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Presence of Danube barbel Barbus balcanicus was investigated at the westernmost portion of its distribution area (Italian portion of the Isonzo River Basin). Genetic analyses carried out on specimens collected in different watercourses confirmed B. balcanicus presence in the same locations where Barbus caninus was erroneously classified in the past. More precisely, 4 Cyt b haplotypes belonging to the Balkanic species were described, three of which were evidenced for the first time. Analysis of meristic characters also confirmed genetic results and completed the taxonomical assessment. At the same time, a target population was studied to deepen knowledge about the species ecology. In this case, 120 specimens belonging to five age classes (from 0+ to 4+) were collected with monthly frequency in Barbucina Creek, representing the model watercourse inhabited by the species in the study area. Regression between total weight (W) and standard length (SL) did not differ significantly between males and females, therefore not displaying sexual dimorphism. SL values showed wide ranges, often overlapping among age classes. Mean condition factor (Kmean) decreased significantly with growth and age, as small individuals were in better nutritional condition. From an ecological point of view, biometric parameters seemed to be affected by habitat conditions and, specifically, to the limited space of the creeks, rather than by trophic conditions. Finally, trends of gonadosomatic index (GSI) showed that B. balcanicus reproductive period stretches between April and late May/early June. Results indicated that sexual maturity is reached at 1+ age, corresponding to a mean standard length equal to 5.50 ± 0.66 for female and 5.71 ± 0.53 for male breeders. In conclusion, experimental results highlighted the presence and adaptability of this “forgotten” species of the Italian fish fauna, which certainly will deserve attention in a future amendment of the Italian IUCN Red List of vertebrates.

Abstract Objective Lennox–Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult‐to‐control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long‐term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long‐term functional and adaptive behavior in adult patients with LGS. Methods This cross‐sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS‐II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS‐II scores. Results The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS‐II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS‐II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. Significance This study provides relevant insights into the long‐term challenges faced by adults with Lennox–Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. Plain Language Summary This study examined adults with Lennox–Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long‐term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Background: Low-dose computed tomography-based lung cancer screening (LCS) has demonstrated efficacy in reducing lung cancer mortality. However, concerns about overdiagnosis and overtreatment hinder global LCS implementation. Methods: Here, we report the unique case of a slow-growing 1 cm pure ground-glass opacity (GGO) of the lung, known for 15 years, which unexpectedly developed into a 5 cm mixed GGO within 1 year, with an increased solid component and FDG-PET uptake. Results: The patient, asymptomatic, underwent right upper lobectomy and lymphadenectomy, even complicated with postoperative chylothorax, later revealing to be affected by only an unchanged adenocarcinoma in situ (AIS). Conclusions: This case serves as a reminder of the potential behavior of pre-invasive lesions, which can mimic invasive neoplasia and may lead to overtreatment, and underscores the challenge of distinguishing indolent lesions from potentially aggressive malignancies in LCS, highlighting the need for the ongoing refinement of LCS protocols to mitigate this risk.

Abstract Background Cardiovascular diseases (CVD) affect over half a billion people worldwide and are the leading cause of global deaths. In particular, due to population aging and worldwide spreading of risk factors, the prevalence of heart failure (HF) is also increasing. HF accounts for approximately 36% of all CVD-related deaths and stands as the foremost cause of hospitalization. Patients affected by CVD or HF experience a substantial decrease in health-related quality of life compared to healthy subjects or affected by other diffused chronic diseases. Main body For both CVD and HF, prediction models have been developed, which utilize patient data, routine laboratory and further diagnostic tests. While some of these scores are currently used in clinical practice, there still is a need for innovative approaches to optimize CVD and HF prediction and to reduce the impact of these conditions on the global population. Epigenetic biomarkers, particularly DNA methylation (DNAm) changes, offer valuable insight for predicting risk, disease diagnosis and prognosis, and for monitoring treatment. The present work reviews current information relating DNAm, CVD and HF and discusses the use of DNAm in improving clinical risk prediction of CVD and HF as well as that of DNAm age as a proxy for cardiac aging. Conclusion DNAm biomarkers offer a valuable contribution to improving the accuracy of CV risk models. Many CpG sites have been adopted to develop specific prediction scores for CVD and HF with similar or enhanced performance on the top of existing risk measures. In the near future, integrating data from DNA methylome and other sources and advancements in new machine learning algorithms will help develop more precise and personalized risk prediction methods for CVD and HF.

