Search results for: lung microbiome
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 592

Search results for: lung microbiome

592 Analysis of the Lung Microbiome in Cystic Fibrosis Patients Using 16S Sequencing

Authors: Manasvi Pinnaka, Brianna Chrisman

Abstract:

Cystic fibrosis patients often develop lung infections that range anywhere in severity from mild to life-threatening due to the presence of thick and sticky mucus that fills their airways. Since many of these infections are chronic, they not only affect a patient’s ability to breathe but also increase the chances of mortality by respiratory failure. With a publicly available dataset of DNA sequences from bacterial species in the lung microbiome of cystic fibrosis patients, the correlations between different microbial species in the lung and the extent of deterioration of lung function were investigated. 16S sequencing technologies were used to determine the microbiome composition of the samples in the dataset. For the statistical analyses, referencing helped distinguish between taxonomies, and the proportions of certain taxa relative to another were determined. It was found that the Fusobacterium, Actinomyces, and Leptotrichia microbial types all had a positive correlation with the FEV1 score, indicating the potential displacement of these species by pathogens as the disease progresses. However, the dominant pathogens themselves, including Pseudomonas aeruginosa and Staphylococcus aureus, did not have statistically significant negative correlations with the FEV1 score as described by past literature. Examining the lung microbiology of cystic fibrosis patients can help with the prediction of the current condition of lung function, with the potential to guide doctors when designing personalized treatment plans for patients.

Keywords: bacterial infections, cystic fibrosis, lung microbiome, 16S sequencing

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591 Metagenomics, Urinary Microbiome, and Chronic Prostatitis

Authors: Elmira Davasaz Tabrizi, Mushteba Sevil, Ercan Arican

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Directly or indirectly, the human microbiome, or the population of bacteria and other microorganisms living in the human body, has been linked with human health. Various research has examined the connection with both illness status and the composition of the human microbiome, even though current studies indicate that the gut microbiome influences the mucosa and immune system. A significant amount of effort is being put into understanding the human microbiome's natural history in terms of health outcomes while also expanding our comprehension of the molecular connections between the microbiome and the host. To maintain health and avoid disease, these efforts ultimately seek to find efficient methods for recovering human microbial communities. This review article describes how the human microbiome leads to chronic diseases and discusses evidence for an important significant disorder that is related to the microbiome and linked to prostate cancer: chronic prostatitis (CP).

Keywords: urobiome, chronic prostatitis, metagenomic, urinary microbiome

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590 Calculation of Lungs Physiological Lung Motion in External Lung Irradiation

Authors: Yousif Mohamed Y. Abdallah, Khalid H. Eltom

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This is an experimental study deals with measurement of the periodic physiological organ motion during lung external irradiation in order to reduce the exposure of healthy tissue during radiation treatments. The results showed for left lung displacement reading (4.52+1.99 mm) and right lung is (8.21+3.77 mm) which the radiotherapy physician should take suitable countermeasures in case of significant errors. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, the calculation of tumour mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a high resolution CT scan with a margin of 3-5 mm is appropriate.

Keywords: physiological motion, lung, external irradiation, radiation medicine

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589 Liquid Biopsy Based Microbial Biomarker in Coronary Artery Disease Diagnosis

Authors: Eyup Ozkan, Ozkan U. Nalbantoglu, Aycan Gundogdu, Mehmet Hora, A. Emre Onuk

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The human microbiome has been associated with cardiological conditions and this relationship is becoming to be defined beyond the gastrointestinal track. In this study, we investigate the alteration in circulatory microbiota in the context of Coronary Artery Disease (CAD). We received circulatory blood samples from suspected CAD patients and maintain 16S ribosomal RNA sequencing to identify each patient’s microbiome. It was found that Corynebacterium and Methanobacteria genera show statistically significant differences between healthy and CAD patients. The overall biodiversities between the groups were observed to be different revealed by machine learning classification models. We also achieve and demonstrate the performance of a diagnostic method using circulatory blood microbiome-based estimation.

Keywords: coronary artery disease, blood microbiome, machine learning, angiography, next-generation sequencing

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588 Spatio- Temporal Gender Based Patterns of Lung Cancer in the Punjab Province of Pakistan, 2008-2012

Authors: Rubab Z. Kahlon, Ibtisam Butt, Isma Younis, Aamer G. Mufti

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Worldwide lung cancer 1.61 million cases were seen in both genders. Lung carcinoma is the major cause of both morbidity and mortality in the world. Purpose of the present study was to describe the spatio- temporal trends of lung cancer in both genders. A retrospective study was conducted. Total 1498 patients of lung carcinoma were examined. Only lung cancer patients from all over the Punjab were included in the present study. MS Excel 2010 was used for data tabulation and calculation while the Arc GIS version 9.3 was used for geographical representation of the data. 1498 cases of Lung cancer were found from 2008-2012. The number of male patients was 1236 and female was 262. Majority of the patients were from Lahore districts with 807 patients. Lung cancer was more prevalent in male as compared to female in our region. Increase in the prevalence of lung cancer was prominently seen in the most populated and industrial areas of the Punjab province. Time trend of five years showed fluctuation in the lung cancer incidence during the study period.

Keywords: districts, gender, lung cancer trends, Punjab province of Pakistan

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587 Automatic Segmentation of Lung Pleura Based On Curvature Analysis

Authors: Sasidhar B., Bhaskar Rao N., Ramesh Babu D. R., Ravi Shankar M.

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Segmentation of lung pleura is a preprocessing step in Computer-Aided Diagnosis (CAD) which helps in reducing false positives in detection of lung cancer. The existing methods fail in extraction of lung regions with the nodules at the pleura of the lungs. In this paper, a new method is proposed which segments lung regions with nodules at the pleura of the lungs based on curvature analysis and morphological operators. The proposed algorithm is tested on 06 patient’s dataset which consists of 60 images of Lung Image Database Consortium (LIDC) and the results are found to be satisfactory with 98.3% average overlap measure (AΩ).

Keywords: curvature analysis, image segmentation, morphological operators, thresholding

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586 The Metaproteomic Analysis of HIV Uninfected Exposed Infants’ Gut Microbiome to Help Understand Their Poor Health Statuses in An African Cohort

Authors: Tara Miller, Tariq Ganief, Jonathan Blackburn

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Millions of babies are still born to HIV-infected mothers each year despite the ramped-up HAART use. However, these infants are HIV uninfected but exposed, which is now a growing population that has weakened immune systems and poorer outcomes. Due to HIV exposure and possible ARV exposure during pregnancy and breastfeeding, these infants are believed to have altered immune responses and microbiomes when compared to their healthy counterparts. The gut microbiome roles an important role in infant development, specifically in the immune system. Research has shown these HIV-exposed, uninfected infants have weaker immune responses to their neonate vaccines, and in developing countries, this leaves them vulnerable to opportunistic disease. By gaining a deeper understanding of the gut microbiome and the products of the microbes via metaproteomic analysis, we can hopefully understand and improve the immune system and health of these infants. To investigate the metaproteome of the infants’ guts, mass spectrometry will be used, followed by data analysis using DIA-NN. The hypothesized results are that the HIV-exposed, uninfected infants have an altered microbiome compared to their healthy counterparts. Additionally, the differences found are hypothesized to be involved with inflammation which would contribute to the poor health of the infants.

Keywords: HIV, mass spectrometry, metaproteomics, microbiome

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585 The Comparison Study of Human Microbiome in Chronic Rhinosinusitis between Adults and Children

Authors: Il Ho Park, Joong Seob Lee, Sung Hun Kang, Jae-Min Shin, Il Seok Park, Seok Min Hong, Seok Jin Hong

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Introduction: The human microbiota is the aggregate of microorganisms, and the bacterial microbiome of the human digestive tract contributes to both health and disease. In health, bacteria are key components in the development of mucosal barrier function and in innate and adaptive immune responses, and they also work to suppress the establishment of pathogens. In human upper airway, the sinonasal microbiota might play an important role in chronic rhinosinusitis (CRS). The purpose of this study is to investigate the human upper airway microbiome in CRS patients and to compare the sinonasal microbiome of adults with children. Materials and methods: A total of 19 samples from 19 patients (Group1; 9 CRS in children, aged 5 to 14 years versus Group 2; 10 CRS in adults aged 21 to 59 years) were examined. Swabs were collected from the middle meatus and/or anterior ethmoid region under general anesthesia during endoscopic sinus surgery or tonsillectomy. After DNA extraction from swab samples, we analysed bacterial microbiome consortia using 16s rRNA gene sequencing approach (the Illumina MiSeq platform). Results: In this study, relatively abundance of the six bacterial phyla and tremendous genus and species found in substantial amounts in the individual sinus swab samples, include Corynebacterium, Hemophilus, Moraxella, and Streptococcus species. Anaerobes like Fusobacterium and Bacteroides were abundantly present in the children group, Bacteroides and Propionibacterium were present in adults group. In genus, Haemophilus was the most common CRS microbiome in children and Corynebacterium was the most common CRS microbiome in adults. Conclusions: Our results show the diversity of human upper airway microbiome, and the findings will suggest that CRS is a polymicrobial infection. The Corynebacterium and Hemophilus may live as commensals on mucosal surfaces of sinus in the upper respiratory tract. The further study will be needed for analysis of microbiome-human interactions in upper airway and CRS.

Keywords: microbiome, upper airway, chronic rhinosinusitis, adult and children

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584 A Study of Fecal Sludge Management in Auroville and Its Surrounding Villages in Tamilnadu, India

Authors: Preethi Grace Theva Neethi Dhas

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A healthy human gut microbiome has commensal and symbiotic functions in digestion and is a decisive factor for human health. The soil microbiome is a crucial component in the ecosystem of soils and their health and resilience. Changes in soil microbiome are linked to human health. Ever since the industrial era, the human and the soil microbiome have been going through drastic changes. The soil microbiome has changed due to industrialization and extensive agricultural practices, whereas humans have less contact with soil and increased intake of highly processed foods, leading to changes in the human gut microbiome. Regenerating the soil becomes crucial in maintaining a healthy ecosystem. The nutrients, once obtained from the soil, need to be given back to the soil. Soil degradation needs to be addressed in effective ways, like adding organic nutrients back to the soil. Manure from animals and humans needs to be returned to the soil, which can complete the nutrient cycle in the soil. On the other hand, fecal sludge management (FSM) is a growing concern in many parts of the developing world. Hence, it becomes crucial to treat and reuse fecal sludge in a safe manner, i.e., low in risk to human health. Co-composting fecal sludge with organic wastes is a practice that allows the safe management of fecal sludge and the safe application of nutrients to the soil. This paper will discuss the possible impact of co-composting fecal sludge with coconut choir waste on the soil, water, and ecosystem at large. Impact parameters like nitrogen, phosphorus, and fecal coliforms will be analyzed. The overall impact of fecal sludge application on the soil will be researched and presented in this study.

Keywords: fecal sludge management, nutrient cycle, soil health, composting

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583 Evaluation of Promoter Hypermethylation in Tissue and Blood of Non-Small Cell Lung Cancer Patients and Association with Survival

Authors: Ashraf Ali, Kriti Upadhyay, Puja Sohal, Anant Mohan, Randeep Guleria

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Background: Gene silencing by aberrant promoter hypermethylation is common in lung cancer and is an initiating event in its development. Aim: To evaluate the gene promoter hypermethylation frequency in serum and tissue of lung cancer patients. Method: 95 newly diagnosed untreated advance stage lung cancer patients and 50 cancer free matched controls were studied. Bisulfite modification of tissue and serum DNA was done; modified DNA was used as a template for methylation-specific PCR analysis. Survival was assessed for one year. Results: Of 95 patients, 82% were non-small cell lung cancer (34% squamous cell carcinoma, 34% non-small cell lung cancer and 14% adenocarcinoma) and 18% were small cell lung cancer. Biopsy revealed that tissue of 89% and 75% of lung cancer patients and 85% and 52% of controls had promoter hypermethylated for MGMT (p=0.35) and p16(p<0.001) gene, respectively. In serum, 33% and 49% of lung cancer patients and 28% and 43% controls were positive for MGMT and p16 gene. No significant correlation was found between survival and clinico-pathological parameters. Conclusion: High gene promoter methylation frequency of p16 gene in tissue biopsy may be linked with early stages of carcinogenesis. Appropriate follow-up is required for confirmation of this finding.

Keywords: lung cancer, MS- PCR, methylation, molecular biology

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582 Remodeling of Gut Microbiome of Pakistani Expats in China After Intermittent Fasting/Ramadan Fasting

Authors: Hafiz Arbab Sakandar

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Time-restricted intermittent fasting (TRIF) impacts host’s physiology and health. Plenty of health benefits have been reported for TRIF in animal models. However, limited studies have been conducted on humans especially in underdeveloped economies. Here, we designed a study to investigate the impact of TRIF/Ramadan fasting (16:8) on the modulation of gut-microbiome structure, metabolic pathways, and predicted metabolites and explored the correlation among them at different time points (during and after the month of Ramadan) in Pakistani Expats living in China. We observed different trends of Shannon-Wiener index in different subjects; however, all subjects showed substantial change in bacterial diversity with the progression of TRIF. Moreover, the changes in gut microbial structure by the end of TRIF were higher vis-a-vis in the beginning, significant difference was observed among individuals. Additionally, metabolic pathways analysis revealed that amino acid, carbohydrate and energy metabolism, glycan biosynthesis metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short chain fatty acid showed substantial difference at different time points based on the predicted metabolism. In conclusion, these results contribute to further our understanding about the key relationship among, dietary intervention (TRIF), gut microbiome structure and function. The preliminary results from study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome-tailored interventions among the Pakistani populace. Nonetheless, extensive, and rigorous large-scale research on the Pakistani population is necessary to expound on the association between diet, gut microbiome, and overall health.

