Search results for: tumor visualization

Authors: Alyaa Farouk Ibrahim, Gehan ElSayed, Ola Mamdouh, Nazek AbdelGhany

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Background: Primary health care (PHC) can be considered the first contact between the patient and the health care system. It includes all the basic health care services to be provided to the community. Patient's satisfaction regarding health care has often improved the provision of care, also considered as one of the most important measures for evaluating the health care. Objective: This study aims to identify patient’s satisfaction with services provided at the primary health care settings in Alexandria. Setting: Seven primary health care settings representing the seven zones of Alexandria governorate were selected randomly and included in the study. Subjects: The study comprised 386 patients attended the previously selected settings at least twice before the time of the study. Tools: Two tools were utilized for data collection; sociodemographic characteristics and health status structured interview schedule and patient satisfaction scale. Reliability test for the scale was done using Cronbach's Alpha test, the result of the test ranged between 0.717 and 0.967. The overall satisfaction was computed and divided into high, medium, and low satisfaction. Results: Age of the studied sample ranged between 19 and 62 years, more than half (54.2%) of them aged 40 to less than 60 years. More than half (52.8%) of the patients included in the study were diabetics, 39.1% of them were hypertensive, 19.2% had cardiovascular diseases, the rest of the sample had tumor, liver diseases, and orthopedic/neurological disorders (6.5%, 5.2% & 3.2%, respectively). The vast majority of the study group mentioned high satisfaction with overall service cost, environmental conditions, medical staff attitude and health education given at the PHC settings (87.8%, 90.7%, 86.3% & 90.9%, respectively), however, medium satisfaction was mostly reported concerning medical checkup procedures, follow-up data and referral system (41.2%, 28.5% & 28.9%, respectively). Score level of patient satisfaction with health services provided at the assessed Primary health care settings proved to be significantly associated with patients’ social status (P=0.003, X²=14.2), occupation (P=0.011, X²=11.2), and monthly income (P=0.039, X²=6.50). In addition, a significant association was observed between score level of satisfaction and type of illness (P=0.007, X²=9.366), type of medication (P=0.014, X²=9.033), prior knowledge about the health center (P=0.050, X²=3.346), and highly significant with the administrative zone (P=0.001, X²=55.294). Conclusion: The current study revealed that overall service cost, environmental conditions, staff attitude and health education at the assessed primary health care settings gained high patient satisfaction level, while, medical checkup procedures, follow-up, and referral system caused a medium level of satisfaction among assessed patients. Nevertheless, social status, occupation, monthly income, type of illness, type of medication and administrative zones are all factors influencing patient satisfaction with services provided at the health facilities.

Keywords: patient satisfaction, chronic illness, quality of health service, quality of service indicators

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Authors: Ahmedou Moulaye Idriss, Yahya Tfeil

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Medical imaging technology has become an indispensable tool in many branches of the biomedical, health area, and research and is vitally important for the training of professionals in these fields. It is not only about the tools, technologies, and knowledge provided but also about the community that this training project proposes. In order to be able to raise the level of anatomy teaching in the medical school of Nouakchott in Mauritania, it is necessary and even urgent to facilitate access to modern technology for African countries. The role of technology as a key driver of justifiable development has long been recognized. Anatomy is an essential discipline for the training of medical students; it is a key element for the training of medical specialists. The quality and results of the work of a young surgeon depend on his better knowledge of anatomical structures. The teaching of anatomy is difficult as the discipline is being neglected by medical students in many academic institutions. However, anatomy remains a vital part of any medical education program. When anatomy is presented in various planes medical students approve of difficulties in understanding. They do not increase their ability to visualize and mentally manipulate 3D structures. They are sometimes not able to correctly identify neighbouring or associated structures. This is the case when they have to make the identification of structures related to the caudate lobe when the liver is moved to different positions. In recent decades, some modern educational tools using digital sources tend to replace old methods. One of the main reasons for this change is the lack of cadavers in laboratories with poorly qualified staff. The emergence of increasingly sophisticated mathematical models, image processing, and visualization tools in biomedical imaging research have enabled sophisticated three-dimensional (3D) representations of anatomical structures. In this paper, we report our current experience in the Faculty of Medicine in Nouakchott Mauritania. One of our main aims is to create a local learning community in the fields of anatomy. The main technological platform used in this project is called 3D Slicer. 3D Slicer platform is an open-source application available for free for viewing, analysis, and interaction with biomedical imaging data. Using the 3D Slicer platform, we created from real medical images anatomical atlases of parts of the human body, including head, thorax, abdomen, liver, and pelvis, upper and lower limbs. Data were collected from several local hospitals and also from the website. We used MRI and CT-Scan imaging data from children and adults. Many different anatomy atlases exist, both in print and digital forms. Anatomy Atlas displays three-dimensional anatomical models, image cross-sections of labelled structures and source radiological imaging, and a text-based hierarchy of structures. Open and free online anatomical atlases developed by our anatomy laboratory team will be available to our students. This will allow pedagogical autonomy and remedy the shortcomings by responding more fully to the objectives of sustainable local development of quality education and good health at the national level. To make this work a reality, our team produced several atlases available in our faculty in the form of research projects.

