Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results

Background: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. Methods and results: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/β-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/β-catenin, NF-κβ, and STAT3 signaling pathways. Conclusions: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19

Neoplasmas oculares e de anexos em cães e gatos no Rio Grande do Sul: 265 casos (2009 -2014)

Neoplasias oculares causam desconforto, problemas de visão e podem refletir doenças sistêmicas. Um estudo retrospectivo foi realizado para identificar e analisar neoplasmas oculares e de anexos obtidos por biópsias enviadas ao Setor de Patologia Veterinária (SPV) da Universidade Federal do Rio Grande do Sul (UFRGS). Durante o período de janeiro de 2009 a dezembro de 2014 realizou-se 265 diagnósticos de neoplasmas oculares e de anexos, destes 87,5% na espécie canina e em 12,5% na espécie felina. As neoplasias ocorreram mais em animais com idade superior a 12 meses e idosos, e os cães (52/232) e gatos (21/33) sem raça definida foram os mais acometidos. A pálpebra foi o local mais acometido na espécie canina (164/232) e felina (20/33), seguida pela terceira pálpebra em cães (20/232) e órbita nos felinos (5/33). O tumor mais diagnosticado nos cães foi o adenoma meibomiano (82/232) e nos gatos o carcinoma de células escamosas (10/33), ambos em pálpebras. Foram identificados nos cães 24 tipos tumorais e nos gatos 16. Em caninos as neoplasias benignas representaram o maior número de diagnósticos (56%) sendo que em felinos o maior número de casos foi de neoplasias malignas (75,8%)

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting