Journals
2026 EN
Guarnaccia Maria · La Cognata Valentina · Gentile Giulia
+2 more
ABSTRACT Gliomas are among the most malignant and aggressive tumors of the central nervous system, characterized by the absence of early diagnostic markers, poor prognosis, and a lack of effective treatments. Advances in high‐throughput technologies have facilitated a refined molecular classification of gliomas, incorporating genetic features. However, diagnosis and clinical management based on isolated genetic data often fail to capture the full histological and molecular complexity of these tumors, posing significant challenges. In the era of computational methodologies and artificial intelligence, the integration of multiple omics layers—genomics, transcriptomics (including sex‐dependent differential expression patterns), epigenomics, proteomics, metabolomics, radiomics, single‐cell analysis, and spatial omics—into a comprehensive framework holds the potential to deepen our understanding of glioma biology and enhance diagnostic precision, prognostic accuracy, and treatment efficacy. Herein, we provide a comprehensive overview of multi‐omics strategies used to decipher the adult‐type diffuse glioma molecular taxonomy and describe how the integration of multilayer data combined with machine‐learning‐based algorithms is paving the way for advancements in patient prognosis and the development of personalized, targeted therapeutic interventions.
Journals
2026 EN
Greco Guido · Motta Caterina · Marchionni Enrica
+5 more
ABSTRACT The FMR1 gene premutation (55–200 CGG repeats) is usually associated with a wide range of symptoms and phenotypes within the Fragile X‐tremor/ataxia syndrome (FXTAS), but may also manifest as predominant or isolated cognitive decline. We describe three male patients referred for progressive cognitive impairment and behavioral changes. Standard work‐up, including MRI, FDG‐PET, CSF biomarkers, and neuropsychological testing, excluded common dementias. Brain MRI imaging revealed callosal and peduncular white matter changes, while 18FDG‐PET showed consistent anterior cingulate hypometabolism. Genetic analysis confirmed FMR1 premutation in all cases. Clinicians in memory clinics should consider this diagnosis in cases of unexplained cognitive decline.
Journals
2026 EN
Barry Austin · England Bryant R. · Sayles Harlan
+14 more
Objective Although treat‐to‐target urate‐lowering therapy (ULT) is endorsed as best practice in gout management, limited data exist on its impact on health‐related quality of life (HRQoL). We assessed the impact of treat‐to‐target ULT on HRQoL among participants receiving protocolized gout care, identifying factors associated with HRQoL and HRQoL change. Methods This was a post hoc analysis of a 72‐week randomized trial, pooling data from allopurinol and febuxostat treatment arms. The Veterans RAND‐12 Item Health Survey and EuroQol 5‐Dimension 3‐Level (EQ‐5D‐3L) were administered at baseline and at 24, 48, and 72 weeks. HRQoL changes over follow‐up were examined using paired t ‐tests. Factors associated with baseline HRQoL were evaluated using multivariable linear regression. General estimating equations were used to identify determinants of HRQoL change over follow‐up. Results Participants (N = 878) in this analysis were 98.9% male, had a mean age of 62.4 years, and 67.4% self‐reported White race. HRQoL scores overall, and particularly the domains of physical function, mobility and pain, improved significantly over 72 weeks ( P < 0.001) with improvements noted by 24 weeks. Poorer enrollment HRQoL was associated with younger age, non‐White race, tophi (for EQ‐5D‐3L), higher serum urate level, and greater comorbidity. Baseline factors associated with HRQoL improvements over 72 weeks of ULT included lower C‐reactive protein level and lower comorbidity scores with similar changes observed by ULT assignment. Conclusion Treat‐to‐target ULT in gout is accompanied by HRQoL improvements evident by 24 weeks and sustained through 72 weeks. HRQoL gains with treat‐to‐target ULT are most prominent in the domains of physical function, mobility, and pain and are greatest in those with lower baseline levels of inflammation and comorbidity.
Journals
2026 EN
Fava Andrea · Wagner Catriona A. · Guthridge Carla J.
+23 more
Objective Lupus nephritis (LN) management remains challenging, and novel noninvasive biomarkers are needed. This study quantified serum soluble mediators in the Accelerating Medicines Partnership (AMP) LN cohort to identify biomarkers of histologic features and treatment response. Methods Patients with systemic lupus erythematosus (SLE) (n = 268) undergoing clinically indicated kidney biopsies (urine protein/creatinine ratio [UPCR] ≥ 0.5) were recruited through the AMP Rheumatoid Arthritis and SLE Network. Serum was collected at biopsy and 3‐, 6‐, and 12‐month postbiopsy, alongside samples from 22 healthy controls. Concentrations of 66 immune mediators were quantified using xMAP multiplex assays, and (TACE) measured by enzyme‐linked immunosorbent assay. Seven mediators with >95% values below detection limits were excluded from analyses. Bootstrapped least absolute shrinkage and selection operator (LASSO) regression identified proliferative LN (class III/IV ± V) predictors from baseline mediators. Associations with 12‐month treatment response (complete/partial vs no response) were tested using three‐month changes in LASSO‐selected mediators and UPCR via logistic regression. Molecular clustering of mediator profiles was performed to identify LN subgroups. Results Proliferative patients with LN (class [III or IV] ± V; n = 160) displayed a distinct mediator profile compared with nonproliferative LN (class I, II, or V; n = 96). LASSO regression identified 20 mediators predictive of proliferative LN (areas under the curve, 0.82; 95% confidence interval [CI], 0.81–0.91), including elevated syndecan‐1, tumor necrosis factor receptor type I, tumor necrosis factor receptor type II, and vascular cell adhesion molecule 1 (VCAM‐1), as well as decreased CCL3//macrophage inflammatory protein 1α, CD40 ligand, and interleukin‐5 levels. Among proliferative patients with LN, 3‐month reductions in syndecan‐1 and VCAM‐1, mediators associated with intrarenal LN activity and/or chronicity, predicted the 12‐month treatment response. A model incorporated these reductions and a decline in UPCR‐predicted treatment response in proliferative LN (0.90; 95% CI, 0.82–0.98). Molecular clustering revealed four distinct LN subgroups with unique soluble mediator signatures and clinical features not captured by histology alone. Conclusion Serum soluble mediators, particularly syndecan‐1 and VCAM‐1, reflect LN histologic activity, and early decreases predict treatment response, supporting their potential use as noninvasive longitudinal biomarkers. The substantial heterogeneity within LN highlights the potential for biomarker‐guided reclassification to advance precision medicine approaches.
Journals
2026 EN
Aquilani Angela · Marinaro Francesca · Tarantino Giusyda
+10 more
Objective We evaluated the immunogenicity of SARS‐CoV‐2 mRNA vaccines in patients with juvenile idiopathic arthritis (JIA), focusing on the generation of spike‐specific memory B cells (MBCs) and of neutralizing antibodies, and assessed the impact of disease‐modifying antirheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi). Methods This study enrolled 35 adolescent and young adult patients with JIA. Data concerning disease characteristics and SARS‐CoV‐2 vaccination and infection were collected. We analyzed the frequency of low‐affinity spike‐specific and high‐affinity spike‐specific MBCs by flow cytometry. We measured total anti‐spike antibodies levels using a chemiluminescence microparticle immunoassay and assessed neutralizing antibody titers with a microneutralization assay. Results Patients with JIA showed a reduced frequency of high‐affinity MBCs compared to controls, with a notably poorer response among those receiving TNFi treatment. Additionally, their ability to bind the Omicron variant was significantly lower, particularly among TNFi‐treated patients. SARS‐CoV‐2 infection alone was not able to generate high‐affinity MBCs and neutralizing antibodies in patients with JIA. After receiving three vaccine doses, 43% of patients with JIA exhibited a reduced frequency of high‐affinity MBCs and neutralizing antibodies. Conclusion Patients with JIA undergoing treatment with TNFi demonstrated a diminished immunogenic response to SARS‐CoV‐2 vaccination, with lower frequencies of high‐affinity MBCs and decreased neutralizing antibody titers. These findings underscore the need for customized vaccination protocols, including the potential use of booster doses, to enhance immunoprotection in this group. Additionally, the development of reliable biomarkers to distinguish between patients with and without adequate protective immunity is imperative to refine therapeutic interventions and ensure optimal patient outcomes.
Journals
2026 EN
Sevillano Juan · AbdelWahab Noha · Zhou Yixuan
+2 more
Objective Immune checkpoint inhibitors (ICIs) are effective cancer therapies but often cause serious immune‐related adverse events (irAEs). Patients with preexisting autoimmune diseases, including vasculitis, are excluded from trials. We aimed to evaluate the frequency, severity, and outcomes of vasculitis flares and irAEs in this population. Methods We performed a retrospective review of cancer patients with prior vasculitis treated with ICIs at our institution and conducted a literature search for additional cases. Data included baseline features, vasculitis flares, irAEs, treatments, and tumor response. Results Twenty‐five patients were identified (16 from our institution and 9 from the literature). Median age was 71 years; 13 (52%) were female. Vasculitis types included giant cell arteritis (GCA, n = 9), granulomatosis with polyangiitis (GPA, n = 8), eosinophilic granulomatosis with polyangiitis (EGPA, n = 2), leukocytoclastic vasculitis (n = 2), other cutaneous vasculitis (n = 2), and Henoch–Schönlein purpura and Behçet disease (1 each). Cancer types were diverse. Most patients received anti–programmed death‐1 monotherapy (n = 17). Eight patients (31%) experienced a vasculitis flare after ICI initiation (2/9 GCA, 4/8 GPA, 2/4 cutaneous vasculitis). Flares occurred after a median of seven weeks. Treatment included glucocorticoids in seven patients, combined with biologic or cytotoxic agents depending on vasculitis type. Seven of eight flares resolved, and four patients continued ICI therapy. Three additional patients developed de novo irAEs: severe hepatitis (n = 1), grade 3 colitis (n = 1), and grade 3 autoimmune hemolytic anemia (n = 1), all improving with treatment. One patient with GCA died due to a flare; no deaths were attributed to de novo irAEs. Overall, more than one‐third of patients achieved a favorable tumor response. Conclusion Nearly one‐third of patients with preexisting vasculitis experienced a disease flare during ICI therapy, with one fatal case. For most, outcomes were favorable with effective flare management. Preexisting vasculitis should not be considered an absolute contraindication for cancer immunotherapy with ICI.
Journals
2026 EN
Barreto da Silveira Wagner · Jefferson Dias de Oliveira Evald Paulo · Vieira Hollweg Guilherme
+3 more
ABSTRACT This work presents a robust model reference adaptive control with a full adaptive super‐twisting sliding mode action (RMRAC‐FASTSM) and its discrete‐time stability analysis using the Lyapunov criterion. The control structure differs from the literature by using a couple of adaptive gains to automatically adjust the weights on the nonlinear and integral components of the STSM action. This strategy alleviates the chattering phenomenon because it reduces the sliding mode action when the system reaches the steady state, improving the closed‐loop system performance and simplifying the controller design process by reducing the number of tuning hyperparameters required during this stage. The proposed control strategy emerges from the union of robust model reference adaptive control and a full adaptive super‐twisting algorithm, resulting in a novel adaptive and robust single‐loop control strategy. The stability analysis provides the controller design constraints, while also demonstrating that tracking error tends to a residual set in the steady state, even when the system is subject to matched and unmatched dynamics. Furthermore, the boundedness of all closed‐loop signals is also proved. The resulting controller is able to control a partially modeled system, where the only required system information is the sign of the high‐frequency gain and the relative degree of the nominal system transfer function. Simulation results corroborate the robustness of the controller dealing with relevant system perturbations and its superiority in relation to other adaptive super‐twisting controllers from the literature.
Journals
2026 EN
Leite Marcel Nani · Rios Natália Aparecida de Paula · Viegas Juliana Santos Rosa
+4 more
ABSTRACT One important step for evaluating and selecting a drug is toxicity studies, which are responsible for eliminating molecules that are considered promising for treating a certain disease based on their effectiveness in clinical studies, but are unsafe to go to the pharmaceutical market. We proposed an evaluation of dacarbazine as a positive control in toxicity effects in the context of macro‐ and micro effects represented by tissue and cell responses. A resazurin assay is used to evaluate cytotoxicity in cells (melanoma cells A375, Sk‐Mel‐103, and 1205Lu; immortalized skin cells HaCat and 3T3), and hematoxylin/eosin staining and TUNEL staining are used in skin explants. There is no toxicity demonstrated in the immortalized cells at the studied concentrations, whereas in the melanoma cells, A375 is the most sensitive to dacarbazine, with a high toxicity at all concentrations over 72 h ( p < 0.05), Sk‐Mel‐103 showed toxicity effects only at 200 µg/mL, and 1205Lu showed no evidence of toxicity. Histological data showed that the entire skin structure of the explants is preserved, and no apoptotic cells are observed. Thus, we can conclude that cell lines behave differently when exposed to a drug, in this case Dacarbazine proved to be a good control for toxicity tests.
Journals
2026 EN
Cojocari Maria · Ibrahim Eman · Basharin Alexey
We report on the design, fabrication, and experimental characterization of a free‐standing terahertz metasurface supporting quasi‐bound states in the continuum (quasi‐BICs). The metasurface, realized by laser cutting double‐slot apertures in a thin brass foil, exhibits a tunable transition from symmetry‐protected BICs to sharp Fano‐type resonances when structural asymmetry is introduced. Terahertz time‐domain spectroscopy measurements confirm high‐Q resonances in good agreement with simulations. Multipole decomposition reveals that the trapped mode response is dominated by the in‐plane electric quadrupole component, which governs the confinement and radiation properties of the quasi‐BIC. The free‐standing design eliminates substrate‐induced losses and opens a robust route toward versatile, high‐performance terahertz devices. These findings demonstrate the potential of quasi‐BIC metasurfaces as compact, tunable high‐Q resonators for applications in sensing, filtering, and terahertz photonics.
Journals
2026 EN
Bruno Mauro Daniel Luigi · Ferraro Antonio · Palermo Giovanna
+3 more
Physical unclonable functions (PUFs) are the new paradigm for the development of anticounterfeiting devices. Optical PUFs, which use the properties of light and how it interacts with materials to create unique identifiers, are attractive due to their high complexity. Cholesteric liquid crystals (CLCs), with their peculiar optical properties, are excellent candidates for optical PUF fabrication. Here, we present new fabrication methods to easily obtain complex random optical patterns, resembling human fingerprints, in CLC microspheres by exploiting temperature variations or mechanical stresses. Both methods enable large‐scale production of unclonable identifiers, easy to be encapsulated in polymeric thin films to create flexible anticounterfeiting labels. The authentication procedure of the labels is performed through image recognition algorithms. Through this procedure, an additional security feature is added. Each set of labels is used to generate a signature of the set itself. The signature represents a further and strong encoding level that guarantees the security of the labels against cyberattacks.