Università degli Studi di Palermo

Tumor invasion follows a complex mechanism which involves cell migration and proliferation. To study the processes in which primary and secondary metastases invade and damage the normal cells, mathematical models are often extremely useful. In this manuscript, we present a mathematical model of acid-mediated tumor growth consisting of radially symmetric reaction-diffusion equations. The assumption on the radial symmetry of the solutions is imposed here in view that tumors present spherical symmetry at the microscopic level. Moreover, we consider various empirical mechanisms which describe the propagation of tumors by considering cancer cells, normal cells, and the concentration of H + ions. Among other assumptions, we suppose that these components follow logistic-type growth rates. Evidently, this is an important difference with respect to various other mathematical models for tumor growth available in the literature. Moreover, we also add competition terms of normal and tumor cells growth. We carry out a balancing study of the equations of the model, and a numerical model is proposed to produce simulations. Various practical remarks derived from our assumptions are provided in the discussion of our the simulations. Response to Reviewers: % In LaTeX format. Please, compile the file. \documentclass[letterpaper,10pt]{article} \usepackage{color} \usepackage{amssymb} \setlength{\leftmargini}{0.3in} % \setlength{\parindent}{0.5in} % \setlength{\topmargin}{-0.75in} % Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

The aim of this work was to study the effect of organic loading rate on the production of Polyhydroxyalkanoates (PHA) from sewage sludge. Synthesis of PHA using sewage sludge as platform was achieved in this work. Three pilot-scale selection-sequencing batch reactors (S-SBR) were used for obtaining a culture able to accumulate PHA following a strategy of aerobic dynamic feeding (ADF) at different volumetric organic-loading-rate (vOLR): 1.3, 1.8 and 0.8 g COD L−1 d−1 for S-SBR 1, S-SBR 2 and S-SBR 3, respectively. Decreasing the vOLR enhanced the general performance of the process as for organic matter removal (from 99.2% ± 0.3% in S-SBR-3 to 92 ± 2 in S-SBR-2) while the opposite trend was recorded for PHA production (6.0 PHA % w/w in S-SBR-3 vs 13.7 PHA % w/w in S-SBR-2 at the end of the feast phase). Furthermore, indirect and direct emissions, as N2O, were evaluated during the process for the first time. Finally, three accumulation tests were performed achieving 24% w/w.

To investigate the intra- and inter-rater reliability of the total radiomics quality score (RQS) and the reproducibility of individual RQS items’ score in a large multireader study. Nine raters with different backgrounds were randomly assigned to three groups based on their proficiency with RQS utilization: Groups 1 and 2 represented the inter-rater reliability groups with or without prior training in RQS, respectively; group 3 represented the intra-rater reliability group. Thirty-three original research papers on radiomics were evaluated by raters of groups 1 and 2. Of the 33 papers, 17 were evaluated twice with an interval of 1 month by raters of group 3. Intraclass coefficient (ICC) for continuous variables, and Fleiss’ and Cohen’s kappa (k) statistics for categorical variables were used. The inter-rater reliability was poor to moderate for total RQS (ICC 0.30–055, p < 0.001) and very low to good for item’s reproducibility (k − 0.12 to 0.75) within groups 1 and 2 for both inexperienced and experienced raters. The intra-rater reliability for total RQS was moderate for the less experienced rater (ICC 0.522, p = 0.009), whereas experienced raters showed excellent intra-rater reliability (ICC 0.91–0.99, p < 0.001) between the first and second read. Intra-rater reliability on RQS items’ score reproducibility was higher and most of the items had moderate to good intra-rater reliability (k − 0.40 to 1). Reproducibility of the total RQS and the score of individual RQS items is low. There is a need for a robust and reproducible assessment method to assess the quality of radiomics research. There is a need for reproducible scoring systems to improve quality of radiomics research and consecutively close the translational gap between research and clinical implementation. • Radiomics quality score has been widely used for the evaluation of radiomics studies. • Although the intra-rater reliability was moderate to excellent, intra- and inter-rater reliability of total score and point-by-point scores were low with radiomics quality score. • A robust, easy-to-use scoring system is needed for the evaluation of radiomics research.