Keywords: gut microbiome, health, fasting, functionality

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581 The Relation Between Oxidative Stress, Inflammation, and Neopterin in the Paraquat-Induced Lung Toxicity

Authors: M. Toygar, I. Aydin, M. Agilli, F. N. Aydin, M. Oztosun, H. Gul, E. Macit, Y. Karslioglu, T. Topal, B. Uysal, M. Honca

Abstract:

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p< 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p 1/4 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Keywords: paraquat, inflammation, oxidative stress, neopterin, lung toxicity

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580 PathoPy2.0: Application of Fractal Geometry for Early Detection and Histopathological Analysis of Lung Cancer

Authors: Rhea Kapoor

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Fractal dimension provides a way to characterize non-geometric shapes like those found in nature. The purpose of this research is to estimate Minkowski fractal dimension of human lung images for early detection of lung cancer. Lung cancer is the leading cause of death among all types of cancer and an early histopathological analysis will help reduce deaths primarily due to late diagnosis. A Python application program, PathoPy2.0, was developed for analyzing medical images in pixelated format and estimating Minkowski fractal dimension using a new box-counting algorithm that allows windowing of images for more accurate calculation in the suspected areas of cancerous growth. Benchmark geometric fractals were used to validate the accuracy of the program and changes in fractal dimension of lung images to indicate the presence of issues in the lung. The accuracy of the program for the benchmark examples was between 93-99% of known values of the fractal dimensions. Fractal dimension values were then calculated for lung images, from National Cancer Institute, taken over time to correctly detect the presence of cancerous growth. For example, as the fractal dimension for a given lung increased from 1.19 to 1.27 due to cancerous growth, it represents a significant change in fractal dimension which lies between 1 and 2 for 2-D images. Based on the results obtained on many lung test cases, it was concluded that fractal dimension of human lungs can be used to diagnose lung cancer early. The ideas behind PathoPy2.0 can also be applied to study patterns in the electrical activity of the human brain and DNA matching.

Keywords: fractals, histopathological analysis, image processing, lung cancer, Minkowski dimension

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579 Recurrence of Papillary Thyroid Cancer with an Interval of 40 Years. Report of an Autopsy Case

Authors: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

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A 75-year-old woman took thyroidectomy forty years previously. Enlarged masses were seen at autopsy just above and below the left clavicle. We proved the diagnosis of papillary thyroid cancer (PTC) and lung metastasis by histological examinations. The prognosis of PTC is excellent; the 10-year survival rate ranges between 85 and 99%. Lung metastases may be found in 10% of the patients with PTC. We report an unusual case of recurrence of PTC with metastasis to the lung.

Keywords: papillary thyroid cancer, lung metastasis, autopsy, histopathological findings

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578 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

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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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577 Blood Microbiome in Different Metabolic Types of Obesity

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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576 The Effects of Terrein: A Secondary Metabolite from Aspergillus terreus as Anticancer and Antimetastatic Agent on Lung Cancer Cells

Authors: Paiwan Buachan, Maneekarn Namsa-Aid, Suchada Jongrungruangchok, Foengchat Jarintanan, Wanlaya Uthaisang-Tanechpongtamb

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Lung cancer or pulmonary carcinoma is the uncontrolled growth of abnormal cells in one or both of the lungs. These abnormal cells can spread to other organs of the body through lymphatic system or bloodstream which is called metastatic stage that leading cause of cancer death. Terrein (C₈H₁₀O₃; MW= 154.06 kDa) is a secondary bioactive fungal metabolite, which was isolated from the Aspergillus terreus. In this study, we investigated the effects of terrein on the inhibition of human lung cancer cell proliferation and metastasis. The A549 human non-small cell lung cancer cell line was used as a model. Terrein significantly inhibited lung cancer cell proliferation measuring by a colorimetric MTT assay (IC₅₀ 0.32 mM) and significantly inhibited metastatic processes including migration, invasion, and adhesion that determined by wound healing assay, transwell assay, and adhesion assay, respectively. These findings indicate that terrein could be a potential therapeutic agent for lung cancer.

Keywords: terrein, lung cancer, anticancer, antimetastatic

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575 Green Tea Extract: Its Potential Protective Effect on Bleomycin Induced Lung Injuries in Rats

Authors: Azza EL-Medany, Jamila EL-Medany

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Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present work studied the effect of green tea extract on bleomycin–induced lung fibrosis in rats. Animals were divided into three groups: (1) Saline control group; (2) bleomycin group in which rats were injected with bleomycin (15mg/kg,i.p.) three times a week for four weeks; (3) bleomycin and green tea group in which green tea extract was given to rats (100mg/kg/day, p.o) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the experiment. Bleomycin–induced pulmonary injury and lung fibrosis that was indicated by increased lung hydroxyproline content, elevated nitric oxide synthase, myeoloperoxidase (MPO), platelet activating factor (PAF), tumor necrosis factor α (TNF_α), transforming growth factor 1β (TGF1β) and angiotensin converting enzyme (ACE) activity in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration (GSH). Moreover, bleomycin resulted in a severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and green tea extract reduced bleomycin–induced lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, levels of MPO, PAF, TNF-α, and ACE in lung tissues. Furthermore, green tea extract ameliorated bleomycin– induced reduction in GSH concentration. Finally, histological evidence supported the ability of green tea extract to attenuate bleomycin–induced lung fibrosis and consolidation. Thus, the finding of the present study provides that green tea may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Keywords: bleomycin, lung fibrosis, green tea, oxygen species

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574 Surgical Outcomes of Lung Cancer Surgery in Tasmania

Authors: Ayeshmanthe Rathnayake, Ashutosh Hardikar

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Introduction: Lung cancer is the most common cause of cancer death in Australia, with more than 13000 cases per year. Until now, there has been a major deficiency of national comprehensive thoracic surgery data. The thoracic workload for surgeons as well as caseload per unit, is highly variable, with some centres performing less than 15 cases per annum, thus raising concerns about optimal care at low-volume sites. This is an attempt to review the outcomes of lung cancer surgery in Tasmania. Method: The objective of this study is to determine the surgical outcomes of lung cancer surgery at Royal Hobart Hospital (RHH) with the primary outcome of surgical mortality. Four hundred fifty-one cases were analysed retrospectively from 2010 to May 2022. Results: A total of 451 patients underwent thoracic surgery with a primary diagnosis of lung cancer. The primary outcome of 30-day mortality was <0.5%. The mean age was 65.3 years, with male predominance and a 4.2% prevalence of Indigenous Australians. The mean LOS was 7.5 days. The surgical approach was either VATS (50.3%) or Thoracotomy (49.7%), with a trend towards the former in recent years with an increase in the proportion of VATS from 18.2% to 51% (p<0.05) in complex resections since 2019. A corresponding reduction in conversion rate to open was observed (18% vs. 5.5%), and there were no deaths within this subgroup. Lung resections were divided into lobectomy (55.4%), wedge resection (36.8%), segmentectomy (2.9%) and pneumonectomy (4.9%). The RHH demonstrates good surgical outcomes for lung cancer and provides a sustainable service for Tasmania. Conclusion: This retrospective study reports the surgical outcomes of lung cancer surgery at the Royal Hobart Hospital, thereby providing insight into the surgical management of lung cancer in the state thus far. The state has been slow to catch up on the minimally invasive program, but the overall results have been comparable to most peers.

Keywords: lung cancer, thoracic surgery, lung resection, surgical outcomes

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573 Hsa-miR-329 Functions as a Tumor Suppressor through Targeting MET in Non-Small Cell Lung Cancer

Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2, and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.

Keywords: hsa-miRNA-329(miR-329), MET, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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572 Insights into Archaeological Human Sample Microbiome Using 16S rRNA Gene Sequencing

Authors: Alisa Kazarina, Guntis Gerhards, Elina Petersone-Gordina, Ilva Pole, Viktorija Igumnova, Janis Kimsis, Valentina Capligina, Renate Ranka

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Human body is inhabited by a vast number of microorganisms, collectively known as the human microbiome, and there is a tremendous interest in evolutionary changes in human microbial ecology, diversity and function. The field of paleomicrobiology, study of ancient human microbiome, is powered by modern techniques of Next Generation Sequencing (NGS), which allows extracting microbial genomic data directly from archaeological sample of interest. One of the major techniques is 16S rRNA gene sequencing, by which certain 16S rRNA gene hypervariable regions are being amplified and sequenced. However, some limitations of this method exist including the taxonomic precision and efficacy of different regions used. The aim of this study was to evaluate the phylogenetic sensitivity of different 16S rRNA gene hypervariable regions for microbiome studies in the archaeological samples. Towards this aim, archaeological bone samples and corresponding soil samples from each burial environment were collected in Medieval cemeteries in Latvia. The Ion 16S™ Metagenomics Kit targeting different 16S rRNA gene hypervariable regions was used for library construction (Ion Torrent technologies). Sequenced data were analysed by using appropriate bioinformatic techniques; alignment and taxonomic representation was done using Mothur program. Sequences of most abundant genus were further aligned to E. coli 16S rRNA gene reference sequence using MEGA7 in order to identify the hypervariable region of the segment of interest. Our results showed that different hypervariable regions had different discriminatory power depending on the groups of microbes, as well as the nature of samples. On the basis of our results, we suggest that wider range of primers used can provide more accurate recapitulation of microbial communities in archaeological samples. Acknowledgements. This work was supported by the ERAF grant Nr. 1.1.1.1/16/A/101.

Keywords: 16S rRNA gene, ancient human microbiome, archaeology, bioinformatics, genomics, microbiome, molecular biology, next-generation sequencing

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571 Iterative Method for Lung Tumor Localization in 4D CT

Authors: Sarah K. Hagi, Majdi Alnowaimi

Abstract:

In the last decade, there were immense advancements in the medical imaging modalities. These advancements can scan a whole volume of the lung organ in high resolution images within a short time. According to this performance, the physicians can clearly identify the complicated anatomical and pathological structures of lung. Therefore, these advancements give large opportunities for more advance of all types of lung cancer treatment available and will increase the survival rate. However, lung cancer is still one of the major causes of death with around 19% of all the cancer patients. Several factors may affect survival rate. One of the serious effects is the breathing process, which can affect the accuracy of diagnosis and lung tumor treatment plan. We have therefore developed a semi automated algorithm to localize the 3D lung tumor positions across all respiratory data during respiratory motion. The algorithm can be divided into two stages. First, a lung tumor segmentation for the first phase of the 4D computed tomography (CT). Lung tumor segmentation is performed using an active contours method. Then, localize the tumor 3D position across all next phases using a 12 degrees of freedom of an affine transformation. Two data set where used in this study, a compute simulate for 4D CT using extended cardiac-torso (XCAT) phantom and 4D CT clinical data sets. The result and error calculation is presented as root mean square error (RMSE). The average error in data sets is 0.94 mm ± 0.36. Finally, evaluation and quantitative comparison of the results with a state-of-the-art registration algorithm was introduced. The results obtained from the proposed localization algorithm show a promising result to localize alung tumor in 4D CT data.

Keywords: automated algorithm , computed tomography, lung tumor, tumor localization

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570 Cadaveric Study of Lung Anatomy: A Surgical Overview

Authors: Arthi Ganapathy, Rati Tandon, Saroj Kaler

Abstract:

Introduction: A thorough knowledge of variations in lung anatomy is of prime significance during surgical procedures like lobectomy, pneumonectomy, and segmentectomy of lungs. The arrangement of structures in the lung hilum act as a guide in performing such procedures. The normal pattern of arrangement of hilar structures in the right lung is eparterial bronchus, pulmonary artery, hyparterial bronchus and pulmonary veins from above downwards. In the left lung, it is pulmonary artery, principal bronchus and pulmonary vein from above downwards. The arrangement of hilar structures from anterior to posterior in both the lungs is pulmonary vein, pulmonary artery, and principal bronchus. The bronchial arteries are very small and usually the posterior most structures in the hilum of lungs. Aim: The present study aims at reporting the variations in hilar anatomy (arrangement and number) of lungs. Methodology: 75 adult formalin fixed cadaveric lungs from the department of Anatomy AIIMS New Delhi were observed for variations in the lobar anatomy. Arrangement of pulmonary hilar structures was meticulously observed, and any deviation in the pattern of presentation was recorded. Results: Among the 75 adult lung specimens observed 36 specimens were of right lung and the rest of left lung. Seven right lung specimens showed only 2 lobes with an oblique fissure dividing them and one left lung showed 3 lobes. The normal pattern of arrangement of hilar structures was seen in 22 right lungs and 23 left lungs. Rest of the lung specimens (14 right and 16 left) showed a varied pattern of arrangement of hilar structures. Some of them showed alterations in the sequence of arrangement of pulmonary artery, pulmonary veins, bronchus, and others in the number of these structures. Conclusion: Alterations in the pattern of arrangement of structures in the lung hilum are quite frequent. A compromise in knowledge of such variations will result in inadvertent complications like intraoperative bleeding during surgical procedures.

