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Abstract With the rapid global warming in recent decades, the Tibetan Plateau (TP) has suffered severe impacts, such as glacier retreat, glacial lake expansion, and permafrost degradation, which threaten the lives and properties of the local and downstream populations. Regional Reanalysis (RR) is vital for TP due to the limitations of observations. In this work, a 62-year (1961–2022) long atmospheric regional reanalysis with spatial resolution of 9 km (convective gray-zone scale) and temporal resolution of 1 hour over the TP (TPRR) was developed using the Weather Research and Forecasting (WRF) model, combined with re-initialization method, spectral nudging (SN), and several optimizations. TPRR is forced by ERA5 at hourly intervals. TPRR outperforms ERA5, realistically capturing climatological characteristics and seasonal variations of precipitation and T2m (air temperature at 2m above ground level). Moreover, TPRR better reproduces the frequency and intensity of precipitation, as well as the diurnal cycle of precipitation. This study also quantifies the wetting trend of 0.0071 mm/year over the TP amid global warming using TPRR.

Abstract The cloud classification algorithm widely used in the International Satellite Cloud Climatology Project (ISCCP) tends to underestimate low clouds over the Tibetan Plateau (TP), often mistaking water clouds for high‐level clouds. To address this issue, we propose a new algorithm based on cloud‐top temperature and optical thickness, which we apply to TP using Advanced Himawari Imager (AHI) geostationary satellite data. Compared with Clouds and the Earth's Radiant Energy System cloud‐type products and ISCCP results obtained from AHI data, this new algorithm markedly improved low‐cloud detection accuracy and better aligned with cloud phase results. Validation with lidar cloud‐type products further confirmed the superiority of this new algorithm. Diurnal cloud variations over the TP show morning dominance shifting to afternoon high clouds and evening mid‐level clouds. Winter is dominated by high clouds, summer by mid‐level clouds, spring by daytime low clouds and nighttime high clouds, and autumn by low and mid‐level clouds.

Abstract Distant metastasis is the leading cause of death in breast cancer (BC). The timing of distant metastasis differs according to subtypes of BCs and there is a need for identification of biomarkers for the prediction of early and late metastasis. To identify biomarker candidates whose abundance level can discriminate metastasis types, we performed a high-throughput proteomics assay using tissue samples from BCs with no metastasis, late metastasis, and early metastasis, processed data with machine learning-based feature selection, and found that low VWA5A could be responsible for shorter duration of metastasis-free interval. Low expression of VWA5A gene in METABRIC cohort was associated with poor survival in BCs, especially in hormone receptor (HR)-positive BCs. In-vitro experiments confirmed tumor suppressive effect of VWA5A on BCs in HR+ and triple-negative BC cell lines. We found that expression of VWA5A can be assessed by immunohistochemistry (IHC) on archival tissue samples. Decreasing nuclear expression of VWA5A was significantly associated with advanced T stage and lymphatic invasion in consecutive BCs of all subtypes. We discovered lower expression of VWA5A as the potential biomarker for metastasis-prone BCs, and our results support the clinical utility of VWA5A IHC, as an adjunctive tools for prognostication of BCs.

We investigate the effects of incorporating single-walled carbon nanotubes (CNTs) into sol–gel-derived ZnO thin films to enhance their optoelectronic properties for photodetector applications. ZnO thin films were fabricated on c-plane sapphire substrates with varying CNT concentrations ranging from 0 to 2.0 wt%. Characterization techniques, including high-resolution X-ray diffraction, photoluminescence, and atomic force microscopy, demonstrated the preferential growth of the ZnO (002) facet and improved optical properties with the increase in the CNT content. Electrical measurements revealed that the optimal CNT concentration of 1.5 wt% resulted in a significant increase in the dark current (from 0.34 mA to 1.7 mA) and peak photocurrent (502.9 µA), along with enhanced photoresponsivity. The rising and falling times of the photocurrent were notably reduced at this concentration, indicating improved charge dynamics due to the formation of a p-CNT/n-ZnO heterojunction. The findings suggest that the incorporation of CNTs not only modifies the structural and optical characteristics of ZnO thin films but also significantly enhances their electrical performance, positioning CNT-ZnO composites as promising candidates for advanced photodetector technologies in optoelectronic applications.

Under extended-phase-shift (ESP) control, the current stress of the dual active bridge converter (DAB) is relatively high, which reduces the efficiency of the converter. To solve this problem, a particle swarm optimization (PSO) algorithm based on minimizing the current stress is proposed in this paper. The optimal phase-shift ratio of the DAB converter with ESP control is obtained by using the algorithm’s optimization characteristic. This approach ensures that the converter achieves minimal current stress, thereby enhancing the steady-state performance of the DAB converter. Moreover, in terms of dynamic performance, traditional PI control has poor dynamic response ability when there are sudden changes in load and input voltage. To solve this problem, the voltage dynamic matrix control (DMC) algorithm is introduced to combine with the PSO algorithm to minimize the current stress of the DAB converter under EPS control while enhancing the dynamic response capability of the DAB converter. A simulation model was constructed for comparative validation on MATLAB/Simulink 2019, demonstrating the correctness and effectiveness of the improved control method.

