Search Results (3,196)

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor ²²⁵Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized ²²⁵Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care. Full article

(1) Background: Hemifacial spasm (HFS) is most commonly caused by neurovascular compression at the root exit zone (REZ) of the facial nerve; however, isolated compression along the distal cisternal segment is uncommon and remains poorly characterized. This study aimed to analyze the clinical features, intraoperative neurophysiological patterns, and surgical outcomes of patients with HFS caused by cisternal segment arterial compression. (2) Methods: Among 874 patients who underwent microvascular decompression (MVD) for HFS, 18 (2.1%) were identified as having isolated neurovascular conflict at the cisternal segment, all involving the anterior inferior cerebellar artery (AICA). Clinical characteristics, offender location, intraoperative monitoring results including lateral spread response (LSR), brainstem auditory evoked potentials, and postoperative outcomes were retrospectively evaluated. A standardized Teflon interposition technique was used in all cases. (3) Results: Postoperatively, 83.3% of patients experienced immediate spasm relief, and at the latest available follow-up, 94.4% achieved significant improvement without severe complications. (4) Conclusions: Although rare, cisternal segment arterial compression can produce typical HFS and should be considered when REZ compression is unclear or when intraoperative neuromonitoring does not respond as expected. Microvascular decompression using Teflon interposition is a safe and effective treatment option for this anatomically challenging offender location. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains the seventh most common cancer worldwide, characterized by late-stage diagnosis and poor 5-year survival rates. Oral squamous cell carcinoma (OSCC) is the most prevalent subtype. The identification of robust diagnostic, prognostic, and predictive markers is essential for personalized treatment monitoring. Methods: Following PRISMA and PICO standards, we conducted a comprehensive review of studies published over the past 10 years across PubMed/MEDLINE, Scopus, and Web of Science. The selection process was facilitated by AI-powered tools (Rayyan QCRI), and study quality was assessed using NOS or QUIPS. Results: 34 articles (including meta-analyses and original trials) were identified. Established clinical markers, such as p16-positivity (HR ≈ 0.55) and PD-L1 (CPS), remain significant. However, the molecular landscape is expanding to include high-risk lncRNA signatures (HR ≈ 2.50), immune checkpoints such as TIGIT (HR ≈ 1.85), and genomic alterations, including IL-10 promoter polymorphisms. We highlight that epigenetic silencing of p16 affects only about 25% of patients, while metabolic regulators (e.g., GLUT-1) and protein markers (e.g., MASPIN) offer critical predictive value for therapy response. Conclusions: The diagnostic and predictive paradigm is shifting toward a multi-omic approach that integrates DNA, RNA, proteins, and metabolic indicators. Future clinical use will rely on AI-driven multimarker panels and non-invasive liquid biopsies to enable real-time monitoring and de-escalation of treatment strategies. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background/Objectives: Dementia represents a growing public health challenge. The WHO Global Action Plan on the Public Health Response to Dementia emphasizes early detection, risk reduction, and innovation as key priorities. Mild Behavioral Impairment (MBI), defined as the emergence of persistent neuropsychiatric symptoms in older individuals, represents a potential marker of early neurodegeneration and possible window for early intervention. This review explores the role of MBI in dementia prevention, mapping current evidence within the WHO Global Action Plan framework. Methods: A comprehensive search was performed in PubMed, Scopus, and the official WHO website, during 1 September 2025–10 November 2025, without time restrictions. Eligible sources included original clinical studies, reviews, and policy documents addressing MBI, dementia prevention, and public health. Data were thematically synthesized according to the seven objectives of WHO: (1) dementia as a public health priority, (2) dementia awareness and friendliness, (3) dementia risk reduction, (4) dementia diagnosis, treatment, care and support, (5) support for dementia carers, (6) information systems for dementia, and (7) dementia research and innovation. Results: Accumulating evidence indicates that MBI assessment can capture early behavioral manifestations of neurodegenerative and other forms of dementia, correlating with fluid, neuroimaging and genetic biomarkers. Integrating MBI screening through the easy-to-administer MBI Checklist (MBI-C) into clinical and community-based care, including telemedicine pathways and research, may enhance early identification and personalized interventions, enrich the pool for clinical trials, and facilitate research in biomarker and therapy. MBI-related research further supports its integration in remote digital monitoring and population-based prevention. Conclusions: Embedding MBI-informed screening and interventions into national dementia strategies aligns with WHO objectives for early, equitable and scalable prevention and brain health. Full article

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL); however, a significant proportion of patients fail to achieve a durable response, underscoring the need for reliable predictive biomarkers. We characterize T-lymphocyte subpopulations in apheresis samples from 23 r/r large B-cell lymphoma (LBCL) patients who received axicabtagene ciloleucel (axi-cel) to identify pre-treatment cell biomarkers associated with CAR T-cell kinetics and clinical outcomes. Immunophenotyping of T-cells within fresh apheresis samples and monitoring of circulating CAR T-cells were performed by multiparametric flow cytometry. The median peak CAR T-cell count was 45.2 CAR T-cells/mL. Strong CAR-T expanders (≥45.2 CAR T-cells/mL) exhibited higher values of both CD4⁺ (p = 0.011) and CD8⁺ (p = 0.023) central memory T-cells (T_CM; CCR7⁺CD45RA⁻), as well as lower proportions of CD8⁺CD38⁺ T-cells in apheresis samples. In apheresis, a cut-off value of >4.3% of CD8⁺ T_CM predicted strong CAR-T expansion (AUC: 0.80; p = 0.023) and superior progression-free survival (p = 0.04) compared with patients who had CD8⁺ T_CM below the cut-off. Our data suggest that high frequencies of CD8⁺ T_CM cells in apheresis samples may represent a promising pre-treatment biomarker associated with strong CAR-T expansion and superior clinical outcome in r/r LBCL patients following axi-cel. Full article

The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects. Full article

Newborns are unable to reliably express changes in their physical condition due to their physiological immaturity and limited capacity for communication; therefore, continuous and systematic monitoring during phototherapy is essential to ensure timely detection of adverse responses and maintenance of therapeutic safety. This study extends our prior work, which introduced an indirect method for measuring light intensity to improve precision in monitoring newborn skin illumination. Light-emitting diode (LED) phototherapy has attracted considerable attention as an effective treatment for neonatal jaundice (NNJ). This study introduces an three-dimensional configuration of blue LEDs. An Arduino Mega 2560 microcontroller with pulse-width modulation (PWM) technology was employed to independently regulate the intensity of LED strips, enabling precise control of light output. The strips were mounted on an arc-shaped structure that can be adjusted mechanically and electronically through pre-programmed instructions embedded in the microcontroller. The results demonstrate that blue light at a wavelength of 460 ± 10 nm aligns with the peak absorption spectrum of bilirubin, thereby optimizing the efficacy of phototherapy for NNJ. Both observed absorption peaks were within the therapeutically effective range. Computer simulations confirmed that stable output contours can be achieved using rapid electronic scanning with a PID control algorithm to dynamically adjust the duty cycle. Experimental data showed that LED radiation output was largely linear. This supports the use of linear control algorithms and confirms the platform’s feasibility for future research. Full article

Background: Chronic periodontitis (CP) is a prevalent inflammatory disease worldwide, characterized by the destruction of periodontal tissue due to an immune response triggered by periodontopathogenic bacteria and the prolonged release of reactive oxygen species (ROS). Excess ROS leads to tissue damage through mechanisms such as lipid peroxidation and DNA damage. The aim of this study was to evaluate oxidative and genotoxic damage by quantifying 8-hydroxy-2-deoxiguanosine (8-OHdG), malondialdehyde (MDA), and nuclear abnormalities (NAs) in individuals with CP. Methods: The participants were divided into a CP group (n = 30) and a control group without CP (n = 30). Saliva was collected to quantify 8-OHdG (via ELISA) and MDA (via spectrophotometry). Buccal mucosa samples were collected to assess NAs. Periodontal parameters, probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), were recorded. Results: The levels of 8-OHdG and MDA were significantly higher in the CP group. NAs were also significantly increased. Positive correlations were observed between 8-OHdG, MDA levels and NAs with clinical parameters. Conclusions: The elevated levels of 8-OHdG, MDA and NAs reflect oxidative and genotoxic damage correlated with CP severity. These biomarkers could complement diagnosis, monitor progression, and assess treatment efficacy. Their elevation may also indicate increased systemic disease risk. Full article

Background and Clinical Significance: Cutaneous Rosai-Dorfman disease (CRDD) is a rare, benign histiocytic proliferative disorder, accounting for approximately 3% of all Rosai-Dorfman disease (RDD) cases. Currently, the diagnosis of CRDD relies on invasive pathological examination due to the absence of reliable non-invasive alternatives. This case series evaluates the potential utility of high-frequency ultrasound (HFUS) as an adjunctive diagnostic tool for CRDD. Case Presentation: We present three CRDD cases, correlating HFUS features with histopathology. All cases showed hypoechoic lesions with varying infiltration depths and morphologies, though no specific diagnostic features were identified. HFUS clearly delineated involvement of the dermal and subcutaneous layers, assessed morphological characteristics like contour regularity and border definition, and evaluated vascularity. This information is crucial for clinical decision-making. HFUS also demonstrated value in therapeutic follow-up. In Case 1, it objectively showed a reduction in lesion size and decreased internal vascularity, providing clear evidence of treatment response. Conclusions: Although HFUS cannot independently diagnose CRDD and histopathology remains the gold standard, it serves as a valuable complementary tool. HFUS allows evaluation of deeper tissue structures, infiltration depth, and vascularity. As a non-invasive modality, it is useful for treatment monitoring, therapy guidance, and prognosis assessment. Integrating HFUS into the CRDD workflow enables more comprehensive and precise management. Full article

