BRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine.

Background: BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the Homologous Recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation called HR deficiency. Since their identification, pathogenic variants and other alterations of BRCA1 and BRCA2 genes have been associated with an increased risk of developing mainly breast and ovarian cancer.

BioTextQuest v2.0: An evolved tool for biomedical literature mining and concept discovery.

The process of navigating through the landscape of biomedical literature and performing searches or combining them with bioinformatics analyses can be daunting, considering the exponential growth of scientific corpora and the plethora of tools designed to mine PubMed(®) and related repositories. Herein, we present BioTextQuest v2.0, a tool for biomedical literature mining.

Intratumoral Microbiome: Foe or Friend in Reshaping the Tumor Microenvironment Landscape?

The role of the microbiome in cancer and its crosstalk with the tumor microenvironment (TME) has been extensively studied and characterized. An emerging field in the cancer microbiome research is the concept of the intratumoral microbiome, which refers to the microbiome residing within the tumor. This microbiome primarily originates from the local microbiome of the tumor-bearing tissue or from translocating microbiome from distant sites, such as the gut.

Mitochondrial Fraction of Circulating Cell-Free DNA as an Indicator of Human Pathology.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA.

Label-Free Human Disease Characterization through Circulating Cell-Free DNA Analysis Using Raman Spectroscopy.

Circulating cell-free DNA (ccfDNA) is a liquid biopsy biomaterial attracting significant attention for the implementation of precision medicine diagnostics. Deeper knowledge related to its structure and biology would enable the development of such applications. In this study, we employed Raman spectroscopy to unravel the biomolecular profile of human ccfDNA in health and disease.

Efficacy of Bioelectrical Impedance Analysis for the Evaluation of Physical Impairment in Chronic Low Back Pain. Results from a Cohort Study.

Introduction: Determining the effect of body composition on chronic low back pain seems to have the potential to improve our understanding of its mechanism and to develop novel preventive and therapeutic approaches. Aim: The purpose of the present study was to assess by electrical impedance the composition of lower extremities of individuals with chronic low back pain.

Materials And Methods: One hundred and twenty-one adult participants with diagnosed chronic low back pain were recruited in this study.

MINIMA Short Stem Versus Standard Profemur (TL) Stem in Primary Total Hip Replacement: A Comparative Study.

Background: The objective of our study was to compare a novel squared section, tapered design - with four conicity - short stem, the MINIMA® short stem with the cementless Profemur® TL standard femoral stem in primary total hip arthroplasty (THA) in terms of functional outcomes, radiologic evaluation and other peri-operative and post-operative data.

Material And Methods: This is a comparative study including 46 patients undergoing primary THA. In 23 patients, the MINIMA® short stem was used.

Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker.

Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 () gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described methylation profiles in health and multiple malignancies and demonstrated correlation to its aberrant expression. Here we focus on breast cancer (BrCa), analyzing in silico publicly available BrCa methylome datasets, to identify differentially methylated CpGs (DMCs) and correlate them with expression.

Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach.

Tissue-specific gene methylation events are key to the pathogenesis of several diseases and can be utilized for diagnosis and monitoring. Here, we established an in silico pipeline to analyze high-throughput methylome datasets to identify specific methylation fingerprints in three pathological entities of major burden, i.e.

Liquid Biopsy in Type 2 Diabetes Mellitus Management: Building Specific Biosignatures via Machine Learning.

Background: The need for minimally invasive biomarkers for the early diagnosis of type 2 diabetes (T2DM) prior to the clinical onset and monitoring of β-pancreatic cell loss is emerging. Here, we focused on studying circulating cell-free DNA (ccfDNA) as a liquid biopsy biomaterial for accurate diagnosis/monitoring of T2DM.

Methods: ccfDNA levels were directly quantified in sera from 96 T2DM patients and 71 healthy individuals via fluorometry, and then fragment DNA size profiling was performed by capillary electrophoresis.

Local Antibiotic Delivery Systems in Diabetic Foot Osteomyelitis: A Brief Review.

Diabetic foot osteomyelitis (DFO) is a severe, difficult to treat infection. Local antibiotic delivery has been studied as a potential therapeutic adjunct following surgery for DFO. This review aims to summarize the evidence on local antibiotic delivery systems in DFO.

Automated machine learning optimizes and accelerates predictive modeling from COVID-19 high throughput datasets.

COVID-19 outbreak brings intense pressure on healthcare systems, with an urgent demand for effective diagnostic, prognostic and therapeutic procedures. Here, we employed Automated Machine Learning (AutoML) to analyze three publicly available high throughput COVID-19 datasets, including proteomic, metabolomic and transcriptomic measurements. Pathway analysis of the selected features was also performed.

Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer.

The corticotropin-releasing factor (CRF) system has been strongly associated with gastrointestinal pathophysiology, including colorectal cancer (CRC). We previously showed that altered expression of CRF receptors (CRFRs) in the colon critically affects CRC progression and aggressiveness through regulation of colonic inflammation. Here, we aimed to assess the potential of methylation levels as putative biomarkers in CRC.

Deciphering the Methylation Landscape in Breast Cancer: Diagnostic and Prognostic Biosignatures through Automated Machine Learning.

DNA methylation plays an important role in breast cancer (BrCa) pathogenesis and could contribute to driving its personalized management. We performed a complete bioinformatic analysis in BrCa whole methylome datasets, analyzed using the Illumina methylation 450 bead-chip array. Differential methylation analysis vs.

Local Antibiotic Delivery Systems in the Surgical Treatment of Diabetic Foot Osteomyelitis: Again, No Benefit?

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8).

Accurate Blood-Based Diagnostic Biosignatures for Alzheimer's Disease via Automated Machine Learning.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia and its timely diagnosis remains a major challenge in biomarker discovery. In the present study, we analyzed publicly available high-throughput low-sample -omics datasets from studies in AD blood, by the AutoML technology Just Add Data Bio (JADBIO), to construct accurate predictive models for use as diagnostic biosignatures. Considering data from AD patients and age-sex matched cognitively healthy individuals, we produced three best performing diagnostic biosignatures specific for the presence of AD: A.

Supercapsular Percutaneously Assisted total hip arthroplasty versus lateral approach in Total Hip Replacement. A prospective comparative study.

Background: Supercapsular Percutaneously Assisted total hip arthroplasty (SuperPATH approach) is a relatively new minimal invasive approach which has been associated with encouraging postoperative outcomes. The aim of this study is to compare the minimal invasive (MIS) SuperPATHapproach with the standard modified Hardinge approach at the base of muscle damage due to serum markers, functional results and other perioperative and postoperative data.

Material And Methods: Forty eight (48) consecutive patients undergone primary total hip arthroplasty (THA) by the same surgeon (GD), were enrolled in our study.

Gentamycin elution from polymethylmethacrylate and bone graft substitute: Comparison between commercially available and home-made preparations.

Polymethylmethacrylate (PMMA) represents the current gold standard as an antibiotic delivery carrier in orthopaedic surgery. Despite the accepted use of local antibiotic carriers, there aren't any conclusive data comparing PMMA to Bone Graft Substitutes. The aim of this study was to compare the elution profile of gentamicin from various preparations of PMMA cements and Herafill beads.

Circulating cell-free DNA in breast cancer: size profiling, levels, and methylation patterns lead to prognostic and predictive classifiers.

Blood circulating cell-free DNA (ccfDNA) is a suggested biosource of valuable clinical information for cancer, meeting the need for a minimally-invasive advancement in the route of precision medicine. In this paper, we evaluated the prognostic and predictive potential of ccfDNA parameters in early and advanced breast cancer. Groups consisted of 150 and 16 breast cancer patients under adjuvant and neoadjuvant therapy respectively, 34 patients with metastatic disease and 35 healthy volunteers.

Circulating cell-free DNA release in vitro: kinetics, size profiling, and cancer-related gene methylation.

Circulating cell-free DNA (ccfDNA) is a biological entity of great interest due to its potential as liquid biopsy biomaterial carrying clinically valuable information. To better understand its nature, we studied ccfDNA in vitro in two human cancer cell lines MCF-7 and HeLa. Normalized indexes of ccfDNA per cell population decreased over time of culture but were significantly elevated after exposure to IC doses of the demethylating/apoptotic agent 5-azacytidine (5-AZA-CR).

Development of novel real-time RT-qPCR methodologies for quantification of the COL11A1 mRNA general and C transcripts and evaluation in non-small cell lung cancer specimens.

Purpose: The purpose of this study was the development of new quantitative methodologies for the general (total) COL11A1 gene and the C transcript (RT-qPCR methods for A and E transcripts have already been developed by our group previously), the quantification of all COL11A1 transcripts and the investigation for the first time of their potential association with histopathological prognostic factors in lung cancer.

Methods: Real-time RT-qPCR methodologies with dual hybridization probes were developed on the Light Cycler 1.5 platform (Roche,Germany).

Search for Pharmacoepigenetic Correlations in Type 2 Diabetes Under Sulfonylurea Treatment.

Sulfonylureas are insulin secretagogues which act in pancreatic β cells by blocking the K channels encoded by KCNJ11 and ABCC8 genes. In the present study, a pharmacoepigenetic approach was applied for the first time, investigating the correlation of KCNJ11 and ABCC8 gene promoter methylation with sulfonylureas-induced mild hypoglycemic events as well as the KCNJ11 E23K genotype. Sodium bisulfite-treated genomic DNA of 171 sulfonylureas treated T2DM patients previously genotyped for KCNJ11 E23K, including 88 that had experienced drug-associated hypoglycemia and 83 that had never experienced hypoglycemia, were analyzed for DNA methylation of KCNJ11 and ABCC8 gene promoters via quantitative Methylation-Specific PCR.

Epigenetics-by-Sex Interaction for Coronary Artery Disease Risk Conferred by the Cystathionine γ-Lyase Gene Promoter Methylation.

Coronary artery disease (CAD) is a major global health burden whereby gene-by-environment-by-sex interactions play an important role. Coronary artery bypass graft (CABG) surgery involves patients with well-documented and severe CAD. Hence, the study of CAD in a context of the CABG surgery serves as an advantageous model for disease phenotype ascertainment and genetic association studies.