Search results for: Yu Lung Lau
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 507

Search results for: Yu Lung Lau

357 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

Abstract:

Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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356 A Natural Killer T Cell Subset That Protects against Airway Hyperreactivity

Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

Abstract:

We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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355 Visualizing Imaging Pathways after Anatomy-Specific Follow-Up Imaging Recommendations

Authors: Thusitha Mabotuwana, Christopher S. Hall

Abstract:

Radiologists routinely make follow-up imaging recommendations, usually based on established clinical practice guidelines, such as the Fleischner Society guidelines for managing lung nodules. In order to ensure optimal care, it is important to make guideline-compliant recommendations, and also for patients to follow-up on these imaging recommendations in a timely manner. However, determining such compliance rates after a specific finding has been observed usually requires many time-consuming manual steps. To address some of these limitations with current approaches, in this paper we discuss a methodology to automatically detect finding-specific follow-up recommendations from radiology reports and create a visualization for relevant subsequent exams showing the modality transitions. Nearly 5% of patients who had a lung related follow-up recommendation continued to have at least eight subsequent outpatient CT exams during a seven year period following the recommendation. Radiologist and section chiefs can use the proposed tool to better understand how a specific patient population is being managed, identify possible deviations from established guideline recommendations and have a patient-specific graphical representation of the imaging pathways for an abstract view of the overall treatment path thus far.

Keywords: follow-up recommendations, follow-up tracking, care pathways, imaging pathway visualization

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354 Cylindrical Spacer Shape Optimization for Enhanced Inhalation Therapy

Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

Abstract:

Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

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353 Prevalence of Trichomonas Tenax in Patients with Pulmonary Disease and Watersheds and Its Potential Implications for Pulmonary Virus Infection

Authors: Pei Chi Fang, Wei Chen Lin

Abstract:

Trichomonas tenax is a microaerophilic oral protozoan found in patients with poor oral hygiene. It participates in the inflammatory process of periodontal disease and can potentially be aspirated into the lungs, giving rise to pulmonary trichomoniasis. However, the precise roles of T. tenax in the pulmonary system remain largely unexplored and warrant comprehensive epidemiological investigation. To assess the prevalence of T. tenax infection, we collected bronchoalveolar lavage fluid (BALF) samples from hospitalized patients with lung diseases. A specific nested PCR approach was employed to determine prevalence rates, yielding 21 positive cases out of 61 samples from Ditmanson Medical Foundation Chia-Yi Christian Hospital, and 11 positive cases out of 55 samples from National Cheng Kung University Hospital. Furthermore, there is a critical need for comprehensive data regarding the presence of T. tenax in environmental surface watersheds. In this context, we present findings from investigations in the Yanshuei and Donggang river basins in southern Taiwan, which are crucial sources for public drinking water in the region. In order to elucidate potential implications on pulmonary virus infections, we conducted an analysis of gene expression level changes in H292 cell line after exposure to T. tenax. Our findings revealed significant regulation of multiple virus-related genes, including IFI44L and IFITM3. Ongoing research endeavors are focused on identifying the key components within T. tenax responsible for these observed effects. Crucially, this study lays the groundwork for a preliminary understanding of T. tenax prevalence in patients with pulmonary diseases. It also seeks to establish a meaningful correlation between lung infections and oral hygiene practices, with the ultimate aim of informing distinct treatment and prevention strategies.

Keywords: parasitology, genes, virus, human health, infection, lung

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352 Using Multiomic Plasma Profiling From Liquid Biopsies to Identify Potential Signatures for Disease Diagnostics in Late-Stage Non-small Cell Lung Cancer (NSCLC) in Trinidad and Tobago

Authors: Nicole Ramlachan, Samuel Mark West

Abstract:

Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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351 Covid-19, Diagnosis with Computed Tomography and Artificial Intelligence, in a Few Simple Words

Authors: Angelis P. Barlampas

Abstract:

