Radiation Research Research Articles

Abstract PO3-10-09: The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients?

Abstract Background: Breast cancer is a global health challenge and the highest incident cancer globally, with over 2 million new cases and 685,000 deaths in 2020, making it the highest incident cancer globally. Furthermore, it is the most prevalent cancer, resulting in the loss of more disability-adjusted life years than any other malignancy. Research is thus crucial to improving outcomes and reducing suffering for breast cancer patients worldwide. This study aimed to analyse global patterns of funding for breast cancer research. Methods: We have previously created a comprehensive database of awards for human cancer research in this period using publicly available data on research funding awards. From this database we extracted all awards relating to breast cancer research, and categorised these by cancer type, cross-cutting research theme and phase of research. Findings: We identified 7051 awards with a total investment of $2.6 billion in 2016-2020, representing 11.2% of all global public and philanthropic cancer research funding during this period. Breast cancer research funding fell year on year, from $773.4 million in 2016 to $243.8 million in 2020. The majority of the investment was in pre-clinical research ($1.9 billion, 73.9%), with clinical trials ($276 million, 10.7%) and public health ($269.2 million, 10.5%) receiving roughly equivalent amounts of funding. The USA accounted for 66.9% of all global breast cancer research investment, with China ($110.4 million, 4.3%) and the UK ($96.6 million, 3.8%) the next largest funders. By research theme, cancer biology research received most funding ($926.2 million, 37.5% of investment), with drug treatment the next best funded research area ($600.5 million, 23.4%), and diagnosis, screening and monitoring third ($396 million, 15.4%). Surgery ($65.2 million, 2.5%) and radiotherapy ($35.3 million, 1.4%) accounted for only a small proportion of research investment. There was minimal investment into breast cancer as a global health issue ($8.1 million, 0.3%). Research into metastatic disease received a greater proportion of investment in breast cancer than in the overall cancer portfolio (23.2% in breast cancer, $597.4 million, compared with 11.7% across all cancers). Conclusions: Breast cancer public and philanthropic research funding is largely invested in pre-clinical research in high-income countries, with the main areas of investment being cancer biology research and drug treatment. The direct benefit to patients from such research is likely to be low and only apparent after a substantial time lag (if at all). Despite their pivotal role in the treatment of the majority of breast cancer patients, surgery and radiotherapy research received a tiny proportion of the overall research investment. Furthermore, relatively little investment is directed towards cancer prevention and early detection, despite their acknowledged key role in cancer control globally. Finally, more equitable research funding is required to align with the global burden of breast cancer, with increased funding for low- and middle-income countries, which account for an increasing proportion of this burden. These data should be considered by funders and policymakers in the allocation of finite resources, which must be invested wisely. Citation Format: Stuart McIntosh, Ellen Copson, Ramsey Cutress, Michael Head. The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-09.

The Study and Improvement of Pressure Degradation of Helium Cryogenic System at NSRRC

This paper is aimed at studying and improving the phenomenon of pressure degradation in a helium cryogenic system. There are two 450W helium cryogenic systems for the Taiwan light source (TLS) and one 890W helium cryogenic system for the Taiwan photon source (TPS) housed at the National Synchrotron Radiation Research Center (NSRRC). The TLS helium cryogenic system is used for one superconducting radio frequency (SRF) cavity and five superconducting magnets. The TPS helium cryogenic system is used for two SRF cavities at the present stage. These three helium cryogenic systems have experienced pressure degradation, which reduced their performance and increased liquid nitrogen consumption for precooling over the past few years. A cryogenic adsorber was set up in an effort to capture the impurities, but this made no difference for pressure degradation in the system. The impurities were comprised of not only gas but also moisture. It was found that the cryogenic adsorber was not efficient enough to remove the moisture. This paper presents the study for the phenomena of pressure degradation. A moisture removal system was designed which is also discussed.

A random sampling method for radiobiological modeling

Various radiobiological models have been proposed to describe the clonogenic cell survival after radiation. Least square model fitting to match experimental survival data can be tedious and sometimes difficult for complex models with multiple parameters. In this work, a random sampling method is developed to optimize the model parameters automatically to achieve best fitting with the experimental data. A computer program is developed to read the experimental data and to calculate the cell survival fractions based on a given mathematical model. Model parameters are randomly sampled, and the model predictions are compared with the experimental data. The mean square error (MSE) is used as an objective function to drive the iterative process. The goodness-of-fit of the linear quadratic (LQ), multitarget (MT), universal survival curves (USC) and multimode (MM) model was compared between the new method and previous studies for melanoma and non–small-cell lung cancer (NSCLC) cell lines. Good fitting was obtained for the MM model with the NSCLC data (MSE = 0.0005), which was better than the fits to the LQ, MT and USC models (MSE = 0.0019, 0.0082, 0.0024, respectively). The parameters used for the LQ, MT and USC models were α = 0.33Gy, α/β = 10Gy, D0 = 1.25Gy, n = 4.22 and DT = 6.2Gy. The parameters for the MM model (n = 4) were D1 = 3.0Gy, D2 = 8.27Gy, and D3 = 2.93Gy and D4 = 10.6Gy. It is concluded that the random sampling method provides a useful tool for the parameterization of radiobiological models for radiation research and clinical applications.

Abstract P20: Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma using an Advanced Human in vitro Model of the Blood-brain Barrier and Glioblastoma

Abstract Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with a dismal prognosis of 15 months. This is despite decades of research and improvements in surgery and radiotherapy. Temozolomide (TMZ) is the only first-in-line chemotherapeutic; however, resistance is frequent and multifactorial. While many molecular and genetic factors have been linked to TMZ resistance, the role of the solid tumor morphology and the tumor microenvironment (TME), particularly the blood-brain barrier (BBB), is unknown. Complex 3D in vitro models are able to recapitulate aspects of clinical disease such as the tumor microenvironment, such that research into the role of the TME and how it affects tumor biology and therapy resistance can be studied more easily and accurately. We have developed a complex 3D in vitro model for GBM and its surrounding BBB, that recapitulates important clinical features such as a dense tumor core with tumor cells that invade along the perivascular space; and a perfusable BBB with a physiological permeability with morphology that is altered in the presence of a tumor spheroid. We demonstrate that TMZ sensitivity decreases with increasing cancer cell spatial organization, and that the BBB can contribute to TMZ resistance. Proteomic analysis of cultured microtissues using low volume sample workflows revealed proteins linked to aggressive tumors and TMZ resistance. Notably, proteomic analysis revealed a potential role for cell cycle proteins in TMZ resistance. Preliminary data with tumor spheroids formed by patient derived GBM progenitor cells revealed a similar trend of an increase in proteins associated with tumor aggressiveness upon co-culture with a BBB. The data demonstrate the utility of combining complex physiological in vitro models and next generation mass spectrometry for interrogating the tumour microenvironment, tumor biology and accurate in vitro therapy validation. Citation Format: Maxine SY Lam, Joey JY Aw, Damien Tan, Ragavi Vijayakumar, Hui Yi Grace Lim, Swathi Yada, Qing You Pang, Nick Barker, Carol Tang, Beng Ti Ang, Radoslaw M. Sobota, Andrea Pavesi. Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma using an Advanced Human in vitro Model of the Blood-brain Barrier and Glioblastoma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P20.

Focused ultrasound-mediated blood–brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma

BackgroundDiffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood–brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT.MethodsTo establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53−/−). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI).ResultsFUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3–4 weeks post-RT.ConclusionRepeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