Study aim : Obesity is a serious public health problem that has spread over the past 40 years in industrialized countries. This condition can predispose to the onset of several chronic diseases for instance hyperlipidemia which is involved in multiple signaling pathways for bone homeostasis. There is a communication between adipose tissue and bone, which can regulate each other through feedback mechanisms including glucose consumption by bone, also regulating insulin levels. In our observational study, we analyzed the effects of low-impact training, particularly swimming, combined with a mediterranean diet on obese pre-adolescents. Material and methods : Six-month of an observational study was performed involving twenty pre-adolescents aged between 8 and 12 years with diagnosed obesity with z-BMI >2, according to the World Health Organization guidelines. Results : The assessment was carried out at the beginning of the intervention (T0) and at the end of treatment (T1). All participants were randomly assigned to either: the control group (CG) just followed the mediterranean diet whilst the experimental group (EG) over the mediterranean diet followed a planned physical activity. The results showed statistically significant differences between T0 and T1 in both CG and EG, especially concerning 1,25(OH) 2 D and insulin levels. However, the differences were more impressive in EG (1,25(OH) 2 D 9.27 vs 25.64; Insulin 29.31 vs 12.66) compared with CG (1,25(OH) 2 D 8.7 vs 13.7; Insulin 28.45 vs 22.76). Conclusions : In conclusion, these results showed the importance of diet and low-impact exercise intervention to improve pre-adolescent’s health especially those with obesity.

In recent years, understanding how the managers of tourism attractors (such as archaeological parks, museums, seaside resorts, nature reserves, etc...) adopt, refuse, integrate, and benefit from the digital transformation has received growing interest. In addition, consistent case-study literature highlights how adopting technologically advanced tools can generate positive externalities for the territories in which such attractors are located. However, it is still unclear how different tourism stakeholders value including Metaverse tools in their strategies. In this paper, we explore stake-holders' preferences for embedding metaverse tools in their strategy, and we check for the existence of cluster of preferences. The study applies a recent development of Q-methodology which allows substituting classical q-statements formulation with multi-attribute and multi-level formulations. Data are collected by involving stake-holders from Sicilian territories. The results of this exploratory study demonstrate that the use of the Metaverse tool is influenced by the perception of the stakeholders and confirm the existence of heterogeneous preferences among groups of stakehold-ers, as expected in a diffusion model of innovation. The dominant point of view considers a full awareness of the metaverse tools and perceives them as slightly worse than the social ones. Some stakeholders do not have adequate knowledge of the Metaverse. We can argue that we are still in a moment of transition in the diffusion of the Metaverse between the phase of persuasion and that of evaluation and decision on the basis of the impact effects of the Metaverse on competitiveness within the tourism sector. The critical mass may not have been reached yet in the adoption rate of Metaverse innovation.

Properly training LSTMs requires long time and extensive amount of data. To improve the training of these models, this paper proposes a novel residual and recurrent neural network, Resnet-LSTM, for spatio-temporal pedestrian action recognition from image sequences. The model includes a novel layer, called MapGrad, whose goal is improving stationarity of the feature map sequences processed by the ConvLSTM. The paper demonstrates the effectiveness of the proposed model and the MapGrad layer in the spatio-temporal classification of pedestrian actions through an ablation study and comparison with state-of-the-art methods. Overall, RLSTM achieves an accuracy value of 88% and an average precision of 94% on the JAAD dataset, which is a widely used benchmark in the field. Finally, the paper empirically analyzes the effect of increasing input sequence length on standing action recognition, showing that the proposed method yields a recall of 93%.

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27⁻ and CD27⁺ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.

