University of Milan

Advanced automation tools are promising widerange solutions for the various problems still affecting HighTemperature Superconducting (HTS) magnets, including NonInsulated (NI) ones. However, they are not applicable if reliable models that can run in real-time are not available. This article discusses a preliminary solution for this. For this scope, we propose the construction of reduced-order models, derived from 3D physical-based models. A Volume Integral Formulation (VIM) is presented and reduced using a technique called Proper Orthogonal Decomposition (POD). VIM solves for currents in the conducting domains, relying on Biot-Savart for interactions between elements; meshing insulating domains, such as air, is thus not needed. POD is a reduction technique where the most relevant information is retrieved by processing the fullsystem response through factorizations such as Singular Value Decomposition. The reduced and full models are then compared, showing that the former offers accurate solutions with a fraction of the computation effort of the latter. Finally, some potential applications of this technique are briefly discussed.

IRIS (Innovative Research Infrastructure on applied Superconductivity) is a major project to build a research infrastructure in applied superconductivity, recently approved in Italy and led by INFN. The design and delivery of a Green Superconducting Line (GSL) for power transmission and the construction and commissioning of a test station for GSLs testing are two key deliverables of the project. The test station is under construction at the University of Salerno. It foresees the main building, and a outdoor space for 130 m long cable lodging. Into the building there will be the current and voltage power supplies (40 kA and 50 kV, respectively), a 500W@20 K He-refrigerator, monitor and control systems and diagnostics for GSLs testing. The facility will be kept open to external institutions and companies engaged in the same research field. The GSL will be 130 m long and designed to carry 40 kA at 20 K, isolated for 25 kV operation, i.e. 1 GW of power, with almost zero dissipation. The GSL will be used for the commissioning of the test station. In this paper we will present the line configuration. We updated the design of the line from a four conductors (two phases and two spares for redundancy) inside the same cryostat configuration to a three conductors (two phases and a spear) each inside its own cryostat, in order to have a better insulation between them in case of failure of one phase. Details and preliminary analysis of the updated line design will be presented.

The International Muon Collider Collaboration (IMCC) has been formed with the aim of delivering a feasibility study on a Muon Collider facility, as recommended by the European Strategy for Particle Physics and supported by the European Union through the Grant Agreement 101094300. Such facility would allow to study frontier physics with a 10 km collider ring and a muon center of mass energy of 10 TeV. Several technical challenges arise due to the short rest lifetime of these particles (2.2 $\mu$ s), necessitating the use of cutting-edge technology for all components, particularly the superconducting magnets. In this contribution, we present the main challenges of such magnets, focusing on the performance limits of the available technology and the possible design choices. The LTS (Low Temperature Superconductor) materials Nb-Ti and Nb $_{3}$ Sn and the ReBCO HTS (High Temperature Superconductor) are analysed, comparing costs, mechanical structure feasibility and ease of protection from quench, taking into account also the sustainability of the cooling and the compatibility with the beam dynamics constraints. Furthermore, preliminary designs of arc dipoles in cos $\theta$ coil and block coil configurations is discussed, focusing on the maximum achievable bore field, the stress induced by the electromagnetic forces and the AC losses due to magnetization.

Pursuing rural electrification in developing countries through hybrid generation systems is constrained by a lack of suitable energy modelling tools. Few tools include geographical parameters relevant to capturing specific spatial and socio-economic circumstances. Even less are openly available and find applications for rural areas of developing countries. This work presents an integrated geospatial energy modelling framework based on an extended tool, the GISEle (GIS for rural electrification) model, which aims for a least-cost energy solution. GISEle is an open-source tool supporting rural electrification planning strategies and challenges through optimal hybrid microgrid integration. The developed framework is universally applicable and explains how the extended GISEle tool can be used to become suitable for analysing decentralised hybrid generation systems within the context of rural areas of developing countries. This presented framework includes:•Advancing the approach to proper data collection to better capture local specificities and (future) demand and reporting results in rural areas of developing countries; •Adding the Remote-Areas Multi-energy systems load Profiles (RAMP) to improve load demand assessments, while considering the impact of electrification on growing demand scenarios; •Linking the Soil and Water Assessment Tool (SWAT) model to allow for hydropower sizing in GISEle.

Local full‐thickness resection techniques for rectal cancer are limited by lesion size, location, or poor margin delineation. We aimed to evaluate the feasibility of endoscopic knife‐assisted full‐thickness resection (kFTR) guided by the pocket‐detection method (PDM) for deeply invasive rectal cancer. Consecutive posterior‐lateral rectal lesions suspected of deep submucosal invasion treated at a tertiary care center from February to October 2024 were retrospectively included. kFTR guided by PDM involved creating a submucosal pocket to detect and isolate the suspected invasive component (muscle‐retracting sign), followed by muscularis propria incision and full‐thickness resection. Technical success, accuracy of detecting deep submucosal invasion, and en‐bloc resection rates were 100%. The median procedure time was 141.5 [IQR 123.7–179.5] minutes and the median hospitalization was 1 [IQR 1–7] day. No adverse events occurred. Histopathology showed R1‐vertical margin in patient 1 (pT2 adenocarcinoma) and R0 resection in patients 2, 3, and 4 (pT1bsm3) after refinement of the procedure to include a ≥3 mm muscularis propria margin around the suspected invasive component. There was no recurrence at the first endoscopic follow‐up of patients 1, 2, and 4. Patient 3 was sent to surgical low anterior resection due to multiple high‐risk histological features. The previous kFTR did not impair surgery (no residual rectal carcinoma and 1/17 positive lymph nodes). Endoscopic kFTR guided by the PDM may be a feasible organ‐preserving treatment for the detection and resection of deeply invasive posterior rectal cancer. Future studies are needed to ascertain whether rectal kFTR could represent a viable alternative to conventional surgical local excision techniques.

Background Subjective evaluation of gait by official endurance veterinarians (OEVs) is used to determine ‘fitness‐to‐compete’ in horses participating in endurance competitions. Objective gait analysis systems could aid in quick and verifiable judgements. Objectives To assess the agreement between objective analysis of head and pelvis vertical movement asymmetry performed with a markerless artificial intelligence motion tracking system (AI‐MTS) and subjective lameness assessment performed by an accredited FEI OEV to judge horse gaits. Study Design Cross‐sectional. Methods During three endurance competitions, 110 horses were enrolled. The OEV performed 188 gait examinations, which were simultaneously recorded with a smartphone. The vertical motion asymmetry of the head and pelvis was later analysed from the videos through the AI‐MTS application. The gaits were scored as ‘no asymmetry’, ‘mild asymmetry’ or ‘severe asymmetry’. The agreement was evaluated using Fleiss' multi‐rater kappa statistic (κ). Results The overall agreement between the two methods was fair (k = 0.26, p < 0.001). Within the three gait asymmetry categories, substantial agreement was obtained for the ‘severe’ (k = 0.75, p < 0.001) category, fair agreement was detected for the ‘no asymmetry’ category (k = 0.25, p < 0.001), and no agreement was identified for the ‘mild’ category (k = 0.13, p = 0.08). Main Limitations Comparison between AI‐MTS and a single OEV; absence of a tripod during video recording; and video recording from a different point of view than the OEVs. Conclusions Mild asymmetry was the most challenging gait category to identify. Substantial agreement between the subjective lameness evaluation by OEV and AI‐MTS assessment was observed for the ‘severe’ category. AI‐MTS may be a helpful tool to assist OEVs in decision‐making during endurance competitions.

The research activity is fundamental to improve knowledge in Medicine. In the setting of clinical oncology, radiotherapy (RT) represents a cornerstone for patients treated with curative intent. The aim of this snapshot was to investigate the number and the characteristics of clinical trials currently ongoing in the Lombardy (Italy) RT divisions highlighting involved resources and eventual needs to improve the process of study activation. In April 2024, a survey composed of two parts, a snapshot of clinical and research activity and a database to report data on ongoing clinical trials, was proposed to the 30 RT centers in Lombardy. The snapshot consisted of 19 short answer questions. A total of 26 (87%) centers answered the survey. The total number of active studies was 161. The median age among principal investigators was 51 years. Most studies were multicentric (61%) national (76%). Among 72 studies with available phase, 43% resulted phase III studies. Fifty-three (33%) studies were sponsored. IRCCS (Istituti di Ricovero e Cura a carattere scientifico) RT have a median of 11 active studies vs versus 6 in non-IRCCS structures. More resources are available in IRCCS centers compared to non-IRCCS: data management service 50% vs 25%, dedicated scientific nurses 20% vs 0%, clinical statistics services 60% vs 25%. The main difficulties in conducting clinical trials were bureaucratic difficulties with ethics committees (5 centers), time constraints (5 centers), and a lack of resources and staff (15 centers). The most frequently (58% of the centers) proposed solution was an increase in resources and staff. While the RT centers in Lombardy demonstrate a commendable commitment to clinical research, disparities in resources and infrastructure remain significantly challenging.

Background Total maxillectomy for malignant tumors presents significant challenges for functional and aesthetic rehabilitation. Advances in digital planning and additive manufacturing have reintroduced subperiosteal implants as a promising solution for primary reconstructions. Case report This report details the case of a 59-year-old male with squamous cell carcinoma of the hard palate extending contralaterally, treated with a total maxillectomy and primary reconstruction using an osteomyocutaneous fibula free flap combined with a custom-made, additively manufactured subperiosteal implant. Preoperative planning integrated craniofacial CT scans, dental impressions, and lower limb angiography to design both the implant and fibula cutting guides. The implant, fabricated via direct metal laser sintering, provided a stable framework for fibular segments and future prosthetic rehabilitation. At two years post-surgery, the patient remains disease-free, with no complications and fully functional prosthetic integration. Conclusions This case highlights the feasibility, adaptability, and potential benefits of additively manufactured implants in reconstructing total maxillectomy defects. Clinical trial number N/A

Post-operative cognitive decline (POCD) is characterized by impairments in cognitive functions. Coronary artery bypass grafting (CABG) is associated with a high risk of POCD due to its impact on neuroinflammation and oxidative stress. In this study, we investigated the dynamics of neurotrophic, inflammatory, and oxidative stress markers in a cohort of post-CABG patients to identify potential biomarkers for POCD. Blood samples were collected at baseline (immediately post-surgery) and at 3-month follow-up. Expression levels of NRF2 and other regulators of oxidative stress (GST, GSS, HMOX1, CAT, HSP27, and LOX-1), inflammatory mediators (IL-6, IP-10, and NFκB), and neuroprotective factor (BDNF) were analyzed. Cognitive assessments were performed using RBANS, TMT, TIB and MMSE. POCD patients exhibited an initial upregulation of NRF2-related antioxidant genes, which failed to sustain at 3-months follow-up, leading to a decline in HMOX1, IP-10 and BDNF protein levels, along with increased LOX-1 protein level and NFκB expression, indicating persistent oxidative stress and inflammation. In contrast, non-POCD patients demonstrated a sustained increase in antioxidant and neuroprotective markers, suggesting a more effective compensatory response. ROC analysis identified HMOX1 and BDNF as significant predictors of POCD, with LOX-1 and IP-10 emerging as diagnostic markers at follow-up. In conclusion, our findings highlight the dynamic regulation of oxidative stress and inflammatory pathways in POCD, emphasizing the failure of sustained neuroprotection in affected patients. Further large-scale studies are necessary to validate these findings, and biomarker-based screening could facilitate early risk stratification and targeted interventions to improve cognitive outcomes after cardiac surgery. Graphical Abstract Potential biomarkers of POCD (post-operative cognitive decline) in the circulatory system. It depicts patients without POCD, and highlights the activation of the NRF2 pathway to upregulate downstream genes, which exert antioxidant and anti-inflammatory effects. Central to the scheme is oxidative stress, which causes inflammation and subsequent damage, with protective biomarkers like HSP27, HMOX1, BDNF, and IP-10 counteracting its effects.

Modern data mining applications require to perform incremental clustering over dynamic datasets by tracing temporal changes over the resulting clusters. In this paper, we propose A-Posteriori affinity Propagation (APP), an incremental extension of affinity propagation (AP) based on cluster consolidation and cluster stratification to achieve faithfulness and forgetfulness. APP enforces incremental clustering where i) new arriving objects are dynamically consolidated into previous clusters without the need to re-execute clustering over the entire dataset of objects, and ii) a faithful sequence of clustering results is produced and maintained over time, while allowing to forget obsolete clusters with decremental learning functionalities. Four popular labeled datasets are used to test the performance of APP with respect to benchmark clustering performances obtained by conventional AP and incremental affinity propagation based on nearest neighbor assignment algorithms. Experimental results show that APP achieves comparable clustering performance while enforcing scalability at the same time.

Recent developments in animal motion tracking and pose recognition have revolutionized the study of animal behavior. More recent efforts extend beyond tracking towards affect recognition using facial and body language analysis, with far-reaching applications in animal welfare and health. Deep learning models are the most commonly used in this context. However, their “black box” nature poses a significant challenge to explainability, which is vital for building trust and encouraging adoption among researchers. Despite its importance, the field of explainability and its quantification remains under-explored. Saliency maps are among the most widely used methods for explainability, where each pixel is assigned a significance level indicating its relevance to the neural network’s decision. Although these maps are frequently used in research, they are predominantly applied qualitatively, with limited methods for quantitatively analyzing them or identifying the most suitable method for a specific task. In this paper, we propose a framework aimed at enhancing explainability in the field of animal affective computing. Assuming the availability of a classifier for a specific affective state and the ability to generate saliency maps, our approach focuses on evaluating and comparing visual explanations by emphasizing the importance of meaningful semantic parts captured as segments, which are thought to be closely linked to behavioral indicators of affective states. Furthermore, our approach introduces a quantitative scoring mechanism to assess how well the saliency maps generated by a given classifier align with predefined semantic regions. This scoring system allows for systematic, measurable comparisons of different pipelines in terms of their visual explanations within animal affective computing. Such a metric can serve as a quality indicator when developing classifiers for known biologically relevant segments or help researchers assess whether a classifier is using expected meaningful regions when exploring new potential indicators. We evaluated the framework using three datasets focused on cat and horse pain and dog emotions. Across all datasets, the generated explanations consistently revealed that the eye area is the most significant feature for the classifiers. These results highlight the potential of the explainability frameworks such as the suggested one to uncover new insights into how machines ‘see’ animal affective states.

Background Osteoarthritis is a common degenerative joint disease marked by cartilage degeneration and inflammation. This study investigates the therapeutic potential of adipose-derived stromal cells (ASCs) and their secretome in a rat model of osteoarthritis. Methods ASCs were extracted from human adipose tissue, cultured, and primed with human platelet lysate. The secretome was collected after 48 h of serum-free culture. Osteoarthritis was induced in rats using monosodium iodoacetate, and after 14 days, they were treated with saline solution, ASCs, or secretome. Over five weeks, body weight and histopathological changes were monitored. Results No clinical complications arose post-treatment, and all rats gained weight similarly. ASC treatment increased histopathological changes associated with osteoarthritis, including severe cartilage necrosis and bone remodeling. Conversely, the secretome treatment resulted in mild to moderate cartilage degeneration, similar to that observed in the control group. These findings suggest that ASCs may contribute to disease progression in this model, while the secretome did not show significant effects on cartilage histology compared to the control group. Further studies are needed to determine whether optimizing the secretome composition or dosing could enhance its therapeutic potential. Conclusions This study highlights the complexity of ASC interactions with the immune system, while secretome may be a well-tolerated treatment, further studies are needed to determine its potential therapeutic benefits.