Abstract 699: Targeting radiation-driven invasion and metastasis in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Standard of care includes chemotherapy and radiotherapy (RT) for locally advanced, unresectable disease. Despite radiotherapy being an effective and sometimes curative option for many cancer types, radio-resistance is common, and pre-clinical research in recent years has found that RT can initiate a more aggressive, pro-invasive phenotype in the remaining cells post treatment (1,2). Little is known about the molecular mechanisms responsible for this phenomenon.There is accumulating evidence highlighting a role for the RhoGTPase family in mediating radioresistance and enhanced invasion (2, 3). Understanding their role in PDAC progression may aid the identification of novel chemotherapeutics that could be used alongside RT in the future. We present in vitro data that confirms the pro-migratory effect of RT and importantly indicates a significant increase in metastases formed in a clinically relevant model of PDAC (KPC Pdx1-Cre; KrasG12D/+; Trp53R172H/+) after treatment using a small animal radiation research platform (n=31, p<0.0001). In concurrence with previous literature, we found that PDAC cell motility was dependent on the RhoGTPase pathway, RhoA/ROCK1 (p=0.004). However, post-RT, this dependency was switched to an alternative pathway, CDC42/Rac1/MRCK, indicating a clear change in the balance of RhoGTPase signaling (p=0.002). This switch was confirmed via high-throughput immunofluorescence analysis. To widen this investigation further, we performed an siRNA screen targeting all members of the RhoGTPase family. Preliminary results indicate signaling dependency on Rac2, Rac3 and CDC42 post-RT. Additionally, we have performed RNAseq to investigate pro-invasive gene signatures arising from the acute irradiation of pancreatic cancer cells. This was done at sufficient depth to identify splice variants, with differential transcript expression (DTE) analysis identifying 236 differentially expressed transcripts and the differential transcript usage (DTU) analysis identifying 28 transcripts and 23 genes. Initial functional enrichment analysis found gene signatures relating to cell migration and adhesion, which may be indicative of an invasive phenotype. In conclusion, we present in vitro and in vivo data suggesting RT may promote a more invasive phenotype in PDAC at least in part due to a switch in RhoGTPase signaling. 1. Mueller, A.C., et al., Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer. Cancer Res, 2021. 81(12): p. 3255-3269. 2. Birch, J.L., et al., A Novel Small-Molecule Inhibitor of MRCK Prevents Radiation-Driven Invasion in Glioblastoma. Cancer Res, 2018. 78(22): p. 6509-6522. Citation Format: Kathy Mclay, Mathias Tesson, Dion Gilmour, Jennifer P. Morton, Joanna L. Birch. Targeting radiation-driven invasion and metastasis in pancreatic cancer [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 699.

Simulation-guided design of a target-cooling system for cyclotron-based isotope production

Isotopes are an important aspect of modern medical and scientific research and cyclotron-based isotope production is of particular interest. Cooling devices are required to manage the heat generated by high-energy particle beams to ensure that they can be delivered securely. However, there is considerable scope for further advancements in the design of cooling systems. Therefore, this study uses simulations to investigate the design of innovative cooling systems. Various designs and materials are considered using a variable four-sector collimator and various particle-beam conditions. Thus, new design principles and material and structural optimization strategies are proposed, which can be used to improve the stability and efficiency of isotope production. The results provide insight into technical challenges and may contribute toward advances in medical diagnostics, radiotherapy, and fundamental scientific research. In particular, they can guide the development of isotope-based technologies in nuclear medicine.

Radiosensitization of Allogenic Subcutaneous C6 Glioma Model with Focused Ultrasound-Induced Mild Hyperthermia.

The radiosensitization potential of focused ultrasound (FUS)-induced mild hyperthermia was assessed in an allogenic subcutaneous C6 glioma tumor model in rats. Mild hyperthermia at 42 °C was induced in tumors using a single-element 350 kHz FUS transducer. Radiation was delivered with a small animal radiation research platform using a single-beam irradiation technique. The combined treatment involved 20 min of FUS hyperthermia immediately before radiation. Tumor growth changes were observed one week post-treatment. A radiation dose of 2 Gy alone showed limited tumor control (30% reduction). However, when combined with FUS hyperthermia, there was a significant reduction in tumor growth compared to other treatments (tumor volumes: control-1174 ± 554 mm3, FUS-HT-1483 ± 702 mm3, 2 Gy-609 ± 300 mm3, FUS-HT + 2 Gy-259 ± 186 mm3; ANOVA p < 0.00001). Immunohistological analysis suggested increased DNA damage as a short-term mechanism for tumor control in the combined treatment. In conclusion, FUS-induced mild hyperthermia can enhance the effectiveness of radiation in a glioma tumor model, potentially improving the outcome of standard radiation treatments for better tumor control.

Advanced Technologies in Radiation Research.

The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research. This meeting report provides a comprehensive overview of the research presented at the workshop, which included an assembly of subject matter experts from government, industry, and academia. Topics discussed during the workshop included assessments of acute and delayed effects of radiation exposure using modalities such as clustered regularly interspaced short palindromic repeats (CRISPR) - based gene editing, tissue chips, advanced computing, artificial intelligence, and immersive imaging techniques. These approaches are being applied to develop products to diagnose and treat radiation injury to the bone marrow, skin, lung, and gastrointestinal tract, among other tissues. The overarching goal of the workshop was to provide an opportunity for the radiation research community to come together to assess the technological landscape through sharing of data, methodologies, and challenges, followed by a guided discussion with all participants. Ultimately, the organizers hope that the radiation research community will benefit from the workshop and seek solutions to scientific questions that remain unaddressed. Understanding existing research gaps and harnessing new or re-imagined tools and methods will allow for the design of studies to advance medical products along the critical path to U.S. Food and Drug Administration approval.

A new ductile, tougher resin for impregnation of superconducting magnets

A major remaining challenge for Nb3Sn high field magnets is their training due to random temperature variations in the coils. The main objective of our research is to reduce or eliminate it by finding novel impregnation materials in replacement of the epoxies currently used. An organic olefin-based thermosetting dicyclopentadiene resin, C10H12, commercially available in Japan as TELENE® by RIMTEC, was used to impregnate a short Nb3Sn undulator coil developed by ANL and FNAL. This magnet reached short sample limit after only two quenches, compared with ∼100 when CTD-101K® was used. Ductility, i.e. the ability to accept large strains, and toughness were identified as key properties to achieve these results. In addition, we have been investigating whether mixing TELENE with high heat capacity ceramic powders such as Gd2O3, Gd2O2S, and HoCu2, increases the specific heat (Cp ) of impregnated Nb3Sn superconducting magnets. The viscosity, heat capacity, thermal conductivity, and other physical properties of TELENE with high-Cp powder fillers were measured in this study as a function of temperature and magnetic field. The TELENE-87 wt%Gd2O2S had a peak in Cp between 4.3 K and 5.3 K at fields between 0 and 8 T. We have also investigated the effect on the mechanical properties of pure and mixed TELENE under 10 MGy of gamma ray irradiation at the Takasaki Advanced Radiation Research Institute in Takasaki, Japan. TELENE-87 wt%Gd2O2S exhibited exceptional radiation resistance. Impregnating an undulator coil with TELENE mixed with Gd2O2S powder will verify whether the coils’ thermal stability further improves, or whether its low diffusivity will require engineering the material with high-thermal conductivity components. Short magnet training will lead to better magnet reliability, lower magnet margins, lower risk and substantial saving in accelerators’ commissioning costs. Part of this study is supported by the U.S.-Japan Science and Technology Cooperation Program in high energy physics operated by MEXT in Japan and DOE in the U.S.

Targeted irradiation in an autochthonous mouse model of pancreatic cancer.

The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour targeting, negligible off-target effects and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide a proof of concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.

Radiation evaluation assay using a human three-dimensional oral cancer model for clinical radiation therapy.

With the development of various radiation-based cancer therapies, radiobiological evaluation methods instead of traditional clonogenic assays with monolayer single cell culture are required to bridge gaps in clinical data. Heterogeneity within cancer tissues is the reason for bridging the gap between basic and clinical research in cancer radiotherapy. To solve this problem, we investigated an evaluation assay using a three-dimensional (3D) model of cancer tissue. In this study, a 3D model consisting of tumor and stromal layers was used to compare and verify radiobiological effects with conventional two-dimensional (2D) methods. A significant difference in the response to radiation was observed between the 2D and 3D models. The relative number of cancer cells decreased with X-ray dose escalations in the 2D and 3D models. In contrast, the relative number of normal cells was quite different between the 2D and 3D models. Considering the ability of cells to recover from radiation-induced damage, the histological results of the 3D model were reflected in the clinical data. Histopathological analysis using a 3D model is a potential method for evaluating radiobiological effects on the tumor and tumor margins.

Highlighting the NIAID Radiation and Nuclear Countermeasures Program's Commitment to Training and Diversifying the Radiation Workforce.