Target: The (SARS-CoV-2) is still a threat. AI software could be useful, categorizing the disease into different severities and indicate the extent of the lesions. Materials and methods: AI is a new revolutionary technique, which uses powered computerized systems, to do what a human being does more rapidly, more easily, as accurate and diagnostically safe as the original medical report and, in certain circumstances, even better, saving time and helping the health system to overcome problems, such as work overload and human fatigue. Results: It will be given an effort to describe to the inexperienced reader (see figures), as simple as possible, how an artificial intelligence system diagnoses computed tomography pictures. First, the computerized machine learns the physiologic motives of lung parenchyma by being feeded with normal structured images of the lung tissue. Having being used to recognizing normal structures, it can then easily indentify the pathologic ones, as their images do not fit to known normal picture motives. It is the same way as when someone spends his free time in reading magazines with quizzes, such as <> and <>. General conclusion: The AI mimics the physiological processes of the human mind, but it does that more efficiently and rapidly and provides results in a few seconds, whereas an experienced radiologist needs many days to do that, or even worse, he is unable to accomplish such a huge task.

Keywords: covid-19, artificial intelligence, automated imaging, CT, chest imaging

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350 Isolation of Cytotoxic Compound from Tectona grandis Stem to Be Used as Thai Medicinal Preparation for Cancer Treatment

Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat

Abstract:

A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.

Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone

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349 Generation of High-Quality Synthetic CT Images from Cone Beam CT Images Using A.I. Based Generative Networks

Authors: Heeba A. Gurku

Abstract:

Introduction: Cone Beam CT(CBCT) images play an integral part in proper patient positioning in cancer patients undergoing radiation therapy treatment. But these images are low in quality. The purpose of this study is to generate high-quality synthetic CT images from CBCT using generative models. Material and Methods: This study utilized two datasets from The Cancer Imaging Archive (TCIA) 1) Lung cancer dataset of 20 patients (with full view CBCT images) and 2) Pancreatic cancer dataset of 40 patients (only 27 patients having limited view images were included in the study). Cycle Generative Adversarial Networks (GAN) and its variant Attention Guided Generative Adversarial Networks (AGGAN) models were used to generate the synthetic CTs. Models were evaluated by visual evaluation and on four metrics, Structural Similarity Index Measure (SSIM), Peak Signal Noise Ratio (PSNR) Mean Absolute Error (MAE) and Root Mean Square Error (RMSE), to compare the synthetic CT and original CT images. Results: For pancreatic dataset with limited view CBCT images, our study showed that in Cycle GAN model, MAE, RMSE, PSNR improved from 12.57to 8.49, 20.94 to 15.29 and 21.85 to 24.63, respectively but structural similarity only marginally increased from 0.78 to 0.79. Similar, results were achieved with AGGAN with no improvement over Cycle GAN. However, for lung dataset with full view CBCT images Cycle GAN was able to reduce MAE significantly from 89.44 to 15.11 and AGGAN was able to reduce it to 19.77. Similarly, RMSE was also decreased from 92.68 to 23.50 in Cycle GAN and to 29.02 in AGGAN. SSIM and PSNR also improved significantly from 0.17 to 0.59 and from 8.81 to 21.06 in Cycle GAN respectively while in AGGAN SSIM increased to 0.52 and PSNR increased to 19.31. In both datasets, GAN models were able to reduce artifacts, reduce noise, have better resolution, and better contrast enhancement. Conclusion and Recommendation: Both Cycle GAN and AGGAN were significantly able to reduce MAE, RMSE and PSNR in both datasets. However, full view lung dataset showed more improvement in SSIM and image quality than limited view pancreatic dataset.