Zinc deficiency is a significant global health concern among children, manifesting in various acquired and inherited conditions. This comprehensive overview of acquired and inherited zinc deficiency-related diseases in children aimed to explore the clinical presentations, diagnostic challenges, and management strategies associated with these conditions. This case series elucidates the diverse clinical manifestations of zinc deficiency in pediatric patients, ranging from dermatitis and growth retardation to immune dysregulation and neurological abnormalities, and discusses the underlying genetic mechanisms, clinical phenotypes, and therapeutic interventions. The complexity of zinc deficiency-related diseases in children underscores the need for a multidisciplinary approach involving pediatricians, dermatologists, geneticists, and nutritionists to optimize patient care and outcomes.

Abstract Parthenogenesis, or virgin birth, describes a mode of reproduction where an egg develops into an offspring without fertilization, and is observed across various vertebrate taxa, excluding mammals. Obligate parthenogenesis, found in around 100 vertebrate species and 1000 invertebrate species, is relatively rare. Conversely, facultative parthenogenesis, where females can reproduce both sexually and parthenogenetically, is observed in some vertebrates, including elasmobranchs. Notably, this phenomenon in elasmobranchs is mainly documented in captivity, allowing for detailed long-term observation. Specifically, this study reports the first case of facultative parthenogenesis in the common smooth-hound shark Mustelus mustelus, a species classified by IUCN as endangered. Here we show that the juvenile M. mustelus were born through parthenogenesis, exhibiting homozygosity at each genetic marker, consistent with terminal fusion automixis. Remarkably, this finding reveals that parthenogenesis can occur annually in these sharks, alternating between two females, and conclusively excludes long-term sperm storage as a cause. Consequently, this enhances our understanding of parthenogenesis in elasmobranchs and highlights the reproductive flexibility of M. mustelus. Overall, these results contribute to our broader understanding of reproductive strategies in elasmobranchs, which could inform conservation efforts for endangered species.

Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Societal Impact Statement Forest trees tend to be strongly genetically adapted to their local environments, but climate change will probably subject trees to novel combinations of precipitation, temperature, and photoperiod. Local adaptation was investigated in the ecologically and economically important Patagonian tree species Nothofagus pumilio by characterizing its genetic diversity in relation to the varied environmental conditions across its range. These insights are useful for conservation and management decisions, for example by identifying suitable populations to establish seed source plantations for restoration and characterizing relationships with environmental drivers of selection to better understand how this species will respond to climate change. Summary Nothofagus pumilio is a foundation tree species that inhabits a 2000‐km‐long range in the southern Andes, a region with two perpendicular environmental gradients: temperature and photoperiod (North–South), and precipitation (West–East). We investigated local adaptation patterns by searching for relationships between environmental clines and signatures of adaptation in candidate genes related to stress response, growth, and phenology. Using a paired site sampling design within a landscape genome analysis, we analyzed 493 adult N. pumilio trees in 20 sampling sites across the species' latitudinal range. We screened 47,336 single nucleotide polymorphism (SNP) loci in 1632 contigs (i.e., coding regions along the genome). Population structure and genetic diversity analyses preceded four genome scan analyses using genetic and environmental data. Population structure and genetic diversity are mainly oriented along the latitude axis. Genome scans identified 445 outlier SNPs, which are loci showing signatures of selection. Temperature and photoperiod variables were associated with notably more outliers than precipitation. However, the most frequent biological functions among genes were water deprivation response and cold response, suggesting that stress response is comprised of complex and polygenic traits that are affected by many environmental variables. Our findings suggest that N. pumilio shows signatures of local adaptation to extant climate conditions, including temperature, photoperiod, and precipitation. However, climate change is likely to alter existing relationships among environmental conditions to which this species is currently adapted. These changes may have unpredictable consequences for the species' future survival, adaptation potential, and the people who depend upon these forests.