Keywords: anatomy, education, medical imaging, three dimensional

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Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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Authors: Evgenia Iakovleva, Juha Koivisto, Pasi Karppinen, J. Inkinen, Mikko Alava

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Preventing the spread of infectious diseases throughout the worldwide is one of the most important tasks of modern health care. Infectious diseases not only account for one fifth of the deaths in the world, but also cause many pathological complications for the human health. Touch surfaces pose an important vector for the spread of infections by varying microorganisms, including antimicrobial resistant organisms. Further, antimicrobial resistance is reply of bacteria to the overused or inappropriate used of antibiotics everywhere. The biggest challenges in bacterial detection by existing methods are non-direct determination, long time of analysis, the sample preparation, use of chemicals and expensive equipment, and availability of qualified specialists. Therefore, a high-performance, rapid, real-time detection is demanded in rapid practical bacterial detection and to control the epidemiological hazard. Among the known methods for determining bacteria on the surfaces, Hyperspectral methods can be used as direct and rapid methods for microorganism detection on different kind of surfaces based on fluorescence without sampling, sample preparation and chemicals. The aim of this study was to assess the relevance of such systems to remote sensing of surfaces for microorganisms detection to prevent a global spread of infectious diseases. Bacillus subtilis and Escherichia coli with different concentrations (from 0 to 10x8 cell/100µL) were detected with hyperspectral camera using different filters as visible visualization of bacteria and background spots on the steel plate. A method of internal standards was applied for monitoring the correctness of the analysis results. Distances from sample to hyperspectral camera and light source are 25 cm and 40 cm, respectively. Each sample is optically imaged from the surface by hyperspectral imaging system, utilizing a JAI CM-140GE-UV camera. Light source is BeamZ FLATPAR DMX Tri-light, 3W tri-colour LEDs (red, blue and green). Light colors are changed through DMX USB Pro interface. The developed system was calibrated following a standard procedure of setting exposure and focused for light with λ=525 nm. The filter is ThorLabs KuriousTM hyperspectral filter controller with wavelengths from 420 to 720 nm. All data collection, pro-processing and multivariate analysis was performed using LabVIEW and Python software. The studied human eye visible and invisible bacterial stains clustered apart from a reference steel material by clustering analysis using different light sources and filter wavelengths. The calculation of random and systematic errors of the analysis results proved the applicability of the method in real conditions. Validation experiments have been carried out with photometry and ATP swab-test. The lower detection limit of developed method is several orders of magnitude lower than for both validation methods. All parameters of the experiments were the same, except for the light. Hyperspectral imaging method allows to separate not only bacteria and surfaces, but also different types of bacteria, such as Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. Developed method allows skipping the sample preparation and the use of chemicals, unlike all other microbiological methods. The time of analysis with novel hyperspectral system is a few seconds, which is innovative in the field of microbiological tests.

Keywords: Escherichia coli, Bacillus subtilis, hyperspectral imaging, microorganisms detection

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Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

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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: Daniel Dahis, Haim Azhari

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Noninvasive image-guided intracranial treatments using high intensity focused ultrasound (HIFU) are on the course of translation into clinical applications. They include, among others, tumor ablation, hyperthermia, and blood-brain-barrier (BBB) penetration. Since many of these procedures are associated with local temperature elevation, thermal monitoring is essential. MRI constitutes an imaging method with high spatial resolution and thermal mapping capacity. It is the currently leading modality for temperature guidance, commonly under the name MRgHIFU (magnetic-resonance guided HIFU). Nevertheless, MRI is a very expensive non-portable modality which jeopardizes its accessibility. Ultrasonic thermal monitoring, on the other hand, could provide a modular, cost-effective alternative with higher temporal resolution and accessibility. In order to assess the feasibility of ultrasonic brain thermal monitoring, this study investigated the usage of brain tissue attenuation coefficient (AC) temporal changes as potential estimators of thermal changes. Newton's law of cooling describes a temporal exponential decay behavior for the temperature of a heated object immersed in a relatively cold surrounding. Similarly, in the case of cerebral HIFU treatments, the temperature in the region of interest, i.e., focal zone, is suggested to follow the same law. Thus, it was hypothesized that the AC of the irradiated tissue may follow a temporal exponential behavior during cool down regime. Three ex-vivo bovine brain tissue specimens were inserted into plastic containers along with four thermocouple probes in each sample. The containers were placed inside a specially built ultrasonic tomograph and scanned at room temperature. The corresponding pixel-averaged AC was acquired for each specimen and used as a reference. Subsequently, the containers were placed in a beaker containing hot water and gradually heated to about 45ᵒC. They were then repeatedly rescanned during cool down using ultrasonic through-transmission raster trajectory until reaching about 30ᵒC. From the obtained images, the normalized AC and its temporal derivative as a function of temperature and time were registered. The results have demonstrated high correlation (R² > 0.92) between both the brain AC and its temporal derivative to temperature. This indicates the validity of the hypothesis and the possibility of obtaining brain tissue temperature estimation from the temporal AC thermal changes. It is important to note that each brain yielded different AC values and slopes. This implies that a calibration step is required for each specimen. Thus, for a practical acoustic monitoring of the brain, two steps are suggested. The first step consists of simply measuring the AC at normal body temperature. The second step entails measuring the AC after small temperature elevation. In face of the urging need for a more accessible thermal monitoring technique for brain treatments, the proposed methodology enables a cost-effective high temporal resolution acoustical temperature estimation during HIFU treatments.

Keywords: attenuation coefficient, brain, HIFU, image-guidance, temperature

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Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Christine F. Boos, Fernando M. Azevedo

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Electroencephalogram (EEG) is a record of the electrical activity of the brain that has many applications, such as monitoring alertness, coma and brain death; locating damaged areas of the brain after head injury, stroke and tumor; monitoring anesthesia depth; researching physiology and sleep disorders; researching epilepsy and localizing the seizure focus. Epilepsy is a chronic condition, or a group of diseases of high prevalence, still poorly explained by science and whose diagnosis is still predominantly clinical. The EEG recording is considered an important test for epilepsy investigation and its visual analysis is very often applied for clinical confirmation of epilepsy diagnosis. Moreover, this EEG analysis can also be used to help define the types of epileptic syndrome, determine epileptiform zone, assist in the planning of drug treatment and provide additional information about the feasibility of surgical intervention. In the context of diagnosis confirmation the analysis is made using long term EEG recordings with at least 24 hours long and acquired by a minimum of 24 electrodes in which the neurophysiologists perform a thorough visual evaluation of EEG screens in search of specific electrographic patterns called epileptiform discharges. Considering that the EEG screens usually display 10 seconds of the recording, the neurophysiologist has to evaluate 360 screens per hour of EEG or a minimum of 8,640 screens per long term EEG recording. Analyzing thousands of EEG screens in search patterns that have a maximum duration of 200 ms is a very time consuming, complex and exhaustive task. Because of this, over the years several studies have proposed automated methodologies that could facilitate the neurophysiologists’ task of identifying epileptiform discharges and a large number of methodologies used neural networks for the pattern classification. One of the differences between all of these methodologies is the type of input stimuli presented to the networks, i.e., how the EEG signal is introduced in the network. Five types of input stimuli have been commonly found in literature: raw EEG signal, morphological descriptors (i.e. parameters related to the signal’s morphology), Fast Fourier Transform (FFT) spectrum, Short-Time Fourier Transform (STFT) spectrograms and Wavelet Transform features. This study evaluates the application of these five types of input stimuli and compares the classification results of neural networks that were implemented using each of these inputs. The performance of using raw signal varied between 43 and 84% efficiency. The results of FFT spectrum and STFT spectrograms were quite similar with average efficiency being 73 and 77%, respectively. The efficiency of Wavelet Transform features varied between 57 and 81% while the descriptors presented efficiency values between 62 and 93%. After simulations we could observe that the best results were achieved when either morphological descriptors or Wavelet features were used as input stimuli.

Keywords: Artificial neural network, electroencephalogram signal, pattern recognition, signal processing

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

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Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

Abstract:

Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Qianwei Cheng, A. K. M. Mahbubur Rahman, Anis Sarker, Abu Bakar Siddik Nayem, Ovi Paul, Amin Ahsan Ali, M. Ashraful Amin, Ryosuke Shibasaki, Moinul Zaber

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Thomas Friedman, in his famous book, argued that the world in this 21st century is flat and will continue to be flatter. This is attributed to rapid globalization and the interdependence of humanity that engendered tremendous in-flow of human migration towards the urban spaces. In order to keep the urban environment sustainable, policy makers need to plan based on extensive analysis of the urban environment. With the advent of high definition satellite images, high resolution data, computational methods such as deep neural network analysis, and hardware capable of high-speed analysis; urban planning is seeing a paradigm shift. Legacy data on urban environments are now being complemented with high-volume, high-frequency data. However, the first step of understanding urban space lies in useful categorization of the space that is usable for data collection, analysis, and visualization. In this paper, we propose a pragmatic categorization method that is readily usable for machine analysis and show applicability of the methodology on a developing world setting. Categorization to plan sustainable urban spaces should encompass the buildings and their surroundings. However, the state-of-the-art is mostly dominated by classification of building structures, building types, etc. and largely represents the developed world. Hence, these methods and models are not sufficient for developing countries such as Bangladesh, where the surrounding environment is crucial for the categorization. Moreover, these categorizations propose small-scale classifications, which give limited information, have poor scalability and are slow to compute in real time. Our proposed method is divided into two steps-categorization and automation. We categorize the urban area in terms of informal and formal spaces and take the surrounding environment into account. 50 km × 50 km Google Earth image of Dhaka, Bangladesh was visually annotated and categorized by an expert and consequently a map was drawn. The categorization is based broadly on two dimensions-the state of urbanization and the architectural form of urban environment. Consequently, the urban space is divided into four categories: 1) highly informal area; 2) moderately informal area; 3) moderately formal area; and 4) highly formal area. In total, sixteen sub-categories were identified. For semantic segmentation and automatic categorization, Google’s DeeplabV3+ model was used. The model uses Atrous convolution operation to analyze different layers of texture and shape. This allows us to enlarge the field of view of the filters to incorporate larger context. Image encompassing 70% of the urban space was used to train the model, and the remaining 30% was used for testing and validation. The model is able to segment with 75% accuracy and 60% Mean Intersection over Union (mIoU). In this paper, we propose a pragmatic categorization method that is readily applicable for automatic use in both developing and developed world context. The method can be augmented for real-time socio-economic comparative analysis among cities. It can be an essential tool for the policy makers to plan future sustainable urban spaces.