Keywords: CT images, CBCT images, cycle GAN, AGGAN

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348 Detection of Elephant Endotheliotropic Herpes Virus in a Wild Asian Elephant Calf in Thailand by Using Real-Time PCR

Authors: Bopit Puyati, Anchittha Kaewchana, Nuntita Ruksachat

Abstract:

In January 2018, a male wild elephant, approximately 2 years old, was found dead in Phu Luang Wildlife Sanctuary, Loei province. The elephant was likely to die around 2 weeks earlier. The carcass was decayed without any signs of attack or bullet. No organs were removed. A deadly viral disease was suspected. Different organs including lung, liver, intestine and tongue were collected and submitted to the veterinary research and development center, Surin province for viral detection. The samples were then examined with real-time PCR for detecting U41 Major DNA binding protein (MDBP) gene and with conventional PCR for the presence of specific polymerase gene. We used tumor necrosis factor (TNF) gene as the internal control. In our real-time PCR, elephant endotheliotropic herpesvirus (EEHV) was recovered from lung, liver, and tongue whereas only tongue provided a positive result in the conventional PCR. All samples were positive with TNF gene detection. To our knowledge, this is the first report of EEHV detection in wild elephant in Thailand. EEHV surveillance in this wild population is strongly suggested. Linkage between EEHV in wild and domestic elephants should be further explored.

Keywords: elephant endotheliotropic herpes virus, PCR, Thailand, wild Asian elephant

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347 LncRNA NEAT1 Promotes NSCLC Progression through Acting as a ceRNA of miR-377-3p

Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

Abstract:

Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis

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346 Metabolomics Profile Recognition for Cancer Diagnostics

Authors: Valentina L. Kouznetsova, Jonathan W. Wang, Igor F. Tsigelny

Abstract:

Metabolomics has become a rising field of research for various diseases, particularly cancer. Increases or decreases in metabolite concentrations in the human body are indicative of various cancers. Further elucidation of metabolic pathways and their significance in cancer research may greatly spur medicinal discovery. We analyzed the metabolomics profiles of lung cancer. Thirty-three metabolites were selected as significant. These metabolites are involved in 37 metabolic pathways delivered by MetaboAnalyst software. The top pathways are glyoxylate and dicarboxylate pathway (its hubs are formic acid and glyoxylic acid) along with Citrate cycle pathway followed by Taurine and hypotaurine pathway (the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine, serine, and threonine pathway (the hubs are glycine and L-serine). We studied interactions of the metabolites with the proteins involved in cancer-related signaling networks, and developed an approach to metabolomics biomarker use in cancer diagnostics. Our analysis showed that a significant part of lung-cancer-related metabolites interacts with main cancer-related signaling pathways present in this network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway, and NFKB pathway. These results can be employed for use of metabolomics profiles in elucidation of the related cancer proteins signaling networks.

Keywords: cancer, metabolites, metabolic pathway, signaling pathway

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345 Indoor Air Pollution: A Major Threat to Human Health

Authors: Pooja Rawat, Rakhi Tyagi

Abstract:

Globally, almost 3 billion people rely on biomass (wood, charcoal, dung and crop residues) and coal as their primary source of domestic energy. Cooking and heating with solid fuels on open fire give rise to major pollutants. Women are primarily affected by these pollutants as they spend most of their time in the house. The WHO World Health Report 2002 estimates that indoor air pollution (IAP) is responsible for 2.7% of the loss of disability adjusted life years (DALYs) worldwide and 3.7% in high mortality developing countries. Indoor air pollution has the potential to not only impact health, but also impact the general economic well-being of the household. Exposure to high level of household pollution lead to acute and chronic respiratory conditions (e.g.: pneumonia, chronic obstructive pulmonary disease, lung cancer and cataract). There has been many strategies for reducing IAP like subsidize cleaner fuel technologies, for example use of kerosene rather than traditional biomass fuels. Another example is development, promotion of 'improved cooking stoves'. India, likely ranks second- distributing over 12 million improved stoves in the first seven years of a national program to develop. IAP should be reduced by understanding the welfare effects of reducing IAP within households and to understanding the most cost effective way to reduce it.

