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Coal-fired power plants are a main source of energy in Poland. In the rapidly growing demand for the reduction of CO 2 emission in the energy industry, the use of biomass for energy purposes has increased significantly. The combustion of biomass results in the generation of fly ash, with higher levels of CaO, K 2 O, P 2 O 5 , in contrast to the fly ash derived from the combustion of coal. The aim of this study was to examine the influence of phosphate compounds on fly ash-based geopolymer mortars. Geopolymers were made by mixing two types of fly ash-one from the combustion of wood biomass and the second from the combustion of coal in a heat and power station. Basic activators (NaOH and Na 2 SiO 3 ) were used for the alkali activation. The maximum level of tetraphosphorus decaoxide addition was established at 5% of the total mass of the aluminosilicate precursors mass. The results showed that the phosphate oxide concentration within the specimens demonstrated a positive correlation with flexural and compressive strength across all temporal intervals (7, 28, and 56 days). The porosity, however, for samples with a 5% addition of P 4 O 10 , increased more than twofold in comparison to reference samples (from 4.26% to 9.98%).

The sense of smell is generated by electrical currents that are influenced by the concentration of ions in olfactory sensory neurons and mucus. In contrast to the extensive morphological and molecular characterization of sensory neurons, there has been little description of the cells that control ion concentrations in the zebrafish olfactory system. Here, we report the molecular and ultrastructural characterization of zebrafish olfactory ionocytes. Transcriptome analysis suggests that the zebrafish olfactory epithelium contains at least three different ionocyte types, which resemble Na + /K + -ATPase-rich (NaR), Na + /Cl - cotransporter (NCC), and H + -ATPase-rich (HR) cells, responsible for calcium, chloride, and pH regulation, respectively, in the zebrafish skin. NaR-like and HR-like ionocytes are usually adjacent to one another, whereas NCC-like cells are usually solitary. The distinct subtypes are differentially distributed: NaR-like/HR-like cell pairs are found broadly within the olfactory epithelium, whereas NCC-like cells reside within the peripheral non-sensory multiciliated cell zone. Comparison of gene expression and serial-section electron microscopy analysis indicates that the NaR-like cells wrap around the HR-like cells and are connected to them by shallow tight junctions. The development of olfactory ionocyte subtypes is also differentially regulated, as pharmacological Notch inhibition leads to a loss of NaR-like and HR-like cells, but does not affect NCC-like ionocyte number. These results provide a molecular and anatomical characterization of olfactory ionocytes in a stenohaline freshwater teleost. The paired ionocytes suggest that both transcellular and paracellular transport regulate ion concentrations in the olfactory epithelium, while the solitary ionocytes may enable independent regulation of multiciliated cells., Competing Interests: Competing Interests The authors declare no competing interests.

Introduction: The shape of the energy spectrum is an essential component of any electron beam Monte Carlo model. Due to specialized equipment and the long measurement time for the direct methods for determining the energy spectrum, attractive alternatives are backward spectrum reconstructions from the measured data. One such approach is solving the first-degree Fredholm integral equation with appropriate regularization. It makes it possible to calculate the depth distribution as the sum of the distributions from monoenergetic beams. This study aims to determine the optimal value of the regularization parameter for the problem of determining the spectrum of the electron beam produced by a mobile accelerator used during intraoperative radiotherapy., Material and Methods: The Geant4 package was used to generate the distributions of deep doses for monoenergetic beams for two models with different degrees of complexity, i.e. simple (theoretical) and full (for the mobile accelerator). The dose distributions for four different shapes of energy spectrum (for each model) were obtained similarly. They were established as the reference data for further calculations. The Dual Annealing optimization method was used to obtain the reconstructed spectrum. The multiple optimizations that differ by the regularization parameter (ranging from 0 to 1) were performed. For each reconstruction, similarity indicators of the energy spectrum and the dose distribution to the referenced data were calculated to determine the optimal regularization parameters., Results: Optimal regularization parameters determined by similarity indicators for the spectrum and the dose distribution differ for geometry models considered in the study. The regularization parameter for the simple geometry ranged from 0.03 to 0.05, while for full geometry, they were from 0.05 to 0.06. The results for conventional linear accelerators found in the literature range from 0.5 to 1.1., Conclusion: The Dual Annealing optimization method can be effectively used to solve the Fredholm equation with Tikhonov regularization to reconstruct an electron beam's energy spectrum. The regularization parameter value depends on the beam-forming system. Its value for the mobile accelerator considered in the study ranges from 0.05 to 0.06, depending on the nominal beam energy value., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Regeneration and homeostatic turnover of solid tissues depend on the proliferation of symmetrically dividing adult stem cells, which either remain stem cells or differentiate based on their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, stem and progenitor cell proliferation are independently regulated by two cyclinD genes. Loss of ccnd2a impairs stem cell proliferation during development, while loss of ccndx disrupts hair cell progenitor proliferation but allows normal differentiation. Notably, ccnd2a can functionally replace ccndx , indicating that the respective effects of these Cyclins on proliferation are due to cell type-specific expression. However, even though hair cell progenitors differentiate normally in ccndx mutants, they are mispolarized due to hes2 and Emx2 downregulation. Thus, regulated proliferation ensures that equal numbers of hair cells are polarized in opposite directions. Our study reveals cell type-specific roles for cyclinD genes in regulating the different populations of symmetrically dividing cells governing organ development and regeneration, with implications for regenerative medicine and disease., Competing Interests: Declaration of interests: The authors declare no competing interests.

Organisms cope with environmental fluctuations and maintain fitness in part via reversible phenotypic changes (acclimation). Aquatic animals are subject to dramatic seasonal fluctuations in water salinity, which affect osmolarity of their cells and consequently cellular function. Mechanosensory lateral line hair cells detect water motion for swimming behavior and are especially susceptible to salinity changes due to their direct contact with the environment. To maintain hair cell function when salinity decreases, neuromast (Nm)-associated ionocytes differentiate and invade lateral line neuromasts. The signals that trigger the adaptive differentiation of Nm ionocytes are unknown. We demonstrate that new Nm ionocytes are rapidly specified and selectively triggered to proliferate by low Ca2+ and Na+/Cl- levels. We further show that Nm ionocyte recruitment and induction is affected by hair cell activity. Once specified, Nm ionocyte differentiation and survival are associated with sequential activation of different Notch pathway components, a process different from other tissue-specific ionocytes. In summary, we show how environmental changes activate a signaling cascade that leads to physiological adaptation. This may prove essential for survival not only in seasonal changing environments but also in changing climates., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

