was defined as antibody titre < 200mIU/ml. The mean antibody levels were compared between the two groups at the four time points. Results: The mean gestation of term babies was 38.5±1.2 weeks; and pre-term babies 34.7±2.8 weeks. The respective mean birth weights were 2655±215g and 1985±175g. Reliable maternal vaccination record was available in only 7 of the 90 mothers. Mean anti-measles IgG antibody (±SD) in terms babies was 3165±533 IU/ml at birth, 1074±272 IU/ml at 3 months, 314±153 IU/ml at 6 months, and 68±21 IU/ml at 9 months. The corresponding levels in pre-term babies were 2875±612 IU/ml, 948±377 IU/ml, 265±98 IU/ml, and 72±33 IU/ml at 9 months (p > 0.05 for all inter-group comparisons). The proportion of susceptible term infants at birth, 3months, 6months and 9months was 0%, 16%, 67% and 96%. The corresponding proportions in the pre-term infants were 0%, 29%, 82%, and 100% (p > 0.05 for all inter-group comparisons). Conclusion: Majority of infants are susceptible to measles before 9 months of age suggesting the need to anticipate measles vaccination, but there was no statistically significant difference between the proportion of susceptible term and pre-term infants, at any of the four-time points. A larger study is required to confirm these findings and compare sero-protection if vaccination is anticipated to be administered between 6 and 9 months.

Keywords: measles, preterm, susceptibility, term infant

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Authors: Zeina Merabi, Arij Dao

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The temporal order of information processing in the brain is an important code in many acoustic signals, including speech, music, and animal vocalizations. Despite its significance, surprisingly little is known about its underlying cellular mechanisms and network manifestations. In the songbird telencephalic nucleus HVC, a subset of neurons shows temporal combination sensitivity (TCS). These neurons show a high temporal specificity, responding differently to distinct patterns of spectral elements and their combinations. HVC neuron types include basal-ganglia-projecting HVCX, forebrain-projecting HVCRA, and interneurons (HVC¬INT), each exhibiting distinct cellular, electrophysiological and functional properties. In this work, we develop conductance-based neural network models connecting the different classes of HVC neurons via different wiring scenarios, aiming to explore possible neural mechanisms that orchestrate the combination sensitivity property exhibited by HVCX, as well as replicating in vivo firing patterns observed when TCS neurons are presented with various auditory stimuli. The ionic and synaptic currents for each class of neurons that are presented in our networks and are based on pharmacological studies, rendering our networks biologically plausible. We present for the first time several realistic scenarios in which the different types of HVC neurons can interact to produce this behavior. The different networks highlight neural mechanisms that could potentially help to explain some aspects of combination sensitivity, including 1) interplay between inhibitory interneurons’ activity and the post inhibitory firing of the HVCX neurons enabled by T-type Ca2+ and H currents, 2) temporal summation of synaptic inputs at the TCS site of opposing signals that are time-and frequency- dependent, and 3) reciprocal inhibitory and excitatory loops as a potent mechanism to encode information over many milliseconds. The result is a plausible network model characterizing auditory processing in HVC. Our next step is to test the predictions of the model.

Keywords: combination sensitivity, songbirds, neural networks, spatiotemporal integration

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Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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Authors: Jakub Vávra, Milan Valenta, Petr Kosek

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This article presents a perspective on the conduct of the dramatherapy process with persons with addictive behaviours with regard to the directiveness of the process. Although drama therapy as one of the creative arts approaches is rather non-directive in nature, depending on the clientele, there may be a need to structure the process more and, depending on the needs of the clients, to guide the process more directive. The specificity for people with addictive behaviours is discussed through the prism of the dramatherapeutic perspective, where we can find both a psychotherapeutic component as well as a component touching on expression and art, which is rather non-directive in nature. Within the context of practice with clients, this theme has repeatedly emerged and dramatherapists themselves have sought to find ways of coping with clients' demands and needs for structure and guidance within the dramatherapy process. Some of the outcomes from the supervision work also guided the research. Based on this insight, the research questions were approached. The first research question asks: in what ways is directive in dramatherapy manifested and manifested in the process? The second research question then complements the first and asks: to which phenomena are directivity in dramatherapy linked? In relation to the research questions, data were collected using focus groups and field notes. The qualitative approach of Content analysis and Relational analysis was chosen as the methodology. For analyzing qualitative research, we chose an Inductive coding scheme: Open coding, Axial coding, Pattern matching, Member checking, and Creating a coding scheme. In the presented partial research results, we find recurrent schemes related to directive coding in drama therapy. As an important element, directive leadership emerges in connection with safety for the client group, then in connection with the clients' order and also the department of the facility, and last but not least, to the personality of the drama therapist. By careful analysis and looking for patterns in the research results, we can see connections that are impossible to interpret at this stage but already provide clues to our understanding of the topic and open up further avenues for research in this area.

