Search Results (322)

Background/Objectives: Long-acting injectable antipsychotics (LAIs) represent a significant advancement in the treatment of schizophrenia (SCZ), particularly for improving adherence and long-term outcomes. This study aimed to assess the clinical outcomes of patients receiving atypical LAIs compared to those on various oral antipsychotics over a one-year follow-up in a naturalistic setting. Methods: Sixty patients with SCZ were subdivided in two groups, those receiving LAIs (n = 25) and those receiving oral antipsychotics (n = 35). The groups were comparable for age, gender, educational attainment, employment status, marital status, smoking habits, and baseline SCZ severity, with no differences in baseline chlorpromazine equivalent dosages. Results: Over the follow-up period, patients in the LAI group discontinued treatment less frequently (χ² = 4.72, p = 0.030), showed fewer suicide attempts (χ² = 5.63, p = 0.018), fewer hospitalizations (χ² = 4.95, p = 0.026), and fewer relapses (χ² = 6.61, p = 0.010). Significant differences also emerged on the Drug Attitude Inventory (DAI-10) scores (F = 8.76, p = 0.005) and Body Mass Index (BMI) values (F = 8.32, p = 0.007), with the LAI group showing more favorable outcomes. Conclusions: LAIs, compared to oral antipsychotics, may promote treatment adherence, as shown by decreased hospitalization; furthermore, their use is related with better outcomes, like fewer relapses and less suicide attempts in individuals with SCZ in real-world settings. Full article

Paeonia ludlowii, a critically endangered species endemic to Tibet, China, possesses significant ornamental, culinary, and medicinal value. However, its mitochondrial genome remains understudied, limiting insights into its evolutionary mechanisms and constraining conservation genetics applications and molecular breeding programs. We present the first complete assembly and comprehensive analysis of the P. ludlowii mitochondrial genome. Most remarkably, we discovered that the P. ludlowii mitogenome exhibits an atypical dual-circular structure, representing the first documented occurrence of this architectural feature within the genus Paeonia. The assembled genome spans 314,371 bp and encodes 42 tRNA genes, 3 rRNA genes, and 31 protein-coding genes, with a pronounced adenine–thymine bias. This multipartite genome structure is characterized by abundant repetitive elements (112 functionally annotated SSRs, 33 tandem repeats, and 945 dispersed repeats), which potentially drive genome rearrangements and facilitate adaptive evolution. Analyses of codon usage bias and nucleotide diversity revealed highly conserved gene expression regulation with limited variability. Phylogenetic reconstruction confirms that P. ludlowii, P. suffruticosa, and P. lactiflora form a monophyletic clade, reflecting close evolutionary relationships, while extensive syntenic collinearity with other Paeonia species underscores mitochondrial genome conservation at the genus level. Extensive inter-organellar gene transfer events, particularly from chloroplast to mitochondrion, suggest that such DNA exchanges enhance genetic diversity and promote environmental adaptation. The discovery of the dual-circular architecture provides novel insights into plant mitochondrial genome evolution and structural plasticity. This study elucidates the unique structural characteristics of the P. ludlowii mitochondrial genome and establishes a crucial genetic foundation for developing targeted conservation strategies and facilitating molecular-assisted breeding programs for this endangered species. Full article

