Journals
2026 EN
Bettinelli Andrea · Marturano Francesca · Pirrone Giovanni
+9 more
Abstract Background Radiomics involves extracting and analyzing quantitative imaging features to support medical decision‐making, particularly in radiology and oncology. When applied to radiotherapy dose distributions, this approach, referred to as ‘dosiomics’, aims to identify the spatial dose patterns associated with treatment outcomes. However, software discrepancies in feature extraction may hinder reproducibility and limit the clinical adoption of radiomic/dosiomic models. Purpose This study presents the first comprehensive evaluation of software agreement and feature reproducibility across tools in the field of dosiomics, assessing seven feature‐extraction tools. The evaluation focused on the impact of built‐in image pre‐processing steps (e.g., interpolation and discretization), feature‐extraction configurations (i.e., aggregation methods), and the morphological characteristics of the regions of interest (ROIs), such as the presence of holes or disconnected components. Materials and methods Five open‐source programs (MIRP, S‐IBEX, RaCaT, SERA, and PyRadiomics) and two proprietary tools (SPAARC and RadiomiCRO) were evaluated. The Image Biomarker Standardization Initiative (IBSI) digital phantom was used to preliminarily assess software IBSI‐compliance and to identify and exclude features with inconsistent implementation from subsequent analyses. Dosiomic features were then extracted from a digital dataset comprising eight Intensity Modulated Radiation Therapy (IMRT) dose distributions emulating a head and neck radiotherapy plan (available in both isotropic and anisotropic formats) and 10 ROIs, following a systematic feature extraction framework. The effects of pre‐processing parameters, feature‐extraction configurations, and ROI morphological characteristics were analyzed systematically. The evaluation metrics included the percentage of matching features across software to the third significant digit, the Agreement metric, and the coefficient of variation (CV) to quantify both software performance and dosiomic feature variability across them. Results The preliminary IBSI‐compliance evaluation showed that MIRP, S‐IBEX, RaCaT, and SERA achieved over 94% matching features with IBSI benchmark values. In contrast, SPAARC, RadiomiCRO, and PyRadiomics demonstrated lower compliance due to non‐computable features. On dose distributions, all tools exhibited high match percentages (>77%) for the isotropic dataset, which did not require software‐specific interpolation. However, discrepancies increased significantly with program‐specific interpolation for the anisotropic dose dataset, with match rates dropping to 14%. Agreement across software was consistently high for the isotropic dataset but notably lower for the anisotropic dataset. This trend was less evident when looking at the CV, which showed only a mild increase for the anisotropic format. Fixed bin size (FBS) discretization displayed lower Agreement and higher CV values, particularly in the cumulative intensity‐volume histogram (IVH) feature family. High CV values were predominantly observed for some feature family‐ROI combinations, including GLRLM, GLSZM, and NGLDM computed using 2.5D/3D aggregation methods. Additionally, we observed that some binary masks were incorrectly generated (e.g., without holes) when using the DICOM format, therefore, we relied on NRRD input files whenever possible, resulting in feature reproducibility remaining unaffected by this aspect. Conclusion The findings of this study indicate that, when properly configured, the tools show good overall agreement, with variability limited to specific features and pre‐processing choices. While variations in program‐specific resampling and FBS discretization implementation are present, their overall impact on dosiomic feature reproducibility remains minimal.
Journals
2026 EN
Mebarek Saida · Jacob Killian · Pierro Carmela Ilaria
+2 more
Synthetic vaccines represent a promising avenue in cancer immunotherapy by promoting targeted immune responses. Liposomal technologies have further advanced synthetic vaccinology by enabling the efficient delivery of tumor‐associated carbohydrate antigens. Despite this progress, the toxicity and reproducibility of such platforms remain underexplored. In this preliminary study, we synthesized a series of neoglycolipids bearing the Thomsen–Nouveau (Tn) antigen using bio‐orthogonal thiol–ene click chemistry. Here we present the results obtained using a set of neoglycolipids that were evaluated for their ability to self‐assemble into liposomal vesicles and for in vitro cytotoxicity. The resulting neoglycolipids exhibited no detectable cytotoxicity and formed stable liposomal structures when formulated with palmitic acid and 1‐palmitoyl‐2‐oleoyl‐ sn ‐glycero‐3‐phosphocholine via a freeze–thaw/extrusion process. This early‐stage work presents a proof of concept for a tunable, liposomal‐based synthetic vaccine platform.
