Low-dose Radiation Research Articles

Lesson learned in pediatric haploidentical transplantation in a low-resource environment: delivering melphalan IV and using low dose radiation reduce graft failure

ABSTRACT Objectives: Primary graft failure (pGF) after hematopoietic stem-cell transplant is associated with considerable morbidity and mortality. The incidence in haplo-HSCT has been reported to be between 0% and 30%. In 2018, we identified a pGF incidence of 35% in our pediatric haplo-HSCT recipients with hematologic malignancies, which motivated us to enact changes to the conditioning regimen. Methods: We performed a single-center prospective, pre–post study of consecutive patients under 16 years with hematologic malignancies, from January 2015 to December 2022 who received a haplo-HSCT. Twenty-six pediatric patients received a haplo-HSCT before September 2018 (G1) and 36 patients after (G2). The main conditioning regimen for G1 was myeloablative with Flu/Cy/Bu, and for G2 the main regimen was reduced intensity Flu/Cy/Mel/TBI2. Results: Nine patients (35%) in G1 had primary graft failure, while in G2 there were no patients with pGF. The median follow-up for G1 was 15.9 months, and for G2 was 24.8 months, with an estimated overall survival at 12 months of 63% (95% CI 47–76) versus 85% (95% CI 73–93), and at 24 months of 47% (95% CI 31–64) versus 70% (95% CI 54–82) respectively (p = .007). Conclusion: After September 2018 conditioning regimen modifications were implemented with the objective of reducing primary failure, consisting mainly of switching from busulfan to melphalan as the alkylating agent of choice, and adding, when clinically possible TBI. Primary failure has been significantly reduced in our institution since then.

Protracted Exposure to a Sub-background Radiation Environment Negatively Impacts the Anhydrobiotic Recovery of Desiccated Yeast Sentinels.

Experiments that examine the impacts of subnatural background radiation exposure provide a unique approach to studying the biological effects of low-dose radiation. These experiments often need to be conducted in deep underground laboratories in order to filter surface-level cosmic radiation. This presents some logistical challenges in experimental design and necessitates a model organism with minimal maintenance. As such, desiccated yeast ( Saccharomyces cerevisiae ) is an ideal model system for these investigations. This study aimed to determine the impact of prolonged sub-background radiation exposure in anhydrobiotic (desiccated) yeast at SNOLAB in Sudbury, Ontario, Canada. Two yeast strains were used: a normal wild type and an isogenic recombinational repair-deficient rad51 knockout strain ( rad51 Δ). Desiccated yeast samples were stored in the normal background surface control laboratory (68.0 nGy h -1 ) and in the sub-background environment within SNOLAB (10.1 nGy h -1 ) for up to 48 wk. Post-rehydration survival, growth rate, and metabolic activity were assessed at multiple time points. Survival in the sub-background environment was significantly reduced by a factor of 1.39 and 2.67 in the wild type and rad51 ∆ strains, respectively. Post-rehydration metabolic activity measured via alamarBlue reduction remained unchanged in the wild type strain but was 26% lower in the sub-background rad51 ∆ strain. These results demonstrate that removing natural background radiation negatively impacts the survival and metabolism of desiccated yeast, highlighting the potential importance of natural radiation exposure in maintaining homeostasis of living organisms.

Low-Dose Radiation Therapy Impacts Microglial Inflammatory Response without Modulating Amyloid Load in Female TgF344-AD Rats.

Low-dose radiation therapy (LD-RT) has demonstrated in preclinical and clinical studies interesting properties in the perspective of targeting Alzheimer's disease (AD), including anti-amyloid and anti-inflammatory effects. Nevertheless, studies were highly heterogenous with respect to total doses, fractionation protocols, sex, age at the time of treatment and delay post treatment. Recently, we demonstrated that LD-RT reduced amyloid peptides and inflammatory markers in 9-month-old TgF344-AD (TgAD) males. As multiple studies demonstrated a sex effect in AD, we wanted to validate that LD-RT benefits are also observed in TgAD females analyzed at the same age. Females were bilaterally treated with 2 Gy×5 daily fractions, 2 Gy×5 weekly fractions, or 10 fractions of 1 Gy delivered twice a week. The effect of each treatment on amyloid load and inflammation was evaluated using immunohistology and biochemistry. A daily treatment did not affect amyloid and reduced only microglial-mediated inflammation markers, the opposite of the results obtained in our previous male study. Moreover, altered fractionations (2 Gy×5 weekly fractions or 10 fractions of 1 Gy delivered twice a week) did not influence the amyloid load or neuroinflammatory response in females. A daily treatment consequently appears to be the most efficient for AD. This study also shows that the anti-amyloid and anti-inflammatory response to LD-RT are, at least partly, two distinct mechanisms. It also emphasizes the necessity to assess the sex impact when evaluating responses in ongoing pilot clinical trials testing LD-RT against AD.

