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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.

This study examined the effects of extruded linseed and algae Padina pavonica extract on the reproductive performance, milk production, and gastrointestinal health of female rabbits. Thirty-six nulliparous New Zealand White female rabbits were randomly assigned to three groups (n = 12) with different diets. The control group (CNT) received a standard diet, while the other two groups received modified isoenergetic diets in which part of the CNT diet ingredients were replaced with 5% extruded linseed (L5%) and 5% extruded linseed plus 0.2% Padina pavonica algae extract (L5%PP). The rabbits were monitored from artificial insemination until the weaning of the rabbit kits, evaluating different reproductive parameters. Our results indicate that extruded linseed and alga Padina pavonica extract did not affect the feed intake or body weight of female rabbits. Additionally, no clinically significant histological changes were observed at the gastrointestinal level. The reproductive parameters, including litter size, litter weight, and milk yield, showed no significant differences among groups. Notably, perinatal and pre-weaning mortalities were reduced in litters born to females receiving omega-3 integrated diets (p < 0.05). While these findings are promising, further studies are needed to confirm these results and explore the specific mechanisms by which omega-3 affects reproductive function and litter health.

Prickly pear (Opuntia ficus indica L.) could be used in rabbit nutrition in compliance with circular economy principles, global warming issues, and reduction of production costs. This study aims to evaluate the effects of dietary incorporation of prickly pear seed cake (PPSC) on growth, physiological, and histometric parameters in rabbits. A total of 105 rabbits were divided into three experimental groups (n = 35) and fed different diets: a commercial feed (C group), the same feed with alfalfa replaced by PPSC at 10% (10PP group), and at 20% (20PP group). They were group-housed in cages with 5 animals per cage from weaning until slaughtering. While body weights and weight gains were similar in all groups, the coefficients of nutrient digestibility of dry matter, fibers, and ashes, as well as the characteristics of intestinal villi, were improved in the 10PP group compared to the others (p < 0.05). The 20PP group showed a reduction in perirenal and interscapular fat (p < 0.05), as well as lower plasma concentrations of triglycerides and cholesterol compared to the C group (p < 0.001). In conclusion, PPSC can be incorporated into the diets of growing rabbits up to 20% as a partial substitute for alfalfa without the impairment of growth performance. Additionally, the inclusion of PPSC enhanced nutrient digestibility and increased the intestinal absorption surface area.

Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background.

The aim of this study was to evaluate the use of horse and donkey meat in the production of kaddid—a traditional dish typically not made with these meats—from a physical and chemical perspective. The results showed that both meats exhibit similar water retention during cooking, contributing to comparable tenderness and juiciness, with no significant differences in pH values, indicating similar quality (p > 0.05). However, their amino acid profiles differ: horse meat contains lower levels of glutamate (p < 0.05), methionine (p < 0.01), isoleucine (p < 0.05), and leucine (p < 0.05), but higher levels of proline (p < 0.05), histidine (p < 0.01), and lysine (p < 0.001) compared to donkey meat. Both meats provide essential amino acids. Horse meat is richer in saturated and monounsaturated fatty acids (32.44% and 39.58%, respectively), while donkey meat has a higher content of polyunsaturated fatty acids (31.51%), with a more favorable PUFA/SFA ratio, suggesting better cardiovascular health benefits. In terms of dried meat, donkey kaddid has a higher protein (17.45 g/100 g) and lower fat content (2.1 g/100 g) compared to horse kaddid (16.7 g/100 g, and 3.5 g/100 g, respectively) (p < 0.05). These findings inform consumer choices and production practices, promoting the use of horse and donkey meat for kaddid production.

Clinical differentiation of progressive supranuclear palsy (PSP) from Parkinson’s disease (PD) is challenging due to overlapping phenotypes and the late onset of specific atypical signs. Therefore, easily assessable diagnostic biomarkers are highly needed. Since PD is a synucleopathy while PSP is a tauopathy, here, we investigated the clinical usefulness of serum oligomeric-α-synuclein (o-α-synuclein) and 181Thr-phosphorylated tau (p-tau181), which are considered as the most important pathological protein forms in distinguishing between these two parkinsonisms. We assessed serum o-α-synuclein and p-tau181 by ELISA and SIMOA, respectively, in 27 PSP patients, 43 PD patients, and 39 healthy controls (HC). Moreover, we evaluated the correlation between serum biomarkers and biological and clinical features of these subjects. We did not find any difference in serum concentrations of p-tau181 and o-α-synuclein nor in the o-α-synuclein/p-tau181 ratio between groups. However, we observed that serum p-tau181 positively correlated with age in HC and PD, while serum o-α-synuclein correlated positively with disease severity in PD and negatively with age in PSP. Finally, the o-α-synuclein/p-tau181 ratio showed a negative correlation with age in PD.

ObjectiveTo investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET.MethodsWe enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100–300 msec). MRI data (cortical thickness, volumes, surface area, roughness, mean curvature and subcortical volumes) were extracted using Freesurfer on T1-weighted images. We employed two decision tree-based ML classification algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) combining MRI data and BRrc values to differentiate between rET and ET patients.ResultsML models based exclusively on MRI features reached acceptable performance (AUC: 0.85–0.86) in differentiating rET from ET patients and from HC. Similar performances were obtained by ML models based on BRrc data (AUC: 0.81–0.82 in rET vs. ET and AUC: 0.88–0.89 in rET vs. HC). ML models combining imaging data (cortical thickness, surface, roughness, and mean curvature) together with BRrc values showed the highest classification performance in distinguishing between rET and ET patients, reaching AUC of 0.94 ± 0.05. The improvement in classification performances when BRrc data were added to imaging features was confirmed by both ML algorithms.ConclusionThis study highlights the usefulness of adding a simple electrophysiological assessment such as BRrc to MRI cortical morphometric features for accurately distinguishing rET from ET patients, paving the way for a better classification of these ET syndromes.

Introduction: Postural instability (PI) is a common disabling symptom in Parkinson’s disease (PD) patients, but the brain alterations underlying this sign are not fully understood yet. This study aimed to investigate the association between PI and callosal damage in PD and progressive supranuclear palsy (PSP) patients, using multimodal MR imaging. Methods: One-hundred and two PD patients stratified according to the presence/absence of PI (PD-steady N=58; PD-unsteady N=44), 69 PSP patients, and 38 healthy controls (HC) underwent structural and diffusion 3T brain MRI. Thickness, fractional anisotropy (FA) and mean diffusivity (MD) were calculated over 50 equidistant points covering the whole midsagittal profile of the corpus callosum (CC) and compared among groups. Associations between imaging metrics and postural instability score were investigated using linear regression. Results: Both PSP and PD-unsteady patient groups showed CC involvement in comparison with HC, while no difference was found between PD-steady patients and controls. The CC damage was more severe and widespread in PSP than in PD patients. The CC genu was the regions most damaged in PD-unsteady patients compared with PD-steady patients, showing significant microstructural alterations of MD and FA metrics. Linear regression analysis pointed at the MD in the CC genu as the main contributor to PI among the considered MRI metrics. Conclusion: This study identified callosal microstructural alterations associated with PI in unsteady PD and PSP patients, which provide new insights on PI pathophysiology and might serve as imaging biomarkers for assessing postural instability progression and treatment response.

Introduction Depression is common in schizophrenia and is correlated with suicide risk and poor long-term outcomes. However, the presence of depressive symptoms is often underestimated in both research and treatment, particularly at the illness onset. Objectives The goals of this study were: (a) to longitudinally observe anxious-depressive symptom levels in patients with First Episode Schizophrenia (FES) during a 24 months of follow-up period, and (b) to examine their associations with other psychopathology and the intervention patients received in an “Early Intervention in Psychosis” (EIP) program during the follow-up period. Methods The Global Assessment of Functioning (GAF) and the Positive And Negative Syndrome Scale (PANSS) were completed by 159 FES patients both at baseline and across the follow-up. Data were analyzed by linear regression analysis and Spearman’s coefficients. Results Anxious-depressive symptoms had significant longitudinal associations with GAF deterioration and PANSS “Positive Symptoms”, “Negative Symptoms” and “Disorganization” subscores. During the follow-up period, FES participants significantly improved the level of anxious-depressive symptoms. This was significantly associated with the number of case management and individual psychotherapy meetings the patient engaged in, as well as with lower antipsychotic doses prescribed during the follow-up period. Conclusions In conclusion, anxious-depressive symptoms are prominent in FES and at the initial entry into EIP programs. Anxious-depressive symptom severity tends to diminish overtime, especially with the provision of specialized EIP treatments. However, since we did not have a control population studied in parallel, we cannot say whether these results are specific to the protocols of EIP programs or just to the intensity of engagement in care. Disclosure of Interest None Declared

