Combining low-dose CT-based radiomics and metabolomics for early lung cancer screening support

Due to its predominantly asymptomatic or mildly symptomatic progression, lung cancer is often diagnosed in advanced stages, resulting in poorer survival rates for patients. As with other cancers, early detection significantly improves the chances of successful treatment. Early diagnosis can be facilitated through screening programs designed to detect lung tissue tumors when they are still small, typically around 3mm in size. However, the analysis of extensive screening program data is hampered by limited access to medical experts. In this study, we developed a procedure for identifying potential malignant neoplastic lesions within lung parenchyma. The system leverages machine learning (ML) techniques applied to two types of measurements: low-dose Computed Tomography-based radiomics and metabolomics. Using data from two Polish screening programs, two ML algorithms were tested, along with various integration methods, to create a final model that combines both modalities to support lung cancer screening

The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women

Objectives: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis.Material and methods: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method.Results: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters.Conclusions: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis

The role of comprehensive two-dimensional gas chromatography in mineral oil determination.

peer reviewedMineral oil hydrocarbons (MOH) contain a wide structural diversity of molecules, for which the reference method of analysis is the online coupled liquid chromatography-gas chromatography with flame ionization detection (LC-GC-FID). These compounds are very heterogeneous from a toxicological viewpoint, and an accurate risk assessment when dealing with a MOH contamination can only be performed if sufficient information is available on the types of structures present (i.e., number of carbons, degree of alkylation, number of aromatic rings). Unfortunately, the separation performances of the current LC-GC-FID method are insufficient for such characterization, not even mentioning the possible coelution of interfering compounds which additionally hinder MOH determination. Comprehensive two-dimensional gas chromatography (GC × GC), while mostly used for confirmation purposes in the past, starts to prove its relevance for overcoming the weaknesses of the LC-GC method and reaching even better the analytical requirements defined in the latest EFSA opinion. The present paper therefore aims at highlighting how GC × GC has contributed to the understanding of the MOH topic, how it has developed to meet the requirements of MOH determination, and how it could play a role in the field for overcoming many of the current analytical and toxicological challenges related to the topic

Towards the Use of Multidimensional Gas Chromatography Techniques in Routine Analysis: The Mineral Oil Case

editorial reviewe

LC GC × GC TOF MS/FID: A COMPREHENSIVE APPROACH TO TACKLE THE COMPLEXITY OF MINERAL OIL

editorial reviewe

Impact of column temperature on triacylglycerol regioisomers separation in silver ion liquid chromatography using heptane-based mobile phases.

peer reviewedThis work presents the investigation of the use of heptane as an alternative and less toxic mobile phase to the most used hexane for triacylglycerols (TAGs) analysis in silver ion high-performance liquid chromatography (Ag+-HPLC). The impact of column temperature (in the 5 °C-35 °C range) on the retention and resolution of five pairs of regioisomers relevant for the confectionery industry was investigated using a heptane-based mobile phase modified with acetonitrile (ACN). The retention behaviour was compared for a standard TAG mixture and an interesterified cocoa butter. The temperature effect previously observed with hexane-based mobile phases was confirmed for this new system, and it was also observed that the ACN concentration had an important impact on the strength of the temperature effect, with a higher ACN concentration leading to a lesser impact of temperature on the TAGs' elution behaviour. In general, the study allowed to conclude on the equivalence of hexane and heptane for TAGs regioisomers separation in Ag+-HPLC, independently of the used temperature or the ACN concentration. In addition, the applicability of heptane-based mobile phases for the separation of TAGs regioisomers was demonstrated on three other confectionary fat samples, namely palm olein, interesterified palm olein, and interesterified shea olein

Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol–induced neuronal nitric oxide synthase uncoupling in metastatic osteosarcoma cells

2-methoxyestradiol (2-ME) is a physiological anticancer compound, metabolite of 17β-estradiol. Previously, our group evidenced that from mechanistic point of view one of anticancer mechanisms of action of 2-ME is specific induction and nuclear hijacking of neuronal nitric oxide synthase (nNOS), resulting in local generation of nitro-oxidative stress and finally, cancer cell death. The current study aims to establish the substantial mechanism of generation of reactive nitrogen species by 2-ME. We further achieved to identify the specific reactive nitrogen species involved in DNA-damaging mechanism of 2-ME. The study was performed using metastatic osteosarcoma 143B cells. We detected the release of biologically active (free) nitric oxide (•NO) with concurrent measurements of peroxynitrite (ONOO−) in real time in a single cell of 143B cell line by using •NO/ONOO− sensitive microsensors after stimulation with calcium ionophore. Detection of nitrogen dioxide (•NO2) and determination of chemical rate constants were carried out by a stopped-flow technique. The affinity of reactive nitrogen species toward the guanine base of DNA was evaluated by density functional theory calculations. Expression and localization of nuclear factor NF-kB was determined using imaging cytometry, while cell viability assay was evaluated by MTT assay. Herein, we presented that 2-ME triggers pro-apoptotic signalling cascade by increasing cellular reactive nitrogen species overproduction – a result of enzymatic uncoupling of increased nNOS protein levels. In particular, we proved that ONOO− and •NO2 directly formed from peroxynitrous acid (ONOOH) and/or by auto-oxidation of •NO, are inducers of DNA damage in anticancer mechanism of 2-ME. Specifically, the affinity of reactive nitrogen species toward the guanine base of DNA, evaluated by density functional theory calculations, decreased in the order: ONOOH > ONOO− > •NO2 > •NO. Therefore, we propose to consider the specific inducers of nNOS as an effective tool in the field of chemotherapy

The Role of Muscle Decline in Type 2 Diabetes Development: A 5-Year Prospective Observational Cohort Study

The major risk factors of T2DM (type 2 diabetes mellitus) development are still under investigation. We evaluate the possible risk factors associated with type 2 diabetes (T2DM) in adult subjects during a five-year prospective cohort study. We recruited 1160 subjects who underwent oral glucose tolerance test, anthropometric measurements, and body composition and body fat distribution analysis at a baseline visit and again at follow-up after approximately five years. The conclusions of this study are based on observation of 219 subjects who attended both the first and follow-up visits. The fasting serum insulin was measured, and HOMA-IR (homeostatic model assessment of insulin resistance) was calculated. During the follow-up period, T2DM was diagnosed in 7.4% of participants, impaired fasting glucose in 37.7%, and impaired glucose tolerance in 9.3%. Logistic regression models, adjusted for age, were constructed. The changes in glucose concentration, visceral fat tissue content, insulin resistance, and %loss of muscle mass were chosen as the potential predictors for T2DM development. A set of independent variables was extracted. The constructed feature set comprised change in HOMA-IR (OR (odds ratio) = 1.01, p < 0.01) and change in %loss of muscle mass (OR = 0.84, p < 0.03). With an aim to validate the prediction capability using the selected attributes, a support vector machine classifier and leave-one-out cross-validation procedure was applied, yielding 92.78% classification accuracy. Our results show the correlation between the %loss of muscle mass and T2DM development in adults, independent of changes in insulin resistance

Participants flow diagram.

Participants flow diagram.</p