The Karamaili Granite Belt (KGB) in the southern margin of the Eastern Junggar is the most important tin metallogenic belt in the southwestern Central Asian Orogenic Belt. The plutons in the western part have a close genetic relationship with tin mineralization. The zircon U-Pb ages of the Kamusite, Laoyaquan, and Beilekuduke plutons are 315.1 ± 3.4 Ma, 313.6 ± 2.9 Ma, and 316.5 ± 4.6 Ma, respectively. The plutons have high silica (SiO₂ = 75.53%–77.85%), potassium (K₂O = 4.43%–5.42%), and alkalis (K₂O + Na₂O = 8.17%–8.90%) contents and low ferroan (Fe₂O₃^T = 0.90%–1.48%), calcium, and magnesium contents and are classified as metaluminous–peraluminous, high-potassium, calc-alkaline iron granite. The rocks are enriched in Rb, Th, U, K, Pb, and Sn and strongly depleted in Ba, Sr, P, Eu, and Ti. They have strongly negative Eu anomalies (δEu = 0.01–0.05), 10,000 Ga/Al = 2.87–4.91 (>2.6), showing the geochemical characteristics of A-type granite. The zircon U/Pb ratios indicate that the above granites should be I- or A-type granite, which is generally formed under high-temperature (768–843 °C), low-pressure, and reducing magma conditions. The high Rb/Sr ratio (a mean of 48 > 1.2) and low K/Rb ratio (53.93–169.94) indicate that the tin-bearing plutons have undergone high differentiation. The positive whole-rock εNd(t) values (3.99–5.54) and the relatively young Nd T_2DM model ages (616–455 Ma) suggest the magma is derived from partially melted juvenile crust, and the underplating of basic magma containing mantle materials that affected the source area. The results indicate the KGB was formed in the tectonic transition period in the late Carboniferous subduction post-collision environment. Orogenic compression influenced the tin-bearing plutons in the western part of the KGB, forming highly differentiated and reduced I, A-type transition granite. An extensional environment affected the plutons in the eastern sections, creating A-type granite with dark enclaves that suggest magma mixing with little evidence of tin mineralization. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is one of the most frequently diagnosed endocrine and metabolic disorders in women of reproductive age before menopause. It is associated with excess androgens and ovarian dysfunction, reduced fertility, the presence of obstetric disorders, but also metabolic disorders, and, among others, insulin resistance, obesity and type II diabetes. Its close relationship with changes in the diversity of the vaginal microbiome, vaginal inflammation and changes in the vaginal microenvironment, which can pave the way for pathogenic microorganisms, is emphasized. Methods: The research in the presented paper focuses on a group of women with PCOS (n = 490) of reproductive age (26–43 years), in whom the frequency of infections of the reproductive system caused by atypical pathogens, Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma spp., were analyzed, and then the immune system response was assessed in terms of the level of serum proinflammatory cytokines, IL-1β, IL-6 and TNF-α. Results: Our results showed a 40% infection rate in the studied group of patients with PCOS, with C. trachomatis being the most common pathogen (17.7%), followed by Ureaplasma spp. (10%) and M. hominis (4.9%). In some cases, co-infections such as Mycoplasma and Ureaplasma were also observed in 3.1% or all three atypical bacteria, M. hominis, Ureaplasma spp. and C. trachomatis, in 4.3% of patients with PCOS. In our study, in women with PCOS and confirmed infection with any atypical pathogen (n = 196), we analyzed the levels of proinflammatory cytokines, IL-1 β a, IL-6 and TNF-α. The results were compared with a control group (control group A) consisting of patients with the same underlying disease, i.e., PCOS (n = 39), who did not experience infection with atypical pathogens or symptoms of gynecological infection. Additionally, a control group B (n = 28) consisting of healthy women (without PCOS and without infection) was introduced. The results regarding the levels of cytokines studied in this work (IL-1β, IL-6, TNF-α) may suggest that the presence of intracellular C. trachomatis in the infection will play a dominant role in the immune system response. In the infections with atypical pathogens analyzed in this study in patients with PCOS, no characteristic clinical features were observed, apart from indications in the form of an increase in the number of leukocytes in the assessment of the vaginal biocenosis, suggesting cervicitis and reported reproductive failure or lower abdominal pain. An additional problem is the inability to detect the presence of atypical pathogens in routine microbiological tests; therefore, confirmation of such etiology requires referral of the patient for targeted tests. Conclusions: Invasion of host cells by atypical pathogens such as C. trachomatis and infections with “genital mycoplasmas” can disrupt the function of these cells and lead to many complications, including infertility. The immune response with the production of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6, observed in response to infection with C. trachomatis, M. hominis, and Ureaplasma spp., induces or amplifies inflammation by activating immune cells or controlling infection, but may lead to the facilitation of the survival of pathogenic microorganisms and irreversible damage to fallopian tube tissues. Especially in the case of the proinflammatory cytosine TNF-α, there seems to be a close correlation with infections with atypical pathogens and a marked immune response, as well as with increased IL-1β and IL-6 values compared with the absence of infection (both in the presence and absence of PCOS). The presented study may suggest the importance of extended diagnostics to include atypical pathogens in the case of PCOS and the importance of research in this area also from the point of view of the immune response. Full article

Background/Objectives: This study aimed to develop a reliable scoring system combining clinical and radiological parameters to distinguish atypical lipomatous tumours (ALTs) from lipomas, improving diagnostic accuracy and reducing expensive molecular pathology testing. Methods: A retrospective analysis of 188 patients who underwent surgery for lipomatous tumours was conducted. Patient data, including medical history, pathology, and MRI imaging results, were reviewed. Four predictive models were developed using various clinical and imaging parameters, including age, tumour size, location, and MRI characteristics (homogeneity, contrast enhancement). Statistical analysis, including ROC curve analysis and logistic regression, was performed to assess the accuracy of these models. Results: The highest predictive accuracy was achieved with Model 1, which included seven parameters, yielding an AUC of 0.952. This model achieved a sensitivity of 96.4% and a negative predictive value (NPV) of 97.2%. Reducing the number of parameters lowered the accuracy, with contrast enhancement playing a significant role in Model 1. A risk calculator based on the optimal model was developed, offering an effective tool for clinical use that can be provided. Notably, 21 out of 37 ALTs lacked atypia and would have been missed without molecular testing. Conclusions: The developed scoring system, based on clinical and imaging parameters, accurately distinguishes ALTs from lipomas, offering a practical alternative to molecular pathology testing. This multi-parameter approach significantly improves diagnostic reliability, reducing the risk of misclassification and false negatives, while also potentially lowering healthcare costs. Full article

Foot-and-mouth disease virus (FMDV) continues to pose a significant threat to livestock health and the global agricultural economy, particularly in endemic regions of Asia, Africa, and the Middle East. Current vaccines based on chemically inactivated FMDV present several challenges, including biosafety risks, high production costs, and limited effectiveness against emerging viral variants. To overcome these limitations, we developed virus-like particle (VLP) vaccines targeting FMDV serotypes O, A, and Asia1 using a recombinant Escherichia coli expression system. The resulting VLPs self-assembled into 25–30 nm particles with native-like morphology and antigenic properties, as confirmed by transmission electron microscopy, SDS-PAGE, and Western blot analysis. Immunogenicity was evaluated in mice and pigs using ELISA and virus neutralization tests (VNT), and protective efficacy was assessed through viral challenge studies. All VLPs induced strong serotype-specific antibody responses, with ELISA PI values exceeding 50% and significantly increased VNT titers after booster immunization. In mice, PD₅₀ values were 73.5 (A-type), 32.0 (O-type), and 55.7 (Asia1-type); in pigs, PD₅₀ values reached 10.6 (O-type) and 22.6 (Asia1-type). Notably, the vaccines induced robust immune responses even at lower antigen doses, suggesting the feasibility of dose-sparing formulations. These findings demonstrate that FMDV VLPs produced in E. coli are highly immunogenic and capable of eliciting protective immunity, highlighting their promise as safe, scalable, and cost-effective alternatives to conventional inactivated FMD vaccines. Full article

Background/Objectives: 123I-FP-CIT dopamine transporter imaging is commonly used for the diagnosis of Parkinsonian syndromes in patients whose clinical presentation is atypical. Prolonged immobility, which can be difficult to maintain in this population, is required to perform SPECT acquisition. In this study we aimed to develop a Convolutional Neural Network (CNN) able to predict the outcome of the full examination based on the first acquired projection, and reliably detect normal patients. Methods: All 123I-FP-CIT SPECT performed in our center between June 2017 and February 2024 were included and split between a training and a validation set (70%/30%). An additional 100 SPECT were used as an independent test set. Examinations were labeled by two independent physicians. A VGG16-like CNN model was trained to assess the probability of examination abnormality from the first acquired projection (anterior and posterior view at 0°), taking age into consideration. A threshold maximizing sensitivity while maintaining good diagnostic accuracy was then determined. The model was validated in the independent testing set. Saliency maps were generated to visualize the most impactful areas in the classification. Results: A total of 982 123I-FP-CIT SPECT were retrieved and labelled (training set: 618; validation set: 264; independent testing set: 100). The trained model achieved a sensibility of 98.0% and a negative predictive value of 96.3% (one false negative) while maintaining an accuracy of 75.0%. The saliency maps confirmed that the regions with the greatest impact on the final classification corresponded to clinically relevant areas (basal ganglia and background noise). Conclusions: Our results suggest that this trained CNN could be used to exclude presynaptic dopaminergic loss with high reliability from the first acquired projection. It could be particularly useful in patients with compliance issues. Confirmation with images from other centers will be necessary. Full article