Keywords: semantic segmentation, urban environment, deep learning, urban building, classification

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Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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Authors: Ainura Tursunalieva, Irene Hudson

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Continuous improvement of both the quality and safety of health care is an important goal in Australia and internationally. The intensive care unit (ICU) receives patients with a wide variety of and severity of illnesses. Accurately identifying patients at risk of developing complications or dying is crucial to increasing healthcare efficiency. Thus, it is essential for clinicians and researchers to have a robust framework capable of evaluating the risk profile of a patient. ICU scoring systems provide such a framework. The Acute Physiology and Chronic Health Evaluation III and the Simplified Acute Physiology Score II are ICU scoring systems frequently used for assessing the severity of acute illness. These scoring systems collect multiple risk factors for each patient including physiological measurements then render the assessment outcomes of individual risk factors into a single numerical value. A higher score is related to a more severe patient condition. Furthermore, the Mortality Probability Model II uses logistic regression based on independent risk factors to predict a patient’s probability of mortality. An important overlooked limitation of SAPS II and MPM II is that they do not, to date, include interaction terms between a patient’s vital signs. This is a prominent oversight as it is likely there is an interplay among vital signs. The co-existence of certain conditions may pose a greater health risk than when these conditions exist independently. One barrier to including such interaction terms in predictive models is the dimensionality issue as it becomes difficult to use variable selection. We propose an innovative scoring system which takes into account a dependence structure among patient’s vital signs, such as systolic and diastolic blood pressures, heart rate, pulse interval, and peripheral oxygen saturation. Copulas will capture the dependence among normally distributed and skewed variables as some of the vital sign distributions are skewed. The estimated dependence parameter will then be incorporated into the traditional scoring systems to adjust the points allocated for the individual vital sign measurements. The same dependence parameter will also be used to create an alternative copula-based model for predicting a patient’s probability of mortality. The new copula-based approach will accommodate not only a patient’s trajectories of vital signs but also the joint dependence probabilities among the vital signs. We hypothesise that this approach will produce more stable assessments and lead to more time efficient and accurate predictions. We will use two data sets: (1) 250 ICU patients admitted once to the Chui Regional Hospital (Kyrgyzstan) and (2) 37 ICU patients’ agitation-sedation profiles collected by the Hunter Medical Research Institute (Australia). Both the traditional scoring approach and our copula-based approach will be evaluated using the Brier score to indicate overall model performance, the concordance (or c) statistic to indicate the discriminative ability (or area under the receiver operating characteristic (ROC) curve), and goodness-of-fit statistics for calibration. We will also report discrimination and calibration values and establish visualization of the copulas and high dimensional regions of risk interrelating two or three vital signs in so-called higher dimensional ROCs.

Keywords: copula, intensive unit scoring system, ROC curves, vital sign dependence

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Irakli Gamkrelidze, David Shengelia, Giorgi Chichinadze, Tamara Tsutsunava, Giorgi Beridze, Tamara Tsamalashvili, Ketevan Tedliashvili, Irakli Javakhishvili

Abstract:

The Caucasus is situated between the Eurasian and Africa-Arabian plates and represents a component of the Mediterranean (Alpine-Himalayan) collision belt. The Loki crystalline massif crops out within one of the terranes of the Caucasus – Baiburt-Sevanian terrane. By the end of 2018, a digital geological map (1:50 000) of the Loki massif was compiled. The presented map is of great importance for the region since there is no large-scale geological map which reflects the present standards of the geological study of the massif up to the last time. The existing State Geological Map of the Loki massif is very outdated. A new map drown by using GIS (Geographic Information System) technology is loaded with multi-informative details that include: specified contours of geological units and separate tectonic scales, key mineral assemblages and facies of metamorphism, temperature conditions of metamorphism, ages of metamorphism events and the massif rocks, genetic-geodynamic types of magmatic rocks. Explanatory note, attached to the map includes the large specter of scientific information. It contains characterization of the geological setting, composition and petrogenetic and geodynamic models of the massif formation. To create a geological map of the Loki crystalline massif, appropriate methodologies were applied: a sampling of rocks, GIS technology-based mapping of geological units, microscopic description of the material, composition analysis of rocks, microprobe analysis of minerals and a new interpretation of obtained data. To prepare a digital version of the map the appropriated activities were held including the creation of a common database. Finally, the design was created that includes the elaboration of legend and the final visualization of the map. The results of the study presented in the explanatory note are given below. The autochthonous gneissose quartz diorites of normal alkalinity and sub-alkaline gabbro-diorites included in them belong to different phases of magmatism. They represent “igneous” granites corresponding to mixed mantle-crustal type granites. Four tectonic plates of the allochthonous metamorphic complex–Lower Gorastskali, Sapharlo–Lok-Jandari, Moshevani, and Lower Gorastskali differ from each other by structure and degree of metamorphism. The initial rocks of these plates are formed in different geodynamic conditions and during the Early Bretonian orogeny while overthrusting due to tectonic compression they form a thick tectonic sheet. The Lower Gorastskali overthrust sheet is a fragment of ophiolitic association corresponding to the Paleotethys oceanic crust. The protolith of the ophiolitic complex basites corresponds to the tholeiitic series of basalts. The Sapharlo–Lok-Jandari overthrust sheet is metapelites, metamorphosed in conditions of greenschist facies of regional metamorphism. The regional metamorphism of Moshevani overthrust sheet crystalline schists quartzites corresponds to a range from greenschist to hornfels facies. The “mélange” is built of rock fragments and blocks of above-mentioned overthrust sheets. Sub-alkaline and normal alkaline post-metamorphic granites of the Loki crystalline massif belong to “igneous” and rarely to “sialic” and “anorogenic” types of granites.

Keywords: digital geological map, 1:50 000 scale, crystalline massif, the caucasus

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Authors: Nisha Govender, Siju Senan, Zeti-Azura Hussein, Wickneswari Ratnam

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Jatropha curcas, a well-described bioenergy crop has been extensively accepted as future fuel need especially in tropical regions. Ideal planting material required for large-scale plantation is still lacking. Breeding programmes for improved J. curcas varieties are rendered difficult due to limitations in genetic diversity. Using a combined transcriptome and physiological data, we investigated the molecular and physiological differences in high and low yielding Jatropha curcas to address plausible heritable variations underpinning these differences, in regard to photosynthesis, a key metabolism affecting yield potentials. A total of 6 individual Jatropha plant from 4 accessions described as high and low yielding planting materials were selected from the Experimental Plot A, Universiti Kebangsaan Malaysia (UKM), Bangi. The inflorescence and shoots were collected for transcriptome study. For the physiological study, each individual plant (n=10) from the high and low yielding populations were screened for agronomic traits, chlorophyll content and stomatal patterning. The J. curcas transcriptomes are available under BioProject PRJNA338924 and BioSample SAMN05827448-65, respectively Each transcriptome was subjected to functional annotation analysis of sequence datasets using the BLAST2Go suite; BLASTing, mapping, annotation, statistical analysis and visualization Large-scale phenotyping of the number of fruits per plant (NFPP) and fruits per inflorescence (FPI) classified the high yielding Jatropha accessions with average NFPP =60 and FPI > 10, whereas the low yielding accessions yielded an average NFPP=10 and FPI < 5. Next generation sequencing revealed genes with differential expressions in the high yielding Jatropha relative to the low yielding plants. Distinct differences were observed in transcript level associated to photosynthesis metabolism. DEGs collection in the low yielding population showed comparable CAM photosynthetic metabolism and photorespiration, evident as followings: phosphoenolpyruvate phosphate translocator chloroplastic like isoform with 2.5 fold change (FC) and malate dehydrogenase (2.03 FC). Green leaves have the most pronounced photosynthetic activity in a plant body due to significant accumulation of chloroplast. In most plants, the leaf is always the dominant photosynthesizing heart of the plant body. Large number of the DEGS in the high-yielding population were found attributable to chloroplast and chloroplast associated events; STAY-GREEN chloroplastic, Chlorophyllase-1-like (5.08 FC), beta-amylase (3.66 FC), chlorophyllase-chloroplastic-like (3.1 FC), thiamine thiazole chloroplastic like (2.8 FC), 1-4, alpha glucan branching enzyme chloroplastic amyliplastic (2.6FC), photosynthetic NDH subunit (2.1 FC) and protochlorophyllide chloroplastic (2 FC). The results were parallel to a significant increase in chlorophyll a content in the high yielding population. In addition to the chloroplast associated transcript abundance, the TOO MANY MOUTHS (TMM) at 2.9 FC, which code for distant stomatal distribution and patterning in the high-yielding population may explain high concentration of CO2. The results were in agreement with the role of TMM. Clustered stomata causes back diffusion in the presence of gaps localized closely to one another. We conclude that high yielding Jatropha population corresponds to a collective function of C3 metabolism with a low degree of CAM photosynthetic fixation. From the physiological descriptions, high chlorophyll a content and even distribution of stomata in the leaf contribute to better photosynthetic efficiency in the high yielding Jatropha compared to the low yielding population.

