Search results for: personalized therapeutics

Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

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Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

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Authors: Anna Guitart Atienza, Ana Fernández del Río, Madhav Nekkar, Jelena Ljubicic, África Periáñez, Eura Shin, Lauren Bellhouse

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The use of digital devices in healthcare or mobile health (mHealth) has increased in recent years due to the advances in digital technology, making it possible to nudge healthy behaviors through individual interventions. In addition, mHealth is becoming essential in poor-resource settings due to the widespread use of smartphones in areas where access to professional healthcare is limited. In this work, we evaluate mHealth interventions in low-income countries with a focus on causal inference. Counterfactuals estimation and other causal computations are key to determining intervention success and assisting in empirical decision-making. Our main purpose is to personalize treatment recommendations and triage patients at the individual level in order to maximize the entire intervention's impact on the desired outcome. For this study, collected data includes mHealth individual logs from front-line healthcare workers, electronic health records (EHR), and external variables data such as environmental, demographic, and geolocation information.

Keywords: causal inference, mHealth, intervention, personalization

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Authors: Hoyeon Park, Yunhwan Keon, Kyoung-Jae Kim

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Location Based Social Network services (LBSNs) is a new term that combines location based service and social network service (SNS). Unlike traditional SNS, LBSNs emphasizes empirical elements in the user's actual physical location. Point-of-Interest (POI) is the most important factor to implement LBSNs recommendation system. POI information is the most popular spot in the area. In this study, we would like to recommend POI to users in a specific area through recommendation system using collaborative filtering. The process is as follows: first, we will use different data sets based on Seoul and New York to find interesting results on human behavior. Secondly, based on the location-based activity information obtained from the personalized LBSNs, we have devised a new rating that defines the user's preference for the area. Finally, we have developed an automated rating algorithm from massive raw data using distributed systems to reduce advertising costs of LBSNs.

Keywords: location-based social network services, point-of-interest, recommender systems, business analytics

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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: Tripti Mishra, Shipra Shukla, Sanjeev Meena, , Ruchi Singh, Mahesh Pal, D. K. Upreti, Dipak Datta

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Roccella montagnei belongs to lichen family Roccelleceae growing luxuriantly along the coastal regions of India. As Roccella has been shown to be bioactive, we prepared methanolic extract and assessed its anticancer potential. The methanolic extract showed significant in vitro cytotoxic activity against four human cancer cell lines such as Colon (DLD-1, SW-620), Breast (MCF-7), Head and Neck (FaDu). This prompted us to isolate bioactive compounds through column chromatography. Two compounds Roccellic acid and Everninic acid have been isolated, out of which Everninic acid is reported for the first time. Both the compounds have been tested for in vitro cytotoxic activity in which Roccellic acid showed strong anticancer activity as compared to the Everninic acid. CDK-10 (Cyclin-dependent kinase) contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases, therefore, constitute biomarkers of proliferation and attractive pharmacological targets for the development of anticancer therapeutics. Therefore both the isolated compounds were tested for in silico molecular docking study against CDK-10 isomer enzyme to support the cytotoxic activity.

Keywords: cytotoxic activity, everninic acid, roccellic acid, R. montagnei

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: M. Sadeghi, H. Pezeshk, R. Tusserkani, A. Sharifi Zarchi, A. Malekpour, M. Foroughmand, S. Goliaei, M. Totonchi, N. Ansari–Pour

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The role and relative importance of intrinsic and extrinsic factors in the development of complex diseases such as cancer still remains a controversial issue. Determining the amount of variation explained by these factors needs experimental data and statistical models. These models are nevertheless based on the occurrence and accumulation of random mutational events during stem cell division, thus rendering cancer development a stochastic outcome. We demonstrate that not only individual genome sequencing is uninformative in determining cancer risk, but also assigning a unique genome sequence to any given individual (healthy or affected) is not meaningful. Current whole-genome sequencing approaches are therefore unlikely to realize the promise of personalized medicine. In conclusion, since genome sequence differs from cell to cell and changes over time, it seems that determining the risk factor of complex diseases based on genome sequence is somewhat unrealistic, and therefore, the resulting data are likely to be inherently uninformative.

Keywords: cancer risk, extrinsic factors, genome sequencing, intrinsic factors

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Authors: Ciaran Friel, Jerry Suls, Mark Butler, Patrick Robles, Samantha Gordon, Frank Vicari, Karina W. Davidson

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Physical activity guidelines focus on increasing moderate-intensity activity for older adults, but adherence to recommendations remains low. This is despite the fact that scientific evidence supports that any increase in physical activity is positively correlated with health benefits. Behavior change techniques (BCTs) have demonstrated effectiveness in reducing sedentary behavior and promoting physical activity. This pilot study uses a Personalized Trials (N-of-1) design to evaluate the efficacy of using four BCTs to promote an increase in low-intensity physical activity (2,000 steps of walking per day) in adults aged 45-75 years old. The 4 BCTs tested were goal setting, action planning, feedback, and self-monitoring. BCTs were tested in random order and delivered by text message prompts requiring participant engagement. The study recruited health system employees in the target age range, without mobility restrictions and demonstrating interest in increasing their daily activity by a minimum of 2,000 steps per day for a minimum of five days per week. Participants were sent a Fitbit® fitness tracker with an established study account and password. Participants were recommended to wear the Fitbit device 24/7 but were required to wear it for a minimum of ten hours per day. Baseline physical activity was measured by Fitbit for two weeks. In the 8-week intervention phase of the study, participants received each of the four BCTs, in random order, for a two-week period. Text message prompts were delivered daily each morning at a consistent time. All prompts required participant engagement to acknowledge receipt of the BCT message. Engagement is dependent upon the BCT message and may have included recording that a detailed plan for walking has been made or confirmed a daily step goal (action planning, goal setting). Additionally, participants may have been directed to a study dashboard to view their step counts or compare themselves to their baseline average step count (self-monitoring, feedback). At the end of each two-week testing interval, participants were asked to complete the Self-Efficacy for Walking Scale (SEW_Dur), a validated measure that assesses the participant’s confidence in walking incremental distances, and a survey measuring their satisfaction with the individual BCT that they tested. At the end of their trial, participants received a personalized summary of their step data in response to each individual BCT. The analysis will examine the novel individual-level heterogeneity of treatment effect made possible by N-of-1 design and pool results across participants to efficiently estimate the overall efficacy of the selected behavioral change techniques in increasing low-intensity walking by 2,000 steps, five days per week. Self-efficacy will be explored as the likely mechanism of action prompting behavior change. This study will inform the providers and demonstrate the feasibility of an N-of-1 study design to effectively promote physical activity as a component of healthy aging.

Keywords: aging, exercise, habit, walking

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Authors: Panagiotis Gkekas, Christos Sougles, Dionysios Kehagias, Dimitrios Tzovaras

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This paper presents the architecture of the “Intelligent cooperative integrated system for road safety and road infrastructure maintenance towards 2020” (ODOS2020) advanced infrastructure, which implements a number of cooperative ITS applications based on Internet of Things and Infrastructure-to-Vehicle (V2I) technologies with the purpose to enhance the active road safety level of vehicles through the provision of a fully automated V2I environment. The primary objective of the ODOS2020 project is to contribute to increased road safety but also to the optimization of time for maintenance of road infrastructure. The integrated technological solution presented in this paper addresses all types of vehicles and requires minimum vehicle equipment. Thus, the ODOS2020 comprises a low-cost solution, which is one of its main benefits. The system architecture includes an integrated notification system to transmit personalized information on road, traffic, and environmental conditions, in order for the drivers to receive real-time and reliable alerts concerning upcoming critical situations. The latter include potential dangers on the road, such as obstacles or road works ahead, extreme environmental conditions, etc., but also informative messages, such as information on upcoming tolls and their charging policies. At the core of the system architecture lies an integrated sensorial network embedded in special road infrastructures (strips) that constantly collect and transmit wirelessly information about passing vehicles’ identification, type, speed, moving direction and other traffic information in combination with environmental conditions and road wear monitoring and predictive maintenance data. Data collected from sensors is transmitted by roadside infrastructure, which supports a variety of communication technologies such as ITS-G5 (IEEE-802.11p) wireless network and Internet connectivity through cellular networks (3G, LTE). All information could be forwarded to both vehicles and Traffic Management Centers (TMC) operators, either directly through the ITS-G5 network, or to smart devices with Internet connectivity, through cloud-based services. Therefore, through its functionality, the system could send personalized notifications/information/warnings and recommendations for upcoming events to both road users and TMC operators. In the course of the ODOS2020 project pilot operation has been conducted to allow drivers of both C-ITS equipped and non-equipped vehicles to experience the provided added value services. For non-equipped vehicles, the provided information is transmitted to a smartphone application. Finally, the ODOS2020 system and infrastructure is appropriate for installation on both urban, rural, and highway environments. The paper presents the various parts of the system architecture and concludes by outlining the various challenges that had to be overcome during its design, development, and deployment in a real operational environment. Acknowledgments: Work presented in this paper was co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation (call RESEARCH–CREATE–INNOVATE) under contract no. Τ1EDK-03081 (project ODOS2020).