Abstract Background Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. Methods Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. Results The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. Conclusions Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

IntroductionCystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del is the most frequent mutation (70% of alleles in Italy), while other mutations have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% in Italy) emerges as a mutation characterized by a severe CFTR folding and trafficking defect.MethodsTo investigate the pharmacological responsiveness of the G85E-CFTR variant, we performed a functional and biochemical characterization in heterologous expression systems and ex vivo models based on patient-derived human nasal epithelial cells (HNEC).ResultsOur study demonstrated that treatment of primary airway cells with elexacaftor and tezacaftor causes a significant (although modest) rescue of CFTR function, that reaches 15%–25% of the activity measured in non-CF epithelia. A detrimental effect of chronic treatment with ivacaftor, further limiting G85E rescue, was also observed. A higher rescue of CFTR function, up to 25%–35% of the normal CFTR activity, with no evidence of negative effects upon chronic potentiator treatment, can be achieved by combining elexacaftor with ARN23765, a novel type 1 corrector endowed with very high potency. Importantly, dose-response relationships suggest that G85E might alter the binding of type 1 correctors, possibly affecting their affinity for the target.DiscussionIn conclusion, our studies suggest that novel combinations of modulators, endowed with higher efficacy leading to increased rescue of G85E-CFTR, are needed to improve the clinical benefit in patients for this variant.

Summary: Background: The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings. Methods: The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453. Findings: With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+ compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4–4.32) and CT+ (RR: 2.6; 95% CI: 1.81–3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC− and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years’ follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0–6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7–24.5) for lung cancer mortality. Interpretation: Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy. Funding: Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

Abstract The global decline in insect biomass has far‐reaching implications for terrestrial and freshwater food webs, impacting species reliant on insects as a crucial component of their diet. This issue extends to species traditionally considered agricultural pests, such as the common cockchafer Melolontha melolontha. In the race to combat cockchafers through collection, insecticide use, and other control methods, the repercussions of their numerical fluctuations on predators, including species of high conservation importance like bats, have been largely overlooked. Drawing on 31‐years of monitoring data for a greater horseshoe bat Rhinolophus ferrumequinum population in the Aosta Valley (Western Italian Alps), we investigated whether annual fluctuations in bat counts are influenced by cockchafer availability and weather conditions. Despite an overall positive trend in bat abundance, we observed pronounced annual fluctuations, mostly driven by cockchafer availability rather than variations in temperature and precipitation. Furthermore, we found a significant association between cockchafer availability and the median date of birth and birth rate of bats. Births occurred approximately 5 days earlier in cockchafer flight years, with earlier births also linked to warmer spring temperatures and higher numbers of warm days in April. Moreover, the ratio pups/older bats was 0.56 in cockchafer flight years, compared to 0.47 in other years. Our results underscore the importance of considering predator–prey dynamics when examining the long‐term population trends of species of conservation concern. We recommend implementing restrictions on the use of chemicals and other potentially harmful practices that may diminish prey abundance or quality, including that of species considered as agricultural pests. In designing conservation strategies, a delicate balance should be struck between the current interests of farmers and the overarching goal of preserving biodiversity against potential future threats.

Background: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methods: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. Results: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p

Background: Patients with metastatic colorectal cancer (mCRC) carrying a deficit in the mismatch repair system/microsatellite instability (dMMR/MSI) show great responses to immune checkpoint inhibitors. However, 30% of patients with dMMR/MSI are primarily immunoresistant, and another 30% develop secondary resistance. Thus several combinations such as anti-programmed cell death protein 1 (anti-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) are being pursued. The combination of radiotherapy and immunotherapy is another avenue of research that can increase the release of neoantigens resulting in the abscopal effect. This phenomenon has demonstrated promising potential activity in colon cancer preclinical studies; nevertheless, clinical results are limited to just a few case series. Patients and methods: We conducted a prospective interventional single-institution study to assess the feasibility, safety, and disease control rate of the combination of pembrolizumab and stereotactic ablative radiotherapy (SABR) in a cohort of 14 consecutive patients with dMMR/MSI mCRC. Results: Among the 14 patients enrolled, 11 received SABR in combination with pembrolizumab as the first to the fourth line. The disease control rate was 50% in the intention-to-treat population, with six patients still maintaining the response after >15 months. Any-grade treatment-related adverse events occurred in 50% of patients, with grade 3 (G3) events in three patients; no treatment-related death occurred. Conclusions: Our findings convey no signal of enhanced systemic efficacy compared with historical data on pembrolizumab alone even if the local control rate is high. To our knowledge, this represents the largest study conducted in this population; further studies could extend the knowledge on the toxicity profile of this combination.