Keywords: chlorophyll, gene expression, genetic variation, stomata

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Lassi Lehto, Jaakko Kahkonen, Juha Oksanen, Tapani Sarjakoski

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The use of raster-formatted data sets in geospatial analysis is increasing rapidly. At the same time, geographic data are being introduced into disciplines outside the traditional domain of geoinformatics, like climate change, intelligent transport, and immigration studies. These developments call for better methods to deliver raster geodata in an efficient and easy-to-use manner. Data cube technologies have traditionally been used in the geospatial domain for managing Earth Observation data sets that have strict requirements for effective handling of time series. The same approach and methodologies can also be applied in managing other types of geospatial data sets. A cloud service-based geodata cube, called GeoCubes Finland, has been developed to support online delivery and analysis of most important geospatial data sets with national coverage. The main target group of the service is the academic research institutes in the country. The most significant aspects of the GeoCubes data repository include the use of multiple resolution levels, cloud-optimized file structure, and a customized, flexible content access API. Input data sets are pre-processed while being ingested into the repository to bring them into a harmonized form in aspects like georeferencing, sampling resolutions, spatial subdivision, and value encoding. All the resolution levels are created using an appropriate generalization method, selected depending on the nature of the source data set. Multiple pre-processed resolutions enable new kinds of online analysis approaches to be introduced. Analysis processes based on interactive visual exploration can be effectively carried out, as the level of resolution most close to the visual scale can always be used. In the same way, statistical analysis can be carried out on resolution levels that best reflect the scale of the phenomenon being studied. Access times remain close to constant, independent of the scale applied in the application. The cloud service-based approach, applied in the GeoCubes Finland repository, enables analysis operations to be performed on the server platform, thus making high-performance computing facilities easily accessible. The developed GeoCubes API supports this kind of approach for online analysis. The use of cloud-optimized file structures in data storage enables the fast extraction of subareas. The access API allows for the use of vector-formatted administrative areas and user-defined polygons as definitions of subareas for data retrieval. Administrative areas of the country in four levels are available readily from the GeoCubes platform. In addition to direct delivery of raster data, the service also supports the so-called virtual file format, in which only a small text file is first downloaded. The text file contains links to the raster content on the service platform. The actual raster data is downloaded on demand, from the spatial area and resolution level required in each stage of the application. By the geodata cube approach, pre-harmonized geospatial data sets are made accessible to new categories of inexperienced users in an easy-to-use manner. At the same time, the multiresolution nature of the GeoCubes repository facilitates expert users to introduce new kinds of interactive online analysis operations.

Keywords: cloud service, geodata cube, multiresolution, raster geodata

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Authors: Abdulkadir Sarauta

Abstract:

Almost every type of industrial process involves the release of trace quantity of toxic organic and inorganic compound that up in receiving water bodies, this study was aimed at assessing the Persistent Organic Pollutant Level in Challawa River Basin of Kano State, Nigeria. And the research formed the basis of identifying the presence of PCBs and PAHs in receiving water bodies in the study area, assessing the PCBs and PAHs concentration in receiving water body of Challawa system, evaluate the concentration level of PCBs and PAHs in fishes in the study area, determine the concentration level of PCBs and PAHs in crops irrigated in the study area as well as compare the concentration of PCBs and PAHs with the acceptable limit set by Nigerian, EU, U.S and WHO standard. Data were collected using reconnaissance survey, site inspection, field survey, laboratory experiment as well as secondary data source. A total of 78 samples were collected through stratified systematic random sampling (i.e., 26 samples for each of water, crops and fish) three sampling points were chosen and designated A, B and C along the stretch of the river (i.e. up, middle, and downstream) from Yan Danko Bridge to Tambirawa bridge. The result shows that the Polychlorinated biphenyls (PCBs) was not detected while, polycyclic aromatic hydrocarbons (PAHs) was detected in the whole samples analysed at the trench of Challawa River basin in order to assess the contribution of human activities to global environmental pollution. The total concentrations of ΣPAH and ΣPCB ranges between 0.001 to 0.087mg/l and 0.00 to 0.00mg/l of water samples While, crops samples ranges between 2.0ppb to 8.1ppb and fish samples ranges from 2.0 to 6.7ppb.The whole samples are polluted because most of the parameters analyzed exceed the threshold limits set by WHO, Nigerian, U.S and EU standard. The analytical results revealed that some chemicals are present in water, crops and fishes are significantly very high at Zamawa village which is very close to Challawa industrial estate and also is main effluent discharge point and drinking water around study area is not potable for consumption. Analysis of Variance was obtained by Bartlett’s test performance. There is only significant difference in water because the P < 0.05 level of significant, But there is no difference in crops concentration they have the same performance, likes wise in the fishes. It is said to be of concern to health hazard which will increase incidence of tumor related diseases such as skin, lungs, bladder, gastrointestinal cancer, this show there is high failure of pollution abatement measures in the area. In conclusion, it can be said that industrial activities and effluent has impact on Challawa River basin and its environs especially those that are living in the immediate surroundings. Arising from the findings of this research some recommendations were made the industries should treat their liquid properly by installing modern treatment plants.