Enhancement of the Tumor Suppression Effect of High-dose Radiation by Low-dose Pre-radiation Through Inhibition of DNA Damage Repair and Increased Pyroptosis.

Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.

Janus ACSP Nanoparticle for Synergistic Chemodynamic Therapy and Radiosensitization.

Protective autophagy and DNA damage repair lead to tumor radio-resistance. Some hypoxic tumors exhibit a low radiation energy absorption coefficient in radiation therapy. High doses of X-rays may lead to side effects in the surrounding normal tissues. In order to overcome the radio-resistance and improve the efficacy of radiotherapy based on the characteristics of the tumor microenvironment, the development of radiosensitizers has attracted much attention. In this study, a Janus ACSP nanoparticle (NP) was developed for chemodynamic therapy and radiosensitization. The reactive oxygen species generated by the Fenton-like reaction regulated the distribution of cell cycles from a radioresistant phase to a radio-sensitive phase. The high-Z element, Au, enhanced the production of hydroxyl radicals (•OH) under X-ray radiation, promoting DNA damage and cell apoptosis. The NP delayed DNA damage repair by interfering with certain proteins involved in the DNA repair signaling pathway. In vivo experiments demonstrated that the combination of the copper-ion-based Fenton-like reaction and low-dose X-ray radiation enhanced the effectiveness of radiotherapy, providing a novel approach for synergistic chemodynamic and radiosensitization therapy. This study provides valuable insights and strategies for the development and application of NPs in cancer treatment.

Treatment Plan Optimization Following Laser Interstitial Thermal Therapy (LITT) for Recurrent Metastasis Using Cleveland Clinic Scaling System (CCSS)

INTRODUCTION: Laser interstitial thermal therapy (LITT) is an effective treatment option for recurrent metastasis (RM). However, determining the best treatment approach for each patient following LITT remains challenging due to mixed pathology and lack of consensus. The Cleveland Clinic Scaling System (CCSS) has been proposed to facilitate decision-making in patients with radiation necrosis (RN) and/or RM following LITT. METHODS: We conducted a retrospective analysis of data from 20 patients who underwent LITT for RN and/or RM between 2019 and 2022 at Cleveland Clinic. Based on the symptomatic RN and/or RM which was confirmed by MRI, LITT, and biopsy were carried out. Three samples were acquired from the superficial, middle, and deep parts of each patient’s lesion. The samples were then classified into three main categories: RN, RM, or a mixture of the two, based on pathological results. Patient management was guided by our novel CCSS. According to CCSS, patients with 100% RN underwent continued observation with a 3-month MRI, individuals with >20% tumor component received a low-dose or standard-dose radiation therapy ± CNS-penetrating targeted therapy, while those with <20% tumor underwent short-term observation with 6-week MRIs ± CNS-penetrating targeted therapy. RESULTS: Among the patients, 57% were females, lung cancer was the most prevalent malignancy (61.4%), and the median age was 52 years (ranging from 25 to 83 years). Our analysis demonstrated that the application of the CCSS protocol significantly improved treatment outcomes after LITT, resulting in 93% lesion control at the 10-month follow-up. CONCLUSIONS: The use of the CCSS protocol can refine the treatment plan for patients with RN and/or RM following LITT. This approach has the potential to enhance patient safety by improving tumor control and minimizing unnecessary radiation.

Low-dose radiation therapy for COVID-19 pneumonia: Comparison of dosimetry and life-time attributable risk of cancer with conventional AP-PA fields and bone marrow sparing VMAT.

