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Boron neutron capture therapy (BNCT) has emerged as a promising cell-selective clinical treatment for recurrent glioblastoma as well as head and neck cancers. In recent years, BNCT has been implemented in several hospitals using accelerator-based neutron sources. However, direct online measurement of the incident neutron beam intensity during clinical BNCT remains a major challenge. Neutron dosimetry is typically inferred from the accumulated electric charge of the incident proton beam delivered to the beryllium neutron-production target. To improve the reliability of neutron beam control, it is essential to implement an online neutron-monitoring system that complements proton beam current measurements. Such a system enables precise real-time regulation of the neutron dose delivered to patients. In this study, we developed a new online neutron-beam monitoring technique capable of measuring the neutron beam intensity in real time. Reliable monitoring of neutron intensity at the patient position was achieved by detecting fast neutrons. The fast-neutron detector consisted of a silicon diode coupled with a high-density polyethylene neutron converter. The spatial distribution of neutrons was evaluated using Monte Carlo simulations to determine the optimal placement of the neutron beam monitor. The proposed method was validated through gold-activation analysis, cell irradiation experiments, and accelerator tuning. Online neutron-beam monitoring was successfully achieved by detecting fast neutrons at the end of the vacuum beam duct, where neutrons propagate directly without traversing radiation shielding. The neutron counting rate increased immediately at the onset of proton-beam irradiation and decreased upon its termination, exhibiting periodic fluctuations throughout the irradiation period. These fluctuations did not significantly affect the integrated neutron counts, as they were averaged over a typical BNCT irradiation time of approximately 30 min. The fast-neutron detector produced a mean counting rate of 124.6 counts per mC of incident proton-beam charge, with a relative standard deviation of 1.2%, and yielded a neutron-calibration factor of 4.9 × 10 6 cm - 2 per monitor unit. The neutron counting rates remained consistent even when different irradiation phantoms were placed at the patient position. The online neutron-beam monitoring technique using a fast-neutron detector demonstrated high reproducibility, as the neutron counting rates remained stable regardless of the irradiation phantom placed downstream.

Charged particle radiation therapy (such as electron, proton and heavy ion therapies) is presently delivered via large linear or circular electromagnetic particle accelerators. There is growing interest in laser plasma accelerators as an alternative source for therapeutic charged particle radiation, including protons, carbon ions, and very high energy electrons. Laser plasma accelerators offer the potential for extremely high dose rates in a very compact physical footprint. While these radiation sources advancing rapidly, there remain many technical challenges to be overcome prior to clinical translation. In this work, we outline the current state of the art in laser-plasma accelerators for proton, carbon ion and very high energy electron radiation therapy, discuss recent in vitro and in vivo experimental results, and identify the key challenges and opportunities offered by this promising family of technologies.

The present study focuses on optimizing radiation dose for whole-body PET/CT in patients while minimizing impacts on image quality. Whole-body PET/CT scans were conducted on two cohorts of consecutive adults. A pre-optimization dose study involving 100 patients was conducted to establish the baseline dose for whole-body PET/CT examinations. A sample of 100 patients was evaluated to assess the reduction in radiation dose following optimization. The effective radiation dose of FDG PET was determined using a conversion coefficient (k) of 0.019 mSv/MBq based on ICRP Publication 106. Absorbed dose coefficients (mGy/MBq) for the bladder, heart, brain, liver, and lungs were obtained from ICRP 106 and multiplied by injected activity to derive organ equivalent doses (mSv). The effective dose (E) from the CT component of the examination was calculated as the product of the dose-length product (DLP) and the relevant conversion coefficient. Image quality was evaluated by measuring the SUVmax of the largest lesion and SUVmean of the liver. The SUV is defined as the activity concentration (Bq/mL) divided by the injected activity (Bq), normalized to body weight (kg). A total of 100 adult PET/CT scans were assessed before protocol optimization, including 53 men and 47 women. The average patient-specific E from a mean injected activity of 18F-FDG at 281.4 MBq was 10.7 ± 3.1 mSv. The five organs that received the highest organ doses were the bladder, heart, brain, liver, and lungs. Following protocol optimization, an additional 100 adult PET/CT scans were evaluated. The average injected 18F-FDG activity decreased to 200.8 MBq. The average E for PET was 4.1 mSv (range: 2.4-14.9 mSv), the average E for CT was 15.3 mSv (range: 7.2-27.8 mSv), and the average total E was 19.7 mSv (range: 10.0-42.5 mSv). Blinded analysis of image quality indicated no clinically significant degradation in the lower-dose studies. Statistical analysis demonstrated that the higher-dose CT scans provided improved visualization of only the carotid arteries and the posterior triangle region. Optimizing FDG injection doses based on body weight resulted in a significant reduction in E without compromising image quality in patients weighing 50-115 kg.

To evaluate the feasibility, reproducibility, and operational impact of a structured, dose-aware 5-star CT image quality (IQ) rating system across multiple institutions and clinical indications. This retrospective, multinational, IAEA study included 2737 adult (1247 chest, 1490 abdomen) CT examinations across six hospitals in five countries of Europe. Three radiologists per hospital scored CT images using a standardized 5-star system designed to evaluate diagnostic IQ with consideration of radiation dose. Data collected included CT scanner type, clinical indication, patient characteristics, CTDIvol, and DLP. Inter-reader agreement, concordance of star ratings, and dose metrics were evaluated per hospital and clinical indication. The rating framework demonstrated robust reproducibility, with three-reader concordance reaching up to 93% in highly standardized centers and complete discordance remaining exceptionally rare (1.6% cases overall). A compelling inverse correlation between CTDIvol and star ratings was observed, especially for larger patients. Analysis by clinical indication revealed that some intrinsically noise-tolerant exams (for pulmonary nodules and kidney stones) showed high radiation exposure, highlighting an opportunity for optimization. Certain centers used higher-dose protocols, heavily skewing toward 2-star ratings. The 5-star CT IQ rating system is reproducible and supports dose-aware CT optimization. Noise-tolerant examinations should maintain diagnostic quality at lower radiation dose, supporting wider use of low-dose protocols. The method highlights opportunities for multinational and manufacturer-level protocol harmonization and may guide optimization strategies, including the number of series and reconstruction approaches.

Adult diffuse gliomas remain challenging to treat because of their infiltrative growth and resistance to multimodal therapy. Although GLIPR2 has been implicated in autophagy regulation and tumor-related processes, its role in glioma remains unclear. In this study, transcriptomic and clinical data from TCGA, CGGA, and GTEx were integrated with western blotting and immunohistochemical validation in human glioma specimens. Prognostic significance was evaluated using Kaplan-Meier and ROC analyses. Functional effects of GLIPR2 knockdown were examined in U138 and U251 glioma cells through assays of proliferation, migration, invasion, apoptosis, DNA damage, and clonogenic survival. KEGG enrichment analysis and western blotting were used to investigate associated signaling pathways. GLIPR2 expression was significantly elevated in gliomas, predominantly localized in the cytoplasm, and positively correlated with tumor grade. High GLIPR2 expression was associated with unfavorable overall survival and demonstrated predictive value for 1-, 3-, and 5-year survival. Silencing GLIPR2 inhibited glioma cell proliferation, migration, and invasion while promoting apoptosis. Moreover, GLIPR2 knockdown enhanced irradiation-induced γ-H2AX accumulation and reduced post-irradiation clonogenic survival, indicating impaired resolution of radiation-induced DNA damage and increased radiosensitivity. Mechanistically, GLIPR2 depletion was accompanied by reduced PI3K/AKT pathway activity and lower p-GSK-3β and MMP9 expression, without altering total GSK-3β levels. These findings identify GLIPR2 as a glioma-associated biomarker linked to malignant progression, unfavorable prognosis, and radioresistance and nominate it as an investigational molecular vulnerability for further validation.

Light therapies, such as photobiomodulation and photodynamic therapy, have demonstrated effective therapeutical response. However, external irradiation and targeting internal organs is challenging due to high light attenuation and the interindividual anatomical variability, strongly affecting light dosimetry. When considering lung diseases, such as pneumonia and inflammatory conditions, light dosimetry using transcutaneous delivery must consider the total light path from skin coupling through thoracic tissues to the fluence rate reaching the lungs. We here present a computational model based on Monte Carlo simulation developed in house to determine the light dosimetry in the lungs for different wavelengths in normal and diseased lungs. The simulation uses the actual anatomical models derived from human CT scans to generate 3D representations of the thoracic cavity, including 12 distinct tissue types. The lungs were segmented into normal, collapsed regions, infiltrate, and blood vessels. Wavelength-dependent absorption and scattering coefficients for each tissue type were estimated by the reported data in the literature. Our analysis focused on normalized energy deposition profiles defined as µa*fluence rate and fluence rate distributions within each lobe from normal, focal, and diffuse pneumonia, and COVID-19 conditions, under different irradiation positions. The results reveal significant variations in energy deposition and fluence rate distribution across different lung conditions and irradiation parameters, highlighting the need for individualized light dosimetry planning.

Recently, the ICRP developed the pregnant-female mesh-type reference computational phantoms (pfMRCPs) to assess radiation doses to the fetus. To support the generation of reference internal fetal dose coefficients, a fetal specific absorbed fraction (SAF) dataset for photons, electrons, neutrons, and alpha particles will be provided in a forthcoming ICRP publication. Prior to their release, in this study, the computed SAFs were validated and their source- and age-dependent dosimetric trends were systematically analyzed for both maternal and fetal source regions. Photon and electron SAFs were computed using the Geant4 Monte Carlo code, while neutron SAFs were produced using PHITS, following the methodologies adopted in ICRP Publication 155 for pediatric SAF calculations. Alpha SAFs were defined analytically based on an assumption of complete local energy deposition due to the limited range of alpha particles. Cross-code validation was performed for photon and neutron SAFs using PHITS and Geant4, demonstrating general agreement across all compared cases. The results demonstrate clear dependencies of SAFs on fetal mass, source-target geometry, and fetal age. For radiations emitted from maternal source regions, SAFs are generally higher for younger fetuses when the source regions are located in close proximity to the fetus, whereas SAFs for older fetuses become larger as the source-target geometry changes with increasing fetal growth. For fetal source regions, SAFs consistently decrease with increasing fetal age due to the increasing mass of fetal target regions with age. The established dataset provides physically consistent fetal SAFs across multiple radiation types and will be used to support the development of standardized fetal dose coefficients in future ICRP publications.

Internal mammary node (IMN) irradiation has the potential to improve the overall survival in nodal positive breast cancer patients. Nevertheless, to achieve these benefits while keeping treatment related morbidity low is technically complex and requires careful patient selection and treatment planning. For this, detection of IMN involvement is of particular importance. This study aims to investigate response of visible IMN to neoadjuvant chemotherapy as potential surrogate for initial IMN involvement. We analyzed 298 non-metastatic breast cancer patients who underwent high-resolution pre-treatment MRI and follow-up MRI after neoadjuvant chemotherapy. If visible IMN were present, diameters were measured in axial and coronal planes on both pre- and post- neoadjuvant chemotherapy (NACT) MRIs. Differences in size were assessed and response systematically classified and correlated with clinical and histopathological response, axillary lymph node metastases (AXN) and tumor characteristics. 175 (58.7%) of 298 breast cancer patients had visible IMN on pretreatment MRI and 158 patients had a histopathological response of the primary tumor. Among these, 62 patients (39.3%) had a response of visible IMN. In patients with AXN the rate of IMN response was particular high with 48.6 %. In patients without AXN 21.8 % of patients with visible IMN showed a response to NACT. Response of visible IMN correlated significantly with medial tumor location and predominant tumor contact with internal mammary perforator vessels (IMPVc). The large majority (76.3 %) of IMN with response to NACT were initially rated as non-suspicious during initial staging and in the interdisciplinary tumor board consensus. Clinical IMN response to NACT may serve as an indicator of previously undetected IMN involvement in a relevant proportion of early breast cancer patients. The observation that approximately 20% of patients without AXN metastases demonstrated a radiologic IMN response warrants further investigation, as this subgroup is not routinely considered for IMN irradiation. These findings highlight the need for prospective validation in larger, well-characterized cohorts using standardized imaging protocols to better define the clinical significance of IMN response to systemic therapy.