Keywords: Challawa River Basin, organic, persistent, pollutant

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Authors: Jiaying Zhang, Xin Mu, Chang Ni, Jeff L. Zhang

Abstract:

Magnetic resonance elastography (MRE) non-invasively assesses tissue elastic properties, such as shear modulus, by measuring tissue’s displacement in response to mechanical waves. The estimated metrics on tissue elasticity or stiffness have been shown to be valuable for monitoring physiologic or pathophysiologic status of tissue, such as a tumor or fatty liver. To quantify tissue shear modulus from MRE-acquired displacements (essentially an inverse problem), multiple approaches have been proposed, including Local Frequency Estimation (LFE) and Direct Inversion (DI). However, one common problem with these methods is that the estimates are severely noise-sensitive due to either the inverse-problem nature or noise propagation in the pixel-by-pixel process. With the advent of deep learning (DL) and its promise in solving inverse problems, a few groups in the field of MRE have explored the feasibility of using DL methods for quantifying shear modulus from MRE data. Most of the groups chose to use real MRE data for DL model training and to cut training images into smaller patches, which enriches feature characteristics of training data but inevitably increases computation time and results in outcomes with patched patterns. In this study, simulated wave images generated by Finite Differential Time Domain (FDTD) simulation are used for network training, and U-Net is used to extract features from each training image without cutting it into patches. The use of simulated data for model training has the flexibility of customizing training datasets to match specific applications. The proposed method aimed to estimate tissue shear modulus from MRE data with high robustness to noise and high model-training efficiency. Specifically, a set of 3000 maps of shear modulus (with a range of 1 kPa to 15 kPa) containing randomly positioned objects were simulated, and their corresponding wave images were generated. The two types of data were fed into the training of a U-Net model as its output and input, respectively. For an independently simulated set of 1000 images, the performance of the proposed method against DI and LFE was compared by the relative errors (root mean square error or RMSE divided by averaged shear modulus) between the true shear modulus map and the estimated ones. The results showed that the estimated shear modulus by the proposed method achieved a relative error of 4.91%±0.66%, substantially lower than 78.20%±1.11% by LFE. Using simulated data, the proposed method significantly outperformed LFE and DI in resilience to increasing noise levels and in resolving fine changes of shear modulus. The feasibility of the proposed method was also tested on MRE data acquired from phantoms and from human calf muscles, resulting in maps of shear modulus with low noise. In future work, the method’s performance on phantom and its repeatability on human data will be tested in a more quantitative manner. In conclusion, the proposed method showed much promise in quantifying tissue shear modulus from MRE with high robustness and efficiency.

Keywords: deep learning, magnetic resonance elastography, magnetic resonance imaging, shear modulus estimation

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

Abstract:

Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

Procedia PDF Downloads 125

Authors: Dhekra Khazri, Hakim Gabtni

Abstract:

Because of Sidi Bouzid water table overexploitation, this study aims at integrating geophysical methods to determinate aquifers geometry assessing their geological situation and geophysical characteristics. However in highly tectonic zones controlled by Atlassic structural features with NE-SW major directions (central Tunisia), Bouguer gravimetric responses of some areas can be as much dominated by the regional structural tendency, as being non-identified or either defectively interpreted such as the case of Sidi Bouzid basin. This issue required a residual gravity anomaly elaboration isolating the Sidi Bouzid basin gravity response ranging between -8 and -14 mGal and crucial for its aquifers geometry characterization. Several gravity techniques helped constructing the Sidi Bouzid basin's residual gravity anomaly, such as Upwards continuation compared to polynomial regression trends and power spectrum analysis detecting deep basement sources at (3km), intermediate (2km) and shallow sources (1km). A 3D Euler Deconvolution was also performed detecting deepest accidents trending NE-SW, N-S and E-W with depth values reaching 5500 m and delineating the main outcropping structures of the study area. Further gravity treatments highlighted the subsurface geometry and structural features of Sidi Bouzid basin over Horizontal and vertical gradient, and also filters based on them such as Tilt angle and Source Edge detector locating rooted edges or peaks from potential field data detecting a new E-W lineament compartmentalizing the Sidi Bouzid gutter into two unequally residual anomaly and subsiding domains. This subsurface morphology is also detected by the used 2D seismic reflection sections defining the Sidi Bouzid basin as a deep gutter within a tectonic set of negative flower structures, and collapsed and tilted blocks. Furthermore, these structural features were confirmed by forward gravity modeling process over several modeled residual gravity profiles crossing the main area. Sidi Bouzid basin (central Tunisia) is also of a big interest cause of the unknown total thickness and the undefined substratum of its siliciclastic Tertiary package, and its aquifers unbounded structural subsurface features and deep accidents. The Combination of geological, hydrogeological and geophysical methods is then of an ultimate need. Therefore, a geophysical methods integration based on gravity survey supporting available seismic data through forward gravity modeling, enhanced lateral and vertical extent definition of the basin's complex sedimentary fill via 3D gravity models, improved depth estimation by a depth to basement modeling approach, and provided 3D isochronous seismic mapping visualization of the basin's Tertiary complex refining its geostructural schema. A subsurface basin geomorphology mapping, over an ultimate matching between the basin's residual gravity map and the calculated theoretical signature map, was also displayed over the modeled residual gravity profiles. An ultimate multidisciplinary geophysical study of the Sidi Bouzid basin aquifers can be accomplished via an aeromagnetic survey and a 4D Microgravity reservoir monitoring offering temporal tracking of the target aquifer's subsurface fluid dynamics enhancing and rationalizing future groundwater exploitation in this arid area of central Tunisia.