Background: The purpose was to analyse the interrelations between planning and complexity metrics and gamma passing rates (GPRs) obtained from VMAT treatments and build the forecasting models for qualitative prediction (QD) of GPRs results., Materials and Method: 802 treatment arcs from the plans prepared for the head and neck, thorax, abdomen, and pelvic cancers were analysed. The plans were verified by portal dosimetry and analysed twice using the gamma method with 3%|2mm and 2%|2mm acceptance criteria. The tolerance limit of GPR was 95%. Red, yellow, and green QDs were established for GPR examination. The interrelations were examined, as well as the analysis of effective differentiation of QD. Three models for QD forecasting based on discriminant analysis (DA), random decision forest (RDF) methods, and the hybrid model (HM) were built and evaluated., Results: Most of the interrelations were small or moderate. The exception is correlations of the join function with the average number of monitor units per control point (R = 0.893) and the beam aperture with planning target volume (R = 0.897). While many metrics allow for the effective separation of the QDs from each other, the study shows that predicting the values of the QD is possible only through multi-component forecasting models, of which the HM is the most accurate (0.894)., Conclusion: Of the three models explored in this study, the HM, which uses DA methods to predict red QD and RDF methods to predict green and yellow QDs, is the most promising one., Competing Interests: Conflict of interests: Authors declare no conflict of interests, (© 2024 Greater Poland Cancer Centre.)

Introduction: Positron emission tomography/computed tomography (PET/CT) has an established role in evaluating patients with lung cancer. The aim of this work was to assess the predictive capability of [ 18 F]Fluorodeoxyglucose ([ 18 F]FDG) PET/CT parameters on overall survival (OS) in lung cancer patients using an artificial neural network (ANN) in parallel with conventional statistical analysis., Methods: Retrospective analysis was performed on a group of 165 lung cancer patients (98M, 67F). PET features associated with the primary tumor: maximum and mean standardized uptake value (SUV max , SUV mean ), total lesion glycolysis (TLG) metabolic tumor volume (MTV) and area under the curve-cumulative SUV histogram (AUC-CSH) and metastatic lesions (SUV maxtotal , SUV meantotal , TLG total , and MTV total ) were evaluated. In parallel with conventional statistical analysis (Chi-Square analysis for nominal data, Student's t test for continuous data), the data was evaluated using an ANN. There were 97 input variables in 165 patients using a binary classification of either below, or greater than/equal to median survival post primary diagnosis. Additionally, phantom study was performed to assess the most optimal contouring method., Results: Males had statistically higher SUV max (mean: 10.7 vs 8.9; p = 0.020), MTV (mean: 66.5 cm 3 vs. 21.5 cm 3 ; p = 0.001), TLG (mean 404.7 vs. 115.0; p = 0.003), TLG total (mean: 946.7 vs. 433.3; p = 0.014) and MTV total (mean: 242.0 cm 3 vs. 103.7 cm 3 ; p = 0.027) than females. The ANN after training and validation was optimised with a final architecture of 4 scaling layer inputs (TLG total , SUV maxtotal , SUV meantotal and disease stage) and receiving operator characteristic (ROC) analysis demonstrated an AUC of 0.764 (sensitivity of 92.3%, specificity of 57.1%)., Conclusion: Conventional statistical analysis and the ANN provided concordant findings in relation to variables that predict decreased survival. The ANN provided a weighted algorithm of the 4 key features to predict decreased survival., Implication for Practice: Identification of parameters which can predict survival in lung cancer patients might be helpful in choosing the group of patients who require closer look during the follow-up., Competing Interests: Conflict of interest statement None., (Copyright © 2024. Published by Elsevier Ltd.)

Speech understanding, watching a movie, listening to music etc., requires perception of the temporal order of at least two incoming events. A history of performing these tasks may be reflected in spontaneous brain activity. Here, we examined the relationship between the complexity (temporal dynamics) of resting‑state EEG (rsEEG) signal, assessed using the multivariate MultiScale Entropy (mMSE) algorithm, and the perception of event ordering, indexed by a visual temporal order threshold (TOT), i.e., the minimum duration necessary to correctly identify the before‑after relation between two stimuli. Healthy adolescents and young adults performed a psychophysical task measuring the TOT and underwent an eyes‑closed rsEEG study. The features of mMSE vectors, namely the area under curve (AUC) that represents total signal complexity, as well as the MaxSlope and the AvgEnt, corresponding to the entropy at fine‑ and coarse‑grained timescales, respectively, were obtained for the central (midline), anterior, middle and posterior channel sets. The greater the AUC and AvgEnt values in the central, left and right posterior areas, and the higher AUC in the right middle region, the higher the TOT. The most significant relationships were found for the midline electrodes (Fz, Cz, Pz, Oz). There were no significant correlations between the MaxSlope values and the TOT. To the best of our knowledge, this is the first study demonstrating that spontaneous EEG signal complexity is associated with the temporal order perception of two stimuli presented in rapid succession. Our findings may indicate that low total and coarse entropy levels of rsEEG signal are beneficial for visual temporal order judgments.

Background: The study aimed to determine how the resting-state EEG (rsEEG) complexity changes both over time and space (channels). The complexity of rsEEG and its sex/gender differences were examined using the multivariate Multiscale Entropy (mMSE) in 95 healthy adults. Following the probability maps (Giacometti et al. in J Neurosci Methods 229:84-96, 2014), channel sets have been identified that correspond to the functional networks. For each channel set the area under curve (AUC), which represents the total complexity, MaxSlope-the maximum complexity change of the EEG signal at thefine scales (1:4 timescales), and AvgEnt-to the average entropy level at coarse-grained scales (9:12 timescales), respectively, were extracted. To check dynamic changes between the entropy level at the fine and coarse-grained scales, the difference in mMSE between the #9 and #4 timescale (DiffEnt) was also calculated., Results: We found the highest AUC for the channel sets corresponding to the somatomotor (SMN), dorsolateral network (DAN) and default mode (DMN) whereas the visual network (VN), limbic (LN), and frontoparietal (FPN) network showed the lowest AUC. The largest MaxSlope were in the SMN, DMN, ventral attention network (VAN), LN and FPN, and the smallest in the VN. The SMN and DAN were characterized by the highest and the LN, FPN, and VN by the lowest AvgEnt. The most stable entropy were for the DAN and VN while the LN showed the greatest drop of entropy at the coarse scales. Women, compared to men, showed higher MaxSlope and DiffEnt but lower AvgEnt in all channel sets., Conclusions: Novel results of the present study are: (1) an identification of the mMSE features that capture entropy at the fine and coarse timescales in the channel sets corresponding to the main resting-state networks; (2) the sex/gender differences in these features., (© 2023. BioMed Central Ltd.)

