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Fracture characterization of ductile polymer cellular model structures manufactured by FDM
No full textThis work addresses specific fundamental and methodological issues regarding the applicability of Fracture Mechanics (FM) testing schemes to polymer open-celled cellular solids with controlled architecture, exhibiting an elastic–plastic response and with pronounced structural heterogeneity at the cell-scale. Acrylonitrile-Butadiene-Styrene (ABS) model structures were manufactured by Fused Deposition Modeling (FDM), and their mode-I fracture response investigated. Structures with different porosity degrees (from ≈ 20% to ≈ 70%) were examined, and initiation fracture toughness (J-integral) data determined. Different modes of mechanical
macro-confinement experienced by the circular cross-section beam-like structural element were noticed, able to drive a transition from true cellular to solid containing isolated pores
PD-1+ NK cell subsets in high grade serous ovarian cancer: an indicator of disease severity and a target for combined immunecheckpoint blockade
No full textAbstract
Background Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women, with High-Grade
Serous Ovarian Carcinoma (HGSC) representing the most aggressive and prevalent subtype. Despite promising results
in other malignancies, immune checkpoint blockade has shown limited efficacy in HGSC, highlighting the need for
alternative immunotherapeutic targets.
Methods We conducted an integrated analysis combining multiparametric flow cytometry, RNA sequencing,
multiplex immunohistochemistry, and functional assays to characterize NK cells isolated from peripheral blood,
peritoneal fluid, primary tumor tissue, and metastases in 60 HGSC patients.
Results We identified a distinct population of PD-1+ NK cells enriched in HGSC tumors and metastatic sites but
absent in healthy donors. These cells, characterized by a CD56dimNKG2A+KIR+/−NKp46+CD57low phenotype, displayed
impaired cytotoxicity against autologous HGSC targets, correlating with poorer prognosis. Crucially, this dysfunction
was reversible upon combined blockade of PD-1/PD-L1, NKG2A, and KIRs. Spatial and molecular profiling revealed
that these cells localize within PD-L1+/HLA-E+ tumor niches, suggesting that immune suppression is spatially andmolecularly coordinated. Transcriptomic analysis confirmed their altered functional state and highlighted actionable
checkpoint targets.
Conclusions Our findings uncover a previously underappreciated population of dysfunctional PD-1+ NK cells in
HGSC and demonstrate that their suppression is reversible through combinatorial checkpoint inhibition. These
insights support the development of spatially-informed, NK-targeted immunotherapies for HGSC patients, particularly
those resistant to T cell-based strategies
Stimulated CAR-T cells from non-Hodgkin lymphomas patients engage and activate monocytes via extracellular vesicles
No full textUse of the Lorenz curve and the Gini index for the evaluation of HIV viral load distribution in an Italian community
No full textBackground: Community viral load (CVL) is defined as an aggregate measure of individual viral loads of people living with HIV who are receiving care in a specific community. It serves as a metric to evaluate the effectiveness of therapy programs. Our study aimed to analyze the overtime trend and the distribution characteristics of viral load. Methods: Using the Lorenz curve, we investigated the demographic characteristics of individuals who comprised the top 10% of viral loads over the years. We applied the Gini index to measure the inequality in the distribution of viral load among the study population. Results: Our data showed a progressive decrease in community viral load over the years, with a sharp decline after 2012 and a rebound in 2020. The Gini index had a specular trend during this period. In all the observed periods, the top 10% of viral loads showed a progressive increase in the proportion of female individuals and non-Italian nationals. Conclusion: Our study highlighted the effectiveness and the improvement of the HIV care cascade over the years, with a decrease in community HIV viral load. The introduction of integrase inhibitors seemed to cause a rapid drop in community viral load in 2012 but with a notable discrepancy in the homogeneity of the population. It is also important to highlight the changes over time in the population representing the top 10% of viral loads, with a gradual but stable increase in the proportion of female and non-Italian individuals
Empowering Public Interest Communication with Argumentation - Project Report