Low-dose radiation therapy (LDRT) to lungs did show encouraging results in COVID-19 patients in some clinical trials. However, there has been some concern regarding the long-term risk of radiation-induced cancer (RIC). Compared to the conventional AP-PA field technique, volumetric modulated arc therapy (VMAT) can potentially reduce the dose to the marrow and other organs at risk (OARs) and thus minimize the risk of cancer. We designed a dosimetry study to study if VMAT can reduce the exposure to the marrow and other OAR doses and curtail the estimated life-time attributable risk (LAR) of cancer. We retrieved the computed tomography scan data of 10 patients (aged 40-60 years, median 48 years) who have been already treated for any malignancy in the region of the thorax. A dose of 1.0 Gy in single fraction was prescribed to both lungs. All the organs were delineated as per the established guidelines. The dosimetry achieved by the two plans was compared to find the difference. Mean OAR doses were used to estimate the LAR for both plans and compared. Planning target volume coverage parameters like conformity index and homogeneity index were significantly better with VMAT (P value < 0.05 for all). The mean dose to most OARs was significantly lower with VMAT (P value < 0.05 for all). The mean dose to the marrow was significantly lower with VMAT (59.05 vs 81.9 cGy with P value < 0.05). The overall LAR was significantly lower with VMAT as compared to the conventional plan (0.357% vs 0.398%, P value < 0.05). Compared to the conventional technique, VMAT provides better OAR dosimetry for lung irradiation (a prescription dose of 1.0 Gy or more) in COVID-19 pneumonia. VMAT significantly reduces the risk of RIC. We therefore suggest if lung LDRT is used for COVID-19 patients, VMAT is the preferred technique for a prescription dose of ≥1.0 Gy.

FSformer: A combined frequency separation network and transformer for LDCT denoising

Low-dose computed tomography (LDCT) has been widely concerned in the field of medical imaging because of its low radiation hazard to humans. However, under low-dose radiation scenarios, a large amount of noise/artifacts are present in the reconstructed image, which reduces the clarity of the image and is not conducive to diagnosis. To improve the LDCT image quality, we proposed a combined frequency separation network and Transformer (FSformer) for LDCT denoising. Firstly, FSformer decomposes the LDCT images into low-frequency images and multi-layer high-frequency images by frequency separation blocks. Then, the low-frequency components are fused with the high-frequency components of different layers to remove the noise in the high-frequency components with the help of the potential texture of low-frequency parts. Next, the estimated noise images can be obtained by using Transformer stage in the frequency aggregation denoising block. Finally, they are fed into the reconstruction prediction block to obtain improved quality images. In addition, a compound loss function with frequency loss and Charbonnier loss is used to guide the training of the network. The performance of FSformer has been validated and evaluated on AAPM Mayo dataset, real Piglet dataset and clinical dataset. Compared with previous representative models in different architectures, FSformer achieves the optimal metrics with PSNR of 33.7714 dB and SSIM of 0.9254 on Mayo dataset, the testing time is 1.825 s. The experimental results show that FSformer is a state-of-the-art (SOTA) model with noise/artifact suppression and texture/organization preservation. Moreover, the model has certain robustness and can effectively improve LDCT image quality.

Investigation of Deconvolution Method with Adaptive Point Spread Function Based on Scintillator Thickness in Wavelet Domain.

In recent years, indirect digital radiography detectors have been actively studied to improve radiographic image performance with low radiation exposure. This study aimed to achieve low-dose radiation imaging with a thick scintillation detector while simultaneously obtaining the resolution of a thin scintillation detector. The proposed method was used to predict the optimal point spread function (PSF) between thin and thick scintillation detectors by considering image quality assessment (IQA). The process of identifying the optimal PSF was performed on each sub-band in the wavelet domain to improve restoration accuracy. In the experiments, the edge preservation index (EPI) values of the non-blind deblurred image with a blurring sigma of σ = 5.13 pixels and the image obtained with optimal parameters from the thick scintillator using the proposed method were approximately 0.62 and 0.76, respectively. The coefficient of variation (COV) values for the two images were approximately 1.02 and 0.63, respectively. The proposed method was validated through simulations and experimental results, and its viability is expected to be verified on various radiological imaging systems.

A dense and U-shaped transformer with dual-domain multi-loss function for sparse-view CT reconstruction.