Keywords: infrastructure to vehicle, intelligent transportation systems, internet of things, road safety

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Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

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Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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Authors: Amel Hannech, Mehdi Adda, Hamid Mcheick

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In this paper, we propose a generic model of user profile integrating several elements that may positively impact the research process. We exploit the classical behavior of users and integrate a delimitation process of their research activities into several research sessions enriched with contextual and temporal information, which allows reflecting the current interests of these users in every period of time and infer data freshness. We argue that the annotation of resources gives more transparency on users' needs. It also strengthens social links among resources and users, and can so increase the scope of the user profile. Based on this idea, we integrate the social tagging practice in order to exploit the social users' behavior to enrich their profiles. These profiles are then integrated into a recommendation system in order to predict the interesting personalized items of users allowing to assist them in their researches and further enrich their profiles. In this recommendation, we provide users new research experiences.

Keywords: user profiles, topical ontology, contextual information, folksonomies, tags' clusters, data freshness, association rules, data recommendation

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Authors: Niloofar Hooman

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The present study aims at investigating the positive and negative effects of using Smartphones on couples committed relationships. Despite the fact that many couples may benefit from the positive aspects of Smartphones, it is not clear how their feeling of trust, intimacy and connection in their relationships get affected by Smartphones. This is important as it highlights the ambivalent influences of Smartphones on couple’s relationships. On the one hand, Smartphones can enhance their social and emotional interactions and on the other hand, they can cause mistrust and isolation between them. Trust, intimacy and honesty are of important factors through which a stable relationship can be constructed. Nevertheless, some characteristics of Smartphones such as being fluid and personalized can harm the relationship and consequently destroy it. Thus, it is necessary to investigate how Iranian couples in committed relationships use Smartphone to manage their relationship and how couples feel Smartphone have enhanced or detracted a sense of trust, intimacy and connection with their partner? In the first phase of the study, in-depth-interview will be conducted with 30 couples and data will be analyzed using NVIVO software. In the next phase of the study, 1500 participants aged 20 and above will be selected based on cluster sampling. Data will be analyzed both qualitatively and quantitatively.

Keywords: couple, family, internet, intimacy, Smartphone, trust

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Jeong Woo Kang, MiYoung Baek, Ki-Suk Kim, Kwang-Jick Lee, ByungJae So

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Introduction: A fast, easy and sensitive detection method was developed and validated by liquid chromatography tandem mass spectrometry for the determination of marbofloxacin in pig plasma which was further applied to study the pharmacokinetics of marbofloxacin. Materials and Methods: The plasma sample (500 μL) was mixed with 1.5 ml of 0.1% formic acid in MeCN to precipitate plasma proteins. After shaking for 20 min, The mixture was centrifuged at 5,000 × g for 30 min. It was dried under a nitrogen flow at 50℃. 500 μL aliquot of the sample was injected into the LC-MS/MS system. Chromatographic analysis was carried out mobile phase gradient consisting 0.1% formic acid in D.W. (A) and 0.1% formic acid in MeCN (B) with C18 reverse phase column. Mass spectrometry was performed using the positive ion mode and the selected ion monitoring (MRM). Results and Conclusions: The method validation was performed in the sample matrix. Good linearities (R2>0.999) were observed and the quantified average recoveries of marbofloxacin were 87 - 92% at level of 10 ng g-1 -100 ng g-1. The percent of coefficient of variation (CV) for the described method was less than 10 % over the range of concentrations studied. The limits of detection (LOD) and quantification (LOQ) were 2 and 5 ng g-1, respectively. This method has also been applied successfully to pharmacokinetic analysis of marbofloxacin after intravenous (IV), intramuscular (IM) and oral administration (PO). The mean peak plasma concentration (Cmax) was 2,597 ng g-1at 0.25 h, 2,587 ng g-1at 0.44 h and 2,355 ng g-1at 1.58 h for IV, IM and PO, respectively. The area under the plasma concentration-time curve (AUC0–t) was 24.8, 29.0 and 25.2 h μg/mL for IV, IM and PO, respectively. The elimination half-life (T1/2) was 8.6, 13.1 and 9.5 for IV, IM and PO, respectively. Bioavailability (F) of the marbofloxacin in pig was 117 and 101 % for IM and PO, respectively. Based on these result, marbofloxacin does not have any obstacles as therapeutics to develop the oral formulations such as tablets and capsules.

Keywords: marbofloxacin, LC-MS/MS, pharmacokinetics, chromatographic

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Authors: Robert van Ling, Alexander Schwahn, Shanhua Lin, Ken Cook, Frank Steiner, Rowan Moore, Mauro de Pra

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Purpose: Demonstration of fast high resolution charge variant analysis for monoclonal antibody (mAb) therapeutics within 5 minutes. Methods: Three commercially available mAbs were used for all experiments. The charge variants of therapeutic mAbs (Bevacizumab, Cetuximab, Infliximab, and Trastuzumab) are analyzed on a strong cation exchange column with a linear pH gradient separation method. The linear gradient from pH 5.6 to pH 10.2 is generated over time by running a linear pump gradient from 100% Thermo Scientific™ CX-1 pH Gradient Buffer A (pH 5.6) to 100% CX-1 pH Gradient Buffer B (pH 10.2), using the Thermo Scientific™ Vanquish™ UHPLC system. Results: The pH gradient method is generally applicable to monoclonal antibody charge variant analysis. In conjunction with state-of-the-art column and UHPLC technology, ultra fast high-resolution separations are consistently achieved in under 5 minutes for all mAbs analyzed. Conclusion: The linear pH gradient method is a platform method for mAb charge variant analysis. The linear pH gradient method can be easily optimized to improve separations and shorten cycle times. Ultra-fast charge variant separation is facilitated with UHPLC that complements, and in some instances outperforms CE approaches in terms of both resolution and throughput.

Keywords: charge variants, ion exchange chromatography, monoclonal antibody, UHPLC

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Authors: Nilki Upathissa, Torin Wirasinghe

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This solution addresses the challenges faced by traditional bookstores and the limitations of digital media, striking a balance between the tactile experience of printed books and the convenience of modern technology. The book exchange system offers a sustainable alternative, empowering users to access a diverse range of books while promoting community engagement. The user-friendly interfaces incorporated into the book exchange system ensure a seamless and enjoyable experience for users. Intuitive features for book management, search, and messaging facilitate effortless exchanges and interactions between users. By streamlining the process, the system encourages readers to explore new books aligned with their interests, enhancing the overall reading experience. Central to the system's success is the hybrid recommendation engine, which leverages advanced technologies such as Long Short-Term Memory (LSTM) models. By analyzing user input, the engine accurately predicts genre preferences, enabling personalized book recommendations. The hybrid approach integrates multiple technologies, including user interfaces, machine learning models, and recommendation algorithms, to ensure the accuracy and diversity of the recommendations. The evaluation of the book exchange system with the hybrid recommendation engine demonstrated exceptional performance across key metrics. The high accuracy score of 0.97 highlights the system's ability to provide relevant recommendations, enhancing users' chances of discovering books that resonate with their interests. The commendable precision, recall, and F1score scores further validate the system's efficacy in offering appropriate book suggestions. Additionally, the curve classifications substantiate the system's effectiveness in distinguishing positive and negative recommendations. This metric provides confidence in the system's ability to navigate the vast landscape of book choices and deliver recommendations that align with users' preferences. Furthermore, the implementation of this book exchange system with a hybrid recommendation engine has the potential to revolutionize the way readers interact with printed books. By facilitating book exchanges and providing personalized recommendations, the system encourages a sense of community and exploration within the reading community. Moreover, the emphasis on sustainability aligns with the growing global consciousness towards eco-friendly practices. With its robust technical approach and promising evaluation results, this solution paves the way for a more inclusive, accessible, and enjoyable reading experience for book lovers worldwide. In conclusion, the developed book exchange system with a hybrid recommendation engine represents a progressive solution to the challenges faced by traditional bookstores and the limitations of digital media. By promoting sustainability, widening access to printed books, and fostering engagement with reading, this system addresses the evolving needs of book enthusiasts. The integration of user-friendly interfaces, advanced machine learning models, and recommendation algorithms ensure accurate and diverse book recommendations, enriching the reading experience for users.