Keywords: fissures, hilum, lobes, pulmonary

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569 Graph Cuts Segmentation Approach Using a Patch-Based Similarity Measure Applied for Interactive CT Lung Image Segmentation

Authors: Aicha Majda, Abdelhamid El Hassani

Abstract:

Lung CT image segmentation is a prerequisite in lung CT image analysis. Most of the conventional methods need a post-processing to deal with the abnormal lung CT scans such as lung nodules or other lesions. The simplest similarity measure in the standard Graph Cuts Algorithm consists of directly comparing the pixel values of the two neighboring regions, which is not accurate because this kind of metrics is extremely sensitive to minor transformations such as noise or other artifacts problems. In this work, we propose an improved version of the standard graph cuts algorithm based on the Patch-Based similarity metric. The boundary penalty term in the graph cut algorithm is defined Based on Patch-Based similarity measurement instead of the simple intensity measurement in the standard method. The weights between each pixel and its neighboring pixels are Based on the obtained new term. The graph is then created using theses weights between its nodes. Finally, the segmentation is completed with the minimum cut/Max-Flow algorithm. Experimental results show that the proposed method is very accurate and efficient, and can directly provide explicit lung regions without any post-processing operations compared to the standard method.

Keywords: graph cuts, lung CT scan, lung parenchyma segmentation, patch-based similarity metric

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568 Hsa-miR-139-5p Acts as a Tumor Suppressor by Targeting C-Met in Non-Small Cell Lung Cancer

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

Abstract:

Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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567 DSC2 Promotes the Proliferation, Metastasis and Drug Resistance of Lung Cancer by Activating the PI3K/AKT Pathway

Authors: Qi LI, Xu Lin, Nengming Lin

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Objective: The aim of this study was to investigate the role of desmocollin 2 (DSC2) protein in the proliferation, migration and drug resistance of lung cancer cells. Method: CCK-8 assays and colony formation assays were used to evaluate the effect of dsc2 regulation on cancer cell viability and colony formation. Transwell assays and wound healing assays were also performed. Cell flow double staining was used to detect the apoptosis rate of cells with DSC2, which was added cisplatin. Western blot assay was used to detect cell cycle, PI3k/Akt and apoptosis-related proteins. Results: Our data showed that dsc2 is upregulated in clinical lung cancer tissues compared with pericarcinomatous tissues, and it is differentially expressed in lung cancer cell lines. The down-regulation of dsc2 in A549 and H358 lung cancer cells significantly suppressed the cell proliferation, metastasis, and motility. In contrast, the opposite effects were observed in overexpression of dsc2 both in H23 and PC9 cell lines. In addition to lung adenocarcinoma cell lines, we also examined its expression in lung squamous cell lines, such as H226. Western blotting showed that dsc2 could reduce the level of phosphorylated Akt (Ser 473) and p-mTOR. Thus, it is speculated that dsc2 up-regulation promotes proliferation and invasiveness through activation of the PI3K/AKT pathway. Also, knockdown of dsc2 in A549 and H226 could significantly decreased in the levels of cyclinB and wee1 protein. Additionally, flow cytometry showed that dsc2 knockdown combined with cisplatin could significantly enhance cell apoptosis rate. Conclusion: These data suggest that dsc2 promotes the proliferation and migration of lung cancer cells in vitro. Also, the results suggested that dsc2 could affect the cell cycle and apoptosis of lung cells. Furthermore, knockdown of dsc2 could sensitize cisplatin in both lung adenocarcinoma and lung squamous cell lines. Thus we suggested that dsc2 can be used as a therapeutic target for lung cancer.

Keywords: desmocollin 2, cisplatin, lung cancer, PI3K/AKT, lung squamous cell

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566 The Impact of Lipids on Lung Fibrosis

Authors: G. Wojcik, J. Gindlhuber, A. Syarif, K. Hoetzenecker, P. Bohm, P. Vesely, V. Biasin, G. Kwapiszewska

