Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.     

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. We provide a comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting.     

Polarographic Study of Thio-acetic Acid

The polarographic behaviour of thio-acetic acid (RSH) at dropping mercury electrode (d.m.e.) has been investigated in presence of KNO₃ in the pH range 2–10.5 at 30.0 ± 0.2°C in 50% alcoholic medium at 0.2 M ionic strength. Well defined anodic waves were obtained at all pH values in the concentration range studied. At pH < 2.2 and > 10.5 ill defined anodic waves were obtained. The effect of pH, concentration of RSH, temperature, drop time and alcohol on the wave characteristic and the mechanism of the reaction occurring at the surface of the mercury drop have been studied in detail. A small prewave was also observed at pH 9.1 and 10.5, which has been assigned adsorption characteristics. The reversibility of the reaction mechanism was confirmed by a number of methods. The wave is diffusion controlled and reversible involving one electron transfer process: Mathematical and experimental evidence shows that the anodic wave of RSH at. d.m.e. does not correspond to formation of (RSSR) but to a mercury compound RSHg according to the above equation. The diffusion coefficient and temperature coefficient for (30–45°C) of i_d at pH 4.0 and 9.1 have been found to be 1.698; 1.965 × 10⁻⁶ cm²/sec and 1.08%; 1.20% per degree respectively. The dissociation constant pKa was found to be 4.25 by the plot of E_1/2 vs. pH. The linearity of i_d with RSH concentrations provides a rapid and precise method for the determination of RSH down to 0.2 mM.     

Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.     

NGF Modulates Cholesterol Metabolism and Stimulates ApoE Secretion in Glial Cells Conferring Neuroprotection against Oxidative Stress

Cholesterol plays a crucial role in the brain, where its metabolism is particularly regulated by astrocytic activity. Indeed, adult neurons suppress their own cholesterol biosynthesis and import this sterol through ApoE-rich particles secreted from astrocytes. Recent evidence suggests that nerve growth factor (NGF) may exert neurotrophic activity by influencing cell metabolism. Nevertheless, the effect of NGF on glial cholesterol homeostasis has still not been elucidated. Thus, the aim of this project is to assess whether NGF could influence cholesterol metabolism in glial cells. To reach this objective, the U373 astrocyte-derived cell line was used as an experimental model. Immunoblot and ELISA analysis showed that proteins and enzymes belonging to the cholesterol metabolism network were increased upon NGF treatment in glial cells. Furthermore, NGF significantly increased ApoE secretion and the amount of extracellular cholesterol in the culture medium. Co-culture and U373-conditioned medium experiments demonstrated that NGF treatment efficiently counteracted rotenone-mediated cytotoxicity in N1E-115 neuronal cells. Conversely, neuroprotection mediated by NGF treatment was suppressed when N1E-115 were co-cultured with ApoE-silenced U373 cells. Taken together, these data suggest that NGF controls cholesterol homeostasis in glial cells. More importantly, NGF exerts neuroprotection against oxidative stress, which is likely associated with the induction of glial ApoE secretion.     

Energy-aware lazy scheduling algorithm for energy-harvesting sensor nodes

The main problem in dealing with energy-harvesting (EH) sensor nodes is represented by the scarcity and non-stationarity of powering, due to the nature of the renewable energy sources. In this work, the authors address the problem of task scheduling in processors located in sensor nodes powered by EH sources. Some interesting solutions have appeared in the literature in the recent past, as the lazy scheduling algorithm (LSA), which represents a performing mix of scheduling effectiveness and ease of implementation. With the aim of achieving a more efficient and conservative management of energy resources, a new improved LSA solution is here proposed. Indeed, the automatic ability of foreseeing at run-time the task energy starving (i.e. the impossibility of finalizing a task due to the lack of power) is integrated within the original LSA approach. Moreover, some modifications have been applied in order to reduce the LSA computational complexity and thus maximizing the amount of energy available for task execution. The resulting technique, namely energy-aware LSA, has then been tested in comparison with the original one, and a relevant performance improvement has been registered both in terms of number of executable tasks and in terms of required computational burden.     

Flexible electronics: Prediction of substrate deformation during different steps of the lithography process

A numerical model was developed to simulate the micro-deformations of a polymeric substrate due to lithographic processing of different layers of a transistor-like structure. The results of the model were validated with the results from experiments. The model, a mechanical-thermal-hygroscopic model, takes into account the dimensional effects of temperature, moisture and stresses. It also includes the temperature dependent visco-elastic behaviour of the polymer substrate. The model can be used to predict overlay accuracies between different functional layers introduced by the lithographic process. It can also be used to understand the underlying processes such that it provides a tool to improve the overlay accuracy during actual processing.     

Mix design and performance analysis of asphalt concretes with electric arc furnace slag

The paper presents the results of a laboratory study, aimed at verifying the possibility to use two particular typologies of electric arc furnace (EAF) steel slags, in substitution of the natural aggregates, in the composition of wearing course asphalt concrete for flexible pavements. The experimental research has been articulated in a preliminary study of the chemical, leaching, physical, and mechanical properties of the EAF steel slag, and in the following mix design and performance characterisation of the bituminous conglomerates, through gyratory compaction tests, permanent deformations tests, Stiffness Modulus tests at various temperatures, fatigue tests and indirect tensile strength tests. All the mixtures with EAF slag have satisfied the requisites for acceptance in the road sector technical standards, thus resulting as suitable for use in the construction of road infrastructures, moreover presenting higher mechanical characteristics than those of the corresponding asphalts with full natural aggregate.     

Post-cracking behaviour of steel and macro-synthetic fibre-reinforced concretes

The present paper describes the results of an experimental investigation on the performances of concrete specimens reinforced with either steel or macro-synthetic fibres under three-point bending. Steel fibres are often used to improve the flexural toughness of concrete and are used in various structural applications while synthetic fibres are more often used to reduce crack opening due to shrinkage. Macro-synthetic fibres have been proposed more recently with the aim of creating an alternative to steel fibres in structural applications but their use is still limited.In the tests performed, specimens cast with the same concrete mix, but containing different dosages of either steel or macro-synthetic fibres, were used and compared. In general steel fibres were more efficient in increasing the toughness of concrete than macro-synthetic fibres, even though their results were significantly more scattered.Test results were used to calculate the parameters of stress-crack opening relations via inverse analysis using a cracked hinge model. This numerical model provided results, in terms of force-Crack Mouth Opening Displacement (CMOD) curves, in very good agreement with the experimental data.