Existing guidelines for ultrasound-guided fine-needle aspiration biopsy lack specifications on sampling sites, but the number of biopsies improves diagnostic reliability. We propose the use of class activation maps (CAMs) and our modified malignancy-specific heat maps that locate important deep representations of thyroid nodules for class predictions.We applied adversarial noise perturbations to the segmented concentric “hot” nodular regions of equal sizes to differentiate regional importance for the malignancy diagnostic performances of an accurate ultrasound-based artificial intelligence computer-aided diagnosis (AI-CADx) system using 2,602 retrospectively collected thyroid nodules with known histopathological diagnosis.The AI system demonstrated high diagnostic performance with an area under the curve (AUC) value of 0.9302 and good nodule identification capability with a median dice coefficient >0.9 when compared to radiologists’ segmentations. Experiments confirmed that the CAM-based heat maps reflect the differentiable importance of different nodular regions for an AI-CADx system to make its predictions. No less importantly, the hot regions in malignancy heat maps of ultrasound images in comparison with the inactivated regions of the same 100 malignant nodules randomly selected from the dataset had higher summed frequency-weighted feature scores of 6.04 versus 4.96 rated by radiologists with more than 15 years of ultrasound examination experience according to widely used ultrasound-based risk stratification American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) in terms of nodule composition, echogenicity, and echogenic foci, excluding shape and margin attributes, which could only be evaluated on the whole rather than on the sub-nodular component levels. In addition, we show examples demonstrating good spatial correspondence of highlighted regions of malignancy heat map to malignant tumor cell-rich regions in hematoxylin and eosin-stained histopathological images.Our proposed CAM-based ultrasonographic malignancy heat map provides quantitative visualization of malignancy heterogeneity within a tumor, and it is of clinical interest to investigate in the future its usefulness to improve fine-needle aspiration biopsy (FNAB) sampling reliability by targeting potentially more suspicious sub-nodular regions. Thyroid nodules are detected in as high as 65% of the population , and thySurprisingly or not, the capability of convolutional neural networks (CNNs) to approximate any arbitrary functions has become a double-edged sword, as any insights about how the models come to their conclusions are hardly accessible to human understanding given their architectural designs. Some proposed circumventing strategies include weighting the predicted classification probability of a CNN model as a contributing factor together with other human-interpretable image features  and takiOther possibilities to retrieve hints using computer-aided artificial intelligence diagnosis as we perceive include generating the class activation map (CAM)  that locTo answer these questions, we designed this proof-of-concept computational study described as the following. We first generated CAMs in two different rendering configurations using the Software Development Kit (SDK) of the artificial intelligence computer-aided diagnosis (AI-CADx) system referred to as “AI-SONIC™ Thyroid” for thyroid nodule diagnoses. In the first configuration, the heat maps were rendered conventionally such that they make no distinctions between benign and malignant cases visually, and the color temperature is supposed to show the associated regional importance in predicting the classification regardless of what the predicted type is. In the second configuration, however, the intensities of these heat maps were normalized to the malignancy probabilities predicted by the AI-CADx system and rendered in such a way that the more reddish the color, the higher probability that the nodule is predicted to be malignant, whereas the bluish color indicates benignity. In other words, the second visualization configuration presents essentially malignancy heat maps.To quantitatively analyze the importance of different regions within the ultrasound-imaged thyroid nodules in the diagnosis by the AI-CADx system, we subdivided each nodular CAM into five concentric areas of the same size and then evaluated the AI diagnostic performances after the adversarial noises  were appThe ultrasound images covering a total of 2,602 thyroid nodules from 2,488 patients were collected between January 2011 and February 2019 by The Cancer Hospital of the University of Chinese Academy of Sciences in Hangzhou, Zhejiang, China. All nodules were diagnosed by surgical pathological examinations, among which 1,581 cases were determined to be benign and 1,021 cases were found to be malignant. The local ethics committee waived the ethical approval in view of the retrospective nature of the study, and all reviews of the ultrasound image and postsurgical hematoxylin and eosin (H&E)-stained pathological images being performed were part of the clinical routine.This study was based on the AI-SONIC™ Thyroid nodule diagnosis system . It is built on the EfficientNet  architecAll the generated heat maps in this study were based on CAM  using glk is the result of performing global average pooling, which is defined as i is For an image, we used By adding In addition, we define Mi as the class activation map for class i, where each spatial element is the product of the weight Therefore, The CAM is a weighted linear sum of the presence of these visual patterns at different spatial locations. By upsampling the class activation map to the size of the input image, we could identify the image regions most relevant to the particular category.We divided each CAM of thyroid nodules into five nearly concentric regions of equal sizes. This was performed first by setting a binarization threshold to 0 to obtain a nodular segmentation with a total area of N. Then, we searched for a second threshold for level setting the CAM to segment the outermost region with the size of N/5. We iterated this process until we segmented out the innermost region with the same size.To illustrate the different importance of each region of the heat map, we added perturbations to the different regions. A commonly employed first-order adversarial attack method—Fast Gradient Sign Method (FGSM) —was usedϕ the parameters of a model, and L the cost function used to train the neural network. Then, we can linearize the cost function about the current value of ϕ, acquiring an optimal max-norm constrained perturbation ofLet x be the input to the model, y the output to the model (the targets associated with x), β is a predefined perturbation size, which represents the maximum change to pixel values of an image. sign is a symbolic function, which is defined aswhere In addition, we used the back-propagation to compute the required gradient.This method can reliably generate perturbations to the input of the model. The single-step FGSM perturbs the original example by a fixed amount along the direction (sign) of the gradient of loss function such that the result from the perturbed image is given by the following:To assess the performance of the AI-CADx system, we computed the receiver operating characteristic (ROC) curve and used the area under the curve (AUC) as the evaluation metric. For each nodule, we randomized five times the positions in segmented nodular regions where perturbation noises were applied, and we used the malignancy probabilities averaged over five times of randomized noise perturbations to compute the ROC curves and the subsequent AUC values. To compare individual ROC curves, we performed DeLong’s test  to evaluFor further statistical significance validation, we evaluated AUC values computed for different regions in each dataset (the division of which is described above), followed by paired t-test for different segmented nodular regions.We randomly selected 100 malignant nodules from our dataset and had the ultrasound features rated by radiologists with 15 years of ultrasound examination experience according to widely used ultrasound-based risk stratification American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS)  in termsH&E staining images of postoperative histopathological slides with saved ultrasound images of matched sectional views were reexamined by a senior pathologist with 25 years of work experience with the boundaries and shapes of the malignant regions of thyroid tumors on the H&E slides outlined using software provided by digital pathology slide scanner KF-PRO-005-EX .Representative examples of the CAMs generated by using AI-SONIC™ Thyroid SDK are shown in In order to evaluate whether different regions of thyroid nodules may contribute differently to their classifications by the AI-CADx system, we first segmented individual CAMs into five concentric areas of equal sizes according to the method section about nodular CAM segmentation as described above. An illustration of how the segmentation of a nodular CAM looks is given in β to be 0.0136 by searching for the maximum absolute gradient of AUC values with respect to the noise magnitudes  to five datasets for the purpose of ensuring reproducibility. The results together with the p-value matrix for pairwise comparisons are summarized in To investigate whether the highlighted regions had a higher correlation with malignancy risks compared to the inactivated regions of our proposed malignancy heat map, radiologists with more than 15 years of ultrasound examination experience evaluated the ultrasound features according to the ACR TI-RADS risk stratification criteria in terms of nodular composition, echogenicity, and echogenic foci, which are applicable to subcomponent evaluations. The results summarized from 100 randomly selected malignant nodules in In order to verify the pathological significance of the heat maps, we first compared the nodule masks generated by the AI system with the masks outlined by the radiologists of different nodule sizes in To further demonstrate and qualitatively verify the pathological relevance of the computed heat maps, we compared the post-operation pathological images with heat maps computed on ultrasound images shown in In this study, we proposed to take advantage of CAMs for differentiating regions in the ultrasound images of thyroid nodules that may contribute differently to the diagnosis by an AI-CADx system. We segmented the CAMs of individual nodule images into five concentric areas of equal sizes, applied adversarial noise perturbations to the different segmented regions, and evaluated the impact on the diagnostic performances of the AI-CADx system. Our results confirmed that the CAMs can reflect the importance of different degrees in different nodular regions for a CNN-based diagnosis system to make its predictions according to our noise perturbation experiments. Surprisingly or not, it was found that it was not the innermost region or in other words the “hottest” region seen in the CAMs that were most severely influenced by the noise perturbations as one might presumably expect. This phenomenon was again observed in experiments where we randomly divided the original dataset into five subsets and verified by the statistical significance tests, suggesting that the regional sensitivities to noise perturbations may not perfectly correlate with the heat intensity profile in conventional CAM for nodular malignancy state predictions.We then tried modifying the conventional CAM by multiplying the heat maps generated by CAM with the predicted malignancy probabilities by the AI-CADx system to produce malignancy heat maps. The resulting heat maps can therefore visually convey information about the malignancy predictions for individual nodules. Furthermore, this malignant nodule-specific modification to the conventional CAM would in principle allow more insightful inspection of regional importance for malignancy assessment and thus provide guidance to doctors about where the FNAB should be mostly directed to. In this case, the innermost nodular area defined by the heat map was found to be the most sensitive region to noise perturbations, which could be due to the multiplication of malignancy probability, which improves its malignancy relevance and subsequently the perturbation responsiveness, though it was not statistically different from the region adjacent to it, which suggests that both regions are the most critical for determining malignant thyroid nodule diagnosis.By comparing the influences of noises on AI-CADx performance for thyroid nodule diagnosis by perturbing regions segmented according to the conventional CAMs that analyze both benign and malignant nodules and our proposed variant that concentrates on suspicious nodules, it can be seen that noise perturbations to inner regions defined in CAMs had a more dramatic effect on datasets not excluding benign nodules predicted with high confidence. This could be because the inner regions of benign nodules are more vulnerable to noise perturbations, while the malignant nodules are more resistant to noise perturbations. This can also explain why the regional differences in suspicious malignant nodules were less abrupt. Nonetheless, the central region defined by the malignancy heat map was significantly more sensitive to noise perturbation, suggesting the potential of this technique for differentiating tumor heterogeneity.As an alternative to the noise perturbation experiments, we have also tried varying binary thresholds to segment the CAMs and evaluated the diagnostic performance of the AI-CADx system directly on the ultrasound images of the regions above the thresholds with the hope of finding an appropriate heat intensity threshold that could permit a satisfactory cutoff to differentiate insignificant regions from regions where special attention would be paid to. However, such a conclusion could not be drawn from this attempt, as the AUC values (As final proof, we qualitatively evaluate the spatial correlation of the malignancy heterogeneity identified by our CAM-based malignancy heat map with the surgical pathology. Due to not only the technical difficulty of automatically registering cross-modality images, i.e., digital histopathology images and ultrasound images, but also more importantly the retrospective nature of this study, we could not specifically collect the ultrasound images of the very nodular cross-sections that best corresponded to those of the histopathology images. Moreover, arbitrary shape changes can be introduced during the surgical operation and fully automatic registration between digital H&E histopathology images, and ultrasound images would also require training of a sufficient good segmentation model for cancer cell-rich regions in histopathology images, which is currently beyond our capacity of assessable resources. It is however important to note that the ultrasound feature evaluations of the highlighted regions performed by radiologists according to ACR TI-RADS criteria show a higher correlation with malignancy risks compared to the inactivated regions, demonstrating the malignancy relevance of the highlighted regions in our proposed variant of CAM heat map. This can be mainly attributed to two facts: the AI system has high accuracy in localizing thyroid nodules with a median dice coefficient >0.9, and the AI system has very high diagnostic accuracy with an AUC value of 0.9302 in this study for discriminating between malignant and benign nodules. The nodule segmentation is a crucial step for the computations of heat maps, and it proves that the corresponding area of the heat map is mainly in the lesion area of the nodule. Good performance in distinguishing malignant from benign nodules also plays a vital role in identifying the “hot” regions in the malignancy heat map to be the key regions for the diagnosis of malignant nodules. Furthermore, other recent studies have shown that the AI system has balanced specificity and sensitivity with overall diagnostic accuracy matching high-performing senior radiologists , can outUltrasound-guided thyroid FNAB has been shown to improve the sampling accuracy for suspicious nodule identification . HoweverFurthermore, currently, the generation of CAMs is based on an AI-CADx system trained on static images. For real-world clinical applications, it will be beneficial to have such heat maps dynamically generated in real-time during ultrasound scanning, which would require the corresponding AI-CADx system to be able to operate in a dynamic mode with high diagnostic accuracy. Practically speaking, ultrasound reflections from needles might interfere with accurate heat map visualization in real time. Another noteworthy limitation of the proposed CAM and its variant presented in this study is that their visualization is currently limited to being two-dimensional and thus not very suited yet to visualizing the degree of malignancy suspiciousness of a targeted cross-sectional plane relative to that of the planes above and below. If a three-dimensional heat map visualization is to be developed such that additional guidance about how deep the needles shall be inserted into the nodules to acquire samplings can be possible. In addition to the applied basic CAM method, there are also other published variants such as Grad-CAM , Score-CThe CAM and its variant generated on ultrasound images through a highly accurate AI-CADx system can provide differential importance of nodular regions for tumor malignancy prediction, which was validated by adding noise perturbations to different regions of thyroid nodules. Our proposed malignancy heat map offers quantitative visualization of malignancy heterogeneity within a tumor, and the highlighted regions are better correlated with the malignancy risk than the inactivated regions. The good spatial correspondence with post-operation pathology warrants clinical interests to investigate further whether such AI-based malignancy-heterogeneity visualization techniques can provide targeted guidance for needle-based aspiration biopsies of tumors in comparison with plain ultrasound imaging to improve sampling accuracy and reduce complications that may associate with the procedures.wanglj844@zjcc.org.cn.The data analyzed in this study is subject to the following licenses/restrictions: It is not within the agreement with the participants to make the original dataset publicly available. The data that support the findings of this study are available on reasonable request from corresponding author L.W. after formal approval by the concerned Chinese regulating authorities.. Requests to access these datasets should be directed to The studies involving human participants were reviewed and approved by The Cancer Hospital of the University of Chinese Academy of Sciences but waived in view of the retrospective nature of the study and all involved ultrasound image reviews being performed were part of the clinical routine. The patients/participants provided their written informed consent to participate in this study.Conceptualization: LPW and LX. Methodology: YW, JY, and WL. Software: YW, WL, and JY. Validation: LPW, LJW, and LX. Formal analysis: YW and DX. Investigation: LPW, YW, DX, and LJW. Resources: LJW and LX. Data curation: LPW, LJW, and DX. Writing—original draft preparation: YW and LX. Writing—review and editing: LX. Supervision: LJW and LX. Project administration: LJW and LX. Funding acquisition: DX and LPW. All authors have read and agreed to the published version of the manuscript.


Following the great interest in the first edition of the Frontiers Research Topic devoted to technology related to the understanding, management, and therapy of atrial fibrillation (AF), we are glad to present a second collection of additional articles on the Research Topic. AF remains the most common sustained clinical arrhythmia , the leaEhnesh et al. analyzed non-contact recordings from inside the left atrium of 10 persistent AF patients and found that spatial correlation between these two features at any given time is poor but they colocalize in certain regions over time, mainly in the septum. In patients in whom high-dominant frequency ablation terminated the AF, there was some overlapping with longer-lasting rotor sites, but the relationship was complex overall. The study by Jenkins et al. focused on the accuracy of quantifying the lifetime of phase singularity points representing AF re-entrant patterns. The paper argues that the duration of the observation can affect the likelihood of detecting long vs. short lifetimes and suggests that to minimize the dependency on the observation duration, the individual lifetimes, rather than averages of probability distributions, should be considered.It has been proposed that high dominant frequency and rotor regions play a significant role in perpetuating AF. Van Schie et al. used a specialized multiple-electrode system to perform intraoperative simultaneous unipolar and omnipolar voltage mapping in opposing endocardial and epicardial right atrial surfaces during sinus rhythm. The study found that the low voltage regions frequently appeared exclusively on either one of the surfaces and suggests that the addition of the omnipolar mapping, where far field and directionality effects are minimized, to the unipolar mapping adds fidelity to the localization of low voltage regions.Regions characterized by low voltage activity in atrial mapping are considered to be arrhythmogenic and a target for ablation. Fambuena-Santos et al. used ECGi and a new rotor detection algorithm to map AF in patients that underwent pulmonary vein isolation. They found that the total rotor number was higher in patients with follow-up arrhythmia recurrence than in those that remained in sinus rhythm and in whom the phase singularity point concentration was higher in the pulmonary vein region. The consistency between the findings on re-entrant pattern distribution and the expected mechanisms suggested the technology could offer useful information.The non-invasive electrocardiographic imaging (ECGi) approach is proposed for an effective mapping of AF and ablation guidance but is still a challenging technology. Yadan et al. the authors applied different mode decomposition algorithms on five simulated and two AF patients datasets to rank the accuracy and efficiency of their performance to hopefully improve the solution of the inverse problem in the clinic.Efforts to optimize the inverse problem solution at the center of the ECGi approach by various time-frequency decomposition techniques are presented in the article by Kang He et al. developed a machine learning method for the single-lead monitoring of patients after cardiac surgery and concluded that their method could improve the detection of postoperative AF in those patients. Ah Ran Oh et al. also used a machine learning method in post-operative patients, however with non-cardiac surgery, and found that including the top five variables of age, lung operation, operation duration, history of coronary artery disease, and hypertension results in the area under the receiver operating characteristic curve for postoperative AF of 0.80 that indicates the ability of prediction.Approximately 30% of patients undergoing cardiac surgery develop AF post-operatively and predicting who will develop arrhythmia on an individual basis could guide therapeutic management. McCann et al. to predict catheter ablation outcomes in persistent AF patients. The investigators developed new indices based in part on a principal component analysis to quantify the reconstruction of the full set of the body surface signals with a subset of the signals, as well as a non-dipolar component index. They then associated the levels of those indices with restoring sinus rhythm or recurrence of arrhythmia following single-procedure catheter ablation.Body surface potential maps were processed by Alken et al. analyzed contact force and local impedance in 730 RF applications of a novel open-irrigated single-tip catheter in 20 repeat AF ablation patients. A drop of more than 20 Ω in local impedance following the ablation was considered as an adequate lesion formation and was found to be better predictable by the combined rather than a separated force and baseline impedance quantification.Radiofrequency (RF) catheter ablation to terminate AF is challenging in some, particularly persistent, AF patients, and efforts are ongoing to increase its success rate. Successful catheter-based RF ablation depends on adequate lesion formation. Ogbomo-Harmitt et al. studied the feature attribution of AF data subjected to deep learning algorithms to interpret the results of the algorithms and enhance confidence in the proposed ablation strategy. They used simplified computer models based on patients’ MRI data to suggest that the regions with the most informative features colocalized with pro-arrhythmogenic regions.Machine learning methods have been proposed to improve the guidance of ablation. Dasi et al. performed simulations on a population of human structurally normal atrial computer models that suggest that AF depends on the formation of discordant alternans. Cardioversion using 10 antiarrhythmic drugs applied to those models was found to be optimal when refractoriness was maximized and was predictable with 70% accuracy from either ionic or ECG properties. Machine learning methods are also used in computer simulation studies to better understand the relationships between pharmacological treatments and the characteristics of the underlying atrial tissue. Sanchez de la Nava et al. used artificial intelligence in a computational proof-of-concept study with the ability to predict susceptibility for conduction blocks in fibrotic atrial tissue and antiarrhythmic drug regime. Simulations on a population of simplified 2D atrial models suggest that fibrosis can alter the expected behavior of several commonly used drugs and that the model profile leading to the different effects might be predicted by data analysis using artificial intelligence.In silico studies are also used to interpret and guide pharmacological intervention to terminate AF. Karlsson et al. studied the influence of several β-blockers and calcium channel blockers on the atrio-ventricular node conduction in a cohort of permanent AF patients and found differential delays that could be important in treatment selection. On a related topic, Plappert et al. demonstrated that the incorporation of the effects of the autonomic nervous system on conduction in a mathematical model of the atrio-ventricular node is necessary to replicate ventricular rate changes in clinical tilt test data. Abdollahpur et al. investigated respiratory modulation as a surrogate for the autonomic nervous system modulation of the atrial activity during AF by analysis of the f-wave frequency. Their proposed orthogonal subspace projection approach (In most patients, in addition to efforts to terminate AF, concomitant pharmacological efforts are also made to decrease the ventricular rate  and woulapproach  showed rWe are excited to present a second Research Topic collection of technology-inclined articles describing recent experimental, computational, and clinical studies on AF. The articles ultimately apply to ablation and pharmacological therapies to restore sinus rhythm or control of the ventricular rate and highlight the need for improved comprehensive management of AF and its associated symptoms . We hope


The aim of the study was to expand the current knowledge on the effects of EEG biofeedback training on the reaction time of judo athletes, as well as to develop an optimal EEG training protocol in terms of the number of sessions and their duration that would significantly improve the reaction time of athletes. The study included 24 male athletes from the national team of the Polish Judo Association. The selected group was randomly divided into two subgroups: experimental and control. The study was conducted in four cycles varying in terms of frequency and duration of neurofeedback (NFB) sessions, both in the control and experimental groups. In the experimental group, each training cycle consisted of 15 sessions, followed by a four-week break. The effects of NFB training on the visual reaction time of judo athletes were evaluated using computerized simple and complex reaction time tests along with selected trials of the Vienna Test System (VTS). Following NFB training according to the theta/beta1 protocol, while maintaining appropriate duration and frequency of individual training sessions, statistically significant improvements in reaction times to visual stimuli of athletes, both in simple and complex tasks, were observed in the experimental group. No such changes were found in the control group. The greatest improvement in reaction times was observed in complex tasks, indicating the high effectiveness of EEG biofeedback training in enhancing this ability. Since its inception in the 1960s, the concept of biofeedback has found diverse applications in fields such as psychology, medicine, parapsychology, business, and sports to enhance athletes' performance. One of the widely used biofeedback techniques is EEG biofeedback training , commonly known as neurofeedback (NFB) .NFB represents a more sophisticated form of biofeedback, employing a technological self-regulating stimulation method to restore brain functioning patterns and improve cognitive, emotional, and behavioral performance . The anaNFB utilizes measured changes in brain activation to assist athletes in regulating the activity or power of designated EEG frequency bands, offering them real-time activation information . EEG hasIn sports like judo, where visual attention and its contribution to decision-making and motor response planning are crucial for success, a high level of concentration and the ability to quickly react to visual stimuli are particularly important. Thus, it is recommended to focus on improving these skills in the training process of judokas, enhancing their visual processing mechanisms and response time to stimuli .Reaction time, i.e., the time elapsed from perceiving a stimulus to reacting to it, serves as an indicator for assessing the internal cognitive-motor resources associated with an athlete’s performance. Parsaee et al.’s (2018) and Pourbehbahani et al.’s (2023) studies, which assessed the impact of NFB training on visual and auditory reaction time, revealed that NFB effectively improved brain functions in terms of visual and auditory reaction time.The objective of the present study was twofold: first, to expand the current knowledge on the effectiveness of EEG biofeedback training to improve the reaction time of judo athletes, and second, to develop an optimal EEG training protocol in terms of the number of sessions and their duration to significantly enhance the reaction time of the studied judokas.The study involved 24 male athletes from the national team of the Polish Judo Associationin the southern region of the country, aged between 22 and 25 years. Subsequently, the group was randomly divided into two subgroups: experimental (n = 12) and control (n = 12). All participants received information about the study's objectives and procedures, they were also informed that they could withdraw from the study at any stage. The research was approved by the Bioethics Committee for Scientific Research at the Jerzy Kukuczka Academy of Physical Education, Katowice, Poland and was conducted as part of the grants (N RSA4 04054).The study was conducted in four cycles, with variations in the frequency and duration of NFB sessions for both the control and experimental groups. In the experimental group, each cycle consisted of 15 training sessions, followed by a four-week break, following the modification of Thompson's training . The durThe primary training protocol employed in the experimental group focused on theta/beta1 training, with the objective of improving concentration and attaining a state often referred to as “narrow attention” among athletes. The control group underwent an identical training regimen to the experimental group, with the same cycle, duration, and frequency of NFB training sessions. However, in the control group, instead of implementing the theta/beta1 protocol, an EEG simulation was displayed that was independent of the brain wave patterns generated by athletes.Before initiating the first training cycle and after completing each subsequent one, simple and complex reaction time tests were conducted in both research groups.EEG biofeedback training, also known as NFB training, was conducted using Biograph Infiniti 6.0 software and a 5-channel decoding device (ProComp5). The EEG sensor used in this setup allowed for high-quality signal reception with minimal noise content. The device's quality was confirmed through ISO certification and CE medical certification. Before recording the EEG signal, the impedance levels of the electrodes and interelectrode impedance were checked using a built-in impedance sensor.To initiate the diagnosis and NFB training, the requirement was to achieve an impedance level below 5 kΩ and a difference of no more than 1 kΩ between electrodes. Each training session in the individual cycle began with a 3-min single-channel EEG diagnosis using three reference connections. During this phase, the participant was instructed to perform specific tasks, including sitting with eyes open for one minute, sitting with eyes closed for one minute, and sitting with eyes open while counting backwards by 7 from 100.For the diagnosis, the reference electrode was placed on the left ear lobe, grounded on the right, and the active electrode at point Cz, following the international 10–20 system. During NFB training, the active electrode was placed at point C3, which allowed the main training objective to be achieved. This objective was to shape the ability of athletes to maintain an optimal balance between fast (beta) and slow (theta) waves, which are responsible for achieving a state of concentration and focus.Throughout each NFB session, the percentage of time spent above the threshold was monitored. This measurement served as the primary indicator of the participant's progress and allowed for the optimization of the training difficulty level for each athlete.During NFB training sessions, real-time feedback was provided to athletes based on their brainwave activity. The main focus was on shaping their ability to enhance the balance between beta and theta waves to achieve an optimal state of concentration and focus. The employed software allowed athletes to visualize their brainwave patterns on a computer screen during training.NFB training consisted of multiple cycles, and each cycle comprised several sessions. In the experimental group, each cycle included 15 training sessions, followed by a four-week break, as mentioned earlier. The duration of training sessions varied across successive rounds of the study, with sessions lasting 10 min and 4 min alternately, as per the modification of Dupee's training method. Throughout NFB training, researchers closely monitored the percentage of time that athletes spent above the predetermined threshold for beta and theta waves. This measure served as the primary indicator of their progress and allowed researchers to adjust the difficulty level of training for each individual, ensuring that training was tailored to their specific needs and responses.The goal of NFB training in the experimental group was to increase concentration and achieve what is known as “narrow attention” in athletes. This enhanced the ability to focus and maintain the optimal balance of brainwave activity what could potentially lead to improved athletic performance.In the control group, NFB training sessions followed the same schedule, duration, and frequency as the experimental group. However, instead of using the theta/beta1 training protocol, the control group underwent an EEG simulation that was independent of their actual brainwave patterns. This setup allowed researchers to assess the specific effects of the theta/beta1 protocol used in the experimental group compared to a non-specific EEG simulation.Before commencing the first cycle of sessions and after completing each subsequent one, both research groups underwent simple and complex reaction time tests. These tests were conducted to assess any changes in reaction times and cognitive performance resulting from NFB training in both the experimental and control groups.Overall, EEG biofeedback training with the theta/beta1 protocol aimed to explore the potential benefits of this specific training method for athletes' concentration and focus . The resThe study aimed to investigate the impact of NFB training on the visual reaction time of judo athletes. To assess this, computerized simple and complex reaction time tests were conducted, along with selected trials from the Vienna Test System (VTS). The tests were carried out in the morning, ensuring optimal conditions for concentration during the tasks. Each trial was repeated twice at 5-min intervals, and the better of the two measurements was recorded for subsequent analysis.The computerized simple reaction speed test consisted of athletes pressing a specified key on the keyboard with either their right or left hand as quickly as possible when a bright square appeared on the monitor screen. The complex reaction time task required pressing a key on the keyboard promptly in response to the location of the square that appeared on the screen. Different keys were used for squares in the right or left position and for squares in the central position. In both tests, the signal appeared 10 times, with intervals ranging from 2 to 6 s. The time from the appearance of the stimulus to the key press was measured with high accuracy of 0.001.For the measurement of simple reaction time to visual stimuli, a reaction speed measuring device (RT) component of the VTS was used. The participant's task was to move their hand as quickly as possible from the “rest key” to the “reaction key” when a yellow LED was lit. The mean reaction time in seconds was then calculated based on the data obtained from the tests.Complex reaction time was assessed using a decision-making device (DG) integrated into the VTS. In this trial, athletes were tasked with swiftly pressing the corresponding key based on the LED's color that illuminated when the stimulus was presented. The software recorded both correct and incorrect responses, the average reaction time, and the standard deviation of the mean reaction time. The signal was presented 15 times during this testing phase. By analyzing the results from these computerized tests, researchers sought to determine whether NFB training had any significant effect on the visual reaction time of judo athletes.The first research cycle comprised 15 training sessions, conducted every other day, with each session lasting 10 min. In the second research cycle, the training frequency increased, while the duration of each session decreased. Training sessions were held daily, and each session lasted 4 min. In the third research cycle, training sessions took place daily, yet their duration was increased to 10 min. Finally, the fourth research cycle consisted of 4-min training sessions held every other day. All four research cycles were interspersed with a four-week break.During each training session in all cycles, the percentage of time spent above the threshold was closely monitored. This threshold was adjusted upward for reinforced waves and downward for inhibited waves. Such an adjustment ensured that the level of difficulty of NFB training was optimal and tailored to individual progress.Overall, the study adopted a progressive approach, modifying the frequency and duration of training sessions across different cycles. By varying these factors, the researchers aimed to assess the effectiveness of NFB training and determine the most suitable training protocol for enhancing athletes' cognitive functions, specifically visual reaction time, and potentially improve their overall performance in judo competitions.p > 0.05).Descriptive statistics, including arithmetic means, standard deviations, and coefficients of variation, were calculated. The normality of variable distribution was checked using the Shapiro-Wilk test. Additionally, the Levene's test was applied to assess the homogeneity of variance among the variables and determine appropriate statistical tools for further analysis. The test results indicated that all variables had a normal or close-to-normal distribution  were presented. When significant differences were found, Tukey's post-hoc tests were performed for equal sample sizes (N).To test hypotheses related to differences between the values of individual variables describing intergroup and intragroup relationships, ANOVA was used. The F-statistics and significance levels  and the Excel package (Microsoft Office 13).After conducting individual training cycles using the EEG biofeedback method, statistically significant differences were observed between the control and the experimental group in the results of simple and complex reaction times in selected trials of the VTS  and 2.p < 0.05) revealed differences in the values of the investigated variables of simple and complex reaction speeds in selected trials of the VTS before and after the application of individual training cycles using the EEG biofeedback method in the experimental group  test indicated significant differences in the obtained simple reaction times in selected trials of the VTS between the third and fourth cycles compared to the first cycle of EEG biofeedback training. However, no significant difference was observed between the fourth and second training cycles. It can be clearly stated that significant improvement in simple reaction time occurred after the third and fourth cycles. Significant differences were noted between the examined variables of complex reaction speed in selected trials of the VTS in relation to the experimental group before the individual NFB training cycles. The analysis of results indicates significant linear differences between the recorded complex reaction times in selected trials of the VTS between the third and fourth cycles compared to the first cycle of NFB training. However, no significant difference was found between the third and second cycles or between the first and second training cycles. It can be concluded that significant improvements in complex reaction time occurred after the third training cycle, and especially after the fourth cycle of NFB training  and 7.The introduction of modern arousal management techniques in mental training of athletes, such as EEG biofeedback training, and the development of optimal training protocols to enhance athletes' potential, can be useful tools in the field of sports psychology. Prior research suggests that athletes can acquire the ability to produce and sustain particular neural brain activity patterns linked to improved performance through EEG biofeedback training (Blumenstein and Orbach, 2012, 2012a; The results of the present study clearly demonstrate the positive effects of NFB training on the reaction times of judo athletes. The experimental group, which underwent NFB training according to the theta/beta1 protocol, showed significant improvements in reaction times to visual stimuli, both in simple and complex tasks. On the other hand, no such changes were observed in the control group, which did not receive NFB training. These findings support previous research that has shown the potential benefits of EEG biofeedback in enhancing cognitive-motor processes and improving sports performance (Chung et al., 2021; Our findings indicate that NFB training can be particularly effective in improving complex reaction times, which are crucial in sports like judo where quick decision-making and response planning are essential for success. This improvement in complex tasks highlights the high effectiveness of EEG biofeedback training in enhancing cognitive abilities related to concentration and focus .The study's contribution to the existing literature is valuable as it provides insights into the practical application of EEG biofeedback training in sports performance enhancement. The development of an optimal training protocol based on EEG measurements offers a structured and systematic approach to improving reaction times in athletes. Such information can be beneficial for coaches, trainers, and sports psychologists working with judo athletes or other sports disciplines where quick reactions and focus are crucial for success.However, there are certain limitations of the study to be considered. Firstly, the sample size was relatively small, consisting of 24 male judo athletes from a specific region. A larger and more diverse sample would increase the generalizability of the findings. Additionally, the study focused solely on male athletes. Future studies could include female participants to understand potential gender differences in the response to NFB training.Furthermore, the study did not explore the long-term effects of NFB training beyond the four training cycles. It would be interesting to investigate whether the improvements in reaction times are sustained over time or whether additional training sessions are needed to maintain the obtained benefits.This study provides valuable insights into the effectiveness of EEG biofeedback training in improving the reaction times of judo athletes. The results suggest that NFB training can be a useful tool in sports performance enhancement, particularly for tasks requiring quick reactions and focused attention. Coaches can use this knowledge to design targeted training protocols for athletes, aiming to improve their cognitive-motor processes and achieve better sports results. However, further research with larger and more diverse samples is needed to validate and extend these findings (Chung et al., 2021; Future research in the field of EEG biofeedback training and sports performance could explore several areas of interest. Firstly, as mentioned earlier, investigating the long-term effects of NFB training is essential. A longitudinal study tracking athletes' reaction times over an extended period, even beyond the training cycles used in this study, would provide valuable insights into the sustainability of the obtained improvements. Understanding whether the benefits persist over time or if periodic booster sessions are required for maintenance would help optimize training protocols.Secondly, it would be beneficial to examine the transferability of the improved reaction times to actual sports performance. While NFB training has been proven effective in enhancing cognitive-motor processes, it is essential to determine whether these improvements translate into real-world situations during judo competitions or other sports events. Observing athletes' reactions in live competitions, as well as their success rates in executing specific moves or strategies, would provide a more comprehensive assessment of the training's practical benefits , 2020.Additionally, expanding the scope of the study to include other sports disciplines would be valuable. Different sports require distinct cognitive and motor skills, and NFB training may have varying effects on athletes from different sports backgrounds. Investigating the impact of EEG biofeedback on athletes in various sports, such as team sports like soccer or individual sports like tennis, could lead to a better understanding of its potential applications across different athletic domains.Furthermore, exploring the individual differences in response to NFB training would be worthwhile. Not all athletes may show the same degree of improvement in reaction times after training. Factors such as baseline cognitive abilities, training adherence, and motivation could influence the outcomes. Identifying individual factors that contribute to training success could help tailor NFB protocols to suit each athlete's needs, making NFB training more personalized and effective.In terms of methodology, future studies could consider incorporating control groups that receive other forms of cognitive training or traditional physical training without NFB. Comparing the effects of NFB training to other interventions would help establish its unique contributions and advantages. Additionally, using a double-blind experimental design, where both participants and researchers conducting the tests are unaware of group assignment, would minimize potential biases and enhance the study's internal validity.Finally, advancing the technology used in EEG biofeedback training could improve its efficacy and practicality. Integrating real-time biofeedback into wearable devices or mobile applications would enable athletes to engage in NFB training outside the laboratory setting, making it more accessible and convenient for regular training sessions.In conclusion, the study on the effectiveness of EEG biofeedback training in improving the reaction times of judo athletes has provided valuable insights into the potential benefits of this technique in sports performance enhancement. The results suggest that NFB training can be a useful tool in sports psychology for enhancing cognitive-motor processes, particularly for tasks requiring quick reactions and focused attention. The development of an optimal training protocol based on EEG measurements offers a structured and systematic approach to improve reaction times in athletes.While the findings are promising, further research with larger and more diverse samples is needed to validate and extend these findings. Investigating the long-term effects of NFB training, the transferability of improvements to real-world sports performance, and potential gender differences in the response to training would contribute to a more comprehensive understanding of the technique's benefits. Moreover, exploring individual factors that influence training effectiveness and incorporating control groups with alternative interventions would strengthen the study's conclusions , 2020.Overall, the study underscores the potential of EEG biofeedback training as a valuable addition to the toolkit of sports psychology, providing a means to enhance athletes' cognitive abilities and improve their sports performance. As sports continue to become more competitive, the pursuit of innovative and effective training methods like NFB can give athletes a competitive edge and help them reach their full potential. Coaches and sports psychologists can utilize this knowledge to design tailored training programs that optimize cognitive-motor processes and foster improved athletic performance in various sports disciplines, not just judo. By continuously exploring and refining the application of EEG biofeedback training, sports science can continue to evolve and contribute to the success of athletes at all levels.The results of the study provide valuable insights into the potential benefits of NFB training on cognitive functions, such as visual reaction time, in athletes. It could also contribute to the understanding of how NFB training may be incorporated into athletic training programs to optimize athletes' mental and cognitive abilities, leading to better sports performance. Future studies could build on this research and address any identified limitations to further explore the potential applications of NFB training in sports performance and cognitive enhancement for athletes.


With the rapid ageing of societies in Europe and worldwide, the issues of social functioning and mental well-being of older adults gain importance and call for effective care solutions. Among the non-pharmacological options, modern technologies are a promising direction. The use of humanoid social robots, at least in selected areas of care for community-dwelling older people, is one of the possibilities to cope with both their mental problems and the increasing shortage of qualified caregivers.We thus investigated which prospective areas of care are scored best by older subjects and their professional caregivers.Opinions of older people , living in the community, and their professional caregivers about a robot in care for older adults were collected using the mixed-methodology Users’ Needs, Requirements and Abilities Questionnaire (UNRAQ), after a 90-150 minute interaction with the TIAGo robot .The robot could decrease the sense of loneliness and improve the mood of the elderly person (p<0.01), The robot should detect the owner’s mood (p<0.05), and The robot should accompany the owner in everyday activities (p<0.01).The robot as a companion of an older person was scored better by older adults than caregivers (p<0.01). Similar results were obtained for the statements Our results, reflecting the opinions and preferences of various stakeholders, indicate a high general acceptance of a robot in care for older people. The indication of best-scored areas provides clues for the robot’s designers as well as those involved in the implementation of robotic solutions in care and their introduction into the lives of older adults.None Declared


The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [11C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain.Long-term alteration of dopaminergic neurotransmission is known to modulate the D Thus,  raclopride was markedly reduced upon challenge with unlabeled ligand in both putamen and caudate nucleus when compared to the baseline condition  as an approximation of the unbound and non-displaceable tracer quantity in brain. For the TREMBLE analysis, we computed the equivalent exchangeable quantity (me) from the measured arterial plasma input concentrations. The computed curve of me initially was higher in the challenge condition than at baseline, suggesting a greater exchangeable quantity of [11C] raclopride as a result of displacement by unlabeled raclopride. This phenomenon was not observed with the TEM analysis.The binding curves obtained by the TREMBLE and TEM analyses of this representative subject are shown in me) exceeded that of the baseline condition, after which time the me curves approached similar levels in both conditions  in putamen by TREMBLE and TEM, respectively. As the two models yielded similar reductions of BPND, we asked whether a scalable difference existed between the results of the two methods. We compared the percentage declines in each subject by TREMBLE and TEM  at two occupancy levels in the absence and presence of unlabelled raclopride, we applied Eadie-Hofstee plots to obtain the receptor density, Bmax, and half-saturation constant, KD, as presented in Bmax with significantly higher density in putamen (26:7 ± 11:9 pmol/cm3) than in caudate nucleus (18 ± 8:9 pmol/cm3). In contrast, analysis with TEM yielded no difference of receptor density between the two parts of the striatum. KD in the two brain regions, regardless of analysis method.With the estimates of specific binding  equilibrium after bolus injection of tracer. This conclusion would also apply to to experiments based on bolus-plus-infusion of the tracer, The reason is that the bolus-plus-infusion experiments focus on the establishment of constant concentrations of all tracer molecules in the tissue, rather than on the requirement of constant levels of bound tracer associated with true equilibrium, a goal that is very difficult to reach. A disadvantage of TREMBLE is the requirement for arterial plasma concentration sampling that makes clinical studies labor intensive, but the approach is important to the detection of moderate changes as found especially in neuropsychiatric disorders, for example.


Multilayer graphene has attracted significant attention because its physical properties can be tuned by stacking its layers in a particular configuration. To apply the intriguing properties of multilayer graphene in various optoelectronic or spintronic devices, it is essential to develop a synthetic method that enables the control of the stacking configuration. This review article presents the recent progress in the synthesis of multilayer graphene by chemical vapor deposition (CVD). First, we discuss the CVD of multilayer graphene, utilizing the precipitation or segregation of carbon atoms from metal catalysts with high carbon solubility. Subsequently, we present novel CVD approaches to yield uniform and thickness-controlled multilayer graphene, which goes beyond the conventional precipitation or segregation methods. Finally, we introduce the latest studies on the control of stacking configurations in bilayer graphene during CVD processes. Graphene is of interest owing to its excellent properties such as its thermal conductivity and electron mobility . Th. Th47]. To further improve the uniformity of multilayer graphene grown on a Cu/Ni alloy, the CVD of graphene on a single-crystal Cu/Ni alloy  was inve−1 K−1, comparable to that of mechanically exfoliated bilayer graphene (~2800 W m−1 K−1), demonstrating the high quality of the synthesized AB-stacked bilayer graphene. In addition, the thickness of the graphene was successfully controlled by tuning the content of Ni in the alloy catalyst.In 2020, Ruoff et al. prepared an extremely large single-crystal Cu/Ni(111) foil as a catalyst for large-area uniform multilayer graphene . First, The graphene growth on the Cu surface is surface mediated, and thus uniform graphene is obtained on the Cu surface. Therefore, uniform multilayer graphene can be obtained once the self-limiting characteristics of the Cu surface are eliminated.4 gases into the inside of Cu pockets is limited, the growth rate of graphene on the inside surface of Cu pockets was considerably lower than that on the outside of the Cu pockets. Therefore, the inside Cu surface can be still open to the adsorption and dehydrogenation of CH4 molecules whereas graphene fully covers the outside Cu surface of the Cu pockets. This leads to asymmetry in the carbon concentration inside the bulk Cu: the carbon concentration is higher near the inner Cu surface. As a result, there is a bulk diffusion of C atoms from the inside surface to the outside surface of Cu pockets, and multilayer graphene can form on the outside even after the monolayer graphene has fully covered the outside Cu surface  have been investigated . The for4 cm2 V−1 s−1 at room temperature . I. I64]. IIn addition to the growth conditions, the crystallographic orientation of the Cu surface is an important factor that determines the stacking orientation of BLG. Cho et al., compared the stacking orientations of BLGs grown on atomically flat (Cu(111)) and stepped Cu surfaces (Cu (311)/Cu(110)) when the other growth conditions were the same for both cases . Bernal-In this review, we covered the CVD method for the synthesis of multilayer graphene, discussing the growth mechanism of graphene on Ni and Cu catalysts and the challenges associated with the provision of uniformity and the control of thickness also see . We highAlthough significant progress has been achieved in the CVD of multilayer graphene, further studies are required to fully understand its growth mechanism and achieve precise control of the thickness and uniformity. An in-depth understanding of the growth mechanism of bilayers is crucial to improve the quality of bilayers, particularly in terms of stacking orientations. Additionally, the production of high-quality graphene at low temperatures is essential for practical applications. Moreover, the development of a catalyst-free CVD method for multilayer graphene synthesis is desirable. Such an approach would eliminate the need for costly catalyst materials and simplify the overall process, including the transfer step, thus reducing production costs.


Although the percentage of women choosing Science, Technology, Engineering, and Mathematics (STEM) fields changes over time, the positions occupied by women within them still tend to be more junior compared to those of men. In this context, each initiative to raise community awareness of this disparity no matter how small, will likely make a difference for the next generations.After decades of invisibilization, it is essential to acknowledge society’s past failures in recognizing women’s contributions to STEM. Biases that are difficult to remove from societal thinking and stereotypes often discourage women from following a career track in science-related fields; the field of Molecular Modeling is especially affected by this and is highly male-dominated.In the study by Frontiers in Molecular Biosciences—Biological Modeling and Simulation had the ambition of contributing to the awareness of gender equality through this Research Topic. Here, we showcase the success of several female researchers at any step in their scientific careers in producing valuable research findings in the field of Modeling and Simulations. It is relevant to note that among the eight contributions  accepted for publication in this Research Topic, several different domains were covered: quantum mechanical models, molecular dynamics simulations, approaches for the integration of experimental biophysical data and molecular modeling, along methods based on network theory to understand protein structures. The articles covered molecular modeling applications across various fields, such as nanoparticles, sensors, proteins, DNA lesions, and metal clusters, attesting to the multidisciplinary nature of these methodologies.Martin et al.) focused on the dynamic nature of protein-protein interfaces to provide a complete picture of protein-protein complexes, considering that they visit distinct interface substates beyond a specific interface size. They studied the interfaces using molecular dynamics (MD) simulations, highlighting the crucial role of water in the binding and strength of the interactions in terms of the number of released water molecules and the number of contacts mediated by water molecules at the interface. The number of water-mediated contacts observed in the simulations of the complexes suggests that in protein-protein docking, the presence of water molecules at the interface may open a new route to predict them.  investigated the possible structural changes of a surface-active intrinsically disordered protein (IDP) induced by adsorption while evaluating seven different force field and water model combinations and comparing them with experiments. They demonstrated the substantial influence of the choice of force field and water model in MD simulations when studying IDPs. proposed can be applied to single-particle XFEL diffraction patterns to obtain plausible 3D structural models by optimizing a known structure to maximize the similarity between the target XFEL and the simulated diffraction patterns from candidate models using Monte Carlo (MC) sampling. The proposed method can serve as an alternative approach for studying the dynamics/conformational transitions of biomolecules in XFEL experiments to seek initial models for 3D reconstruction algorithms and structure determination via 3D reconstruction from a large dataset.Owing to their low diffraction power and the complexity of sample delivery, X-ray free-electron laser (XFEL) experiments and data analyses are challenging for biological systems. The hybrid method  investigated the molecular mechanism of PCBP1 to recognize a damaged RNA strand using all-atom MD simulations. Their results highlighted an allosteric mechanism by comparing RNA and protein behaviors for sequences with six different damage profiles. The GCAT network tool developed by  considers the asymmetry of mutational changes and allows visualization of the mutational influences of amino acid positions on one another. It was built by comparing the position neighborhoods in the amino acid network of the wild-type and mutant forms of the proteins. GCAT opens up several perspectives for improving the understanding of protein variants, and their role in disease onset and drug treatment efficiency by addressing how positions cope with mutations, how to classify position tolerances, and the need for corrections.8-Oxoguanine oxidatively generated lesions on RNA strands constitute a hallmark marker of oxidative stress in the cell, and recognition of these damaged RNA strands by poly-C binding protein 1 (PCBP1) triggers a signaling pathway that leads to cell apoptosis. The study by  have integrated computational and experimental designs of a rationally designed gold-functionalized biosensor capable of capturing a target protein using a biotin-streptavidin pair as a proof-of-concept. They employed atomistic simulations at multiple levels of theory, combining docking by Brownian dynamics and kinetics and classical MD. They provided guidelines on how to exploit the microscopic parameters obtained from simulations to guide the design of biosensors with enhanced sensitivity. The study by  addressed the structure of the active site of [ZnFe] sulerythrin (SulE) isolated from a strictly aerobic archaeon. The function of SulE was investigated using a combination of structural and electronic analyses based on quantum mechanical (QM) calculations. Density functional theory (DFT) computational investigations of the active site geometry of [ZnFe] SulE based on available structural data shed light on the assumed electronic and structural states of the enzyme. discusses the exploitation of colloid science concepts to better understand and predict the phase behavior of functionalized nanoparticles and/or protein–nanoparticle mixtures. They perspectively revisit the phase behavior of isotropic potentials with increasing complexity, illustrating how the additional phases appear as specific features are added to the potential.A review article by (


Trypanosoma brucei gambiense and Trypanosoma brucei rhodesienese. However, the drug was politically instrumentalized by the German government in the 1920s in an attempt to regain possession of its former African colonies lost after the First World War. For this reason, the formula of suramin was kept secret for more than 10 years. Eventually, the French pharmacist Ernest Fourneau uncovered the chemical structure of suramin by reverse engineering and published the formula of the drug in 1924. During the Nazi period, suramin became the subject of colonial revisionism, and the development of the drug was portrayed in books and films to promote national socialist propaganda. Ever since its discovery, suramin has also been tested for bioactivity against numerous other infections and diseases. However, sleeping sickness caused by Trypanosoma brucei rhodesiense is the only human disease for which treatment with suramin is currently approved.Suramin was the first drug developed using the approach of medicinal chemistry by the German Bayer company in the 1910s for the treatment of human African sleeping sickness caused by the two subspecies  Trypanosoma brucei gambiense and Trypanosoma brucei rhodesienseT. b. rhodesiense (Steverding T. brucei SRA+ (Steverding and Tyler Trypanosoma evansi) and dourine (Trypanosoma equiperdum) in camels and horses  for theAs the original company name suggests (Farbenfabriken means dyestuff factories), Bayer was initially an enterprise developing and manufacturing synthetic dyes for the textile industry Bayer . Based oSoon after Bayer 205 was shown to be very effective in eliminating trypanosomes from the blood of infected animals, the first therapeutic attempt was carried out in 1921 on two returning Europeans who contracted sleeping sickness during their stay in southern Africa Mayer . As bothRenaming Bayer 205 with the patriotic name “Germanin” was an attempt by the Germans to politically instrumentalize the drug with a view to repossessing former colonies in Africa Jacobi . In accoAlso, any anticipated commercial success with Germanin was shattered in 1924 when the French pharmacist Ernest Fourneau (1872–1949) Fig.  publisheThose who thought that the disclosure of suramin’s formula and Germany’s renunciation of its former colonies would end the discussion of colonial revisionism in Germany would be proven wrong. When the Nazis came to power in 1933, Germanin was used to illustrate the success of German research and to again promote colonial-revisionist efforts. For example, no opportunity was missed to discredit British and French sleeping sickness control measures and the view was expressed that Germany had demonstrated considerable proficiency in fighting tropical diseases Jacobi . HoweverGermanin - Geschichte einer deutschen Großtat (Eng. transl.: Germanin - Story of a German feat)  published the book t) Unger . AlthougGermanin - Die Geschichte einer kolonialen Tat  and directed by Max W. Kimmich (1893–1980) was premiered at the Hamburg UFA-Palast on the 15th of May 1943 (Eckart The political instrumentalization of Germanin peaked in the filming of Unger’s book. The 92-min-long feature film entitled 3 Eckart ]. The pl3 Eckart . However3 Eckart . Since tOnchocerca volvulus (Wiedemar et al. Even before the formula of suramin was disclosed, the effect of the drug against other diseases was tested. Already in November/December 1922, several individuals suffering from kala-azar were treated with suramin although the drug turned out to be ineffective in curing the patients Napier . Since tThe political instrumentalization of suramin and the non-disclosure of its formula had far-reaching consequences for both the German government at the time and the Bayer company. The government of the Weimar Republic had to acknowledge once and for all the loss of its former colonies. The publication of suramin’s formula destroyed Bayer’s hope for financial profit from the drug. Thus, the non-patenting and non-disclosure of the structure of suramin backfired for Bayer. Because of this, the disclosure of the structures of drugs subsequently became standard practice in pharmaceutical patents Sneader .


Moyamoya disease (MMD) is a rare idiopathic progressive vaso-occlusive disease characterized by irreversible vascular occlusion and collateral development of distal internal carotid arteries. Initially perceived as an exclusive entity to the East Asian population, the disease is now being reported globally, affecting individuals of diverse ethnicities. We present a case of a 55-year-old African American male patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and a prior history of cryptococcal meningitis presenting to the emergency department with recurrent episodic headaches, which was refractory to routine medical therapy. Neuroimaging with computed tomography angiogram of the head and neck and magnetic resonance imaging of the brain led to the subsequent diagnosis of moyamoya syndrome (MMS). To our knowledge, MMS is uncommon in adult HIV/AIDS patients. It is crucial that clinicians are aware of the disease progression. For effective recognition and prevention of the condition, it is of utmost importance that clinicians possess a comprehensive understanding of the disease and its clinical manifestations. Moyamoya disease (MMD) is a gradual narrowing and blockage of the terminal portions of the bilateral internal carotid arteries and their proximal branches, known as steno-occlusive vasculopathy. As a result of this occlusion, collateral vessels develop to compensate for the arterial occlusion ,2. MoyamA 55-year-old man with a past medical history of HIV/acquired immunodeficiency syndrome (AIDS) was admitted to the emergency department in 2017 for an intractable headache. The CT and MRI of the brain showed chronic lacunar infarct in the basal ganglia without acute abnormality. CT imaging performed at a separate emergency visit for the reported headache was unremarkable. A year after his initial presentation, the patient presented to the emergency department with a headache. The brain MRI showed nodular enhancement of the ventricular ependyma along the anterior inferior surface of the lateral ventricles, which extended from the frontal horns to the trigones and temporal horns. On post-contrast scans, choroid plexuses within the atria and occipital horns were enlarged and heterogeneously enhanced. Bilateral foci of clustered ring enhancements were most pronounced in the trigones of the lateral ventricles Figure . IntervaFour years later, the patient presented to the emergency department again with a complaint of headache. CT angiography revealed marked attenuation of the terminus of the right supraclinoid internal carotid artery and near occlusion of the right middle cerebral artery Figure .Brain MRI demonstrated diminished flow void of the right middle cerebral artery, representing the vascular occlusion and collateral formation Figure . T2 fluiThe most recent CT angiography five years later showed attenuation to near occlusion of the left V4 segment of the vertebral artery Figure  and compMMD is a chronic cerebrovascular condition of unknown cause, marked by the narrowing and blockage of the intracranial blood vessels. This condition is accompanied by the formation of new irregular collateral blood vessels as a compensatory response. In most cases, moyamoya disease appears bilaterally. However, moyamoya may initially occur unilaterally and proceed gradually into bilateral changes ,2. AccorMoyamoya disease primarily affects the anterior circulation in the brain. However, the disease affects the posterior circulation in about 30% of the cases . The mosGenerally, MMD was commonly linked to Asian people, but currently, it has been recognized to occur in individuals from various ethnicities around the World, including European and North American populations. MMD predominantly impacts individuals of Asian descent, especially Japanese, Korean, Chinese, and Indians, and the incidence is approximately 0.54/100,000/year, with a prevalence of 6/100,000 . In the Imaging plays a crucial role in the diagnosis of moyamoya vasculopathy. It is characterized by stenosis of the distal internal carotid arteries (ICAs) along with their proximal branches. The presence of moyamoya vessels and collateral circulation indicates neovascularization. Posterior vascular involvement is seen in one-third of cases and is likely an extension of the stenotic process from the anterior circulation. The occlusive lesions in the posterior circulation show steady progression like the pattern seen in the anterior circulation. Occlusion of ICAs, basilar and vertebral arteries exist in our case, which may have the same etiology .Determining the actual occurrence of cerebrovascular complications in AIDS is challenging to establish due to the frequent association between HIV and opportunistic infections. Morgello et al. previously described the association between moyamoya and HIV/AIDS in adults. They documented a rare case of quaternary neurosyphilis in a 22-year-old Haitian man, which resulted in MMS . Our casThe mechanisms underlying this association are not well understood. It has been suggested that HIV infection or complications of opportunistic infections result in postinfectious central nervous system (CNS) vasculitis. The pathogenesis of CNS vasculitis in HIV/AIDS involves various mechanisms, such as infection of endothelial cells by HIV or other opportunistic infections, immune complex deposition and dysregulation of cytokines, and attaching syntax. Alterations of the vascular systems and vasospasm result in ischemia and thrombosis leading to arterial narrowing of the supraclinoid portion of the internal carotid arteries with vessel wall irregularities, focal dilations, and thrombo-occlusions -13. HoweIn summary, further research is required to explore the pathogenesis of moyamoya syndrome in the context of HIV infection. It is plausible that opportunistic infections linked to HIV might be associated with the pathological changes that give rise to cerebrovascular disease and the development of the moyamoya phenomenon. Gaining a deeper understanding of these connections can offer valuable insight into the complex interplay between HIV and MMS, potentially leading to advancements in diagnosis and treatment strategies for affected individuals. We describe a case of MMS in an HIV patient who presented several years after cryptococcal meningitis. There could be an association between cryptococcal meningitis and the later development of MMS. This case highlights uncommon involvement of the anterior and progressive involvement of the posterior artery system, which is considered as the whole cerebral artery-involved type MMS. Furthermore, our case report emphasizes the infrequent occurrence of moyamoya syndrome in the African-American population and highlights the significance of employing CT angiography as a valuable diagnostic modality for its detection. To our knowledge, there is no reported case of MMS in an HIV patient with a history of post cryptococcal meningitis and subsequent occlusion of the whole cerebral artery. Awareness of the presentation and evolution of MMS in HIV patients is important to permit early intervention and improve outcomes.


Recreational sports are commonly recommended for their health-enhancing effects. But broadening the perspective on planetary health raises the question of how they impact the environment. While there is a body of evidence on the impacts of professional sports on planetary health, there is currently a lack of studies investigating the sustainability of grassroots level sports, in particular team sports in recreational leagues. This study set out to explore travel patterns in different recreational leagues in the sports of football and handball in Germany.We derived data including club location and game schedules for amateur football and handball teams in the region of Erlangen, Germany, from official websites of sport federations. Using google maps, we calculated the travel distances for every match-up in season 2022/23 and highlighted the distribution of teams in divisions by mapping.Even on a low recreational level, significant travel distances are accrued by teams over a season. In general, playing in a more competitive league results in longer travel distances for football teams. On average, women teams cover longer travel distances compared to men’s teams. Playing handball results in more travel compared to playing football. The current set-up of divisions can be improved to limit travel distances.Despite some limitations , this investigation sheds light on the environmental impact of recreational league play. The sheer number of sports teams suggests the importance of investigating recreational league play and supporting sport federations to optimize game schedules to limit travel emissions.The study was not funded.


In 2018, within the Horizon 2020 program, RECOVER-E project activities were initiated in Montenegro. During the years 2019 and 2020 Community mental health team (CMHT) within the Special Psychiatric Hospital Kotor was established. This team became responsible for management of treatment of a group of users with severe mental health illnesses, based on the principles of „Flexible Assertive Community Treatment (FACT – A Dutch model). Objectives: The main objective of this research was to establish whether there were substantial differences regarding the use of seclusions, restraints and forced medication during the hospital readmissions in the group of patients treated by the CMHT, compared to usual mental health care in Montenegro.A sample of 202 users of mental health services from Kotor and surrounding municipalities were recruited. Patients were randomized into two similar-sized groups - intervention group, whose treatment was managed by the multidisciplinary CMHT, and control group where treatment as usual was continued .To estimate and follow-up the frequency of application of coercive measures in this research, hospital documentation was used.Patients in the intervention group had statistically significant less coercive intervention  during the study. There were no significant differences in the number of hospital days and readmission rates.This study showed that CMHT care could reduce some of the coercive measures during the treatment of severe mental illnesses.None Declared


Aim: To evaluate the impression defects and compare the dimensional accuracy of three different impression techniques  for fixed partial dentures using a digital intraoral scanner in the anterior maxillary region.Materials and methods: Thirty subjects, above the age of 18 years with maxillary central/lateral incisor requiring fixed prostheses were selected according to the inclusion and exclusion criteria. The impressions were rated and evaluated using Heine C2.3K Binocular loupes . An intraoral scanner and digital vernier calipers were used to study and compare the dimensional accuracy of all three impression techniques. Results: Statistical analysis using the chi-square test revealed that the single-step double mix technique showed the least number of defects (40%), followed by the two-step without spacer (56.7%) and then the two-step with spacer (80%) impression techniques. Using Kruskal Wallis and Mann Whitney U test for dimensional accuracy, it was found that the two-step with spacer impression technique was closer to the control group  followed by the two-step without spacer and then the single-step double mix impression techniques.Conclusion: All three impression techniques showed the presence of impression defects, mainly voids and bubbles. The single-step double mix and two-step without spacer techniques had more favourable outcomes compared to the two-step with spacer impression technique. The two-step with spacer impression technique was dimensionally more accurate compared to the two-step without spacer and single-step double mix techniques for fixed partial dentures. The most common treatment modality in replacement of a missing tooth structure or teeth is fabrication of a fixed prosthesis . PreciseThe journey towards successful restoration begins with making accurate impressions . With prThe accuracy and dimensional stability of impression are in turn dependent upon impression materials and techniques. The fit of the final restoration is thus affected by the choice of impression technique selected for making an impression . The impFixed partial denture (FPD) impressions can be made with different techniques that are available which include the single-step technique , double-step technique , monophase technique  and single copper band technique . InaccurAmong the studies done on dimensional accuracy of fixed partial denture impressions, it was observed that with the improvement of impression materials, the impression technique used rather than the material itself has a greater influence on the dimensional accuracy. There are still many controversies that exist despite several studies on the accuracy of impression materials and/or impression techniques . ClinicaHence, this study was planned to compare both, impression defects and dimensional accuracy by three different impression techniques in fixed partial dentures.The present in vivo study was conducted in the Department of Prosthodontics and Crown & Bridge, Career Post Graduate Institute of Dental Sciences and Hospital, Lucknow. The study proceeded after acquiring the necessary approval from the ethical committee of the institution (CPGIDSH/22/304). Thirty subjects, irrespective of male or female, were selected among the patients coming for dental treatment in the Department of Prosthodontics and Crown & Bridge, above the age of 18 years with clinically and radiographically healthy endodontic abutment tooth requiring fixed prosthesis in maxillary central/lateral incisor. Subjects with gingival recession, anterior malocclusion, crowding, rotation, diastema, attachment loss and clinical mobility on the abutment teeth were not included in the study. After explaining the detailed procedure of treatment, written consent was taken from each subject in his/her own language.Tooth preparation, followed by gingival retraction Figure  using a For standardization of amount of impression material used and accurate placement of trays after loading of impression material, three custom trays with a spacer of 4 mm for each subject were fabricated with tissue stops (3x3 mm) over posterior sides on both sides of the arch and in the incisor area. On the side where the prepared tooth was situated, the stop was cut distal to the preparation . For theAll three impressions were also visually examined with the help of Heine C2.3K headband binocular loupes  for impression defects like voids, bubbles, tears and pull defects along with the location  for obtaining maximum accuracy, and the die stone casts obtained using the three techniques  were compared with the measurements of the control group. On the digital intraoral scan, three reference points, A, B and C, were selected where point A represented the mesioincisal edge of maxillary central/lateral incisor and points B and C represented the canine tips of the right and left cuspids, respectively. The distance between these three reference points of the intraoral scan was measured and compared with the measurements obtained by digital vernier caliper  on the die stone models of the three impressions. The distances were measured as shown in Figure The same three reference points  for each impression technique as the control group were considered on the die stone model. The distances on the casts were measured using a digital vernier caliper (Zhart) Figure . On evaluation of dimensional accuracy of Subgroups Ib, Ic and Id with Subgroup Ia (Control) by using Mann Whitney U statistical test, it was found that the mean value of distances AB, AC and BC of Subgroup Id was closer to Subgroup Ia Table .Comparison among the three subgroups showed significant results in the mean of distance AB (P <0.001) and insignificant results in the mean of distance AC (P = 0.006) and BC (P = 0.66) for all the three subgroups in which the mean value of Subgroup Id was closer to Subgroup Ia followed by Subgroups Ic and Ib Table . On evaluation of impression defects for Subgroups Ib, Ic and Id, it was found that voids and bubbles were the majority of defects seen in all the subgroups. Whereas on comparison, with the help of Chi square statistical analysis test, highly statistically significant results were found (P <0.001) in which Subgroup Ib showed the least number of defects and Subgroup Id with maximum number of defects were observed Table .The fabrication of a successful prosthesis for fixed partial dentures begins with the precise replication of dental and dentoalveolar structures during the impression-making procedure. Apart from the selection of appropriate impression material, certain other factors like tray selection, tray adhesive, and impression technique also play a crucial role in reproducing accurate and dimensionally stable impressions .Among the different types of elastomeric impression materials that are available, addition silicones, commonly known as polyvinylsiloxane, are widely being used in prosthetic dentistry. PVS qualities like having excellent mechanical and physical properties, excellent dimensional stability, ease of manipulation, best elastic recovery with no by-product on polymerization, facilitating pouring of impression at the convenience of the operator and allowing to make a second pour when required have made its use extremely popular in the recent practice. The advantage of the available auto mix system in these materials over hand mixing leads to less number of defects like voids, bubbles, and pull defects that might occur during the process of impression making thereby affecting the dimensional accuracy .There have been several discussions among authors regarding the most critical factor affecting dimensional accuracy. According to Hung et al. , the choIn the current study, only maxillary central/lateral incisors were selected for all subjects as these teeth are less prone to wear and tear with advanced age and can be easily scanned intraorally with intraoral scanner as compared to the remaining teeth . DigitalThe results found in this study were in agreement with studies conducted by Caputi et al. , Nissan On the other hand, in the two-step impression technique with or without spacer, the finish lines of the prepared teeth are recorded with the light body material resulting in better detail reproduction. The possible reason mainly lies in the ability to control the wash bulk of the impression thereby resulting in accurate casts which is not possible in the case of the single-step double mix technique. Also, after the putty has polymerized, further contraction of the light body impression material leads to only minimal dimensional changes .The selection of an appropriate impression tray is one of the critical variables in the choice of impression techniques to be used . In thisUniformity of the wash space also plays a crucial role in determining the dimensional accuracy of an impression . In the The findings in our study showed that the two-step impression technique with spacer was more dimensionally accurate than the two-step impression technique without spacer and the single-step double mix technique. This was in contraindication to studies conducted by Luthardt et al.  and PandStudies conducted by Hung et al. , Idris eA study by Idris et al. for evaluation of impression defects revealed that bubbles are the most common defects that are seen in the single-step impression technique which can be reduced by using the two-step technique for impression making . The finFurther clinical studies using different impression materials, impression techniques, single and multiple abutment teeth, evaluators should be considered with a larger sample size for the complete clinical assessment of impression defects seen in PVS impression materials. Many in vitro studies have been done to determine the dimensionally accurate impression technique but there are hardly any in vivo studies that can prove the same. Due to the very limited literature available, there is a need for further in vivo studies to be conducted in order to support the findings as seen in the present study. Also, more research needs to be done on the advancements in impression techniques that can be used for impressions in fixed partial dentures.Limitations of the studyThe potential limitations of this study could be that the subjects were confined to a limited area of the dentition, the dimensional accuracy and impression defects were noted for only one prepared tooth, mandibular arch was not taken into account, only three impression techniques were taken into consideration in this study and only one brand of addition silicone impression material was considered.Within the limitations of this study, the following conclusions were drawn: On evaluation of dimensional accuracy of single-step double mix, two-step without spacer and two-step with spacer, the mean value of two-step with spacer was found to be closer to digital intraoral scanner (Control). Two-step impression technique with spacer was dimensionally more accurate when compared to two-step technique without spacer and single-step double mix technique. Voids and bubbles were the most commonly seen impression defects in all three impression techniques. Single-step double mix technique showed the least number of impression defects followed by two-step without spacer and two-step with spacer.