Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma

Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. Experimental design: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. Results: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. Conclusions: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM

Salvatio Memoriae. Studies for the Virtual Reconstruction of the Medieval Sculptural Heritage

The use of ICT technologies and Augmented Reality is now commonly accepted and proven in the arts, but there are still few studies related to medieval sculptural apparatuses. These, already since the Modern Age, have often been subject to manipulations that have caused the loss of parts and changes in their location, use and meaning. This research highlights the role that new technologies, three-dimensional reconstructions and AR strategies can play in this area of study. Specifically, the mausoleum of Luca Fieschi, a 14th-century funerary monument originally erected in Genoa's Cathedral of San Lorenzo and the subject of numerous relocations and rearrangements over the centuries, is presented as a case study. Today the tomb is a puzzle of 124 sculptural remains, and its original conformation is still a topic of debate among scholars. Some of the pieces are now being remounted in the crypts of the Diocesan Museum of Genoa: while this will allow the return of one of its greatest Gothic symbols to the city, it will also imply a reduction in scientific studies, configurational evidence and comparative analysis of the fragments. The paper shows how advanced techniques of representation can support physical museum setting, making explicit the design methodologies judged most appropriate. The construction of a catalog of digital twins will allow scholars a continuity of investigation of individual sculptural pieces and their configuration in reconstructive hypotheses; through specific AR narratives, museum publics will be given the opportunity to enjoy additive digital content in a playful and interactive manner

Minority stress and mental health in European transgender and gender diverse people: A systematic review of quantitative studies

The current study aimed at systematically reviewing evidence on the relationships between gender minority stress and mental health outcomes among European transgender and gender diverse (TGD) individuals. A systematic search was conducted in PsycINFO, PubMED, Scopus, and Google Scholar. It was based on Boolean operators to combine terms related to minority stress, TGD identities, and mental health. Thirty studies were identified as eligible. The results confirmed that gender minority stress factors are significantly related with mental health problems among European TGD individuals. Distal stressors were identified as strongly associated with poorer mental health, with gender-related discrimination emerging as the most documented risk factor. The significant role of proximal stressors was also highlighted, with some mediation analyses detecting an indirect effect on mental health. However, identity concealment appeared unrelated to mental health outcomes. Resilience-promoting factors buffering the impact of stressors were also identified, including self-esteem, pride, transitioning, and social support. Conversely, data on community connectedness as a source of resilience were inconclusive. The studies reviewed have several limitations, including lack of longitudinal designs, sampling bias, variability in measurement methods, and unaccounted ethnic variables. Research and clinical recommendations in this field are reported

The Effect of Model Misspecification of the Bounded Transformed Gamma Process on Maintenance Optimization

Although the degradation growth of several technological units is naturally bounded, stochastic models used to describe them are typically unbounded. In general, this manifest contradiction does not significantly affect the effectiveness of unbounded degradation models, because degrading units are conventionally considered failed when their degradation level exceeds a threshold that is far below the physical bound. Yet, this is not always the case. Motivated by these arguments, the main aim and novel contribution of this paper is investigating the impact on a condition based maintenance policy and related costs of using a degradation model that neglects the presence of the bound when it exists. In particular, the paper focuses on situations where bound and failure threshold have comparable values. The study is conducted considering as competing models a bounded and an unbounded transformed gamma. The competing models are used to formulate a condition-based maintenance policy for the liners of a marine engine. An example of application based on real data is firstly developed. Hence, the results of a Monte Carlo simulation study are presented and discussed. Obtained results highlight that, neglecting the presence of the upper bound when it really exists, can cause substantial (unnecessary) additional maintenance costs

ON MINIMAL GORENSTEIN HILBERT FUNCTIONS

.We conjecture that a class of Artinian Gorenstein Hilbert algebras called full Perazzo algebras always have minimal Hilbert function,fixing codimension and length.We prove the conjecture in length four and five,in low codimension.We also prove the conjecture for a particular subclass of algebras that occurs in every length and certain codimensions.As a consequence of our methods we give a new proof of part of a known result about the asymptotic behavior of the minimum entry of a Gorenstein Hilbert function

The energy performances of an elastocaloric device for air conditioning through numerical investigation