Micro(nano)plastics (MNPs) are pervasive pollutants posing significant environmental and health risks. Selecting appropriate sentinel species to assess MNPs in terrestrial and aquatic environments involves considering factors such as species behavior, habitat, exposure pathways, and the feasibility of sampling. For these reasons, it was imperative to launch a virtual special issue (VSI) in Ecological Indicators. This editorial summarizes the contributions submitted to the VSI, which invited research on bioindicators of MNPs, including sampling protocols, monitoring strategies, and analytical methods, to advance our understanding and management of plastic pollution. The VSI received a total of 12 contributions from four countries, with a significant majority originating from Italy. To present the contributions, we have organized the sections into original articles and reviews. The original articles are further divided into sections on the occurrence of MNPs in biotic and abiotic compartments, the selection of bioindicators, and the effects and risk assessment of MPs. The reviews are categorized based on their focus on aquatic and terrestrial ecosystems. Future ecotoxicology studies should select bioindicators based on exposure to MNPs, conservation status, ecological roles, and human consumption.

Abstract Background Glioblastoma (GBM) presents as an aggressive brain cancer, notorious for its recurrence and resistance to conventional treatments. This study aimed to assess the efficacy of the EMulate Therapeutics Voyager®, a non-invasive, non-thermal, non-ionizing, battery-operated, portable experimental medical device, in treating GBM. Using ultra-low radiofrequency energy (ulRFE) to modulate intracellular activity, previous preliminary results in patients have been encouraging. Now, with a focus on murine models, our investigation seeks to elucidate the device's mechanistic impacts, further optimizing its therapeutic potential and understanding its limitations. Methods The device employs a silicone over molded coil to deliver oscillating magnetic fields, which are believed to interact with and disrupt cellular targets. These fields are derived from the magnetic fluctuations of solvated molecules. Xenograft and syngeneic murine models were chosen for the study. Mice were injected with U-87 MG or GL261 glioma cells in their flanks and were subsequently treated with one of two ulRFE cognates: A1A, inspired by paclitaxel, or A2, based on murine siRNA targeting CTLA4 + PD1. A separate group of untreated mice was maintained as controls. Results Mice that underwent treatments with either A1A or A2 exhibited significantly reduced tumor sizes when compared to the untreated cohort. Conclusion The EMulate Therapeutics Voyager® demonstrates promising potential in inhibiting glioma cells in vivo through its unique ulRFE technology and should be further studied in terms of biological effects in vitro and in vivo.

BackgroundAlthough physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC.MethodsSix case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates.ResultsThe meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]).ConclusionsNo association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Background The management of subsolid nodules (SSNs) in lung cancer screening (LCS) is still a topic of debate, with no current uniform strategy to deal with these lesions at risk of overdiagnosis and overtreatment. The BioMILD LCS trial has implemented a prospective conservative approach for SSNs, managing with annual low-dose computed tomography nonsolid nodules (NSNs) and part-solid nodules (PSNs) with a solid component