Keywords: open fire, indoor pollution, lung diseases, indoor air pollution

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344 Analysis of Anti-Tuberculosis Immune Response Induced in Lungs by Intranasal Immunization with Mycobacterium indicus pranii

Authors: Ananya Gupta, Sangeeta Bhaskar

Abstract:

Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

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343 Prone Positioning and Clinical Outcomes of Mechanically Ventilated Patients with Severe Acute Respiratory Distress Syndrome

Authors: Maha Salah Abdullah Ismail, Mahmoud M. Alsagheir, Mohammed Salah Abd Allah

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Acute respiratory distress syndrome (ARDS) is characterized by permeability pulmonary edema and refractory hypoxemia. Lung-protective ventilation is still the key of better outcome in ARDS. Prone position reduces the trans-pulmonary pressure gradient, recruiting collapsed regions of the lung without increasing airway pressure or hyperinflation. Prone ventilation showed improved oxygenation and improved outcomes in severe hypoxemic patients with ARDS. This study evaluates the effect of prone positioning on mechanically ventilated patients with ARDS. A quasi-experimental design was carried out at Critical Care Units, on 60 patients. Two tools were utilized to collect data; Socio demographic, medical and clinical outcomes data sheet. Results of the present study indicated that prone position improves oxygenation in patients with severe respiratory distress syndrome. The study recommended that use prone position in patients with severe ARDS, as early as possible and for long sessions. Also, replication of this study on larger probability sample at the different geographical location is highly recommended.

Keywords: acute respiratory distress syndrome, critical care, mechanical ventilation, prone position

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342 The Utilization of FSI Technique and Two-Way Particle Coupling System on Particle Dynamics in the Human Alveoli

Authors: Hassan Athari, Abdurrahim Bolukbasi, Dogan Ciloglu

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This study represented the respiratory alveoli system, and determined the trajectory of inhaled particles more accurately using the modified three-dimensional model with deformable walls of alveoli. The study also considered the tissue tension in the model to demonstrate the effect of lung. Tissue tensions are transferred by the lung parenchyma and produce the pressure gradient. This load expands the alveoli and establishes a sub-ambient (vacuum) pressure within the lungs. Thus, at the alveolar level, the flow field and movement of alveoli wall lead to an integrated effect. In this research, we assume that the three-dimensional alveolus has a visco-elastic tissue (walls). For accurate investigation of pulmonary tissue mechanical properties on particle transport and alveolar flow field, the actual relevance between tissue movement and airflow is solved by two-way FSI (Fluid Structure Interaction) simulation technique in the alveolus. Therefore, the essence of real simulation of pulmonary breathing mechanics can be achieved by developing a coupled FSI computational model. We, therefore conduct a series of FSI simulations over a range of tissue models and breathing rates. As a result, the fluid flows and streamlines have changed during present flexible model against the rigid models and also the two-way coupling particle trajectories have changed against the one-way particle coupling.

Keywords: FSI, two-way particle coupling, alveoli, CDF

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341 Numerical Simulation on Airflow Structure in the Human Upper Respiratory Tract Model

Authors: Xiuguo Zhao, Xudong Ren, Chen Su, Xinxi Xu, Fu Niu, Lingshuai Meng

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The respiratory diseases such as asthma, emphysema and bronchitis are connected with the air pollution and the number of these diseases tends to increase, which may attribute to the toxic aerosol deposition in human upper respiratory tract or in the bifurcation of human lung. The therapy of these diseases mostly uses pharmaceuticals in the form of aerosol delivered into the human upper respiratory tract or the lung. Understanding of airflow structures in human upper respiratory tract plays a very important role in the analysis of the “filtering” effect in the pharynx/larynx and for obtaining correct air-particle inlet conditions to the lung. However, numerical simulation based CFD (Computational Fluid Dynamics) technology has its own advantage on studying airflow structure in human upper respiratory tract. In this paper, a representative human upper respiratory tract is built and the CFD technology was used to investigate the air movement characteristic in the human upper respiratory tract. The airflow movement characteristic, the effect of the airflow movement on the shear stress distribution and the probability of the wall injury caused by the shear stress are discussed. Experimentally validated computational fluid-aerosol dynamics results showed the following: the phenomenon of airflow separation appears near the outer wall of the pharynx and the trachea. The high velocity zone is created near the inner wall of the trachea. The airflow splits at the divider and a new boundary layer is generated at the inner wall of the downstream from the bifurcation with the high velocity near the inner wall of the trachea. The maximum velocity appears at the exterior of the boundary layer. The secondary swirls and axial velocity distribution result in the high shear stress acting on the inner wall of the trachea and bifurcation, finally lead to the inner wall injury. The enhancement of breathing intensity enhances the intensity of the shear stress acting on the inner wall of the trachea and the bifurcation. If human keep the high breathing intensity for long time, not only the ability for the transportation and regulation of the gas through the trachea and the bifurcation fall, but also result in the increase of the probability of the wall strain and tissue injury.

Keywords: airflow structure, computational fluid dynamics, human upper respiratory tract, wall shear stress, numerical simulation

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340 A Case of Acupuncture Induced Pneumothorax

Authors: Azka Naeem, Kimberly Mae Soultan, Shree Laya Vemula, Marlon Rivera Boadla, Shaurya Sharma, Ravikaran Singh Patti

Abstract:

Context: This case report discusses a rare and serious complication of acupuncture induced pneumothorax. The patient presented with acute chest pain and shortness of breath following acupuncture treatment for chronic elbow pain. Despite the generally safe reputation of acupuncture, pneumothorax can occur as a result of the procedure. This case highlights the importance of recognizing pneumothorax in patients who have undergone acupuncture treatment without any significant pre-existing lung disorder. Research Aim: The aim of this study is to report a case of acupuncture-induced pneumothorax and emphasize the importance of early detection to prevent the development of tension pneumothorax. The study also aims to raise awareness about the potential safety concerns of acupuncture for individuals who are lean and/or have underlying lung disorders, particularly when treatment is administered in high-risk areas such as the interscapular region. Methodology: The research methodology used in this study involved a retrospective chart review. Following informed consent, the researchers obtained information from the patient's medical records to gather relevant details about the case, including the patient's symptoms, medical history, and the acupuncture procedure performed. Findings: The case report describes the symptoms and physical examination findings of the patient, which led to the diagnosis of pneumothorax. The patient experienced sudden onset chest pain and shortness of breath, which occurred one hour after receiving acupuncture treatment. Physical examination revealed a mild increase in the work of breathing, reduced right sided chest excursion, and decreased breath sounds in the right upper lobe. A chest X-ray was done, which confirmed the presence of a moderate-sized right apical pneumothorax. Prompt intervention with a right pigtail catheter prevented the development of tension pneumothorax, and the patient's lung expansion was restored. Theoretical Importance: This case report highlights the importance of considering acupuncture-induced pneumothorax as a potential complication, even in patients without identifiable risk factors. It emphasizes the significance of early detection and appropriate management to prevent potential life-threatening complications. The study also contributes to the existing literature by drawing attention to the safety concerns associated with acupuncture for thin, lean individuals, particularly those with underlying lung disorders. Data Collection and Analysis Procedures: The data for this study were collected through a retrospective chart review. Information was obtained from the patient's medical records, including symptoms, medical history, and diagnostic findings. The analysis involved examining the relationship between the acupuncture procedure and the development of pneumothorax, as well as the effectiveness of the intervention in preventing tension pneumothorax. Conclusion: In conclusion, this case report highlights a rare but serious complication of acupuncture - pneumothorax. It emphasizes the need for vigilance and clinical suspicion in patients who present with chest pain and dyspnea following acupuncture treatment. Early detection and appropriate intervention can prevent the progression of tension pneumothorax. Clinicians should exercise caution when performing acupuncture on individuals with underlying lung disorders, particularly in high-risk areas.

