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PRE ACT is an EU funded project that aims to predict the risk of radiotherapy side effects, including arm lymphedema in breast cancer patients based on 4 multicenter international studies CANTO, HYPOG-01 and REQUITE. Because of inter-investigators variability and clinical practice diversity across different centers and cohorts, manual contours are not homogeneous enough to extract necessary features to train the predictive model. The aim of this study is to conduct qualitative and comparative evaluation of the automatic and manual contours to showcase the reliability of the former. We have generated Organ-at-Risk (OAR) contours with Annotate module from ART-Plan (from TheraPanacea) for six crucial OARs for dose planning of breast cancer loco regional radiotherapy, i.e. esophagus, thyroid, heart, ipsilateral lung, ipsilateral humeral head and contralateral breast. For this evaluation, four independent international radiation oncologists have been presented blindly with both automatic and manual contours from a randomly selected subset of left and right breast cancer patients from the PRE ACT dataset (7052 patients). 10 automatic and manual cases were presented across two sessions, with a washout of a minimum of 48 hours. Rating of the contours followed an A-B-C grid, with A for satisfactory contours, B requiring minor changes, and C needing major changes or redoing. A and B contours were estimated as acceptable, therefore ratings of A and B contours define the acceptance rate for each organ. Average qualitative evaluations are presented in table 1. Automatic contours acceptance ranges from 92 to 100%, whilst manual contours acceptance ranges from 72% to 100%. Inter-expert agreement varies a lot across organs. The lowest inter-expert agreement was obtained for humeral head and heart (45 % for both) for automatic contours and thyroid for manual contours (38,3%). The highest inter-expert agreement was for esophagus and left breast (68.3%) for automatic contours and left breast for manual contours (66.7%). These values are averaged across 4 experts. With this study, we demonstrate that automatic contouring is an excellent and reliable tool to obtain segmentation of OARs with a robust a homogeneous clinical acceptability across diverse cohorts, with many applications to clinical trials. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most common and malignant primary tumor of the central nervous system. Disease recurrence occurs shortly after initial treatment, potentially overlapping with the period between surgery and radiotherapy initiation. This complicates tumor target identification, leading to tedious and variable contouring of the Gross Tumor Volume (GTV) for radiotherapy planning. Hence, the development of efficient automatic segmentation of GBM to improve reproducibility and gain time is an important challenge in the field. In this study, we present an auto-segmentation model GTV in GB undergoing biopsy, evaluating its ability to generate clinically valid contours to address these challenges. We employed the UNet architecture to develop a tumor segmentation model, trained and tested on T1 contrast-enhanced MRI images from a multicentric dataset comprising N = 1100 patients for training and N = 275 for testing on biopsy patients. Trained radiation oncologists validated enhancing tumor and necrotic regions within the dataset, combined to form a clinical pre-radiotherapy GTV. Evaluation of automatic versus manual contours' similarities on the test dataset using Dice similarity coefficient (DSC) and Hausdorff distance (HD95) guided the selection of a qualitative evaluation subset of 24 cases. This subset testing dataset comprised 12 automatic contours and 12 manual contours that were presented for a blinded review to three radiation oncologists. Contours were rated on an A-B-C grid, with A for satisfactory, B for minor changes, and C for major changes. A and B ratings were considered acceptable, defining the acceptance rate for each organ. Automatic contours achieved an average DSC of 0.90, and an average HD95 of 7.3mm compared to manual contours across all test datasets. Qualitative evaluation on subset test dataset results is summarized in table 1. Average ratings across all experts show no difference in A+B ratings between automatic and manual contours. Similarly, inter-expert agreements were comparable between automatic and manual contours; for automatic contours, experts agreed on the rating attributed to 33% of contours (4/12 cases) whilst they agreed on 42% of manual contours (5/12) cases. Table 1. Qualitative evaluation of N = 12 automatic contours and N = 12 manual contours on pre-operative GBM cases. In conclusion, our results indicate that the automatic contouring approach demonstrates comparable qualitative performance to manual delineation, as evidenced by the agreement in A+B ratings among experts and the similar levels of inter-expert consensus between automatic and manual contours. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes., Methods: 40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test., Results: Within our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data., Conclusion: WMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Dentists must be prepared to manage medical emergencies, which are arisen during dental practice together with the increase of age population and medically compromised patients. This study aims at assessing the occurrence of medical emergencies in a cohort of Italian dentists, to ascertain their level of confidence in the management of these conditions, also based on their educational training and type of medical graduation, and, finally, to know their educational needs, in order to plan appropriate institutional interventions for specific training., Methods: A national-based cross-sectional study was carried out by means of an online survey sent to all dentists working in Italy., Results: The survey included 6818 questionnaires. Most of the respondents (n = 4443; 65.2%) reported the occurrence of at least one medical emergency during their professional life. The events rarely resulted in death as declared by only 62 (0.9%) of respondents. The commonest medical emergency was the vasovagal syndrome. Most medical emergencies occurred during the dental procedure (n = 4883; 71.6%). An average degree of satisfaction about the ability to diagnose and manage medical emergencies was reported by most of respondents, with high level of confidence in treating vasovagal syndrome, while a lack in preparedness about the management of myocardial infarction or transient ischemic attack (TIA) and stroke. Medical doctors were more confident in managing the emergencies than dentistry graduates (p < .01). Considering the educational needs, almost all of participants (n = 6721; 98.6%) declared the need to improve their training and expressed their interest in theoretical-practical institutional courses as well as in the establishment of an official national register for medical emergencies occurred in dental practice., Conclusions: Medical emergencies are not negligible and the dentist should receive adequate training and continuing education to be updated and ready for their correct management., Clinical Significance: The dentist should be ready to deal with medical emergencies and provide first aid to the patient. The dentist is not always prepared to manage the most complex emergencies; therefore, there is the need to organize post-graduate courses and to set up an emergency register., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Introduction: Difficulties faced while walking are common symptoms after stroke, significantly reducing the quality of life. Walking recovery is therefore one of the main priorities of rehabilitation. Wearable powered exoskeletons have been developed to provide lower limb assistance and enable training for persons with gait impairments by using typical physiological movement patterns. Exoskeletons were originally designed for individuals without any walking capacities, such as subjects with complete spinal cord injuries. Recent systematic reviews suggested that lower limb exoskeletons could be valid tools to restore independent walking in subjects with residual motor function, such as persons post-stroke. To ensure that devices meet end-user needs, it is important to understand and incorporate their perspectives. However, only a limited number of studies have followed such an approach in the post-stroke population., Methods: The aim of the study was to identify the end-users needs and to develop a user-centered-based control system for the TWIN lower limb exoskeleton to provide post-stroke rehabilitation. We thus describe the development and validation, by clinical experts, of TWIN-Acta: a novel control suite for TWIN, specifically designed for persons post-stroke. We detailed the conceived control strategy and developmental phases, and reported evaluation sessions performed on healthy clinical experts and people post-stroke to evaluate TWIN-Acta usability, acceptability, and barriers to usage. At each developmental stage, the clinical experts received a one-day training on the TWIN exoskeleton equipped with the TWIN-Acta control suite. Data on usability, acceptability, and limitations to system usage were collected through questionnaires and semi-structured interviews., Results: The system received overall good usability and acceptability ratings and resulted in a well-conceived and safe approach. All experts gave excellent ratings regarding the possibility of modulating the assistance provided by the exoskeleton during the movement execution and concluded that the TWIN-Acta would be useful in gait rehabilitation for persons post-stroke. The main limit was the low level of system learnability, attributable to the short-time of usage. This issue can be minimized with prolonged training and must be taken into consideration when planning rehabilitation., Discussion: This study showed the potential of the novel control suite TWIN-Acta for gait rehabilitation and efficacy studies are the next step in its evaluation process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Semprini, Lencioni, Hinterlang, Vassallo, Scarpetta, Maludrottu, Iandolo, Carè, Laffranchi, Chiappalone, Ferrarin, De Michieli and Jonsdottir.)

