Wave energy converters deployed in farms can experience intense hydrodynamic interactions due to the scattered and radiated waves on the free surface, making farm modeling challenging in realistic sea states. This study introduces a spatial-temporal surrogate model based on a transformer encoder architecture to predict the motion of multiple interacting wave energy converters in various sea states. The framework leverages experimental data from the SWELL dataset, predicting array responses in a previously unseen layout, i.e., a farm configuration, not available during the model's training phase. The model embeds incident wave time series together with device coordinates into a unified spatial-temporal representation. Self-attention then jointly captures the temporal evolution of motion dynamics and inter-device spatial dependencies. Across three irregular sea states, the model predicts device responses with high accuracy, showing close agreement with experimental measurements. These findings provide an initial proof-of-concept, highlighting the potential of an attention-based spatial-temporal surrogate model as a building block for predicting the dynamics of several interacting wave energy converters in previously unseen array configurations.
Organ-on-chip (OoC) platforms are increasingly adopted for predictive in vitro testing. However, most remain limited by soft-lithography-derived 2.5D microfluidic architectures and nonphysiological rigid materials, or bioprinting approaches that require complex and failure-prone post-fabrication assembly. Here, we present a versatile approach that integrates tomographic volumetric additive manufacturing (TVAM) directly within preassembled microfluidic chips, enabling rapid, contactless fabrication of freeform 3D OoCs. Leveraging our open-source optical simulation framework, Dr.TVAM, we perform TVAM in custom-designed chips, eliminating post-printing manual assembly steps that commonly lead to leakage, contamination, and poor reproducibility. This strategy, termed TVAM-in-a-chip, supports the generation of diverse 3D channel architectures in multiple biocompatible photoresins spanning a wide range of chemistries and mechanical properties, including cell-laden formulations. We demonstrate multi-channel designs, compatibility with confocal imaging, and dynamic culture of epithelial and endothelial models. Overall, TVAM-in-a-chip overcomes key limitations of current OoC technologies and paves the way for a new generation of scalable, biomimetic 3D platforms for advanced in vitro modeling.
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This paper develops a constraint based hypothesis from established physics and published experimental measurements. De Broglie's relation predicts that electronic quantum effects become part of the physical regime when functional structures approach nanometer dimensions. The semiconductor industry provides a test case, as reliable classical switching at few nanometer scales requires architectural intervention biological systems lack. Microtubule tryptophan networks operate at 1 to 2 nm spacing and exhibit energy migration with a 6.6 nm diffusion length that classical Förster theory cannot account for, alongside superradiant behavior across over 105 transition dipoles with robustness that increases with system size. Photosynthesis provides biological precedent for organizing quantum dynamics through molecular architecture and energy flow. These premises support the case that the brain operates with quantum effects at the microtubule scale. The functional question is whether these processes matter for higher order neural function. Six pharmacological and cross species constraints address this question. Anesthetics reduce microtubule energy migration by 12 to 15 percent, and anesthetic potency tracks collective tubulin oscillation changes across chemically diverse compounds with R2 = 0.999. Volatile anesthetics suppress organized responsiveness across eukaryotic organisms without nervous systems, while microtubule stabilizing drugs delay anesthetic induced unconsciousness with a large effect size. Open energy pumped architecture addresses physiological viability, and psychedelic phenethylamines that enhance microtubule polymerization provide an opposite pharmacological test. Together, these constraints support the hypothesis that microtubule tryptophan networks and collective tubulin dynamics participate in the maintenance of higher order neural function and conscious states.
Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive X-linked neuromuscular disorder for which disease-modifying therapies are under investigation. SBMA Functional Rating Scale (SBMAFRS), its subscale (mSBMAFRS), and Six-Minute Walk Test (6MWT) are commonly used trial endpoints, but thresholds for clinically meaningful change remain undefined. Minimal clinically important difference (MCID) estimates are needed to interpret longitudinal outcomes and inform trial design. We retrospectively analysed ambulatory, genetically confirmed SBMA patients. Eighty consecutive visit pairs from 44 patients included concurrent Global Rating of Change (GRC) assessments, and 47 visit pairs from 30 patients included concurrent 6MWT data. At follow-up, patients rated overall change since the previous visit on a 3‑level GRC (unchanged, slightly worse, much worse). Anchor-based MCIDs for worsening were derived from differences in change scores between GRC categories and compared with distribution-based estimates (0.5 baseline standard deviation). Sensitivity analyses and Monte Carlo resampling assessed robustness. Anchor‑based MCID estimates for worsening were -1.13 and -1.46 points for the SBMAFRS total score, -0.53 and -1.09 points for the mSBMAFRS, and -34.5 and -32.4 m for the 6MWT. The mSBMAFRS showed the most consistent gradient across GRC categories and remained significant in sensitivity analyses. Distribution‑based MCIDs (2.30, 1.42 points and 61.85 m, respectively) were consistently larger than anchor‑based values. Age, disease duration, and CAG repeat length did not predict perceived worsening. These data provide the first patient‑anchored MCID estimates for SBMA outcome measures, support use of the mSBMAFRS, and offer thresholds for responder definitions and sample-size calculations in future SBMA trials.