Journals
2026 EN
Patamia Vincenzo · Saccullo Erika · Larocca Michele
+5 more
This study introduces a new class of α‐helical antimicrobial peptides designed to combat multidrug‐resistant bacteria. The peptides were created using a structure‐based approach guided by the main mechanical forces (MMFs) methodology, which promotes stable helical conformations by considering chemical interactions between amino acid side chains. Key features of the design of these peptides include: (1) amphipathic nature: hydrophobic and cationic residues are strategically positioned on opposite sides of the helix to disrupt bacterial membranes and (2) MMFs approach: enables precise control over the peptide's 3D structure through dihedral angle calculation. The peptides exhibited antimicrobial activity against various bacterial strains, including both Gram‐positive and Gram‐negative species, as well as a multidrug‐resistant pathogen. This effect was particularly enhanced when coadministered with allomaltol, a chelating agent capable of sequestering essential metals (such as iron), thereby disrupting bacterial metabolism and providing a secondary mechanism of action. This work validates the MMFs methodology as an accurate prediction tool for peptide secondary structure, reproducing NMR‐derived helical features of the HT2 peptide and enabling rational design of new analogs. Moreover, the covalent introduction of a chelating group markedly improved antimicrobial potency (MIC 18.75 μM vs. 300 μM), confirming the functional synergy between amphipathic helicity and metal‐ion sequestration.
Journals
2026 EN
Harris Emily M. · Montcrieff Caitlin · O'Farrell Candelaria
+4 more
ABSTRACT Background Avatrombopag, a second‐generation thrombopoietin receptor agonist (TPO‐RA), is approved for treatment of chronic immune thrombocytopenia (ITP) in adults and has been studied in a Phase 3 trial in pediatric ITP. The reported efficacy, oral administration, safety profile, and lack of dietary restrictions are appealing treatment characteristics for children. Data on real‐world use in children are limited. Methods This multicenter cohort study included patients diagnosed with ITP at age < 21 years treated with avatrombopag. Clinical features were collected from electronic medical records. Overall platelet response was defined as platelet count ≥ 30 × 10 9 /L and doubling from baseline. Results A total of 58 pediatric patients were treated with avatrombopag. Median time from diagnosis to treatment initiation was 4.6 years, with a median of 3 (range 0–11) prior treatments. Overall platelet response was 89.3% with similar response in primary and secondary ITP. Most patients achieved a response on the initial dose. Response rates did not differ by age at treatment initiation. Median time to platelet response was 13.5 days. High‐grade bleeding scores were lower after initiation of treatment. Most patients (62%) switched from another TPO‐RA to avatrombopag. Response to prior TPO‐RA was associated with higher likelihood of response to avatrombopag (OR 15.00, 95% CI 1.824–187.7, p = 0.017). Of 12 patients with no response to prior TPO‐RA, 8 responded to avatrombopag. Adverse effects were rare. Conclusions In this real‐world study, avatrombopag was highly effective at both improving platelet counts and reducing bleeding in children with ITP, even in patients with secondary ITP or who had failed other TPO‐RAs.
Journals
2026 EN
Mollan Katie R. · Pence Brian W. · Westreich Daniel
+15 more
ABSTRACT Background Dolutegravir (DTG)‐based antiretroviral treatment (ART) is broadly prescribed to treat HIV. Effective family planning methods are important for the health of women with HIV (WWH) and their families. For WWH on DTG‐based ART, we compared the typical‐use effectiveness of levonorgestrel (LNG) implant and Depot‐Medroxyprogesterone‐Acetate (DMPA) injectable, two commonly used contraceptive methods. Methods We analyzed a prospective cohort study conducted in Lilongwe, Malawi from 2017 to 2021. Eligible participants were WWH ages 18–40 years who desired not to get pregnant for ≥ 4 years and chose to initiate either LNG implant or provider‐administered DMPA injectable 0–28 days before study enrollment. Incident pregnancies were measured by urine pregnancy testing and pregnancy diagnoses at study visits every 24 weeks. The parametric g‐formula was applied to estimate the contraceptive effectiveness of LNG implant compared to provider‐administered DMPA injectable, assuming the entire study cohort had used DTG‐based ART throughout. Contraceptive effectiveness was measured during typical, continued use. Results Overall, 1359 eligible participants were enrolled. At enrollment, the median age was 30 (IQR: 26, 34), and 63% were breastfeeding. With DTG‐based ART, the estimated 96‐week pregnancy risk was 0.5% with LNG implant and 8.9% with DMPA injectable. The estimated 192‐week pregnancy risk was 2.6% with LNG implant and 16.1% with DMPA injectable (risk difference: −13.5 percentage points, 95% CI: −20.1%, −7.5%). Conclusions For WWH on DTG‐based ART who are seeking reversible contraception, the LNG implant is an effective contraceptive and has substantially higher effectiveness than provider‐administered DMPA injectables.
Journals
2026 EN
Borges Ianca Oliveira · Shashiki André Tetsuo · Satiro Jhonatan Sales
+7 more
ABSTRACT The increasing demand for sustainable materials has led to the development of bio‐based polymer composites reinforced with natural fibers. In this study, sisal fibers were surface‐modified using alkaline treatment (NaOH) and corona discharge and incorporated into castor oil–derived polyurethane matrices. The physicochemical, morphological, mechanical, thermal, and surface properties of the resulting composites were investigated. NaOH treatment significantly improved fiber morphology and reduced lignin and extractive content, resulting in a 52% increase in tensile strength (6.34 MPa) and a 66% increase in Young's modulus (24.97 MPa) compared to the control. Corona‐treated composites exhibited the lowest water absorption (0.43%) and enhanced interfacial compatibility, confirmed via SEM, AFM, and Raman spectroscopy. All composites showed low thermal conductivity (0.02–0.03 W/m K), indicating their potential use as lightweight thermal insulators. This study demonstrates the synergistic effect of chemical and physical surface modifications on fiber matrix interactions, opening avenues for high‐performance, eco‐friendly polymer composites.
Journals
2026 EN
Valluvar Oli Arivazhagan · Kaur Kulwinder · Melchiorre Michele
+10 more
ABSTRACT This study underscores the pivotal role of sodium (Na) supply in optimizing the optoelectronic properties of wide bandgap (~1.6 eV) Cu(In,Ga)S 2 (CIGS) thin‐film absorbers for high‐efficiency solar cells. Our findings demonstrate that the synergistic use of Na from the glass substrate, in conjunction with in situ sodium fluoride (NaF) co‐evaporation, significantly enhances the structural and optoelectronic properties of the CIGS. CIGS grown under either Na‐deficient or excess conditions exhibit inferior microstructural and optoelectronic properties, whereas an optimal Na supply leads to enhanced photovoltaic performance. Optimal Na incorporation minimizes vertical gallium fluctuations and improves the grain size and crystallinity. An absolute 1 sun calibrated photoluminescence (PL) measurement reveals a substantial suppression of bulk defects and a reduction in non‐radiative losses, resulting in a high quasi‐Fermi level splitting (Δ E F ) of 1.07 eV, 93 meV higher than in Na‐deficient CIGS with the same bandgap. Optimal Na supply further increases excited carrier decay time, as revealed from time‐resolved PL, and hole doping density. Cross‐sectional hyperspectral cathodoluminescence mapping reveals that optimal Na supply significantly reduces defect density near the surface, thereby effectively translating Δ E F to open‐circuit voltage ( V OC ). As a result, a champion wide bandgap CIGS solar cell with a cadmium‐free ZnSnO x buffer layer achieved an impressive V OC of 971 mV and an active area power conversion efficiency of 15.7%, highlighting its potential for advancing tandem photovoltaic technologies with a stable inorganic top cell.
Journals
2026 EN
Ghirardo Sergio · Madini Barbara · Ullmann Nicola
+26 more
ABSTRACT Introduction Bronchiolitis is the leading cause of infant hospitalizations worldwide, primarily driven by respiratory syncytial virus (RSV). Methods This multicenter retrospective comparative study assessed the impact of immunoprophylaxis with nirsevimab against RSV on bronchiolitis‐related hospitalizations in Italy during the 2024–2025 winter season. Results Data from nine Italian hospitals showed a substantial 48% decrease in bronchiolitis admissions compared to the previous season (438 vs. 832 admissions). Among hospitalized infants, only 23% had received immunoprophylaxis. RSV positivity dropped significantly among immunized patients (48%) versus non‐immunized (73%, p < 0.0001), with fewer RSV‐related coinfections. Discussion While indicators of illness severity—such as ICU admission, respiratory support needs, and complications—were generally lower, no statistically significant differences in disease course were observed between immunized and non‐immunized hospitalized infants. A shift in viral epidemiology was noted, with a reduction in RSV dominance and increased detection of rhinovirus and enterovirus, suggesting a pathogen replacement effect. The 2024–2025 season also saw a lower intubation rate (< 0.5%), pointing to an overall milder disease course. Conclusions This study supports the effectiveness of nirsevimab in reducing RSV‐associated hospitalizations and reshaping the virological landscape of bronchiolitis in Italy. Early and widespread implementation of immunoprophylaxis is recommended to maximize public health benefits.
Journals
2026 EN
Waqas Muhammad · Natale Benito · Roggia Michele
+3 more
Abstract Engineering protein stability is a powerful strategy across biotechnology and medicine, supporting a broad range of applications such as atomic structure determination, discovery of therapeutic molecules, biomanufacturing, diagnostic reagents, industrial biocatalysis, etc. However, achieving rapid and significant improvements has been historically challenging due to the vast mutational space and the complex interplay of sequence, structure, and function. Indeed, traditional experimental and computational methods often struggle to predict the impact of multiple mutations and effectively integrate diverse data types. To address these limitations, we developed StabLyzeGraph, a novel computational framework powered by Graph Neural Networks (GNNs) for protein mutational analysis and classification of stabilizing mutations. StabLyzeGraph represents proteins as graphs, integrating amino acid physicochemical properties, evolutionary conservation scores, and mapped three‐dimensional structural information. The framework consists of a Benchmarking module to evaluate performance, and a Screening module to identify and rank impactful mutations. Benchmarking across 23 diverse datasets demonstrated strong predictive performance, highlighting the GNN's ability to leverage integrated features. Mutational analysis enables the generation and probability scoring of single‐ and multi‐site mutants, demonstrating the model's capacity to classify beneficial combinations of mutants based on learned structural impact rather than mere mutation frequency. StabLyzeGraph also features a user‐friendly Graphical User Interface and demonstrates reasonable computational efficiency and scalability for exploring mutational landscapes. This tool provides a robust and versatile approach to accelerate the efficient discovery of stabilizing mutations with tailored properties and represents a step forward in rational protein design, poised to accelerate the creation of novel biologics with enhanced performance. StabLyzeGraph is freely available on GitHub ( https://github.com/cosconatilab/StabLyzeGraph ) as an open‐source tool.
Journals
2026 EN
Romei Andrea · Orsatti Carolina · Allegra Andrea Gaetano
+8 more
ABSTRACT Introduction Prostate‐specific antigen bounce (PSAb), characterized by a transient elevation in PSA levels followed by a spontaneous decline, is a well‐documented phenomenon in prostate cancer (PC) patients undergoing radiotherapy. While PSAb can cause diagnostic uncertainty, mimicking biochemical recurrence, its etiology and clinical implications remain poorly understood. This study aims to analyze the incidence, characteristics, and prognostic significance of PSAb in a cohort of PC patients treated with stereotactic body radiotherapy (SBRT) using a 1.5 T MR‐Linac platform. Methods A total of 305 patients with low‐to‐intermediate risk PC (stage T1‐T2, Gleason score ≤ 4 + 3) were treated with SBRT in five fractions (35–36.25 Gy) using an adaptive workflow guided by pretreatment MRI and real‐time cine‐MRI monitoring. PSAb was defined as a temporary increase in PSA levels ≥ 0.2 ng/mL above the nadir, followed by a return to or below the nadir. Statistical analyses evaluated correlations between PSAb and clinical/dosimetric variables, including tumor volume, treatment scheduling, and toxicity. The Chi‐square test was used for categorical variables, while Spearman′s correlation and linear regression assessed continuous variables. Results PSAb occurred in 25% of patients, with a median time to bounce of 11 months posttreatment. The incidence of PSAb within the first 6 months was 86.4%. The median time to post‐bounce nadir (PSAn) was 25 months, with a mean PSAn of 0.90 ng/mL (range: 0.05–5.02 ng/mL). Biochemical relapse was observed in only 2,95% of patients. No significant associations were found between PSAb and tumor volume metrics or treatment scheduling. Toxicity analysis revealed predominantly mild‐to‐moderate acute events, including cystitis (28.2%) and proctitis (4.6%), with minimal late toxicity (cystitis: 9.2%; proctitis: 2.9%; sexual impotence: 4.3%). Univariate analysis demonstrates a significant correlation between PSAb and improved biochemical relapse‐free survival ( p = 0.016). Conclusions PSAb is a common and benign phenomenon in PC patients treated with SBRT, associated with favorable oncological outcomes. The absence of significant correlations with tumor volume or treatment scheduling suggests that PSAb may be influenced by individual biological factors rather than dosimetric or procedural variables. These findings underscore the importance of distinguishing PSAb from true biochemical recurrence.