Search results for: lung segmentation

Authors: Libing Zhu, Waichung Chen, Kwaicing Lo, Lei Li

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Background: Tian Jiu Therapy (a medicinal vesiculation therapy according to traditional Chinese medicine theory) in San Fu Days (the three hottest days in a year is calculated by the Chinese ancient calendar) is widely used by patients with chronic asthma in China although from modern medicine perspective there is insufficient evidence of its effectiveness and safety issues. We investigated the efficacy and safety of Tian Jiu Therapy compared with placebo in patients with chronic asthma. Methods: Patients with chronic asthma were randomly assigned to Tian Jiu treatment group (n=165), placebo control group (n=158). Registered Chinese Medicine practitioners, in Orthopedics-Traumatology, Acupuncture, and Tui-na Clinical Centre for Teaching and Research, School of Chinese Medicine, The University of Hong Kong, administered Tian Jiu Therapy and placebo treatment in 3 times over 2 months. Patients completed questionnaires and lung function test before treatment and after treatment, 3, 6, 9, and 11 months, respectively. The primary outcome was the no of asthma-related sub-healthy symptoms and the percentage of patients with twenty-three symptoms. Results: 451 patients were recruited totally, 111 patients refused or did not participate according the appointment time and 17 did not meet the inclusion criteria. Consequently, 323 of eligible patients were enrolled. There was nothing difference between Tian Jiu Therapy group and placebo control group at the end of all treatments neither primary nor secondary outcomes. While Tian Jiu Therapy as compared with placebo significantly reduced the percentage of participants who are susceptible waken up by asthma symptoms from 27% to 14% at 2nd follow-up (P < 0.05). Similarly, Tian Jiu Therapy significantly reduced the proportion of participants who had the symptom of running nose and sneezing before onset from 18% to 8% at 2nd follow-up (P < 0.05). Additionally, Tian Jiu Therapy significantly reduced the level of asthma, the proportion of participants who don’t need to processed during asthma attack increased from 6% to 15% at 1st follow-up and 0% to 7% at 3rd follow-up (P < 0.05). Improvements also occurred with Tian Jiu Therapy group, it reduced the proportion of participants who were spontaneously sweating at 3rd follow up and diarrhea after intake of oily food at 4th follow-up (P < 0.05). Conclusion: When added to a regimen of foundational therapy for chronic asthma participants, Tian Jiu Therapy further reduced the need for medications to control asthma, improved the quality of participants’ life, and significantly reduced the level of asthma. What is more, this benefit seems to have an accumulative effect over time was in accordance with the TCM theory of 'winter disease is being cured in summer'.

Keywords: asthma, Tian Jiu Therapy, San Fu Days, triaditional Chinese medicine, clinical trial

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Authors: Malek Makki

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The main purpose of this research study is to assist non-profit organizations (NPOs) to better segment a group of least developing countries and to optimally target the most needier areas, so that the provided aids make positive and lasting differences. We applied international marketing and strategy approaches to segment a sub-group of candidates among a group of 151 countries identified by the UN-G77 list, and furthermore, we point out the areas of priorities. We use reliable and well known criteria on the basis of economics, geography, demography and behavioral. These criteria can be objectively estimated and updated so that a follow-up can be performed to measure the outcomes of any program. We selected 12 socio-economic criteria that complement each other: GDP per capita, GDP growth, industry value added, export per capita, fragile state index, corruption perceived index, environment protection index, ease of doing business index, global competitiveness index, Internet use, public spending on education, and employment rate. A weight was attributed to each variable to highlight the relative importance of each criterion within the country. Care was taken to collect the most recent available data from trusted well-known international organizations (IMF, WB, WEF, and WTO). Construct of equivalence was carried out to compare the same variables across countries. The combination of all these weighted estimated criteria provides us with a global index that represents the level of development per country. An absolute index that combines wars and risks was introduced to exclude or include a country on the basis of conflicts and a collapsing state. The final step applied to the included countries consists of a benchmarking method to select the segment of countries and the percentile of each criterion. The results of this study allowed us to exclude 16 countries for risks and security. We also excluded four countries because they lack reliable and complete data. The other countries were classified per percentile thru their global index, and we identified the needier and the areas where aids are highly required to help any NPO to prioritize the area of implementation. This new concept is based on defined, actionable, accessible and accurate variables by which NPO can implement their program and it can be extended to profit companies to perform their corporate social responsibility acts.

Keywords: developing countries, international marketing, non-profit organization, segmentation

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Authors: Abdolreza Farhadian, Anh Phan, Zahra Taheri Rizi, Elaheh Sadeh

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The utilization of solidified gas technology based on hydrates exhibits considerable promise for carbon capture, storage, and natural gas transportation applications. The pivotal factor impeding the industrial implementation of hydrates lies in the need for efficient and non-foaming promoters. In this study, a biosurfactant with sulfonate, amide, and carboxyl groups (BS) was synthesized as a methane hydrate formation promoter, replicating the chemical characteristics of amino acids and sodium dodecyl sulfate (SDS). The synthesis of BS follows a simple, three-step process that is amenable to industrial scale production. The first two steps of the process are solvent-free, which helps reduce potential environmental impacts and makes scaling up more feasible. Additionally, the final step utilizes a water-isopropanol mixture, which is an easily accessible and cost-effective solvent system for large-scale production. High-pressure autoclave experiments demonstrated a significant enhancement in methane hydrate formation kinetics with low BS concentrations. 50 ppm of BS yielded a maximum water-to-hydrate conversion of 66.9%, equivalent to a storage capacity of 119.9 v/v in distilled water. With increasing BS concentration to 500 ppm, the conversion degree and storage capacity reached 97% and 162.6 v/v, respectively. Molecular dynamic simulation revealed that BS molecules acted as collectors for methane molecules, augmenting hydrate growth rate and increasing the number of hydrate cavities. Additionally, BS demonstrated a biodegradability exceeding 60% within 28 days. Toxicity assessments confirmed BS's biocompatibility, with cell viability above 70% for skin and lung cells at concentrations up to 160 and 80 µg/mL, respectively. BS showed significant potential as an environmentally friendly alternative to synthetic surfactants like SDS for methane storage. These findings suggest that the synthesis of effective, such as BS, holds promise for diverse applications, including seawater desalination, carbon capture, and gas storage. Acknowledgments This study was funded by Russian Science Foundation according to the research project № 24-73-10069.

Keywords: solidified methane, gas storage, gas hydrates, green surfactant, gas hydrate promoter, computational simulation, sustainability

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Authors: Akimitsu Kugimiya, Kouhei Iwato, Toru Saito, Jiro Kohda, Yasuhisa Nakano, Yu Takano

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The measurement of amino acid content is reported to be useful for the diagnosis of several types of diseases, including lung cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, and diabetes. The conventional detection methods for amino acid are high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS), but they have several drawbacks as the equipment is cumbersome and the techniques are costly in terms of time and costs. In contrast, biosensors and biosensing methods provide more rapid and facile detection strategies that use simple equipment. The authors have reported a novel approach for the detection of each amino acid that involved the use of aminoacyl-tRNA synthetase (aaRS) as a molecular recognition element because aaRS is expected to a selective binding ability for corresponding amino acid. The consecutive enzymatic reactions used in this study are as follows: aaRS binds to its cognate amino acid and releases inorganic pyrophosphate. Hydrogen peroxide (H₂O₂) was produced by the enzyme reactions of inorganic pyrophosphatase and pyruvate oxidase. The Trinder’s reagent was added into the reaction mixture, and the absorbance change at 556 nm was measured using a microplate reader. In this study, an amino acid-sensing method using histidyl-tRNA synthetase (HisRS; histidine-specific aaRS) as molecular recognition element in combination with the Trinder’s reagent spectrophotometric method was developed. The quantitative performance and selectivity of the method were evaluated, and the optimal enzyme reaction and detection conditions were determined. The authors developed a simple and rapid method for detecting histidine with a combination of enzymatic reaction and spectrophotometric detection. In this study, HisRS was used to detect histidine, and the reaction and detection conditions were optimized for quantitation of these amino acids in the ranges of 1–100 µM histidine. The detection limits are sufficient to analyze these amino acids in biological fluids. This work was partly supported by Hiroshima City University Grant for Special Academic Research (General Studies).

Keywords: amino acid, aminoacyl-tRNA synthetase, biosensing, enzyme reaction

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Authors: R. Nandhini, Gaurab Mudbhari

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Ranging from the field of health care to self-driving cars, machine learning and deep learning algorithms have revolutionized the field with the proper utilization of images and visual-oriented data. Segmentation, regression, classification, clustering, dimensionality reduction, etc., are some of the Machine Learning tasks that helped Machine Learning and Deep Learning models to become state-of-the-art models for the field where images are key datasets. Among these tasks, classification and clustering are essential but difficult because of the intricate and high-dimensional characteristics of image data. This finding examines and assesses advanced techniques in supervised classification and unsupervised clustering for image datasets, emphasizing the relative efficiency of Convolutional Neural Networks (CNNs), Vision Transformers (ViTs), Deep Embedded Clustering (DEC), and self-supervised learning approaches. Due to the distinctive structural attributes present in images, conventional methods often fail to effectively capture spatial patterns, resulting in the development of models that utilize more advanced architectures and attention mechanisms. In image classification, we investigated both CNNs and ViTs. One of the most promising models, which is very much known for its ability to detect spatial hierarchies, is CNN, and it serves as a core model in our study. On the other hand, ViT is another model that also serves as a core model, reflecting a modern classification method that uses a self-attention mechanism which makes them more robust as this self-attention mechanism allows them to lean global dependencies in images without relying on convolutional layers. This paper evaluates the performance of these two architectures based on accuracy, precision, recall, and F1-score across different image datasets, analyzing their appropriateness for various categories of images. In the domain of clustering, we assess DEC, Variational Autoencoders (VAEs), and conventional clustering techniques like k-means, which are used on embeddings derived from CNN models. DEC, a prominent model in the field of clustering, has gained the attention of many ML engineers because of its ability to combine feature learning and clustering into a single framework and its main goal is to improve clustering quality through better feature representation. VAEs, on the other hand, are pretty well known for using latent embeddings for grouping similar images without requiring for prior label by utilizing the probabilistic clustering method.

Keywords: machine learning, deep learning, image classification, image clustering

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Authors: Sultan Mahmud, Qamar Zaman, Travis Esau, Young Chang

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Strawberry powdery mildew (PM) is a serious disease that has a significant impact on strawberry production. Field scouting is still a major way to find PM disease, which is not only labor intensive but also almost impossible to monitor disease severity. To reduce the loss caused by PM disease and achieve faster automatic detection of the disease, this paper proposes an approach for detection of the disease, based on image texture and classified with support vector machines (SVMs) and k-nearest neighbors (kNNs). The methodology of the proposed study is based on image processing which is composed of five main steps including image acquisition, pre-processing, segmentation, features extraction and classification. Two strawberry fields were used in this study. Images of healthy leaves and leaves infected with PM (Sphaerotheca macularis) disease under artificial cloud lighting condition. Colour thresholding was utilized to segment all images before textural analysis. Colour co-occurrence matrix (CCM) was introduced for extraction of textural features. Forty textural features, related to a physiological parameter of leaves were extracted from CCM of National television system committee (NTSC) luminance, hue, saturation and intensity (HSI) images. The normalized feature data were utilized for training and validation, respectively, using developed classifiers. The classifiers have experimented with internal, external and cross-validations. The best classifier was selected based on their performance and accuracy. Experimental results suggested that SVMs classifier showed 98.33%, 85.33%, 87.33%, 93.33% and 95.0% of accuracy on internal, external-I, external-II, 4-fold cross and 5-fold cross-validation, respectively. Whereas, kNNs results represented 90.0%, 72.00%, 74.66%, 89.33% and 90.3% of classification accuracy, respectively. The outcome of this study demonstrated that SVMs classified PM disease with a highest overall accuracy of 91.86% and 1.1211 seconds of processing time. Therefore, overall results concluded that the proposed study can significantly support an accurate and automatic identification and recognition of strawberry PM disease with SVMs classifier.

Keywords: powdery mildew, image processing, textural analysis, color co-occurrence matrix, support vector machines, k-nearest neighbors

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Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

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Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

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Authors: Carolina Silva Ansélmo

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Airports are demand-generating poles that affect the flow of traffic around them. The airport access system must be fast, convenient, and adequately planned, considering its potential users. An airport with good ground access conditions can provide the user with a more satisfactory access experience. When several transport options are available, service providers must understand users' preferences and the expected quality of service. The present study focuses on airport access in a comparative scenario between bus, private vehicle, subway, taxi and urban mobility transport applications to São Paulo/Guarulhos International Airport. The objectives are (i) to identify the factors that influence the choice, (ii) to measure Willingness to Pay (WTP), and (iii) to estimate the market share for each modal. The applied method was Adaptive Choice-based Conjoint Analysis (ACBC) technique using Sawtooth Software. Conjoint analysis, rooted in Utility Theory, is a survey technique that quantifies the customer's perceived utility when choosing alternatives. Assessing user preferences provides insights into their priorities for product or service attributes. An additional advantage of conjoint analysis is its requirement for a smaller sample size compared to other methods. Furthermore, ACBC provides valuable insights into consumers' preferences, willingness to pay, and market dynamics, aiding strategic decision-making to provide a better customer experience, pricing, and market segmentation. In the present research, the ACBC questionnaire had the following variables: (i) access time to the boarding point, (ii) comfort in the vehicle, (iii) number of travelers together, (iv) price, (v) supply power, and (vi) type of vehicle. The case study questionnaire reached 213 valid responses considering the scenario of access from the São Paulo city center to São Paulo/Guarulhos International Airport. As a result, the price and the number of travelers are the most relevant attributes for the sample when choosing airport access. The market share of the selection is mainly urban mobility transport applications, followed by buses, private vehicles, taxis and subways.

Keywords: adaptive choice-based conjoint analysis, ground access to airport, market share, willingness to pay

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Authors: Dumont Maxime, Correia Carlos, Sauvage Jean-François, Schwartz Noah, Gray Morgan

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Context: The concept of the segmented telescope is unavoidable to build extremely large telescopes (ELT) in the quest for spatial resolution, but it also allows one to fit a large telescope within a reduced volume of space (JWST) or into an even smaller volume (Standard Cubesat). Cubesats have tight constraints on the computational burden available and the small payload volume allowed. At the same time, they undergo thermal gradients leading to large and evolving optical aberrations. The pupil segmentation comes nevertheless with an obvious difficulty: to co-phase the different segments. The CubeSat constraints prevent the use of a dedicated wavefront sensor (WFS), making the focal-plane images acquired by the science detector the most practical alternative. Yet, one of the challenges for the wavefront sensing is the non-linearity between the image intensity and the phase aberrations. Plus, for Earth observation, the object is unknown and unrepeatable. Recently, several studies have suggested Neural Networks (NN) for wavefront sensing; especially convolutional NN, which are well known for being non-linear and image-friendly problem solvers. Aims: We study in this paper the prospect of using NN to measure the phasing aberrations of a segmented pupil from the focal-plane image directly without a dedicated wavefront sensing. Methods: In our application, we take the case of a deployable telescope fitting in a CubeSat for Earth observations which triples the aperture size (compared to the 10cm CubeSat standard) and therefore triples the angular resolution capacity. In order to reach the diffraction-limited regime in the visible wavelength, typically, a wavefront error below lambda/50 is required. The telescope focal-plane detector, used for imaging, will be used as a wavefront-sensor. In this work, we study a point source, i.e. the Point Spread Function [PSF] of the optical system as an input of a VGG-net neural network, an architecture designed for image regression/classification. Results: This approach shows some promising results (about 2nm RMS, which is sub lambda/50 of residual WFE with 40-100nm RMS of input WFE) using a relatively fast computational time less than 30 ms which translates a small computation burder. These results allow one further study for higher aberrations and noise.

Keywords: wavefront sensing, deep learning, deployable telescope, space telescope

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

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The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

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Authors: C. Román, M. Guevara, P. Salas, D. Duclap, J. Houenou, C. Poupon, J. F. Mangin, P. Guevara

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Diffusion Magnetic Resonance Imaging (dMRI) allows the non-invasive study of human brain white matter. From diffusion data, it is possible to reconstruct fiber trajectories using tractography algorithms. Our previous work consists in an automatic method for the identification of short association bundles of the superficial white matter (SWM), based on a whole brain inter-subject hierarchical clustering applied to a HARDI database. The method finds representative clusters of similar fibers, belonging to a group of subjects, according to a distance measure between fibers, using a non-linear registration (DTI-TK). The algorithm performs an automatic labeling based on the anatomy, defined by a cortex mesh parcelated with FreeSurfer software. The clustering was applied to two independent groups of 37 subjects. The clusters resulting from both groups were compared using a restrictive threshold of mean distance between each pair of bundles from different groups, in order to keep reproducible connections. In the left hemisphere, 48 reproducible bundles were found, while 43 bundles where found in the right hemisphere. An inter-hemispheric bundle correspondence was then applied. The symmetric horizontal reflection of the right bundles was calculated, in order to obtain the position of them in the left hemisphere. Next, the intersection between similar bundles was calculated. The pairs of bundles with a fiber intersection percentage higher than 50% were considered similar. The similar bundles between both hemispheres were fused and symmetrized. We obtained 30 common bundles between hemispheres. An atlas was created with the resulting bundles and used to segment 78 new subjects from another HARDI database, using a distance threshold between 6-8 mm according to the bundle length. Finally, a laterality index was calculated based on the bundle volume. Seven bundles of the atlas presented right laterality (IP_SP_1i, LO_LO_1i, Op_Tr_0i, PoC_PoC_0i, PoC_PreC_2i, PreC_SM_0i, y RoMF_RoMF_0i) and one presented left laterality (IP_SP_2i), there is no tendency of lateralization according to the brain region. Many factors can affect the results, like tractography artifacts, subject registration, and bundle segmentation. Further studies are necessary in order to establish the influence of these factors and evaluate SWM laterality.

Keywords: dMRI, hierarchical clustering, lateralization index, tractography

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Authors: Walid Al-Qerem, Ruba Zumot

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Background: The rise of obesity among children and adolescents remains a primary challenge for healthcare providers globally and in the Middle East. The aim of the present study is to determine the prevalence of obesity among 5-20 years old Jordanians based on CDC criteria. Method: A total of 5722 Jordanians (37% males; 63% females) aged 5-20 years data were retrieved from the Jordanian Ministry of Health electronic database (Hakeem). As per the CDC selection criteria, the chosen data pertains exclusively to healthy Jordanian children and adolescents who are medically sound, not suffering from health conditions, and not undergoing any treatments that could hinder normal growth patterns, such as severe infection, chronic kidney disease (CKD), Down’s syndrome, attention deficit hyperactivity disorder, cancer, heart disease, lung disease, cystic fibrosis, Crohn’s disease, type 1 diabetes, hormonal disturbances, any stress-related conditions, hormonal therapy such as corticosteroids, Growth hormones (GHS) or gonadotropin-releasing hormone agonists, insulin, and amphetamines or any other stimulants. In addition, participants with missing or invalid data values for anthropometric measurements were excluded from the study. Weight for age and body mass index for age were analyzed comparatively for Jordanian children and adolescents against the international growth standards. The Z-score for each record was computed based on CDC equations. As per CDC classifications, BMI for age percentiles, values ≥85th and < 95th are classified as overweight, and value at ≥ 95th is classified as obesity. Results: The average age of the evaluated sample was 12.33 ±4.39 years (10.79 ±3.39 for males and 13.23 ± 4.66 for females). The mean weight for males and females were 33.16±14.17 Kg and 133.54±17.17 cm for males, 43.86 ±18.82 Kg, and 142.19±18.35 for females, while for BMI the mean was for boys and girls 17.81±3.88 and 20.52±5.03 respectively. The results indicated that based on CDC criteria, 8.9% of males were classified as children/adolescents with overweight, and 9.7% were classified as children/adolescents with obesity, while in females, 17.8% were classified as children/adolescents with overweight and 10.2% were classified as children/adolescents with obesity. Discussion: The high prevalence of obesity reported in the present study emphasizes the importance of applying different strategies to prevent childhood obesity, including encouraging physical activity, promoting healthier food options, and behavioral changes. Conclusion: The results presented in this study indicated the high prevalence of overweight/obesity among Jordanian adolescents and children, which must be tagged by healthcare planners and providers.

Keywords: CDC, obesity, childhood, Jordan

Procedia PDF Downloads 57

Authors: Sung-Hee Nam, Kwang-Gill Lee, You-Young Jo, HaeYong Kweon

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and From ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores. Yamanaka reported that although a complete fruiting body can be produced under optimal culture conditions, it should be regarded as synnemata because it does not develop into an ascoma bearing ascospores.

Keywords: paecilomyces tenuipes, entomopathogenic fungi, silkworm larva, bombyx mori

Procedia PDF Downloads 321

Authors: Jiaxin Shi, Kaifeng Hao, Qingfan An, Zeng Peng

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Due to a lack of data sources and data processing techniques, it has always been difficult to quantify public space quality, which includes urban construction quality and how it is perceived by people, especially in large urban areas. This study proposes a quantitative research method based on the consideration of emotional health and physical health of the built environment. It highlights the low quality of public areas in Tianjin, China, where there are many negative elements. Deep learning technology is then used to measure how effectively people perceive urban areas. First, this work suggests a deep learning model that might simulate how people can perceive the quality of urban construction. Second, we perform semantic segmentation on street images to identify visual elements influencing scene perception. Finally, this study correlated the scene perception score with the proportion of visual elements to determine the surrounding environmental elements that influence scene perception. Using a small-scale labeled Tianjin street view data set based on transfer learning, this study trains five negative spatial discriminant models in order to explore the negative space distribution and quality improvement of urban streets. Then it uses all Tianjin street-level imagery to make predictions and calculate the proportion of negative space. Visualizing the spatial distribution of negative space along the Tianjin Inner Ring Road reveals that the negative elements are mainly found close to the five key districts. The map of Tianjin was combined with the experimental data to perform the visual analysis. Based on the emotional assessment, the distribution of negative materials, and the direction of street guidelines, we suggest guidance content and design strategy points of the negative phenomena in Tianjin street space in the two dimensions of perception and substance. This work demonstrates the utilization of deep learning techniques to understand how people appreciate high-quality urban construction, and it complements both theory and practice in urban planning. It illustrates the connection between human perception and the actual physical public space environment, allowing researchers to make urban interventions.

Keywords: human perception, public space quality, deep learning, negative elements, street images

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Authors: Suraj Sam Issaka, Anita Asamoah, Abass Gibrilla, Joseph Richmond Fianko

