Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses.

We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups.

Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50.

Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

Considering the beneficial role played by IL-22 in alleviating radiation-induced intestinal injury through its promotion of epithelial regeneration, it was hypothesized that individuals with elevated IL-22 levels might display either minimal intestinal injury or increased resistance following ionizing irradiation exposure. To assess the impact of IL-22 on intestinal radiosensitivity, IL-22 expression levels was detected in serum of normal mice. Mice naturally with high or low levels of IL-22 or pretreated with IL-22 or anti-IL-22 were subjected to 10 Gy of total abdominal radiation (TAI). Daily observation, morphometric analysis, quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and western blot were employed to measure weight loss, survival rate, cell proliferation and death, and DNA damage. Furthermore, influence of IL-22 pretreatment on survival of intestinal organoid exposed to 6 Gy X-rays was evaluated. The results showed that IL-22 expression levels were varied between individuals. Surprisingly, mice with high IL-22 levels displayed exacerbated intestinal injury manifesting as increased weight loss, reduced regeneration capacity and more cell apoptosis. Notably, a strong positive correlation between weight loss and IL-22 expression level was observed. Additionally, pretreatment with IL-22 resulted in increased mortality accompanied by enhanced cell apoptosis and DNA damage in crypt of early exposure, as well as diminished survival of intestinal organoid, while pretreatment with anti-IL-22 antibody alleviated the intestinal injury. In this study, we established a direct link between IL-22 and radiosensitivity, suggesting IL-22 could be used as a potential biomarker for predicting individual intestinal radiosensitivity prior to radiation exposure.

Human settlements on the Moon, crewed missions to Mars and space tourism will become a reality in the next few decades. Human presence in space, especially for extended periods of time, will therefore steeply increase. However, despite more than 60 years of spaceflight, the mechanisms underlying the effects of the space environment on human physiology are still not fully understood. Animals, ranging in complexity from flies to monkeys, have played a pioneering role in understanding the (patho)physiological outcome of critical environmental factors in space, in particular altered gravity and cosmic radiation. The use of animals in biomedical research is increasingly being criticized because of ethical reasons and limited human relevance. Driven by the 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, major efforts have been focused in the past decades on the development of alternative methods that fully bypass animal testing or so-called new approach methodologies. These new approach methodologies range from simple monolayer cultures of individual primary or stem cells all up to bioprinted 3D organoids and microfluidic chips that recapitulate the complex cellular architecture of organs. Other approaches applied in life sciences in space research contribute to the reduction of animal experimentation. These include methods to mimic space conditions on Earth, such as microgravity and radiation simulators, as well as tools to support the processing, analysis or application of testing results obtained in life sciences in space research, including systems biology, live-cell, high-content and real-time analysis, high-throughput analysis, artificial intelligence and digital twins. The present paper provides an in-depth overview of such methods to replace or reduce animal testing in life sciences in space research.

We aimed to explore the risk of secondary prostate cancer (SPC) and secondary bladder cancer (SBC) in male rectal cancer (RC) patients after radiotherapy (RT) and to assess survival outcomes.

This large population-based study included men with RC from nine registries in the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2015. Fine-Gray competing risks and Poisson regression were used to assess the RT-related risk of SPC and SBC in patients who received RT versus those who did not (NRT).

After exclusion, 28,886 RC patients were included in further analysis, including 9763 RT-treated patients (33.8%) and 19,123 patients not treated with RT (66.2%). In competing risk regression analysis, RT was associated with a low risk of developing SPC (adjusted HR = 0.67; 95% CI = 0.64-0.82; P < 0.001) and with a high risk of developing SBC (adjusted HR = 1.44; 95% CI = 1.15-1.80; P = 0.001). In the survival analysis of SPC patients, the NRT group exhibited better 10-year OS and CSS than the RT group (OS: HR = 0.52; 95% CI = 0.43-0.64; P < 0.001; CSS: HR = 0.39; 95% CI = 0.26-0.56; P < 0.001).

Male rectal cancer patients receiving RT had a decreased risk of SPC and an increased risk of SBC, and the prognosis of SPC patients in the RT group was worse compared to that of the NRT group. Follow-up and monitoring of SBC and SPC should not be ignored.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection via surveillance plays a crucial role in enabling curative treatment and improving survival rates. Since the initial randomized controlled trial, biannual ultrasound (US) has been established as the standard surveillance method because of its accessibility, safety, and low cost. However, US has some limitations, including operator dependency, suboptimal sensitivity for early-stage HCC, and challenges such as a limited sonic window that may result in inadequate examination. Alternative imaging modalities, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), have demonstrated higher sensitivity for detecting very early-stage HCC. Recent advancements, such as low-dose CT with deep learning-based reconstruction, have enhanced the safety and feasibility of CT-based surveillance by reducing radiation exposure and amount of contrast media. MRI, particularly with gadoxetic acid or abbreviated protocols, offers superior tissue contrast and sensitivity, although its accessibility and cost remain challenges. Tailored surveillance strategies based on individual risk profiles and integration of advanced imaging technologies have the potential to enhance the detection performance and cost-effectiveness. This review highlights the recent developments in imaging technologies for HCC surveillance, focusing on their respective strengths and limitations.

X-ray, computed tomography (CT), and digital subtraction angiography (DSA) techniques are indispensable in managing critically ill neurosurgical patients. However, repeated diagnostic imaging leads to cumulative radiation exposure, raising concerns about long-term risks such as malignancies. This study evaluates the frequency, dosage, and implications of radiation exposure in a neurosurgical intensive care unit (NICU) patient cohort.

A retrospective analysis was conducted on 589 patients admitted to the NICU between 2013 and 2018 with the diagnosis of traumatic brain injury (TBI), intracerebral hemorrhage (ICH), subarachnoidal hemorrhage (SAH), and stroke with >24 h of mechanical ventilation time. The cumulative radiation dose per patient from X-ray, CT, and DSA imaging was calculated and stratified by diagnostic indication, patient condition, and clinical course. To contextualize the findings, international benchmarks were compared.

The cohort's median cumulative effective dose (ED) was 17.8 mSv (range: 1.7-194.3 mSv). CT scans accounted for 81.95 % of the total radiation exposure, with head and thorax imaging being the most frequently performed studies. Younger age and a shorter ventilation time revealed a significant increase in the calculated lifetime attributable risk (LAR) of radiation-induced cancer in multivariate testing. Comparisons with international data revealed a comparable level of radiation exposure in this cohort. Despite the high radiation burden, imaging was deemed clinically essential, with direct implications for patient outcomes.

While radiation exposure in NICU patients is substantial, the benefits of timely and accurate diagnostic information outweigh the potential long-term risks. In critical care settings, where patients face life-threatening conditions, the judicious use of diagnostic imaging is essential. Future efforts should focus on optimizing imaging protocols to minimize radiation exposure without compromising diagnostic quality.

Radiation treatments [radiotherapy and radionuclide treatments (RNTs)] are one of the main and effective treatment modalities of cancer. Globally, the number of cancer patients treated with radionuclides are much less as compared to number of radiotherapy cases but with the development of new radiotracers, most notably 177 Lu and 225 Ac-labeled prostate-specific membrane antigen ligands, and 223 Ra-dichloride for prostate cancer and 177 Lu-somatostatin analogs for neuroendocrine tumors, there is a significant rise in RNTs in the last decade. As therapeutic applications of nuclear medicine is on the rise, the aim of this review is to summarize biological responses to radiation treatments and molecular mechanisms of radiation-induced cell death (e.g. ionization, DNA damages such as double-strand breaks, DNA repair mechanisms, types of cell deaths such as apoptosis, necrosis, and immunogenic cell death), histopathological changes with radiation treatments, and role of PET imaging in RNTs as part of radionuclide theranostics for selecting and planning patients for RNTs, dosimetry, predicting and assessing response to RNTs, predicting toxicities, and other possible PET findings which may be seen after RNTs such as activation of immune system.

The air-gap method is a technique employed to control dose distribution and radiation scattering in medical imaging. By introducing a layer of air between the radiation source and the object, this method effectively reduces the impact of scattered radiation. The purpose of this study was to investigate the suitability of the air-gap method for radiation dose reduction in pediatric patients during computed tomography (CT) examinations. Only one type of neonate phantom is used with 64 detector-row CT scanner while helical scanning the chest. The distance between the CT table and the subject was 0 mm at the conventional method and 150 mm at the air-gap method. The values of the real-time skin dosimeter on the dorsal surface of the body, and on the left and right mammary glands and image noise are measured and compared for each method. Compared with the conventional method, it was possible to reduce the exposure dose and image noise by approximately 10% and 15%, respectively, using the air-gap method (p < 0.05). The air-gap method was useful for reducing the radiation dose during pediatric CT examinations compared with the conventional method.

Osteoarthritis (OA) is the most common degenerative arthropathy, impacting the quality of life for millions worldwide. It typically presents with chronic pain, stiffness, and reduced mobility in the affected joints. Nonsurgical treatments like physiotherapy or pharmacotherapy may provide limited relief and may have adverse effects and complications. Recently, low-dose radiation therapy (LDRT) has emerged as a potential alternative for managing OA, utilizing its anti-inflammatory effects. LDRT's anti-inflammatory effects involve modulating immune responses, reducing pro-inflammatory cytokines, and inducing apoptosis in inflammatory cells. Clinical studies show varying degrees of symptom relief, with some patients experiencing pain reduction and improved joint mobility while others show minimal response. The variability in LDRT treatment designs, radiation dosages, and patient populations complicates standardized treatment protocols and raises concerns about potential carcinogenic risks. Despite these issues, LDRT shows promise as an alternative to other OA treatments, especially for patients who don't respond to other treatments. This review aims to provide updated information on the effectiveness, mechanisms, and safety of LDRT in treating OA. We reviewed the literature of studies on the safety and efficacy of LDRT on affected joints by OA, its biological effects, potential therapeutic and adverse effects, application and contraindications, clinical outcomes, and clinical evidence in subjects with OA.