Citron Kinase (CITK) is a protein encoded by the CIT gene, whose pathogenic variants underlie microcephalic phenotypes that characterize MCPH17 syndrome. In neural progenitors, CITK loss leads to microtubule instability, resulting in mitotic spindle positioning defects, cytokinesis failure, and accumulation of DNA double strand breaks (DSBs), ultimately resulting in TP53-dependent senescence and apoptosis. Although DNA damage accumulation has been associated with impaired homologous recombination (HR), the role of CITK in this process and whether microtubule dynamics are involved is still unknown. In this report we show that CITK is required for proper BRCA1 localization at sites of DNA DSBs. We found that CITK’s scaffolding, rather than its catalytic activity, is necessary for maintaining BRCA1 interphase levels in progenitor cells during neurodevelopment. CITK regulates the nuclear levels of HDAC6, a modulator of both microtubule stability and DNA damage repair. Targeting HDAC6 in CITK-deficient cells increases microtubule stability and recovers BRCA1 localization defects and DNA damage levels to that detected in controls. In addition, the CIT-HDAC6 axis is functionally relevant in a MCPH17 zebrafish model, as HDAC6 targeting recovers the head size phenotype produced by interfering with the CIT orthologue gene. These data provide novel insights into the functional interplay between HR and microtubule dynamics and into the pathogenesis of CITK based MCPH17, which may be relevant for development of therapeutic strategies.

Background Adult patients in oncological palliative care often do not readily express their concerns to physicians or nurses, leading to the oversight of needs that remain unexplored and require additional support. These needs that remain unaddressed are classified as unmet needs. Aim This study aimed to construct a conceptual framework of the unmet needs of cancer patients in palliative care settings. Method: Charmaz’s constructivist grounded theory approach was adopted. Semi-structured interviews were conducted with eligible patients until theoretical saturation was reached, as outlined by the methodology. The interviews were transcribed and analyzed through two coding cycles: line-by-line coding and focused coding, using NVIVO 14 software. Setting/participants A total of 29 patients were recruited from home palliative care, hospice, and outpatient settings at the Istituto Nazionale dei Tumori of Milan’s Palliative Care - Hospice, Pain Therapy, and Rehabilitation Complex Unit. Results This process led to the identification of five categories: Seeking Empowerment Through Daily Support, Need to Contain the Risk of Losing Dignity, Support in Managing the Progression of the Disease, Understanding and Openness to the Future, and Seeking Existential Support, along with a core category defined as the Need for Acknowledgment. The core category encompasses patients’ need to express their most intimate needs, emphasizing how crucial it is for them to be seen and understood not only as individuals facing illness but as people with unique, complex life stories. Conclusions The conceptual model developed enabled the identification of these hidden needs, providing a deeper understanding of the emotional and psychological dimensions that shape the experience of advanced illness.

Background Prostate cancer (PCa) is the second most common cancer affecting men globally, especially those aged 50 years and above. Despite substantial progress in terms of both prognosis and therapy, PCa remains a significant health concern, necessitating the identification of novel therapeutic targets. Innate lymphoid cells (ILCs) have emerged as critical modulators of tumor immunity, exhibiting both pro- and antitumoral effects. However, little is known yet about their contribution in PCa. This study investigated the phenotypic and functional profiles of ILC subsets in the peripheral blood mononuclear cells (PBMCs) of patients with PCa stratified by Gleason score. Methods PBMCs were isolated by Lymphoprep. ILC frequency and activity were evaluated by flow cytometry. The levels of ILC-activating cytokines were analyzed by multiplex assay in the serum of healthy donors (HDs) and patients with PCa. To evaluate the crosstalk between ILC2s and cancer cells, PC3 and DU145 human PCa cell lines were used. Results We found a stage-dependent increase in the protumoral ILC2 frequency and a concurrent decrease in antitumoral ILC1s in patients with PCa compared with healthy controls. Interestingly, the frequency of ILC2s was higher in patients with elevated prostate-specific antigen (PSA) values, suggesting their potential as molecular predictor for defining the risk category of patients with PCa at diagnosis. Importantly, patients with PCa exhibited hyperactivated ILC2s, characterized by elevated interleukin (IL)-13 and IL-5 production, while ILC1s displayed reduced tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion. Furthermore, serum levels of ILC2-activating cytokines IL-33, IL-18, and prostaglandin D2 (PGD2) were elevated in patients with PCa. In vitro co-culture experiments demonstrated that PCa cell lines, capable of secreting these cytokines, could directly enhance ILC2 activity. Likewise, ILC2-derived IL-13 promoted PCa cell migration and invasion. Conclusions Collectively, our findings highlight a dysregulated ILC profile in PCa, characterized by ILC2 dominance and heightened activity at the expense of ILC1s, suggesting both ILC1s and ILC2s as potential therapeutic targets for PCa treatment. Graphical Abstract

Background Tumor-Associated Macrophages (TAMs) are the main immune component of the tumor stroma with heterogeneous functional activities, predominantly suppressing the immune response and promoting tumor progression, also via secretion of different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated with disease progression in several tumor types. Malignant pleural mesothelioma (MPM) a severe neoplasia with poor prognosis, is characterized by an abundancy of TAMs, testifying the presence of a long-lasting inflammation which is pathogenetic of the disease. However, the role of GPNMB in MPM is unclear. Methods Clinical samples from patients with MPM were used to measure RNA and protein levels of GPNMB. The functional role of GPNMB in vivo was studied in an orthotopic mouse model of mesothelioma using the murine cell lines AB1 and AB22. Experiments included in vivo tumor growth in wild type and in GPNMB-deficient mice and blocking of GPNMB-induced signaling with anti-CD44 antibodies. Results We show that in human and murine MPM tissues the protein GPNMB is mainly produced by infiltrating TAMs. Gpnmb RNA levels in MPM patients from TCGA are significantly associated with lower survival. Using an orthotopic mouse model of mesothelioma we observed that in GPNMB-defective mice (DBA2/J mice) unable to produce the protein, tumors formed by AB1 and AB22 mesothelioma cells grow significantly less than in GPNMB-proficient mice (DBA2/J-Gpnmb+ mice), indicating that host GPNMB is involved in tumor progression. Likewise, the ectopic expression of GPNMB in AB1 and AB22 cells causes an acceleration of tumor growth in vivo, significantly different compared to mock-transduced cells. Treatment of tumor-bearing mice with blocking anti-CD44 (a major receptor for GPNMB) results in a significant reduction of tumor growth. Conclusions Overall, these results indicate that the protein GPNMB, a product and marker gene of TAMs, is a driver of mesothelioma progression and may constitute a promising therapeutic target.

Large earnings losses are likely to cause financial hardship, lower consumption, and trigger poverty and material deprivation. While the phenomenon has received significant attention in the US, it remains relatively under-researched in Europe. Our study aims to fill this gap. We examine the incidence and the distribution of earnings shocks, defined as year-on-year losses of at least 20% of gross individual earnings, in four South European countries (Greece, Italy, Spain, and Portugal) and in four comparator countries (France, Germany, the Netherlands, and Denmark), in 2006–2017, using longitudinal EU-SILC data. The paper proceeds to identifying the relative weight of economic conditions (proxied by GDP growth), and labour market characteristics (employment status, occupational class, and earnings quintile prior to the shock), and goes some way towards clarifying the nature of the effect of each explanatory variable on the incidence of earnings shocks in the eight countries, ceteris paribus. Our results confirm the hypothesis that the reason Southern Europe was more susceptible to earnings shocks during the Great Recession and the Euro crisis was the interplay of more unfavourable economic conditions with higher share of non-standard work (especially self-employment and fixed-term contracts), which left a higher share of the workforce exposed.