Journals
2026 EN
Mancini Silvia · Toffolutti Federica · Zamagni Federica
+23 more
ABSTRACT Background In Italy, cure indicators of cutaneous malignant melanoma according to Breslow tumour thickness have never been assessed. Objectives To evaluate the time trend in 1‐year net survival (NS), 5|1‐year conditional NS (CNS) and cure fraction (CF). Methods Data from 10 cancer registries and 13,377 patients aged 15–74 years were used. Five|1‐year CNS was defined as the probability of surviving 5 years given that the patient has survived 1 year. CF was defined as the proportion of patients with the same life expectancy as the general population. One‐year NS and 5|1‐year CNS were contrasted between 2013–2017 and 2003–2007, and CF between 2015 and 2005. Results For lesions up to 4 mm thick, 1‐year NS reached a level > 98.0%. In 2013–2017, 5|1‐year CNS was above 90% for men and women with lesions up to 2.0 mm thick and increased markedly for men with lesions > 2.0–4.0 mm thick (65.1% to 82.4%) and > 4.0 mm thick (57.6% to 69.4%). The CF of patients with a melanoma ≤ 1.0 mm thick was approximately 100% in both sexes, and nearly doubled from 2005 to 2015 (28% to 54%) for men aged 55–74 years with a melanoma > 4.0 mm thick. Conclusions Patients with a melanoma ≤ 1 mm thick have the same life expectancy as the general population. The increase in the CF of men with thick lesions supports the hypothesis that novel therapies, approved in Italy since 2013, offer the possibility of cure.
Journals
2026 EN
Giudici Fabiola · De Vidi Sara · Guzzinati Stefano
+17 more
ABSTRACT Background This study aims to estimate the long‐term risk of metastatic recurrence (MR) among Italian women with breast cancer (BC) by period, age, stage, and surrogate molecular profile. Methods Data on 59,968 women below age 75 years diagnosed in 1997–2017 with stage I‐III BC from 7 population‐based Italian cancer registries were analyzed. We used a novel modeling method, based on an illness–death process coupled with a mixture cure model, to estimate relative survival and MR risks up to 15 years after BC diagnosis according to calendar period, age, stage, and profile. Results The risk of MR for the entire cohort at 15 years decreased from 20.6% in 1997–2006 to 12.3% in 2007–2017, when MR risk within 15 years was 3.0% for stage I, 16.0% for stage II, and 42.7% for stage III. The conditional risk of MR decreased with time since diagnosis, with stage I–III triple‐negative BC having a higher risk of developing MR in the first 5 years regardless of age (16.0% at age 15–54 years and 18.3% at 55–74 years), but < 1% once they survived for 5 years without recurrence. In contrast, hormone receptor‐positive BC had a lower but persisting risk of MR of about 6% for both age groups in the first 10 years, halving to about 3% in the following 5 years after diagnosis. Conclusions This study provides a population‐based estimate of the long‐term risk of MR for women with BC by major prognostic factors. These findings may help in tailoring follow‐up strategies through informative risk stratification.
Journals
2026 EN
Bidoli Carlotta · Yang Wenjian · Karol Seth E.
+3 more
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Thiopurines such as 6‐mercaptopurine (6MP) are essential in ALL maintenance therapy. However, dose‐limiting toxicities can significantly disrupt treatment. While genetic variants in TPMT and NUDT15 are known to affect thiopurine response, many patients with normal function genotypes in these genes still experience adverse effects, suggesting that additional genes might be involved. We analyzed 663 pediatric ALL patients enrolled in the AALL03N1 trial to identify novel genetic determinants of 6MP sensitivity, focusing on individuals with normal function TPMT and NUDT15 genotypes. A transcriptome‐wide association study (TWAS) was conducted to focus on expression quantitative trait loci (eQTLs). Findings were validated in two independent cohorts: St. Jude Total Therapy XV ( n = 390) and XVI ( n = 552). TWAS identified 31 genes associated with 6MP dose intensity ( q ‐value < 0.90). Of these, the imputed GNAQ expression was positively correlated with 6MP dose intensity and passed multiple testing thresholds in the validation cohorts. The rs60561071 variant, the eQTL in the GNAQ TWAS model, was associated with reduced gene expression and lower 6MP dose intensity. This study identifies GNAQ as a novel gene associated with thiopurine tolerance in ALL patients lacking known risk alleles in TPMT and NUDT15 . Moreover, this research highlighted the innovative use of TWAS, providing deeper insights into the molecular mechanisms that explain drug response variability.
Journals
2026 EN
Antonella Lezo · Annalisa Mascheroni · Ersilia Troiano
+7 more
ABSTRACT Objective Hospitalised patients with eating disorders (EDs) often present with severe malnutrition, electrolyte imbalances, and metabolic complications that require specialised nutritional approaches. This consensus aimed to develop evidence‐informed, expert‐driven recommendations for the nutritional management of hospitalised patients with EDs, addressing risk stratification, caloric progression, refeeding protocols, formulation selection, supplementation and long‐term monitoring. Methods An eight‐expert panel conducted a modified Delphi process in two online rating rounds. One hundred six statements were formulated across 12 thematic sections and evaluated on a 5‐point Likert scale (≥ 85% accepted, 80%–84.9% revised, < 80% rejected). Revised statements were re‐evaluated in Round 2 and, if necessary, finalised at an online meeting. Results Of the 106 original statements, 89 (84.0%) reached immediate consensus, 14 (13.2%) required revision, and three (2.8%) were eliminated. Ten revised statements exceeded the ≥ 85% threshold in Round 2, one was rejected, and three ‘pending’ statements were approved in a conclusive online meeting. The final statements span key domains of inpatient care of EDs, including comprehensive nutritional assessment, stepwise refeeding regimens, careful electrolyte and biochemical monitoring, personalised approaches for those at high risk of refeeding syndrome and tailored considerations for paediatric and perinatal populations. Discussion The final consensus statements provide a structured framework for the nutritional rehabilitation of hospitalised patients with EDs, emphasising balanced yet flexible refeeding protocols, vigilant metabolic monitoring, ethical considerations in limited‐capacity cases, and continuity of care through discharge and relapse prevention. By aligning clinical practice with specialist insight and existing guidelines, these recommendations aim to standardise and enhance inpatient ED management.
Journals
2026 EN
Etrusco Andrea · Agrifoglio Vittorio · Chiantera Vito
+11 more
Abstract Background Hysteroscopy has evolved from a diagnostic to a diagnostic and operative tool, and currently represents the reference standard for both the diagnosis and treatment of intrauterine diseases. In this context, the hysteroscopic morcellator is increasingly gaining popularity because of its simplified approach. Objectives To evaluate the efficacy, safety, and feasibility of the hysteroscopic morcellator for the treatment of intrauterine pathologies. Search Strategy Electronic databases were searched for English‐language trials describing surgical procedures for uterine pathologies performed with the hysteroscopic morcellator until February 1, 2024. Selection Criteria Retrospective or prospective original studies reporting the treatment of uterine pathologies with the hysteroscopic morcellator were included. Data Collection and Analysis Data were collected on study features, characteristics of included populations, surgical procedures, complications, and results/outcomes. Main Results Thirty‐nine papers that met the inclusion criteria were included in this systematic review. A descriptive synthesis of the results was provided according to the pathology that was hysteroscopically removed/corrected: endometrial polyps, uterine leiomyomas, and retained products of conception. Conclusions The hysteroscopic morcellator offers effective and efficient removal of intrauterine lesions, with minimal risk of complications. Despite some limitations identified, such as potential bleeding and the need for additional surgical steps in certain cases, the overall findings support the utility of this technique in clinical practice.
Journals
2026 EN
Librici Calogero · Bambina Paola · Madonia Ettore
+4 more
ABSTRACT Biochar is a multifunctional soil amendment that improves soil structure, enhances water‐holding capacity, and contributes to carbon sequestration. However, the dose–response relationship between biochar addition and soil behavior remains underexplored, particularly at high application rates. In this study, fifteen soil–biochar mixtures were prepared with biochar mass fractions from 0 to 1 ( f BC = 0–1) to evaluate in detail the changes induced in a Sicilian clay soil. The mixtures were investigated for pH, electrical conductivity, bulk density, water‐holding capacity, and water activity (Aw). Biochar addition caused pronounced increases in alkalinity, porosity, and water retention, following nonlinear dose–response trends with clear thresholds beyond f BC ≈ 0.3–0.5. FT‐IR spectroscopy revealed the progressive appearance of oxygenated and aromatic functional groups, accompanied by a reduction in signals from adsorbed water and native soil polar groups. Fast Field‐Cycling NMR relaxometry provided molecular‐scale insight into soil–water interactions. At high biochar contents, water proton T 1 relaxation times were markedly lengthened, indicating a reduced overall efficiency of surface‐driven relaxation. Correlation‐time ( τ c ) analysis further revealed the emergence of water populations with longer correlation times and a redistribution of relaxation pathways toward outer‐sphere dominated mechanisms. Overall, the results indicate that biochar improves soil water retention not by strong surface adsorption but through effective pore‐space storage, keeping water available for biological use. The combined spectroscopic and relaxometric approach establishes a direct link between molecular‐level water dynamics and macroscopic soil properties, highlighting the value of FFC‐NMR as a powerful tool for studying natural porous systems.
Journals
2026 EN
Wehr Nina · Bartalucci Ettore · Smid Sabrina
+4 more
Abstract Spider silks are proteinaceous fiber materials inspiring material design in various technical and biomedical fields due to their exceptional toughness, which exceeds that of most natural and artificial fibers. Solid‐state nuclear magnetic resonance (NMR) spectroscopy has been used herein to obtain insights into the structure and dynamics of 13 C/ 15 N isotope‐labeled nanofibrils and microparticles made of the recombinantly produced, engineered spider silk protein eADF4(C16), for which structural information was still lacking. Although these two β‐sheet‐rich morphologies differ substantially in their microscopic appearance (nanofibrils vs. microparticles), the solid‐state NMR spectra reveal high structural and dynamic similarities at the atomic level. For both morphologies, it was found that the rigid alanine stretch in the eADF4 sequence forms a mixture of rectangular and staggered β‐sheets extending to the flanking serine residues. In addition, our data reveal that the tyrosine sidechains are rigidified, which suggests their engagement in π–π‐stacking interactions. All of the glutamic acid residues were found to be deprotonated, which implies their localization on the outside of the fibril, where their negative charge can be compensated. Trans ‐ as well as cis ‐conformations were observed for proline residues, which suggests that they might further control the formation and extension of the poly‐alanine β‐sheet region during the self‐assembly process. The gained understanding of structure, dynamics, and assembly of the engineered spider silk protein eADF4(C16) will enable the tailored design of functional spider silk‐based biomaterials in the future. It will be especially useful in context of chemical modifications and genetic fusions supporting the development of fibril‐based hydrogel systems in the field of biosensing and tissue engineering.
Journals
2026 EN
Caravita Sergio · Baratto Claudia · Dewachter Céline
+11 more
ABSTRACT Invasive exercise hemodynamics are used to diagnose heart failure with preserved ejection fraction (HFpEF), based on pulmonary artery wedge pressure (PAWP) or left atrial (LA) pressure elevations. We hypothesized that applying unsupervised cluster analysis to comprehensive hemodynamic characterization might provide data‐driven phenotypes, with pathophysiological and prognostic implications. Eighty consecutive HFpEF patients underwent right heart catheterization at rest, during passive leg raise, and at peak exercise. We performed unsupervised k ‐means clustering analysis, using eight hemodynamic variables that were not strongly correlated (Pearson correlation coefficient < 0.80). Hemodynamics and clinical characteristics, as well as event‐free survival, were assessed. k = 5 clusters were identified. Hemodynamic severity increased from Cluster 1 to Clusters 4–5 ( p < 0.01 for most of the hemodynamic variables), mirrored by different event‐free survival (log‐rank test p < 0.001). Clusters 1 and 2 presented with either steep PAWP rise or LA hypertension and pulmonary hypertension (PH) only during exercise. Cluster 3 presented with LA hypertension and PH already at rest, as well as with tall PAWP V waves during exercise. Cluster 4 presented with post‐ and precapillary PH, tall PAWP V waves, right atrial (RA) hypertension, dynamic tricuspid regurgitation (TR), and low cardiac output (CO) reserve. Cluster 5 presented with TR and RA hypertension, low CO, and a lack of decrease in PVR. Data‐driven unsupervised cluster analysis of advanced invasive hemodynamics allowed for the identification of distinct HFpEF phenotypes across the spectrum of disease severity. We found a progressive involvement of the pulmonary circulation and of the right heart, coupled with a worse prognosis.
Journals
2026 EN
Gallo Ettore
Recent empirical research has highlighted the role played by public investment in stimulating economic activity, while addressing a variety of systemic challenges such as climate change and supply chain resilience. However, theoretical considerations regarding the capacity-building effect of public capital formation have been often overlooked in the demand-led growth literature. The paper addresses this gap by introducing a public investment component within a supermultiplier model, treating government investment and consumption spending as two separate components of autonomous demand, growing at different rates over the long run. The model is proven to be stable as long as the non-capacity-creating component of demand grows faster than public investment. Even though the latter does not have long-term growth effects in the steady state, it does affect economic activity during the traverse. The model is then calibrated and simulated, showing that movements between steady-state positions are extremely long-lasting, thus reinforcing the idea that supermultiplier models are better suited to describe out-of-equilibrium dynamics, while pointing out the potential role of public investment in shaping macroeconomic outcomes in the short, medium, and long run.
Resource
2026 EN
Ettore Zauli · Giacomo Vella · Luca Gastaldi
As firms increasingly rely on business ecosystems for value creation across organizational boundaries, understanding how diverse actors coordinate while preserving autonomy remains a central challenge. Despite the growing adoption of blockchain technology and tokenization as coordination solutions, their impact on ecosystem modularity – a foundational architectural principle governing how components interact – remains largely unexplored. This study investigates how blockchain tokens enhance modularity in business ecosystems. Through an abductive, multiple case study analysis of twelve token implementations across diverse industries, we examine how focal actors leverage tokens as coordination mechanisms functioning as standardized interfaces. Our findings reveal three key token-enabled interactions (information exchange, ownership transfers and ownership verification) through which tokens reshape ecosystem coordination. Across these interactions, two critical dimensions – accessibility and reliability – emerge as modularity enhancers that complement established standardization approaches. The study contributes to modularity theory by extending design rules for digital contexts beyond structural considerations, providing a more nuanced explanation of how business ecosystems position along the modularity continuum, and introducing digital ownership as a boundary-spanning mechanism distinct from traditional information-centric interfaces. For engineering managers, our research offers actionable guidance on strategically designing token-based interfaces to reduce transaction costs, enable permissionless innovation, and facilitate complementor integration into business ecosystems.