Cancer immunotherapy is often hindered by the immunosuppressive tumor microenvironment and the inefficient activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway under hypoxic conditions. To address these challenges, we developed a hierarchical core-shell Au@Co-EGCG/Mn-EGCG (ACM) nanoplatform that synergistically integrates radiosensitization with a dual-track STING amplification strategy. Owing to its high-Z gold core and robust catalase-like activity, the ACM nanostructure effectively alleviates tumor hypoxia and maximizes X-ray energy deposition, leading to an intense burst of reactive oxygen species (ROS) and irreparable DNA damage. This synergy in turn triggers potent immunogenic cell death and substantial mitochondrial DNA (mtDNA) leakage. Critically, the hierarchical release of Mn2+ and Co2+ ions within tumor cells establishes a "sequential synergistic cascade": Mn2+ sensitizes cGAS for enhanced DNA recognition, while Co2+ acts as a high-gain amplifier by enhancing the binding affinity of STING for 2', 3'-cyclic GMP-AMP (cGAMP). This molecular relay ignites a systemic surge of pro-inflammatory cytokines, notably IFN-β, effectively converting "cold" tumors into "hot" ones. In vivo, ACM-mediated radiotherapy not only achieves thorough in situ tumor ablation but also elicits a powerful abscopal effect, suppressing distant metastasis through enhanced T-cell infiltration and macrophage repolarization. Collectively, this work establishes a potent radio-metalloimmunotherapy paradigm to overcome radioresistance and systemic cancer progression. STATEMENT OF SIGNIFICANCE: The majority of colorectal cancers are microsatellite stable (MSS) and resistant to immunotherapy due to a "cold" tumor microenvironment. In this study, we introduce a hierarchical core-shell nanoparticle that, upon X-ray irradiation, sequentially releases two metal ions to activate the cGAS-STING pathway cooperatively. Unlike conventional single-agent STING agonists, our design separates the DNA sensitization provided by Mn2+ from the signal amplification driven by Co2+, creating a synergistic cascade that overcomes hypoxia-induced immunosuppression. This dual-track mechanism transforms resistant MSS tumors into immune-responsive "hot" lesions, eliminating primary tumors and suppressing distant metastases. The work establishes a new paradigm of radio-metalloimmunotherapy, offering a translatable strategy to convert radiation into a systemic immune adjuvant.

Thermal transport by fluids has numerous applications, including thermal radiators, thermal and cooling systems, MHD generators, etc. In this study, the thermal transport performance of the Casson fluid is investigated in response to the inclusion of three combinations of nanoscale particles. These combinations are: (i) [Formula: see text], (ii) [Formula: see text]-[Formula: see text] and (iii) [Formula: see text]-[Formula: see text]-[Formula: see text]. These combinations are called mono-nanoparticles, di-nanoparticles, and tri-nanoparticles, respectively. Kerosene oil is used as the base fluid. The boundary layer approximations are used for the simplification of the system of governing PDEs under local thermal equilibrium. A local similarity transformation is used to reduce the governing equations to a system of ODEs. Numerical solutions of the transformed system of BVPs using a numerical method called BVP4C. The optimization in thermal enhancement is aimed at increasing the thermal conductivity due to the dispersion of multi-nanoscale particles. A porous medium creates a resistance to the flow, which reduces the convective heat transfer. Consequently, the heat transport rate decreases. Eventually, the local Nusselt number decreases. Thus, flow in practical applications should not be in the porous medium where the local Nusselt number needs to be optimized. The viscoplasticity reduces the skin friction coefficient. Moreover, the boundary layer thickness associated with tri-nanofluid ([Formula: see text]-[Formula: see text]-[Formula: see text]-kerosene oil) is wider than that with [Formula: see text]-[Formula: see text]-kerosene oil and [Formula: see text]-Kerosene oil. It is established in this study that kerosene containing [Formula: see text] and [Formula: see text] has the highest effective thermal conductivity in comparison with kerosene oil, having [Formula: see text]and [Formula: see text] and kerosene oil with [Formula: see text]. Therefore, it is concluded that among[Formula: see text]-[Formula: see text]-[Formula: see text]-kerosene oil, [Formula: see text]-[Formula: see text]-kerosene oil and [Formula: see text]-kerosene oil, [Formula: see text]-[Formula: see text]-[Formula: see text]-kerosene oil is the best working fluid concerning heat transport. The thermal radiations are electromagnetic waves that carry heat energy with them, and therefore, the thermal boundary layer thickness is reduced, and the local Nusselt number is increased with an increase in the thermal radiations.