Keywords: acupuncture, pneumothorax, pigtail catheterization, pleuritic chest pain

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339 Algorithm for Quantification of Pulmonary Fibrosis in Chest X-Ray Exams

Authors: Marcela de Oliveira, Guilherme Giacomini, Allan Felipe Fattori Alves, Ana Luiza Menegatti Pavan, Maria Eugenia Dela Rosa, Fernando Antonio Bacchim Neto, Diana Rodrigues de Pina

Abstract:

It is estimated that each year one death every 10 seconds (about 2 million deaths) in the world is attributed to tuberculosis (TB). Even after effective treatment, TB leaves sequelae such as, for example, pulmonary fibrosis, compromising the quality of life of patients. Evaluations of the aforementioned sequel are usually performed subjectively by radiology specialists. Subjective evaluation may indicate variations inter and intra observers. The examination of x-rays is the diagnostic imaging method most accomplished in the monitoring of patients diagnosed with TB and of least cost to the institution. The application of computational algorithms is of utmost importance to make a more objective quantification of pulmonary impairment in individuals with tuberculosis. The purpose of this research is the use of computer algorithms to quantify the pulmonary impairment pre and post-treatment of patients with pulmonary TB. The x-ray images of 10 patients with TB diagnosis confirmed by examination of sputum smears were studied. Initially the segmentation of the total lung area was performed (posteroanterior and lateral views) then targeted to the compromised region by pulmonary sequel. Through morphological operators and the application of signal noise tool, it was possible to determine the compromised lung volume. The largest difference found pre- and post-treatment was 85.85% and the smallest was 54.08%.

Keywords: algorithm, radiology, tuberculosis, x-rays exam

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338 Indirect Genotoxicity of Diesel Engine Emission: An in vivo Study Under Controlled Conditions

Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin

Abstract:

Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.

Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length

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337 The Outcome of Using Machine Learning in Medical Imaging

Authors: Adel Edwar Waheeb Louka

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Purpose AI-driven solutions are at the forefront of many pathology and medical imaging methods. Using algorithms designed to better the experience of medical professionals within their respective fields, the efficiency and accuracy of diagnosis can improve. In particular, X-rays are a fast and relatively inexpensive test that can diagnose diseases. In recent years, X-rays have not been widely used to detect and diagnose COVID-19. The under use of Xrays is mainly due to the low diagnostic accuracy and confounding with pneumonia, another respiratory disease. However, research in this field has expressed a possibility that artificial neural networks can successfully diagnose COVID-19 with high accuracy. Models and Data The dataset used is the COVID-19 Radiography Database. This dataset includes images and masks of chest X-rays under the labels of COVID-19, normal, and pneumonia. The classification model developed uses an autoencoder and a pre-trained convolutional neural network (DenseNet201) to provide transfer learning to the model. The model then uses a deep neural network to finalize the feature extraction and predict the diagnosis for the input image. This model was trained on 4035 images and validated on 807 separate images from the ones used for training. The images used to train the classification model include an important feature: the pictures are cropped beforehand to eliminate distractions when training the model. The image segmentation model uses an improved U-Net architecture. This model is used to extract the lung mask from the chest X-ray image. The model is trained on 8577 images and validated on a validation split of 20%. These models are calculated using the external dataset for validation. The models’ accuracy, precision, recall, f1-score, IOU, and loss are calculated. Results The classification model achieved an accuracy of 97.65% and a loss of 0.1234 when differentiating COVID19-infected, pneumonia-infected, and normal lung X-rays. The segmentation model achieved an accuracy of 97.31% and an IOU of 0.928. Conclusion The models proposed can detect COVID-19, pneumonia, and normal lungs with high accuracy and derive the lung mask from a chest X-ray with similarly high accuracy. The hope is for these models to elevate the experience of medical professionals and provide insight into the future of the methods used.

