Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as ...free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as ...free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents. PUBLICATION ABSTRACT
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A machine learning approach for on-line fault recognition via automatic image processing is developed to timely identify material defects due to process non-conformities in Selective Laser Melting ...(SLM) of metal powders. In-process images acquired during the layer-by-layer SLM processing are analyzed via a bi-stream Deep Convolutional Neural Network-based model, and the recognition of SLM defective condition-related pattern is achieved by automated image feature learning and feature fusion. Experimental evaluations confirmed the effectiveness of the machine learning method for on-line detection of defects due to process non-conformities, providing the basis for adaptive SLM process control and part quality assurance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Additive manufactured components require polishing to improve their inherently rough surface finish. In this work, an innovative laser polishing process based on wobbling of the laser beam is ...proposed for surface finish enhancement of additive manufactured parts made of Cr–Cu precipitation hardening steel, widely employed for mechanical components in the automotive industry. Parts were fabricated by selective laser melting and subjected to the innovative laser polishing under different process conditions. Surface characterization was performed by microstructural analysis and surface roughness measurement. Machine learning-based CNN processing of polished surface images was employed for automatic identification of optimal LP condition.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, ...the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy ...and to estimate the proportion of TC cases potentially attributable to overdiagnosis.
Data on TC cases reported to Italian cancer registries during 1998–2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region.
In Italy between 1998–2002 and 2008–2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998–2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008–2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders.
Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.
•Incidence rates of thyroid cancer (TC) in Italy are among the highest worldwide.•Cancer data were collected from Italian cancer registries for the period 1998–2012, and time trends were analysed.•Large increasing heterogeneity of TC incidence rates was observed across regions and areas in Italy.•We used a previously developed method to estimate overdiagnosis of TC.•The steady increases of TC incidence in Italy are largely due to overdiagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
COPD is a worsening condition that leads to a pathologic degeneration of the respiratory system. It represents one of the most important causes of mortality and morbidity in the world, and it is ...characterized by the presence of associated comorbidity. This article analyzes gastroesophageal reflux disease (GERD) and low back pain (LBP) in patients with COPD and tries to produce anatomo-clinical considerations on the reasons of the presence of these comorbidities. The considerations of the authors are based on the anatomic functions and characteristics of the respiratory diaphragm that are not always considered, from which elements useful to comprehend the symptomatic status of the patient can be deduced, finally improving the therapeutic approach. The information contained in the article can be of help to the clinician and for physiotherapy, and to all health professionals who gravitate around the patient's care, improving the approach to the diaphragm muscle.
Recently, the role of nutrition in the management of Crohn's disease (CD) is of increasing interest and the exploration of novel nutritional interventions to improve long-term management of the ...disease is challenging. So far, the majority of the studies on the role of exclusive enteral nutrition (EEN) in CD are conducted in the pediatric population and have highlighted the efficacy of EEN for achieving mucosal healing. This implicates that a similar approach would be beneficial in adult patients. However, the evidence for EEN in adults is heterogeneous, with meta-analyses reporting it as inferior to steroids while growing data demonstrate improvement in complicated CD. Currently, EEN is less used in adult patients with IBD. Indeed, the lack of palatability of enteral formula leads to difficulties in acceptance and compliance. The search for more tolerable and still effective diets has become an intense area of research aiming to explore the potential role of diet to control inflammation in patients with CD. Thus, this narrative review provides the state-of-the-art on the use of EEN treatment in CD and highlights the perceived barriers to its implementation in adult CD patients.
A prolonged and exceptionally intense air mass advection event transporting biomass burning aerosols generated in Alaska affected Ny-Ålesund in the mid of July 2015. This paper reports the ...morphochemical characteristics and mixing state of individual aerosol particles collected during the event. To this aim aerosol samples were collected on nucleopore polycarbonate membrane filters using a DEKATI 12-stage low volume impactor and analyzed by scanning electron microscopy (SEM) techniques. Results of SEM investigations depict a complex aerosol characterized by an external mixing between a main part of carbonaceous organic particles (tar balls and organic particles), lower ammonium sulfate and minor potassium chloride and mineral dust amounts. The carbonaceous particles are spherical to slightly elongated and the organic particles show an internal mixing of low density organics and/or ammonium sulfate upon denser nuclei. Most particles are in the accumulation mode size range although the size and the morphology of the chloride and the sulfate salts evidence the growth of these species both in the air and upon the sampling membranes. Individual particle analyses were complemented by aerosol size distribution (Aerodynamic Particle Sizer, Scanning Mobility Particle Sizer) and optical (Particle Soot Absorption Photometer, nephelometer) measurements at ground level in order to retrieve the optical and radiative properties of the aerosol in the atmosphere and to predict the fate and behaviour of particles upon deposition at ground level. Individual particle analyses were also compared with bulk chemical analyses on daily sampling filters and back-trajectory analyses of the air mass movement in order to enucleate distinct sources of the aerosol during the long range transport.
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•Brown carbon (organic, tar ball) and ammonium sulfate particles dominate.•Black carbon is not directly observed in the samples.•Its presence in the samples is suggested by the absorption Ångström exponent values.•Little particle aging is documented despite the prolonged long range transport.•Particles tend to persist in the lower troposphere for a long time before deposition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP