Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1.

Introduction: Matching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.

Methods: In this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.

A consensus-based classification workflow to determine genetically inferred ancestry from comprehensive genomic profiling of patients with solid tumors.

Disparities in cancer diagnosis, treatment, and outcomes based on self-identified race and ethnicity (SIRE) are well documented, yet these variables have historically been excluded from clinical research. Without SIRE, genetic ancestry can be inferred using single-nucleotide polymorphisms (SNPs) detected from tumor DNA using comprehensive genomic profiling (CGP). However, factors inherent to CGP of tumor DNA increase the difficulty of identifying ancestry-informative SNPs, and current workflows for inferring genetic ancestry from CGP need improvements in key areas of the ancestry inference process.

Photodynamic therapy: An emerging therapeutic modality in dentistry.

Photodynamic Therapy (PDT) is a rapidly evolving, non-invasive treatment modality with considerable promise in dental pharmacotherapeutics. This review article comprehensively examines PDT, beginning with its principles and then delving into its diverse applications in dentistry, including periodontal disease, endodontics, oral cancer, dental implants, and dental caries. Each area presents the latest research and discusses the potential benefits and challenges.

Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer.

Introduction: Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking.

Methods: We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients.

The Impact of Prior Single-Gene Testing on Comprehensive Genomic Profiling Results for Patients with Non-Small Cell Lung Cancer.

Introduction: Tissue-based broad molecular profiling of guideline-recommended biomarkers is advised for the therapeutic management of patients with non-small cell lung cancer (NSCLC). However, practice variation can affect whether all indicated biomarkers are tested. We aimed to evaluate the impact of common single-gene testing (SGT) on subsequent comprehensive genomic profiling (CGP) test outcomes and results in NSCLC.

RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.

NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4397 solid tumor formalin-fixed, paraffin-embedded samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen NRG1 fusions were found in 17 unique patients, across multiple tumor types, including non-small-cell lung (n = 7), breast (n = 2), colorectal (n = 3), esophageal (n = 2), ovarian (n = 1), pancreatic (n = 1), and unknown primary (n = 1) carcinomas, with a cumulative incidence of 0.

Langerhans cell histiocytosis: A diagnostic enigma in the oral cavity.

Langerhans cell histiocytosis (LCH) is a rare reactive and proliferative disease of histiocytes. The disease occurs predominantly in children and rarely in adults. This disease of unknown etiology exhibits extreme clinical heterogeneity.

Genomic Profiling of Circulating Tumor DNA From Cerebrospinal Fluid to Guide Clinical Decision Making for Patients With Primary and Metastatic Brain Tumors.

Despite advances in systemic therapies for solid tumors, the development of brain metastases remains a significant contributor to overall cancer mortality and requires improved methods for diagnosing and treating these lesions. Similarly, the prognosis for malignant primary brain tumors remains poor with little improvement in overall survival over the last several decades. In both primary and metastatic central nervous system (CNS) tumors, the challenge from a clinical perspective centers on detecting CNS dissemination early and understanding how CNS lesions differ from the primary tumor, in order to determine potential treatment strategies.

Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers.

RAF family protein kinases signal through the MAPK pathway to orchestrate cellular proliferation, survival, and transformation. Identifying BRAF alterations in pediatric cancers is critically important as therapeutic agents targeting BRAF or MEK may be incorporated into the clinical management of these patients. In this study, we performed comprehensive genomic profiling on 3,633 pediatric cancer samples and identified a cohort of 221 (6.

Accuracy of Demirjian's and Indian-specific formulae in age estimation using eight-teeth method in Kanyakumari population.

Background: Most of the scientific formulae for age estimation in forensic odontology were tested among western population and hence cannot be applied to the Indian population consistently. Therefore, it was in this context that Dr. Ashith B.

Genomic Landscape of Adult and Pediatric -Like B-Lymphoblastic Leukemia Using Parallel DNA and RNA Sequencing.

BCR-ABL1-like B-Acute Lymphoblastic Leukemia (B-ALL) is a subset of B-ALL with a poor prognosis that is found in all age groups. Definitive identification of these patients is difficult in routine clinical practice as gene expression profiling, the gold standard test, is not widely available. Comprehensive genomic profiling performed on 450 patients with extensive fusion profiling revealed a wide range of genomic alterations which were consistent with a classification of BCR-ABL1-like B-ALL in 29% of cases.

Precision Neuro-oncology: the Role of Genomic Testing in the Management of Adult and Pediatric Gliomas.

In recent years, large-scale genomic studies have expanded our knowledge regarding genomic drivers in tumors of the central nervous system. While histopathologic analysis of brain tumors remains the primary method for tumor classification, the clinical utility of molecular and genomic testing to support and/or complement tumor classification continues to expand. This approach enhances diagnostic accuracy and provides clinicians with objective data to facilitate discussions regarding prognosis and treatment decisions, including selection of clinical trials.

Genotoxic Effects of Silver Amalgam and Composite Restorations: Micronuclei-Based Cohort and Case-Control Study in Oral Exfoliated Cells.

Context: A huge number of people carry dental fillings which contain either mercury-based amalgam and/or the recently introduced methacrylate-based resins. It has been shown that both these materials are known to be leached into the oral cavity and induce genotoxic alterations in the buccal mucosal cells. Because of its low cost and ease of manipulation, dental amalgam is still widely used as a restorative material in developing countries.

Virtopsy: An integration of forensic science and imageology.

In an era where noninvasive and minimally invasive techniques are heralding medical innovations and health science technology, necrological analysis is not bereft of this wave. Virtopsy is virtual autopsy. It is a new-age complimentary documentation approach to identify and analyze the details of demise.

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

Unlabelled: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis.

Coordination of self-renewal in glioblastoma by integration of adhesion and microRNA signaling.

Background: Cancer stem cells (CSCs) provide an additional layer of complexity for tumor models and targets for therapeutic development. The balance between CSC self-renewal and differentiation is driven by niche components including adhesion, which is a hallmark of stemness. While studies have demonstrated that the reduction of adhesion molecules, such as integrins and junctional adhesion molecule-A (JAM-A), decreases CSC maintenance.

REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells.

Our previous studies have shown that the regulatory network that maintains pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context-dependent manner and can be modulated, at least in part, by re-calibration of an intracellular network of pluripotency factors as well as cues arising from the extracellular matrix. The transcriptional repressor REST represses miR-21 and, thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse embryonic fibroblast feeder cell effects.

Linear IgA dermatosis adult variant with oral manifestation: A rare case report.

Linear immunoglobulin A (IgA) dermatosis (LAD) is a rare autoimmune disorder that presents as a vesiculo-bullous lesion with cutaneous manifestations, but rare oral mucosal involvement. Here we discuss a case of a vesiculobullous lesion with severe oral and ocular mucosal involvement mimicking pemphigoid with histopathological evidence of subepithelial blisters. Direct immunofluorescence (DIF) confirmed the lesion as LAD of adult variant, although with atypical clinical features.

Macular Thickness Variability in Primary Open Angle Glaucoma Patients using Optical Coherence Tomography.

Aim: To compare the difference of retinal macular thickness and macular volume using optical coherence tomography (OCT) in primary open angle glaucoma (POAG) patients with the normal subjects.

Materials And Methods: This observational case control study included primary open angle glaucoma (POAG) patients (n = 124 eyes) and healthy subjects in the control group (n = 124 eyes). All subjects underwent detailed history, general and systemic exami -nation.

miR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma.

Glioblastoma multiforme (GBM) and the mesenchymal GBM subtype in particular are highly malignant tumors that frequently exhibit regions of severe hypoxia and necrosis. Because these features correlate with poor prognosis, we investigated microRNAs whose expression might regulate hypoxic GBM cell survival and growth. We determined that the expression of microRNA-218 (miR-218) is decreased significantly in highly necrotic mesenchymal GBM, and orthotopic tumor studies revealed that reduced miR-218 levels confer GBM resistance to chemotherapy.

Suppression and epigenetic regulation of MiR-9 contributes to ethanol teratology: evidence from zebrafish and murine fetal neural stem cell models.

Background: Fetal alcohol exposure produces multiorgan defects, making it difficult to identify underlying etiological mechanisms. However, recent evidence for ethanol (EtOH) sensitivity of the miRNA miR-9 suggests one mechanism, whereby EtOH broadly influences development. We hypothesized that loss of miR-9 function recapitulates aspects of EtOH teratology.

A novel volume-age-KPS (VAK) glioblastoma classification identifies a prognostic cognate microRNA-gene signature.

Background: Several studies have established Glioblastoma Multiforme (GBM) prognostic and predictive models based on age and Karnofsky Performance Status (KPS), while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM classification that can easily and non-invasively be determined upon patient admission.

Drug induced oral erythema multiforme: A rare and less recognized variant of erythema multiforme.

Oral erythema multiforme (EM) is considered as a third category of EM other than EM minor and major. Patients present with oral and lip ulcerations typical of EM but without any skin target lesions. It has been reported that primary attacks of oral EM is confined to the oral mucosa but the subsequent attacks can produce more severe forms of EM involving the skin.