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Pulmonary fibrosis is a rare disease where uncontrolled wound healing processes damage the lung structure. Intensive changes within the extracellular matrix (ECM) and its interaction with fibroblasts have a major role in pulmonary fibrosis development. Among others, collagen is one of the main components of the ECM, and it is important for lung structure. In IPF, constant production of collagen by fibroblast, through TGFβ1-SMAD2/3 pathways, leads to an uncontrolled deposition of matrix and hence lung remodeling. Abnormal changes in lipid production, alterations in fatty acids (FAs) metabolism, enhanced oxidative stress, and lipid peroxidation in fibrotic lung and fibrotic fibroblasts have been reported; however, the interplay between the collagen and lipids is not yet established. One of the FAs influx regulators is Angiopoietin-like 4 (ANGPTL4), which inhibits lipoprotein lipase work, decreasing the availability of FAs. We hypothesized that altered lipid composition or availability could have the capability to influence the phenotype of different fibroblast populations in the lung and hence influence lung fibrosis. To prove our hypothesis, we aim to investigate lipids and their influence on human, animal, and in vitro levels. In the bleomycin model, treatment with the well-known metabolic drugs Rosiglitazone or Metformin significantly lower collagen production. Similar results were noticed in ANGPTL4 KO animals, where the KO of ANGPTL4 leads to an increase of FAs availability and lower collagen deposition after the bleomycin challenge. Currently, we study the treatment of different FAs on human lung para fibroblasts (hPF) isolated from donors. To understand the lipid composition, we are collecting human lung tissue from donors and pulmonary fibrosis patients for Liquid chromatography-mass spectrometry. In conclusion, our results suggest the lipid influence on collagen deposition during lung fibrosis, but further research needs to be conducted to understand the matter of this relationship.

Keywords: collagen, fibroblasts, lipidomics, lung, pulmonary fibrosis

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565 Carvacrol Attenuates Lung Injury in Rats with Severe Acute Pancreatitis

Authors: Salim Cerig, Fatime Geyikoglu, Pınar Akpulat, Suat Colak, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Kubra Koc

Abstract:

This study was designed to evaluate whether carvacrol (CAR) could provide protection against lung injury by acute pancreatitis development. The rats were randomized into groups to receive (I) no therapy; (II) 50 μg/kg cerulein at 1h intervals by four intraperitoneal injections (i.p.); (III) 50, 100 and 200 mg/kg CAR by one i.p.; and (IV) cerulein+CAR after 2h of cerulein injection. 12h later, serum samples were obtained to assess pancreatic function the lipase and amylase values. The animals were euthanized and lung samples were excised. The specimens were stained with hematoxylin-eosin (H&E), periodic acid–Schif (PAS), Mallory's trichrome and amyloid. Additionally, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The results showed that the serum activity of lipase and amylase in AP rats were significantly reduced after the therapy (p<0.05). We also found that the 100 mg/kg dose of CAR significantly decreased 8-OH-dG levels. Moreover, the severe pathological findings in the lung such as necrosis, inflammation, congestion, fibrosis, and thickened alveolar septum were attenuated in the AP+CAR groups when compared with AP group. Finally, the magnitude of the protective effect on lung is certain, and CAR is an effective therapy for lung injury caused by AP.

Keywords: antioxidant activity, acute pancreatitis, carvacrol, experimental, lung injury, oxidative DNA damage

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564 Changes in the fecal Microbiome of Periparturient Dairy Cattle and Associations with the Onset of Salmonella Shedding

Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing

Abstract:

Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.

Keywords: dairy cattle, microbiome, periparturient, Salmonella

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563 The Mediating Role of Resilience in the Association Between Stigma and Psychosocial Adjustment: A Cross-sectional Study Among Young and Middle-Aged Patients With Lung Cancer

Authors: Ziyun Li, Jiudi Zhong, June Zhang

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Background: The diagnosis and treatment of lung cancer lead to varying degrees of psychological and social maladjustment among patients with lung cancer. Understanding psychosocial adjustment (PA) and its influencing factors in young and middle-aged lung cancer patients is essential to help them return to society and lead a normal life. Objectives: This study aims to examine the mediating role of resilience in the association between stigma and psychosocial adjustment among young and middle-aged patients with lung cancer. Methods: A total of 235 patients with lung cancer were recruited from a tertiary grade A cancer center in southern China and investigated using a self-designed general information questionnaire, Psychosocial Adjustment to Illness Scale Self-Report, Social Impact Scale, and Conner-Davidson Resilience Scale. Results: The mean score of PA was (32.61±14.75), and its influencing factors included treatment modalities, stigma, and resilience. The total effect of stigma on PA was significant (total effect=0.418, SE=0.045, 95%CI [0.310-0.497]), and a positive indirect effect was identified for stigma on PA via resilience (indirect effect=0.143, SE=0.041, 95% CI [0.075-0.236]). Conclusion: Stigma and resilience are significantly associated with PA, and resilience is also a mediating variable between stigma and PA. This study suggests that individualized interventions can be made to improve the PA by alleviating their stigma, or by enhancing their resilience in young and middle-aged lung cancer patients.

Keywords: psychosocial adjustment, lung cancer, cancer caring, nursing, young and middle-aged

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