Keywords: artificial intelligence, convolutional neural networks, deeplearning, image processing, machine learningSarapin, intraarticular, chronic knee pain, osteoarthritisFNS, trauma, hip, neck femur fracture, minimally invasive surgery

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336 An Experimental Study on the Influence of Brain-Break in the Classroom on the Physical Health and Academic Performance of Fourth Grade Students

Authors: Qian Mao, Xiaozan Wang, Jiarong Zhong, Xiaolin Zou

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Introduction: As a result of the decline of students' physical health level and the increase of study pressure, students’ academic performance is not so good. Objective: This study aims to verify whether the Brain-Break intervention in the fourth-grade classroom of primary school can improve students' physical health and academic performance. Methods: According to the principle of no difference in pre-test data, students from two classes of grade four in Fuhai Road Primary School, Fushan district, Yantai city, Shandong province, were selected as experimental subjects, including 50 students in the experimental class (25 males and 25 females) and 50 students in the control class (24 males and 26 females). The content of the experiment was that the students were asked to perform a 4-minute Brain-Berak program designed by the researcher in the second class in the morning and the afternoon, and the intervention lasted for 12 weeks. In addition, the lung capacity, 50-meter run, sitting body forward bend, one-minute jumping rope and one-minute sit-ups stipulated in the national standards for physical fitness of students (revised in 2014) were selected as the indicators of physical health. The scores of Chinese, Mathematics, and English in the unified academic test of the municipal education bureau were selected as the indicators of academic performance. The independent-sample t-test was used to compare and analyze the data of each index between the two classes. The paired-sample t-test was used to compare and analyze the data of each index in the two classes. This paper presents only results with significant differences. Results: in terms of physical health, lung capacity (P=0.002, T= -2.254), one-minute rope skipping (P=0.000, T=3.043), and one-minute sit-ups (P=0.045, T=6.153) were significantly different between the experimental class and the control class. In terms of academic performance, there is a significant difference between the Chinese performance of the experimental class and the control class (P=0.009, T=4.833). Conclusion: Adding Brain-Berak intervention in the classroom can effectively improve the cardiorespiratory endurance (lung capacity), coordination (jumping rope), and abdominal strength (sit-ups) of fourth-grade students. At the same time, it can also effectively improve their Chinese performance. Therefore, it is suggested to promote micro-sports in the classroom of primary schools throughout the country so as to help students improve their physical health and academic performance.

Keywords: academic performance, brain break, fourth grade, physical health

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335 Oral Microbiota as a Novel Predictive Biomarker of Response To Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer Patients

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

Abstract:

Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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334 Extra Skeletal Manifestations of Histocytosis in Pediatrics

Authors: Ayda Youssef, Mohammed Ali Khalaf, Tarek Rafaat

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Background: Langerhans cell histiocytosis (LCH) is a rare multi-systemic disease that shows an abnormal proliferation of these kinds of cells associated with a granular infiltration that affects different structures of the human body, including the lung, liver, spleen, lymph nodes, brain, mucocutaneous, soft tissue (head and neck), and salivary glands. Evaluation of the extent of disease is one of the major predictors of patient outcome. Objectives: To recognize the pathogenesis of Langerhans cell histiocytosis (LCH), describe the radiologic criteria that are suggestive of LCH in different organs rather than the bones and to illustrate the appropriate differential diagnoses for LCH in each of the common extra-osseous sites. Material and methods: A retrospective study was done on 150 biopsy-proven LCH patients from 2007 to 2012. All patients underwent imaging studies, mostly US, CT, and MRI. These patients were reviewed to assess the extra-skeletal manifestations of LCH. Results: In 150 patients with biopsy-proven LCH, There were 33 patients with liver affection, 5 patients with splenic lesions, 55 patients with enlarged lymph nodes, 9 patient with CNS disease and 11 patients with lung involvement. Conclusions: Because of the frequent LCH children and evaluation of the extent of disease is one of the major predictors of patient outcome. Radiologist need to be familiar with its presentation in different organs and regions of body outside the commonest site of affection (bones). A high-index suspicion should be raised a biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality.

