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European cancer mortality predictions for the year 2026: the levelling of female lung cancer mortality
No full textBackground: We provided updated cancer mortality estimates for 2026 in the European Union (EU) and its five most populous countries, with a focus on lung cancer. Materials and methods: Cancer death certifications and population data were obtained from the World Health Organization and United Nations databases. For the EU, France, Germany, Italy, Poland, Spain, and the UK, we derived data for all cancers combined and major cancer sites since 1970. Linear regression models, based on the most recent age-specific trends identified by Poisson joinpoint regression, were used to estimate deaths in 2026. The number of averted deaths between 1989 and 2026 was computed by applying the 1988 peak rate to subsequent populations. Results: For 2026, we estimated ∼1 230 000 EU cancer deaths, corresponding to age-standardised rates of 114.1/100 000 males (-7.8% versus 2020-2022) and 74.7/100 000 females (-5.9%). In the EU countries and the whole EU, favourable trends are predicted for most major cancers, except female pancreatic cancer. In the UK, predicted rates are also favourable, except female colorectal cancer. Lung cancer mortality continues to decrease markedly among males, while we predicted a levelling off of rates, around 12.5/100 000, among females in all considered countries and the whole of EU, except for Spain (+2.4%). Among females, lung cancer mortality declines are confined to those aged <65 years, while unfavourable trends continued in older age groups. Around 7.3 (5.0 in males, 2.3 in females) million total cancer deaths have been avoided in the EU since the peak observed in 1988. The corresponding figure for lung cancer is 1.8 million among males, while no averted deaths were recorded among females. Conclusion: Lung cancer mortality predictions for 2026 indicate a levelling off among EU females, with age- and country-specific differences. Mortality trends in ASRs for most cancers remain favourable in the EU and the UK, though the absolute number of cancer deaths is not declining due to population ageing
Emerging Trends and Possible Futures of the Telecommunication Networks in Italy
No full textThis chapter explores the possible futures for the telecommunication
ecosystem in Italy, by focusing on a medium- and long-term
perspective through the application of Strategic Foresight techniques.
Our goal is identifying the most promising new directions and policies
for driving the ecosystem evolution towards the preferable scenario, by
working on different dimensions: market/economic models, technical advancement,
regulatory frameworks, and users’ expectations/perspectives.
Regarding the first aspect, we analyze the emerging opportunities for
companies in terms of enabling technologies and digital services that can
be built on top of connectivity services, by also discussing the status
of the network infrastructures in Italy. Then, the chapter examines the
technical dimension, assessing the potential impact of technologies such
as low-orbit satellites and aerial networks, the edge expansion, new materials
and devices for reducing the carbon footprint of networks, artificial
intelligence and programmability of networks, as well as the development
of novel communication services based on immersive applications. Moreover,
the research also analyzes the regulatory landscape, assessing the
influence of policies on the evolution of telecommunication networks. It
evaluates existing regulations and recommends reforms to stimulate innovation
and greater industry participation. Finally, innovative requirements
on the user side are presented. All these aspects are then projectedinto four strategic scenarios, that have been developed by identifying key
forces that could impact development trajectories, categorizing them as
“predetermined” (i.e., with a clear trend) or “variables” (i.e., subject to
unpredictable outcomes). In particular, we considered the combinations
of high-impact extreme outcomes along the identified axes (namely, a
unified European role: yes/no; level of urbanization: high/low) in scenarios
entitled United States of Europe, City-States 2.0, Distributed States
of Europe, and Digital Feudalism, for imaging the impact on the future
telecommunication ecosystem
Mutant p53 affects the mitochondrial proteome, promoting mitochondrial fragmentation and OXPHOS in pancreatic ductal adenocarcinoma cells
No full textPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer marked by poor prognosis and frequent gain-of-function mutations in the TP53 tumor suppressor gene. Given the crucial role of mutant p53 in the context of metabolic reprogramming and aggressive tumor behavior, we explored its role on mitochondria, which may present a valuable therapeutic target. In this study, we characterized the unique mitochondrial proteome observed in PDAC cells harboring the gain-of-function TP53R273H mutation and discovered a strong mutant p53-dependent upregulation of myosin heavy chain 14 (MYH14), a nonmuscle myosin, implicated in mitochondrial dynamics. We deeply investigated the role of mutant p53 in the regulation of mitochondrial architecture and functionality in PDAC cells. Our morphological and morphometric analyses with transmission electron microscopy and three-dimensional confocal imaging revealed that mutant p53 induced marked mitochondrial fragmentation, whereas wild-type p53 stimulated mitochondrial elongation. Interestingly, the fragmented mitochondrial morphology is associated with higher mitochondrial respiration levels and more efficient mitochondrial cristae. These findings support the role of oncogenic mutant p53 isoforms in inducing mitochondrial fragmentation through a mechanism involving MYH14, resulting in an increased oxidative phosphorylation level that may support PDAC cell growth and aggressiveness
Uremic Toxin‐Driven Vascular Calcification in Chronic Kidney Disease: Molecular Pathways and Integrated Phenotypes
No full textBackground: Vascular calcification (VC) affects up to 90% of patients with end‐stage renal
disease and increases cardiovascular mortality 3‐ to 5‐fold. Once considered passive mineral
deposition, VC is now recognized as an active, toxin‐driven process orchestrating vascular
smooth muscle cell transdifferentiation, endothelial dysfunction, and matrix remodeling.
However, current uremic toxin classifications remain biochemically oriented, providing
limited clinical guidance for risk stratification and therapeutic selection. Methods: This
comprehensive review reframes uremic toxin‐driven VC through an integrated phenotypic
lens, synthesizing molecular mechanisms, clinical biomarkers, and therapeutic targets into a
unified translational framework. Results: We propose five mechanistic‐clinical phenotypes
representing distinct biological trajectories of vascular injury. These include (1) inflammatory‐
oxidative (dominated by indoxyl sulfate, p‐cresyl sulfate, NLRP3 inflammasome activation),
(2) mineral‐metabolic (hyperphosphatemia, FGF23 excess, Klotho deficiency), (3) epigenetic‐
senescent (histone modifications, microRNA dysregulation, cellular senescence), (4)
endocrine cross‐talk (vitamin D, PTH, gut‐derived metabolites), and (5) integrated toxic
continuum (convergence of multiple pathways in advanced disease). A comprehensive
biomarker panel spanning inflammatory markers, mineral metabolism parameters, epigenetic
indicators, and endocrine‐gut metabolites enables phenotypic stratification and therapeutic
monitoring. Emerging therapies—including tissue‐nonspecific alkaline phosphatase
inhibition, ectonucleotide pyrophosphatase/phosphodiesterase 1 enzyme replacement,
vitamin K2 activation, senolytic agents, and SNF472 crystal‐growth blockade—are mapped to
their optimal phenotypic contexts. Conclusions: This phenotype‐oriented paradigm
transforms VC from an inevitable complication into a targetable and potentially reversible
manifestation of uremic toxicity, establishing a translational foundation for precision‐based
vascular medicine in chronic kidney disease. The framework enables biomarker‐guided
patient stratification, rational therapeutic selection, and phenotype‐enriched clinical trial
design
Dealing with Decadence: (Re)flourishing the Giardino dei Semplici Under Targioni Tozzetti’s Administration
No full textIn 1545, Duke Cosimo I founded the Giardino dei Semplici, a botanical garden for the exclusive use of medical students at the University of Pisa. At the beginning of the eighteenth century, under the impetus of Cosimo III and Gian Gastone, the garden was opened to the public under the direction of Giovanni Targioni Tozzetti (1712-83), a physician and botanist who considered it a typical expression of Medici cultural policy, deserving of attention from the wide public. In this paper, I intend to reflect on the case study of the Giardino dei Semplici as a scientific and cultural institution of ancient origins that flourished in a moment traditionally viewed as one of crisis and decline for the grand duchy. In fact, not only did Targioni Tozzetti proposed to open this garden to the public, freeing it from its solely didactic value, but also wanted to rationalize its structure and botanical collections, with a view to representing power as a patron and protector of the sciences and arts. From this case study, it is possible to glimpse Gian Gastone's desire to continue the previous grand ducal tradition and innovate it according to the new cultural stimuli of the early eighteenth century
Grape-associated yeasts as promising antagonists against fungal pathogens
No full textBiocontrol, a practice for using living organisms to target plant pathogens, offers a promising, sustainable agricultural strategy. This study involves epiphytic yeasts isolated from Vitis vinifera ssp. sylvestris and ssp. vinifera as natural antagonists against Aspergillus carbonarius, Botrytis cinerea, and Penicillium expansum. Twenty-one of 37 yeasts were chosen based on the Pathology Intensity (PA) score during preliminary in vivo screening. Following identification, dual-culture assays, VOC production, copper tolerance, and commercial fungicide resistance were assessed. On YPD and GJ medium, Saccharomyces isolates were the strongest antagonists, whereas P. terricola UMY197 inhibited Penicillium and Aspergillus. H. uvarum UMY1473 was notably effective against B. cinerea. VOC analysis confirmed that S. cerevisiae UMY1430 was the most effective against Aspergillus, likely owing to its production of oxalic acid, while S. cerevisiae UMY1438 was a producer of various esters and phenylethyl alcohol. C. intermedia UMY189, M. pulcherrima UMY1472, H. uvarum UMY1473, and S. cerevisiae UMY1436 were the most copper-resistant. Yeast activity on chemical fungicide SWITCH (up to 1 g/L) depended on culture media usage; in fact, a higher viability on YPD than on GJ was observed, where only 4 yeasts were able to grow. Thus, since several yeasts exhibit promising inhibitory activity through various mechanisms and against different molds, the use of synthetic consortia could represent a powerful and essential tool in field trials to limit fungicide use while preventing the emergence of resistance
Adverse in-hospital outcomes in patients with paraplegia who undergo radical prostatectomy
No full textObjective: To test for the association between paraplegia and perioperative complications as well as in-hospital mortality after radical prostatectomy (RP) for non-metastatic prostate cancer. Patients and Methods: We identified patients who underwent RP (National Inpatient Sample [NIS] 2000–2019), stratified according to paraplegia status. The NIS is an inpatient database that rests on data contributed by ~20% of community hospitals within the United States. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models (LRMs) were used. Results: Of 260 302 patients who underwent RP, there were 223 (0.1%) with paraplegia. The patients with paraplegia who underwent RP were younger (age 60 vs 62 years; P = 0.002) and more frequently had Charlson Comorbidity Index ≥3 (46% vs 2.2%; P < 0.001). After 1:10 PSM, 223/223 (100%) patients with paraplegia and 2230/260 079 (0.9%) without paraplegia who underwent RP were included in further analyses. In multivariable LRMs, patients with paraplegia who underwent RP exhibited significantly higher in-hospital mortality (adjusted odds ratio [aOR] 10.7), higher rates of wound complications (aOR 8.2), infectious complications (aOR 6.2), genitourinary complications (aOR 3.5), intraoperative complications (aOR 2.8), cardiac complications (aOR 2.8), pulmonary complications (aOR 2.6), overall complications (aOR 2.4), blood transfusions (aOR 1.8), and longer length of stay ≥75th percentile (aOR 1.7) (all P ≤ 0.01). Conclusion: Although patients with paraplegia who undergo RP are rare, adverse in-hospital outcomes are substantially more frequent in these individuals. These observations should be carefully considered in clinical decision making and informed consent prior to RP, if such procedure is contemplated in patients with paraplegia
EVALUATION OF AN EDUCATIONAL PROGRAM OF DIET AND PHYSICAL ACTIVITY ON HEALTH AND QUALITY OF LIFE IN WOMEN DIAGNOSED WITH BREAST CANCER.
No full textBackground: Healthy diets and exercise are two modifiable lifestyle factors associated with more favourable breast cancer (BC) outcomes and cardiometabolic health. We tested a low glycemic index (GI) Mediterranean diet (MedDiet) and exercise, within vitamin D sufficiency, on BC recurrence, cardiometabolic risk factors and quality of life.
Methods: Women were contacted within 12 months of primary BC diagnosis (stages I-III) in 7 oncologic centres in Italy. Consenting participants were randomized to one of two lifestyle treatments lasting 33 months: 1) positive control (n=249), lower intensity advice on Mediterranean diet and avoidance of sedentary behavior; 2) test (n=243), higher intensity advice on low-GI MedDiet and 30-minute daily brisk walking. Oral vitamin D3 was administered to avoid insufficiency. Data were collected quarterly on health status, anthropometry, 7-day food records, daily steps and serum 25-OH-D. Intention-to-treat analysis was conducted for the main outcome (recurrence) comparing test to control. Hazard ratios (HR) and 95% confidence intervals (CI) were computed by Cox models. An observational analysis of the entire cohort was also performed testing the association between adherence to the higher intensity program and risk of disease recurrence. Differences in dietary and body weight parameters were tested at 1-year with Student’s t-test and ANCOVA where fit.
