Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Machine learning methods for short‐term bid forecasting in the renewable energy market: A case study in Italy

In liberalized markets, there usually exists a day‐ahead session where energy is sold and acquired for the following production day. Owing to the high uncertainty of its production, renewable energy (wind in particular) can significantly influence the network imbalance of the following day. In this work, we consider the problem of predicting the sum of the bid volumes for wind energy of all the producers inside the day‐ahead energy market. This is a valuable tool to be used by an energy provider in order to determine the imbalance of a market zone and, thus, properly size its bids. In particular, we focus on the estimation of the possible relationship between the meteorological forecasts and the wind power offered on the market by the companies for a market zone. We propose a machine learning model which is used to compute a 1‐day‐ahead forecast. The input‐output mapping is obtained by support vector regression. The input feature vector is defined by a suitable feature extraction technique since the meteorological forecasts are given on a lattice of thousands of geographical points. The computational experiments are performed considering the Italian market as a case study (years 2012‐2016). The results show that the proposed feature extraction technique, selecting only some geographical zones, manages to reduce the error attained using all the features. Moreover, classical statistical methods are shown to be outperformed by machine learning models. The analysis reveals also some weaknesses of the model, which may be due to other nonmeteorological factors at play.     

Assessing the health research’s social impact: a systematic review

Scientometrics - In recent year, a growing attention is dedicated to the assessment of research’s social impact. While prior research has often dealt with results of research, the last decade...     

Multicarrier energy systems: Optimization model based on real data and application to a case study

Multicarrier energy systems are increasingly used for a number of applications, among which the supply of electricity, heating, and cooling in buildings. The possibility of switching between different energy sources is a crucial advantage for the optimal fulfillment of the energy demand. The flexibility of these systems can benefit from the integration with smart grids, which have strong variations in time during their operation. The energy price is the parameter that is usually considered, but also the primary energy factor and the greenhouse gases emissions need to be accounted. This paper presents an application of an operational optimization method for a multicarrier energy system, based on real data–driven model and applied to different countries. The generation plant of a hospital is considered as case study, coping with multiple energy needs by relying on different conversion technologies. The optimal operation of the system shows a wide range of variability, depending on the chosen objective function, the hour of the day, the season, and the country. The results are affected mostly by the energy mix of the electricity supplied from the power grid, which has a direct influence on the primary energy consumption and the greenhouse gases emissions and an indirect influence on the electricity prices.     

Current technologies and new insights for the recovery of high valuable compounds from fruits by-products

The recovery of high valuable compounds from food waste is becoming a tighten issue in food processing. The large amount of non-edible residues produced by food industries causes pollution, difficulties in the management, and economic loss. The waste produced during the transformation of fruits includes a huge amount of materials such as peels, seeds, and bagasse, whose disposal usually represents a problem. Research over the past 20 years revealed that many food wastes could serve as a source of potentially valuable bioactive compounds, such as antioxidants and vitamins with increasing scientific interest thanks to their beneficial effects on human health. The challenge for the recovery of these compounds is to find the most appropriate and environment friendly extraction technique able to achieve the maximum extraction yield without compromising the stability of the extracted products. Based on this scenario, the aim of the current review is twofold. The first is to give a brief overview of the most important bioactive compounds occurring in fruit wastes. The second is to describe the pro and cons of the most up-to-dated innovative and environment friendly extraction technologies that can be an alternative to the classical solvent extraction procedures for the recovery of valuable compounds from fruit processing. Furthermore, a final section will take into account published findings on the combination of some of these technologies to increase the extracts yields of bioactives.     

Sensitivity Analysis and Model Validation of a 2-DoF Mini Spherical Robot

This paper is focused on the development and validation of an error kinematic model of a mini spherical robot, aimed at its kinematic calibration. The robot is actually a spatial five-bar linkage, provided with two rotational degrees of freedom. A non-overconstrained kinematics is assumed for the robot in order to provide a simple mathematical model and allow a sensitivity analysis of all the involved geometric parameters. A simplified version of the model is proposed. It differs only for the degree of approximation. A comparison between full and reduced models is presented by means of numerical simulations, analyzing their behavior in a significant region of the robot workspace. In order to validate both of them a robot calibration is carried out on a physical prototype of the robot using a vision system, namely a fixed camera in a eye-to-hand configuration. An iterative algorithm aimed at the experimental identification of the geometric data of the robot is used. Some experimental results show the effectiveness of the study.     

Design,Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome-Preventive Agents

Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC₅₀ of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [¹⁸F] 3b was successfully developed. Unfortunately, the stability of [¹⁸F] 3b turned out to be insufficient to pursue imaging studies.     

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.     

Ultrathin hydroxyapatite coating on pure magnesium substrate prepared by pulsed electron ablation technique

Magnesium (Mg) as a potential material for biodegradable implants is attractive due to its mechanical similarity to the bone tissue and nontoxic corrosion products. However, the rapid corrosion rate of bare magnesium is associated with hydrogen release, which may complicate the healing process. The corrosion rate may be reduced by suitable alloying, but concurrently the biocompatibility of such alloy might be deteriorated. Another way of reduction of the corrosion rate is coating. Hydroxyapatite (HA)-based coating is considered to improve biocompatibility as well as decrease the corrosion rate by the barrier effect. In this study, ultrathin (150 nm) HA and HA containing Sr coatings are deposited via pulsed electron ablation technique on pure Mg. The microstructure of the coating was assessed by scanning electron microscopy. Electrochemical methods were used to investigate the corrosion properties of prepared coatings. The materials covered by this layer were characterized by superior corrosion behavior, with corrosion rates of coated samples up to five times lower as compared with the uncoated ones. Such coating is the thinnest coating found in the literature sources.