Developing and maintaining a robust and diverse scientific workforce is crucial to advance knowledge, drive innovation, and tackle societal issues that impact the economy and human health. The shortage of trained professionals in radiation and nuclear sciences derives from many factors, such as scarcity of specialized coursework, programming, professional development, and experiential learning at educational institutions, which significantly disrupt the training pipeline. Other challenges include small numbers of faculty and educators with specialized radiation/nuclear expertise that are continually overextended professionally and scientifically, with the burden of training falling on this subset of individuals. Even more alarming is the recent loss of radiobiologists due to increased retirements and deaths, leaving the radiobiology community with a void of mentors and knowledge. Lastly, inconsistency in acquiring stable grant funding to recruit and retain scientists is a major hurdle to training the next generation of radiation and nuclear scientists. Recommendations from the scientific community and the National Academies of Sciences, Engineering, and Medicine describe the need to bolster educational resources and provide more hands-on training experiences. Of equal importance was the suggestion that funding agencies provide more opportunities for training and tracking the radiation workforce. The Radiation and Nuclear Countermeasures Program (RNCP), and the Office of Research Training and Special Programs (ORTSP), both within the National Institute of Allergy and Infectious Diseases (NIAID) are committed to helping to develop and sustain the radiation research workforce. This commentary illustrates the importance of addressing radiation workforce development and outlines steps that the RNCP is taking to help mitigate the issue. In addition, the role for Diversity, Equity, Inclusion, and Accessibility (DEIA) in helping to increase the number of students trained in the radiation sciences is discussed, and the NIH's DEIA priorities and RNCP efforts to improve DEIA in the research community are highlighted. One of the main goals of this commentary is to provide awareness of available educational (i.e., development of a radiation biologist eBook) and funding resources. A summary of available awards targeting early- to mid-stage investigators and diversity candidates is given, and it is hoped that this list, although not exhaustive and not specific for all focus areas in radiation (e.g., cancer research), will encourage more radiation biologists to explore and apply to these under-utilized opportunities.

A Review: Multi-Omics Approach to Studying the Association between Ionizing Radiation Effects on Biological Aging.

Multi-omics studies have emerged as powerful tools for tailoring individualized responses to various conditions, capitalizing on genome sequencing technologies' increasing affordability and efficiency. This paper delves into the potential of multi-omics in deepening our understanding of biological age, examining the techniques available in light of evolving technology and computational models. The primary objective is to review the relationship between ionizing radiation and biological age, exploring a wide array of functional, physiological, and psychological parameters. This comprehensive review draws upon an extensive range of sources, including peer-reviewed journal articles, government documents, and reputable websites. The literature review spans from fundamental insights into radiation effects to the latest developments in aging research. Ionizing radiation exerts its influence through direct mechanisms, notably single- and double-strand DNA breaks and cross links, along with other critical cellular events. The cumulative impact of DNA damage forms the foundation for the intricate process of natural aging, intersecting with numerous diseases and pivotal biomarkers. Furthermore, there is a resurgence of interest in ionizing radiation research from various organizations and countries, reinvigorating its importance as a key contributor to the study of biological age. Biological age serves as a vital reference point for the monitoring and mitigation of the effects of various stressors, including ionizing radiation. Ionizing radiation emerges as a potent candidate for modeling the separation of biological age from chronological age, offering a promising avenue for tailoring protocols across diverse fields, including the rigorous demands of space exploration.

Pathology of the pelvic bones and its correction in bladder exstrophy

There are many studies regarding treatment methods for bladder exstrophy, but it is impossible to single out the only correct one. When treating bladder exstrophy, all defects can be eliminated separately, but the effect of such interventions will be incomplete. When analyzing the anatomy of patients with this pathology, pronounced splitting and divergence of the pelvic muscles is noted due to dysplasia and the wide position of the iliac and pubic bones. Due to the inferiority of the pelvic bones, the functions of all its organs are disrupted. Modern methods of radiation research have made it possible to better understand the main causes of such changes: outwardly rotated iliac bones, retroversion of the acetabulum and femur, shortened branches of the pubic bones, a backward curved acetabulum and flabby sacroiliac joint, increased distance between the triradial cartilages. Such changes are difficult to eliminate with soft tissue plastic surgery, so specialists who use osteotomy of the pelvic bones in the treatment of this pathology have more positive results. Since 1958, in the treatment of children with exstrophy of the bladder, osteotomy has been used in various versions, which makes it possible to restore the pelvic ring, improve the results of soft tissue plastic surgery and urinary continence. The authors noted a high rate of continence success in patients who underwent primary bladder closure without complications such as wound infection, dehiscence, or any degree of bladder prolapse. Thus, correction of the skeletal system serves as a basic element in the correction of bladder exstrophy.

Morphometric features of the human parotid salivary gland depending on the shape of the skull according to radiation research methods

BACKGROUND: Intravital study of the parotid salivary gland individual characteristics using radiation research methods can be used by clinicians for more accurate diagnosis and planning of surgical treatment of the parotid salivary gland diseases.&#x0D; AIM: Study of the parotid salivary glands’ morphometric parameters in people with different shapes of the facial and cerebral skull using radiation research methods.&#x0D; MATERIAL AND METHODS: An analysis of the database of studies performed using magnetic resonance and computed tomography of 120 patients of different ages was carried out. Based on computed tomography data, cranial diameters were measured and cranial indices were calculated, according to which the studied material was divided into groups depending on the shape of the facial (leptena, mesena, eurienae) and cerebral (brachycranes, dolichocranes and mesocranes) parts of the skull. Based on magnetic resonance imaging data of the same patients, the morphometric parameters of the parotid salivary glands were analyzed in three planes. Groups were compared using the Kruskal–Wallis method, followed by pairwise comparisons using the Mann–Whitney method with the Bonferroni correction.&#x0D; RESULTS: In the leptene group, the frontal size of the gland was statistically significantly smaller compared to similar sizes in the group of euriens (right p 0.0001, left p 0.0001) and mesenes (right p=0.0057, left p=0.012). The sagittal size of the gland was statistically significantly different between the brachy-, meso- and dolichocranial groups (p 0.0001 on the right and left). A significant tendency was revealed for a decrease in the sagittal size of the parotid salivary glands from 4.27 (3.77; 4.66) cm (right) and 4 (3.8; 4.6) cm (left) in dolichocraniform individuals to 3.57 (3.22; 3.86) cm (right) and 3.37 (3.16; 3.99) cm (left) in individuals with a brachiocranial skull shape. When measuring the frontal size in people with different skull shapes, a statistically significant difference in gland thickness between groups was found (p 0.0001 on the right and left).&#x0D; CONCLUSION: In people with different forms of the facial skull, there is a difference in the vertical and frontal sizes of the parotid salivary glands, and with different forms of the brain skull, there is a difference in the sagittal and frontal sizes of the glands.

Multimodal approach in radiation diagnostics to determining the intramedullary phase of strictly hematogenic osteomyelitis in children: a prospective study

INTRODUCTION: Despite the fact that acute hematogenous osteomyelitis is classified as a sufficiently studied disease, the percentage of diagnostic errors is still quite high. Timely diagnosis is crucial for the successful outcome of the disease, therefore, visualization should be aimed at early diagnosis and, as a result, successful treatment of the disease.OBJECTIVE: To identify early patterns in the intramedullary phase of the course of acute hematogenous osteomyelitis (CSO) with a multimodal approach of radiation research methods.MATERIALS AND METHODS: Twenty patients underwent a comprehensive examination, including multispiral computed tomography (MSCT) using color mapping techniques.RESULTS: In the intramedullary phase of the course of CSF, no pathological changes were detected during X-ray examination of the affected limb. Ultrasound in 75% of observations revealed a thickening of the periosteum of more than 1 millimeter (mm) in the affected bone. When using MRI in 93% of cases, and with MSCT in 95% of patients, signs of bone marrow edema were detected.DISCUSSION: The role of computed tomography in the diagnosis of acute hematogenous osteomyelitis in children has received significant recognition in pediatric surgical practice in recent years, and the use of MSCT in the diagnosis of CSO has found application in domestic healthcare. At the same time, a fairly large number of researchers reported on the high informativeness of MSCT in the diagnosis of CSOs.CONCLUSION: MSCT using the color mapping technique has a higher specificity compared to MRI and can be used as an integral method of the first level in the diagnosis of the intramedullary phase of the CSF course.