The urgent needing to address global warming and the rapid depletion of fossil fuel reserves has led to a demand for immediate research in sustainable and clean energy technologies. Elastocaloric cooling is a promising proposal for clean refrigeration because of the zero global warming potential of the shape memory alloys, which are solid-state materials showing elastocaloric effect. The latter manifests when the shape memory alloys are stressed through a mechanical loading, transforming from the austenite phase toward the martensite one and releasing heat, dually transforming from the martensite phase into the austenite phase and absorbing heat. The updated literature accounts for 15 elastocaloric cooling devices, but none is close to commercialization. The efforts are devoted to making this decisive step by implementing new efficient devices. This paper analyses the energy performances of an elastocaloric rotary prototype employing binary NiTi wires through the first rotary bidimensional numerical model based on the finite element method to attain the device's potential cooling and heating capacities. In this paper, the energy performances of an elastocaloric rotary prototype employing binary NiTi wires are analyzed through a 2D numerical model based on the finite element method to attain the device's potential cooling and heating capacities. The model reproduces the thermo-fluid-dynamic behaviour of an experimental rotary device for air conditioning; meanwhile, the secondary fluid in the device is air. The accuracy of the rotary model easily allows to optimize the operating parameters of the elastocaloric prototype under construction. Results in terms of outlet air temperature, cooling power and coefficient of performance are presented for different air velocities inside the air channel and different rotation frequencies of the device. A performance map has been obtained by exploring the device's behaviour in the cooling mode under variable working conditions to identify the optimal configuration. A maximum COP of 6.22 (corresponding to a second law analysis efficiency of 60%) was evaluated under an airflow speed of 6 m s−1 and a frequency of 0.3 Hz, corresponding to . 28.5 K and 5400 W kg−1 are the reached peaks of temperature span and cooling power

A simple rheological method for the experimental assessment of the fiber percolation threshold in short fiber biocomposites

The identification of the percolation threshold (Φc) in short fiber composites is a challenging problem in Composite Science. Above Φc the fibers form a continuous network that causes substantial changes in mechanical and transport properties. Besides, percolation of natural fibers in biodegradable polymer matrices allows water and other pro-degradative species to access the inner parts of the material from the external environment, accelerating biodegradation. Whether such a speeding up is desired or not, assessing Φc in composites is of utmost importance. Unfortunately, natural fibers are not conductive and exhibit highly variable shape and physical properties. This prevents the use of many experimental and theoretical approaches for the estimate of Φc. Here we propose an original rheological approach borrowed from the viscoelastic modelling of polymer nanocomposites. The method was applied to two systems made of poly(lactic acid) filled with hemp or kenaf fibers (average length 3 weeks) dielectric spectroscopy analyses (∼10.1 and 18.5 vol%)

Exploring the molecular and toxicological mechanism associated with interactions between heavy metals and the reproductive system of Mytilus galloprovincialis

A large number of heavy metals resulted toxic to the reproductive system, but invertebrate infertility has been poorly explored, and above all, there are limited molecular, cellular and toxicological studies. In the present work, we exposed Mytilus galloprovincialis to three individual metal chlorides (CuCl2 15 μM, CdCl2 1.5 μM, NiCl2 15 μM) and their mixture for 24 h, to evaluate the effects on the protamine-like proteins (PLs), sperm DNA and on their interaction in the formation of sperm chromatin. Under all exposure conditions, but particularly after exposure to the metals mix, relevant changes in the electrophoretic pattern, by AU-PAGE and SDS-PAGE, and in fluorescence spectroscopy measurements of PLs were shown. In addition, alterations in DNA binding of these proteins were observed by Electrophoretic Mobility Shift Assay (EMSA) and through their release from sperm nuclei. Moreover, there was evidence of increased accessibility of micrococcal nuclease to sperm chromatin, which was also confirmed by toluidine blue staining. Furthermore, morphological analyses indicated severe gonadal impairments which was also corroborated by increased PARP expression, by Western blotting, and sperm DNA fragmentation, by comet assay. Finally, we investigated the expression of stress genes, gst, hsp70 and mt10, in gonadal tissue. The latter investigations also showed that exposure to this metals mix was more harmful than exposure to the individual metals tested. The present results suggest that these metals and in particular their mixture could have a negative impact on the reproductive fitness of M. galloprovincialis. Based on these evidences, we propose a molecular mechanism

Effect of design and molecular interactions on the food preserving properties of alginate/pullulan edible films loaded with grape pomace extract

Natural phenolic compounds were extracted from grape and integrated into edible biopolymeric films intended for food preservation. The extract contained mainly catechin, epicatechin and condensed tannins as main phenolic components, and showed promising antioxidant efficacy and a negligible tendency to form clusters. The extract was integrated into alginate/pullulan film-forming dispersions and the inter-molecular interactions were investigated, showing that the biopolymers partially dissolve the phenolic compounds. The characterization of extract-containing films, prepared using a sequential casting method, highlighted the micro-segregation of the phenolic compounds and their functional integration into the composite film in terms of antioxidant and antimicrobial properties. Results show the possibility to tune the food preservation properties of the composite through its multi-layered design, in terms of composition and assembly of each layer, opening new perspectives in the optimal re-use of grape pomace extracts