Although leukemia in the Japanese atomic bomb survivor data has long exhibited upward curvature, until recently this appeared not to be the case for solid cancer. It has been suggested that the recently observed upward curvature in the dose response for the Japanese atomic bomb survivor solid cancer mortality data may be accounted for by flattening of the dose response in the moderate dose range (0.3-0.7 Gy). To investigate this, the latest version available of the solid cancer mortality and incidence datasets (with follow-up over the years 1950-2003 and 1958-2009 respectively) for the Life Span Study cohort of atomic bomb survivors was used to assess possible departures from linearity in the moderate dose range. Linear-spline models were fitted, also up to 6th order polynomial models in dose (higher order polynomials tended not to converge). The organ dose used for all solid cancers was weighted dose to the colon. There are modest indications of departures from linearity for the mortality data, whether using polynomial or linear-spline models. Use of the Akaike information criterion (AIC) suggests that the optimal model for the mortality data is given by a 5th order polynomial in dose. There is borderline significant (P = 0.071) indication of improvement provided by a linear-spline model in the mortality data. The low-dose extrapolation factor (LDEF), which measures the degree of overestimation of low-dose linear slope by the linear slope fitted over some specified dose range, is generally between 1.1-2.0 depending on the dose range, with upper confidence limits that sometimes exceed 10; although LDEF < 1 for the lowest dose range (<0.5 Gy), there are substantial uncertainties, with an upper confidence limit that exceeds 1.6. There are generally only modest indications of departures from linearity for the solid cancer incidence data, whether using polynomial or linear-spline models. In contrast to the mortality data, there are much weaker indications of improvement in fit provided by higher order polynomials, and only weak indications (P > 0.2) of improvement provided by linear-spline models. Nevertheless, use of AIC suggests that the optimal model for the incidence data is given by a 3rd order polynomial. LDEF evaluated over various dose ranges is generally between 1.2-1.4 with upper confidence limits that generally exceed 1.6; although LDEF < 1 for the lowest dose range (<0.5 Gy), there are substantial uncertainties, with an upper confidence limit that substantially exceeds 2.0. In summary, the evidence we have presented for higher order powers than the second in the dose response is not overwhelmingly strong, and is to some extent dependent on dose range. A feature of the dose response, which is reflected in the higher-order polynomials fitted to the data, is a leveling off or even a downturn in the response at doses >2 Gy. The linear-quadratic model is very widely used for modeling of dose response, and has been widely used in radiotherapy oncology applications as part of treatment planning. There is a theoretical basis for this model, based on the two-target model, although the data used to validate this has been mainly in vitro; there may be more complicated interactions than are implied by a two-target model, but the contributions made by these, which would contribute to higher order (than quadratic) powers of dose, may not be very pronounced over moderate ranges of dose.

This study investigated the additional radiation exposure, influencing factors, and clinical significance of overlappingZ-axis coverage in abdominopelvic CT scans performed consecutively after same-day chest CT scans. Data from 761 patients were analyzed, with measuring the total and overlappingZ-axis coverage of the portal venous phase in abdominopelvic CT scans. The average overlapping portion was 33.8 ± 12.1 mm, accounting for approximately 7.0% of the total scan length, contributing a dose-length product of 33.4 mGy*cm and an effective radiation dose of 0.5 mSv. Male sex and the total scan length were identified as significant factors influencing overlap (p= 0.002 and < 0.001, respectively). Despite overlapping scans frequently imaging the lower lungs, only 8.4% of abdominopelvic CT reports specifically mentioned lower lung abnormalities, indicating limited clinical utility. These findings underscore the importance of optimizing CT protocols to minimize the total length of the body covered in abdominopelvic scans, thereby reducing unnecessary radiation exposure during concurrent chest and abdominopelvic CT scans.

Despite undergoing surgery and chemoradiotherapy, patients with first primary lung cancer (FPLC) remain at risk for second primary lung cancer (SPLC), which is associated with a poor prognosis. The effects of FPLC chemoradiotherapy on SPLC prognosis and its sensitivity to re-chemoradiotherapy have not been adequately investigated.

This cohort study analyzed data from 23,827 patients who underwent FPLC surgery during 1973-2021, drawn from the Surveillance, Epidemiology, and End Results database. Among these, 5,302 FPLC patients developed SPLC within 5 years of their initial diagnosis. We employed the Fine-Gray competitive risk model, Cox proportional hazards model, and restricted mean survival time analysis to assess the effects of FPLC radiotherapy and chemotherapy on SPLC risk and survival differences.

The competitive risk model indicated that FPLC radiotherapy and chemotherapy did not significantly change the risk of developing SPLC. However, the Cox proportional hazards model revealed that FPLC radiotherapy was associated with decreased overall survival (OS; HR=1.251, P<0.001) and cancer-specific survival (CSS; HR=1.228, P=0.001) in patients with SPLC. Conversely, FPLC chemotherapy was linked to improved OS (HR=0.881, P=0.012) in this population. Patients with SPLC who received combined chemoradiotherapy for FPLC exhibited significantly reduced survival times (OS: HR=1.157, P=0.030; CSS: HR=1.198, P=0.018), a finding confirmed across multiple models. For SPLC patients with prior FPLC chemoradiotherapy, subsequent SPLC radiotherapy significantly improved prognosis. Notably, this benefit is even more pronounced in patients who have not received prior chemoradiotherapy. While SPLC chemotherapy enhanced OS for patients who did not receive FPLC chemotherapy, it was associated with reduced CSS for those who had.

Overall, FPLC chemoradiotherapy influences SPLC prognosis and influences sensitivity to treatment. Tailoring SPLC management to FPLC treatment regimens may improve survival outcomes.

Conservative management of most pediatric clavicle fractures is standard. Despite a predictable nonoperative course, evidence about the timeliness of healing is lacking. The goal of this study was to identify when radiographic signs of healing should be expected during routine conservative management of closed pediatric diaphyseal clavicle fractures.

Patients 18 years or younger with an acute diaphyseal clavicle fracture treated at a large academic multispecialty orthopaedic practice over 5 years were retrospectively reviewed. Patients who completed nonoperative management until radiographic and clinical evidence of union were included and categorized into 3 age groups: infants and toddlers (0 to 2 y old), school-aged children (3 to 9 y old), and adolescents (10 to 18 y old). Radiographic healing was analyzed within each 2- to 4-week interval.

Among 390 patients, 303 met inclusion criteria. Overall shortening and displacement averaged 0.3±0.6 centimeters and 42.6%±43.0%, respectively. Follow-up averaged 50±24 days with an orthopaedic physician and 16.3±14.8 months for a well-child check. No clinically relevant or statistically significant improvements in the number of cortices bridged were observed in infants/toddlers after 4 weeks (average 20.4±4.3 d from injury), in school-aged children after 8 weeks (average 39.7±7.9 d from injury), or in adolescents after 12 weeks (average 66.4±8.1 d from injury).

This study provides an age-dependent timeline during which adequate radiographic healing should be expected in nonoperatively managed pediatric diaphyseal clavicle fractures. Radiographic protocols can be purposefully timed to visualize sufficient healing in infants and toddlers by 4 weeks, school-aged children by 8 weeks, and adolescents by 12 weeks.

Level III.

Radiation, a universal component of Earth's environment, is categorized into non-ionizing and ionizing forms. While non-ionizing radiation is relatively harmless, ionizing radiation possesses sufficient energy to ionize atoms and disrupt DNA, leading to cell damage, mutation, cancer, and cell death. The extensive use of radionuclides and ionizing radiation in nuclear technology and medical applications has sparked global concern for their capacity to cause acute and chronic illnesses. Ionizing radiation induces DNA damage either directly through strand breaks and base change or indirectly by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS) via radiolysis of water. This damage triggers a complex cellular response involving recognition of DNA damage, cell cycle arrest, DNA repair mechanisms, release of pro-inflammatory cytokines, and cell death. This review focuses on the mechanisms of radiation-induced cellular damage, recognition of DNA damage and subsequent activation of repair processes, and the critical role of the innate immune response in resolution of the injury. Emphasis is placed on pattern recognition receptors (PRRs) and related receptors that detect damage-associated molecular patterns (DAMPs) and initiate downstream signaling pathways. Radiation-induced cell death pathways are discussed in detail. Understanding these processes is crucial for developing strategies to mitigate the harmful effects of radiation and improve therapeutic outcomes.

We previously reported endogenous activation of the DNA damage response (DDR) in the epidermis surrounding basal cell carcinoma resected from Nagasaki atomic bomb survivors, suggesting the presence of genomic instability (GIN) in the survivors as a late effect of radiation. Dual-color immunofluorescence (IF) analysis of TP53-binding protein-1 (53BP1) and a proliferative indicator, Ki-67, to elucidate GIN in tumor tissues revealed that abnormal 53BP1 expression is closely associated with carcinogenesis in several organs. The present study aimed to confirm the presence of radiation-induced GIN in the non-neoplastic epidermis of patients with radiation-induced skin cancer. Formalin-fixed paraffin-embedded tissues were obtained from all participants between 2008 and 2019 at the Nagasaki University Hospital. 53BP1 nuclear expression was examined using dual-color IF analysis with Ki-67 expression to assess the extent and integrity of the DDR. Expressions of gamma-H2AX, p53 and p21 were also analyzed using the dual-color IF analysis for their association with 53BP1. The results of this study provide evidence for sporadic activation of the DDR in medically irradiated and ultraviolet-exposed epidermis as a long-lasting radiation effect, which is a predisposition to skin cancer. Furthermore, the incidence of abnormal 53BP1 expression in cancer cells was higher than in non-neoplastic epidermal cells surrounding cancer, suggesting a correlation between the type of 53BP1 and the malignant potential of skin tumors. This study highlights the usefulness of dual-color IF for 53BP1 (and Ki-67) as an indicator to estimate the level of GIN as a long-lasting health effect of radiation exposure.

Radiation induces various changes in biological specimens; however, the evaluation of these changes is usually complicated and can be achieved only through investment in time and labor. Optical methods reduce the cost of such evaluations as they require less pretreatment of the sample, are adaptable to high-throughput screening and are easy to automate. Optical methods are also advantageous, owing to their real-time and onsite evaluation capabilities. Here, we discuss three optical technologies to evaluate the effects of radiation on biological samples: single-molecule tracking microscopy to evaluate the changes in the physical properties of DNA, Raman spectral microscopy for dosimetry using human hair and second-harmonic generation microscopy to evaluate the effect of radiation on the differentiation of stem cells. These technologies can also be combined for more detailed information and are applicable to other biological samples. Although optical methods are not commonly used to evaluate the effects of radiation, advances in this technology may facilitate the easy and rapid assessment of radiation effects on biological samples.

Ionizing radiation is widely used in various industrial and medical applications, resulting in increased exposure for certain populations. Lessons from radiation accidents and occupational exposure have highlighted the cardiovascular and cerebrovascular risks associated with radiation exposure. In addition, radiation therapy for cancer has been linked to numerous cardiovascular complications, depending on the distribution of the dose by volume in the heart and other relevant target tissues in the circulatory system. The manifestation of symptoms is influenced by numerous factors, and distinct cardiac complications have previously been observed in different groups of patients with cancer undergoing radiation therapy. However, in contemporary radiation therapy, advances in treatment planning with conformal radiation delivery have markedly reduced the mean heart dose and volume of exposure, and these variables are therefore no longer sole surrogates for predicting the risk of specific types of heart disease. Nevertheless, certain cardiac substructures remain vulnerable to radiation exposure, necessitating close monitoring. In this Review, we provide a comprehensive overview of the consequences of radiation exposure on the cardiovascular system, drawing insights from various cohorts exposed to uniform, whole-body radiation or to partial-body irradiation, and identify potential risk modifiers in the development of radiation-associated cardiovascular disease.

Cancer risks attributable to low-dose and low-dose-rate radiation are a serious concern for public health. Radiation risk assessment is based on lifespan studies among Hiroshima-Nagasaki A-bomb survivors; however, there are statistical limitations due to a small sample size for low-dose radiation. Therefore, basic biological studies are helpful in understanding the mechanism of radiation carcinogenesis. The detrimental effects of ionising radiation (IR) are caused by reactive oxygen species (ROS)-mediated oxidative DNA damage. IR-induced delayed ROS are produced in the electron transport chain reaction of the mitochondrial complex. Thus, mitochondria are a source of ROS and a primary target for ROS attacks. Consequently, mitochondrial dysfunction is thought to be a key event in the metabolic changes of cancer cells and is important in radiation-induced carcinogenesis. In this paper, we present recent findings on radiation carcinogenesis effect assessment, focusing on mitochondrial function as stress sensors.

In estimating radiation-related risk of cancer and other diseases based on the RERF Life Span Study (LSS), joint analyses can be performed where multiple health outcome endpoints are combined in the same model, allowing some parameters to be estimated in common among all endpoints with possible increase in precision of radiation risk and other model parameter estimates. Using as a basis excess relative risk (ERR) and excess absolute risk (EAR) models of the type commonly used in analysis of LSS data at RERF, we use maximum likelihood theory to compute the asymptotic relative standard error of endpoint-specific radiation effect and other parameter estimates using joint analyses as compared to traditional independent analysis. We show that some gains in precision of endpoint-specific radiation risk parameter estimates can be achieved by sharing effect modifier and other model parameters, but only small or negligible gains in precision are achieved for endpoint-specific background modifying or effect modifying parameters when other model parameters are shared. The magnitude of the precision gain for radiation risk estimates depends on the number of endpoints, the baseline incidence rate of the endpoint, and the type of model being used.

Prenatal exposure to environmental factors may play an important role in the aetiopathogenesis of autism spectrum disorder (ASD). We aim to investigate the potential effects of low-dose x-rays from dental diagnostic x-rays on neurodevelopment and molecular mechanisms associated with ASD in developing zebrafish embryos. Zebrafish embryos were divided into four groups and exposed using a dental x-ray unit: control, 0.08, 0.15 and 0.30 seconds, which are exemplary exposure settings for periapical imaging. These exposure times were measured as 7.17, 23.17 and 63.83 mSv using optical stimulated luminescence dosimeters. At the end of 72 hours post-fertilization, locomotor activity, oxidant-antioxidant status, and acetylcholine esterase (AChE) activity were analyzed. Expression of genes related to apoptosis (bax, bcl2a, p53), neurogenesis (α1-tubulin, syn2a, neurog1, elavl3) and ASD (eif4eb, adsl2a, shank3) was determined by RT-PCR. Even at reduced doses, developmental toxicity was observed in three groups as evidenced by pericardial edema, yolk sac edema and scoliosis. Deleterious effects of dental x-rays on neurogenesis through impaired locomotor activity, oxidative stress, apoptosis and alterations in genes associated with neurogenesis and ASD progression were more pronounced in the 0.30s exposure group. Based on these results we suggest that the associations between ASD and low-dose ionizing radiation need a closer look.

The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly fourfold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development after HZE radiation exposure, we irradiated Rbfl/fl, Trp53fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X rays or 600 MeV/n 56Fe ions and monitored them for any radiation-induced malignancies. We conducted complete necropsy and histopathology of major organs on 183 male and 157 female mice after following them for 350 days postirradiation. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in mice exposed to X rays and 56Fe ions, respectively. In addition, 1 Gy 56Fe-ion exposure compared to X-ray exposure led to a significantly increased incidence of lung adenomas/carcinomas (P = 0.02) and ENBs (P < 0.0001) in mice. However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in ENBs induced by X rays and 56Fe ions. Thus, our data revealed that 56Fe-ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.

In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses.

We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V20Gy), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose.

VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected.

In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified.

Radiotherapy (RT) for breast cancer (BC) may raise the risk of second primary cancers (SPCs), a relationship inadequately studied.

We analyzed 248268 female BC patients from 9 SEER registries, 1988-2018, identifying SPCs >5 years after initial treatment, comparing SPC risks between RT and non-RT cohorts using Fine-Gray and Poisson regressions.

Of all participants, 55.4 % received surgery and RT. The RT group had a higher SPC incidence, with excess incidence significantly dropped from 6.9 % in 1990 to 0.2 % in 2012. The 30-year SPC incidence was 24.69 % in the RT cohort and 18.11 % in the NRT cohort. RT increased the risk of SPCs(HR, 1.29 [95%CI,1.26-1.33]; P < 0.001), BC(HR, 1.58[1.52-1.64]; P < 0.001), cancer of respiratory system(HR, 1.21[1.13-1.30]; P = 0.013), skin cancer(HR, 1.26[1.10-1.44]; P < 0.001), leukemia(HR, 1.30[1.11-1.54]; P = 0.001), soft tissue cancer(HR, 1.78[1.34-2.37]; P < 0.001), and eye & orbit cancer(HR, 2.21[1.02-4.80]; P = 0.044), except for reducing the risk of multiple myeloma (HR 0.76). Notably, RT-related risks(RR) for BC declined with increasing age and the year of BC diagnosed, increased with longer latency, but the dynamic RR for cancer of respiratory system presented the almost opposite trends. The RT cohort had higher standardized incidence ratios for SPCs compared to both the NRT cohort and the general population overall. Although 15-year overall survival for SPCs was similar between RT and NRT cohorts, SPC presence significantly lowered 30-year survival from 35.64 % to 23.90 %.

RT might increase susceptibility to SPC in breast, respiratory system, skin, soft tissue, eye and orbit, and leukemia in BC survivors. Efforts should be made to timely diagnose SPCs based on their specific patterns to improve patient's quality of life.

Studies on the relationship between personal history of irradiation and breast cancer have been reported for a long time. Still, epidemiological studies have not been conclusive, and the causal relationship is unclear. To address this issue, we employed Mendelian randomisation (MR) analysis to examine the association between individual radiation exposure history and breast cancer.

We used a series of quality control methods to select single nucleotide polymorphism (SNP) closely related to exposure. Meanwhile, several analysis methods were used to analyse the sample data to make the conclusion more reliable. To evaluate the horizontal pleiotropy, heterogeneity and stability of SNPs for breast cancer, the MR-Egger intercept test, Cochran's Q test and 'leave one' sensitivity analysis were used. Finally, the outlier variation determined by the Mendelian Randomisation Pleiotropy RESidual Sum and Outlier test is gradually eliminated to reduce the influence of heterogeneity and horizontal pleiotropy.

After implementing rigorous quality control procedures, we carefully chose 102 qualified instrumental variables closely associated with the selected exposure for sensitivity analysis. This was conducted to evaluate the heterogeneity, level multiplicity, and stability of SNPs in the context of personal radiation history and its correlation with breast cancer. The results of the inverse variance weighted method analysis revealed a positive correlation between personal radiation and a heightened risk of breast cancer (odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.30-1.77). We also validated on another data set; the results were similar (OR = 1.51; 95% CI = 1.27-1.81). Furthermore, the findings from the sensitivity analysis were consistent. At the genetic level, our research demonstrated that personal radiation exposure is associated with an elevated risk of breast cancer.

Using genetic data provides evidence and strengthens the causal link that personal radiation causes breast cancer.

Ionizing radiation promotes mammary carcinogenesis. Induction of DNA double-strand breaks (DSBs) is the initial event after radiation exposure, which can potentially lead to carcinogenesis, but the dynamics of DSB induction and repair are not well understood at the tissue level. In this study, we used female rats, which have been recognized as a useful experimental model for studying radiation effects on the mammary gland. We focused on differences in DSB kinetics among basal cells, luminal progenitor and mature cells in different parts of the mammary duct. 53BP1 foci were used as surrogate markers of DSBs, and 53BP1 foci in each mammary epithelial cell in immunostained tissue sections were counted 1-24 h after irradiation and fitted to an exponential function of time. Basal cells were identified as cytokeratin (CK) 14+ cells, luminal progenitor cells as CK8 + 18low cells and luminal mature cells as CK8 + 18high cells. The number of DSBs per nucleus tended to be higher in luminal cells than basal cells at 1 h post-irradiation. A model analysis indicated that basal cells in terminal end buds (TEBs), which constitute the leading edge of the mammary duct, had significantly fewer initial DSBs than the two types of luminal cells, and there was no significant difference in initial amount among the cell types in the subtending duct. The repair rate did not differ among mammary epithelial cell types or their locations. Thus, luminal progenitor and mature cells are more susceptible to radiation-induced DSBs than are basal cells in TEBs.

Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-CreERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis.

Potassium iodide has demonstrated several therapeutic applications over time, being the choice for shielding the thyroid during radiation emergencies involving radioiodine release. Amidst the ongoing military conflict between Ukraine and Russia and the growing concern regarding the potential deployment of nuclear weapons, there has been a surge in the demand for potassium iodide across Europe. This work aimed to comprehensively review the current knowledge regarding the pharmacology, physiology, adverse effects, the protective role in reducing the risk of thyroid cancer and recommendations for potassium iodide use during radiation emergencies. Evidence on adverse effects is scarce, as potassium iodide is generally well-tolerated. Guidelines for thyroid blocking with potassium iodide during radiation emergencies suggest that, among populations vulnerable to radioiodine exposure, the benefits of potassium iodide outweigh the risks of adverse effects. Controversial topics surrounding the utilization of potassium iodide in radiation emergencies include the prophylaxis in iodine-deficient regions and following the detonation of dirty bombs, whether granule formulations versus tablets should be used and mental health concerns. Although the rise in demand seems to be a justified security measure, it is essential to recognize that potassium iodide protects the thyroid from radioiodine and does not impact the body's absorption of other radioactive materials or defend against external radiation exposure.