Background: Greater trochanteric pain syndrome (GTPS) is associated with structural tendon alterations and functional impairment. Extracorporeal shockwave therapy (ESWT) is a common treatment, but objective monitoring of tendon remodeling and motor recovery remains limited. Objective: This study aimed to integrate shear-wave elastography (SWE) expressed in m/s and wearable inertial measurement unit (IMU) as biosensing tools for the quantitative assessment of tendon elasticity, morphology, and hip motion after ESWT in GTPS. Methods: In a prospective cohort of adults with chronic GTPS, shear wave elastography (SWE) quantified gluteus medius tendon (GMT) elasticity and thickness, while hip abduction range of motion (ROM) was measured using a triaxial inertial measurement unit. Clinical scores on the Visual Analogue Scale (VAS), Harris Hip Score (HHS), Low Extremity Functional Scale (LEFS), and Roles and Maudsley score (RM) were collected at baseline (T0) and at 6 months (T1). Results: Thirty-five patients completed follow-up. Pain and function improved significantly (VAS, HHS, LEFS, RM; all p < 0.05). SWE values of the affected GMT increased, while tendon thickness decreased yet remained greater than on the contralateral side. Hip abduction ROM increased significantly from T0 to T1 (p < 0.05). Correlation analysis showed a negative association between abduction and pain at T1 (r = −0.424; p = 0.011) and, at baseline, between abduction and VAS (r = −0.428; p = 0.010) and RM (r = −0.346; p = 0.042), and a positive association with LEFS (r = 0.366; p = 0.031). SWE correlated negatively with VAS at T1 (r = −0.600; p < 0.05) and positively with HHS at T1 (r = 0.400; p < 0.05). Conclusions: Integrating elastography with inertial sensor-based motion analysis provides complementary, quantitative insights into tendon remodeling and functional recovery after ESWT in GTPS. These findings support combined imaging and wearable motion measures to monitor treatment response over time. Full article

Artificial intelligence (AI) and machine learning (ML) are reshaping cancer research and care. In pediatric oncology, early evidence—most robust in imaging—suggests value for diagnosis, risk stratification, and assessment of treatment response. Pediatric endocrine tumors are rare and heterogeneous, including intra- and extra-adrenal paraganglioma (PGL), adrenocortical tumors (ACT), differentiated and medullary thyroid carcinoma (DTC/MTC), and gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Here, we provide a pediatric-first, entity-structured synthesis of AI/ML applications in endocrine tumors, paired with a methods-for-clinicians primer and a pediatric endocrine tumor guardrails checklist mapped to contemporary reporting/evaluation standards. We also outline a realistic EU-anchored roadmap for translation that leverages existing infrastructures (EXPeRT, ERN PaedCan). We find promising—yet preliminary—signals for early non-remission/recurrence modeling in pediatric DTC and interpretable survival prediction in pediatric ACT. For PGL and GEP-NEN, evidence remains adult-led (biochemical ML screening scores; CT/PET radiomics for metastatic risk or peptide receptor radionuclide therapy response) and serves primarily as methodological scaffolding for pediatrics. Cross-cutting insights include the centrality of calibration and validation hierarchy and the current limits of explainability (radiomics texture semantics; saliency ≠ mechanism). Translation is constrained by small datasets, domain shift across age groups and sites, limited external validation, and evolving regulatory expectations. We close with pragmatic, clinically anchored steps—benchmarks, multi-site pediatric validation, genotype-aware evaluation, and equity monitoring—to accelerate safe, equitable adoption in pediatric endocrine oncology. Full article

Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m² every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m² every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article

Background and Objectives: Toll-like receptors (TLRs) are pattern recognition receptors with an essential role in regulating both the innate and adaptive immune response. Given their pleiotropic effects in mounting an immune response, previous studies have proposed targeting these TLRs might render alternative strategies for cancer therapy. Synthetic immune response modifiers, such as imidazoquinolines, stimulate the immune cells by activating Toll-like receptors, particularly TLR7/8 receptors, consequently mounting an immune response. Agonists of this class activate, via TLR-mediated signaling, dendritic and B cells, as well as myeloid cells and T cells, thus exhibiting good prospects for cancer immunotherapy. In the present study, we sought to evaluate the effect of imiquimod and gardiquimod, two TLR 7 and 7/8 agonists, respectively, on tumor growth and phenotype of NK cells associated with melanoma. Materials and Methods: We generated a syngeneic model of melanoma in C57BL/6J mice by subcutaneously injecting murine melanoma cells and monitoring tumor growth. Starting on day 8 or 14, we applied TLR agonists either intratumorally or topically and followed the tumor dynamics and NK cell-associated pattern. Results: Our results suggest that both TLR agonists displayed an antitumor effect along with a phenotypically activated profile of NK cells. Both imiquimod and gardiquimod treatment inhibited tumor growth, with gardiquimod showing an increased potency compared to imiquimod. Conclusions: This implies that TLR agonists like imiquimod and gardiquimod could serve as neoadjuvant, adjuvant, or complementary immunotherapeutic agents in melanoma therapy. Full article