Keywords: recommendation systems, hybrid recommendation systems, machine learning, data science, long short-term memory, recurrent neural network

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Authors: Venkat Garigapati

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Cell-based therapies are limited due to underlying host immune system activity. Microencapsulation of living cells to overcome this issue has some serious drawbacks, such as limitations of nutrient and oxygen diffusion, which pose a threat to the function and longevity of cells. The conformal coating could overcome the issues which are generally involved in traditional microencapsulation. Some of the theoretical advantages of conformal coating include superior nutrient and oxygen supply to cells, prolonged lifespan, improved drug-secreting cell functionality and an opportunity to load high cell doses in small volumes. Despite several advantages to the conformal coating, there are no suitable methods available to apply to living cells. The ultra-thin conformal coating was achieved utilizing click-reactive methacryloyloxyethyl phosphorylcholine (MPC) polymers, which are capable of specifically reacting one polymer to another at neutral pH in the aqueous isotonic system at the desired temperature suitable for living cells without the need of deleterious initiators. ARPE-19 (Adult Retinal Pigment Epithelial cell line-19) cell-spheroids and rat pancreatic islets were used in the formulation studies. The in vitro studies of coated ARPE-19 cell-spheroids and rat islets indicate that the coat was intact; cells were viable and functioning. The in vitro study results revealed that the conformal coating technology seems promising and in vivo studies are being planned.

Keywords: cells, hydrogel, conformal coating, microencapsulation, insulin

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Authors: Islam Sherif, Ahmed Ashour, Ahmed Hassan, Hatem Osman

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Anterior Cruciate Ligament (ACL) injuries are common among athletes and individuals participating in sports with sudden stops, pivots, and changes in direction. Arthroscopic surgery is the gold standard for ACL reconstruction, aiming to restore knee stability and function. Recent years have witnessed significant advancements in arthroscopic surgery techniques, graft materials, and technological innovations, revolutionizing the field of ACL reconstruction. This presentation delves into the latest advancements in arthroscopic surgery techniques for ACL reconstruction and their potential impact on patient outcomes. Traditionally, autografts from the patellar tendon, hamstring tendon, or quadriceps tendon have been commonly used for ACL reconstruction. However, recent studies have explored the use of allografts, synthetic scaffolds, and tissue-engineered grafts as viable alternatives. This abstract evaluates the benefits and potential drawbacks of each graft type, considering factors such as graft incorporation, strength, and risk of graft failure. Moreover, the application of augmented reality (AR) and virtual reality (VR) technologies in surgical planning and intraoperative navigation has gained traction. AR and VR platforms provide surgeons with detailed 3D anatomical reconstructions of the knee joint, enhancing preoperative visualization and aiding in graft tunnel placement during surgery. We discuss the integration of AR and VR in arthroscopic ACL reconstruction procedures, evaluating their accuracy, cost-effectiveness, and overall impact on surgical outcomes. Beyond graft selection and surgical navigation, patient-specific planning has gained attention in recent research. Advanced imaging techniques, such as MRI-based personalized planning, enable surgeons to tailor ACL reconstruction procedures to each patient's unique anatomy. By accounting for individual variations in the femoral and tibial insertion sites, this personalized approach aims to optimize graft placement and potentially improve postoperative knee kinematics and stability. Furthermore, rehabilitation and postoperative care play a crucial role in the success of ACL reconstruction. This abstract explores novel rehabilitation protocols, emphasizing early mobilization, neuromuscular training, and accelerated recovery strategies. Integrating technology, such as wearable sensors and mobile applications, into postoperative care can facilitate remote monitoring and timely intervention, contributing to enhanced rehabilitation outcomes. In conclusion, this presentation provides an overview of the cutting-edge advancements in arthroscopic surgery techniques for ACL reconstruction. By embracing innovative graft materials, augmented reality, patient-specific planning, and technology-driven rehabilitation, orthopedic surgeons and sports medicine specialists can achieve superior outcomes in ACL injury management. These developments hold great promise for improving the functional outcomes and long-term success rates of ACL reconstruction, benefitting athletes and patients alike.