CT image reconstruction from sparse-view projections is an important imaging configuration for low-dose CT, as it can reduce radiation dose. However, the CT images reconstructed from sparse-view projections by traditional analytic algorithms suffer from severe sparse artifacts. Therefore, it is of great value to develop advanced methods to suppress these artifacts. In this work, we aim to use a deep learning (DL)-based method to suppress sparse artifacts. Inspired by the good performance of DenseNet and Transformer architecture in computer vision tasks, we propose a Dense U-shaped Transformer (D-U-Transformer) to suppress sparse artifacts. This architecture exploits the advantages of densely connected convolutions in capturing local context and Transformer in modelling long-range dependencies, and applies channel attention to fusion features. Moreover, we design a dual-domain multi-loss function with learned weights for the optimization of the model to further improve image quality. Experimental results of our proposed D-U-Transformer yield performance improvements on the well-known Mayo Clinic LDCT dataset over several representative DL-based models in terms of artifact suppression and image feature preservation. Extensive internal ablation experiments demonstrate the effectiveness of the components in the proposed model for sparse-view computed tomography (SVCT) reconstruction. The proposed method can effectively suppress sparse artifacts and achieve high-precision SVCT reconstruction, thus promoting clinical CT scanning towards low-dose radiation and high-quality imaging. The findings of this work can be applied to denoising and artifact removal tasks in CT and other medical images.

Хемилюминесцентные характеристики периферической крови при облучении in vitro в диапазоне доз 100–500 мГр

Abstract. Nowadays a lot of examinations are dedicated to determination of radiobiological effects under low doses of ionising radiation. It is known that ionising radiation in the cells of an organism increases generation of reactive oxygen species (ROS). The purpose of the work is to determine basic parameters of chemiluminescent kinetics of ROS in peripheral blood under in vitro radiation in the range of 100–500 mGy doses. The research will extend the knowledge of the impact degree of ionising radiation in low doses on organism tissue of farm animals. Scientific novelty is that the results of the research will allow to predict radiobiological effects of low doses in a multicellular organism. The research is included in practical and fundamental directions of radiobiology. Research methods. In vitro radiation of blood samples in the range of 100–500 mGy doses. The kinetics of generation of ROS is registered on 36-channel chemiluminometer 3604-PC. Results. The doses in the range of 100–300 mGy accelerated the time of the first peak of spontaneous and activated generation of radicals, under 500 mGy dose the formation of the first peak of spontaneous and activated generation of primary ROS decelerated. Under the impact of low absorbed doses maximum intensity of primary and secondary radicals generation decreased. The inhibition of primary radicals spontaneous production occurred under 100–300 mGy doses, the inhibition of antigen activated generation of primary ROS was under 400 mGy. The reduction of the amount of spontaneous secondary ROS was registered under 100 mGy dose. The decrease of antigen activated secondary radicals production occurred under 100–300 mGy doses. 500 mGy dose inhibited a reaction ability of blood cells to generate primary radicals. The external in vitro gamma radiation in the range of 100–500 mGy had a negative impact on peripheral blood cells showing an acceleration of chemiluminescent reaction as well as decrease of maximum intensity of the first peak of spontaneous and antigen activated primary and secondary radicals production. As a consequence, a decrease of the amount of primary and secondary radicals production was revealed.

Low Dose Radiation and Solid Tumors Mortality Risk.

US nuclear capable shipyard workers have increased potential for occupational radiation exposure. The aim of the study is to examine solid tumor mortality risks at low doses. 437,937 workers working from 1957 to 2004 at eight US shipyards were studied. Radiation workers with a median life-time dose at 0.82 mSv had a significantly lower solid tumor mortality risk (relative risk [RR]: 0.96, 95% confidence interval [CI]: 0.94-0.98) than nonradiation workers. Among 153,930 radiation workers, the RRs of solid tumors increased with increasing dose categories without statistical significance. The dose category >0-<25 mSv had significantly lower RR (0.95, 95% CI: 0.91-0.99) versus 0 dose and the excess relative risk was 0.05/100 mSv (95% CI: 0.01-0.08). Solid tumor risk might increase with radiation dose, but not linearly at low doses. Actual mortality risk may be dependent on dose received.

Abstract 5743: Liposome platform enables X-ray induced photodynamic therapy treatment against human triple negative breast cancer cells

Abstract In this study, we employed X-ray induced photodynamic therapy (X-PDT) for the treatment on triple negative breast cancer (TNBC) cells. To do this, we rationally developed a liposome delivery system co-loaded with protoporphyrin IX (PPIX) and perfluorooctyl bromide (PFOB). Low-dose X-ray at 2Gy was employed to activate PPIX for reactive oxygen species (ROS) generation, and the co-loading of PFOB provided additional oxygen to augment ROS production. The highly toxic ROS triggered TNBC cell death. In vitro X-PDT effects including intracellular ROS generation, cytotoxicity, cell viability and apoptosis/necrosis assay in TNBC cells were studied. Our results indicate that the nanocarriers effectively induced X-PDT effect with very low dose radiation, which makes it possible to damage cancer cells. Our strategy may offer a paradigm-shifting treatment alternative for TNBC patients who need neoadjuvant radiotherapy but wish to avoid long term detrimental effect on functional outcome by undergoing X-PDT using only a fraction of the conventional radiotherapy. Citation Format: Biyao Yang, Rui Sang, Yi Li, Ewa Goldys, Wei Deng. Liposome platform enables X-ray induced photodynamic therapy treatment against human triple negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5743.