Keywords: dramatherapy, directivity, personal approach, aims of dramatherapy process, safetyness

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Authors: Sergio Alejandro Cuevas, Catherine Etchebest, Fernando Luis Barroso Da Silva

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The flavivirus genus has several organisms responsible for generating various diseases in humans. Special in Brazil, Zika (ZIKV), Dengue (DENV) and Yellow Fever (YFV) viruses have raised great health concerns due to the high number of cases affecting the area during the last years. Diagnostic is still a difficult issue since the clinical symptoms are highly similar. The understanding of their common structural/dynamical and biomolecular interactions features and differences might suggest alternative strategies towards differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV, DENV and YFV non-structural proteins 1 (NS1) protein. By means of computational studies, we calculated the main physical chemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil that could suggest possible molecular mechanisms for the increase of the virulence of ZIKV. It is interesting to note that despite the small changes in the protein sequence due to the high sequence identity among the studied strains, the electrostatic properties are strongly impacted by the pH which also impact on their biomolecular interactions with partners and, consequently, the molecular viral biology. African and Asian strains are distinguishable. Exploring the interfaces used by NS1 to self-associate in different oligomeric states, and to interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can explain the different immunological response. By the comparison with the known antibody structure available for the West Nile virus, we demonstrated that the antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high specificity antibodies.

Keywords: zika, biomolecular interactions, electrostatic interactions, molecular mechanisms

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Authors: Sofiqul Islam, V. Murugan, Prema Kumari, Hari

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Gentamicin is a broad spectrum water-soluble aminoglycoside antibiotics produced by the fermentation process of microorganism known as Micromonospora purpurea. It is widely used for the treatment of infection caused by both gram positive and gram negative bacteria. Gentamicin consists of a mixture of aminoglycoside components like C1, C1a, C2a, and C2. The molecular structure of Gentamicin and its related substances showed that it has lack of presence of chromophore group in the molecule due to which the detection of such components were quite critical and challenging. In this study, a simple Reversed Phase-High Performance Liquid Chromatographic (RP-HPLC) method using ultraviolet (UV) detector was developed and validated for quantification of the related substances present in Gentamicin drug substances. The method was achieved by using Thermo Scientific Hypersil Gold analytical column (150 x 4.6 mm, 5 µm particle size) with isocratic elution composed of methanol: water: glacial acetic acid: sodium hexane sulfonate in the ratio 70:25:5:3 % v/v/v/w as a mobile phase at a flow rate of 0.5 mL/min, column temperature was maintained at 30 °C and detection wavelength of 330 nm. The four components of Gentamicin namely Gentamicin C1, C1a, C2a, and C2 were well separated along with the related substance present in Gentamicin. The Limit of Quantification (LOQ) values were found to be at 0.0075 mg/mL. The accuracy of the method was quite satisfactory in which the % recovery was resulted between 95-105% for the related substances. The correlation coefficient (≥ 0.995) shows the linearity response against concentration over the range of Limit of Quantification (LOQ). Precision studies showed the % Relative Standard Deviation (RSD) values less than 5% for its related substance. The method was validated in accordance with the International Conference of Harmonization (ICH) guideline with various parameters like system suitability, specificity, precision, linearity, accuracy, limit of quantification, and robustness. This proposed method was easy and suitable for use for the quantification of related substances in routine analysis of Gentamicin formulations.