No full textThe EPICA (Empowering Public Interest Communication with Argumentation) project aims to improve Public Interest Communication (PIC) through the use of advanced Computational Argumentation (CA) techniques. This paper provides a summary of the technical results of the project and discusses future research direction
Progress and policies to achieve the zero pollution action plan and EU 2024/2881 PM2.5 targets in Northern Italy
No full text: Fine particulate matter (PM2.5) is a major contributor to air pollution-related mortality in Europe. The European Zero Pollution Action Plan (ZPAP) aims to reduce PM2.5-attributable deaths by 55% by 2030 relative to 2005, while the EU Directive 2024/2881 states the new Ambient Air Quality targets. The open questions are: (1) has the ZPAP and the EU Directive 2024/2881 target for PM2.5 already been reached? If not, (2) will the current policy allow the ZPAP and EU 2024/2881 target for PM2.5 to be met in 2030, or (3) is an additional policy needed? This work proposes a methodology to estimate the attributable deaths caused by PM2.5 exposure in 2005, 2019 (question 1), and 2030 projection, considering the current legislation (CLE2030, question 2) and a policy (OPT2030, question 3), solution of a multi-objective problem that minimizes PM2.5 concentration and measure costs. The methodology was tested on the Po Valley in Northern Italy, one of the most polluted areas in Europe. Results show that premature deaths decreased by 36% on average from 2005 to 2019. By 2030, under current legislation (CLE2030), 18 of the 29 major cities are projected to meet the ZPAP target, while only 2 are expected to comply with the PM2.5 target of the Directive (EU) 2024/2881. With the implementation of additional measures (OPT2030), the number of cities meeting the ZPAP target rises to 26, and 13 are projected to achieve the PM2.5 limit recommended by the Directive (EU) 2024/2881
Describing phenotypes in FSHD: an update of the comprehensive clinical evaluation form
No full textBackground: Facioscapolohumeral muscular dystrophy is characterized by a wide clinical variability; the underlying reasons and the relation between them and the genetic markers are still not clear. In fact, the different phenotypes could show a different disease progression and/or imply distinct genetic mechanisms. As clinical trials are approaching also for FSHD, the correct description and stratification of patients becomes mandatory. To address these matters, in 2016 the Italian Clinical Group for FSHD developed the Comprehensive Clinical Evaluation Form (CCEF), aimed at describing the different observed phenotypes in FSHD. Methods: A working group composed by the former developers of the CCEF and other expert clinicians re-evaluated the whole structure of the CCEF, to develop a simplified version for use in clinical practice; also, other expert clinicians not referring to the Italian Clinical Group for FSHD read and approved the CCEF revised version for its international use. Results: We present the CCEF-R, a revised and simplified version of the CCEF, that while maintaining all the core structure and items of the previous validated version, has been modified with new friendlier graphics, focused on the key anamnestic and neurological examination findings, to facilitate its understanding and use in clinical practice. Conclusions: The phenotypical classification combined with the genetic signature should be considered during the diagnostic work out for guiding genetic analysis and for genotype–phenotype correlations and genetic counseling. The CCEF could have a significant role in the clinical stratification process of patients for clinical trials and in laying the groundwork for evidence-based medical decision making
Quantitative Neuroanatomical Measurement on Photogrammetric Model: Validation Study
No full textObjective: To examine and compare the accuracy of measurements obtained from photogrammetric models versus direct measurements taken on dry skulls, with the aim to verify the feasibility of photogrammetry for quantitative analysis in microsurgical neuroanatomy. Methods: Two dry human skulls were used. Each was scanned using the dual camera system of a smartphone The selected photos were separately processed using 2 different softwares to create three-dimensional models. Subsequently, 41 anatomical measurements (both linear and curvilinear) based on common anatomical landmarks were taken both directly on dry skulls and on photogrammetric models and compared. Analyzed factors included measurement error, intrarater and interrater reliability, and intermodality agreement. Results: Four photogrammetric models were created. Analysis revealed similar errors when comparing photogrammetric and direct measurements. Measurements from digital models exhibited