Abstract 6642: Exploring the x-ray psoralen activated cancer therapy mechanism of action in a genetically engineered mouse model of soft tissue sarcoma

Abstract BACKGROUND: Psoralen is a natural ultraviolet activated compound that has been used for over 70 years to treat skin cancer, psoriasis, and vitiligo. Recently, to expand its use beyond external treatment, a novel therapeutic called X-PACT (X-ray psoralen activated cancer therapy) was created to treat internal tumors. A combination of 8-methoxypsoralen and phosphors that convert low doses of x-ray radiation to ultraviolet (UV) light are injected into solid tumors and subsequently activated by x-ray photons with considerable antineoplastic effect. Notably, canine clinical trials have observed significant abscopal effects of X-PACT therapy on metastatic lesions throughout patients, but the immunomodulatory mechanisms of action are unclear (Nolan et al, in submission). Here, we present preliminary data investigating the immune response to X-PACT therapy in a murine soft tissue sarcoma (STS) model. METHODS: Six mice of the inducible KrasG12D/+; p53flox/flox (KP) murine STS model with palpable, gastrocnemius tumors were used in this initial study. Four mice underwent treatment with X-PACT. In this group, psoralen was mixed with energy converters and injected into the tumor. The mice then received low-level radiation to activate the drug. Treatment was performed five times over a 15-day period and the animals were sacrificed within 48 hours of final treatment. The other two mice with induced tumors received no treatment prior to sacrifice. For both groups, a cardiac blood draw was performed at the time of sacrifice to obtain plasma serum for analysis. Luminex xMAP technology was used for multiplexed quantification of 45 mouse cytokines, chemokines and growth factors. RESULTS: There were five markers that showed significantly different levels between the treated and control groups. Results indicated significantly higher (p = 0.006) plasma concentrations of macrophage derived chemokine (MDC) following five rounds of treatment with X-PACT therapy. Additionally, the treated mice displayed significantly lower concentrations of granulocyte colony-stimulating factor (G-CSF, p = 0.003), eotaxin (p = 0.016), tissue inhibitor of matrix metalloproteinase 1 (TIMP1, p = 0.024), and interleukin-1β (IL-1β, p = 0.033) compared to untreated mice with STS. CONCLUSION: In humans, MDC levels are associated with longer survival and lower cancer severity. G-CSF, eotaxin, TIMP1, and IL-1β are upregulated in cancer patients and correlate with disease severity. Together, the lower concentrations of G-CSF, Eotaxin, TIMP1, and IL-1β suggest a softening of cancer severity following X-PACT treatment. Further studies and larger sample sizes are necessary to confirm and expand upon these preliminary findings. Citation Format: Beatrice Schleupner, Alexandra Hunter Aitchison, Elle MacAlpine, Nicole Cantor, Jason Somarelli, Brian Brigman, Julia Visgauss, Michael Monument, William Eward. Exploring the x-ray psoralen activated cancer therapy mechanism of action in a genetically engineered mouse model of soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6642.

Abstract 1178: Tissue nanomechanics as a novel, clinically translatable predictive early biomarker of response in combination immunotherapy