Acute, high-dose radiation exposure results in life-threatening acute radiation syndrome (ARS) and debilitating delayed effects of acute radiation exposure (DEARE). The DEARE are a set of chronic multi-organ illnesses that can result in early death due to malignancy and other diseases. Animal models have proven essential in understanding the natural history of ARS and DEARE and licensure of medical countermeasures (MCM) according to the FDA Animal Rule. Our lab has developed models of hematopoietic (H)-ARS and DEARE in inbred C57BL/6J and Jackson Diversity Outbred (JDO) mice of both sexes and various ages and have used these models to identify mechanisms of radiation damage and effective MCMs. Herein, aggregate data from studies conducted over decades in our lab, consisting of 3,250 total-body lethally irradiated C57BL/6J young adult mice and 1,188 H-ARS survivors from these studies, along with smaller datasets in C57BL/6J pediatric and geriatric mice and JDO mice, were examined for lifespan and development of thymic lymphoma in survivors up to 3 years of age. Lifespan was found to be significantly shortened in H-ARS survivors compared to age-matched nonirradiated controls in all four models. Males and females exhibited similar lifespans except in the young adult C57BL/6J model where males survived longer than females after 16 months of age. The incidence of thymic lymphoma was increased in H-ARS survivors from the young adult and pediatric C57BL/6J models. Consistent with our findings in H-ARS, geriatric mice appeared more radioresistant than other models, with a lifespan and thymic lymphoma incidence more similar to nonirradiated controls than other models. Increased levels of multiple pro-inflammatory cytokines in DEARE bone marrow and serum correlated with shortened lifespan and malignancy, consistent with other animal models and human data. Of interest, G-CSF levels in bone marrow and serum 8-11 months after irradiation were significantly increased in females. Importantly, treatment with granulopoietic cytokine MCM for radiomitigation of H-ARS did not influence the long-term survival rate or incidence of thymic lymphoma in any model. Taken together, these findings indicate that the lifespan of H-ARS survivors was significantly decreased regardless of age at time of exposure or genetic diversity, and was unaffected by earlier treatment with granulopoietic cytokines for radiomitigation of H-ARS.

The article explores the potential risk of secondary cancer (SC) due to radiation therapy (RT) and highlights the necessity for new modeling techniques to mitigate this risk.

By employing machine learning (ML) models, specifically decision trees, in the research process, a practical framework is established for forecasting the occurrence of SC using patient data.

This framework aids in categorizing patients into high-risk or low-risk groups, thereby enabling personalized treatment plans and interventions. The paper also underscores the many factors that contribute to the likelihood of SC, such as radiation dosage, patient age, and genetic predisposition, while emphasizing the limitations of current models in encompassing all relevant parameters. These limitations arise from the non-linear dependencies between variables and the failure to consider factors such as genetics, hormones, lifestyle, radiation from secondary particles, and imaging dosage. To instruct and assess ML models for predicting the occurrence of SC based on patient data, the paper utilizes a dataset consisting of instances and attributes.

The practical implications of this research lie in enhancing our understanding and prediction of SC following RT, facilitating personalized treatment approaches, and establishing a framework for leveraging patient data within the realm of ML models.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Breast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a condition associated with an increased risk of various malignancies, including radiation therapy (RT)-induced malignancies (RIM) within previously irradiated areas. Our study aimed to assess the incidence of RIM in patients with LFS and early-stage BC treated with adjuvant RT, including the effect of RT dose and technique.

We examined patients with a germline pathogenic/likely pathogenic TP53 variant diagnosed with early-stage BC and monitored by a hereditary cancer team at a single cancer center. The study endpoints included RIM frequency, the association of RIM with the dose and type of RT (2-dimensional [2D] RT, 3-dimensional [3D] RT, and intensity modulated RT [IMRT]), and BC recurrence.

We analyzed 48 patients with a median age of 39 years (range, 21-62). The majority (71%) had the TP53 R337H variant, and 87% were unaware of their LFS diagnosis at the time of BC treatment. Treatment modalities included mastectomy (62%), (neo)adjuvant chemotherapy (66%), and RT (62%), with RT being more common after breast-conserving surgery (87% vs 46% with mastectomy, P = .010). Among the 30 patients treated with RT, 10% developed RIM in the irradiated field, consisting of 3 soft tissue malignancies. RT dose (≤40.8 or >40.8 Gy) did not influence RIM occurrence, but the type of RT did. RIM was observed in 100% of cases with 2D RT (2/2), 50% with IMRT (1/2), and 0% with 3D RT (0/16) (P = .004).

Our study underscores a concerning rate of RIM after adjuvant RT, emphasizing the importance of a thorough risk-benefit evaluation before recommending RT, with preference for its avoidance if possible. Although subgroup sizes were limited, the risk of RIM appeared to be influenced by the RT technique, with higher rates observed with 2D RT and IMRT compared with 3D RT. Early TP53 testing is essential to guide the BC treatment plan.

Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number.

Expanding human presence in space through long-duration exploration missions and commercial space operations warrants improvements in approaches for quantifying crew space radiation health risks. Currently, risk assessment models for radiogenic cancer and cardiovascular disease consider age, sex, and tobacco use, but do not incorporate other modifiable (e.g., body weight, physical activity, diet, environment) and non-modifiable individual risk factors (e.g., genetics, medical history, race/ethnicity, family history) that may greatly influence crew health both in-mission and long-term. For example, clonal hematopoiesis of indeterminate potential (CHIP) is a relatively common age-related condition that is an emerging risk factor for a variety of diseases including cardiovascular disease and cancer. CHIP carrier status may therefore exacerbate health risks associated with space radiation exposure.