This study aimed at identifying neuropsychological sub-phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks. We used individual task-/item-level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non-demented ALS to derive neuropsychological sub-phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo-spatial measures. The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub-phenotypes were identified: dysexecutive MCI-single- and multiple-domain (dMCI-sd: 63%; dMCI-md: 24%, respectively); non-dysexecutive MCI-single- and multiple-domain (ndMCI-sd: 12%; ndMCI-md: 1%, respectively). MBI was classified as follows: apathetic MBI-single- and multiple-domain (aMBI-sd: 40%; aMBI-md: 20%, respectively); apathetic-disinihibited/perseverative MBI-multiple domain (ad/pMBI-md: 21%); disinihibited/perseverative MBI-multiple domain (d/pMBI-md: 7%); psychotic MBI-single- and multiple-domain (psyMBI-sd: 2%; psyMBI-md: 3%, respectively); unclassifiable MBI-multiple domain (uMBI-md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI). This study delivers a provisional, ECAS-based classification for the neuropsychological sub-phenotyping of non-demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.
Oral finasteride is a cornerstone in the treatment of male androgenetic alopecia (AGA), yet concerns regarding systemic adverse events often limit patient adherence. Topical finasteride 0.25% has emerged as a promising alternative to minimize systemic exposure while maintaining local efficacy. To evaluate the effectiveness and safety of topical finasteride 0.25% as monotherapy in male patients with AGA over 52 weeks in a real-world setting. A retrospective observational study was conducted at the Dermatology Unit of the University of Turin. Medical records of male patients treated with topical finasteride 0.25% monotherapy between April 2022 and November 2025 were reviewed. 123 adult men with AGA were included. Patients were evaluated at baseline (T0) and after 52 weeks (T52) using standardized clinical photography and videodermoscopy (VIDIX system), with paired intra-patient comparisons. Efficacy was assessed via trichoscopic changes in Total Hair Number (THN). Secondary outcomes included hair shaft thickness (HST), terminal-to-vellus hair ratio, Physician Global Assessment (PGA), patient-reported outcomes, and safety. A total of 123 male patients (mean age 32.4 ± 8.1 years) were included. At 52 weeks, significant increases in THN were observed in both the vertex (+21.8 hairs/cm2; P < 0.001) and temporal regions (+29.4 hairs/cm2; P < 0.001). Significant improvements were also noted in HST and the terminal-to-vellus ratio. The treatment was well tolerated; 7.3% of patients reported mild, transient local irritation. No systemic adverse events related to sexual function or mood were reported. Topical finasteride 0.25% monotherapy demonstrates sustained clinical efficacy and a favorable safety profile after one year of treatment. These findings support its use as a viable therapeutic option for male AGA, particularly for patients reluctant to undergo systemic therapy.
We report an experimental investigation of the reactions n[over ¯]p→2π^{+}π^{-}, n[over ¯]p→2π^{+}π^{-}π^{0}, and n[over ¯]p→2π^{+}π^{-}2π^{0} using (10.087±0.044)×10^{9}  J/ψ events collected with the BESIII detector at the BEPCII storage ring. The antineutron (n[over ¯]) is produced in the decay J/ψ→pπ^{-}n[over ¯] with studied momentum from 200 to 1174  MeV/c, while the target proton originates from the hydrogen nuclei in the cooling oil of the beam pipe. This novel method pioneers the study of n[over ¯]-nucleon interactions at an e^{+}e^{-} collider, providing the first experimental data for n[over ¯] momenta exceeding 800  MeV/c.