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Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds that can form in edible oils during repeated frying and accumulate in fried foods. This study assesses the chances of health risks (carcinogenic and non-carcinogenic) due to PAHs levels in popular finger foods (bean cakes, plantain chips, doughnuts) fried in edible oils (mixed vegetable, sunflower, soybean) from the Ghanaian market. Employing probabilistic health risk assessment that considers variability and uncertainty in exposure and risk estimates provides a more realistic representation of potential health risks. Monte Carlo simulations with 10,000 iterations were used to estimate carcinogenic, mutagenic, and non-carcinogenic risks for different age groups (A: 6-10 years, B: 11-20 years, C: 20-70 years), food types (bean cake, plantain chips, doughnut), oil types (soybean, mixed vegetable, sunflower), and re-usage frying oil frequencies (once, twice, thrice). Our results suggest that, for age Group A, doughnuts posed the highest probability of carcinogenic risk (91.55%) exceeding the acceptable threshold, followed by bean cakes (43.87%) and plantain chips (7.72%), as well as the highest probability of unacceptable mutagenic risk (89.2%), followed by bean cakes (40.32%). Among age Group B, doughnuts again had the highest probability of exceeding carcinogenic risk limits (51.16%) and mutagenic risk limits (44.27%). At the same time, plantain chips exhibited the highest maximum carcinogenic risk. For adults age Group C, bean cakes had the highest probability of unacceptable carcinogenic (50.88%) and mutagenic risks (46.44%), though plantain chips showed the highest maximum values for both carcinogenic and mutagenic risks in this age group. Also, on non-carcinogenic risks across different age groups, it was found that age Group A) who consumed doughnuts had a 68.16% probability of a hazard quotient (HQ) greater than 1, suggesting potential cognitive impairment and lower IQ scores due to early PAH exposure. This group also faced risks from consuming plantain chips and bean cake. For age Group B, the consumption of plantain chips was associated with a 36.98% probability of HQ greater than 1, indicating a potential risk of reduced lung function. In age Group C, the consumption of plantain chips was linked to a 35.70% probability of HQ greater than 1, suggesting a potential risk of cardiovascular diseases.

Keywords: PAHs, fried foods, carcinogenic risk, non-carcinogenic risk, Monte Carlo simulations

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Authors: Eva de Mingo-Fernández, Lourdes Rubio Rico, Carmen Ortega-Segura, Montserrat Querol-García, Raúl González-Jauregui

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Today, one of the great challenges that the university faces is to get closer to society and transfer knowledge. The competency-based training approach favours a continuous interaction between practice and theory, which is why it is essential to establish real experiences with reflection and debate and to contrast them with personal and professional knowledge. Service-learning (SL) consists of an integration of academic learning with service in the community, which enables teachers to transfer knowledge with social value and students to be trained on the basis of experience of real needs and problems with the aim of solving them. SLE combines research, teaching, and social value knowledge transfer with the real social needs and problems of a community. Goal: The objective of this study was to design, implement, and evaluate a service-learning program in the subject of adult nursing for second-year nursing students. Methodology: After establishing collaboration with eight associations of people with different pathologies, the students were divided into eight groups, and each group was assigned an association. The groups were made up of 10-12 students. The associations willing to participate were for the following conditions: diabetes, multiple sclerosis, cancer, inflammatory bowel disease, fibromyalgia, heart, lung, and kidney diseases. The methodological design consisting of 5 activities was then applied. Three activities address personal and individual reflections, where the student initially describes what they think it is like to live with a certain disease. They then express their reflections resulting from an interview conducted by peers, in person or online, with a person living with this particular condition, and after sharing the results of their reflections with the rest of the group, they make an oral presentation in which they present their findings to the other students. This is followed by a service task in which the students collaborate in different activities of the association, and finally, a third individual reflection is carried out in which the students express their experience of collaboration. The evaluation of this activity is carried out by means of a rubric for both the reflections and the presentation. It should be noted that the oral presentation is evaluated both by the rest of the classmates and by the teachers. Results: The evaluation of the activity, given by the students, is 7.80/10, commenting that the experience is positive and brings them closer to the reality of the people and the area.

Keywords: academic learning integration, knowledge transfer, service-learning, teaching methodology

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Authors: Gautier Viaud, Paul-Henry Cournède

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Plant growth models have been used extensively for the prediction of the phenotypic performance of plants. However, they remain most often calibrated for a given genotype and therefore do not take into account genotype by environment interactions. One way of achieving such an objective is to consider Bayesian hierarchical models. Three levels can be identified in such models: The first level describes how a given growth model describes the phenotype of the plant as a function of individual parameters, the second level describes how these individual parameters are distributed within a plant population, the third level corresponds to the attribution of priors on population parameters. Thanks to the Bayesian framework, choosing appropriate priors for the population parameters permits to derive analytical expressions for the full conditional distributions of these population parameters. As plant growth models are of a nonlinear nature, individual parameters cannot be sampled explicitly, and a Metropolis step must be performed. This allows for the use of a hybrid Gibbs--Metropolis sampler. A generic approach was devised for the implementation of both general state space models and estimation algorithms within a programming platform. It was designed using the Julia language, which combines an elegant syntax, metaprogramming capabilities and exhibits high efficiency. Results were obtained for Arabidopsis thaliana on both simulated and real data. An organ-scale Greenlab model for the latter is thus presented, where the surface areas of each individual leaf can be simulated. It is assumed that the error made on the measurement of leaf areas is proportional to the leaf area itself; multiplicative normal noises for the observations are therefore used. Real data were obtained via image analysis of zenithal images of Arabidopsis thaliana over a period of 21 days using a two-step segmentation and tracking algorithm which notably takes advantage of the Arabidopsis thaliana phyllotaxy. Since the model formulation is rather flexible, there is no need that the data for a single individual be available at all times, nor that the times at which data is available be the same for all the different individuals. This allows to discard data from image analysis when it is not considered reliable enough, thereby providing low-biased data in large quantity for leaf areas. The proposed model precisely reproduces the dynamics of Arabidopsis thaliana’s growth while accounting for the variability between genotypes. In addition to the estimation of the population parameters, the level of variability is an interesting indicator of the genotypic stability of model parameters. A promising perspective is to test whether some of the latter should be considered as fixed effects.