Artificial intelligence in biology and medicine, and radioprotection research: perspectives from Jerusalem.

While AI is widely used in biomedical research and medical practice, its use is constrained to few specific practical areas, e.g., radiomics. Participants of the workshop on "Artificial Intelligence in Biology and Medicine" (Jerusalem, Feb 14-15, 2023), both researchers and practitioners, aimed to build a holistic picture by exploring AI advancements, challenges and perspectives, as well as to suggest new fields for AI applications. Presentations showcased the potential of large language models (LLMs) in generating molecular structures, predicting protein-ligand interactions, and promoting democratization of AI development. Ethical concerns in medical decision making were also addressed. In biological applications, AI integration of multi-omics and clinical data elucidated the health relevant effects of low doses of ionizing radiation. Bayesian latent modeling identified statistical associations between unobserved variables. Medical applications highlighted liquid biopsy methods for non-invasive diagnostics, routine laboratory tests to identify overlooked illnesses, and AI's role in oral and maxillofacial imaging. Explainable AI and diverse image processing tools improved diagnostics, while text classification detected anorexic behavior in blog posts. The workshop fostered knowledge sharing, discussions, and emphasized the need for further AI development in radioprotection research in support of emerging public health issues. The organizers plan to continue the initiative as an annual event, promoting collaboration and addressing issues and perspectives in AI applications with a focus on low-dose radioprotection research. Researchers involved in radioprotection research and experts in relevant public policy domains are invited to explore the utility of AI in low-dose radiation research at the next workshop.

Role of the mechanical microenvironment on CD-44 expression of breast adenocarcinoma in response to radiotherapy

The biological effects of ionizing radiation are exploited in the clinical practice of radiotherapy to destroy tumour cells while sparing the surrounding normal tissue. While most of the radiotherapy research focused on DNA damage and repair, recently a great attention is going to cells' interactions with the mechanical microenvironment of both malignant and healthy tissues after exposure. In fact, the stiffness of the extracellular matrix can modify cells' motility and spreading through the modulation of transmembrane proteins and surface receptors' expression, such as CD-44. CD-44 receptor has held much interest also in targeted-therapy due to its affinity with hyaluronic acid, which can be used to functionalize biodegradable nanoparticles loaded with chemotherapy drugs for targeted therapy. We evaluated changes in CD-44 expression in two mammary carcinoma cell lines (MCF10A and MDA-MB-231) after exposure to X-ray (2 or 10 Gy). To explore the role of the mechanical microenvironment, we mimicked tissues' stiffness with polyacrylamide's substrates producing two different elastic modulus values (0.5 and 15 kPa). We measured a dose dependent increase in CD-44 relative expression in tumour cells cultured in a stiffer microenvironment. These findings highlight a crucial connection between the mechanical properties of the cell's surroundings and the post-radiotherapy expression of surface receptors.

Methods of research of radiothermal radiation of cryospheric objects in the microwave range

Many cryospheric formations on Earth have an inaccessible location. For example, when studying ice sheets located on the water surface, at the initial moment of ice formation, it becomes difficult to take samples. Remote monitoring methods in the microwave range can be used to study such objects. For example, install a microwave radiometer on an unmanned aerial vehicle and use its own thermal radiation from a cryogenic object to record various kinds of features. For radiometric measurements using microwave radiometers, it is necessary to calibrate the measuring device. In this paper, the radiometer calibration method is considered. For these purposes, two objects with known radiative characteristics were measured. The first is fresh open water with a known surface area and thermodynamic temperature against the background of a frozen cloudless atmosphere. The second is a section of the sky reflected from a metal sheet, with the same area. As an example, radiometric measurements of the ice cover of the Ingoda River, located in the Transbaikal Territory (Russia) at a frequency of 34 GHz, were performed. This measurement technique will be useful to specialists in the field of environmental monitoring of cryospheric formations by microwave remote methods in winter.