The XEN ® gel stent reduces intraocular pressure (IOP) in glaucoma. XEN ® -45 is widely used; the newer XEN ® -63 has a larger lumen targeting potentially lower IOP outcomes. We retrospectively compared the first 15 XEN ® -63 cases to 15 matched XEN ® -45 controls. With a preoperative IOP of 18.1 ± 3.9 mmHg (mean ± SD) and a final IOP of 9.1 ± 2.0 mmHg, XEN ® -63 implantation resulted in an IOP reduction of 44.6 ± 16.5%. Similarly, with a preoperative IOP of 18.3 ± 4.5 mmHg and a final IOP of 10.3 ± 2.1 mmHg, XEN ® -45 implantation resulted in an IOP reduction of 40.1 ± 17.2%. The median follow-up period was 204 days (range 78-338 days) for the XEN ® -63 group and 386 days (range 99-1688 days) for the XEN ® -45 group. In total, 5/15 eyes of each group underwent open conjunctival bleb revision within the period of observation. Three eyes of the XEN ® -63 group had secondary glaucoma surgery. One eye in the XEN ® -63 group and three eyes in the XEN ® -45 group required a restart of antiglaucomatous medication. In conclusion, both stents effectively lower IOP and medication. XEN ® -63 achieved a slightly lower IOP over a short follow-up. Complication and revision rates were similar.

Phase contrast is one of the most important microscopic methods for making visible transparent, unstained cells. Cell cultures are often cultivated in microtiter plates, consisting of several cylindrical wells. The surface tension of the culture medium forms a liquid lens within the well, causing phase contrast conditions to fail in the more curved edge areas, preventing cell observation. Adaptive phase contrast microscopy is a method to strongly increase the observable area by optically compensating for the meniscus effect. The microscope's condenser annulus is replaced by a transmissive LCD to allow dynamic changes. A deformable, liquid-filled prism is placed in the illumination path. The prism's surface angle is adaptively inclined to refract transmitted light so that the tangential angle of the liquid lens can be compensated. Besides the observation of the phase contrast image, a beam splitter allows to simultaneously view condenser annulus and phase ring displacement. Algorithms analyze the displacement to dynamically adjust the LCD and prism to guarantee phase contrast conditions. Experiments show a significant increase in observable area, especially for small well sizes. For 96-well-plates, more than twelve times the area can be examined under phase contrast conditions instead of standard phase contrast microscopy., (© 2023. The Author(s).)

Background: The cultivation, analysis, and isolation of single cells or cell cultures are fundamental to modern biological and medical processes. The novel LIFTOSCOPE technology aims to integrate analysis and isolation into one versatile, fully automated device., Methods: LIFTOSCOPE's three core technologies are high-speed microscopy for rapid full-surface imaging of cell culture vessels, AI-based semantic segmentation of microscope images for localization and evaluation of cells, and laser-induced forward transfer (LIFT) for contact-free isolation of cells and cell clusters. LIFT transfers cells from a standard microtiter plate (MTP) across an air gap to a receiver plate, from where they can be further cultivated. The LIFT laser is integrated into the optical path of an inverse microscope, allowing to switch quickly between microscopic observation and cell transfer., Results: Tests of the individual process steps prove the feasibility of the concept. A prototype setup shows the compatibility of the microscope stage with the LIFT laser. A specifically designed MTP adapter to hold a receiver plate has been designed and successfully used for material transfers. A suitable AI algorithm has been found for cell selection., Conclusion: LIFTOSCOPE speeds up cell cultivation and analysis with a target process time of 10 minutes, which can be achieved if the cell transfer is sped up using a more efficient path-finding algorithm. Some challenges remain, like finding a suitable cell transfer medium., Significance: The LIFTOSCOPE system can be used to extend existing cell cultivation systems and microscopes for fully automated biotechnological applications., (© 2023. The Author(s).)

The sustained release of multiple anti-cancer drugs using a single delivery carrier to achieve a synergistic antitumor effect remains challenging in biomaterials and pharmaceutics science. In this study, a supramolecular hydrogel based on the host-guest complexes between pH-responsive micelle derived poly(ethylene glycol) chains and α-cyclodextrin was designed for codelivery of two kinds of anti-cancer agents, hydrophilic 8-hydroxyquinoline glycoconjugate and hydrophobic doxorubicin. The host-guest interactions were characterized using X-ray diffraction and differential scanning calorimetry techniques. The resultant supramolecular hydrogel showed thixotropic properties, which are advantageous to drug delivery systems. In vitro release studies revealed that the supramolecular hydrogel exhibited faster drug release profiles in acidic conditions. The MTT assay demonstrated a synergistic cancer cell proliferation inhibition of DOX/8HQ-Glu mixture. In vitro cytotoxicity studies indicated excellent biocompatibility of the supramolecular hydrogel matrix, whereas the DOX/8HQ-Glu-loaded supramolecular hydrogel showed a sustained inhibition efficacy against cancer cells. The codelivery of hydrophobic anti-cancer drugs and hydrophilic anti-cancer drug glycoconjugates via a pH-responsive supramolecular hydrogel opens up new possibilities for the development of an effective cancer treatment based on the tumor-specific Warburg effect.

The study aimed to determine the relationship between the millisecond timing, measured by visual temporal order threshold (TOT), i.e. a minimum gap between two successive stimuli necessary to judge a before-after relation, and resting-state fMRI functional connectivity (rsFC). We assume that the TOT reflects a relatively stable feature of local internal state networks and is associated with rsFC of the temporal parietal junction (TPJ). Sixty five healthy young adults underwent the visual TOT, fluid intelligence (G f ) and an eyes-open resting-state fMRI examination. After controlling for the influence of gender, the higher the TOT, the stronger was the left TPJ's rsFC with the left postcentral and the right precentral gyri, bilateral putamen and the right supplementary motor area. When the effects of G f and TOT × G f interaction were additionally controlled, the TOT-left TPJ's rsFC relationship survived for almost all above regions with the exception of the left and right putamen. This is the first study demonstrating that visual TOT is associated with rsFC between the areas involved both in sub-second timing and motor control. Current outcomes indicate that the local neural networks are prepared to process brief, rapidly presented, consecutive events, even in the absence of such stimulation., (© 2022. The Author(s).)

Macrophages are essential for tissue repair and regeneration. Yet, the molecular programs, as well as the timing of their activation during and after tissue injury are poorly defined. Using a high spatio-temporal resolution single cell analysis of macrophages coupled with live imaging after sensory hair cell death in zebrafish, we find that the same population of macrophages transitions through a sequence of three major anti-inflammatory activation states. Macrophages first show a signature of glucocorticoid activation, then IL-10 signaling and finally the induction of oxidative phosphorylation by IL-4/Polyamine signaling. Importantly, loss-of-function of glucocorticoid and IL-10 signaling shows that each step of the sequence is independently activated. Lastly, we show that IL-10 and IL-4 signaling act synergistically to promote synaptogenesis between hair cells and efferent neurons during regeneration. Our results show that macrophages, in addition to a switch from M1 to M2, sequentially and independently transition though three anti-inflammatory pathways in vivo during tissue injury in a regenerating organ., (© 2022. The Author(s).)

Since the introduction of computed tomography for planning purposes in the 1970s, we have been observing a continuous development of different imaging methods in radiotherapy. The current achievements of imaging technologies in radiotherapy enable more than just improvement of accuracy on the planning stage. Through integrating imaging with treatment machines, they allow advanced control methods of dose delivery during the treatment. This article reviews how the integration of existing and novel forms of imaging changes radiotherapy and how these advances can allow a more individualised approach to cancer therapy. We believe that the significant challenge for the next decade is the continued integration of a range of different imaging devices into linear accelerators. These imaging modalities should show intra-fraction changes in body morphology and inter-fraction metabolic changes. As the use of these more advanced, integrated machines grows, radiotherapy delivery will become more accurate, thus resulting in better clinical outcomes: higher cure rates with fewer side effects., Competing Interests: Conflict of interest None declared., (© 2022 Greater Poland Cancer Centre.)

Introduction: This study aimed to assess and compare the capabilities of two commercially available deformable image registration algorithms implemented in Raystation 9A (A 1 ) and Velocity AI (A 2 ) for possible usage in adaptive prostate radiotherapy based on the propagation of anatomical contours from computed tomography (CT) images to cone-beam CT (CBCT) images., Material and Methods: Ten patients were retrospectively selected from a group treated for localized prostate cancer. The propagation of rectum contours was analyzed in a set of CT-CBCT pairs. Two independent observers carried out qualitative analysis using the two-level descriptive scale (meet/fail). Quantitative analysis was done using landmark points distances based on implanted markers as navigation points and differently obtained contours (manually and automatically using DIR algorithms). Quantitative analysis was taken on sets preselected by qualitative analysis., Results: Qualitative analysis shows that 83.7% of the rectum contours were scored identically (meet or fail) for both algorithms, from which 53.5% and 55.8% are failed results for A 1 and A 2 , respectively. For the rectum size (RWD parameter), differences between referenced and deformation-based values were 5.5 and 5.8mm, and for the rectum wall, the prostate marker distance (WMD parameter) was 4.5 and 5.5mm for A 1 and A 2 , respectively. The differences between the WMD parameters were statistically significant (p=0.007)., Conclusions: In both tested algorithms, neither effectiveness nor measured uncertainties in the propagation of rectum contour process in prostate patient cases were satisfactory. Careful selection of input images followed by case/set-based verification of every deformable registration is a substantial step to avoid inappropriate results., (Copyright © 2021. Published by Elsevier GmbH.)

Purpose: Plan complexity and robustness are two essential aspects of treatment plan quality but there is a great variability in their management in clinical practice. This study reports the results of the 2020 ESTRO survey on plan complexity and robustness to identify needs and guide future discussions and consensus., Methods: A survey was distributed online to ESTRO members. Plan complexity was defined as the modulation of machine parameters and increased uncertainty in dose calculation and delivery. Robustness was defined as a dose distribution's sensitivity towards errors stemming from treatment uncertainties, patient setup, or anatomical changes., Results: A total of 126 radiotherapy centres from 33 countries participated, 95 of them (75%) from Europe and Central Asia. The majority controlled and evaluated plan complexity using monitor units (56 centres) and aperture shapes (38 centres). To control robustness, 98 (97% of question responses) photon and 5 (50%) proton centres used PTV margins for plan optimization while 75 (94%) and 5 (50%), respectively, used margins for plan evaluation. Seventeen (21%) photon and 8 (80%) proton centres used robust optimisation, while 10 (13%) and 8 (80%), respectively, used robust evaluation. Primary uncertainties considered were patient setup (photons and protons) and range calculation uncertainties (protons). Participants expressed the need for improved commercial tools to control and evaluate plan complexity and robustness., Conclusion: Clinical implementation of methods to control and evaluate plan complexity and robustness is very heterogeneous. Better tools are needed to manage complexity and robustness in treatment planning systems. International guidelines may promote harmonization., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Radical treatment of patients diagnosed with inoperable and locally advanced head and neck cancers (LAHNC) is still a challenge for clinicians. Prediction of incomplete response (IR) of primary tumour would be of value to the treatment optimization for patients with LAHNC. Aim of this study was to develop and evaluate models based on clinical and radiomics features for prediction of IR in patients diagnosed with LAHNC and treated with definitive chemoradiation or radiotherapy. Clinical and imaging data of 290 patients were included into this retrospective study. Clinical model was built based on tumour and patient related features. Radiomics features were extracted based on imaging data, consisting of contrast- and non-contrast-enhanced pre-treatment CT images, obtained in process of diagnosis and radiotherapy planning. Performance of clinical and combined models were evaluated with area under the ROC curve (AUROC). Classification performance was evaluated using 5-fold cross validation. Model based on selected clinical features including ECOG performance, tumour stage T3/4, primary site: oral cavity and tumour volume were significantly predictive for IR, with AUROC of 0.78. Combining clinical and radiomics features did not improve model's performance, achieving AUROC 0.77 and 0.68 for non-contrast enhanced and contrast-enhanced images respectively. The model based on clinical features showed good performance in IR prediction. Combined model performance suggests that real-world imaging data might not yet be ready for use in predictive models.

Background: The purpose of the study was to discuss whether 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) study protocol should include brain imaging., Materials and Methods: Analysis of international societies recommendations compared with the original data obtained in over 1000 consecutive torso and brain 18 F-FDG PET/CT studies collected in 2010., Results: According to the international societies recommendations, the 18 F-FDG should not be the radiotracer of choice considering the brain region PET/CT study. However, it can be performed as an additional brain imaging tool. Based on at least a 3-year follow-up, we detected 8 cases of suspicious brain findings and no primary lesion among over 1000 consecutive torso and brain 18F-FDG PET/CT scans performed in 2010. However, in 5 out of 8 patients, the brain lesion was the only metastasis detected, affecting further therapy., Conclusions: The 18 F-FDG PET/CT study may help detect malignant brain lesions and, therefore, including brain region imaging into the study protocol should be considered., Competing Interests: Conflict of interest None declared., (© 2022 Greater Poland Cancer Centre.)

Induced pluripotent stem cells (iPS cells) represent a particularly versatile stem cell type for a large array of applications in biology and medicine. Taking full advantage of iPS cell technology requires high throughput and automated iPS cell culture and differentiation. We present an automated platform for efficient and robust iPS cell culture and differentiation into blood cells. We implemented cell cluster sorting for analysis and sorting of iPS cell clusters in order to establish clonal iPS cell lines with high reproducibility and efficacy. Patient-specific iPS cells were induced to differentiate towards hematopoietic cells via embryoid body (EB) formation. EB size impacts on iPS cell differentiation and we applied cell cluster sorting to obtain EB of defined size for efficient blood cell differentiation. In summary, implementing cell cluster sorting into the workflow of iPS cell cloning, growth and differentiation represent a valuable add-on for standard and automated iPS cell handling., Competing Interests: FS and RP are employee and scientific director, respectively, of Union Biometrica Inc., Holliston, MA, USA, and provided technical support. The remaining 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 Ma, Toledo, Wanek, Elsafi Mabrouk, Smet, Pulak, Pieske, Piotrowski, Herfs, Brecher, Schmitt, Wagner and Zenke.)

No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol—the Best for Adaptive Radiotherapy (B-ART) protocol—to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables—advanced stage disease (T3−T4), chemoradiation, increased weight loss, and oropharyngeal localization—were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes.

Purpose: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum., Material and Methods: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process., Results: A 4-year training period has been proposed, with a total of 240 ECTS (European Credit Transfer and Accumulation System). Training entrance levels have been defined ensuring the necessary physics and mathematics background. The concept of competency-based education has been reinforced by introducing the CanMEDS role framework. The updated CC includes (ablative) stereotactic-, MR-guided- and adaptive RT, particle therapy, advanced automation, complex quantitative data analysis (big data/artificial intelligence), use of biological images, and personalized treatments. Due to the continuously increasing RT complexity, more emphasis has been given to quality management. Clear requirements for a research project ensure a proper preparation of MPE residents for their central role in science and innovation in RT., Conclusion: This updated, 3 rd edition of the CC provides an MPE training framework for safe and effective practice of modern RT, while acknowledging the significant efforts needed in some countries to reach this level. The CC can contribute to further harmonization of MPE training in Europe., 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 © 2022 Elsevier B.V. All rights reserved.)

Metal artefacts degrade clinical image quality which decreases the confidence of using computed tomography (CT) for the delineation of key structures for treatment planning and leads to dose errors in affected areas. In this work, we investigated accuracy of doses computed by the Eclipse treatment planning system near and inside metallic elements for two different computation algorithms. An impact of CT metal artefact reduction methods on the resulting calculated doses has also been assessed. A water phantom including Gafchromic film and metal inserts was irradiated (max dose 5 Gy) using a 6 MV photon beam. Three materials were tested: titanium, alloy 600, and tungsten. The phantom CT images were obtained with the pseudo-monoenergetic reconstruction (PMR) and the iterative metal artefact reduction (iMAR). Image sets were used for dose calculation using an Eclipse treatment planning station (TPS). Monte Carlo (MC) simulations were used to predict the true dose distribution in the phantom allowing for comparison with doses measured by film and calculated by TPS. Measured and simulated percentage depth doses (PDDs) were not statistically different (p > 0.618). Regional differences were observed at edges of metallic objects (max 8% difference). However, PDDs simulated with and without film were statistically different (p < 0.002). PDDs calculated by the Acuros XB algorithm based on the dose-to-medium approach best matched the MC reference regardless of the CT reconstruction methods and inserts used (p > 0.078). PDDs obtained using other algorithms significantly differ from the MC values (p < 0.011). The Acuros XB algorithm with a dose-to-medium approach provides reliable dose calculation in all metal regions when using the Varian system. The inability of the AAA algorithm to model backscatter dose significantly limits its clinical application in the presence of metal. No significant impact on the dose calculation was found for a range of metal artefact reduction strategies., (© 2022. The Author(s).)

Loss of sensory hair cells (HCs) in the mammalian inner ear leads to permanent hearing and vestibular defects, whereas loss of HCs in zebrafish results in their regeneration. We used single-cell RNA sequencing (scRNA-seq) to characterize the transcriptional dynamics of HC regeneration in zebrafish at unprecedented spatiotemporal resolution. We uncovered three sequentially activated modules: first, an injury/inflammatory response and downregulation of progenitor cell maintenance genes within minutes after HC loss; second, the transient activation of regeneration-specific genes; and third, a robust re-activation of developmental gene programs, including HC specification, cell-cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are relevant not only for our understanding of HC regeneration and how we might be able to trigger it in mammals but also for regenerative processes in general. The data are searchable and publicly accessible via a web-based interface., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recent comparison of an ultra-hypofractionated radiotherapy (UF-RT) boost to a conventionally fractionated (CF-RT) option showed similar toxicity and disease control outcomes. An analysis of the treatment plans for these patients is needed for evaluating calculated doses for different organs, treatment beam-on time, and requirements for human and financial resources. Eighty-six plans for UF-RT and 93 plans for CF-RT schemes were evaluated. The biologically equivalent dose, EQD2, summed for the first phase and the boost, was calculated for dose-volume parameters for organs at risk (OARs), as well as for the PTV1. ArcCHECK measurements for the boost plans were used for a comparison of planned and delivered doses. Monitor units and beam-on times were recorded by the Eclipse treatment planning system. Statistical analysis was performed with a significance level of 0.05. Dosimetric parameter values for OARs were well within tolerance for both groups. EQD2 for the PTV1 was on average 84 Gy for UF-RT patients and 76 Gy for CF-RT patients. Gamma passing rate for planned/delivered doses comparison was above 98% for both groups with 3 mm/3% distance to agreement/dose difference criteria. Total monitor units per fraction were 647 ± 94 and 2034 ± 570 for CF-RT and UF-RT, respectively. The total delivery time for boost radiation for the patients in the UF-RT arm was, on average, four times less than the total time for a conventional regimen with statistically equal clinical outcomes for the two arms in this study.

Purpose: The purpose of this study was to evaluate the accuracy of dose delivery during stereotactic radiotherapy of the lung (SBRT) and brain (SRT) tumours by registered CT (rCT) images obtained from CT used for planning (pCT) and cone-beam CT (CBCT)., Methods: The study is based on two groups of patients (10 patients each) undergoing SBRT and SRT. To assess the correctness of the propagation of the GTV (brain group) and ITV (lung group) contours, the volumes calculated on the pCT and rCT studies were analysed. The Dice-Sørensen similarity coefficient (DSC) was used to check the variability in the position of GTV/ITV observed between pCT and rCT. The dose recalculated on rCT was compared with the dose from pCT., Result: GTV and ITV determined on pCT and rCT studies did not differ statistically (p = 0.770 for ITV and p = 0.086 for GTV). DSC obtained for the lung group was statistically smaller than that for the brain group (p < 0.001). Differences between doses obtained for 99% of the ITV/GTV on pCT and rCT studies were within ±10% and did not exceed the clinically acceptable tolerance., Conclusion: The observed changes in the volume (ITV/GTV) were within the area of the original PTV volume. The differences between the planned and delivered doses in the ITV/GTV were not clinically significant., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The study aimed to show that including the brain region into the standard 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) study protocol may result in detecting clinically silent brain tumours. We retrospectively analyzed the group of 10,378 from the total of 12,011 consecutive patients who underwent the torso and brain [18F]FDG PET/CT scanning, considering an ability of the method to evaluate undetected before brain tumours in patients diagnosed and treated in our institution. While collecting the database, we followed the inclusion criteria: at least 1-year of follow-up, a full medical history collected in our institution, histopathologic examination or other studies available to confirm the type of observed lesion, and the most importantly-no brain lesions reported in the patients' medical data. In this study, performing the torso and brain [18F]FDG PET/CT imaging helped to detect clinically silent primary and metastatic brain tumours in 129 patients, and the benign lesions in 24 studied cases, in whom no suspicious brain findings were reported prior to the examination. In conclusion, including the brain region into the standard [18F]FDG PET/CT protocol can be considered helpful in detecting clinically silent malignant and benign brain tumours., (© 2021. The Author(s).)

According to the international societies' recommendations, the 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) technique should not be used as the method of choice in brain tumour diagnosis. Therefore, the brain region can be omitted during standard [ 18 F]FDG PET/CT scanning. We performed comprehensive literature research and analysed results from 14,222 brain and torso [ 18 F]FDG PET/CT studies collected in 2010-2020. We found 131 clinically silent primary and metastatic brain tumours and 24 benign lesions. We concluded that the brain and torso [ 18 F]FDG PET/CT study provides valuable data that may support therapeutic management by detecting clinically silent primary and metastatic brain tumours.

Background: The aim of the study was to compare the TNM classification with 2-[ 18 F]FDG PE T biological parameters of primary tumor in patients with NSCLC., Materials and Methods: Retrospective analysis was performed on a group of 79 newly diagnosed NSCLC patients. PET scans were acquired on Gemini TF PET/CT scanner 60-70 min after injection of 2-[ 18 F]FDG with the mean activity of 364 ± 75 MBq, with the area being examined from the vertex to mid-thigh. The reconstructed PET images were evaluated using MIM 7.0 Software for SUV max , MTV and TLG values., Results: The analysis of the cancer stage according to TNM 8 th edition showed stage IA2 in 8 patients, stage IA3 - 6 patients, stage IB - 4 patients, IIA - 3 patients, 15 patients with stage IIB, stage IIIA - 17 patients, IIIB - 5, IIIC - 5, IVA in 7 patients and stage IVB in 9 patients. The lowest TLG values of primary tumor were observed in stage IA2 (11.31 ± 15.27) and the highest in stage IIIC (1003.20 ± 953.59). The lowest value of primary tumor in SUV max and MTV were found in stage IA2 (6.8 ± 3.8 and 1.37 ± 0.42, respectively), while the highest SUV max of primary tumor was found in stage IIA (13.4 ± 11.4) and MTV in stage IIIC (108.15 ± 127.24)., Conclusion: TNM stages are characterized by different primary tumor 2-[ 18 F]FDG PET parameters, which might complement patient outcome., Competing Interests: Conflict of interest None declared., (© 2021 Greater Poland Cancer Centre.)

Background: This study aims to develop a useful tool for robust plan analysis which includes the effects of soft tissue deformations on simulated dose distributions. The solution was benchmarked in the light of the commercial method implemented in Eclipse TM treatment planning system (TPS)., Materials and Methods: Study was carried out on data of one patient with prostate-restricted cancer. The workflow of the procedure developed focused on three executive elements: in-house script to create a set of artificial CT images and for movement simulation of the CT V; the Velocity TM software for the calculations of the deformation matrixes and, then, to generate deformed CT sets; the Eclipse TM TPS for dose re-calculations and analysis. Two scenarios were examined - first when the recalculation was done for the original geometry and second, when the isocentre from the original plan geometry was moved according to the movement of the CT V. The dose distributions were analysed on dose volume histograms (DVHs) in the light of the results obtained from the method implemented in the Eclipse TM TPS., Results: The DVHs from our methods are more informative than the DVH from commercially implemented tools. For the first scenario, the highest impact on dose uncertainty has boundary positions of the CT V to the CT V-PTV margin. Using the second scenario, it is the relation of the CT V position to the whole body that has the highest effect on dose uncertainty., Conclusion: Our method enables a more accurate analysis of the treatment plan robustness than the method currently implemented in Eclipse TM TPS., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (© 2021 Greater Poland Cancer Centre.)

Mammalian inner ear and fish lateral line sensory hair cells (HCs) detect fluid motion to transduce environmental signals. Actively maintained ionic homeostasis of the mammalian inner ear endolymph is essential for HC function. In contrast, fish lateral line HCs are exposed to the fluctuating ionic composition of the aqueous environment. Using lineage labeling, in vivo time-lapse imaging and scRNA-seq, we discovered highly motile skin-derived cells that invade mature mechanosensory organs of the zebrafish lateral line and differentiate into Neuromast-associated (Nm) ionocytes. This invasion is adaptive as it is triggered by environmental fluctuations. Our discovery of Nm ionocytes challenges the notion of an entirely placodally derived lateral line and identifies Nm ionocytes as likely regulators of HC function possibly by modulating the ionic microenvironment. Nm ionocytes provide an experimentally accessible in vivo system to study cell invasion and migration, as well as the physiological adaptation of vertebrate organs to changing environmental conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A combination of multiple nondestructive testing (NDT) methods speeds up the assessment of concrete and increases the precision. This is why the UIR-Scanner was developed at Warsaw University of Technology. The scanner uses an Impact-Echo (IE) method with a unique arrangement of multiple transducers. This paper presents the development of the IE module using numerical models validated with experimental testing. It was found that rectangular arrangement of four transducers with the impactor in the middle is optimal for quick scanning of area for faults and discontinuities, changing the method from punctual to volumetric. A numerical study of void detectability depending on its position with respect to the IE module is discussed as well. After confirmation of the findings of models using experimental tests, the module was implemented into the scanner.

Purpose: ESTRO-EFOMP intend to update the core curriculum (CC) for education and training of medical physicists in radiotherapy in line with the European Commission (EC) guidelines on Medical Physics Experts (MPE), the CanMEDS methodology and recent developments in radiotherapy. As input, a survey of the current structure of radiotherapy MPE national training schemes (NTS) in Europe was carried out., Methods: A 35-question survey was sent to all European medical physics national societies (NS) with a focus on existence of an NTS, its format and duration, required entry-level education, and financial support for trainees., Results: Twenty-six of 36 NS responded. Twenty had an NTS. Minimum required pre-training education varied from BSc in physics or related sciences (5/2) to MSc in medical physics, physics or related sciences (6/5/2) with 50-210 ECTS in fundamental physics and mathematics. The training period varied from 1 to 5 years (median 3 years with 50% dedicated to radiotherapy). The ratio of time spent on university lectures versus hospital training was most commonly 25%/75%. In 14 of 20 countries with an NTS, a research project was mandatory. Residents were paid in 17 of 20 countries. The recognition was mostly obtained by examination. Medical physics is recognised as a healthcare profession in 19 of 26 countries., Conclusions: The NTS entrance level, duration and curriculum showed significant variations. This survey serves to inform the design of the updated CC to define a realistic minimum training level for safe and effective practice aiming at further harmonization in line with EC guidelines., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Penile cancer is a rarely diagnosed cancer that affects 0.4%-0.6% of all male population. Metastases to the bones from various human cancers are common; however, acrometastases are extremely rare with the most common primary tumor from lung, kidney, and breast. We report the first case of a patient with acrometastases to the left wrist reported from penile cancer., Competing Interests: None

Human induced pluripotent stem cells (hiPSCs) are capable of differentiating into a variety of human tissue cells. They offer new opportunities for personalized medicine and drug screening. This requires large quantities of high quality hiPSCs, obtainable only via automated cultivation. One of the major requirements of an automated cultivation is a regular, non-invasive analysis of the cell condition, e.g. by whole-well microscopy. However, despite the urgency of this requirement, there are currently no automatic, image-processing-based solutions for multi-class routine quantification of this nature. This paper describes a method to fully automate the cell state recognition based on phase contrast microscopy and deep-learning. This approach can be used for in process control during an automated hiPSC cultivation. The U-Net based algorithm is capable of segmenting important parameters of hiPSC colony formation and can discriminate between the classes hiPSC colony, single cells, differentiated cells and dead cells. The model achieves more accurate results for the classes hiPSC colonies, differentiated cells, single hiPSCs and dead cells than visual estimation by a skilled expert. Furthermore, parameters for each hiPSC colony are derived directly from the classification result such as roundness, size, center of gravity and inclusions of other cells. These parameters provide localized information about the cell state and enable well based treatment of the cell culture in automated processes. Thus, the model can be exploited for routine, non-invasive image analysis during an automated hiPSC cultivation. This facilitates the generation of high quality hiPSC derived products for biomedical purposes., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim of the Study: To evaluate the agreement between planned and delivered doses and its potential correlation with the plans' complexity subjected to dosimetric verification., Material and Methods: Four isocentre volumetric modulated arc therapy for total marrow irradiation plans optimized simultaneously with (P1) and without (P2) MU reduction were evaluated dosimetrically by γ method performed in a global mode for 4 combinations of γ-index criteria (2%/2 mm, 2%/3 mm, 3%/2 mm, and 3%/3 mm). The evaluation was conducted for 4 regions (head and neck, chest, abdomen and upper pelvis, and lower pelvis and thighs) that were determined geometrically by the isocentres. The Wilcoxon test was used to detect significant differences between γ passing rate (GPR) analysis results for the P1 and P2 plans. The Pearson correlation was used to check the relationship between GPR and the plans' complexity., Results: Except for the head and neck region, the P2 plans had better GPRs than the P1 plans. Only for hard combinations of γ-index criteria (i.e. 2%/3 mm, 2%/2 mm) were the GPRs differences between P1 and P2 clinically meaningful, and they were detected in the chest, abdomen and upper pelvis, and lower pelvis and thighs regions. The highest correlations between GPR and the indices describing the plans' complexity were found for the chest region. No correlation was found for the head and neck region., Conclusions: The P2 plans showed better agreement between planned and delivered doses compared to the P1 plans. The GPR and the plans' complexity depend on the anatomy region and are most important for the chest region., (Copyright © 2021 Termedia.)

Background: Cortical regions that support cognitive control are increasingly well recognized, but the functional mechanisms that promote such control over emotional and behavioral hyperreactivity to alcohol in recently abstinent alcohol-dependent patients are still insufficiently understood. This study aimed to identify neurophysiological biomarkers of maintaining abstinence in alcohol-dependent individuals after alcohol treatment by investigating the resting-state EEG-based functional connectivity in the cognitive control network (CCN)., Methods: Lagged phase synchronization between CCN areas by means of eLORETA as well as the Barratt Impulsiveness Scale (BIS-11) and Beck Depression Inventory (BDI) were assessed in abstinent alcohol-dependent patients recruited from treatment centers. A preliminary prospective study design was used to classify participants into those who did and did not maintain abstinence during a follow-up period (median 12 months) after discharge from residential treatment., Results: Alcohol-dependent individuals, who maintained abstinence (N = 18), showed significantly increased lagged phase synchronization between the left dorsolateral prefrontal cortex (DLPFC) and the left posterior parietal cortex (IPL) as well as between the right anterior insula cortex/frontal operculum (IA/FO) and the right inferior frontal junction (IFJ) in the delta band compared to those who later relapsed (N = 16). Regression analysis showed that the increased left frontoparietal delta connectivity in the early period of abstinence significantly predicted maintaining abstinence over the ensuing 12 months. Furthermore, right frontoinsular delta connectivity correlated negatively with impulsivity and depression measures., Conclusions: These results suggest that the increased delta resting-state functional connectivity in the CCN may be a promising neurophysiological predictor of maintaining abstinence in individuals with alcohol dependence., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The aim was to validate the dosimetric and geometric accuracy of radiotherapy treatment plans for prostate cancer based on magnetic resonance (MR) imaging only and a solution based on computed tomography (CT) supported by MR imaging., Material and Methods: We used CT and MR images of ten prostate cancer patients implanted with three fiducial markers (FM) in the prostate gland. Rigid registration based on FM was performed to assess the fusion accuracy between MR and CT images. The differences between prostate contours (clinical target volume - CTV) on CT (CTV CT ) and MR (CTV MR ) images were scored using the Dice similarity coefficient and directly comparing the outlined volumes. The volumetric modulated arc therapy plans were designed and optimised on synthetic CT (sCT) to obtain the dose distribution for the MR-only solution. In the next step, the sCT images were replaced by conventional CT images and the plans were recalculated. The doses obtained on sCT and CT were compared by direct dose subtraction and the gamma method., Results: The averaged fiducial registration error was equal to 0.5 mm. All CTV CT volumes were significantly bigger than corresponding CTV delineated on MR images ( p = 0.005). The direct dose comparison shows that for 97.1% of patients' bodies, the differences were smaller than 0.1%. The average gamma passing rates were higher than 0.970., Conclusions: MR imaging allows for a more precise delineation of the prostate compared to CT imaging. The workflow of plan preparation based on MR and CT is burdened with an FM registration error that is eliminated by an MR-only solution with no compromise on dose distribution., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Brain activity pattern recognition from EEG or MEG signal analysis is one of the most important method in cognitive neuroscience. The SUPFUNSIM library is a new MATLAB toolbox which generates accurate EEG forward model and implements a collection of spatial filters for EEG source reconstruction, including the linearly constrained minimum-variance (LCMV), eigenspace LCMV, nulling (NL), and minimum-variance pseudo-unbiased reduced-rank (MV-PURE) filters in various versions. It also enables source-level directed connectivity analysis using partial directed coherence (PDC) measure. The SUPFUNSIM library is based on the well-known FIELDTRIP toolbox for EEG and MEG analysis and is written using object-oriented programming paradigm. The resulting modularity of the toolbox enables its simple extensibility. This paper gives a complete overview of the toolbox from both developer and end-user perspectives, including description of the installation process and use cases.

Purpose: The aim of the study was to assess selected methods of image registration available in the RaySearch software and their impact on the accuracy of mapping of doses deposited in the bladder during brachytherapy (BRT) of cervical cancer in images used during external beam radiotherapy (EBRT)., Material and Methods: The study was based on data from ten patients. Cone-beam computed tomography (CBCT) images (BRT) were aligned with CT images (EBRT) using four registration methods: Reg&#95;1 (rigid), Reg&#95;2a, Reg&#95;2b (hybrid), and Reg&#95;3 (biomechanical). Image mapping accuracy was evaluated based on bladder's anatomy. Sørensen-Dice coefficient (DSC) values were analyzed for all the registrations. Discrepancies between triangular mesh points set on the basis of bladder contours were analyzed. Dose distributions from BRT were transformed according to registration results and mapped on CT images. Original BRT doses deposited in 2 cm 3 volume of the bladder were compared to those transformed and associated with bladder's volume determined on CT images., Results: Mean DSC values amounted to 0.36 (Reg&#95;1), 0.87 and 0.88 (Reg&#95;2a and Reg&#95;2b), and 0.97 (Reg&#95;3). Significant differences were found between DSC for the following comparisons: Reg&#95;3/Reg&#95;1 ( p = 0.001), Reg&#95;2a/Reg&#95;1 ( p = 0.011), and Reg&#95;2b/Reg&#95;1 ( p = 0.014). The lowest discrepancies between triangular mesh points were for Reg&#95;3 ( p < 0.001, Reg&#95;3 vs. Reg&#95;1, and p = 0.039, Reg&#95;3 vs. Reg&#95;2b). Finally, the lowest discrepancies between the original and transformed doses were found for Reg&#95;3. Nevertheless, only 5 out of 10 observations for Reg&#95;3 yielded error of less than 5%., Conclusions: Biomechanical registration (Reg&#95;3) enabled the most accurate alignment between CBCT and CT images. Satisfactory registration results of anatomical structures do not guarantee a correct mapping of primary BRT doses on the bladder delineated on CT images during EBRT. The results of dose transformation based on biomechanical registration had an error of less than 5% for only 50% of the observations., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Plan evaluation is a key step in the radiotherapy treatment workflow. Central to this step is the assessment of treatment plan quality. Hence, it is important to agree on what we mean by plan quality and to be fully aware of which parameters it depends on. We understand plan quality in radiotherapy as the clinical suitability of the delivered dose distribution that can be realistically expected from a treatment plan. Plan quality is commonly assessed by evaluating the dose distribution calculated by the treatment planning system (TPS). Evaluating the 3D dose distribution is not easy, however; it is hard to fully evaluate its spatial characteristics and we still lack the knowledge for personalising the prediction of the clinical outcome based on individual patient characteristics. This advocates for standardisation and systematic collection of clinical data and outcomes after radiotherapy. Additionally, the calculated dose distribution is not exactly the dose delivered to the patient due to uncertainties in the dose calculation and the treatment delivery, including variations in the patient set-up and anatomy. Consequently, plan quality also depends on the robustness and complexity of the treatment plan. We believe that future work and consensus on the best metrics for quality indices are required. Better tools are needed in TPSs for the evaluation of dose distributions, for the robust evaluation and optimisation of treatment plans, and for controlling and reporting plan complexity. Implementation of such tools and a better understanding of these concepts will facilitate the handling of these characteristics in clinical practice and be helpful to increase the overall quality of treatment plans in radiotherapy., 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 © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Neural complexity is thought to be associated with efficient information processing but the exact nature of this relation remains unclear. Here, the relationship of fluid intelligence (gf) with the resting-state EEG (rsEEG) complexity over different timescales and different electrodes was investigated. A 6-min rsEEG blocks of eyes open were analyzed. The results of 119 subjects (57 men, mean age = 22.85 ± 2.84 years) were examined using multivariate multiscale sample entropy (mMSE) that quantifies changes in information richness of rsEEG in multiple data channels at fine and coarse timescales. gf factor was extracted from six intelligence tests. Partial least square regression analysis revealed that mainly predictors of the rsEEG complexity at coarse timescales in the frontoparietal network (FPN) and the temporo-parietal complexities at fine timescales were relevant to higher gf. Sex differently affected the relationship between fluid intelligence and EEG complexity at rest. In men, gf was mainly positively related to the complexity at coarse timescales in the FPN. Furthermore, at fine and coarse timescales positive relations in the parietal region were revealed. In women, positive relations with gf were mostly observed for the overall and the coarse complexity in the FPN, whereas negative associations with gf were found for the complexity at fine timescales in the parietal and centro-temporal region. These outcomes indicate that two separate time pathways (corresponding to fine and coarse timescales) used to characterize rsEEG complexity (expressed by mMSE features) are beneficial for effective information processing., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

While human induced pluripotent stem cells (hiPSCs) provide novel prospects for disease-modeling, the high phenotypic variability seen across different lines demands usage of large hiPSC cohorts to decipher the impact of individual genetic variants. Thus, a much higher grade of parallelization, and throughput in the production of hiPSCs is needed, which can only be achieved by implementing automated solutions for cell reprogramming, and hiPSC expansion. Here, we describe the StemCellFactory, an automated, modular platform covering the entire process of hiPSC production, ranging from adult human fibroblast expansion, Sendai virus-based reprogramming to automated isolation, and parallel expansion of hiPSC clones. We have developed a feeder-free, Sendai virus-mediated reprogramming protocol suitable for cell culture processing via a robotic liquid handling unit that delivers footprint-free hiPSCs within 3 weeks with state-of-the-art efficiencies. Evolving hiPSC colonies are automatically detected, harvested, and clonally propagated in 24-well plates. In order to ensure high fidelity performance, we have implemented a high-speed microscope for in-process quality control, and image-based confluence measurements for automated dilution ratio calculation. This confluence-based splitting approach enables parallel, and individual expansion of hiPSCs in 24-well plates or scale-up in 6-well plates across at least 10 passages. Automatically expanded hiPSCs exhibit normal growth characteristics, and show sustained expression of the pluripotency associated stem cell marker TRA-1-60 over at least 5 weeks (10 passages). Our set-up enables automated, user-independent expansion of hiPSCs under fully defined conditions, and could be exploited to generate a large number of hiPSC lines for disease modeling, and drug screening at industrial scale, and quality., (Copyright © 2020 Elanzew, Nießing, Langendoerfer, Rippel, Piotrowski, Schenk, Kulik, Peitz, Breitkreuz, Jung, Wanek, Stappert, Schmitt, Haupt, Zenke, König and Brüstle.)

Purpose: To evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method., Methods: Pseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70-130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers., Results: AD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034)., Conclusion: The use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning., 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 © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Restricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects., Methods: Four VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions., Results: 6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ± 0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics., Conclusions: Generally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects., (© 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)