Keywords: aquifer geometry, geophysics, 3D gravity modeling, improved depths, source edge detector

Procedia PDF Downloads 256

Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

Abstract:

Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

Procedia PDF Downloads 107

Authors: Danyi Wang, Andrew Schriefer, Dennis O'Rourke, Brajendra Kumar, Yang Liu, Fei Zhong, Juergen Scheuenpflug, Zheng Feng

Abstract:

Purpose: It has been recognized that the microbiome plays critical roles in disease pathogenesis, including cancer, autoimmune disease, and multiple sclerosis. To develop a clinical-grade assay for exploring microbiome-derived clinical biomarkers across disease areas, a two-phase approach is implemented. 1) Identification of the optimal sample preparation reagents using pre-mixed bacteria and healthy donor stool samples coupled with proprietary Sigma-Aldrich® bioinformatics solution. 2) Exploratory analysis of patient samples for enabling precision medicine. Study Procedure: In phase 1 study, we first compared the 16S sequencing results of two ATCC® microbiome standards (MSA 2002 and MSA 2003) across five different extraction kits (Kit A, B, C, D & E). Both microbiome standards samples were extracted in triplicate across all extraction kits. Following isolation, DNA quantity was determined by Qubit assay. DNA quality was assessed to determine purity and to confirm extracted DNA is of high molecular weight. Bacterial 16S ribosomal ribonucleic acid (rRNA) amplicons were generated via amplification of the V3/V4 hypervariable region of the 16S rRNA. Sequencing was performed using a 2x300 bp paired-end configuration on the Illumina MiSeq. Fastq files were analyzed using the Sigma-Aldrich® Microbiome Platform. The Microbiome Platform is a cloud-based service that offers best-in-class 16S-seq and WGS analysis pipelines and databases. The Platform and its methods have been extensively benchmarked using microbiome standards generated internally by MilliporeSigma and other external providers. Data Summary: The DNA yield using the extraction kit D and E is below the limit of detection (100 pg/µl) of Qubit assay as both extraction kits are intended for samples with low bacterial counts. The pre-mixed bacterial pellets at high concentrations with an input of 2 x106 cells for MSA-2002 and 1 x106 cells from MSA-2003 were not compatible with the kits. Among the remaining 3 extraction kits, kit A produced the greatest yield whereas kit B provided the least yield (Kit-A/MSA-2002: 174.25 ± 34.98; Kit-A/MSA-2003: 179.89 ± 30.18; Kit-B/MSA-2002: 27.86 ± 9.35; Kit-B/MSA-2003: 23.14 ± 6.39; Kit-C/MSA-2002: 55.19 ± 10.18; Kit-C/MSA-2003: 35.80 ± 11.41 (Mean ± SD)). Also, kit A produced the greatest yield, whereas kit B provided the least yield. The PCoA 3D visualization of the Weighted Unifrac beta diversity shows that kits A and C cluster closely together while kit B appears as an outlier. The kit A sequencing samples cluster more closely together than both the other kits. The taxonomic profiles of kit B have lower recall when compared to the known mixture profiles indicating that kit B was inefficient at detecting some of the bacteria. Conclusion: Our data demonstrated that the DNA extraction method impacts DNA concentration, purity, and microbial communities detected by next-generation sequencing analysis. Further microbiome analysis performance comparison of using healthy stool samples is underway; also, colorectal cancer patients' samples will be acquired for further explore the clinical utilities. Collectively, our comprehensive qualification approach, including the evaluation of optimal DNA extraction conditions, the inclusion of positive controls, and the implementation of a robust qualified bioinformatics pipeline, assures accurate characterization of the microbiota in a complex matrix for deciphering the deep biology and enabling precision medicine.

Keywords: 16S rRNA sequencing, analytical validation, bioinformatics pipeline, metagenomics

Procedia PDF Downloads 129

Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

Abstract:

Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

Procedia PDF Downloads 103