Keywords: arthroscopic surgery, ACL, autograft, allograft, graft materials, ACL reconstruction, synthetic scaffolds, tissue-engineered graft, virtual reality, augmented reality, surgical planning, intra-operative navigation

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Fatemeh Deldarabdolmaleki, Nur Dalilah Dahlan, Farzad Hejazi

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Human individual physiological and psycho-physical responses widely affect thermal comfort and preferences. They should be carefully researched to help improve the design and comfort of indoor environments. This paper aims to explore and test the degree and importance of individual physiological and psycho-physical differences, reviewing the most preferred, neutral, and comfortable temperature in previous studies conducted across the world. Basic individual physiological differences like gender, age, BMI and etc., have been the focus of this research. There is no unique consensus in the literature to date in regard to providing a universal thermal comfort formula that meets all individual physiological and psycho-physical needs. In order to achieve a balanced, thermally comfortable indoor environment, studying and evaluating individual needs in different parts of the world could be helpful. Even though personalized comfort systems in indoor environments sound promising, they might not be easily achieved in bigger office interiors, considering the cost and current open-plan office trends.

Keywords: thermal comfort, indoor environments, occupants' physiological response, occupants psycho-physical response

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Authors: Selma Bouasria, Mahi Abdelkader, Abbès Azzi, Herouz Keltoum

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Ventilation in buildings is a key element to provide high indoor air quality. Its efficiency appears as one of the most important factors in maintaining thermal comfort for occupants of buildings. Personal displacement ventilation is a new ventilation concept that combines the positive features of displacement ventilation with those of task conditioning or personalized ventilation. This work aims to study numerically the supply air flow in a room to optimize a comfortable microclimate for an occupant. The room is heated, and a dummy is designed to simulate the occupant. Two types of configurations were studied. The first consist of a room without windows; and the second one is a local equipped with a window. The influence of the blowing speed and the solar radiation coming from the window on the thermal comfort of the occupant is studied. To conduct this study we used the turbulence models, namely the high Reynolds k-e, the RNG and the SST models. The numerical tool used is based on the finite volume method. The numerical simulation of the supply air flow in a room can predict and provide a significant information about indoor comfort.

Keywords: local, comfort, thermique, ventilation, internal environment

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Authors: Ciaran Friel, Jerry Suls, Patrick Robles, Frank Vicari, Joan Duer-Hefele, Karina W. Davidson