This study investigates the impact of spin-coating speed on the performance of carbon nanotube (CNT)-based optoelectronic synaptic devices, focusing on their long-term memory properties. CNT films fabricated at lower spin speeds exhibited a greater thickness and density compared to those at higher speeds. These denser films showed enhanced persistent photoconductivity, resulting in higher excitatory postsynaptic currents (EPSCs) and the prolonged retention of memory states after UV stimulation. Devices coated at a lower spin-coating speed of 2000 RPM maintained EPSCs above 70% for 3600 s, outperforming their higher-speed counterparts in long-term memory retention. Additionally, the study demonstrated that the learning efficiency improved with repeated UV stimulation, with fewer pulses needed to achieve the maximum EPSC in successive learning cycles. These findings highlight that optimizing spin-coating speeds can significantly enhance the performance of CNT-based synaptic devices, making them suitable for applications in neuromorphic computing and artificial neural networks requiring robust memory retention and efficient learning.

Cancer is typically treated with combinatorial therapy, and such combinations may be synergistic. However, discovery of these combinations has proven difficult as brute force combinatorial screening approaches are both logistically complex and resource-intensive. Therefore, computational approaches to augment synergistic drug discovery are of interest, but current approaches are limited by their dependencies on combinatorial drug screening training data or molecular profiling data. These dataset dependencies can limit the number and diversity of drugs for which these approaches can make inferences. Herein, we describe a novel computational framework, ReCorDE (Recurrent Correlation of Drugs with Enrichment), that uses publicly-available cell line-derived monotherapy cytotoxicity datasets to identify drug classes targeting shared vulnerabilities across multiple cancer lineages; and we show how these inferences can be used to augment synergistic drug combination discovery. Additionally, we demonstrate in preclinical models that a drug class combination predicted by ReCorDE to target shared vulnerabilities (PARP inhibitors and Aurora kinase inhibitors) exhibits class-class synergy across lineages. ReCorDE functions independently of combinatorial drug screening and molecular profiling data, using only extensive monotherapy cytotoxicity datasets as its input. This allows ReCorDE to make robust inferences for a large, diverse array of drugs. In conclusion, we have described a novel framework for the identification of drug classes targeting shared vulnerabilities using monotherapy cytotoxicity datasets, and we showed how these inferences can be used to aid discovery of novel synergistic drug combinations.

Abstract To respond to the external environmental changes for survival, bacteria regulates expression of a number of genes including transcription factors (TFs). To characterize complex biological phenomena, a biological system-level approach is necessary. Here we utilized six computational biology methods to infer regulatory network and to characterize underlying biologically mechanisms relevant to radiation-resistance. In particular, we inferred gene regulatory network (GRN) and operons of radiation-resistance bacterium Spirosoma montaniterrae DY10 $$^T$$ T and identified the major regulators for radiation-resistance. Our results showed that DNA repair and reactive oxygen species (ROS) scavenging mechanisms are key processes and Crp/Fnr family transcriptional regulator works as a master regulatory TF in early response to radiation.

Real-time monitoring of rainfall areas based on satellite remote sensing is of vital importance for extreme rainfall research and disaster prediction. In this study, a new rainfall area identification algorithm was developed for the new generation of geostationary satellites with high spatial and temporal resolution and rich bands. As the main drivers of the rainfall process, the macro and micro physical properties of clouds play an important role in the formation and development of rainfall. We considered differences in the absorption capacity of the water vapor absorption channels in the infrared band and introduced a sensitivity difference of rainfall area in water vapor channels to construct a sensitive detection of the water vapor region. The results of this algorithm were evaluated using Global Precipitation Measurement (GPM) satellite products and CloudSat measurements in various scenarios, with hit rates of 70.03% and 81.39% and false alarm rates of 2.05% and 21.34%, respectively. Spatiotemporal analysis revealed that the types of upper clouds in the rainfall areas mainly consisted of deep convection, cirrostratus, and nimbostratus clouds. Our study provides supporting data for weather research and disaster prediction, as well as an efficient and reliable method for capturing temporal and spatial features.

Measurement(s) land surface temperature Technology Type(s) satellite imaging Sample Characteristic - Environment planetary surface Sample Characteristic - Location global

The measurement of bidirectional reflectivity for ground-based objects is a highly intricate task, with significant limitations in the capabilities of both ground-based and satellite-based observations from multiple viewpoints. In recent years, unmanned aerial vehicles (UAVs) have emerged as a novel remote sensing method, offering convenience and cost-effectiveness while enabling multi-view observations. This study devised a polygonal flight path along the hemisphere to achieve bidirectional reflectance distribution function (BRDF) measurements for large zenith angles and all azimuth angles. By employing photogrammetry’s principle of aerial triangulation, accurate observation angles were restored, and the geometric structure of “sun-object-view” was constructed. Furthermore, three BRDF models (M_Walthall, RPV, RTLSR) were compared and evaluated at the UAV scale in terms of fitting quality, shape structure, and reflectance errors to assess their inversion performance. The results demonstrated that the RPV model exhibited superior inversion performance followed, by M_Walthall; however, RTLST performed comparatively poorly. Notably, the M_Walthall model excelled in capturing smooth terrain object characteristics while RPV proved applicable to various types of rough terrain objects with multi-scale applicability for both UAVs and satellites. These methods and findings are crucial for an extensive exploration into the bidirectional reflectivity properties of ground-based objects, and provide an essential technical procedure for studying various ground-based objects’ in-plane reflection properties.

Abstract In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague–Dawley rats (NSC‐pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with β‐tubulin III [also called Tuj1]) was significantly increased in the NSC‐pGNP gel group (***p

Accurate high-resolution atmospheric temperature profiles are essential for precisely characterizing the evolution of the atmosphere and developing numerical forecasts. Atmospheric datasets, such as ERA5 (the fifth-generation ECMWF Reanalysis) and MERRA-2 (the Modern-Era Retrospective Analysis for Research and Applications, Version 2), provide global and continuous temperature profiles, with fine vertical distribution and horizontal resolution. RAOB (Radiosonde Observation) sounding data have high confidence and representativeness and are usually used for data accuracy verification. Due to the difficulty of updating existing products, and the scarcity of research on mesospheric temperature profiles, this work maximizes the high observation accuracy of RAOB data, combines the benefits of ERA5’s horizontal resolution and MERRA-2’s vertical distribution, and employs the optimal interpolation method to combine the data, in order to produce a fused result with high spatial resolution. After converting all of the data to the same spatial distribution, the optimal interpolation method was used to combine the two datasets from separate places and different pressure layers in order to produce the fused results, which had a vertical distribution of 45 layers and a spatial resolution of 0.25°. The fused data’s RMSE and MAE were 6.0 K and 5.0 K lower than those of the MERRA-2 temperature profile data, respectively, and 0.3 K and 0.4 K lower than those of the ERA5 temperature profile data, respectively. The validation, using data from 2019, showed that the fused data exhibits better correlation and data accuracy than the other two datasets, which demonstrated that the fused algorithm can potentially be used to generate reliable datasets for future meteorological research.

The use of ionising radiation (IR) for medical diagnosis and treatment procedures has had a major impact on the survival of paediatric patients. Although the benefits of these techniques lead to efficient health care, evaluation of potential associated long-term health effects is required. HARMONIC aims to better understand the increased risk of cancer and non-cancer effects after exposure to medical IR in children with cancer treated with modern external beam radiotherapy (EBRT) – radiation energy in MeV range – and in children with cardiac defects diagnosed and treated with cardiac fluoroscopy procedures (CFP) – radiation energy in keV range. The project investigates, among survivors of paediatric cancer, potential endocrine dysfunction, cardiovascular and neurovascular damage, health-related quality of life and second (and subsequent) primary cancer (SPC). The cardiac component builds a pooled cohort of approximately 90 000 paediatric patients who underwent CFP during childhood and adolescence to investigate cancer risk following exposure to IR and explore the potential effects of conditions predisposing to cancer. HARMONIC develops software tools to allow dose reconstruction in both EBRT and CFP to enable epidemiological investigations and future optimisation of treatments. With the creation of a biobank of blood and saliva samples, HARMONIC aims to provide a mechanistic understanding of radiation-induced adverse health effects and identify potential biomarkers that can predict these effects.

Concerns about the safety of anesthetic agents in children arose after animal studies revealed disruptions in neurodevelopment after exposure to commonly used anesthetic drugs. These animal studies revealed that volatile inhalational agents, propofol, ketamine, and thiopental may have detrimental effects on neurodevelopment and cognitive function, but dexmedetomidine and xenon have been shown to have neuroprotective properties. The neurocognitive effects of benzodiazepines have not been extensively studied, so their effects on neurodevelopment are undetermined. However, experimental animal models may not truly represent the pathophysiological processes in children. Multiple landmark studies, including the MASK, PANDA, and GAS studies have provided reassurance that brief exposure to anesthesia is not associated with adverse neurocognitive outcomes in infants and children, regardless of the type of anesthetic agent used.

Molecular and sequencing technologies have been successfully used in decoding biological mechanisms of various diseases. As revealed by many novel discoveries, the role of non-coding RNAs (ncRNAs) in understanding disease mechanisms is becoming increasingly important. Since ncRNAs primarily act as regulators of transcription, associating ncRNAs with diseases involves multiple inference steps. Leveraging the fast-accumulating high-throughput screening results, a number of computational models predicting ncRNA-disease associations have been developed. These tools suggest novel disease-related biomarkers or therapeutic targetable ncRNAs, contributing to the realization of precision medicine. In this survey, we first introduce the biological roles of different ncRNAs and summarize the databases containing ncRNA-disease associations. Then, we suggest a new trend in recent computational prediction of ncRNA-disease association, which is the mode of action (MoA) network perspective. This perspective includes integrating ncRNAs with mRNA, pathway and phenotype information. In the next section, we describe computational methodologies widely used in this research domain. Existing computational studies are then summarized in terms of their coverage of the MoA network. Lastly, we discuss the potential applications and future roles of the MoA network in terms of integrating biological mechanisms for ncRNA-disease associations.

Prebiotics are non-digestible food ingredients that promote the growth of beneficial gut microorganisms and foster their activities. The performance of prebiotics has often been tested in mouse models in which the gut ecology differs from that of humans. In this study, we instead performed an in vitro gastrointestinal digestion and fecal fermentation experiment to evaluate the efficiency of eight different prebiotics. Feces obtained from 11 different individuals were used to ferment digested prebiotics. The total DNA from each sample was extracted and sequenced through Illumina MiSeq for microbial community analysis. The amount of short-chain fatty acids was assessed through gas chromatography. We found links between community shifts and the increased amount of short-chain fatty acids after prebiotics treatment. The results from differential abundance analysis showed increases in beneficial gut microorganisms, such as Bifidobacterium, Faeclibacterium, and Agathobacter, after prebiotics treatment. We were also able to construct well-performing machine-learning models that could predict the amount of short-chain fatty acids based on the gut microbial community structure. Finally, we provide an idea for further implementation of machine-learning techniques to find customized prebiotics.

The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown. Here, we uncover a mitotic chromatin-marking pathway that governs the segregation of UV-induced damage in human cells. Our mechanistic analyses reveal two layers of control: histone ADP-ribosylation, and the incorporation of newly synthesized histones at UV damage sites, that both prevent local mitotic phosphorylations on histone H3 serine residues. Functionally, this chromatin-marking pathway drives the asymmetric segregation of UV damage in the cell progeny with consequences on daughter cell fate. We propose that this mechanism may help preserve the integrity of stem cell compartments during asymmetric cell divisions., Competing Interests: COMPETING INTERESTS STATEMENT The authors declare no competing interests.

The maintenance of genome integrity by DNA damage response machineries is key to protect cells against pathological development. In cell nuclei, these genome maintenance machineries operate in the context of chromatin, where the DNA wraps around histone proteins. Here, we review recent findings illustrating how the chromatin substrate modulates genome maintenance mechanisms, focusing on the regulatory role of histone variants and post-translational modifications. In particular, we discuss how the pre-existing chromatin landscape impacts DNA damage formation and guides DNA repair pathway choice, and how DNA damage-induced chromatin alterations control DNA damage signaling and repair, and DNA damage segregation through cell divisions. We also highlight that pathological alterations of histone proteins may trigger genome instability by impairing chromosome segregation and DNA repair, thus defining new oncogenic mechanisms and opening up therapeutic options., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks 1-4 . Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues 5-9 . However, the systemic impact of the gut microbiome on the germline-and consequently on the F 1 offspring it gives rise to-is unexplored 10 . Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory 'gut-germline axis' in males, which is sensitive to environmental exposures and programmes offspring fitness through impacting placenta function., (© 2024. The Author(s).)

Background: In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models., Results: Measurements of the ambient dose rate equivalent Ḣ * (10) at 1 m from the NM patient have been successfully compared against MC simulations with 5 different codes using the ICRP adult reference computational voxel phantoms, for typical clinical procedures with 99m Tc-HDP/MDP, 18 FDG and Na 131 I. All measurement data fall in the 95% confidence intervals, determined for the average simulated results. Moreover, the different MC codes (MCNP-X, PHITS, GATE, GEANT4, TRIPOLI-4®) have been compared for a more realistic scenario where the effective dose rate Ė of an exposed individual was determined in positions facing and aside the patient model at 30 cm, 50 cm and 100 cm. The variation between codes was lower than 8% for all the radiopharmaceuticals at 1 m, and varied from 5 to 16% for the face-to face and side-by-side configuration at 30 cm and 50 cm. A sensitivity study on the influence of patient model morphology demonstrated that the relative standard deviation of Ḣ * (10) at 1 m for the range of included patient models remained under 16% for time points up to 120 min post administration., Conclusions: The validated computational approach will be further used for the evaluation of effective dose rates per unit administered activity for a variety of close-contact configurations and a range of radiopharmaceuticals as part of risk assessment studies. Together with the choice of appropriate dose constraints this would facilitate the setting of release criteria and patient restrictions., (© 2024. The Author(s).)

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses., (© 2023. The Author(s).)

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment., Materials and Methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al., Results: Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μ Sv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μ Sv (testes) and 48 μ Sv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs., Conclusion: The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Saint-Hubert, Boissonnat, Schneider, Bäumer, Verbeek, Esser, Wulff, Stuckmann, Suesselbeck, Nabha, Dabin, Vasi, Radonic, Rodriguez, Simon, Journy, Timmermann, Thierry-Chef and Brualla.)

This paper studies blind source separation (BSS) for frequency hopping (FH) sources. These radio frequency (RF) signals are observed by a uniform linear array (ULA) over (i) line-of-sight (LOS), (ii) single-cluster, and (iii) multiple-cluster Spatial Channel Model (SCM) settings. The sources are stationary, spatially sparse, and their activity is intermittent and assumed to follow a hidden Markov model (HMM). BSS is achieved by leveraging direction of arrival (DOA) information through an FH estimation stage, a DOA estimation stage, and a pairing stage with the latter associating FH patterns with physical sources via their estimated DOAs. Current methods in the literature do not perform the association of multiple frequency hops to the sources they are transmitted from. We bridge this gap by pairing the FH estimates with DOA estimates and labeling signals to their sources, irrespective of their hopped frequencies. A state filtering technique, referred to as hidden state filtering (HSF), is developed to refine DOA estimates for sources that follow a HMM. Numerical results demonstrate that the proposed approach is capable of separating multiple intermittent FH sources.

Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (β = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (β = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (β = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.

In the cell nucleus, DNA damage signaling and repair machineries operate on a chromatin substrate, the integrity of which is critical for cell function and viability. Here, we review recent advances in deciphering the tight coordination between chromatin maintenance and the DNA damage response (DDR). We discuss how the DDR impacts chromatin marks, organization and mobility, and, in turn, how chromatin alterations actively contribute to the DDR, providing additional levels of regulation. We present our current knowledge of the molecular bases of these critical processes in physiological and pathological conditions, and also highlight open questions that emerge in this expanding field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate the effectiveness of currently available radioprotective (RP) devices in reducing the dose to interventional cardiology staff, especially to the eye lens and brain., Methods: The performances of five RP devices (masks, caps, patient drapes, staff lead and lead-free aprons and Zero-Gravity (ZG) suspended radiation protection system) were assessed by means of Monte Carlo (MC) simulations. A geometry representative of an interventional cardiology setup was modelled and several configurations, including beam projections and staff distance from the source, were investigated. In addition, measurements on phantoms were performed for masks and drapes., Results: An average dose reduction of 65% and 25% to the eyes and the brain respectively was obtained for the masks by MC simulations but a strong influence of the design was observed. The cap effectiveness for the brain ranges on average between 13% and 37%. Nevertheless, it was shown that only some upper parts of the brain were protected. There was no significant difference between the effectiveness of lead and lead-free aprons. Of all the devices, the ZG system offered the highest protection to the brain and eye lens and a protection level comparable to the apron for the organs normally covered., Conclusion: All investigated devices showed potential for dose reduction to specific organs. However, for masks, caps and drapes, it strongly depends on the design, exposure conditions and staff position. Therefore, for a clinical use, it is recommended to evaluate their effectiveness in the planned conditions of use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Extremity exposure during the handling of unsealed radioactive sources is a matter of concern for nuclear medicine workers. Next to 99m Tc and 18 F, other radiopharmaceuticals have seen an increase in their use over the last decade. However, limited information on their impact on extremity dose is available. This study aimed to gain insight into the status of extremity exposure and dose monitoring in Europe., Methods: A survey was conducted at the end of 2020 among the European Association of Nuclear Medicine community. It contained 24 questions considering department characteristics, worker tasks, dosimeter use, typical worker extremity dose, department workload for selected radionuclides ( 99m Tc, 18 F, 68 Ga, 177 Lu, 90 Y) and protective measures., Results: A total of 106 replies were received, 92% of which were from Europe. About half of the respondents were from academic hospitals. Ninety-nine departments implement extremity dose monitoring for a total of 1335 workers. Most workers (95%) wear a ring dosimeter, generally on the non-dominant hand, and 44% on the index finger. Monthly doses were generally low (median values at different ring position: 0.4-1.8 mSv), although higher doses were reported (20.8-38.8 mSv). About 1/3 of workers performed the full task range (preparation, dispensing, and administration). Administration is associated with significantly lower extremity doses. Interestingly, no correlation between department workload and collective dose was found. The adoption of vial and syringe shielding, as well as distance tools, was common. The workers dispensing 99m Tc without syringe shielding or PET nuclides without automated system received a significantly higher dose. Handling 68 Ga, 177 Lu and 90 Y did not appear to have an impact on the reported doses., Conclusions: Protective measures play a significant role in lowering extremity doses, while department workload and more recently introduced radionuclides seem not to be major dose determinants.

The International Commission on Radiation Units and Measurements (ICRU) proposed a new set of operational quantities for radiation protection for external radiation in its Report Committee 26 ( ICRU 95 ). The new proposal aims to improve the coherence between the operational quantities and the definitions of the protection quantities in the recommendations of the International Commission on Radiological Protection set out in 2007 ( Ann. ICRP 37 ). It is expected that this change in operational quantities will impact current dosimeter designs. Although for many photon energies, the conversion coefficients from physical field quantities to the new operational quantities will change relatively little, for radiation fields with low energy photon components, such as medical x-ray applications, there will be a significant decrease in the values of the conversion coefficients. This means that the numerical values of the new operational quantities will be much lower for the same radiation field. These values will be closer to the effective dose, but this change can still cause confusion for medical staff. It is important to examine the effect of the new set of dose conversion coefficients on the personal dose in realistic radiation fields. We performed a study to assess the effect of changing the definition of the operational quantity, personal dose equivalent (Hp), in realistic radiation fields in interventional radiology (IR) workplaces. The x-ray tube kilovoltage peak (kVp) in IR ranges between 60 and 120 kV. The medical staff is exposed to the scattered photons which have a wide range of energies depending on the beam configuration and the patient size. The objective of this study is to 'quantitatively' estimate the impact of implementing the new ICRU quantities of Report 95 in IR radiation fields using Monte Carlo simulations. Simulations of 560 different configurations in IR were performed using MCNPX to calculate fluence binned per energy and angle of incidence.HpandHp(10)were then calculated for each configuration using dose conversion coefficients from fluence given by ICRU Reports 95 and 57, respectively. The results show that the mean of the ratio,Hp(10)/Hp, is 1.6 for all simulated scenarios. This reduction will correct the current overestimation of the effective dose and should result in better compliance with the dose limits in IR. However, it may also have negative consequences on the safety culture among the medical staff. Special care will be needed when interpreting these lower doses., (© 2023 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Introduction: Although the use of 68 Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to 68 Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of 68 Ga-labelled radiopharmaceuticals., Method: Workers in eight centres wore a ring dosimeter for all tasks involving 68 Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during 68 Ga procedures was also identified in one centre., Results: The median normalised ring dose for 68 Ga procedures was found to be 0.25 mSv GBq -1 (range 0.01-3.34). The normalised 68 Ga ring doses recorded in this study are similar to that found in the literature for 18 F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual 68 Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv)., Conclusion: When appropriate shielding and radiation protection practices are employed, the extremity dose due to 68 Ga is comparable to that of 18 F and is expected to be well below the regulatory limits for the majority of workers., (Creative Commons Attribution license.)

Background: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer., Methods: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination., Findings: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded., Interpretation: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible., Funding: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England., Competing Interests: Declaration of interests CJ reports honoraria from Pfizer, Janssen, and Astellas, and owns stocks in Y-mAbs, Novo Nordisk, Novozymes, Hansa, Zealand, Bavarian Nordic, and BioCryst Pharmaceuticals. MK reports grants from Stockholm County for clinical research within the frame of employment as a radiologist at the Karolinska University Hospital. CR reports a grant from the Dutch Cancer Society for Junior Group Leaders. All other authors declared no competing interests., (Copyright © 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Background: Optimizing patient exposure in interventional cardiology is key to avoid skin injuries., Purpose: To establish predictive models of peak skin dose (PSD) during percutaneous coronary intervention (PCI), chronic total occlusion percutaneous coronary intervention (CTO), and transcatheter aortic valve implantation (TAVI) procedures., Material and Methods: A total of 534 PCI, 219 CTO, and 209 TAVI were collected from 12 hospitals in eight European countries. Independent associations between PSD and clinical and technical dose determinants were examined for those procedures using multivariate statistical analysis. A priori and a posteriori predictive models were built using stepwise multiple linear regressions. A fourfold cross-validation was performed, and models' performance was evaluated using the root mean square error (RMSE), mean absolute percentage error (MAPE), coefficient of determination (R²), and linear correlation coefficient (r)., Results: Multivariate analysis proved technical parameters to overweight clinical complexity indices with PSD mainly affected by fluoroscopy time, tube voltage, tube current, distance to detector, and tube angulation for PCI. For CTO, these were body mass index, tube voltage, and fluoroscopy contribution. For TAVI, these parameters were sex, fluoroscopy time, tube voltage, and cine acquisitions. When benchmarking the predictive models, the correlation coefficients were r = 0.45 for the a priori model and r = 0.89 for the a posteriori model for PCI. These were 0.44 and 0.67, respectively, for the CTO a priori and a posteriori models, and 0.58 and 0.74, respectively, for the TAVI a priori and a posteriori models., Conclusion: A priori predictive models can help operators estimate the PSD before performing the intervention while a posteriori models are more accurate estimates and can be useful in the absence of skin dose mapping solutions.

Background: Patients can be exposed to high skin doses during complex interventional cardiology (IC) procedures., Purpose: To identify which clinical and technical parameters affect patient exposure and peak skin dose (PSD) and to establish dose reference levels (DRL) per clinical complexity level in IC procedures., Material and Methods: Validation and Estimation of Radiation skin Dose in Interventional Cardiology (VERIDIC) project analyzed prospectively collected patient data from eight European countries and 12 hospitals where percutaneous coronary intervention (PCI), chronic total occlusion PCI (CTO), and transcatheter aortic valve implantation (TAVI) procedures were performed. A total of 62 clinical complexity parameters and 31 technical parameters were collected, univariate regressions were performed to identify those parameters affecting patient exposure and define DRL accordingly., Results: Patient exposure as well as clinical and technical parameters were collected for a total of 534 PCI, 219 CTO, and 209 TAVI. For PCI procedures, body mass index (BMI), number of stents ≥2, and total stent length >28 mm were the most prominent clinical parameters, which increased the PSD value. For CTO, these were total stent length >57 mm, BMI, and previous anterograde or retrograde technique that failed in the same session. For TAVI, these were male sex, BMI, and number of diseased vessels. DRL values for Kerma-area product ( P KA ), air kerma at patient entrance reference point ( K a,r ), fluoroscopy time (FT), and PSD were stratified, respectively, for 14 clinical parameters in PCI, 10 in CTO, and four in TAVI., Conclusion: Prior knowledge of the key factors influencing the PSD will help optimize patient radiation protection in IC.

Objectives: The study aim was to analyse the influence of the lead free cap on doses received by interventional cardiologists. The impact of lead free cap on doses to the head were evaluated in number of studies. As different methods used to assess the attenuation properties of protective cap can lead to ambiguous results, a detailed study was performed., Material and Methods: The effectiveness of a lead free cap in reducing the doses to the skin was assessed in clinic by performing measurements with thermoluminescent dosimeters attached inside and outside the cap first during individual coronary angiography (CA) or CA/percutaneous transluminal coronary angioplasty (CA/PTCA) procedures and then cumulated during few procedures of the same type. In order to investigate the effect of the cap on reducing the doses to the brain additional measurements were performed with a male Alderson Rando and polymethyl methacrylate (PMMA) phantoms representing the physician and the patient, respectively for different projections. The brain dose per procedure, annual and cumulated during entire working practice were estimated for both cases working with and without the cap., Results: The dose reduction factor (RF) for the skin (the quotient of doses outside and inside the cap) vary from 1.1 up to 4.0 in clinical conditions; on average 2.3-fold reduction is observed in the most exposed left temple. The RFs determined for the part of the head covered by the cap range from 1.4 to 1.8 while for the brain from 1.0 to 1.1 depending on the projection. The estimated annual brain dose for interventional cardiologist performing yearly 550 CA/PTCA procedures without any protective shields is 7.2 mGy and it is reduced with the lead free cap by an average factor of 1.1., Conclusions: The study results proved the considerable effectiveness of lead free cap to protect the skin but very limited to protect the brain. Int J Occup Med Environ Health. 2022;35(5):549-60., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: The out-of-the-field absorbed dose affects the probability of primary second radiation-induced cancers. This is particularly relevant in the case of pediatric treatments. There are currently no methods employed in the clinical routine for the computation of dose distributions from stray radiation in radiotherapy. To overcome this limitation in the framework of conventional teletherapy with photon beams, two computational tools have been developed-one based on an analytical approach and another depending on a fast Monte Carlo algorithm. The purpose of this work is to evaluate the accuracy of these approaches by comparison with experimental data obtained from anthropomorphic phantom irradiations., Materials and Methods: An anthropomorphic phantom representing a 5-year-old child (ATOM, CIRS) was irradiated considering a brain tumor using a Varian TrueBeam linac. Two treatments for the same planned target volume (PTV) were considered, namely, intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). In all cases, the irradiation was conducted with a 6-MV energy beam using the flattening filter for a prescribed dose of 3.6 Gy to the PTV. The phantom had natLiF : Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs) in its 180 holes. The uncertainty of the experimental data was around 20%, which was mostly attributed to the MCP-N energy dependence. To calculate the out-of-field dose, an analytical algorithm was implemented to be run from a Varian Eclipse TPS. This algorithm considers that all anatomical structures are filled with water, with the exception of the lungs which are made of air. The fast Monte Carlo code dose planning method was also used for computing the out-of-field dose. It was executed from the dose verification system PRIMO using a phase-space file containing 3x10 9 histories, reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1 ) on all voxels scoring more than 50% of the maximum dose. The standard statistical uncertainty of out-of-field voxels in the Monte Carlo simulation did not exceed 5%. For the Monte Carlo simulation the actual chemical composition of the materials used in ATOM, as provided by the manufacturer, was employed., Results: In the out-of-the-field region, the absorbed dose was on average four orders of magnitude lower than the dose at the PTV. For the two modalities employed, the discrepancy between the central values of the TLDs located in the out-of-the-field region and the corresponding positions in the analytic model were in general less than 40%. The discrepancy in the lung doses was more pronounced for IMRT. The same comparison between the experimental and the Monte Carlo data yielded differences which are, in general, smaller than 20%. It was observed that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT., Conclusions: The proposed computational methods for the routine calculation of the out-of-the-field dose produce results that are similar, in most cases, with the experimental data. It has been experimentally found that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT for a given PTV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Saint-Hubert, Suesselbeck, Vasi, Stuckmann, Rodriguez, Dabin, Timmermann, Thierry-Chef, Schneider and Brualla.)