Keywords: reversed phase-high performance liquid chromatographic (RP-HPLC), high performance liquid chromatography, gentamicin, isocratic, ultraviolet

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Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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Authors: Ching-Yuan Chen, Lung-Kwang Pan

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Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

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Authors: Godwin Dennison, C. E. Boulind, O. Gould, B. de Lacy Costello, J. Allison, P. White, P. Ewings, A. Wicaksono, N. J. Curtis, A. Pullyblank, D. Jayne, J. A. Covington, N. Ratcliffe, N. K. Francis

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Background: Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. Methods: A prospective, multi-centre, observational feasibility study was performed across three sites. Patients referred on NHS fast-track pathways for potential CRC provided a urine sample which underwent Gas Chromatography Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. Results: 558 patients participated with 23 (4.1%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity=0.878, specificity=0.882, AUROC=0.884). Conclusion: Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified therefore suggesting VOC analysis may have future utility as a triage tool. Acknowledgment: Funding: NIHR Research for Patient Benefit grant (ref: PB-PG-0416-20022).

Keywords: colorectal cancer, volatile organic compound, gas chromatography mass spectrometry, field asymmetric ion mobility spectrometry, selected ion flow tube mass spectrometry

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Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze

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Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.

Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants

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Authors: Rana Tabassum, Ravi Kant, Banshi D. Gupta

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Malic acid is an extensively distributed organic acid in numerous horticultural products in minute amounts which significantly contributes towards taste determination by balancing sugar and acid fractions. An enhanced concentration of malic acid is utilized as an indicator of fruit maturity. In addition, malic acid is also a crucial constituent of several cosmetics and pharmaceutical products. An efficient detection and quantification protocol for malic acid is thus highly demanded. In this study, we report a novel detection scheme for malic acid by synergistically collaborating fiber optic surface plasmon resonance (FOSPR) and distinctive features of nanomaterials favorable for sensing applications. The design blueprint involves the deposition of an assembly of malate dehydrogenase enzyme entrapped in ZnO nanowires forming the sensing route over silver coated central unclad core region of an optical fiber. The formation and subsequent decomposition of the enzyme-analyte complex on exposure of the sensing layer to malic acid solutions of diverse concentration results in modification of the dielectric function of the sensing layer which is manifested in terms of shift in resonance wavelength. Optimization of experimental variables such as enzyme concentration entrapped in ZnO nanowires, dip time of probe for deposition of sensing layer and working pH range of the sensing probe have been accomplished through SPR measurements. The optimized sensing probe displays high sensitivity, broad working range and a minimum limit of detection value and has been successfully tested for malic acid determination in real samples of fruit juices. The current work presents a novel perspective towards malic acid determination as the unique and cooperative combination of FOSPR and nanomaterials provides myriad advantages such as enhanced sensitivity, specificity, compactness together with the possibility of online monitoring and remote sensing.

Keywords: surface plasmon resonance, optical fiber, sensor, malic acid

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Authors: Teklay Gebrecherkos

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Background: Serological testing for SARS-CoV-2 plays an important role in epidemiological studies, in aiding the diagnosis of COVID-19 and assess vaccine responses. Little is known about the dynamics of SARS-CoV-2 serology in African settings. Here, we aimed to characterize the longitudinal antibody response profile to SARS-CoV-2 in Ethiopia. Methods: In this prospective study, a total of 102 PCR-confirmed COVID-19 patients were enrolled. We obtained 802 plasma samples collected serially. SARS-CoV-2 antibodies were determined using four lateral flow immune assays (LFIAs) and an electrochemiluminescent immunoassay. We determined longitudinal antibody response to SARS-CoV-2 as well as seroconversion dynamics. Results: Serological positivity rate ranged between 12%-91%, depending on timing after symptom onset. There was no difference in the positivity rate between severe and non-severe COVID-19 cases. The specificity ranged between 90%-97%. Agreement between different assays ranged between 84%-92%. The estimated positive predictive value (PPV) for IgM or IgG in a scenario with seroprevalence at 5% varies from 33% to 58%. Nonetheless, when the population seroprevalence increases to 25% and 50%, there is a corresponding increase in the estimated PPVs. The estimated negative-predictive value (NPV) in a low seroprevalence scenario (5%) is high (>99%). However, the estimated NPV in a high seroprevalence scenario (50%) for IgM or IgG is reduced significantly from 80% to 85%. Overall, 28/102 (27.5%) seroconverted by one or more assays tested within a median time of 11 (IQR: 9–15) days post symptom onset. The median seroconversion time among symptomatic cases tended to be shorter when compared to asymptomatic patients [9 (IQR: 6–11) vs. 15 (IQR: 13–21) days; p = 0.002]. Overall, seroconversion reached 100% 5.5 weeks after the onset of symptoms. Notably, of the remaining 74 COVID-19 patients included in the cohort, 64 (62.8%) were positive for antibodies at the time of enrollment, and 10 (9.8%) patients failed to mount a detectable antibody response by any of the assays tested during follow-up. Conclusions: Longitudinal assessment of antibody response in African COVID-19 patients revealed heterogeneous responses. This underscores the need for a comprehensive evaluation of serum assays before implementation. Factors associated with failure to seroconvert need further research.