The implementation of psycho-oncological support has shown important results in positively influencing treatment outcomes and quality of life in cancer patients and survivors. In the last few decades, the importance of mental health has been brought to attention to the general public and healthcare professionals on a national, institutional and organisational level. Official guidelines, policies, and training programs have been developed suggesting that psycho-oncological support should be considered as a non-negotiable requirement for quality cancer care in many hospitals and clinical centres across Europe. Health organisations, associations, institutions, and societies, such as the International Psycho-Oncology Society (IPOS) and the European Partnership for Action Against Cancer (EPAAC), are forming alliances, funding research projects and organising congresses in order to study, understand, and discuss the reasons for barriers and disparities in psycho-oncological support and, eventually, to overcome the existing cancer divide. Nevertheless, the World Health Organization's (WHO) estimations indicate that the cancer burden is still increasing, and relevant barriers and disparities in accessing psycho-oncological support continue to exist and influence the health conditions and quality of life of cancer patients and survivors. The present work will present the current disparities and barriers regarding assessment, access to and use of psycho-oncological support in the countries of the European Union, making suggestions for further research and possible solutions.

Background and purpose Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. Methods A prospective systematic genetic screening for ATTRv‐PN was proposed in patients presenting with a sensory–motor idiopathic polyneuropathy and two or more “red flags” among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. Results In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv‐PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv‐PN patients and 26 presymptomatic carriers) among 84 first‐degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. Conclusions A systematic screening for ATTRv‐PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv‐PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow‐up at the clinical onset.

Background and Aims As screening for the liver disease and risk‐stratification pathways are not established in patients with type‐2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost‐utility of different screening strategies for MASLD in the community. Methods Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score‐4 (FIB‐4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality‐adjusted life year (QALY) gained and calculated the incremental cost‐effectiveness ratio (ICER) over a lifetime horizon. Results Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB‐4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB‐4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost‐utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB‐4. Conclusion Screening for MASLD in the diabetic population in primary care is cost‐effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB‐4 and ELF, underestimate the presence of significant liver disease in this setting.

The need to obtain solid adhesive scaffolds that can be processed to create friendly microenvironments, direct cellular behaviors, and tissue regeneration is growing. A facile method was used to incorporate a mussel-inspired adhesive moiety, dopamine, into segmented polyurethanes based on polycaprolactone–polyethylene glycol–polycaprolactone (PCL–PEG–PCL) copolymers. Dopamine was chemically bonded to lysine and used as a chain extender to obtain a solid biodegradable elastomer capable of strongly adhering to different materials after melting occurs. Lysine alone was used as a chain extender to produce a similar polyurethane control group. The low melting point (55 °C) opens multiple possible applications for this polyurethane. A complete chemical–physical characterization was performed, and adhesion strength was evaluated in a lap shear configuration. The interaction with a high-energy surface like glass and aluminum at room temperature was remarkable (respectively 2.8 and 2.6 MPa). The adhesion was also evaluated with porcine skin underwater at 37 °C, resulting in 30 kPa. Over a period of 6 months, the material undergoes slow hydrolytic degradation. Nevertheless, the material and its degradation products were not cytotoxic. The polymer was then processed with melt extrusion three-dimensional (3D) printing to obtain oriented microfibers, producing different scaffolds.

An isolate of chili pepper mild mottle virus (CPMMV-Sp; GenBank OQ920979) with a 99% identity to CPMMV (GenBank MN164455.1) was found in symptomatic pepper plants in Spain. RACE analysis, performed using a stem-loop primer developed in this study to prime at the end of the introduced poly(A)/(U) tail, revealed the presence of an extra 22 nt at the 5' end, starting with a cytosine, which were essential to generate infectious clones. However, the 5' terminal cytosine was dispensable for initiating the infection. The design of two specific digoxigenin riboprobes targeting the more divergent area of CPMMV-Sp, compared to the closely related bell pepper mot-tle virus (BPeMV) (identity percentage of 80.6% and 75.8%, respectively), showed that both probes specifically detected CPMMV-Sp when the hybridization was performed at 68ºC and 60ºC, respectively. However, the BPeMV probe, targeting a region with an 89.4% identity percentage to CPMMV-Sp, showed cross-hybridization at 60ºC but not at 68ºC. The comparison of the detection limits between molecular hybridization and RT-PCR techniques revealed that the former was 125 times less sensitive than RT-PCR. The analysis of the vertical transmission of CPMMV-Sp using seeds from naturally or mechanically infected pepper plants revealed a transmission percentage ranging from 0.9% to 8.5%. Finally, the analysis of the resistance of cap-sicum species carrying different alleles of the L gene (L1, L2, L3, and L4) revealed that varieties with the L1 gene were infected by CPMMV-Sp (20-40% of Clara Ontañón and Mikel Ojinaga Both authors have contributed equally to the study and are considered as co-first authors independently. Supplementary Information The online version contains supplementary material available at https:// doi. inoculated plants), while varieties with the L2, L3, and L4 genes were resistant.