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Functional assessment in wheelchair basketball (WB) has three evaluation stages: analysis of isolated functions, combined functional measures, and the observation of volume of action (VoA) in a sporting context. Sport class allocation relies on VoA assessed in controlled conditions (VoA-capacity), which corresponds to combined functional measures, and during game observation (VoA-performance). However, the contribution of each assessment phase to sport class allocation remains insufficiently understood. This study examines how trunk and hip muscle strength influences VoA-capacity and evaluates the extent to which VoA-capacity is associated with sport class. Additionally, it compares trunk muscle strength and VoA-capacity across sport classes to characterize functional differences between groups. A cross-sectional observational study was conducted with 40 officially classified WB players (sport classes 1.0-4.5). Trunk and hip muscle strength were assessed using the Manual Muscle Test (MMT). VoA-capacity was calculated as the sum of maximal trunk reaches in six directions (flexion, extension, rotation for both sides and lateral flexion for both sides) using an Inertial Measurement Unit (IMU) positioned at C7 (seventh cervical vertebra). Multiple linear regression, ordinal regression, Kruskal-Wallis, and Dunn's post-hoc tests were applied. Total Trunk-Hip muscle strength significantly predicted VoA-capacity (p < 0.001), explaining 80% of its variance (R 2 = 0.80). When analyzed separately, both trunk strength (p < 0.001) and hip strength (p = 0.006,) were significantly associated of VoA-capacity. VoA-capacity was a significant predictor of sport class (p < 0.001). Significant differences were found between sport classes for VoA-capacity (p < 0.001) and for total Trunk-Hip muscle strength (p < 0.001), with post-hoc comparisons showing the largest contrasts between lower (1.0-2.0) and higher (4.0-4.5) sport classes. Trunk and hip muscle strength showed associations with VoA capacity, suggesting their relevance for understanding players' ability to perform dynamic seated movements. VoA-capacity, was also associated with sport class allocation. Although muscle strength is not a classification criterion in WB, profiling players' muscular strength may offer complementary insights in complex classification scenarios. These findings provide preliminary functional evidence of WB classification and support future investigations integrating VoA-performance to refine assessment models.
Cognitive reserve (CR) has been proposed as a key factor explaining inter-individual variability in cognitive performance despite comparable neuropathology. However, its role across the Alzheimer's disease (AD) continuum remains unclear. This study investigates stage-dependent effects of CR on the relationship between memory performance and brain structural network integrity across healthy subjects (HS), individuals with subjective cognitive decline (SCD), and patients with amnestic mild cognitive impairment (a-MCI), and AD dementia. A total of 209 participants underwent a comprehensive neuropsychological assessment and 3T MRI. Source-based morphometry identified three grey matter structural covariance networks, involving orbitofrontal-temporal-insular regions (OTIN), precuneus-posterior cingulate cortex (PreCiN), and cingulate-hippocampal regions (CHiN). A composite memory score was derived using factor analysis. Regression and moderation models examined the predictive and moderating effects of CR (operationalized as years of education) and network integrity on cognitive performance within each group. OTIN and PreCiN showed progressive structural vulnerability along the AD continuum, whereas CHiN showed no significant between-group differences. Across the sample, OTIN and PreCiN integrity significantly predicted cognitive performance. In HS, CR was positively associated with memory performance independently of structural network integrity, suggesting an additive protective role of cognitive reserve in healthy aging. In the SCD group, CR was not directly associated with memory, and only limited effects emerged, indicating early alterations in reserve-related processes. In a-MCI patients, the significant interaction between CR and OTIN integrity suggested patterns consistent with compensatory mechanisms, with higher reserve supporting memory despite structural decline. In AD patients, CR and its interaction with structural networks no longer predicted cognitive outcomes, suggesting a possible exhaustion of reserve capacity. These findings support a stage-dependent model of CR, characterized by an additive protective role in healthy aging, patterns consistent with compensatory recruitment in early cognitive decline, and a possible loss of reserve effectiveness beyond a critical neuropathological threshold. Distinct network vulnerabilities and stage-specific CR effects highlight potential windows for reserve-enhancing interventions across the AD continuum.