Keywords: langerhans cell histiocytosis, extra-skeletal, pediatrics, radiology

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333 Deep Learning in Chest Computed Tomography to Differentiate COVID-19 from Influenza

Authors: Hongmei Wang, Ziyun Xiang, Ying liu, Li Yu, Dongsheng Yue

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Intro: The COVID-19 (Corona Virus Disease 2019) has greatly changed the global economic, political and financial ecology. The mutation of the coronavirus in the UK in December 2020 has brought new panic to the world. Deep learning was performed on Chest Computed tomography (CT) of COVID-19 and Influenza and describes their characteristics. The predominant features of COVID-19 pneumonia was ground-glass opacification, followed by consolidation. Lesion density: most lesions appear as ground-glass shadows, and some lesions coexist with solid lesions. Lesion distribution: the focus is mainly on the dorsal side of the periphery of the lung, with the lower lobe of the lungs as the focus, and it is often close to the pleura. Other features it has are grid-like shadows in ground glass lesions, thickening signs of diseased vessels, air bronchi signs and halo signs. The severe disease involves whole bilateral lungs, showing white lung signs, air bronchograms can be seen, and there can be a small amount of pleural effusion in the bilateral chest cavity. At the same time, this year's flu season could be near its peak after surging throughout the United States for months. Chest CT for Influenza infection is characterized by focal ground glass shadows in the lungs, with or without patchy consolidation, and bronchiole air bronchograms are visible in the concentration. There are patchy ground-glass shadows, consolidation, air bronchus signs, mosaic lung perfusion, etc. The lesions are mostly fused, which is prominent near the hilar and two lungs. Grid-like shadows and small patchy ground-glass shadows are visible. Deep neural networks have great potential in image analysis and diagnosis that traditional machine learning algorithms do not. Method: Aiming at the two major infectious diseases COVID-19 and influenza, which are currently circulating in the world, the chest CT of patients with two infectious diseases is classified and diagnosed using deep learning algorithms. The residual network is proposed to solve the problem of network degradation when there are too many hidden layers in a deep neural network (DNN). The proposed deep residual system (ResNet) is a milestone in the history of the Convolutional neural network (CNN) images, which solves the problem of difficult training of deep CNN models. Many visual tasks can get excellent results through fine-tuning ResNet. The pre-trained convolutional neural network ResNet is introduced as a feature extractor, eliminating the need to design complex models and time-consuming training. Fastai is based on Pytorch, packaging best practices for in-depth learning strategies, and finding the best way to handle diagnoses issues. Based on the one-cycle approach of the Fastai algorithm, the classification diagnosis of lung CT for two infectious diseases is realized, and a higher recognition rate is obtained. Results: A deep learning model was developed to efficiently identify the differences between COVID-19 and influenza using chest CT.

Keywords: COVID-19, Fastai, influenza, transfer network

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332 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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331 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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330 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer

Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

Abstract:

Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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329 COVID-19 Detection from Computed Tomography Images Using UNet Segmentation, Region Extraction, and Classification Pipeline

Authors: Kenan Morani, Esra Kaya Ayana

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This study aimed to develop a novel pipeline for COVID-19 detection using a large and rigorously annotated database of computed tomography (CT) images. The pipeline consists of UNet-based segmentation, lung extraction, and a classification part, with the addition of optional slice removal techniques following the segmentation part. In this work, a batch normalization was added to the original UNet model to produce lighter and better localization, which is then utilized to build a full pipeline for COVID-19 diagnosis. To evaluate the effectiveness of the proposed pipeline, various segmentation methods were compared in terms of their performance and complexity. The proposed segmentation method with batch normalization outperformed traditional methods and other alternatives, resulting in a higher dice score on a publicly available dataset. Moreover, at the slice level, the proposed pipeline demonstrated high validation accuracy, indicating the efficiency of predicting 2D slices. At the patient level, the full approach exhibited higher validation accuracy and macro F1 score compared to other alternatives, surpassing the baseline. The classification component of the proposed pipeline utilizes a convolutional neural network (CNN) to make final diagnosis decisions. The COV19-CT-DB dataset, which contains a large number of CT scans with various types of slices and rigorously annotated for COVID-19 detection, was utilized for classification. The proposed pipeline outperformed many other alternatives on the dataset.

Keywords: classification, computed tomography, lung extraction, macro F1 score, UNet segmentation

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328 A Comparative Time-Series Analysis and Deep Learning Projection of Innate Radon Gas Risk in Canadian and Swedish Residential Buildings

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

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Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

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