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The use of graphene-based materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene’s peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that single-layer graphene increases neuronal firing by altering membrane-associated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene–ion interactions that are maximized when single-layer graphene is deposited on electrically insulating substrates are crucial to these effects.

In resected perihilar cholangiocarcinoma (PHC), positive ductal margin (DM) is associated with poor survival. There is currently little knowledge about the impact of positive radial margin (RM) when DM is negative. The aim of this study was to evaluate the incidence and the role of positive RM. Patients who underwent surgery between 2005 and 2017 where retrospectively reviewed and stratified according to margin positivity: an isolated RM-positive group and DM ± RM group. Of the 75 patients identified; 34 (45.3%) had R1 resection and 17 had positive RM alone. Survival was poorer in patients with R1 resection compared to R0 (p = 0.019). After stratification according to margin positivity; R0 patients showed better survival than DM ± RM-positive patients (p = 0.004; MST 43.9 vs. 23.6 months), but comparable to RM-positive patients (p = 0.361; MST 43.9 vs. 39.5 months). Recurrence was higher in DM ± RM group compared to R0 (p = 0.0017; median disease-free survival (DFS) 15 vs. 30 months); but comparable between RM and R0 group (p = 0.39; DFS 20 vs. 30 months). In univariate and multivariate analysis, DM positivity resulted as a negative prognostic factor both for survival and recurrence. In conclusion, positive RM resections appear to have different recurrence patterns and survival rates than positive DM resections.

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and 2023, we treated 1341 patients with HCC using L-MWA. From this cohort, patients with Child-Pugh class A liver function, HCC within the Milan criteria, no contraindications to transplantation, and ≥12 months of follow-up were selected. SLT failure was defined as non-transplantable recurrence or death, resulting in the loss of a potentially curative therapeutic opportunity. The primary endpoint was overall survival (OS); secondary endpoints included predictors of survival and SLT failure. Results: A total of 341 patients met the inclusion criteria. Five-year OS was 62%. Independent predictors of poorer survival included the presence of cardiac disease or oesophageal varices, a Child-Pugh score of 6, tumour size, and elevated alpha-fetoprotein (AFP) levels. Treatment was successful in 255 patients (74.8%): 102 (29.9%) underwent SLT, 67 (19.6%) received alternative therapies, and 93 (27.3%) remained recurrence-free. Treatment failure occurred in 86 patients (25.2%) due to non-transplantable recurrence or death. Independent predictors of failure included older age, non-HBV aetiology, and elevated AFP levels. Five-year OS rates were 79% in the success group and 22% in the failure group (p < 0.001). Conclusions: A combined L-MWA and SLT strategy is safe and effective, yielding a 62% 5-year OS rate. This approach supports more efficient graft use with a consequent increase in the population transplant benefit. Improved selection may further reduce failure rates.

The XXL trial represents the first prospective validation of “biological downstaging” in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of “matching-adjusted indirect comparison” was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, d value = |0.683|). The survival curves of our LT group (n = 68) overlapped with those of the LT-XXL group (p = 0.846). Survival curves of non-LT candidates with a sustained complete response (n = 64) were similar to those of transplanted patients (p = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.

In the context of spreading interest in textbook outcome (TO) evaluation in different fields, we aimed to investigate an uncharted procedure, that is, laparoscopic microwave ablation (MWA) for hepatocellular carcinoma (HCC). Absence of post-MWA complications, a hospital stay of three days, no mortality nor readmission within 30 days, and complete response of the target lesion at post-MWA CT scan defined TO achievement. Patients treated between January 2014 and March 2021 were retrospectively reviewed, and of the 521 patients eligible for the study, 337 (64.7%) fulfilled all the quality indicators to achieve the TO. The absence of complications was the main limiting factor for accomplishing TO. At multivariable analysis, Child–Pugh B cirrhosis, age of more than 70 years old, three nodules, and MELD score ≥ 15 were associated with decreased probabilities of TO achievement. A score based on these factors was derived from multivariable analysis, and patients were divided into three risk groups for TO achievement. At survival analysis, overall survival (OS) was significantly (p = 0.001) higher in patients who achieved TO than those who did not. Moreover, OS evaluation in the three risk groups showed a trend coherent with TO achievement probability. The present study, having assessed the first TO for laparoscopic MWA for HCC, encourages further broader consensus on its definition and, on its basis, on the development of clinically relevant tools for managing treatment allocation.

Many advantages have been reported with the use of machine perfusion (MP) to rescue extended criteria donor (ECD) grafts, improving both short- and long-term post-liver transplantation (LT) outcomes. Acute kidney injury (AKI) is a common post-LT complication associated with these grafts and may compromise patient outcomes and increase LT-related costs. The aim of the study was to analyze the incidence of AKI in recipients of MP-treated grafts compared with those receiving conventionally cold-stored (SCS) grafts, both before and after a propensity score matching (PSM). From a prospectively maintained database, LT recipients of MP-treated grafts were compared with SCS grafts transplanted in the same study period (January 2022–May 2025). PSM was performed based on donor risk index (DRI), macrosteatosis (≥ or <30%), and recipient NaMELD score using a 3:1 (MP vs. SCS) ratio. Of the 177 consecutive LTs, 30 were performed with MP-treated grafts (MP group) and 147 using SCS (SCS group). The MP group displayed more marginal characteristics: older age (72 vs. 62 years, p = 0.02), higher proportion of DCD (10% vs. 0, p = 0.04), and higher frequency of moderate steatosis (macro ≥ 30%, 10% vs. 2.7%, p = 0.09). AKI rates were similar between groups (63% vs. 45.6%, p = 0.16), as was the distribution across AKI stages. After PSM, donor and recipient characteristics were balanced, and AKI rates remained similar between groups (58.6% vs. 47.1%, p = 0.39). Donor diabetes and recipient age were independent predictors of AKI in multivariate analysis (donor diabetes OR 3.29, 95% CI 1.347–8.030; recipient age: OR 1.06, 95% CI 1.015–1.097, both p < 0.05). MCP-1 and TNF-α levels measured in the perfusate fluid within the first minutes of perfusion were positively correlated with post-LT creatinine peak (MCP-1, p = 0.00023, R = 0.58; TNF-α, p = 0.0004, R = 0.57). In conclusion, machine perfusion remains a valuable strategy for rescuing ECD liver grafts. In the current era—characterized by increasing use of machine-perfused grafts and extended criteria donors—recipients demonstrate postoperative renal outcomes comparable to those receiving conventionally preserved grafts.

Polyfurfuryl alcohol (PFA) is one of the most intriguing polymers because, despite its easy polymerization in acid environment, its molecular structure is definitely not obvious. Many studies have been performed in recent decades, and every time, surprising aspects came out. With the present study, we aim to take advantage of all of the findings of previous investigations and exploit them for the interpretation of the completely cured PFA spectra registered with three of the most powerful techniques for the characterization of solid, insoluble polymers: Solid-State 13C-NMR, Attenuated Total Reflectance (ATR), Fourier Transform Infrared (FTIR) spectroscopy, and UV-resonant Raman spectroscopy at different excitation wavelengths, using both an UV laser source and UV synchrotron radiation. In addition, the foreseen structures were modeled and the corresponding 13C-NMR and FTIR spectra were simulated with first-principles and semi-empiric methods to evaluate their matching with experimental ones. Thanks to this multi-technique approach, based on complementary analytical tools and computational support, it was possible to conclude that, in addition to the major linear unconjugated polymerization, the PFA structure consists of Diels-Alder rearrangements occurring after the opening of some furanic units, while the terminal moieties of the chain involves γ-lactone arrangements. The occurrence of head-head methylene ether bridges and free hydroxyl groups (from unreacted furfuryl alcohol, FA, or terminal chains) could be excluded, while the conjugated systems could be considered rather limited.

Background Mental health problems among young people are of growing concern globally. UK adolescent mental health services are increasingly restricted to those with the most severe needs. Many young people turn to the internet for advice and support, but little is known about the effectiveness, and potential harms, of online support. Kooth is a widely-used, anonymised and moderated online platform offering access to professional and peer support. This pilot evaluation sought to assess changes in the wellbeing and mental health of Kooth users, and changes in their use of formal services, over one month. We explored how community aspects of the site were used, and we considered the economic implications for commissioners making Kooth available to young people. Methods We surveyed young people when they first accessed Kooth and again one month later (n = 302). Respondents completed measures of mental health and wellbeing, including family relationships and pandemic-related anxiety, and reported on their use of services and, at follow-up, their perceptions of whether and how they had benefitted. We carried out qualitative interviews with ten participants, exploring perceptions of the Kooth community and its impact. Results We found improvements across nearly all measures, including reductions in psychological distress, suicidal ideation and loneliness. Subsample analyses suggested similar benefits for those who used only the community/peer parts of Kooth as for those who engaged with Kooth’s counsellors. Participants reported learning from peers’ suggestions and experiences, described as different from the advice given by professionals. Helping others gave users a sense of purpose; participants learnt self-help strategies and became more confident in social interactions. Service use and opinion data suggested Kooth experiences may help users make more appropriate and effective use of formal services. Conclusion This pilot evaluation suggests that Kooth is likely to be a cost-effective way of providing preventative support to young people with concerns about their mental health, with possible benefits across a range of domains which could be investigated in a future controlled trial.

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.

One of the keys towards sustainable policies and advanced air quality monitoring is the detailed assessment of all factors that affect the surface concentrations of greenhouse gases (GHGs) and aerosols. While the development of new atmospheric tracers can pinpoint emission sources, the atmosphere itself plays a relevant role even at local scales: Its dynamics can increase, or reduce, surface concentrations of pollutants harmful to human health and the environment. PBL (planetary boundary layer), or peplospheric, variability is known to affect such concentrations. In this study, an unprecedented characterization of PBL cycles and patterns is performed at the WMO/GAW regional coastal site of Lamezia Terme (code: LMT) in Calabria, Southern Italy, in conjunction with the analysis of key GHGs and aerosols. The analysis, accounting for five months of 2024 data, indicates that peplospheric variability and wind regimes influence the concentrations of key GHGs and aerosols. In particular, PBLH (PBL height) patterns have been tested to further influence the surface concentrations of carbon monoxide (CO), black carbon (BC), and particulate matter (PM). This research introduces four distinct wind regimes at LMT: breeze, not complete breeze, eastern synoptic, and western synoptic, each with its peculiar influences on the local transport of gases and aerosols. This research demonstrates that peplosphere monitoring needs to be considered when ensuring optimal air quality in urban and rural areas.