The lens of the eye can be damaged by ionising radiation, so individuals whose eyes are exposed to radiation during their work may need to protect their eyes from exposure. Lead glasses are widely available, but there are questions about their efficiency in providing eye protection. In this study, Monte Carlo simulations are used to assess the efficiency of lead glasses in protecting the sensitive volume of the eye lens. Two designs currently available for interventional cardiologists are a wraparound (WA) style and ones with flat frontal lenses with side shielding. These designs were considered together with four modifications that would impact upon their efficiency: changing the lead equivalent thickness, adding lead to the frames, elongating the frontal lenses, and adding a closing shield to the bottom rim. For the eye closest to the source, standard models of lead glasses only decrease the radiation reaching the most sensitive region of the eye lens by 22% or less. Varying the lead thickness between 0.4 mm and 0.75 mm had little influence on the protection provided in the simulation of clinical use, neither did adding lead to the frames. Improved shielding was obtained by elongating the frontal lens, which could reduce radiation reaching the eye lens by up to 76%. Glasses with lenses that had a rim at the base, extending towards the face of the user, also provided better shielding than current models, decreasing the dose by up to 80%. In conclusion, elongating the frontal lens of lead glasses, especially of the WA design, could provide a three-fold increase in shielding efficiency and this is still valid for lenses with 0.4 mm lead equivalence., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Background: Natural cellulosome multi-enzyme complexes, their components, and engineered 'designer cellulosomes' (DCs) promise an efficient means of breaking down cellulosic substrates into valuable biofuel products. Their broad uptake in biotechnology relies on boosting proximity-based synergy among the resident enzymes, but the modular architecture challenges structure determination and rational design., Results: We used small angle X-ray scattering combined with molecular modeling to study the solution structure of cellulosomal components. These include three dockerin-bearing cellulases with distinct substrate specificities, original scaffoldins from the human gut bacterium Ruminococcus champanellensis (ScaA, ScaH and ScaK) and a trivalent cohesin-bearing designer scaffoldin (Scaf20L), followed by cellulosomal complexes comprising these components, and the nonavalent fully loaded Clostridium thermocellum CipA in complex with Cel8A from the same bacterium. The size analysis of R g and D max values deduced from the scattering curves and corresponding molecular models highlight their variable aspects, depending on composition, size and spatial organization of the objects in solution., Conclusions: Our data quantifies variability of form and compactness of cellulosomal components in solution and confirms that this native plasticity may well be related to speciation with respect to the substrate that is targeted. By showing that scaffoldins or components display enhanced compactness compared to the free objects, we provide new routes to rationally enhance their stability and performance in their environment of action., (© 2022. The Author(s).)

Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments. Unfortunately, no method exists in clinics for the computation of the out-of-field dose distributions in proton therapy. To help overcome this limitation, a computational tool has been developed based on the Monte Carlo code TOPAS. The purpose of this work is to evaluate the accuracy of this tool in comparison to experimental data obtained from an anthropomorphic phantom irradiation. An anthropomorphic phantom of a 5-year-old child (ATOM, CIRS) was irradiated for a brain tumor treatment in an IBA Proteus Plus facility using a pencil beam dedicated nozzle. The treatment consisted of three pencil beam scanning fields employing a lucite range shifter. Proton energies ranged from 100 to 165 MeV. A median dose of 50.4 Gy(RBE) with 1.8 Gy(RBE) per fraction was prescribed to the initial planning target volume (PTV), which was located in the cerebellum. Thermoluminescent detectors (TLDs), namely, Li-7-enriched LiF : Mg, Ti (MTS-7) type, were used to detect gamma radiation, which is produced by nuclear reactions, and secondary as well as recoil protons created out-of-field by secondary neutrons. Li-6-enriched LiF : Mg,Cu,P (MCP-6) was combined with Li-7-enriched MCP-7 to measure thermal neutrons. TLDs were calibrated in Co-60 and reported on absorbed dose in water per target dose (μGy/Gy) as well as thermal neutron dose equivalent per target dose (μSv/Gy). Additionally, bubble detectors for personal neutron dosimetry (BD-PND) were used for measuring neutrons (>50 keV), which were calibrated in a Cf-252 neutron beam to report on neutron dose equivalent dose data. The Monte Carlo code TOPAS (version 3.6) was run using a phase-space file containing 10 10 histories reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1) on all voxels scoring more than 50% of the maximum dose. The primary beam was modeled following a Fermi-Eyges description of the spot envelope fitted to measurements. For the Monte Carlo simulation, the chemical composition of the tissues represented in ATOM was employed. The dose was tallied as dose-to-water, and data were normalized to the target dose (physical dose) to report on absorbed doses per target dose (mSv/Gy) or neutron dose equivalent per target dose (μSv/Gy), while also an estimate of the total organ dose was provided for a target dose of 50.4 Gy(RBE). Out-of-field doses showed absorbed doses that were 5 to 6 orders of magnitude lower than the target dose. The discrepancy between TLD data and the corresponding scored values in the Monte Carlo calculations involving proton and gamma contributions was on average 18%. The comparison between the neutron equivalent doses between the Monte Carlo simulation and the measured neutron doses was on average 8%. Organ dose calculations revealed the highest dose for the thyroid, which was 120 mSv, while other organ doses ranged from 18 mSv in the lungs to 0.6 mSv in the testes. The proposed computational method for routine calculation of the out-of-the-field dose in proton therapy produces results that are compatible with the experimental data and allow to calculate out-of-field organ doses during proton therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Saint-Hubert, Verbeek, Bäumer, Esser, Wulff, Nabha, Van Hoey, Dabin, Stuckmann, Vasi, Radonic, Boissonnat, Schneider, Rodriguez, Timmermann, Thierry-Chef and Brualla.)