Molecular Characterization of Metastatic Endometrial Cancer by Mass Spectrometry

One of the most reliable prognostic factors in endometrial cancer is the presence of lymph node metastasis. Clinicians presently face the challenge that radiological imaging and conventional surgical-pathological variables such as tumour size, depth of invasion and grade of disease are unreliable in determining if the endometrial cancer has metastasized. Although only 10% of endometrial cancer patients suffer from lymph node metastasis, the majority of them undergo lymphadenectomy, which can be associated with significant complications including lower extremity lymphedema. Based on the assumption that metastasis is mainly determined by the properties of the primary tumour and its interaction with the surrounding tissues, a tissue based proteomic approach combining two complementary methods, peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI) and liquid chromatographytandem mass spectrometry (LC-MS/MS) was undertaken to identify molecular discriminators in primary endometrial cancers which correlate with lymph node metastasis. In a discovery approach, MALDI MSI was carried out on two tissue micro arrays (TMA), containing a total of 43 patients. Upon data acquisition, a canonical correlation analysis (CCA) based method was applied to rank the acquired m/z values based on their power to discriminate the primary carcinomas with and without metastatic potential. The highly ranked m/z values were able to classify 38 out of 43 patients (88.4%) correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. The differential abundance of the two identified proteins, plectin and α-Actin- 2 was further validated using data independent acquisition LC-MS/MS and immunohistochemistry. In a targeted approach, we aimed to improve the prediction model for endometrial cancer metastasis preoperatively. From publically available data and published research, we compiled a list of 60 target proteins with the potential to display differential abundance between primary endometrial cancers with lymph node metastasis versus those without. Using data dependent acquisition LC-MS/MS, we were able to detect 23 of these proteins in an independent cohort of endometrial cancer patients. Using data independent acquisition LC-MS/MS, the differential abundance of 5 of those proteins was observed (p < 0.05). Upon validation by immunohistochemistry, our data indicates that annexin A2 is upregulated while annexin A1 and alpha actinin 4 were downregulated in primary endometrial cancers with lymph node metastasis versus those without. The results of this immunohistochemistry analysis were used to generate a predictive model of endometrial cancer metastasis. Additionally the predictive model using highly ranked m/z values identified by MALDI MSI was generated and compared with other models containing the histopathological variables. However, when compared the MALDI MSI model showed significantly higher predictive accuracy than the model using immunohistochemistry data. Our results showed that the highly ranked m/z values identified from MALDI MSI data serve as new independent prognostic information beyond the established risk factors. The developed molecular classification tool has the potential to predict which tumours have metastasized and which patients would therefore benefit from radical surgery while avoiding those who will not benefit from it and consequently decreasing the risk of post-surgical morbidity. In conclusion, these findings demonstrate a successful application of MALDI MSI for the identification of protein biomarkers of endometrial cancer metastasis.Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 201

Identification and Modelling of Religious Tourism Supply Chain Enablers in Post-Covid Era Using ISM

Post-Covid-19 pandemic, the supply chains of all the trades faced a setback, but the tourism sector faced an extended jolt of this disaster. Religious tourism, which has been adding a sizeable revenue to Indian GDP, came to a downfall. This manuscript aims to identify and model the enablers of the religious tourism supply chain for reviving the economy in the post-Covid era. The research paper elucidates that post-shock of Covid-19, understanding religious tourism enablers will provide opportunities to all the stakeholders of this chain. Eleven enablers for the religious tourism supply chain were identified. The modelling of these enablers using ISM (Interpretive Structural Modelling), provides insight into their hierarchy and interdependence upon each other. The ISM model also illustrates that the enabler Pilgrims belief and value, a mandatory obligation is the most crucial enabler and influence all other enablers. Religious tourism supply chain stakeholders can employ this model to formulate strategies to overcome the post-pandemic challenges. Subsequently focusing upon the key enablers essential in reviving the tourism sector economy.

Obesity in Adolescents: Prevalence and Association with Sociodemographic and Lifestyle Factors

Introduction: Overweight and obesity has become a worldwide epidemic and is a growing public health concern. The increase in prevalence and severity of obesity among children and adolescents has been attributed largely to behavioral factors such as changing eating habits and sedentary lifestyles. Objective: To determine prevalence of obesity and abdominal obesity among adolescents and its association with sociodemographic factors and lifestyle. Methods: Present cross-sectional study was conducted in the urban field practice area under the Community Medicine Department of LLRM Medical College, Meerut, among 872 adolescents. All localities in the field area were covered and house to house survey was done. Questions were asked about eating patterns, physical activity and sedentary lifestyle. Data was collected and analyzed using appropriate statistical tests. Results: The prevalence of overweight and obesity was 17.43, 6.88%, respectively. Obesity was significantly higher among females, those who indulged in unhealthy eating habits were physically inactive, watched television for a longer duration and ate junk while watching television. Conclusion: In the present study, we found that high junk food consumption and a sedentary lifestyle were found to be significantly associated with childhood overweight/obesity. As a result, timely interventions should be taken to improve awareness about healthy lifestyle behavior to prevent obesity and its complications among adolescents

Successfully treated synchronous double malignancy of the breast and esophagus: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of multiple primary cancers is reported to be between 0.3% and 4.3%. The second primary lesion is identified either simultaneously with the primary lesion (synchronous) or after a period of time (metachronous). Few cases of metastasis of breast carcinoma to the esophagus and vice versa have been reported in the past.</p> <p>Case presentation</p> <p>We report an extremely rare case of a 55-year-old Indian woman who had carcinomas in both the esophagus and the breast simultaneously. She was treated successfully using combined modalities of surgery, chemotherapy and radiation therapy.</p> <p>Conclusion</p> <p>Cases of synchronous double malignancies can be treated by dealing with the malignancy in the two sites as independent carcinomas. We have to take into consideration the total dose of radiation to a critical organ as well as the effect of the total dose of toxic chemotherapeutic drugs on our patient.</p

Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird

The unique ornamental features and extreme sexual traits of Peacock have always intrigued scientists and naturalists for centuries. However, the genomic basis of these phenotypes are yet unknown. Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch. Genes involved in early developmental pathways including TGF-β, BMP, and Wnt signaling, which have been shown to be involved in feather patterning, bone morphogenesis, and skeletal muscle development, revealed signs of adaptive evolution and provided useful clues on the phenotypes of peacock. Innate and adaptive immune genes involved in complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the predictions of the Hamilton–Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding toward the phenotypic evolution of Indian peacock

Comparison of Healthy and Dandruff Scalp Microbiome Reveals the Role of Commensals in Scalp Health

Several scalp microbiome studies from different populations have revealed the association of dandruff with bacterial and fungal dysbiosis. However, the functional role of scalp microbiota in scalp disorders and health remains scarcely explored. Here, we examined the bacterial and fungal diversity of the scalp microbiome and their potential functional role in the healthy and dandruff scalp of 140 Indian women. Propionibacterium acnes and Staphylococcus epidermidis emerged as the core bacterial species, where the former was associated with a healthy scalp and the latter with dandruff scalp. Along with the commonly occurring Malassezia species (M. restricta and M. globosa) on the scalp, a strikingly high association of dandruff with yet uncharacterized Malassezia species was observed in the core mycobiome. Functional analysis showed that the fungal microbiome was enriched in pathways majorly implicated in cell-host adhesion in the dandruff scalp, while the bacterial microbiome showed a conspicuous enrichment of pathways related to the synthesis and metabolism of amino acids, biotin, and other B-vitamins, which are reported as essential nutrients for hair growth. A systematic measurement of scalp clinical and physiological parameters was also carried out, which showed significant correlations with the microbiome and their associated functional pathways. The results point toward a new potential role of bacterial commensals in maintaining the scalp nutrient homoeostasis and highlights an important and yet unknown role of the scalp microbiome, similar to the gut microbiome. This study, therefore, provides new perspectives on the better understanding of the pathophysiology of dandruff

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals