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Background and Aims: Holmium-166 ( 166 Ho) radioembolization could offer a more individualized approach in terms of imaging and dosimetry. We aim to evaluate the feasibility and safety of 166 Ho selective internal radiation therapy (SIRT) using a higher tumour dose than previously administered determined by 166 Ho-scout as a surrogate marker in HCC patients., Methods: This is an open-label, prospective, non-randomized, single-centre pilot study that included patients with HCC that received 166 Ho-SIRT if the work-up using 166 Ho-scout showed a tumour-absorbed dose ≥150 Gy, a non-tumoural liver absorbed dose less than 60 Gy and a lung absorbed dose less than 30 Gy. Primary endpoints were feasibility and safety-toxicity profiles at 24-48 h and 1 month. Overall response rates (ORR) at 3 months (mRECIST, RECIST 1.1 and metabolic response by FDG and choline PET CT) and time to progression (TTP) represented the secondary endpoints., Results: Fifteen patients with large tumours (mean diameter 55.67 ± 28.42 mm) received 17 166 Ho-SIRT treatments between July 2020 and June 2022. All the attempted treatments were accomplished. Mean administered tumour dose was 183.18 ± 71.71 Gy, while non-tumour liver dose was 30.29 ± 14.56 Gy. Median time of follow-up was 12 months (IQR 9-16). Only grade 1-2 clinical and biological AEs were observed. There were no liver decompensations. At 3 months, objective response was achieved for all target lesions (CR 78.57%, PR 21.43% according to mRECIST). Median TTP was 18.8 (range 2.9; n.e.) months., Conclusion: Personalized 166 Ho-SIRT with a tumour delivered dose ≥150 Gy was feasible and safe for HCC patients with promising response rates., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 ( 166 Ho). However, due to the complexity of the scatter components in 166 Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data., Methods: Dual energy window (DEW) and triple energy window (TEW) methods were investigated for scatter correction purposes and compared using Contrast Recovery Coefficients (CRC) and Contrast to Noise Ratios (CNR). First, MC simulations were carried out to assess all the scatter components in the energy windows used, also to confirm the choice of the parameter needed for the DEW method. Then, MC simulations of acquisitions of a Jaszczak phantom were conducted with conditions mimicking an ideal scatter correction. These simulated projections can be reconstructed and compared with real acquisitions corrected by both methods and then reconstructed. Finally, both methods were applied on patient data and their impact on personalized dosimetry was evaluated., Results: MC simulations confirmed the use of k = 1 for the DEW method. These simulations also confirmed the complexity of scatter components in the main energy window used with a high energy gamma rays component of about half of the total counts detected, together with a negligible X rays component and a negligible presence of fluorescence. CRC and CNR analyses, realized on simulated scatter-free projections of the phantom and on scatter corrected acquisitions of the same phantom, suggested an increased efficiency of the TEW method, even at the price of higher level of noise. Finally, these methods, applied on patient data, showed significant differences in terms of non-tumoral liver absorbed dose, non-tumoral liver fraction under 50 Gy, tumor absorbed dose, and tumor fraction above 150 Gy., Conclusions: This study demonstrated the impact of scatter correction on personalized dosimetry on patient data. The use of a TEW method is proposed for scatter correction in 166 Ho SPECT imaging., (© 2024. The Author(s).)

Background: One of the main limitations of 99m technetium-dimercaptosuccinic acid (DMSA) scan is the long acquisition time., Objective: To evaluate the feasibility of short DMSA scan acquisition times using a cadmium-zinc-telluride-based single-photon emission computed tomography (SPECT) system in children., Materials and Methods: The data of 27 children (median age: 4 years; 16 girls) who underwent DMSA SPECT were retrospectively analyzed. Both planar and SPECT DMSA were performed. SPECT images were analyzed using coronal-simulated planar two-dimensional images. A reduction in SPECT acquisition time was simulated to provide 4 series (SPECT-15 min, SPECT-10 min, SPECT-5 min and SPECT-2.5 min). A direct comparison of the planar and SPECT series was performed, including semi-quantification reproducibility, image quality (mean quality score on a scale of 0 to 2) and inter- and intra-observer reproducibility of the scintigraphic patterns., Results: The overall image quality score (± standard deviation) was 1.3 (± 0.6) for the planar data set, 1.6 (± 0.5) for the SPECT-15 min data set, 1.4 (± 0.5) for the SPECT-10 min data set, 1.0 (± 0.5) for the SPECT-5 min data set and 0.6 (± 0.6) for the SPECT-2.5 min data set. Median Kappa coefficients for inter-observer agreement between planar and SPECT images were greater than 0.83 for all series and all readers except one reader for the SPECT-2.5 min series (median Kappa coefficient = 0.77)., Conclusion: Shortening SPECT acquisitions to 5 min is feasible with minimal impact on images in terms of quality and reproducibility., (© 2023. The Author(s).)

Background: Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC)., Aim: We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity 90 ® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry., Methods: This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit 90 Y® and the activity actually administered determined by the standard approach., Results: Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3-55) in group A and 21 months (range 4-39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit 90 Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity., Conclusions: Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment., (© 2023. The Author(s).)

Background: Selective internal radiotherapy based on transarterial radioembolization (TARE) with yttrium-90 ( 90 Y) microspheres is an established treatment for primary or metastatic liver disease., Purpose: The objective of this work is to optimize the dosimetry of patients treated with 90 Y TARE, using positron emission tomography (PET) images., Methods: The NEMA 2012 PET phantom was filled with nearly 3.9 GBq of 90 Y activity and acquired at days 0, 3, 5, 7, and 9 on a classic time-of-flight PET/computed tomography (CT) scanner (Philips TF64) and on a silicon photomultiplier (SiPM)-based PET/CT scanner (Philips Vereos). Acquisitions were carried on following the guidelines proposed in a previously published multicentric trial and images were reconstructed by varying and combining the available parameters. Comparisons were performed to identify the best set(s) of parameters leading to the most accurate 90 Y-PET image(s), in terms of activity distribution. Then, for both scanners, the best images were analyzed with Simplicit 90 Y, a personalized dosimetry software using multicompartmental Medical Internal Radiation Dose model. The comparison between measured and true doses allowed to identify the image granting the most consistent dose estimations and, therefore, to designate the set of parameters to be applied on patients' data for the reconstruction of optimized clinical images. Posttreatment dosimetry of four patients was then realized with Simplicit 90 Y using optimized imaging datasets., Results: Based on activity distribution comparisons and dose estimations over phantom and patients data, the SiPM-based PET/CT system appeared more suitable than the photomultiplier tube-based TF64 for 90 Y-PET imaging. With the SiPM-based PET/CT system, reconstructed images with a 2-mm voxel size combined with the application of the point spread function correction led to the most accurate results for quantitative 90 Y measures., Conclusions: For the SiPM-based PET/CT scanner, an optimized set of reconstruction parameters has been identified and applied on patients' data in order to generate the most accurate image to be used for an improved personalized 90 Y-PET dosimetry, ensuring a reliable evaluation of the delivered doses., (© 2022 American Association of Physicists in Medicine.)

Background: Driving anxiety can have deleterious effects not only on driving behavior, but also on life quality. The interaction between motor vehicle collision (MVC) experiences and driving anxiety has been studied from different standpoints. However, the comparison with other events triggering it has been scarcely considered. Objectives: To analyze the body manifestations and the driving cognitions related to the accident, social and panic concerns in people suffering from different levels of driving anxiety. Method : A total of 260 participants suffering from driving anxiety were included in a survey, including Driving Cognition Questionnaire and Body Sensation Questionnaire. Results: Panic attacks and criticisms are the most relevant onsets of driving anxiety, more than MVC. Only 11.4% of MVC victims considered it as the onset. People with MVC history showed lower scores in social concerns than people without MVC experience and neither the responsibility of the MVC nor the role (driver/passenger) seemed to have an impact on the anxiety level. Conclusions: Although the most relevant body sensations, heart palpitations and sweating, were the same in people with panic attack experiences and MVC victims, a discrimination of the emotions behind the concept of "driving anxiety" is desirable to clarify the psychological effects of different onsets.

Cognitive training has been shown to increase neural plasticity and cognitive reserve, potentially reducing the risk of developing dementia. Music learning, specifically piano playing, has been shown to be an effective form of multimodal cognitive training. This pilot study explored the feasibility and efficacy of using a socially assistive robot to provide a piano learning cognitive training intervention to older adults with mild cognitive impairment. Participants (N=11) engaged in a four-week feasibility study, which included a one-hour piano lesson per week led by a remotely controlled robot. Participants experienced improved cognitive function in the verbal memory ( p =0.04), executive function ( p =0.01), reaction time ( p =0.04), and cognitive flexibility ( p =0.003) domains, as well as in the calculated neurocognitive index score ( p =0.03). Socially assistive robots may have the potential to provide cognitive training in the form of piano lessons for older adults with mild cognitive impairment, especially adults who cannot access traditional services.

Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca(++), Mg(++), Zn(++); MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-κB-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-κB signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds., (Copyright © 2015. Published by Elsevier B.V.)

Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants.

Rear-end collisions represent about 30% of all car crashes and generate a significant economic cost for society. Driver inattention has been identified as the most important contributing factor in rear-end collisions. One possible countermeasure is the use of systems that warn drivers of potential collisions. Nevertheless, because of technical constraints, the conception of perfect warning systems is difficult to achieve and technical literature shows that these kinds of systems can be prone to false alerts or misses. The main objective of this study is to assess the impact of such a warning system on the processing of a relevant driving visual cue while taking into account the reliability of the system and the attentional state of the participants. For this, we designed a laboratory experiment during which we recorded behavioral data and brain activity (event related potential, ERP) following the detection of a visual target. Three warning conditions were designed: (1) no alert was presented before the visual target; (2) an auditory alert was presented before each target; (3) an alert was presented before the target in 70% of the trials (15% only had the alert without the target, and 15% only had the target without the alert). In addition, participants had to perform this visual detection task either alone (simple task) or with a concurrent problem-solving task (dual task). Behavioral and electrophysiological data contribute to revealing (1) that there is a behavioral gain induced by the alert and (2) that this gain is at least linked with a time-saving aspect at both the sensory and cognitive stages of neural information processing. Nevertheless, this impact depends on the attentional states of the participant and on the reliability of the alert., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo. Similarly, treatment of BR5-1-derived tumors with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis and necrosis, reduction in intraperitoneal dissemination, and selective reduction of intratumoral FoxP3(+) regulatory T cells (Treg). Compared with controls, CXCR4 blockade greatly increased T-cell-mediated antitumor immune responses, conferring a significant survival advantage to AMD3100-treated mice. In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model. Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.