Abstract Background: Recently, the successful integration of immunotherapy with other treatment modalities has demonstrated its efficacy in enhancing immune activation and suppressing tumors in solid cancers. The most promising of such efforts include the use of low dose radiation (LD-XRT) to prime the tumor microenvironment and enhance the T cell infiltration and activation [Barsoumian HB, et al., 2020; Patel RR, et al., 2021; He K, et al., 2023]. With these advancements, there is an urgent need to develop clinical biomarkers to predict response and optimize treatment decisions. Recent evidence underscores the importance of nanomechanical alterations within the tumor microenvironment as mechanistic indicators of aggressiveness [Plodinec M, et al., 2012]. This study aims to demonstrate the value of ARTIDIS nanomechanical signature as early predictor of elucidate of response to combination LD-XRT/immune checkpoint inhibitors (ICI). Our measurement protocol in mice follows the same settings for biopsies acquired in routine biopsy collection protocol, thus supporting prompt clinical translation and integration. Methods: We established a mouse model of 344SQ lung adenocarcinoma tumors that exhibited resistance to anti-PD1 treatment in 129Sv/Ev mice. These mice underwent treatment protocols involving a combination of anti-PD1 and anti-CTLA4 antibodies, both with and without LD-XRT pre-treatment. Throughout the study, we closely monitored survival rates and tumor growth across diverse experimental groups. Employing the ARTIDIS platform, a cutting-edge technology that integrates atomic force microscopy with proprietary artificial intelligence algorithms, we extracted a multiparametric nanomechanical signature and we evaluated its outcome prediction value. This signature was then complemented by histopathology, multiplex immunofluorescence, and Nanostring assays to elucidate mechanisms of stroma remodulation and immune infiltration. Results: This study identifies the unique nanomechanical signature predictive of response to immunotherapy alone or in combination with radiation. Using the tissue nanomechanical signature as a predictive biomarker, we achieved precise differentiation between responders and non-responders, boasting a 90% sensitivity, 99.1% specificity, and a 96% AUC. To our knowledge, this study is the first to demonstrate the response-predicting power of a tissue derived nanomechanical signature for immune checkpoint inhibitors administered in combination with LD-XRT. These findings support clinical translation of the ARTIDIS nanomechanical signature as a pivotal tool for clinically predicting and evaluating responses to integrated radiation and immunotherapy approaches. Citation Format: Gitika Srivastava, Sara Nizzero, Mark Wasley, Mingee Kim, Kathleen Graham, Papa Diogop Ndiaye, Mariam Gachechiladze, Nahum Puebla-Osorio, Philipp Oertle, Tobias Appenzeller, Vittorio Cristini, Marko Loparic, Marija Plodinec, James W. Welsh. Tissue nanomechanics as a novel, clinically translatable predictive early biomarker of response in combination immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1178.

The effects of electromagnetic field radiation of extremely low frequency on growth parameters and nucleotide substitutions in L. minor clones

Current technologies have become a source of electromagnetic pollution resulting from artificially generated electromagnetic radiation (EMR). To understand the influence of the EMR on living organisms, we investigated the long-term effects of EMR of 50 Hz frequency on duckweed (Lemna minor) clones. Experimental groups of duckweed were treated directly and indirectly by changing EMR generating magnetic flux (MF) starting from 2 µT (0–11 weeks from the beginning of the experiment) and switching to 300 µT (12–48 weeks) MF density during the second part of the experiment. The growth parameters (plant growth, frond area, and frond number) and the point mutations appearing at the antioxidant genes DNA sequences [ascorbate peroxidase (APx), glutathione peroxidase (GPx), and catalase (Cat)] were analyzed. The significantly enhanced number of nucleotide substitutions in DNA sequences of L. minor clones directly affected by LF EMR in comparison to indirectly affected clones was revealed at the introns of APx, GPx, and Cat genes starting from the 10th week of the experiment. The results indicate that even low-dose chronic electromagnetic radiation may contribute to the changes in growth parameters and generation of point mutations in antioxidant gene sequences, especially in the intron regions.

Distinguish response of low-dose radiation with different dose-rate on gene expression of human coronary artery endothelial cells: a bioinformatic study based on transcriptomic sequencing

Purpose People are exposed to low-dose radiation in medical diagnosis, occupational, or life circumstances, but the effect of low-dose radiation on human health is still controversial. The biological effects of radiation below 100 mGy are still unproven. In this study, we observed the effects of low-dose radiation (100 mGy) on gene expression in human coronary artery endothelial cells (HCAECs) and its effect on molecular signaling. Materials and methods HCAECs were exposed to 100 mGy ionizing radiation at 6 mGy/h (low-dose-rate) or 288 mGy/h (high-dose-rate). After 72 h, total RNA was extracted from sham or irradiated cells for Quant-Seq 3'mRNA-Seq, and bioinformatic analyses were performed using Metascape. Gene profiling was validated using qPCR. Results Compared to the non-irradiated control group, 100 mGy of ionizing radiation at 6 mGy/h altered the expression of 194 genes involved in signaling pathways related to heart contraction, blood circulation, and cardiac myofibril assembly differentially. However, 100 mGy at 288 mGy/h altered expression of 450 genes involved in cell cycle-related signaling pathways, including cell division, nuclear division, and mitosis differentially. Additionally, gene signatures responding to low-dose radiation, including radiation dose-specific gene profiles (HIST1H2AI, RAVER1, and POTEI) and dose-rate-specific gene profiles (MYL2 for the low-dose-rate and DHRS9 and CA14 for the high-dose-rate) were also identified. Conclusions We demonstrated that 100 mGy low-dose radiation could alter gene expression and molecular signaling pathways at the low-dose-rate and the high-dose-rate differently. Our findings provide evidence for further research on the potential impact of low-dose radiation on cardiovascular function.

Public knowledge, sentiments, and perceptions of low dose radiation (LDR) and power production, with special reference to reactor accidents

Abstract People’s perceptions concerning radiation inform decision making in relation to nuclear power production. There have been extensive studies of people’s perceptions of radiation including in relation to the Fukushima and Chernobyl nuclear events. This paper reports on a social science literature review study and is concerned with public responses to low dose radiation (LDR) and nuclear facilities, particularly in the marine environment. This review confirms that people with little knowledge about radiation have the highest risk perceptions in relation to nuclear power; conversely people with a broader knowledge have lower risk perceptions and are more favourable to nuclear power. Education can increase positive perceptions, but the influence of underlying experience of feeling, emotion, attachment, or mood may dampen this effect. This paper reports studies which document anxiety within the Japanese community in relation to the Fukushima nuclear accident. Literature concerning specific radionuclides released is described. While there are uncertainties about the presence of health impacts following LDR exposures, public attitudes are not in line. There is a need for better dialogue between nuclear professionals and scientists to achieve better nuclear education and public communication outcomes; more specific communication surrounding multi-isotopes, and multi-elements of nuclear power plant disaster releases is warranted. Trusted communicators should include nuclear and social scientists as well as regulators. Given the importance of decarbonization in the context of climate change, this is increasingly important.

A potential novel technique for measurement of pulp volume on periapical radiography: A pilot study.

Pulp volume can be assessed during dental treatment. Three-dimensional imaging techniques are not routinely used for this purpose because of high radiation doses. This study aimed to develop a novel method to measure pulp volume using periapical radiography. In this study, cone-beam computed tomography (CBCT) was used as a reference method. Periapical radiography and CBCTs obtained from the same patients (n = 32) were recorded. Pulp volume was determined by observing the density differences between the pulp and peripheral structures using ImageJ. A method of graph and volume calculation was developed for each tooth. The Shapiro-Wilk test and Mann-Whitney U test were used to show normality and non-normal distributions. The Bland-Altman plot was used to show the scattering of the mean versus difference values of the measurements of the two methods used to calculate the pulp volume. Normality was evaluated using the Shapiro-Wilk test. CBCT measurements are normally distributed (p = 0.307), while ImageJ is not normally distributed (p = 0.027). Therefore, the mean difference between the two groups was analyzed using the nonparametric Mann-Whitney U test. There was a statistically significant difference between the CBCT and ImageJ measurements (p = 0.01). According to Spearman's correlation analysis, the results obtained from the novel method were moderately correlated with those obtained from the reference method (r = 0.444). The results of this study indicated that a novel method-based Java software can be used to calculate pulp volume using low-dose radiation containing periapical radiography.

Proteomic changes in the hippocampus of large mammals after total-body low dose radiation.

There is a growing interest in low dose radiation (LDR) to counteract neurodegeneration. However, LDR effects on normal brain have not been completely explored yet. Recent analyses showed that LDR exposure to normal brain tissue causes expression level changes of different proteins including neurodegeneration-associated proteins. We assessed the proteomic changes occurring in radiated vs. sham normal swine brains. Due to its involvement in various neurodegenerative processes, including those associated with cognitive changes after high dose radiation exposure, we focused on the hippocampus first. We observed significant proteomic changes in the hippocampus of radiated vs. sham swine after LDR (1.79Gy). Mass spectrometry results showed 190 up-regulated and 120 down-regulated proteins after LDR. Western blotting analyses confirmed increased levels of TPM1, TPM4, PCP4 and NPY (all proteins decreased in various neurodegenerative processes, with NPY and PCP4 known to be neuroprotective) in radiated vs. sham swine. These data support the use of LDR as a potential beneficial tool to interfere with neurodegenerative processes and perhaps other brain-related disorders, including behavioral disorders.