Keywords: bayesian, genotypic differentiation, hierarchical models, plant growth models

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Authors: D. F. Carvalho, A. O. Uscamayta, J. C. Guerrero, H. F. Oliveira, P. M. Azevedo-Marques

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The creation of vector contours slices (ROIs) on body silhouettes in oncologic patients is an important step during the radiotherapy planning in clinic and hospitals to ensure the accuracy of oncologic treatment. The radiotherapy planning of patients is performed by complex softwares focused on analysis of tumor regions, protection of organs at risk (OARs) and calculation of radiation doses for anomalies (tumors). These softwares are supplied for a few manufacturers and run over sophisticated workstations with vector processing presenting a cost of approximately twenty thousand dollars. The Brazilian project SIPRAD (Radiotherapy Planning System) presents a proposal adapted to the emerging countries reality that generally does not have the monetary conditions to acquire some radiotherapy planning workstations, resulting in waiting queues for new patients treatment. The SIPRAD project is composed by a set of integrated and interoperabilities softwares that are able to execute all stages of radiotherapy planning on simple personal computers (PCs) in replace to the workstations. The goal of this work is to present an image processing technique, computationally feasible, that is able to perform an automatic contour delineation in patient body silhouettes (SIPRAD-Body). The SIPRAD-Body technique is performed in tomography slices under grayscale images, extending their use with a greedy algorithm in three dimensions. SIPRAD-Body creates an irregular polyhedron with the Canny Edge adapted algorithm without the use of preprocessing filters, as contrast and brightness. In addition, comparing the technique SIPRAD-Body with existing current solutions is reached a contours similarity at least 78%. For this comparison is used four criteria: contour area, contour length, difference between the mass centers and Jaccard index technique. SIPRAD-Body was tested in a set of oncologic exams provided by the Clinical Hospital of the University of Sao Paulo (HCRP-USP). The exams were applied in patients with different conditions of ethnology, ages, tumor severities and body regions. Even in case of services that have already workstations, it is possible to have SIPRAD working together PCs because of the interoperability of communication between both systems through the DICOM protocol that provides an increase of workflow. Therefore, the conclusion is that SIPRAD-Body technique is feasible because of its degree of similarity in both new radiotherapy planning services and existing services.

Keywords: radiotherapy, image processing, DICOM RT, Treatment Planning System (TPS)

Procedia PDF Downloads 296

Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

Procedia PDF Downloads 451

Authors: N. D'Amico, E. Grossi, B. Colombo, F. Rigiroli, M. Buscema, D. Fazzini, G. Cornalba, S. Papa

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Purpose: To characterize, through a radiomic approach, the nature of nodules considered non-specific by expert radiologists, recognized in magnetic resonance mammography (MRm) with T1-weighted (T1w) sequences with paramagnetic contrast. Material and Methods: 47 cases out of 1200 undergoing MRm, in which the MRm assessment gave uncertain classification (non-specific nodules), were admitted to the study. The clinical outcome of the non-specific nodules was later found through follow-up or further exams (biopsy), finding 35 benign and 12 malignant. All MR Images were acquired at 1.5T, a first basal T1w sequence and then four T1w acquisitions after the paramagnetic contrast injection. After a manual segmentation of the lesions, done by a radiologist, and the extraction of 150 radiomic features (30 features per 5 subsequent times) a machine learning (ML) approach was used. An evolutionary algorithm (TWIST system based on KNN algorithm) was used to subdivide the dataset into training and validation test and to select features yielding the maximal amount of information. After this pre-processing, different machine learning systems were applied to develop a predictive model based on a training-testing crossover procedure. 10 cases with a benign nodule (follow-up older than 5 years) and 18 with an evident malignant tumor (clear malignant histological exam) were added to the dataset in order to allow the ML system to better learn from data. Results: NaiveBayes algorithm working on 79 features selected by a TWIST system, resulted to be the best performing ML system with a sensitivity of 96% and a specificity of 78% and a global accuracy of 87% (average values of two training-testing procedures ab-ba). The results showed that in the subset of 47 non-specific nodules, the algorithm predicted the outcome of 45 nodules which an expert radiologist could not identify. Conclusion: In this pilot study we identified a radiomic approach allowing ML systems to perform well in the diagnosis of a non-specific nodule at MR mammography. This algorithm could be a great support for the early diagnosis of malignant breast tumor, in the event the radiologist is not able to identify the kind of lesion and reduces the necessity for long follow-up. Clinical Relevance: This machine learning algorithm could be essential to support the radiologist in early diagnosis of non-specific nodules, in order to avoid strenuous follow-up and painful biopsy for the patient.

Keywords: breast, machine learning, MRI, radiomics

Procedia PDF Downloads 267

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

Procedia PDF Downloads 177

Authors: Maria Sciammarella, Uttam M. Shrestha, Youngho Seo, Grant T. Gullberg, Elias H. Botvinick

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Background: Myocardial perfusion imaging (MPI) is typically performed with static imaging protocols and visually assessed for perfusion defects based on the relative intensity distribution. Dynamic cardiac SPECT, on the other hand, is a new imaging technique that is based on time varying information of radiotracer distribution, which permits quantification of myocardial blood flow (MBF). In this abstract, we report a progress and current status of dynamic cardiac SPECT using conventional gamma camera (Infinia Hawkeye 4, GE Healthcare) for estimation of myocardial blood flow and coronary flow reserve. Methods: A group of patients who had high risk of coronary artery disease was enrolled to evaluate our methodology. A low-dose/high-dose rest/pharmacologic-induced-stress protocol was implemented. A standard rest and a standard stress radionuclide dose of ⁹⁹ᵐTc-tetrofosmin (140 keV) was administered. The dynamic SPECT data for each patient were reconstructed using the standard 4-dimensional maximum likelihood expectation maximization (ML-EM) algorithm. Acquired data were used to estimate the myocardial blood flow (MBF). The correspondence between flow values in the main coronary vasculature with myocardial segments defined by the standardized myocardial segmentation and nomenclature were derived. The coronary flow reserve, CFR, was defined as the ratio of stress to rest MBF values. CFR values estimated with SPECT were also validated with dynamic PET. Results: The range of territorial MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between estimated with PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). But the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The mean stress MBF value was significantly lower for angiographically abnormal than that for the normal (Normal Mean MBF = 2.49 ± 0.61, Abnormal Mean MBF = 1.43 ± 0. 0.62, P < .001). Conclusions: The visually assessed image findings in clinical SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion. The MBF and CFR measured with dynamic SPECT are fully objective and available only with the data generated from the dynamic SPECT method. A quantitative approach such as measuring CFR using dynamic SPECT imaging is a better mode of diagnosing CAD than visual assessment of stress and rest images from static SPECT images Coronary Flow Reserve.

Keywords: dynamic SPECT, clinical SPECT/CT, selective coronary angiograph, ⁹⁹ᵐTc-Tetrofosmin

Procedia PDF Downloads 152

Authors: Syahrir Andi Mangga

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During 1989–1993, the Geological Research and Development Center (recent Geological Survey Institute) Geological Agency, Ministry of Energy and Mineral Resources Republic of Indonesia was the collaboration with British Geological Survey, the United Kingdom to do technical assistance in order to collect data of geology in Sumatra Island. The overall corporation of technical programs was larger concern in stratigraphy, geochemical and age-dating studies. Availability of new data has been stimulated to reassessment of tectonic evolution of Sumatra Island. The study area located in Southern Sumatra within at latitudes 0°-6° S and 99°40’-106’00 E longitudes. The study tectonic is situated within along South Western margin of Sunda land, The Southeast Asia Continental extension arc of the Eurasian Plate and formed as part of Sunda Arc. The oceanic crust of Indian-Australian plate recently is being oblique subduction along the Sunda Trench off the West coast Sumatra. The Mesozoic-Cenozoic of the volcanic and granitic rocks can be divided into northern and southern plutons, defining a series subparallel, controlled by fault, northwest-southeast trending belts, some of the plutons are deformed and under-formed. They are widely exposed along the south-eastern side of the Barisan mountain. Based on the characteristic of minerals and crystallography, rocks found in this study area were granite, granitic, monzogranite and andesitic-Basaltic Volcanic Rock. It belongs to calc Alkaline was predominantly metalumina, I-Type Granite, Volcanic arc granites, Syncollisonal Granites (Syn_COLG) and tholeiitic basalt. It was formed since 169±5 to 20±1 Ma. The origin of magmas in interpreted to be derived from partial melting of igneous rock. The occurrence of the gratoid and volcanic rocks supposed to be closely related to the subduction of the Australian-Hindia oceanic crust beneath the Eurasia/Sunda land Continental Crust as Volcanic arc or continental margin granitic and shown youngest to the southwest. The subduction process having probably been different in position between one terrane to others led to the occurrence of segmentation subduction system. The positional discontinuities of the subduction are probably caused by the difference in time of emplacement and mechanism of volcanic and granitic rock between segments.

Keywords: tectonic setting, I-type granitic, subduction, Southern Sumatra

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

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Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

Procedia PDF Downloads 137

Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

Abstract:

Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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