Multifunctional productive systems based on native species management, a new paradigm that counters colonial worldviews, offer sustainable sources of food and materials while preserving biodiversity. Despite extensive discussions in herbaceous and agricultural systems, applying this concept to native forests in Northern Patagonia remains unclear. Multifunctional system implementation can be approached from a fractal perspective, with evaluations at the stand level being essential for understanding ecological processes across scales. Here, we exemplify research and management for multiple native species, integrating results from 10 years of field experiments on the impacts of biomass harvesting intensity (HI) on nine Nature's Contributions to People (NCPs), including habitat creation, pollination, soil formation, hazard regulation, prevention of invasions, and provision of energy, food, materials, and options. Our findings reveal that some regulating NCPs peak with null HI, while certain material and regulating NCPs maximize at the highest HI. Low to intermediate HI (30–50%) show a more balanced provision of all NCPs. Our results suggest that some biomass extraction is necessary to enhance most NCPs, emphasizing the importance of balancing material provisioning and biodiversity conservation in management schemes. We propose future directions for designing multifunctional forest systems, advocating for low-density plantation of native tree species with high wood quality within the natural forest matrix. This approach may yield higher NCPs levels over time compared to the current cattle breeding and wood extraction system, with implications beyond Patagonia, considering historical associations of such practices with colonial worldviews globally.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts’ societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU’s research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.

The effect of plasticizers, namely glycerol, sorbitol, and citric acid, on the structural and mechanical properties of biodegradable films obtained from xanthan gum (XG) and starch was studied. The plasticizing effect of glycerol, sorbitol, and citric acid on XG-starch films is justified by the destruction of intermolecular contacts between starch and XG macromolecules and the redistribution of hydrogen bonds in the system as a result of the hydrotropic action of plasticizer molecules. The use of glycerol proved to be the most effective for regulating the deformation of films, while the use of sorbitol to preserve strength. The dependence of the film roughness on the type and concentration of plasticizers was characterized. The smallest values of protrusions on the surface of XG-starch films were found in the presence of sorbitol. Considering the effect of the concentration of plasticizers on the stickiness of the surface of XG-starch films and their structural and mechanical properties, 1.5 % concentration of glycerol, sorbitol and citric acid was determined as optimal.

Desde el Grupo de Estudios Sociales y Culturales sobre Deporte (ISEF, UDELAR), hemos venido experimentando sobre la etnografía, como método, enfoque y como texto (Guber, 2001), para mirar y pensar las prácticas deportivas en el Uruguay. Esto ha significado consolidar una perspectiva teórico-metodológica para abordar al fenómeno deportivo, y un posicionamiento particular a la hora de vincularnos con el campo como investigadores/as. Sin embargo, este proceso ha implicado el reconocimiento de una serie de conflictos y dilemas a la hora de tomar decisiones metodológicas, y a la hora de relatar nuestras estadías en el campo. En esta ocasión, nos hemos propuesto analizar el vínculo entre el método etnográfico y las prácticas deportivas, y lo haremos a partir de la experiencia de tres investigaciones individuales: una etnografía en un gimnasio de deportes de combate en Montevideo (Mora, 2018), una etnografía de gimnasia artística (Pastorino, 2023) en Maldonado, y una etnografía en un club de la ciudad de San Carlos en la que se encuentran el fútbol y la murga como prácticas asociadas (Alsina, 2023). No nos importará tanto para este caso describir cada una de las prácticas, sino mostrarlas como ejemplos de la potencialidad del método etnográfico para estudiar las prácticas corporales, y también para reflexionar sobre los lugares de quienes investigamos, las estrategias de posicionamiento en relación al campo estudiado (las distancias y cercanías óptimas y posibles) y los vínculos teóricos que surgen de este proceso.

BackgroundThe primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels.Methods68 pediatric patients aged 6–18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF).ResultsThe group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only.ConclusionDepressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management.

BackgroundCardiovascular diseases (CVDs) pose a significant global health challenge, necessitating innovative approaches for primary prevention. Personalized prevention, based on genetic risk scores (PRS) and digital technologies, holds promise in revolutionizing CVD preventive strategies. However, the clinical efficacy of these interventions requires further investigation. This study presents the protocol of the INNOPREV randomized controlled trial, aiming to evaluate the clinical efficacy of PRS and digital technologies in personalized cardiovascular disease prevention.MethodsThe INNOPREV trial is a four-arm RCT conducted in Italy. A total of 1,020 participants, aged 40–69 with high 10-year CVD risk based on SCORE 2 charts, will be randomly assigned to traditional CVD risk assessment, genetic testing (CVD PRS), digital intervention (app and smart band), or a combination of genetic testing and digital intervention. The primary objective is to evaluate the efficacy of providing CVD PRS information, measured at baseline, either alone or in combination with the use of an app and a smart band, on two endpoints: changes in lifestyle patterns, and modification in CVD risk profiles. Participants will undergo a comprehensive assessment and cardiovascular evaluation at baseline, with follow-up visits at one, five, and 12 months. Lifestyle changes and CVD risk profiles will be assessed at different time points beyond the initial assessment, using the Life's Essential 8 and SCORE 2, respectively. Blood samples will be collected at baseline and at study completion to evaluate changes in lipid profiles. The analysis will employ adjusted mixed-effect models for repeated measures to assess significant differences in the data collected over time. Additionally, potential moderators and mediators will be examined to understand the underlying mechanisms of behavior change.DiscussionAs the largest trial in this context, the INNOPREV trial will contribute to the advancement of personalized cardiovascular disease prevention, with the potential to positively impact public health and reduce the burden of CVDs on healthcare systems. By systematically examining the clinical efficacy of PRS and digital interventions, this trial aims to provide valuable evidence to guide future preventive strategies and enhance population health outcomes.

For handling safely infectious agents, European laboratories must comply with specific EC Directives, national regulations and recommendations from the World Health Organization (WHO). To prevent laboratory acquired infections (LAIs) and pathogens dissemination, a key biosafety rule requires that any infectious material (clinical specimens or research samples) manipulated outside a biosafety cabinet (BSC) must be inactivated unless the lack of infectivity is proven. This inactivation process is a crucial step for biosafety and must be guided by a rigorous experimental qualification and validation procedure. However, for diagnostic or research laboratories, this process is not harmonized with common standard operation procedures (SOPs) but based on individual risk assessment and general international guidelines which can pose problems in emergency situations such as major outbreaks or pandemics. This review focuses on viral inactivation method, outlining the current regulatory framework, its limitations and a number of ways in which biosafety can be improved.

Invasive species threaten native biodiversity, potentially leading to a decline in endemic aquatic species. Thus, understanding their physiological responses and evaluating ecosystem impacts is crucial. The study investigates adaptive responses to oxidative stress in the invasive Sinanodonta woodiana in Lake Candia (northwest Italy). This approach represents a novel perspective in environmental monitoring, utilizing invasive species to gain insights into ecosystem health and potential ecological threats. The investigation delved into oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione S-transferase, glyoxalase I, glyoxalase II, and lactate dehydrogenase, in mussel tissues (gills and digestive gland). Concurrently, environmental factors such as temperature, dissolved oxygen, pH, and conductivity were measured at four stations in Lake Candia during the summer. Environmental factors exhibited homogeneity across selected stations, with positive correlations observed only for temperature and conductivity with catalase and glyoxalase I. A distinct pattern of oxidative stress response was consistently observed in both mussel tissues throughout the sampling period across all monitoring stations, with more pronounced alterations observed in one specific station. This observation aligns with IBRv2 scores, indicating the station's highest impact. Gills exhibited a transient and severe oxidative stress response, while heightened antioxidant defenses in digestive glands suggested the adaptive ability of Chinese pond mussels to environmental disturbances. Proactive inclusion of invasive species in biomonitoring programs reduces reliance on native populations, enhancing strategies for controlling non-native mussels in protected areas like Lake Candia.

Conservation genetic research is essential for the management and recovery of endangered taxa. However, the invasive collection of biological material for DNA analysis is controversial. From an ethical perspective, non-destructive sampling methods leave the aquatic specimen alive and less invasive procedures minimize stress on the animals. DNA can be obtained from fish using minimally invasive techniques such as buccal swabs. Here we evaluated the performance of buccal swabs for long-term storage of DNA obtained from brown trout (Salmo trutta). The buccal swabs were stored at room temperature and cut into pieces, one part of which was used for extraction of an aliquot and the others were stored as a “biobank” of biological material. The elapsed time from sampling to molecular analysis was one and half year. The amplification of three different DNA targets was tested to assess the effectiveness of the extraction: mitochondrial DNA (the D-LOOP region), nuclear DNA (the LDH gene) and microsatellite DNA at multiple loci. The results showed high quantification (mean value: 281.84±72.4 ng/µL), indicating that DNA could be effectively extracted from the buccal swabs. Our study results suggest that buccal swabs for long-term storage of DNA at room temperature are promising for use in field conservation studies.

