Beyond the immune suppression: the immunotherapy in prostate cancer

Prostate cancer (PCa) is the second most common cancer in men.Aswell in many other human cancers, inflammation and immune suppression have an important role in their development.We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression.Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapie

Microtaphofacies analysis of lower Oligocene turbid-water coral assemblages

The presence, distribution, and preservation of coral-rich facies in the lower Oligocene Gornji Grad Beds of Slovenia are analyzed using a microtaphofacies approach. This method allows taphonomic signatures to be recognized in thin section along with the presence of coral specimens and growth forms within and between stratigraphic logs. Coral-dominated limestones within the Gornji Grad Beds are represented by rudstones in a packstone-wackestone matrix. The conditions are generally reconstructedas turbid water due to the prevalence of muddy carbonate matrix, which also leads to excellently preserved morphological features in thin section. These beds represent a reference area for the study of Paleogene corals, especially during the Oligocene, a key phase of reef development during the Cenozoic. This study also contributes to the characterization of fossil reefs in turbid-water environments. The evaluated coral fauna is dominated by delicate-branching Stylophora and Acropora, although thickly branching (Actinacis, Goniopora), phaceloid (Caulastrea), and massive forms (Alveopora, Astreopora, Antiguastrea) also occur. Assessed taphonomic signatures include fragmentation, abrasion, bioerosion, and encrustation. Three types of bioerosion traces are distinguished (Entobia, Gastrochoenolites, Trypanites). Encrustation includes both thincrusts and complex multi-taxon sequences dominated by coralline algae. Five microtaphofacies are distinguished based on variation of taphonomic signatures, taxonomic composition, and growth forms. Differences in microtaphofacies are interpreted with respect to turbidity, sediment accumulation, and water turbulence; both parautochthonous and allochthonous deposits are reconstructed. A depositional model based on the distribution of microtaphofacies in the studied sections shows a succession of coral communities with different colonization strategies reflecting generally high stress levels

Sheaf Neural Networks for Graph-based Recommender Systems

Recent progress in Graph Neural Networks has resulted in wide adoption by many applications, including recommendation systems. The reason for Graph Neural Networks' superiority over other approaches is that many problems in recommendation systems can be naturally modeled as graphs, where nodes can be either users or items and edges represent preference relationships. In current Graph Neural Network approaches, nodes are represented with a static vector learned at training time. This static vector might only be suitable to capture some of the nuances of users or items they define. To overcome this limitation, we propose using a recently proposed model inspired by category theory: Sheaf Neural Networks. Sheaf Neural Networks, and its connected Laplacian, can address the previous problem by associating every node (and edge) with a vector space instead than a single vector. The vector space representation is richer and allows picking the proper representation at inference time. This approach can be generalized for different related tasks on graphs and achieves state-of-the-art performance in terms of F1-Score@N in collaborative filtering and Hits@20 in link prediction. For collaborative filtering, the approach is evaluated on the MovieLens 100K with a 5.1% improvement, on MovieLens 1M with a 5.4% improvement and on Book-Crossing with a 2.8% improvement, while for link prediction on the ogbl-ddi dataset with a 1.6% refinement with respect to the respective baselines.Comment: 9 pages, 7 figure

L225P mutation of ABCC8 gene: a case of transient neonatal diabetes mellitus with thrombophilic predisposition and epilepsy

Neonatal diabetes mellitus (NDM) is defined as a rare disorder of glucose metabolism in the first six months of life, transient (TNDM) or permanent (PNDM). TNDM usually resolves by 18 months, though it might relapse later in life; PNDM requires lifelong therapy with insulin or/and sulfonylurea. Etiology of NDM is monogenic and genetically heterogeneous. TNDM is often caused by an over-expression of paternal genes on chromosome 6 or by mutation in KCNJ11. Either way the release of insulin is reduced. PNDM is mostly associated with two genes, KCNJ11and ABCC8, which encode, respectively, Kir 6.2 and SUR1, subunits of beta cells K-ATP channel. K-ATP channel is constitutively open, hyperglycemia increases the intracellular ATP levels that cause the closure of K-ATP channel and the depolarization of beta cell causing release of insulin. Inactivating mutations in Kir 6.2 or SUR1, K-ATP channel remains open leading to impaired insulin secretion and neonatal diabetes. Here, we report a case of a three months old baby with diagnosis of NDM and thrombophilic predisposition, referred to emergency pediatric department because of intercurrent ipsilateral clonus to the upper and lower right limbs from a few days, successor seizures during the recovery and incidental finding of hyperglycemia. Child was initially treated with insulin, subsequently was started therapy with glybenclamide for 13 months with progressive decal age. The child was also successfully weaned by treatment with sulfonylureas and epilepsy was well controlled with Phenobarbital

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology

Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy

#exploreART: il labirinto di A. Pomodoro e i bambini. Un progetto di fruizione condivisa con percorsi sensoriali partecipati

The contribution presents a research project conducted by Fondazione Arnaldo Pomodoro to formulate, design and create, together with children and teachers, and to evaluate – with the help of the University – a different approach to the experience of contemporary art. This project has been implemented thanks to co-funding provided by Fondazione Cariplo. The initial hypothesis, after many years of experimentation on the part of Fondazione Arnaldo Pomodoro in the field of art education, and in the various temporary and permanent exhibitions organized by the foundation, was to explore a series of new possibilities that underline the value of participation, in which the soundscape can also become part of a meaningful experience

Circulating tumor DNA and disease recurrence in early stage breast cancer: From a case-control study to a prospective longitudinal trial

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Self-perceived physical level and fitness performance in children and adolescents with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) UC (n = 24) and IBD unclassified (n = 3), and 70 healthy children. In all children, the Physical Activity Questionnaire (PAQ-C) and the International Fitness Enjoyment Scale were self-reported and recorded. Results: PAQ-C showed significant difference in PA levels in patients with IBD compared to controls (p < 0.001). A decrease in general fitness (p = 0.003), cardiorespiratory fitness (p = 0.002), strength (p = 0.01), speed agility (p = 0.003), and flexibility (p = 0.01) were also detected between patients and controls. Speed agility was related to age (p = 0.02) and BMI z-score (p = 0.01), and flexibility to BMI z-score (p = 0.05). We noted a correlation between PA levels and physician global assessment (p = 0.021) and activity disease severity (p = 0.025). Conclusions: A poorer PA level and poor physical competence were found in patients with IBD compared to healthy children and adolescents. Monitored exercise could provide multiple benefits at both physical and psychological levels

Validation of decisional balance inventory test in Italian: assessment of motivation in weight loss

The decisional balance inventory (DBI) test is a valuable tool to assess motivation to change; we consider its application in enhancing motivation of losing weight. Our aim is the translation, cultural adaption and validation in Italian of this test originally designed and drafted in English. The questionnaire has been translated according to an English → Italian → Italian → English algorithm with reconciliation of the differences. Pilot study and retests were performed on 47 cases [body mass index (BMI) ≥30 kg/m2] and 15 controls (BMI value between 18.5 and 25 kg/m2). The internal consistency of the Italian version of DBI test, was satisfied (Cronbach α 0.87 on patients); test-retest shows a good concordance in pilot [Lin's concordance correlation coefficient (CCC) 0.79; 95% confidence interval (CI) 0.68-0.90] and in patient sample (Lin's CCC 0.83; 95% CI: 0.67 0.99).Our study demonstrated the trans-cultural adaptation and validation of DBI test in Italian