This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of predicting the increase in dose achievable by the addition of sensitizers inside the pellets. As expected, a larger amount of 6Li induces an increase of energy released because of the charged secondary particles (i.e. 3H ions and α-particles) produced after neutron capture. For small depths in water phantom and low-energy neutron spectra the dose increase due to 6Li enrichment is high (more than three orders of magnitude with respect to the case of with 7Li). In case of epithermal neutron beams the energy released in 6Li-enriched LFM compound is smaller but larger than in the case of fast neutron beams. On the other hand, the computational analysis evidenced that gadolinium is less effective than 6Li in improving neutron sensitivity of the LFM pellets. Discussion based on the features of MC transport code is provided. This result suggests that 6Li enrichment of LFM dosemeters would be more effective for neutron sensitivity improvement and these EPR dosemeters could be tested for dosimetric applications in Neutron Capture Therapy.

In recent years, the theoretical investigation about the notions of “diagram” and “gesture” has become increasingly popular and widespread. Fields like mathematics, semiotics and linguistics have been particularly attentive to the ways in which such notions are used and codified.

The text aims to reconstruct the genesis of a core diagram in Antoine Culioli's Theory of Predicative and Enunciative Operations: the so-called “cam structure”. For the purpose of a clear and rigorous exposition, the formal aspects of this diagram are examined in relation to some key problems of Culiolian theorization: the generative role of the Lexis with respect to the plane of assertion and, more generally, with respect to the work of enunciation. In the last part of the paper, an attempt is made to connect the main results of Culiolian thinking with some of the most stimulating theoretical works on the epistemological value of the diagram: Gilles Deleuze's heterogenesis and Gilles Châtelet's philosophy of mathematics.

The path conceived together with Charles Alunni and Fernando Zalamea aimed to provide an overview of the current debate surrounding the notion of diagrammatic gesture.

Purpose of Review This review aims to access the current state of the evidence in exercise as medicine for cardio-oncology in Hispanic and Latina breast cancer survivors and to provide our preliminary data on the effects of supervised aerobic and resistance training on cardiovascular disease (CVD) risk in this population. Recent Findings Breast cancer survivors have a higher risk of CVD; particularly Hispanic and Latina breast cancer survivors have a higher burden than their White counterparts. Exercise has been shown to reduce CVD risk in breast cancer survivors; however, evidence in Hispanic and Latina breast cancer survivors is scarce. Summary Our review highlights a clear need for exercise oncology clinical trials in Hispanic and Latina breast cancer survivors targeting CVD risk factors. Moreover, our exploratory results highlight that 16 weeks of aerobic and resistance training may reduce the 10-year risk of developing CVD by 15% in Hispanic and Latina breast cancer survivors.

In recent decades, many concrete bridges, built in the 60s and 70s of the 20th Century with a Gerber-girder scheme, show severe damage of the saddles due to concrete degradation and reinforcement corrosion. On the basis of the recent Ministerial Guidelines for the assessment of existing bridges, it is necessary to evaluate the state of the Gerber saddles in a large number of bridges on both main and secondary roads. To do this, it is necessary to apply flexible assessment procedures that can be adapted to several situations and that allow a speedy assessment of the intervention priorities. The methodologies of intervention represent the crucial point for a rapid rehabilitation of these infrastructures. In this paper, on the basis of some case-studies, assessment and strengthening methodologies are proposed that can be applied to different real cases, in consideration of the budget available, with the aim of drafting an operative list of priorities and improving as many bridges as possible, currently in service.