Activity dependent stimulation (ADS) is a closed loop stimulation technique whose neurophysiological effects have not been deeply investigated. Here we explored how Local field Potentials (LFP) are impacted by a focal ischemic lesion and, subsequently, by ADS treatment. Intracortical microelectrode arrays were implanted in the rostral forelimb area (RFA) and in the primary somatosensory area (S1) of anaesthetized rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. The lesion induced an acute depressive trend in LFP power in RFA (evaluated in 6 bands of interest: Delta (1-4Hz), Theta (4-8Hz), Alpha (8-11Hz), Beta (11-30Hz), LowGamma (30-55Hz) and HighGamma (55-80)) followed by a noticeable significant rebound in both areas. Applying ADS induced an overall decrease of power. The lesion impacted the connectivity in a frequency specific manner, resulting in widespread increase in connectivity in Delta both between and within areas. Two hours after the lesion, without stimulation, correlated activity between areas increased in Beta and Gamma. After stimulation, inter-area connectivity increased in Delta, Theta and Alpha, while considerably dropping within RFA in highGamma. By computing phase-amplitude coupling, we found that the lesion produced an incremental increase in the coupling between (Theta) Alpha phase and (lowGamma) highGamma amplitude within RFA, while S1 had a more generalized increase. Likewise, coupling between Theta phase and lowGamma/highGamma amplitudes increased between areas after lesion. ADS induced a similar increase, but greater in magnitude both within and between RFA and S1. These results have important implications on the emerging field of closed-loop adaptive stimulation promoting ADS as an innovative tool for the treatment of neurological disorders.

Recent studies provide novel insights into the meso-scale organization of the brain, highlighting the co-occurrence of different structures: classic assortative (modular), disassortative, and core-periphery. However, the spectral properties of the brain meso-scale remain mostly unexplored. To fill this knowledge gap, we investigated how the meso-scale structure is organized across the frequency domain. We analyzed the resting state activity of healthy participants with source-localized high-density electroencephalography signals. Then, we inferred the community structure using weighted stochastic block-model (WSBM) to capture the landscape of meso-scale structures across the frequency domain. We found that different meso-scale modalities co-exist and are diversely organized over the frequency spectrum. Specifically, we found a core-periphery structure dominance, but we also highlighted a selective increase of disassortativity in the low frequency bands (<8 Hz), and of assortativity in the high frequency band (30-50 Hz). We further described other features of the meso-scale organization by identifying those brain regions which, at the same time, (a) exhibited the highest degree of assortativity, disassortativity, and core-peripheriness (i.e., participation) and (b) were consistently assigned to the same community, irrespective from the granularity imposed by WSBM (i.e., granularity-invariance). In conclusion, we observed that the brain spontaneous activity shows frequency-specific meso-scale organization, which may support spatially distributed and local information processing., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Working memory (WM) performance is very often measured using the n-back task, in which the participant is presented with a sequence of stimuli, and required to indicate whether the current stimulus matches the one presented n steps earlier. In this study, we used high-density electroencephalography (hdEEG) coupled to source localization to obtain information on spatial distribution and temporal dynamics of neural oscillations associated with WM update, maintenance and readout. Specifically, we a priori selected regions from a large fronto-parietal network, including also the insula and the cerebellum, and we analyzed modulation of neural oscillations by event-related desynchronization and synchronization (ERD/ERS). During update and readout, we found larger θ ERS and smaller β ERS respect to maintenance in all the selected areas. γ LOW and γ HIGH bands oscillations decreased in the frontal and insular cortices of the left hemisphere. In the maintenance phase we observed decreased θ oscillations and increased β oscillations (ERS) in most of the selected posterior areas and focally increased oscillations in γ LOW and γ HIGH bands in the frontal and insular cortices of the left hemisphere. Finally, during WM readout, we also found a focal modulation of the γ LOW band in the left fusiform cortex and cerebellum, depending on the response trial type (true positive vs. true negative). Overall, our study demonstrated specific spectral signatures associated with updating of memory information, WM maintenance, and readout, with relatively high spatial resolution., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Objectives: The number of preterm babies is steadily growing world-wide and these neonates are at risk of neuro-motor-cognitive deficits. The observation of spontaneous movements in the first three months of age is known to predict such risk. However, the analysis by specifically trained physiotherapists is not suited for the clinical routine, motivating the development of simple computerized video analysis systems, integrated with a well-structured Biobank to make available for preterm babies a growing service with diagnostic, prognostic and epidemiological purposes., Methods: MIMAS (Markerless Infant Movement Analysis System) is a simple, low-cost system of video analysis of spontaneous movements of newborns in their natural environment, based on a single standard RGB camera, without markers attached to the body. The original videos are transformed into binarized sequences highlighting the silhouette of the baby, in order to minimize the illumination effects and increase the robustness of the analysis; such sequences are then coded by a large set of parameters (39) related to the spatial and spectral changes of the silhouette. The parameter vectors of each baby were stored in the Biobank together with related clinical information., Results: The preliminary test of the system was carried out at the Gaslini Pediatric Hospital in Genoa, where 46 preterm (PT) and 21 full-term (FT) babies (as controls) were recorded at birth (T0) and 8-12 weeks thereafter (T1). A simple statistical analysis of the data showed that the coded parameters are sensitive to the degree of maturation of the newborns (comparing T0 with T1, for both PT and FT babies), and to the conditions at birth (PT vs. FT at T0), whereas this difference tends to vanish at T1. Moreover, the coding method seems also able to detect the few 'abnormal' preterm babies in the PT populations that were analyzed as specific case studies., Conclusions: Preliminary results motivate the adoption of this tool in clinical practice allowing for a systematic accumulation of cases in the Biobank, thus for improving the accuracy of data analysis performed by MIMAS and ultimately allowing the adoption of data mining techniques., Competing Interests: Declaration of Competing Interest Authors have no competing interests to declare., (Copyright © 2020. Published by Elsevier B.V.)

Background/Objective . Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods . A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results . During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.

Goal: Functional connectivity (FC) is an important indicator of the brain's state in different conditions, such as rest/task or health/pathology. Here we used high-density electroencephalography coupled to source reconstruction to assess frequency-specific changes of FC during resting state. Specifically, we computed the Small-World Propensity (SWP) index to characterize network small-world architecture across frequencies. Methods: We collected resting state data from healthy participants and built connectivity matrices maintaining the heterogeneity of connection strengths. For a subsample of participants, we also investigated whether the SWP captured FC changes after the execution of a working memory (WM) task. Results: We found that SWP demonstrated a selective increase in the alpha and low beta bands. Moreover, SWP was modulated by a cognitive task and showed increased values in the bands entrained by the WM task. Conclusions: SWP is a valid metric to characterize the frequency-specific behavior of resting state networks.

The development of an easy to implement, quantitative measure to examine vibration perception would be useful for future application in clinical settings. Vibration sense in the lower limb of younger and older adults was examined using the method of constant stimuli (MCS) and the two-alternative forced choice paradigm. The focus of this experiment was to determine an appropriate stimulation site on the lower limb (tendon versus bone) to assess vibration threshold and to determine if the left and right legs have varying thresholds. Discrimination thresholds obtained at two stimulation sites in the left and right lower limbs showed differences in vibration threshold across the two ages groups, but not across sides of the body nor between stimulation sites within each limb. Overall, the MCS can be implemented simply, reliably, and with minimal time. It can also easily be implemented with low-cost technology. Therefore, it could be a good candidate method to assess the presence of specific deep sensitivity deficits in clinical practice, particularly in populations likely to show the onset of sensory deficits.

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching., (© 2018 Wiley Periodicals, Inc.)

Is there any difference between matching the position of the hands by asking the subjects to move them to the same spatial location or to mirror-symmetric locations with respect to the body midline? If the motion of the hands were planned in the extrinsic space, the mirror-symmetric task would imply an additional challenge, because we would need to flip the coordinates of the target on the other side of the workspace. Conversely, if the planning were done in intrinsic coordinates, in order to move both hands to the same spot in the workspace, we should compute different joint angles for each arm. Even if both representations were available to the subjects, the two tasks might lead to different results, providing some cue on the organization of the "body schema". In order to answer such questions, the middle fingertip of the non-dominant hand of a population of healthy subjects was passively moved by a manipulandum to 20 different target locations. Subjects matched these positions with the middle fingertip of their dominant hand. For most subjects, the matching accuracy was higher in the extrinsic modality both in terms of systematic error and variability, even for the target locations in which the configuration of the arms was the same for both modalities. This suggests that the matching performance of the subjects could be determined not only by proprioceptive information but also by the cognitive representation of the task: expressing the goal as reaching for the physical location of the hand in space is apparently more effective than requiring to match the proprioceptive representation of joint angles.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.

An intact position sense is considered important for neuromotor recovery, but the available methods and protocols for its assessment are still limited. In the clinical practice it is generally tested trough a bimanual position matching test, that consists of replicating with one arm the angular positions of the other arm in space (intrinsic coordinates matching). However, the same test could be carried out by matching the hand location in space (extrinsic coordinates matching). Is there any difference between the procedures that may be relevant to the evaluation of position sense deficits? In this study we compared the performance of eight right handed subjects and two stroke survivors with left hemiparesis performing the test in the two conditions. A robotic manipulandum passively moved the left arm of the participants in twenty-four positions in the workspace. Subjects had to match the left arm position with their right arm either in intrinsic or extrinsic coordinates. The results show that all the subjects (impaired and controls) performed better when using the extrinsic paradigm.