robust reliability among repeated measures and different observers, supported by very high intraclass correlation coefficient values. Mean measurement difference between Agisoft Metashape software–generated models and direct measurement was 0.01 cm with no systematic bias observed. Conversely, the Metascan app–derived models showed a mean measurement difference of −0.35 cm compared with direct measurement, displaying good agreement for smaller measurements and a systematic proportional bias with increasing measurement size. Conclusions: Two photogrammetric models were validated as quantitative analysis techniques for laboratory neuroanatomical studies, showing acceptable measurement error, high intrarater and interrater reliability, and good to very good agreement compared with direct measurement on dry skulls, replacing expensive and time-consuming methods such as computed tomography scans and neuronavigation systems
(Non)canonical Wnt signaling, cytoarchitecture and stemness: new insights from primary nonmetastatic, primary metastatic, regional and distant metastatic models of adrenocortical carcinoma
No full textTumor cells rearrange cytoskeletal networks, harmonize signaling pathways and modulate cell fate to initiate tumor growth and metastasis. Activating mutations in the canonical Wnt–β-catenin pathway are associated with aggressiveness and poor prognosis in adrenocortical carcinoma (ACC). However, the contribution of noncanonical Wnt pathways, which are known to regulate cell polarity and migration, is still widely unknown. Here we comprehensively investigated canonical and noncanonical Wnt signaling along with cytoskeleton networks, stemness programs and HOX gene expression in recently developed 2D and 3D cultures of primary, local and distant metastatic ACC models. We report that tumor spheroids derived from nonmetastatic primary tumors correlated strongly with the overexpression of canonical Wnt signaling components, while metastatic ACC models demonstrated shifts toward noncanonical Wnt pathways together with perturbed expression of matrix–cytoskeleton–nucleoskeleton markers and related changes in the cytoarchitecture of respective tumor spheroids. Consistent with a potential noncanonical Wnt activation in the metastatic models, an abundance and relocalization of proteins associated with tumor aggressiveness such as β-catenin, β-actin, vimentin and nucleolin as well as specific HOX-cluster activation was detected, suggesting strong potential for specific reconfigurations of metastatic tumor niches. Furthermore, all models demonstrated key properties of cancer stem cells, although with varying degrees of expression of progenitor and stem cell markers, which could be dynamically modulated by treatments and therapies. Overall, our results draw parallels between canonical and noncanonical Wnt signaling, differential cytoskeletal remodeling, stemness properties and various cellular plasticities in primary tumor and metastasis-derived models of ACC
Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review
No full textTreatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However, the molecular underpinnings of these effects are not yet understood. This systematic review aimed to synthesize evidence from human and in vitro studies evaluating transcriptional changes associated with ketamine and esketamine treatment, to identify potential biomarkers and clarify molecular pathways relevant to their antidepressant properties. A systematic search conducted on PubMed and Scopus identified 12 studies assessing RNA expression following ketamine or esketamine treatment in patients with unipolar or bipolar depression or in human-derived cell models. Eligibility and quality were evaluated using PRISMA guidelines and a modified version of Downs and Black checklist. Twelve studies met inclusion criteria, only one of which explored the effect of esketamine, while all others focused on racemic ketamine. Five studies examined peripheral blood gene expression in patients with TRD, while seven assessed mRNA changes in vitro using human-derived cells. Transcriptome and candidate gene expression studies revealed modulation of genes and pathways related to glutamatergic signaling (GRM2, GRIN2D), immune regulation (STAT3, CCL22, IL6), and neuroplasticity (IGF2). No consistent peripheral biomarkers emerged, but transcriptional profiling revealed dynamic molecular responses to ketamine and esketamine. Ketamine and esketamine induce diverse transcriptional changes implicating neuroplastic, inflammatory, and metabolic pathways. Transcriptomic profiling offers a promising approach for uncovering biomarkers and mechanisms of antidepressant response, warranting further multi-omics, large-scale studies