Acoustic tweezers provide a versatile approach for contactless particle manipulation by harnessing acoustic radiation forces with acoustic-streaming-induced transport. Although the size-dependent competition between these two mechanisms is well established, the extent to which their force balance is governed by the relationship between the characteristic size of the liquid domain and the acoustic wavelength remains insufficiently quantified. In this paper, we conduct a theoretical and numerical analysis of the acoustic pressure distribution, streaming flow, and particle dynamics based on the bulk acoustic standing wave system in Rayleigh/ Mie-scale liquid domains under different droplet sizes, excitation frequencies, and boundary geometries. Furthermore, we precisely analyzed the acoustic driving forces of a single particle in the time domain as well as the steady-state spatial distribution of that particle, and thereby obtained the spatial average force within the channel. Further research indicates that particles with a diameter greater than 10 μm could be effectively captured at the pressure nodes and form high-density aggregation particle bands. The full-space average acoustic force analysis in Rayleigh/Mie-scale channels shows that the critical particle size is approximately 5-10 μm for a balance state with streaming-induced acoustic drag force and acoustic radiation force. Among these, we found that the resonance caused by the channel size structure also has a significant effect on the arrangement of the particles. These findings can provide a theoretical basis for the design of pre-designed channels for acoustic microfluidics targeting specific-sized particles, thereby offering significant support for clinical analyses of biological particle movement, targeted drug therapy, and diagnostic and therapeutic procedures.

Despite advancements in breast cancer adjuvant therapies, some patients with indications may not receive treatment. We examined the association of self-reported racial/ethnic discrimination in patient-provider interactions and the receipt of clinically indicated therapies. The Pathways Study is a prospective cohort of women diagnosed with invasive breast cancer from 2005 to 2013 at Kaiser Permanente Northern California. Racial/ethnic discrimination in patient-provider interactions was assessed from the Interpersonal Processes of Care survey at baseline, 6 months, and 24 months post-diagnosis. Logistic regression compared women who did not initiate clinically-indicated adjuvant therapy with those who did overall, and by race and ethnicity. Covariates included race and ethnicity, age at diagnosis, country of birth, education level, income, marital status, and American Joint Committee on Cancer staging. Overall, 3,610 women had indication for hormonal therapy, 2,450 for chemotherapy, and 3,258 for radiation therapy. In multivariable analyses, women reporting discrimination were at increased odds of not initiating hormonal therapy (adjusted odds ratio [aOR] = 1.43, 95% CI = 1.05-1.93) than those who did not self-report discrimination, regardless of their race/ethnicity. An increased odds of non-initiation for reported discrimination was found for radiation therapy (aOR = 1.26, 95% CI = 0.99-1.61), although it was not statistically significant. There was no association for chemotherapy initiation (aOR = 0.96, 95% CI = 0.69-1.33). Self-reported racial/ethnic discrimination in patient-provider interactions was associated with the non-initiation of hormonal therapy in women with breast cancer. Further studies are needed to explore the impact of this association on breast cancer prognosis. Not applicable.