Results: In the test arm, after 1-year intervention, dietary GI decreased from 56.4±4.1 to 48.3±5.5 (low-GI<55), adherence to the MedDiet increased by 23%, dietary fiber by 40% to 19g/1000 kcal, physical activity increased from 5624±2730 to 7119±3349 daily steps and serum 25(OH)D increased from 26.9±13.5 to 50.8±12.7 ng/mL. These changes were significantly larger from controls (p<0.03). Weight loss at 1-year was significantly greater in the test arm by -3 kg or -4.2% (BMI from 27.5±5.7 to 26.3±5.4 kg/m2) compared to -1.7 kg or -2.4% (BMI from 27.2±5.1 to 26.6±5.1 kg/m2) in the control arm (p<0.0043). Weight loss was particularly greater in those who consumed higher nuts. Each 10g/d increment of total nuts was associated with an additional body weight loss of 0.36 kg (p<0.028). The anti-atherogenic serum HDL-cholesterol increased from 57.3±14.7 to 63.9±14.9 mg/dL in the test arm and from 58.0±15.2 to 62.4±15.2 mg/dL in controls. Waist circumference, triglycerides and blood pressure significantly decreased in both arms without differences among treatments. Presence of metabolic syndrome dropped by 66% in the test arm and 35% in controls (p=0.008). Improved health-related quality of life (global status) was observed at 1-year follow-up (p<0.001), particularly for parameters regarding physical, role and social functioning, fatigue, dyspnea and constipation. During the 33-month follow-up a total of 37 recurrences were observed by ITT analysis with no differences between arms (HR=0.94; 95%CI: 0.49-1.79). In the observational analysis, those who were more adherent to the higher intensity program showed a tendency of lower BC recurrence (HR=0.61; 95%CI: 0.27-1.40) which reached significance in hormone-positive BC (HR=0.24; 95%CI: 0.06-0.95).
Conclusions: Lifestyle counselling improved diet quality, physical activity and circulating vitamin D and resulted in weight loss, lower prevalence of the metabolic syndrome and improved quality of life. Higher adherence to a low-GI MedDiet together with moderate physical activity on a background of vitamin D sufficiency was associated with lower risk of BC recurrence which reached significance in hormone-positive BC (82% of the total sample). Considering that BC survivors face a high risk of chronic disease and mortality during the long-term adjuvant therapy, it appears reasonable to recommend a safe and low-cost lifestyle program inclusive of Mediterranean diet with low GI carbohydrates, physical activity and avoidance of hypovitaminosis D, to women newly diagnosed with BC
The Paradox of Endometriosis in Mayer-Rokitansky-Kuster-Hauser Syndrome: Applying Three Criteria to Discriminate Between Retrograde Menstruation/Implantation and Coelomic Metaplasia/Embryonic Cell Rests Theories
No full textBackground/Objectives: The scientific community is still divided between supporters of the implantation theory and researchers who advocate the theory of coelomic metaplasia/embryonic cell remnants to explain the initiation of endometriosis. A frequently cited argument in favor of the coelomic metaplasia/embryonic cell remnants theory is the occurrence of endometriosis in the Mayer-Rokitansky-Kuster-Hauser syndrome, since retrograde menstruation is not possible without endometrium. However, nearly all women with uterovaginal agenesis have uterine remnants that harbour islets of endometrium. Methods: To verify the validity of the coelomic metaplasia/embryonic cell rests theory, we analysed all reports of endometriosis in patients with Mayer-Rokitansky-Kuster-Hauser syndrome without endometrium, published between 1980 and 2025. Three criteria had to be met in order to clearly demonstrate the absence of endometrium and the presence of endometriosis: (i) preoperative imaging, (ii) surgical visualization, and (iii) histological examination. Results: None of the nine reports fully met all three criteria, and the presence of endometrium could never be ruled out. In addition, we used ten characteristics to assess the ‘goodness’ of a theory: testability, logical coherence, conceptual clarity and comprehensibility, external consistency, empirical validity, predictive power, parsimony, broad applicability, practical utility, and heuristic value. Conclusions: Overall, the implantation theory appears to fully satisfy all criteria to explain the onset of endometriosis in Mayer-Rokitansky-Kuster-Hauser syndrome. In contrast, the coelomic metaplasia/embryonic cell rests theory satisfies eight criteria only partly and does not satisfy two of them. Therefore, the null hypothesis that endometriosis can be present in the absence of endometrium in patients with utero-vaginal agenesis can be reasonably rejected
Immunomodulatory and Cytotoxic Properties of Enniatin B1 in Porcine Alveolar Macrophages
No full textThis study investigates the immunomodulatory effects of Enniatin B1 (ENNB1), an emerging mycotoxin, on porcine alveolar macrophages (PAMs), a species-specific model relevant to human innate immunity. PAMs were exposed to increasing ENNB1 concentrations (0.5–6 μM) over 6, 24, and 48 h. Results showed a biphasic response: ENNB1 initially enhanced cell viability and induced upregulation of pro-and anti-inflammatory cytokines (e.g., IL-1β, IL-6, IL-10, TNF-α), COX enzymes, and antioxidant gene GPX-2. However, prolonged exposure caused downregulation of these markers and reduced cell viability, indicating cytotoxic and immunosuppressive effects. The temporal and concentration-dependent responses suggest that ENNB1 modulates macrophage function by altering the immune response, with early immune activation followed by immune impairment. These findings provide novel insights into ENNB1’s potential to alter immune homeostasis and highlight the need for further toxicological studies for a correct evaluation of the risk