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Physical activity guidelines focus on increasing moderate intensity activity for older adults, but adherence to recommendations remains low. This is despite the fact that scientific evidence supports that any increase in physical activity is positively correlated with health benefits. Behavior change techniques (BCTs) have demonstrated effectiveness in reducing sedentary behavior and promoting physical activity. This pilot study uses a Personalized Trials (N-of-1) design to evaluate the efficacy of using four BCTs to promote an increase in low-intensity physical activity (2,000 steps of walking per day) in adults aged 45-75 years old. The 4 BCTs tested were goal setting, action planning, feedback, and self-monitoring. BCTs were tested in random order and delivered by text message prompts requiring participant response. The study recruited health system employees in the target age range, without mobility restrictions and demonstrating interest in increasing their daily activity by a minimum of 2,000 steps per day for a minimum of five days per week. Participants were sent a Fitbit Charge 4 fitness tracker with an established study account and password. Participants were recommended to wear the Fitbit device 24/7, but were required to wear it for a minimum of ten hours per day. Baseline physical activity was measured by the Fitbit for two weeks. Participants then engaged with a clinical research coordinator to review comprehension of the text message content and required actions for each of the BCTs to be tested. Participants then selected a consistent daily time in which they would receive their text message prompt. In the 8 week intervention phase of the study, participants received each of the four BCTs, in random order, for a two week period. Text message prompts were delivered daily at a time selected by the participant. All prompts required an interactive response from participants and may have included recording their detailed plan for walking or daily step goal (action planning, goal setting). Additionally, participants may have been directed to a study dashboard to view their step counts or compare themselves with peers (self-monitoring, feedback). At the end of each two week testing interval, participants were asked to complete the Self-Efficacy for Walking Scale (SEW_Dur), a validated measure that assesses the participant’s confidence in walking incremental distances and a survey measuring their satisfaction with the individual BCT that they tested. At the end of their trial, participants received a personalized summary of their step data in response to each individual BCT. Analysis will examine the novel individual-level heterogeneity of treatment effect made possible by N-of-1 design, and pool results across participants to efficiently estimate the overall efficacy of the selected behavioral change techniques in increasing low-intensity walking by 2,000 steps, 5 days per week. Self-efficacy will be explored as the likely mechanism of action prompting behavior change. This study will inform the providers and demonstrate the feasibility of N-of-1 study design to effectively promote physical activity as a component of healthy aging.

Keywords: aging, exercise, habit, walking

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Authors: Ravi Raghav Sonani, Niraj Kumar Singh, Jitendra Kumar, Datta Madamwar

Abstract:

Phycobiliproteins (PBPs) are light harvesting proteins showing very strong absorbance and fluorescence in the visible range of the solar spectrum. Phycoerythrin (PE) and phycocyanin (PC) are majorly found PBPs in the cyanobacteria and red algae. In the present study, we have investigated the reactive oxygen species (ROS)-averting capacity of purified PE and PC of cyanobacterial origin. Furthermore, the possibility - whether the ROS-averting potential of PBPs can be explored in the therapeutics of oxidative stress associated physiological anomalies including aging and neurodegenerative diseases. The nematode Caenorhabditis elegans has been used as model organism in this study. PE and PC treatment moderated normal aging and associated physiological functionalities like pharyngeal pumping and locomotion of C. elegans. Moreover, PE-treatment enhanced the stress (oxidative and heat) tolerance upon PE and PC treatment. Specifically, PE treatment was also noted to moderate the progression of Alzheimer’s disease in transgenic C. elegans CL4176. However, PC-treatment curtailed the polyQ aggregation mediated proteotoxicity in C. elegans AM141 (Huntington disease model) under stressed (paraquat stress) as well as normal conditions. The effectiveness of PE and PC in expanding the lifespan of mutant C. elegans knockout for some up- (daf 16) and down- (daf-2 and age-1) stream regulators of insulin/IGF-1 signalling (IIS) shows the independency of their effects from DAF-2–AGE-1–DAF-16 signalling pathway. In conclusion, the present report demonstrates the anti-aging and neuro-protective potential of cyanobacterial PE and PC.

Keywords: phycobiliproteins, aging, alzheimer, huntington, C. elegans

Procedia PDF Downloads 386

Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

Procedia PDF Downloads 289

Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

Procedia PDF Downloads 427

Authors: Suzanne Ahmed

Abstract:

Nanomotors, also commonly referred to as nanorobotics or nanomachines, have garnered considerable research attention due to their numerous potential applications in biomedicine, including drug delivery and microsurgery. Nanomotors typically consist of inorganic or polymeric particles that are powered to undergo motion. These artificial, man-made nanoscale motors operate in the low Reynolds number regime and typically have no moving parts. Several methods have been developed to actuate the motion of nanomotors including magnetic fields, electrical fields, electromagnetic waves, and chemical fuel. Since their introduction in 2012, ultrasonically powered nanomotors have been explored in biocompatible fluids and even within living cells. Due to the common use of ultrasound within the biomedical community for both imaging and therapeutics, the introduction of ultrasonically propelled nanomotors holds significant potential for biomedical applications. In this work, metallic nanomotors are electrochemically plated within porous anodic alumina templates to have a diameter of 300 nm and a length that is 2-4 µm. Nanomotors are placed within an acoustic chamber capable of producing bulk acoustic waves in the ultrasonic range. The motion of nanomotors within biomimetic confines is explored. The control over nanomotor motion is exerted by virtue of the properties of the acoustic signal within these biomimetic confines to control speed, modes of motion and directionality of motion. To expand the range of control over nanorod motion within biomimetic confines, external forces from biocompatible magnetic fields, are exerted onto the acoustically propelled nanomotors.

Keywords: nanomotors, nanomachines, nanorobots, ultrasound

Procedia PDF Downloads 71

Authors: Cheng Xu

Abstract:

As the metaverse emerges as a dynamic virtual simulacrum of reality, its implications on user privacy have become a focal point of interest. While previous discussions have ventured into metaverse privacy dynamics, a glaring empirical gap persists, especially concerning the effects of personalization in the context of news recommendation services. This study stands at the forefront of addressing this void, meticulously examining how users' privacy concerns shift within the metaverse's personalization context. Through a pre-registered randomized controlled experiment, participants engaged in a personalization task across both the metaverse and traditional online platforms. Upon completion of this task, a comprehensive news recommendation service provider offers personalized news recommendations to the users. Our empirical findings reveal that the metaverse inherently amplifies privacy concerns compared to traditional settings. However, these concerns are notably mitigated when users have a say in shaping the algorithms that drive these recommendations. This pioneering research not only fills a significant knowledge gap but also offers crucial insights for metaverse developers and policymakers, emphasizing the nuanced role of user input in shaping algorithm-driven privacy perceptions.

Keywords: metaverse, privacy concerns, personalization, digital interaction, algorithmic recommendations

Procedia PDF Downloads 109

Authors: Peter Fedichev

Abstract:

We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

Procedia PDF Downloads 271

Authors: Brwa Abdulrahman Abubaker

Abstract:

Recently, there has been a lot of interest in the difficult task of applying reinforcement learning to autonomous mobile robots. Conventional reinforcement learning (TRL) techniques have many drawbacks, such as lengthy computation times, intricate control frameworks, a great deal of trial and error searching, and sluggish convergence. In this paper, a modified Spiking Neural Network (SNN) is used to offer a distinct method for autonomous mobile robot learning and control in unexpected surroundings. As a learning algorithm, the suggested model combines dopamine modulation with spike-timing-dependent plasticity (STDP). In order to create more computationally efficient, biologically inspired control systems that are adaptable to changing settings, this work uses the effective and physiologically credible Izhikevich neuron model. This study is primarily focused on creating an algorithm for target tracking in the presence of obstacles. Results show that the SNN trained with three obstacles yielded an impressive 96% success rate for our proposal, with collisions happening in about 4% of the 214 simulated seconds.

Keywords: spiking neural network, spike-timing-dependent plasticity, dopamine modulation, reinforcement learning

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Authors: Saleit Ron

Abstract:

The Mitar program was established to drive a shift in middle school mathematics education, emphasizing the connection of math to real-life situations, exploring mathematical modeling and literacy, and integrating social and emotional learning (SEL) components for enhanced excellence. The program envisions math coordinators as catalysts for change, equipping them to create educational materials, strengthen leadership skills, and develop SEL competencies within coordinator communities. These skills are then employed to lead transformative efforts within their respective schools. The program engaged 90 participants across six math coordinator communities during 2022-2023, involving 30-60 hours of annual learning. The process includes formative and summative evaluations through questionnaires and interviews, revealing participants' high contentment and successful integration of acquired skills into their schools. Reflections from participants highlighted the need for enhanced change leadership processes, often seeking more personalized mentoring to navigate challenges effectively.

Keywords: math coordinators, mathematical literacy, mathematical modeling, SEL competencies

Procedia PDF Downloads 48