Keywords: COVID-19, antibody, rapid diagnostic tests, ethiopia

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Authors: Michal Krecichwost, Zauzanna Miodonska, Pawel Badura

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The diagnosis of sigmatism is mostly based on the observation of articulatory organs. It is, however, not always possible to precisely observe the vocal apparatus, in particular in the oral cavity of the patient. Speech processing can allow to objectify the therapy and simplify the verification of its progress. In the described study the methodology for classification of incorrectly pronounced phoneme [s] is proposed. The recordings come from adults. They were registered with the speech recorder at the sampling rate of 44.1 kHz and the resolution of 16 bit. The database of pathological and normative speech has been collected for the study including reference assessments provided by the speech therapy experts. Ten adult subjects were asked to simulate a certain type of stigmatism under the speech therapy expert supervision. In the recordings, the analyzed phone [s] was surrounded by vowels, viz: ASA, ESE, ISI, SPA, USU, YSY. Thirteen MFCC (mel-frequency cepstral coefficients) and RMS (root mean square) values are calculated within each frame being a part of the analyzed phoneme. Additionally, 3 fricative formants along with corresponding amplitudes are determined for the entire segment. In order to aggregate the information within the segment, the average value of each MFCC coefficient is calculated. All features of other types are aggregated by means of their 75th percentile. The proposed method of features aggregation reduces the size of the feature vector used in the classification. Binary SVM (support vector machine) classifier is employed at the phoneme recognition stage. The first group consists of pathological phones, while the other of the normative ones. The proposed feature vector yields classification sensitivity and specificity measures above 90% level in case of individual logo phones. The employment of a fricative formants-based information improves the sole-MFCC classification results average of 5 percentage points. The study shows that the employment of specific parameters for the selected phones improves the efficiency of pathology detection referred to the traditional methods of speech signal parameterization.

Keywords: computer-aided pronunciation evaluation, sibilants, sigmatism diagnosis, speech processing

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Authors: Uraib Sharaha, Guy Beck, Joseph Kapelushnik, Adam H. Agbaria, Itshak Lapidot, Shaul Mordechai, Ahmad Salman, Mahmoud Huleihel

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Infectious diseases cause a significant burden on the public health and the economic stability of societies all over the world for several centuries. A reliable detection of the causative agent of infection is not possible based on clinical features, since some of these infections have similar symptoms, including fever, sneezing, inflammation, vomiting, diarrhea, and fatigue. Moreover, physicians usually encounter difficulties in distinguishing between viral and bacterial infections based on symptoms. Therefore, there is an ongoing need for sensitive, specific, and rapid methods for identification of the etiology of the infection. This intricate issue perplex doctors and researchers since it has serious repercussions. In this study, we evaluated the potential of the mid-infrared spectroscopic method for rapid and reliable identification of bacterial and viral infections based on simple peripheral blood samples. Fourier transform infrared (FTIR) spectroscopy is considered a successful diagnostic method in the biological and medical fields. Many studies confirmed the great potential of the combination of FTIR spectroscopy and machine learning as a powerful diagnostic tool in medicine since it is a very sensitive method, which can detect and monitor the molecular and biochemical changes in biological samples. We believed that this method would play a major role in improving the health situation, raising the level of health in the community, and reducing the economic burdens in the health sector resulting from the indiscriminate use of antibiotics. We collected peripheral blood samples from young 364 patients, of which 93 were controls, 126 had bacterial infections, and 145 had viral infections, with ages lower than18 years old, limited to those who were diagnosed with fever-producing illness. Our preliminary results showed that it is possible to determine the infectious agent with high success rates of 82% for sensitivity and 80% for specificity, based on the WBC data.

Keywords: infectious diseases, (FTIR) spectroscopy, viral infections, bacterial infections.

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Authors: Frederico Fialho Teixeira, Islam Mashaly, Maryam Shafiei, Jurij Karlovsek

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The ubiquity of data gathering and smart technologies, advancements in virtual technologies, and the development of the internet of things (IoT) have created urgent demands for the development of frameworks and efficient workflows for data collection, visualisation, and analysis. Digital twin, in different scales of the city into the building, allows for bringing together data from different sources to generate fundamental and illuminating insights for the management of current facilities and the lifecycle of amenities as well as improvement of the performance of current and future designs. Over the past two decades, there has been growing interest in the topic of digital twin and their applications in city and building scales. Most such studies look at the urban environment through a homogeneous or generalist lens and lack specificity in particular characteristics or identities, which define an urban university campus. Bridging this knowledge gap, this paper offers a framework for developing a digital twin for a university campus that, with some modifications, could provide insights for any large-scale digital twin settings like towns and cities. It showcases how currently unused data could be purposefully combined, interpolated and visualised for producing analysis-ready data (such as flood or energy simulations or functional and occupancy maps), highlighting the potential applications of such a framework for campus planning and policymaking. The research integrates campus-level data layers into one spatial information repository and casts light on critical data clusters for the digital twin at the campus level. The paper also seeks to raise insightful and directive questions on how digital twin for campus can be extrapolated to city-scale digital twin. The outcomes of the paper, thus, inform future projects for the development of large-scale digital twin as well as urban and architectural researchers on potential applications of digital twin in future design, management, and sustainable planning, to predict problems, calculate risks, decrease management costs, and improve performance.

Keywords: digital twin, smart campus, framework, data collection, point cloud

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 139

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

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Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

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Authors: Sadeq Al Yaari, Muhammad Alkhunayn, Ayah Al Yaari, Ayman Al Yaari, Montaha Al Yaari, Adham Al Yaari, Sajedah Al Yaari, Fatehi Eissa

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Developmental co-ordination disorder (DCD) (also known as dyspraxia) causes a child to speak less well than expected in social conversations. We propose that the smart speaking technology could help improve sound production mechanism at both phonetic and phonological levels, which leads to better articulation of an utterance. The participants are twelve privately beginner pupils aged between 6-12 years old and diagnosed with DCD (apraxia) divided into two groups: Experimental group (n=6) and control group (called apraxic control group) (n=6). A total of fifty typically developing and achieving (TD) pupils participated as control group 2 in both groups and were preassigned into two groups (27 pupils with the treatment group and 23 with the apraxic control group). Weekly quizzes were given to all participants each week for four continuous months and results were analyzed by psychoneurolinguists and a statistician. Although being taught by the same speech-language therapist (SLT), treatment group along with TD groups were taught a full-time speaking course with sociolinguistic themes covering both phonetic and phonological properties. The course lasted for a whole semester whereby smart speaking aids have become dominant while apraxic control group and its TD group were not. Compared with apraxic control group and its TD subgroup, results show obvious changes in speaking behavioral mechanism of the DCD experimental group and its TD subgroup. Improvement could be taken from the scores where the zero marks disappeared in the fourth week (end of the first month of treatment). Good marks (5 +/10) were seen starting from the eighth week and culminating with full marks in the week number 15 of treatment where some participants scored full mark. This study concludes to support the primacy of the smart educational technology for speaking purposes and also shows that such aids can expand the range of academic performance differential categories. Further research is required to evaluate the current demonizing of smart educational aids and weighting more reasonably the relationship specificity that speaking aids can offer to other language skills, as well as their limitations.

Keywords: smart educational technology, speaking aids, pupils with SCD, apraxia

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Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee

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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.

Keywords: allergen, inflammation, nanodrug, wound

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