Introduction The prognostic prediction of outcomes in individuals at clinical high-risk for psychosis (CHR-P) is still a significant clinical challenge. Among multiple baseline variables of risk calculator models, the role of ongoing pharmacological medications has been partially neglected, despite meta-analytical evidence of higher risk of psychosis transition associated with baseline prescription exposure to antipsychotics (AP) in CHR-P individuals. In particular, baseline AP exposure in CHR-P individuals may be considered as a functional equivalent of the psychometric transition to psychosis, as already postulated in the original ‘Ultra High-Risk’ model. Objectives The main aim of the current study was to test the hypothesis that ongoing AP need at baseline indexes a subgroup of CHR-P individuals with more severe psychopathology and worse prognostic trajectories along a 1-year follow-up period. Methods This research was settled within the ‘Parma At-Risk Mental States’ program. Baseline and 1-year follow-up assessment included the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). CHR-P individuals who were taking AP medications at entry were included in the CHR-P-AP+ subgroup. The remaining participants were grouped as CHR-P-AP-. The acquisition of drug and outcome information was collected both at baseline and across the follow-up period. Finally, logistic regression analyses with dichotomized 1-year outcome parameters (previously showing statistically significant differences in inter-group comparisons) as dependent measures and sociodemographic and clinical characteristics as independent variables were also performed. Results Hundred and seventy-eight CHR-P individuals (aged 12–25 years) were enrolled (91 CHR-P-AP+, 87 CHR-P-AP-). Compared to CHR-P AP-, CHR-P AP+ individuals had older age, greater baseline PANSS ‘Positive Symptoms’ and ‘Negative Symptoms’ factor subscores and a lower GAF score. At the end of our follow-up, CHR-P-AP+ subjects showed higher rates of psychosis transition, new hospitalizations and urgent/non-planned visits compared to CHRP- AP- individuals. Conclusions The current study suggests that AP need is a significant prognostic variable in cohorts of CHR-P individuals and should be included in the current risk calculators. In particular, the results of this study conducted in a realworld clinical setting indicate that the rate of CHR-P individuals who were already exposed to AP at the time of CHR-P status ascription was higher than those reported in recent meta-analyses on this topic. Moreover, our findings confirm that baseline AP prescription appears to increase psychotic transition risk. Disclosure of Interest None Declared

Premature ejaculation (PE) is a common male sexual dysfunction that can cause significant distress in the patient and partner. This study aimed to compare the current international guidelines on PE to highlight their similarities and differences. We examined the latest guidelines from the European Association of Urology (EAU), American Urological Association/Sexual Medicine Society of North America (AUA/SMSNA), and International Society of Sexual Medicine (ISSM) by comparing definitions, classifications, epidemiology, pathophysiology, and recommendations on diagnosis and therapy. The quality of guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) Global Rating Scale (GRS). We found significant variations in the definitions of PE and recommendations on management of patients. The EAU guidelines were the most recent, the AUA/SMSNA guidelines lacked detail in some areas, and the ISSM guidelines were the most complete but also the least updated. The search for a unified definition and the development of standardized diagnostic and therapeutic pathways remain concrete issues to improve the management of patients with PE worldwide.

(1) Background: To identify a particular setting of biopsy-naïve patients in which it would be reasonable to offer only cognitive targeted prostate biopsy (PBx) with a transrectal approach. (2) Methods: We designed an observational retrospective pilot study. Patients with a prostatic specific antigen (PSA) level > 10 ng/mL, either a normal or suspicious digital rectal examination (DRE), and a lesion with a PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone were included. All patients underwent a transrectal PBx, including both systematic and targeted samples. The detection rate of clinically significant prostate cancer (csPCa) (Gleason Score ≥ 7) was chosen as the primary outcome. We described the detection rate of csPCa in systematic PBx, targeted PBx, and overall PBx. (3) A total of 92 patients were included. Prostate cancer was detected in 84 patients (91.30%) with combined biopsies. A csPCa was diagnosed in all positive cases (100%) with combined biopsies. Systematic PBxs were positive in 80 patients (86.96%), while targeted PBxs were positive in 84 men (91.30%). Targeted PBx alone would have allowed the diagnosis of csPCa in all positive cases; systematic PBx alone would have missed the diagnosis of 8/84 (9.52%) csPCa cases (4 negative patients and 4 not csPCa) (p = 0.011). (4) Conclusions: Cognitive targeted PBx with a transrectal approach could be offered alone to diagnose csPCa in biopsy-naïve patients with PSA ≥ 10 ng/mL, either normal or suspicious DRE, and a lesion with PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone.

Abstract Background NUT carcinoma (NUTc) is a rare and aggressive malignant epithelial tumor characterized by rearrangement of the NUT gene on chromosome 15q14. Methods In this article, we present the fifth case worldwide of a young woman affected by a NUTc arising from a submandibular gland, presenting as a rapidly evolving mass. She underwent a right scialoadenectomy and received the initial diagnosis of high‐grade mucoepidermoid carcinoma. Due to evidence of local recurrence at magnetic resonance imaging 1 month later, a subsequent right radical neck dissection was performed. The patient then sought a second opinion at our cancer center and finally received the correct diagnosis of NUT carcinoma. Given the well‐known aggressive behavior of this neoplasm, as well as clinical and radiological features, she underwent adjuvant chemo‐radiation (intensity‐modulated radiotherapy + concurrent chemotherapy with cisplatin). Results After a disease‐free interval of 2.6 months, a widespread metastatic disease led to rapid deterioration of performance status and patient death in a few weeks after metastatic onset. Conclusions We presented a case of NUTc arising from salivary gland aiming to improve the knowledge of this rare malignancy. First, we pointed out that in the setting of rare tumors like salivary gland cancers, the diagnosis should be obtained by expert pathologists, and patients should be referred to tertiary cancer centers for their clinical management. Second, molecular profiling may help to identify possible druggable targets that may be exploited to treat patients suffering from this aggressive malignancy. Sharing the molecular data provided in this case will be useful for further research.