Multimodal data analysis applied to a medical setting

Complex diseases, such as cancer, have traditionally been studied using genetic data, or images alone. To understand the biology of such diseases, joint analysis of multiple data modalities could provide interesting insights. We propose the use of canonical correlation analysis (CCA) as a preliminary discovery tool for identifying connections across modalities, specifically between gene expression and features describing cell and nucleus shape, texture, and stain intensity in histopathological images. It is also important to capture the interaction between different types of cells, an important indicator of disease status. To that end, it is crucial to quantify and utilize the spatial distribution of various cell types within the examined tissue at different scales. We employ Ripley's K-statistic, a traditional feature employed in geographical information systems, which captures spatial distribution patterns of individual point sets and interactions between multiple point sets. We propose to improve the histopathology image features by incorporating this descriptor to capture the spatial distribution of the cells, and interactions between lymphocytes and epithelial cells. Applied to 615 breast cancer samples from The Cancer Genome Atlas, CCA revealed significant correlation of 0.736 (p approx 1e-14) and 0.471, (p approx 7e-3) for CCA and Sparse CCA, respectively, of several image features with expression of PAM50 genes, known to be linked to outcome. Sparse CCA, an extension of CCA based on sparsity, revealed associations with enrichment of pathways implicated in cancer without leveraging prior biological understanding. The utility of the Ripley's K-statistic on 710 TCGA breast invasive carcinoma (BRCA) patients' histopathology images in the context of imaging-genetics is demonstrated by its superior correlations with gene expressions. These findings affirm the utility of CCA for joint phenotype-genotype analysis of cancer, and the importance of capturing spatial features at multiple scales

Association of age and caries experience among adult population - An institutional study

Oral health is closely related with general health and people’s quality of life, through affecting their oral functions and social interactions. Dental caries are the major concerns among oral health.The aim of the study is to assess caries experience based on Decayed Missing Filled Teeth Index (DMFT) index among adults patients visiting a private dental college in Chennai. DMFT index was used to evaluate the caries experience. Patient case sheets were reviewed, index scores and age of the patients were collected . 4567 patients were selected for the study and tabulated in excel sheet and statistically analysed using SPSS. Frequency distribution was done using descriptive statistics and Chisquare test was used to analyse the association of caries experience with different age groups. In this study, it was observed that 18-35 year old patients were most prevalent (47.7%) and DMFT scores ranging from 0-7 were maximum with 58.2%. Within the limits of the study, results of the study showed that DMFT score of more than 8 suggesting higher caries experience was prevalent in study participants above 55 years of age. DMFT score of 0-7 was the most prevalent score among 18-35 years and 36-55 years

Bilateral Radicular Cyst – A Rare Case Presentation

Radicular cyst usually originates as a sequel to a periapical inflammatory process following an injury. This report presents a case of radicular cyst with “bilateral involvement” of permanent central incisors with an atypicalradiographical finding and pathological picture that has been discussed. An extensive review of radicular cyst with rarity as seen in the present case was studied. Further importance on treatment with a long term following up of the patient was noted. A sound knowledge regarding the rarity of this lesion is necessary to aid in early diagnosis with an appropriate treatment plan for general practitioners

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Loss of 4E-BP1 expression has been linked to cancer progression and resistance to mTOR inhibitors, but the mechanism underlying 4E-BP1 downregulation in tumors remains unclear. Here we identify Snail as a strong transcriptional repressor of 4E-BP1. We find that 4E-BP1 expression inversely correlates with Snail level in cancer cell lines and clinical specimens. Snail binds to three E-boxes present in the human 4E-BP1 promoter to repress transcription of 4E-BP1. Ectopic expression of Snail in cancer cell lines lacking Snail profoundly represses 4E-BP1 expression, promotes cap-dependent translation in polysomes, and reduces the anti-proliferative effect of mTOR kinase inhibitors. Conversely, genetic and pharmacological inhibition of Snail function restores 4E-BP1 expression and sensitizes cancer cells to mTOR kinase inhibitors by enhancing 4E-BP1-mediated translation-repressive effect on cell proliferation and tumor growth. Our study reveals a critical Snail-4E-BP1 signaling axis in tumorigenesis, and provides a rationale for targeting Snail to improve mTOR-targeted therapies

Unusual Presentation of Primary Squamous Cell Carcinoma of Mandible

Carcinoma arising primarily from the jaw is a locally aggressive lesion with poor prognosis. Primary intraosseous carcinoma (PIOC) lesion develops either de novo remnants of odontogenic epithelium, odontogenic cyst/tumor, epithelium remnants, or/and salivary gland residues. We describe very interesting case of primary intraosseous carcinoma of mandible. This extensive lesion was sent for oncological opinion and further management. Due to the uncertainty of diagnostic criteria of PIOC, only few cases of this lesion with a typical presentation have been reported. This article presents a case of primary intraosseous carcinoma with a unique appearance and detailed review stating its clinicopathological correlation

Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer

PURPOSE: To study target-specific delivery of doxorubicin (Dox) using an RNA aptamer against epithelial cell adhesion molecule (EpCAM) in retinoblastoma (RB) cells. METHODS: The binding affinity of the EpCAM aptamer to RB primary tumor cells, Y79 and WERI-Rb1 cells, and Müller glial cell lines were evaluated with flow cytometry. Formation of physical conjugates of aptamer and Dox was monitored with spectrofluorimetry. Cellular uptake of aptamer-Dox conjugates was monitored through fluorescent microscopy. Drug efficacy was monitored with cell proliferation assay. RESULTS: The EpCAM aptamer (EpDT3) but not the scrambled aptamer (Scr-EpDT3) bound to RB tumor cells, the Y79 and WERI-Rb1 cells. However, the EpCAM aptamer and the scrambled aptamer did not bind to the noncancerous Müller glial cells. The chimeric EpCAM aptamer Dox conjugate (EpDT3-Dox) and the scrambled aptamer Dox conjugate (Scr-EpDT3-Dox) were synthesized and tested on the Y79, WERI-Rb1, and Müller glial cells. The targeted uptake of the EpDT3-Dox aptamer caused cytotoxicity in the Y79 and WERI-Rb1 cells but not in the Müller glial cells. There was no significant binding or consequent cytotoxicity by the Scr-EpDT3-Dox in either cell line. The EpCAM aptamer alone did not cause cytotoxicity in either cell line. CONCLUSIONS: The results show that the EpCAM aptamer-Dox conjugate can selectively deliver the drug to the RB cells there by inhibiting cellular proliferation and not to the noncancerous Müller glial cells. As EpCAM is a cancer stem cell marker, this aptamer-based targeted drug delivery will prevent the undesired effects of non-specific drug activity and will kill cancer stem cells precisely in RB