The German Uranium Miners’ Biobank—A Biobank for OMICs Radiation Research

Systematic bio- and databanks are key prerequisites for modern radiation research to investigate radiation response mechanisms in the context of genetic, environmental and lifestyle-associated factors. This report presents the current status of the German Uranium Miners’ Biobank. In 2008, the bio- and databank was established at the Federal Office for Radiation Protection, and the sampling of biological materials from former uranium miners with and without lung cancer was initiated. For this purpose, various biological specimens, such as DNA and RNA, were isolated from blood samples as well as from formalin-fixed paraffin-embedded lung tissue. High-quality biomaterials suitable for OMICs research and the associated data on occupational radiation and dust exposure, and medical and lifestyle data from over 1000 individuals have been stored so far. Various experimental data, e.g., genome-wide SNPs, whole genome transcriptomic and miRNA data, as well as individual chromosomal aberration data from subgroups of biobank samples, are already available upon request for in-depth research on radiation-induced long-term effects, individual radiation susceptibility to lung cancer and radon-induced fingerprints in lung cancer. This biobank is the first systematic uranium miners´ biobank worldwide that is suitable for OMICs research on radiation-exposed workers. It offers the opportunity to link radiation-induced perturbations of biological pathways or processes and putative adverse outcome(s) by OMICs profiling at different biological organization levels.

Magnetic Resonance Diffusion-Weighted Imaging for Detecting Fundal Intracholecystic Papillary Neoplasm inside Rokitansky-Aschoff Sinuses: A Comparison of Two Cases and a Literature Review

Rokitansky-Aschoff sinuses (RAS) are a common imaging finding in gallbladder adenomyomatosis (ADM), often presenting as fundal cystic spaces. Intracholecystic papillary neoplasm (ICPN) is a relatively uncommon pre-invasive tumor of the gallbladder epithelium that rarely involves RAS mucosa. We compare two cases that showed similar fundal cystic spaces resembling RAS, in which Magnetic Resonance Diffusion-Weighted Imaging (MR-DWI) was valuable for detecting (or ruling out) an underlying malignant ICPN. Evidence from the literature overall supports the role of MR-DWI for detecting intracholecystic malignant tissue.

Computational Biophysical Modeling of the Radiation Bystander Effect in Irradiated Cells

It is well known that ionizing radiation can cause damages to cells that interact with it directly. However, many studies have shown that damages also occur in cells that have not experienced direct interaction. This is due to the so-called bystander effect, which is observed when the irradiated cell sends signals that can damage neighboring cells. Due to the complexity of this effect, it is not easy to strictly describe it biophysically, and thus it is also difficult to simulate. This article reviews various approaches to modeling and simulating the bystander effect from the point of view of radiation biophysics. In particular, the last model presented within this article is part of a larger project of modeling the response of a group of cells to ionizing radiation using Monte Carlo methods. The new approach presented here is based on the probability tree, the Poisson distribution of signals and the saturated dose-related probability distribution of the bystander effect’s appearance, which makes the model very broad and universal.

Optical Fiber-Based Monitoring of X-ray Pulse Series from a Linear Accelerator

We investigated in this work the radioluminescence properties of a Ce-doped multimode silica-based optical fiber (core diameter of 50 µm) manufactured by the sol–gel technique when exposed to the high-energy X-rays (~600 keV) of the ORIATRON facility of CEA. We demonstrated its potential to monitor in real-time the beam characteristics of this facility that can either operate in a pulsed regime (pulse duration of 4.8 µs, maximum repetition rate of 250 Hz) or in a quasi-continuous mode. The radiation-induced emission (radioluminescence and a minor Cerenkov contribution) linearly grew with the dose rate in the 15–130 mGy(SiO2)/s range, and the afterglow measured after each pulse was sufficiently limited to allow a clear measurement of pulse trains. A sensor with ~11 cm of sensitive Ce-doped fiber spliced to rad-hard fluorine-doped optical fiber, for the emitted light transport to the photomultiplier tube, exhibited interesting beam monitoring performance, even if the Cerenkov emission in the transport fiber was also considered (~5% of the signal). The beam monitoring potential of this class of optical fiber was demonstrated for such facilities and the possibilities of extending the dose rate range are discussed based on possible architecture choices such as fiber type, length or size.

A Validation Study on Immunophenotypic Differences in T-lymphocyte Chromosomal Radiosensitivity between Newborns and Adults in South Africa

Children have an increased risk of developing radiation-induced secondary malignancies compared to adults, due to their high radiosensitivity and longer life expectancy. In contrast to the epidemiological evidence, there is only a handful of radiobiology studies which investigate the difference in radiosensitivity between children and adults at a cellular level. In this study, the previous results on the potential age dependency in chromosomal radiosensitivity were validated again by means of the cytokinesis-block micronucleus (CBMN) assay in T-lymphocytes isolated from the umbilical cord and adult peripheral blood of a South African population. The isolated cells were irradiated with 60Co γ-rays at doses ranging from 0.5 Gy to 4 Gy. Increased radiosensitivities of 34%, 42%, 29%, 26% and 16% were observed for newborns compared to adults at 0.5, 1, 2, 3 and 4 Gy, respectively. An immunophenotypic evaluation with flow cytometry revealed a significant change in the fraction of naïve (CD45RA+) T-lymphocytes in CD4+ and CD8+ T-lymphocytes with age. Newborns co-expressed an average of 91.05% CD45RA+ (range: 80.80–98.40%) of their CD4+ cells, while this fraction decreased to an average of 39.08% (range: 12.70–58.90%) for adults. Similar observations were made for CD8+ cells. This agrees with previous published results that the observed differences in chromosomal radiosensitivity between newborn and adult T-lymphocytes could potentially be linked to their immunophenotypic profiles.

Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier

Limited-stage (LS) small-cell lung cancer (SCLC) is defined as disease confined to a tolerable radiation portal without extrathoracic metastases. Despite clinical research over two decades, the prognosis of LS-SCLC patients remains poor. The current standard of care for LS-SCLC patients is concurrent platinum-based chemotherapy with thoracic radiotherapy (RT). Widespread heterogeneity on the optimal radiation dose and fractionation regimen among physicians highlights the logistical challenges of administering BID regimens. Prophylactic cranial irradiation (PCI) is recommended to patients following a good initial response to chemoradiation due to improved overall survival from historical trials and the propensity for LS-SCLC to recur with brain metastases. However, PCI utilization is being debated due to the greater availability of magnetic resonance imaging (MRI) and data in extensive-stage SCLC regarding close MRI surveillance in lieu of PCI while spurring novel RT techniques, such as hippocampal-avoidance PCI. Additionally, novel treatment combinations incorporating targeted small molecule therapies and immunotherapies with or following radiation for LS-SCLC have seen recent interest and some concepts are being investigated in clinical trials. Here, we review the landscape of progress, limitations, and challenges for LS-SCLC including current standard of care, novel radiation techniques, and the integration of novel therapeutic strategies for LS-SCLC.

Metallic Nanoparticles: A Useful Prompt Gamma Emitter for Range Monitoring in Proton Therapy?

In clinical practice, dose delivery in proton therapy treatment is affected by uncertainties related to the range of the beam in the patient, which requires medical physicists to introduce safety margins on the penetration depth of the beam. Although this ensures an irradiation of the entire clinical target volume with the prescribed dose, these safety margins also lead to the exposure of nearby healthy tissues and a subsequent risk of side effects. Therefore, non-invasive techniques that allow for margin reduction through online monitoring of prompt gammas emitted along the proton tracks in the patient are currently under development. This study provides the proof-of-concept of metal-based nanoparticles, injected into the tumor, as a prompt gamma enhancer, helping in the beam range verification. It identifies the limitations of this application, suggesting a low feasibility in a realistic clinical scenario but opens some avenues for improvement.

Oxygen Depletion in Proton Spot Scanning: A Tool for Exploring the Conditions Needed for FLASH

FLASH radiotherapy is a rapidly developing field which promises improved normal tissue protection compared to conventional irradiation and no compromise on tumour control. The transient hypoxic state induced by the depletion of oxygen at high dose rates provides one possible explanation. However, studies have mostly focused on uniform fields of dose and there is a lack of investigation into the spatial and temporal variation of dose from proton pencil-beam scanning (PBS). A model of oxygen reaction and diffusion in tissue has been extended to simulate proton PBS delivery and its impact on oxygen levels. This provides a tool to predict oxygen effects from various PBS treatments, and explore potential delivery strategies. Here we present a number of case applications to demonstrate the use of this tool for FLASH-related investigations. We show that levels of oxygen depletion could vary significantly across a large parameter space for PBS treatments, and highlight the need for in silico models such as this to aid in the development and optimisation of FLASH radiotherapy.

The Role of NMDAR and BDNF in Cognitive Dysfunction Induced by Different Microwave Radiation Conditions in Rats

Background: To investigate the effects of different levels of microwave radiation on learning and memory in Wistar rats and explore the underlying mechanisms of N-methyl-D-aspartate receptor (NMDAR/NR) and Brain-derived neurotropic factor (BDNF); Methods: A total of 140 Wistar rats were exposed to microwave radiation levels of 0, 10, 30 or 50 mW/cm2 for 6 min. Morris Water Maze Test, high-performance liquid chromatography, Transmission Electron Microscope and Western blotting were used; Results: The 30 and 50 mW/cm2 groups exhibited longer average escape latencies and fewer platform crossings than the 0 mW/cm2 group from 6 h to 3 d after microwave radiation. Alterations in the amino acid neurotransmitters of the hippocampi were shown at 6 h, 3 d and 7 d after exposure to 10, 30 or 50 mW/cm2 microwave radiation. The length and width of the Postsynaptic density were increased. The expression of NR1, NR2A and NR2B increased from day 1 to day 7; Postsynaptic density protein-95 and cortactin expression increased from day 3 to day 7; BDNF and Tyrosine kinase receptor B (TrkB) expression increased between 6 h and 1 d after 30 mW/cm2 microwave radiation exposure, but they decreased after 50mW/cm2 exposure. Conclusions: Microwave exposure (30 or 50 mW/cm2, for 6 min) may cause abnormalities in neurotransmitter release and synaptic structures, resulting in impaired learning and memory; BDNF and NMDAR-related signaling molecules might contribute differently to these alterations.

Legal and Regulatory Framework for AI Solutions in Healthcare in EU, US, China, and Russia: New Scenarios after a Pandemic

The COVID-19 crisis has exposed some of the most pressing challenges affecting healthcare and highlighted the benefits that robust integration of digital and AI technologies in the healthcare setting may bring. Although medical solutions based on AI are growing rapidly, regulatory issues and policy initiatives including ownership and control of data, data sharing, privacy protection, telemedicine, and accountability need to be carefully and continually addressed as AI research requires robust and ethical guidelines, demanding an update of the legal and regulatory framework all over the world. Several recently proposed regulatory frameworks provide a solid foundation but do not address a number of issues that may prevent algorithms from being fully trusted. A global effort is needed for an open, mature conversation about the best possible way to guard against and mitigate possible harms to realize the potential of AI across health systems in a respectful and ethical way. This conversation must include national and international policymakers, physicians, digital health and machine learning leaders from industry and academia. If this is done properly and in a timely fashion, the potential of AI in healthcare will be realized.