Abstract Background Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent. Methods Within the PeRsonalizEd Medicine (PREME) program, patient-derived NB tumors and bone marrow (BM)-infiltrating NB cells, derived from either iliac crests or tumor bone lesions, underwent to histological and to flow cytometry immunophenotyping, respectively. BM samples containing a NB cells infiltration from 1 to 50 percent, underwent to a subsequent NB cells enrichment using immune-magnetic manipulation. Then, NB samples were used for the identification of actionable targets and for the generation of 3D/tumor-spheres and Patient-Derived Xenografts (PDX) and Cell PDX (CPDX) preclinical models. Results Eighty-four percent of NB-patients showed potentially therapeutically targetable somatic alterations (including point mutations, copy number variations and mRNA over-expression). Sixty-six percent of samples showed alterations, graded as “very high priority”, that are validated to be directly targetable by an approved drug or an investigational agent. A molecular targeted therapy was applied for four patients, while a genetic counseling was suggested to two patients having one pathogenic germline variant in known cancer predisposition genes. Out of eleven samples implanted in mice, five gave rise to (C)PDX, all preserved in a local PDX Bio-bank. Interestingly, comparing all molecular alterations and histological and immunophenotypic features among the original patient’s tumors and PDX/CPDX up to second generation, a high grade of similarity was observed. Notably, also 3D models conserved immunophenotypic features and molecular alterations of the original tumors. Conclusions PREME confirms the possibility of identifying targetable genomic alterations in NB, indeed, a molecular targeted therapy was applied to four NB patients. PREME paves the way to the creation of clinically relevant repositories of faithful patient-derived (C)PDX and 3D models, on which testing precision, NB standard-of-care and experimental medicines.

Within the framework of the recent agri-food technological advancement, the design and validation of a methodology for the water content estimation in the Carasau bread manufacturing process is herein presented. Following a thorough evaluation of the dough dielectric properties, a suitable antenna layout has been selected, pointing out the advantages in the choice of a contactless narrow-band antenna in comparison to wide-band and dual-band ones. The presented simulated results are then validated using a prototype sensor and an ad hoc measurement system to confirm the antenna ability to discriminate among doughs with different water content. In addition, an accurate analysis of possible sources of misinterpretation of the results is presented.

Oysters are sessile, filter-feeding bivalve molluscs widely distributed in estuarine and coastal habitats worldwide. They constitute a valuable resource for fisheries and extensive aquaculture and provide essential ecological services. Yet, their genetic diversity and distribution remain understudied. The variability in shell morphology complicates species classification, which is influenced by environmental and genetic factors. Although molecular phylogenetics research has refined oyster taxonomy and identified approximately 100 extant species, numerous taxonomic uncertainties persist. In the present study, we aimed to document the occurrence of small flat oysters of the genus Ostrea along the Mediterranean coastal areas of Liguria and Sardinia (Italy). Specifically, 16S rRNA sequence data were used to identify Ostrea species. Our findings offer novel insights into the O. stentina species complex and O. neostentina, a new species in the Mediterranean coastal areas of Italy. The study data further our understanding of Ostrea species diversity, distribution, and evolutionary patterns.

BACKGROUND: Little is known about risks associated with germline SUFU pathogenic variants (PVs) known as a cancer predisposition syndrome. METHODS: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germline SUFU PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with SUFU PV (89 patients) using the Nelson-Aalen estimator. RESULTS: Overall, 117/172 (68%) SUFU PV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4% (95% CI 6.8 to 21.4), 18.2% (95% CI 9.7 to 25.9) and 44.1% (95% CI 29.7 to 55.5) at the age of 5, 20 and 50 years, respectively. The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. Sixty-four different PVs were reported across the entire SUFU gene and inherited in 73% of cases in which inheritance could be evaluated. CONCLUSION: Germline SUFU PV carriers have a life-long increased risk of tumours with a spectrum dominated by MB before the age of 5, gonadal tumours during adolescence and BCC and meningioma in adulthood, justifying fine-tuned surveillance programmes.