Long-term follow-up of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in children and adolescents managed at a single institution over a 20-year period

Chronic myeloid leukaemia (CML) is rare in childhood. In our Institution we managed 30 consecutive Ph+CML patients aged <18 years, according to our adults’ guidelines. Patients with HLA-identical related donor (RD) underwent stem cell transplant (SCT). Since 1989, patients without RD were systematically treated with -interferon (IFN) (median dosage: 6 MU/day). Of 18/19 evaluable patients, 17 (94.5%) achieved haematologic response (HR), 11/17 (65%) cytogenetic response (CyR), complete (CCyR) in 4 (23.5%). Three patients remain in CCyR, 2 achieved BCR-ABL transcript disappearance. Of 13 patients without CCyR, 5 underwent SCT, 4 switched to STI571, 4 progressed. All patients receiving STI571 in chronic phase (CP) obtained sustained CCyR and 3 a persistent molecular response. 8-year survival among IFN-treated patients, censored or not for subsequent therapies, is 62% and 63%. Overall, 13/30 patients underwent SCT: 5 HLA-identical-RD, 5 matched unrelated donor, 2 mismatched-RD, 1 unrelated mismatched umbilical cord blood. Eight allotransplanted patients (6/6 in 1st CP) are in cytogenetic and molecular remission with 8-year survival of 61% from SCT and 69% from diagnosis. In our 20-year experience, the use of IFN in children without matched RD led to prolonged cytogenetic and molecular responses and long-term survival, without impairing the outcome of subsequent SCT

Private equity and venture capital in Italy

This paper examines private equity and venture capital in Italy. The first part looks at the main features of the Italian market and its recent evolution; the second part considers the results of a survey of firms and intermediaries designed to gather information regarding contract features and the characteristics of investee firms and investing intermediaries. Finally, the paper discusses the main obstacles to the development of the sector using information from the survey of intermediaries.private equity, venture capital

Implant insertion torque value in immediate loading : a retrospective study

The aim of this study is to verify if the Insertion Torque Value (ITV) of 32 Ncm for immediate loading protocol (ILP), as indicated by literature, is still, with the advance in implant research, a real significant cut-off for long-term implant survival. In this retrospective study, data from 224 patients that during three years of clinical practice, were submitted to the insertion of 322 implants with immediate loading protocol, have been recorded, pooled and analyzed. Data were organized based on Insertion Torque Value (ITV): > 32 Ncm (CG) and 32 Ncm are still characterized by a lower crestal bone resorption, there are no statistically significant differences among the two groups for what concerning the failure rate during the 2 years of follow-up and OR. These results permit us to suppose that the cut-off of ITV >32 Ncm for immediate loading implants, could be reduced to inferior values. However further studies are necessary to indicate precise clinical guidelines

Unravelling the regulation pathway of photosynthetic AB-GAPDH

Oxygenic phototrophs perform carbon fixation through the Calvin-Benson cycle. Different mechanisms adjust the cycle and the light-harvesting reactions to rapid environmental changes. Photosynthetic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key enzyme in the cycle. In land plants, different photosynthetic GAPDHs exist: the most abundant isoform is formed by A2B2 heterotetramers and the least abundant by A4 homotetramers. Regardless of the&nbsp;subunit composition, GAPDH is the major consumer of photosynthetic NADPH and its activity is strictly regulated. While A4-GAPDH is regulated by&nbsp;CP12, AB-GAPDH is autonomously regulated through the C-terminal extension (CTE) of its B subunits. Reversible inhibition of AB-GAPDH occurs via the oxidation of a cysteine pair located in the CTE and the substitution of NADP(H) with NAD(H) in the cofactor-binding site. These combined conditions lead to a change in the oligomerization state and enzyme inhibition. SEC-SAXS and single-particle cryo-EM analysis were applied to reveal the structural basis of this regulatory mechanism. Both approaches revealed that spinach (A2B2)n-GAPDH oligomers with n = 1, 2, 4 and 5 co-exist in a dynamic system. B subunits mediate the contacts between adjacent tetramers in A4B4 and A8B8 oligomers. The CTE of each B subunit penetrates into the active site of a B subunit of the adjacent tetramer, which in turn moves its CTE in the opposite direction, effectively preventing the binding of the substrate 1,3-bisphosphoglycerate in the B subunits. The whole mechanism is made possible, and eventually controlled, by pyridine nucleotides. In fact, NAD(H), by removing NADP(H) from A subunits, allows the entrance of the CTE into the active site of the B subunit, hence stabilizing inhibited oligomers

Historical explosive activity of Mount Melbourne Volcanic Field (Antarctica) revealed by englacial tephra deposits

Five tephra layers named BRH1 to 5 were sampled in an ice cliff located on the north-eastern flank of Mount Melbourne (northern Victoria Land, Antarctica). The texture, componentry, mineralogy, and major and trace element compositions of glass shards have been used to characterize these layers. These properties suggest that they are primary fall deposits produced from discrete eruptions that experienced varying degrees of magma/water interaction. The major and trace element glass shard analyses on single glass shards indicate that Mount Melbourne Volcanic Field is the source of these tephra layers and the geochemical diversity highlights that the eruptions were fed by compositionally diverse melts that are interpreted to be from a complex magma system with a mafic melt remobilizing more evolved trachy-andesitic to trachytic magma pockets. Geochemical compositions, along with textural and mineralogical data, have allowed correlations between two of the englacial tephra and distal cryptotephra from Mount Melbourne, recovered within a marine sediment core in the Edisto Inlet (~ 280 km northeast of Mount Melbourne), and constrain the age of these englacial tephra layers to between the third and the fourth century CE. This work provides new evidence of the intense historical explosive activity of the Mount Melbourne Volcanic Field and better constrains the rates of volcanism in northern Victoria Land. These data grant new clues on the eruptive dynamics and tephra dispersal, and considerably expand the geochemical (major and trace elements) dataset available for the Mount Melbourne Volcanic Field. In the future, this will facilitate the precise identification of tephra layers from this volcanic source and will help define the temporal and spatial correlation between Antarctic records using tephra layers. Finally, this work also yields new valuable time-stratigraphic marker horizons for future dating, synchronization, and correlations of different palaeoenvironmental and palaeoclimatic records across large regions of Antarctica

Standardization of body composition status in patients with advanced urothelial tumors: the role of a CT-based aI-powered software for the assessment of sarcopenia and patient outcome correlation

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes

The clinical efficacy of nitrofurantoin for treating uncomplicated urinary tract infection in adults: a systematic review of randomized control trials

OBJECTIVE: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens.SUMMARY: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed

Blood and urine-based biomarkers in prostate cancer: Current advances, clinical applications, and future directions

Prostate cancer (PCa) is one of the most prevalent malignancies in men, characterized by high clinical and molecular heterogeneity. Despite the widespread use of prostate-specific antigen (PSA) for diagnosis and monitoring, its limited specificity and sensitivity necessitate the development of more accurate biomarkers. This review provides a comprehensive overview of current and emerging diagnostic, prognostic, and predictive biomarkers in PCa, highlighting their clinical applications and future perspectives. PSA, though historically central in PCa screening, lacks tumor specificity, often leading to unnecessary biopsies or missed aggressive cancers. Recent blood-based biomarkers, such as the Prostate Health Index (PHI) and 4Kscore, improve specificity by integrating PSA isoforms or kallikrein protein levels with clinical parameters. Urine-based biomarkers like PCA3 and SelectMDx further enhance diagnostic precision, particularly in distinguishing high-grade tumors, and show potential in active surveillance settings. Prognostic markers such as Bcl-2, Ki-67, and EZH2, alongside genetic alterations like MCM7 and 8q gain, help stratify patients by tumor aggressiveness and risk of recurrence. Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), offer non-invasive alternatives for molecular profiling, especially in metastatic castration-resistant PCa (mCRPC), and can identify actionable alterations such as BRCA1/2 or ATM mutations. Emerging technologies such as machine learning and single-cell omics are reshaping biomarker discovery. Artificial intelligence-driven models, like the replication stress signature (RSS), show promise in predicting relapse and therapeutic response. Single-cell RNA sequencing and spatial transcriptomics have deepened our understanding of PCa heterogeneity, tumour microenvironment, and resistance mechanisms. Furthermore, novel biomarkers, including exosome RNAs and immune-related markers (PD-L1, SOX2, TcellinfGEP), offer insights into tumour progression and immunotherapeutic potential. The urinary and gut microbiomes are also being explored for their diagnostic and prognostic roles in PCa. In conclusion, integrating advanced molecular tools and biomarker-guided platforms into clinical practice can significantly enhance early detection, personalized treatment, and monitoring in prostate cancer, paving the way for precision oncology