Multiple myeloma is a neoplastic disease characterised by the proliferation of clonal, atypical plasma cells. In cancer cells, the balance between two paths of cell death, necroptosis and apoptosis, is disrupted. The aim of this study was to analyse the occurrence of polymorphisms in genes encoding key proteins for the necroptosis process, i.e., RIPK-1, RIPK-3 and MAPKAPK2. We investigated the potential relations between the occurrence of genetic variability and the clinical course of the disease. We analysed six single-nucleotide polymorphisms in a population of patients with multiple myeloma (n = 205) and healthy volunteers (n = 100): RIPK1 rs2272990, RIPK1 rs9391981, RIPK3 rs724165, RIPK3rs3212243, MAPKAPK2, rs45514798 and MAPKAPK2 rs4073250. We found that genotypes rs9391981 CG, rs724165 CG, rs3212243 GG, and rs4073250 AA were independent predictors of overall survival, while genotype MAPKAPK2 rs4073250 AA was an independent predictor of progression-free survival. MAPKAPK2 rs45514798 AA was associated with polyneuropathy after thalidomide therapy. In conclusion, some of the SNPs tested have potential prognostic value and could be used as marker of survival in patients with multiple myeloma. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

This study explores the impact of viscous heating on decretion disks around Classical Ae (CAe) stars, with a focus on modeling the disk’s thermal structure. While photoionization is the dominant heating mechanism, viscous dissipation can play an important role in shaping the disk temperature, particularly for cooler CAe subtypes. Our models incorporate viscosity-driven heating and predict that shear heating has a negligible effect for early A-type stars (A0–A1), but it becomes increasingly significant for later spectral types, especially as the viscosity parameter ($\alpha$) increases. This heating also influences the strength of H$\alpha$ emission. Furthermore, our models predict a sharp decline in the number of emission-line stars beyond spectral type A2, a trend observed in CAe populations. However, for sufficiently high $\alpha$ values (≥0.3), a higher fraction of emission-line objects is expected even among later subtypes, such as A5, despite the lack of well-characterized CAe stars observed beyond the spectral type A4. Full article

Scrapie is a notifiable transmissible spongiform encephalopathy (TSE) in sheep that relies on clinical examinations for reporting suspects. A short examination protocol was used in 1002 sheep to define clinical markers suggestive of scrapie. Sheep were naturally or experimentally exposed to a classical, atypical scrapie or bovine spongiform encephalopathy agent; 312 were positive for a transmissible spongiform encephalopathy (TSE) by brain examination and included non-exposed controls. Assessed signs were posture, behaviour, menace, scratch and blindfolding response, wool loss and skin changes, body condition, incoordination and tremor. First, the combined occurrence of two or more clinical signs was compared between TSE-positive and negative sheep. Second, the importance of clinical markers was determined in a general classification and regression tree model. The main clinical markers to predict TSEs according to the tree model were incoordination and a positive scratch test. Test sensitivities and specificities were 70.8–81.5% and 96.1–93.0%, respectively, and predictive values above 87%. The results suggest that the short clinical protocol, which assesses the presence of certain clinical signs associated with a TSE in sheep and is quick to perform, may be useful to reach a suspect diagnosis in both naturally and experimentally generated TSEs. Full article

The atypical activation of the epithelial-to-mesenchymal transition represents one of the main mechanisms driving cancer cell dissemination. It enables epithelial cancer cells to detach from the primary tumor mass and gain survival advantages in the bloodstream, significantly contributing to the spread of circulating tumor cells. Notably, epithelial-to-mesenchymal transition is not a binary process but rather leads to the formation of a wide range of cell subpopulations characterized by the simultaneous expression of both epithelial and mesenchymal markers. Therefore, analyzing the modulation of EMT hallmarks during the conversion from healthy cells to metastatic cancer cells, which acquire stem mesenchymal characteristics, is of particular interest. This study investigates the expression of a panel of epithelial-to-mesenchymal transition-related genes in healthy cells, primary and metastatic cancer cells, and in mesenchymal cell lines, derived from various tissues, including the lung, colon, pancreas, skin, and neuro-ectoderm, with the aim of identifying potential cut-off values for assessing cancer aggressiveness. Interestingly, we found that the expression levels of CDH1, which encodes the epithelial marker E-cadherin, CDH5, encoding vascular endothelial cadherin, and the epithelial-to-mesenchymal transition-transcription factor ZEB1, effectively distinguished primary from metastatic cancer cells. Additionally, our data suggest a tissue-specific signature in the modulation of epithelial-to-mesenchymal transition markers during cancer progression. Overall, our results underscore the importance of investigating epithelial-to-mesenchymal transition as a tissue-specific process to identify the most suitable markers acting as potential indicators of disease aggressiveness and therapeutic responsiveness. Full article

Background: Spitz tumors (STs) are a diverse group of melanocytic lesions that range from benign to malignant. STs pose significant classification challenges due to overlapping histological and immunohistochemical (IHC) features among the STs with different malignant potential. This study aimed to assess the diagnostic value of a melanoma-specific next-generation sequencing (NGS) panel (MelArray) combined with IHC analysis to improve the assessment of diagnostically challenging ST cases. Methods: Patients with STs and available MelArray results were included in this retrospective analysis. Molecular analysis (genetic alterations, tumor mutational burden (TMB), and copy number variations (CNV)), clinical data (demographics and clinical course), and IHC data (scores for markers such as p16, Ki-67, HMB45, PRAME, and Melan A) were evaluated in conjunction and correlated with patient outcomes. Results: Atypical Spitz tumors (ASTs, n = 20) predominantly exhibited heterozygous deletions in melanoma-relevant genes, but these were not accompanied by the multiple damaging mutations commonly associated with melanoma. IHC scores were higher in ASTs compared to Spitz nevi (SN, n = 3), suggesting an intermediate biologic potential. SN exhibited minimal genetic alterations and low IHC scores, reflecting a benign profile. Genetic analysis of the Spitz melanoma (SM, n = 1) revealed a distinct molecular profile with damaging mutations affecting the key regulatory pathways involved in tumor progression, along with a high TMB, and an IHC score comparable to ASTs. During a median follow-up of 36 months (range: 6–48 months, n = 23), no recurrences, distant metastases, or tumor-related deaths were observed. Conclusions: The integration of NGS analysis with the MelArray panel, histology, and immunohistochemistry, enhances the diagnostic accuracy of challenging STs by identifying the genetic alterations linked to malignancy risk. This aids in the detection of high-risk lesions that need a more detailed work-up and more stringent follow-up, and those that will follow a benign course. Larger studies are needed to validate the clinical utility and broader applicability. Full article

Financial stability analysis requires volatility modeling, especially in emerging nations where pension fund systems are very vulnerable to macrofinancial risks. In order to examine the volatility dynamics of Romania’s private pension system, this study uses daily net asset value (NAV) data from 2012 to 2024 to evaluate four GARCH-type models: standard GARCH (sGARCH), exponential GARCH (EGARCH), Glosten–Jagannathan–Runkle GARCH (GJR-GARCH), and component GARCH (C-GARCH). The analysis includes domestic and international equity indices (BET, STOXX), government bond yields (ROMGB 10Y, ROMANI 5Y), short-term interbank rates (ROBOR ON), and exchange rate fluctuations (RON/EUR). Current findings indicate that EGARCH captures asymmetric fluctuations in pension fund performance, where positive shocks generate larger increases in volatility than negative ones, highlighting an atypical asymmetry pattern. Furthermore, the stabilizing effects of government bonds are overshadowed by stock market behavior, which becomes the primary driver of risk. Fluctuations in exchange rates further increase volatility, especially in markets vulnerable to external disturbances. The findings offer empirical evidence for the necessity of more cautious risk management approaches and highlight the importance of regulatory oversight in maintaining market confidence. The study underscores the importance of customized allocation frameworks that reduce vulnerability to disruptive events while maintaining prospects for sustained growth. This new dataset contributes to enhancing the comprehension of pension fund volatility within the context of emerging markets. These insights can assist managers and policymakers seeking to fortify retirement outcomes. Full article

Background: The diagnosis of upper urinary tract urothelial carcinoma (UTUC) in cytological specimens is challenging, particularly the designation of atypical urothelial cells (AUC). The application of the Paris System for Reporting Urinary Cytology (TPS) has improved the performance of lower tract urothelial carcinoma specimens but has shown variable results in upper tract specimens, which are frequently instrumented. Methods: This retrospective study analysed upper tract selective cytology samples from January to December 2023. Samples were classified under TPS 2.0 categories. Histological specimens were used where available as the gold standard to calculate statistical metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Out of 122 samples, 12.2% were considered non-diagnostic or insufficient, with 13.1% designated as Non-high-grade urothelial carcinoma (N-HGUC), 53.3% as atypical urothelial cells (AUC) and 21.3% as positive/suspicious for HGUC. Histopathological correlation was available for 48.7% of cases. The risk of malignancy was: NHGUC (0%), AUC (47%) and HGUC (77.7%). The highest PPV was for HGUC (78%), with a diagnostic accuracy of 81.3% and specificity of 88%. In contrast, AUC had a PPV of 47% in instrumented and non-instrumented samples, rising to 58% in combination with the HGUC category. Conclusion: TPS 2.0 is an effective tool with excellent diagnostic accuracy for HGUC and in excluding malignancies in the N-HGUC category, but in our hands, the high rates of the AUC category, together with the low PPV, remain a major challenge and an obstacle to the correct stratification of patients with UTUC. Full article