In the present study, published CHIP hazard ratios were used to modify background hazard rates for coronary heart disease, stroke, and hematologic cancers in the National Aeronautics and Space Administration space radiation risk assessment model. The risk of radiation exposure-induced death for these endpoints was projected for a future Mars exploration mission scenario.

Here we show appreciable increases in the lifetime risk of exposure-induced death for hematologic malignancies, coronary heart disease, and stroke, which are observed as a function of age after radiation exposure for male and female crew members that are directly attributable to the elevated health risks for CHIP carriers.

We discuss the importance of evaluating individual risk factors such as CHIP as part of a comprehensive space radiation risk assessment strategy aimed at effective risk communication and disease surveillance for astronauts embarking on future exploration missions.

The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies.

A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation.

This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases.

Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

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.

In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement.

The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed.

Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown.

Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases.

To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients.

Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs.

Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower.

Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

The dicentric chromosome assay (DCA), often referred to as the 'gold standard' in radiation dose estimation, exhibits significant challenges as a consequence of its labor-intensive nature and dependency on expert knowledge. Existing automated technologies face limitations in accurately identifying dicentric chromosomes (DCs), resulting in decreased precision for radiation dose estimation. Furthermore, in the process of identifying DCs through automatic or semi-automatic methods, the resulting distribution could demonstrate under-dispersion or over-dispersion, which results in significant deviations from the Poisson distribution. In response to these issues, we developed an algorithm that employs deep learning to automatically identify chromosomes and perform fully automatic and accurate estimation of diverse radiation doses, adhering to a Poisson distribution.

The dataset utilized for the dose estimation algorithm was generated from 30 healthy donors, with samples created across seven doses, ranging from 0 to 4 Gy. The procedure encompasses several steps: extracting images for dose estimation, counting chromosomes, and detecting DC and fragments. To accomplish these tasks, we utilize a diverse array of artificial neural networks (ANNs). The identification of DCs was accomplished using a detection mechanism that integrates both deep learning-based object detection and classification methods. Based on these detection results, dose-response curves were constructed. A dose estimation was carried out by combining a regression-based ANN with the Monte-Carlo method.

In the process of extracting images for dose analysis and identifying DCs, an under-dispersion tendency was observed. To rectify the discrepancy, classification ANN was employed to identify the results of DC detection. This approach led to satisfaction of Poisson distribution criteria by 32 out of the initial pool of 35 data points. In the subsequent stage, dose-response curves were constructed using data from 25 donors. Data provided by the remaining five donors served in performing dose estimations, which were subsequently calibrated by incorporating a regression-based ANN. Of the 23 points, 22 fell within their respective confidence intervals at p < .05 (95%), except for those associated with doses at levels below 0.5 Gy, where accurate calculation was obstructed by numerical issues. The accuracy of dose estimation has been improved for all radiation levels, with the exception of 1 Gy.

This study successfully demonstrates a high-precision dose estimation method across a general range up to 4 Gy through fully automated detection of DCs, adhering strictly to Poisson distribution. Incorporating multiple ANNs confirms the ability to perform fully automated radiation dose estimation. This approach is particularly advantageous in scenarios such as large-scale radiological incidents, improving operational efficiency and speeding up procedures while maintaining consistency in assessments. Moreover, it reduces potential human error and enhances the reliability of results.

It has long been thought that the carcinogenic effect of radiation resulted from the induction of oncogenic mutations which then led to an increase in the proportion of cancer-bearing individuals. However, even as early as the 1960s, there were indications that the carcinogenic effect of radiation might result from the induction of an earlier onset of cancer. Recently, the former notion was challenged by its inability to explain time-dependent decline of the relative risk following an exposure to radiation, and a parallel shift of mouse survival curves toward younger ages following an exposure to radiation. The two observations are clearly understood if it is assumed only that a radiation exposure causes an earlier onset of spontaneously occurring cancers.

In the present study, a critical review was conducted which examined papers that showed dose responses which apparently supported the mutation induction theory of radiation carcinogenesis.

It was found that there were two types of misleading experimental designs: one consisted of studies in which observations were prematurely terminated, and which consequently hid a complete story of radiation carcinogenesis. The other set of papers used age adjustments which were derived from the idea that the life shortening effect of radiation needs to be compensated for since tumor mortality becomes higher among older subjects. This type of adjustment appeared reasonable but was found actually to be a different form of description on an earlier onset of cancer following radiation exposures.

In mouse experiments, radiation exposures did not lead to the induction of a large increase in the proportion of tumor deaths when life-long observations were made. Human epidemiologic data are also in line with the earlier onset hypothesis of radiation action. It should be cautioned, however, that the earlier onset model applies only to malignancies whose mortality increases rapidly with the increase of age and does not apply to diseases of short latency such as childhood leukemia and thyroid cancers.

Any conflict in countries that process nuclear power plants raises concerns of the potential radiation injuries to the people in that region and beyond such as the current conflict in Ukraine. International healthcare organizations and societies should prepare for the potential scenarios of nuclear incidents. The Worldwide Network for Blood and Marrow Transplantation (WBMT) and its members, have recent experience preparing for this type of events such as the Fukushima incident in 2011. In this article, we discuss the risks of radiation exposure, current guidelines, and scientific evidence on hematopoietic support, including the role of hematopoietic stem cell transplant (HCT) for those exposed to nuclear radiation, and the role that the WBMT and other global BMT societies can play in triaging and managing people suffering from radiation injuries.