Search Results (170)

Background/objectives: Renal-cell carcinoma (RCC) accounts for approximately 4% of all solid tumours worldwide. Oligometastatic RCC, frequently defined as the presence of fewer than five metastatic lesions, is increasingly recognised as a clinically and prognostically distinct disease state, yet standardised treatment algorithms remain lacking. Method: This narrative review summarises current local and systemic treatment strategies for oligometastatic RCC and identifies patient populations most likely to benefit based on 26 studies published within the past ten years. Results: Stereotactic ablative radiotherapy (SABR) was the most frequently evaluated local modality, consistently demonstrating high local control rates with favourable toxicity profiles. Systemic therapies showed mixed efficacy and greater treatment-related adverse events, while evidence for radiofrequency ablation, cryoablation, and metastasectomy remains limited but suggests feasibility in selected patients. Conclusions: Overall, current evidence supports local therapy—particularly SABR—in appropriately selected patients with oligometastatic RCC, though most available evidence is retrospective and concentrated in favourable-risk ccRCC populations, limiting generalizability. Further prospective research is needed to refine patient selection criteria and optimise treatment sequencing. Full article

Background: Osteosarcoma remains a biologically complex and clinically challenging malignancy, with survival gains plateauing despite decades of multimodal therapy incorporating surgery and cytotoxic chemotherapy. Unlike cancers in which mutation-centric precision oncology has yielded transformative advances, osteosarcoma is characterized by profound structural variation, copy number alteration dominance, and dynamic clonal evolution, limiting the effectiveness of single-target approaches. These realities motivate alternative strategy-level frameworks that better align treatment selection with evolving disease behavior. Methods: This narrative educational review synthesizes contemporary evidence from osteosarcoma biology, radiobiology, and translational oncology to propose a state-based framework for integrating radiotherapy—particularly stereotactic body radiotherapy (SBRT/SABR) and spatially fractionated radiotherapy (SFRT)—into osteosarcoma management and clinical trial design. Rather than relying solely on static anatomic stage, this framework emphasizes clinically actionable, time-varying state variables, including disease burden patterns (localized, oligometastatic, polymetastatic), tempo of progression, prior systemic response, and feasibility of complete local control. Results: Within this context, radiotherapy is presented not only as a local control modality but also as a hypothesis-generating biologic intervention, capable of perturbing tumor vasculature, inflammatory signaling, innate DNA-sensing pathways, and immune/myeloid programs in a dose-, fractionation-, and spatial-distribution-dependent manner. The review critically examines both the potential opportunities (e.g., local eradication, immune modulation) and limitations (e.g., rarity of abscopal responses, risk of unintended systemic signaling) of radiobiotherapy combinations, emphasizing the need for cautious interpretation and prospective validation. Conclusions: Finally, the article outlines practical implications for state-stratified, biomarker-embedded clinical trials, highlighting endpoints beyond conventional response criteria, including circulating tumor DNA dynamics, immune and myeloid signatures, and long-term patterns of disease progression. Overall, this review frames radiobiotherapy as an educational and investigational paradigm intended to support rational hypothesis generation, multidisciplinary decision-making, and learning-oriented trial designs in osteosarcoma, rather than as definitive clinical guidance. Full article

Background: Neural stability, defined as trial-by-trial fluctuations in neural responses to the repetitive sensory input, is an indicator of neural processing stability. The auditory brainstem response (ABR) can provide an electrophysiological measure of neural stability. Findings on neural stability differences between autistic and neurotypical individuals are inconsistent, potentially due to methodological differences and sample heterogeneity. This study aimed to investigate the relationship between neural stability in the brainstem and autistic traits in a group of children with and without a diagnosis of autism. We examined whether the degree of neural stability differs based on the evoking stimulus and response component analyzed, and whether neural stability relates to parent-reported autistic traits, as measured by the Autism Spectrum Quotient (AQ) and social responsiveness scale-2 (SRS-2). Methods: In total, 41 participants had usable click ABRs and 34 had usable sABRs. Neural stability was quantified using Pearson correlation analyses between binaurally evoked subaverage ABR waveforms. Parent-reported measures of autistic traits were collected. Results: Neural stability differed across ABR components, with the click ABR being significantly more stable than sABR components. Decreased neural stability is significantly related to autistic traits measured by the AQ but not the SRS-2. There was no significant response component by AQ interaction. Conclusions: Neural stability in the auditory brainstem pathway is linked to individual differences in autistic traits measured by the AQ but not the SRS, implying that early sensory processing neural stability may be related to broader features of autistic traits rather than social communication alone. Full article

We performed a protein-docking study for eight DNA aptamers (SEQ1–SEQ8) against chicken Cluster of Differentiation 40 (chCD40), which were experimentally identified via SELEX in our previous study. In silico and molecular docking analyses were performed to predict and obtain the secondary and tertiary structures of the aptamers. Aptamers SEQ3 and SEQ4, which showed the best inhibitory effects, were selected and utilized to produce a DNA-based vaccine adjuvant using rolling circle amplification (RCA). These aptamers had been previously characterized via mass spectroscopy to determine their molecular weight and regions that could potentially interact with chCD40. In the present study, these results were corroborated and expanded. A series of free software methods, including Mfold v.1.0, 3dADN v.2.0, ClusPro v.2.0, Hdock v.1.0, and PLIP v.1.0, were used to determine the aptamers’ secondary and tertiary structures and docking interactions, as well as the specific residues involved in the interactions and their distances. The structures were used to explain and thus understand their effect on the binding, selectivity, and stability of the aptamers. The main objective of the study was to determine whether these aptamers could be used as vaccine adjuvants against viral and bacterial pathogens, specifically chicken avian influenza. The docking results were in good agreement with the experimental and biological results. The procedure employed in this study could be an easy and effective tool for exploring the potential of the new technology of systematic evolution of ligands by exponential enrichment (SELEX) in the preparation of aptamers to control viral and bacterial infections as well as diseases, such as cancer and Alzheimer’s. Full article

Background and Clinical Significance: Parry–Romberg syndrome (PRS), also known as progressive hemifacial atrophy, is a rare disorder characterized by progressive unilateral hemifacial atrophy, with potential involvement of the cranial bones and the brain. Although neurological manifestations are frequently described, central nervous system involvement may be subclinical and detectable only through neuroimaging. Owing to its rarity and the lack of standardized diagnostic criteria, most available data derive from case reports and small case series. Case Presentation: We report the case of a 38-year-old female patient diagnosed with PRS (stage 2 according to the Guerrerosantos classification), with onset in childhood characterized by left parietal alopecia, followed by progressive left-sided hemifacial atrophy and a linear “en coup de sabre” lesion. Neurological examination was normal, with no history of seizures or focal deficits. Brain MRI revealed ipsilateral cutaneous, subcutaneous, muscular, and osseous atrophy, as well as atrophy of the left parotid and submandibular glands. Additionally, subcortical white matter lesions were identified in the left frontal lobe in the absence of hemispheric cerebral atrophy. Conclusions: This case highlights a significant radioclinical dissociation, demonstrating that central nervous system involvement may occur even in clinically stable and paucisymptomatic forms of PRS. This disease may be associated with subclinical intracranial abnormalities, underscoring the need for systematic neuroimaging evaluation even in the absence of neurological manifestations. Based on the available literature and the specific features of the present case, we propose a practical clinical framework and imaging algorithm to facilitate early diagnosis and to contribute to the standardization of the diagnostic approach in this rare disorder. Full article

This study investigates the impact of inoculating seeds with bacterial endophytes isolated from Vitis amurensis Rupr. on endophytic community composition in Arabidopsis thaliana (L.) Heynh. Ten bacterial isolates of the genera Agrobacterium, Bacillus, Curtobacterium, Erwinia, Frondihabitans, Gordonia, Pantoea, Pseudomonas, Sphingomonas, and Xanthomonas were applied to seeds and some visible phenotypic effects were observed on plant growth after two weeks. High-throughput sequencing of 16S rRNA revealed that the native endophytic microbiome of A. thaliana was dominated by Gammaproteobacteria, Actinomycetes, Bacteroidia, and Alphaproteobacteria. The key families were Microscillaceae, Chitinophagaceae, Rhizobiaceae, Rhodanobacteraceae, Nocardioi-daceae, Nocardiaceae, Xanthomonadaceae, Devosiaceae, Microbacteriaceae, Crocinitomi-caceae, Pseudomonadaceae, Solimonadaceae, Comamonadaceae, Caulobacteraceae, and Micrococcaceae. Arabidopsis seed inoculation with Agrobacterium sp. R8SCh-B12, Curtobacterium sp. P7SA-B3, and Gordonia aichiensis P6PL2 significantly reduced alpha diversity (Shannon index) and altered beta diversity relative to controls, indicating strong community restructuring. These three isolates, along with Pseudomonas sp. R8SCh-B2, Sphingomonas sp. RA62c-B5, Xanthomonas sp. R7SCh-B6, and Bacillus velezensis AMR25, successfully colonized the plant tissues, as evidenced by significant increases in genus-specific amplicon sequence variants, ASVs (up to 17,820-fold for Curtobacterium sp. ASV33). In contrast, Pantoea sp. P7SCH-B5, Erwinia sp. R8SCh-B3, and Frondihabitans sp. RA62c-B2 failed to colonize A. thaliana, despite being applied to the seeds, suggesting the existence of mechanisms restraining colonization. These findings demonstrate that only a subset of grapevine-derived endophytes can effectively colonize A. thaliana, and that successful colonization correlates with significant shifts in the native microbiome, even in the absence of overt phenotypic changes. This emphasizes the importance of strain-specific compatibility in plant–endophyte interactions. Thus, we report the first descriptions of several novel endophytes that colonized Arabidopsis plants and establish a convenient model to investigate plant–bacterial interactions. Full article

Oligometastatic prostate cancer represents a distinct biological state between localized and widely metastatic disease, characterized by a limited number of lesions. Stereotactic body radiotherapy (SBRT) has emerged as a key metastasis-directed therapy (MDT), enabling precise ablation of metastatic lesions with minimal toxicity. Prospective clinical trials such as SABR-COMET, STOMP, ORIOLE, RADIOSA, and EXTEND have shown that SBRT delays disease progression, prolongs progression-free survival, and postpones the need for systemic therapy, while maintaining a favorable safety profile. Nevertheless, methodological limitations persist, including heterogeneity in defining oligometastatic disease, variability in dosing and fractionation, and the lack of predictive biomarkers. Ongoing phase III trials aim to validate the integration of SBRT with modern systemic therapies, including next-generation androgen receptor pathway inhibitors, to optimize clinical outcomes in hormone-sensitive and castration-resistant oligometastatic prostate cancer. This review summarizes current evidence, clinical applications, and future directions for SBRT in this patient population. Full article

Background/Objectives: Patients with early-stage non-small cell lung cancer (NSCLC) or limited lung metastases and compromised lung function, such as those with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD), or other factors rendering them high-risk for surgery or medically inoperable, face increased risks of treatment-related toxicity from stereotactic ablative radiation therapy (SABR). This study evaluated a novel treatment approach to mitigate these risks. Methods: We investigated Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR), delivered as pulsed radiation every three weeks, in patients with <5 cm lung tumors and ILD, COPD, or prior therapy. Treatment occurred between 2022 and 2024. Online adaptive radiotherapy (o-ART) was employed in 20 patients (80%) to modify treatment plans when anatomical changes warranted replanning. Primary outcomes included volumetric tumor response, changes in dose to organs at risk (OARs) and acute events, while secondary outcomes included local and tumor control, and overall survival. Results: Twenty-three patients received PULSAR treatment at doses between 40 Gy and 60 Gy in 5 fractions and one patient received 54 Gy in 3 fractions, with a median follow-up time of 16.2 months. Approximately half of treated patients demonstrated volumetric tumor response, with median residual volume of 70% (range 36–100%) at maximal response. Among the 20 patients (80%) who underwent online adaptive replanning, significant reductions in OAR dosimetry were observed for all organs assessed including the Dmax for heart (p = 0.0053), bronchus (p = 0.0003), esophagus (p = 0.0005), spinal cord (p = 0.025), and the lung V20 Gy and V12.5 Gy (p < 0.0001). Treatment-related toxicity included two grade 1–2 adverse events and six grade 3 events consisting of pneumonitis, dyspnea or lung infection, with no grade 4 or 5 events. Median progression-free survival was 21.1 months, with 1-year overall survival of 74% and 1-year local control of 100%. Conclusions: PULSAR shows promise as a feasible treatment option for high-risk patients with NSCLC or lung metastases, demonstrating no grade 5 events and complete tumor control. Additional research is needed to fully evaluate the safety profile of PULSAR in the high-risk subgroups and whether PULSAR’s treatment intervals and adaptive planning advantages lead to improved long-term outcomes compared to conventional, uninterrupted SABR regimens. Full article

This study investigates the flow and heat transfer mechanisms of high-temperature air flowing across staggered lined fine tubes in a SABRE-type precooler. Large-Eddy Simulation (LES) was employed to model three-dimensional unsteady flow under constant-property and variable-property air models at inlet temperatures of 400–800 K. The results show that increasing temperature substantially enhances vorticity, turbulent kinetic energy, heat flux, and Nusselt number, while flow separation and pressure drop are intensified. However, when temperature-dependent air properties are incorporated, the wake width increases and the separated shear layers become thicker, while the turbulence/unsteadiness intensity decreases. Consequently, the near-wall shear is reduced and the heat transfer coefficients are lower. Compared with variable-property predictions, constant-property models overestimate the average Nusselt number by 20–40% and the local pressure drop by 40–65%, and they underestimate the air-side temperature drop along the tube rows. These findings demonstrate that real-gas effects significantly alter both aerodynamic resistance and thermal performance. Overall, accurate representation of temperature-dependent air properties is essential for the reliable design, evaluation, and optimization of micro-tube precoolers. Full article

The nucleating agents with different alkyl chain lengths sodium 4-[(benzyl)amino] benzoate (SAB-Be), sodium 4-[(heptanoyl)amino] benzoate (SAB-7C), and sodium 4-[(stearoyl)amino] benzoate (SAB-18C) were synthesized via chemical to improve the crystallization and mechanical properties of recycled polyethylene terephthalate (rPET) that had been damaged during mechanical recycling. The rPET/nucleating agent blends were prepared by melt blending. The molecular structure and thermal stability of the nucleating agents were characterized using the utilization of fourier transform infrared (FTIR) and thermogravimetric analysis (TGA). The differential scanning calorimetry (DSC) results showed that the crystallization properties of the rPET had been improved. In addition, the glass transition temperatures (T_g) of rPET, rPET/SAB-Be, rPET/SAB-7C, and rPET/SAB-18C were 80.3 ± 0.3 °C, 80.4 ± 0.9 °C, 77.0 ± 1.2 °C, and 69.7 ± 0.9 °C, respectively, demonstrating that the length of the alkyl chain in the nucleating agents was essentially proportional to the lubrication effect on rPET. Meanwhile, the rheological properties also supported the conclusion. The isothermal thermodynamic analysis indicated that the compatibility between nucleating agents and rPET was related to the length of the alkyl chain in the nucleating agents. The scanning electron microscopy (SEM) results of the fracture surfaces of the rPET/nucleating agent blends showed that the longer the alkyl chain in the nucleating agent, the greater the compatibility with rPET. Furthermore, the rPET/SAB-18C exhibited the best mechanical properties of the samples used in this research, with flexural strength and impact strength increased by 5.1% and 58.9%, respectively, compared to rPET. Overall, this work provided the new approach for rPET upcycling by combining molecular design strategies. Full article

Creatine monohydrate is known for its moderate solubility (13 g/L at 25 °C), which limits the feasibility of producing its fast-dissolving forms. Overcoming this limitation is possible through the application of technological approaches, the overview of which is presented in this work, including chemical modification, micronization, granulation, amorphization, formation of solid dispersions, and encapsulation. The results showed the predominance of chemical methods (about 60% of the analyzed patents). At the same time, the use of physical methods and the combination of several technologies can increase both the dissolution rate and the solubility of creatine monohydrate while maintaining its stability. This makes these approaches the most promising for the development of production technology for fast-dissolving forms. Full article

Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease. Full article

Olive leaf tea (OLT), rich in phenolics, exhibits antioxidant, anti-inflammatory, and potential anticancer effects; however, the in vivo efficacy remains unclear. This study evaluated the chemopreventive and systemic effects of OLT in a murine Ehrlich Ascites Tumor (EAT) model, with a focus on the treatment timing. OLT was prepared by aqueous infusion and characterized for total phenolic content (TPC: 25.74 mg GAE/g), DPPH scavenging (197.88 µmol TE/g), FRAP activity (81.23 µmol Fe²⁺/g), and LC-MS/MS profile (oleuropein 77.6%). Mice received OLT orally before or after tumor inoculation. Prophylactic OLT reduced EAT cell counts (from 31.48 × 10⁷ to 21.15 × 10⁷), ascites volume (from 4.58 to 2.98 mL), elevated miR-155-5p (14.34-fold), normalized ALT/AST, and restored hepatic antioxidants without histopathological damage. Co-treatment with 5-FU preserved efficacy while reducing hepatotoxicity. In conclusion, OLT provides timing-dependent anticancer and systemic protective effects in the EAT model, supporting its potential as a cost-effective nutraceutical for cancer prevention and adjunctive therapy. Full article

Parahydrogen-induced hyperpolarization (PHIP), introduced nearly four decades ago, provides an elegant solution to one of the fundamental limitations of nuclear magnetic resonance (NMR)—its notoriously low sensitivity. By converting the spin order of parahydrogen into nuclear spin polarization, NMR signals can be boosted by several orders of magnitude. Here we present a portable, compact, and cost-effective setup that brings PHIP and Signal Amplification by Reversible Exchange (SABRE) experiments within easy reach, operating seamlessly across ultra-low-field (0–10 μT) and high-field (>1 T) conditions at 50% parahydrogen enrichment. The system provides precise control over bubbling pressure, temperature, and gas flow, enabling systematic studies of how these parameters shape hyperpolarization performance. Using the benchmark Chloro(1,5-cyclooctadiene)[1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene]iridium(I) (Ir–IMes) catalyst, we explore the catalyst activation time and response to parahydrogen flow and pressure. Polarization transfer experiments from hydrides to [1-¹³C]pyruvate leading to the estimation of heteronuclear J-couplings are also presented. We further demonstrate the use of Chloro(1,5-cyclooctadiene)[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene]iridium(I) (Ir–SIPr), a recently introduced catalyst that can also be used for pyruvate hyperpolarization. The proposed design is robust, reproducible, and easy to implement in any laboratory, widening the route to explore and expand the capabilities of parahydrogen-based hyperpolarization. Full article

Stereotactic ablative radiotherapy (SABR) has revolutionized the management of patients with oligometastatic and selected primary cancers due to its ability to deliver highly conformal, high-dose radiation in few fractions with minimal toxicity. However, the biological heterogeneity among patients treated with SABR results in variable outcomes, emphasizing the need for predictive and prognostic biomarkers to guide patient selection and post-treatment management. This narrative review discusses the current landscape of biomarker development in the context of SABR across tumor types. Key classes include circulating tumor DNA (ctDNA), extracellular vesicles (EVs), radiomic features, and immunological markers. We highlight the role of each biomarker category in refining therapeutic approaches, their integration into ongoing clinical trials, and future directions for personalized SABR paradigms. Translating these promising biomarker strategies into clinical SABR workflows will require further standardisation, validation, and regulatory alignment. Full article