Reduction mammaplasty for hypertrophic and ptotic breasts becomes particularly challenging when significant nipple-areola complex (NAC) elevation is required while maintaining reliable perfusion and a natural breast shape. Traditional techniques rely on dermoglandular pedicles to safely transpose the NAC, particularly when elevation exceeds 10-12 cm. In our approach, the focus shifts from the sternal notch-nipple distance to the NAC-inframammary fold (IMF) distance, which-when exceeding 15 cm-more accurately defines the true degree of ptosis and secondarily determines the increased notch-nipple distance. In such cases, the breast assumes an ellipsoid "bell-shaped" morphology that no longer requires a pedicle-based NAC transposition. This procedure allows preservation of the NAC-glandular unit as a single anatomical block and restoration of a stable hemispheric contour. To describe the preservation breast reduction (PBR), a reduction mammaplasty technique based on preservation of NAC-glandular anatomical continuity without dermoglandular pedicle dissection. The technique is based on two orthogonal geometric vectors that shorten the NAC-IMF distance, which represent the primary anatomical determinant of breast hypertrophy and ptosis. The controlled reduction of the vertical breast dimension induces a series of consequential morphological changes, including glandular volume reduction, redefinition of the breast base, restoration of projection, and reconstruction of stable hemispheric breast contour. A retrospective study was conducted on 45 consecutive patients (2018-2023) presenting with moderate-to-severe hypertrophy and Regnault grade II-III ptosis. The surgical approach is based on two orthogonal vectors: 1. A progressive vertical dermal plication along the breast meridian, allowing NAC elevation to the Pitanguy point A, without pedicle transposition; 2. en bloc resection of the inferior glandular quadrants along a horizontal plane located 8-10 cm below the new NAC, redefining the IMF position and breast base. When required, additional glandular reshaping was achieved through selective triangular resection beneath the areola to reduce base width and enhance projection. Complications and patient satisfaction (4-point Likert scale, ≥12-month follow-up) were recorded. The NAC-IMF distance was reduced from a mean of 17.5 cm to 8-10 cm and remained stable at follow-up. Complications included one hematoma (2.2%) and three cases (6.6%) of localized, self-limited nodular adiponecrosis (~ 2 cm) at the base of the breast along the vertical plication line, with no impact on final outcomes. No cases of NAC necrosis were observed. Patient satisfaction was 91%. The PBR technique preserves the NAC-glandular unit through maintenance of anatomical continuity, allows significant NAC elevation without dermoglandular pedicle dissection, and achieves consistent geometric rebalancing of the breast. The technique eliminates the need to create a dermoglandular pedicle for preservation of nipple-areola complex (NAC) vascularity. In this preliminary series, it demonstrated reliable vascular safety inferred from clinical outcomes and stable morphological results in selected patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
The use of medial pivot inserts in revision total knee arthroplasty (rTKA) remains limited, with more constrained designs often preferred. This study aimed to evaluate clinical, radiographic and complication outcomes of rTKA performed with a medial pivot insert for aseptic revision indications in selected patients with preserved ligamentous stability. A retrospective analysis was conducted on a prospectively maintained institutional registry. Sixty-three consecutive patients who underwent first-time rTKA with a medial pivot revision system between 2017 and 2023 were included. Indications for revision included aseptic loosening, instability, polyethylene wear and arthrofibrosis, in the presence of mild-to-moderate bone defects (Anderson Orthopaedic Research Institute [AORI] Type I or IIa) and preserved collateral ligament integrity. Clinical outcomes were assessed using the Knee Society Score (KSS), functional KSS (fKSS) and Western Ontario and McMaster Universities Osteoarthritis Index score. Radiographic evaluation included coronal and sagittal alignment parameters and the presence of radiolucent lines (RLLs). A p value < 0.05 was considered statistically significant. Minimum follow-up was 2 years. Significant improvements were observed in all clinical outcome measures and knee range of motion (ROM) from preoperative assessment to final follow-up (all p < 0.001). No significant differences in clinical outcomes were detected between patients with AORI Type I and Type IIa bone defects. Radiographic analysis demonstrated satisfactory restoration of coronal and sagittal alignment, with no evidence of component migration or loosening at final follow-up. RLLs were observed in three cases and were non-progressive. Two patients (3.2%) required reoperation for periprosthetic joint infection (PJI); no revisions for instability or mechanical failure were recorded. rTKA performed with a medial pivot insert for aseptic failure resulted in favourable clinical and radiographic outcomes with a low complication rate at short- to mid-term follow-up. These findings suggest that medial pivot designs may represent a viable option in carefully selected revision cases with mild-to-moderate bone loss and preserved ligamentous stability. Level IV.
Unplanned postoperative reintubation is associated with increased morbidity, mortality, and healthcare use. Unplanned postoperative reintubation represents a heterogeneous clinical endpoint arising from distinct and often overlapping etiopathogenetic mechanisms, including airway compromise, respiratory insufficiency, cardiac dysfunction, neurological impairment and acute organ failure. Early reintubation need is more commonly associated with residual anaesthetic/neuromuscular blocker effects and airway-related factors, whereas intermediate and late restoration of invasive ventilation frequently reflects evolving respiratory, cardiac or multiorgan complications. Risk prediction models and advanced monitoring tools may support early identification of vulnerable patients but are limited by heterogeneous and variable predictive performance. Consequently, preventive strategies are most effective when tailored to specific phenotypes. A phenotype-based approach enables targeted surveillance and interventions, highlighting unplanned postoperative reintubation as a marker of perioperative vulnerability rather than a uniform pathology.
Myocardial infarction remains a global health challenge, necessitating advanced therapeutic strategies to address both acute injury and chronic ventricular remodeling. This study presents an innovative tri-layered bioartificial patch engineered to modulate degradation kinetics and drug release for prolonged cardiac regeneration. By integrating a slower-degrading polycaprolactone (PCL) and gelatine-based inner layer into a microstructured polylactic-co-glycolic acid (PLGA) and gelatine architecture, we developed a system with a highly controlled biphasic degradation profile. Hydrolytic degradation tests revealed that while the external PLGA-based layers undergo bulk degradation and complete dissolution by 60 to 90 days, the internal PCL-based membrane successfully retains its structural integrity and biomimetic micropatterning for up to 90 days. This structural stability also enabled a tailored dual-release of bioactive molecules: a rapid 50-70% burst release of the cardioprotective agent adenosine within the first 5 hours to target acute reperfusion injury, paired with a restricted about 6% release of the antifibrotic drug pirfenidone over 7 days, effectively preserving it for the later stages of tissue healing. Furthermore, the incorporation of the Fmoc-FF peptide conferred a stable electrical conductivity of 4.6 µS cm-1 at 1 Hz without compromising the matrix structure. In vitro biological assessments confirmed excellent cytocompatibility across all layers, supporting an H9c2 cardiomyoblast viability of roughly 90% after 72 hours. Human iPSC-CMs cultured on the patch maintained spontaneous and synchronous beating activity. Moreover, the patch loaded with PIR exhibited significant antifibrotic activity, confirming that the released drug remained biologically active. Ultimately, this multi-layered design provides a promising and functionally active platform for counteracting pathological remodeling and restoring myocardial tissue.
The aim of this study was to evaluate the budget impact of introducing the subcutaneous (SC) form of ocrelizumab for patients with relapsing forms of multiple sclerosis (RMS) with high disease activity (HA) despite previous treatment or with rapidly evolving severe (RES) disease in Italy from the hospital perspective. A 3-year dynamic budget impact model with a Markov structure was developed de novo to simulate patient transitions across Expanded Disability Status Scale-defined health states. The current scenario (without ocrelizumab SC) was compared with an alternative scenario reflecting expected ocrelizumab SC uptake. Number of eligible patients reflected Italian population and projected market shares. Efficacy inputs were obtained from published literature, with adherence and persistence sourced from Italian real-world data. Unit costs-including drug administration, monitoring, adverse events, disease management, and relapse-were collected from Italian sources. Drug acquisition costs were considered in a scenario analysis. Parameter uncertainty was explored through deterministic sensitivity and scenario analyses. Over 3 years, 22,128 patients were eligible, of whom 5389 were assumed to receive ocrelizumab SC. Ocrelizumab SC introduction would generate cumulative savings of about €2.0 million, mainly from reduced administration and monitoring costs, with additional savings from relapse and disease management expenditures. When drug acquisition costs were included, total savings rose to roughly €7.1 million. Sensitivity analyses confirmed the robustness of these findings. Ocrelizumab SC may be a cost-saving and resource-efficient option for HA/RES RMS management in Italy. By reducing administration time while maintaining the established clinical profile of the intravenous (IV) formulation of ocrelizumab, its adoption can enhance hospital efficiency and deliver meaningful budgetary savings.
Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease of the upper airways, frequently characterized by recurrence and impaired quality of life. Persistent inflammation and bacterial biofilms contribute to disease chronicity. Topical plant-derived therapies may offer a preventive strategy in long-term CRS management. This study evaluated the effectiveness of a Pistacia lentiscus-based nasal medical device in reducing the impact of CRS recurrence on patients' daily life. In this retrospective, observational, single- center case-control study, 100 adult patients with chronic rhinosinusitis (CRS) and recurrent disease were identified and included from clinical records. Patients were stratified according to prior exposure to nasal drops containing ultra-fractionated Pistacia lentiscus oil in addition to isotonic saline nasal irrigation, or to isotonic saline nasal irrigation alone, according to routine clinical practice. All patients had undergone a 12-month follow-up regimen with assessments available at baseline, 30 days, and 12 months. The primary outcome was symptom severity measured using the Sino-Nasal Outcome Test (SNOT-22). Secondary outcomes included nasal cytology parameters, biofilm presence, nasal discharge, bacterial elements, supranuclear stria, and ciliary motility. Of the 100 identified subjects, 92 were included in the final analysis due to loss to follow-up. In the exposed group, SNOT-22 scores showed a 40.6% reduction after the first month, compared with a 7.8% reduction observed in the control group (p < 0.001). Only patients exposed to Pistacia lentiscus oil demonstrated statistically significant reductions over time in nasal discharge (p < 0.005), biofilm presence (p < 0.005), and bacterial elements (p < 0.05), while no significant changes were observed in the control group for these parameters. Ciliary motility remained unchanged in both groups across the study period. Overall, within the limits of this retrospective case-control design, patients exposed to Pistacia lentiscus oil in addition to standard saline irrigation showed greater improvement in patient-reported symptoms and selected cytological markers compared with patients treated with saline irrigation alone.
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Biomass offers a low-cost and sustainable carbon source. Yet, conventional pyrolytic routes remain energy intensive and require harsh processing conditions. Laser-induced carbonization provides a rapid, efficient and green alternative for the conversion of biomass into carbon structures. Building on the growing demand for sustainable alternatives to petroleum-derived polymers in laser writing, we investigate laser-induced carbon (LIC) produced from cellulose acetate (CA) membranes, a widely available biopolymer, via CO2 laser irradiation. The flame-retardant bis[2-(methacryloyloxy)ethyl] phosphate (BMEP) enables localized carbonization, overcoming CA's poor thermal stability. By tuning laser parameters, namely the defocus distance and the number of passes, we selectively obtain amorphous carbon, activated carbon (AC), graphene oxide (GO), and laser-induced graphene (LIG). Among these, AC fabricated through a double-pass process at a defocus distance of 7.5 mm achieves outstanding electrochemical performance as a microsupercapacitor (μSC) electrode, delivering an areal capacitance of up to 63 mF cm-2, an energy density of 3.3 µWh cm-2, and a power density of 0.42 mW cm-2. These results outperform those of petroleum-based polymer-derived LIG while utilizing a potentially upcycled precursor. This work expands the scope of LIG precursors and offers a versatile platform for engineering sustainable carbon-based electrodes.
The management of non-metastatic non-small-cell lung cancer (NSCLC) has become increasingly complex with the integration of multimodality strategies and biomarker-driven approaches. Several clinically relevant areas remain insufficiently defined by current evidence and international guidelines. We conducted an international multidisciplinary consensus to address major areas of uncertainty in real-world practice. A modified Delphi process was conducted during a 3-day in-person meeting in Barcelona, Spain (3-5 September 2025). Eighty-nine thoracic oncology experts independently rated predefined clinical statements developed by working groups and refined by a steering committee. Agreement was assessed using a 9-point Likert scale. Consensus was predefined as ≥75% of ratings in the 7-9 range; rejection as ≥75% in the 1-3 range. Ninety-six statements were evaluated. Consensus was achieved for 62 statements (64%), 31 (32%) remained without consensus, and 3 (3%) were rejected. Consensus supported routine FDG PET-CT for staging, histologic confirmation of suspicious mediastinal nodes, reflex PD-L1 testing and DNA-based next-generation sequencing at diagnosis, standardized post-neoadjuvant pathologic assessment, and sublobar resection with systematic nodal evaluation for selected peripheral node-negative tumors ≤2 cm. Consolidation durvalumab after definitive chemoradiotherapy was supported irrespective of PD-L1 expression in unresectable stage II-III disease. Persistent areas of controversy included brain MRI in stage I disease, mediastinal restaging after induction therapy, routine RNA-based testing, and the use of circulating tumor DNA/minimal residual disease to guide perioperative decisions. This international consensus provides structured expert guidance in areas of uncertainty in non-metastatic NSCLC and highlights priorities for future prospective research.