[Informed consent in radiotherapy care]. / Consentement aux soins en radiothérapie.

Obtaining consent to care requires the radiation oncologist to provide loyal information and to ensure that the patient understands it. Proof of such an approach rests with the practitioner. The French Society for Radiation Oncology (SFRO) does not recommend the signature of a consent form by the patient but recommends that the radiation oncologist be able to provide all the elements demonstrating the reality of a complete information circuit.

Integrating Upper-Limb Prostheses with the Human Body: Technology Advances, Readiness, and Roles in Human-Prosthesis Interaction.

Significant advances in bionic prosthetics have occurred in the past two decades. The field's rapid expansion has yielded many exciting technologies that can enhance the physical, functional, and cognitive integration of a prosthetic limb with a human. We review advances in the engineering of prosthetic devices and their interfaces with the human nervous system, as well as various surgical techniques for altering human neuromusculoskeletal systems for seamless human-prosthesis integration. We discuss significant advancements in research and clinical translation, focusing on upper limbprosthetics since they heavily rely on user intent for daily operation, although many discussed technologies have been extended to lower limb prostheses as well. In addition, our review emphasizes the roles of advanced prosthetics technologies in complex interactions with humans and the technology readiness levels (TRLs) of individual research advances. Finally, we discuss current gaps and controversies in the field and point out future research directions, guided by TRLs.

Implications of EMG channel count: enhancing pattern recognition online prosthetic testing.

Introduction: Myoelectric pattern recognition systems have shown promising control of upper limb powered prostheses and are now commercially available. These pattern recognition systems typically record from up to 8 muscle sites, whereas other control systems use two-site control. While previous offline studies have shown 8 or fewer sites to be optimal, real-time control was not evaluated. Methods: Six individuals with no limb absence and four individuals with a transradial amputation controlled a virtual upper limb prosthesis using pattern recognition control with 8 and 16 channels of EMG. Additionally, two of the individuals with a transradial amputation performed the Assessment for Capacity of Myoelectric Control (ACMC) with a multi-articulating hand and wrist prosthesis with the same channel count conditions. Results: Users had significant improvements in control when using 16 compared to 8 EMG channels including decreased classification error (p = 0.006), decreased completion time (p = 0.019), and increased path efficiency (p = 0.013) when controlling a virtual prosthesis. ACMC scores increased by more than three times the minimal detectable change from the 8 to the 16-channel condition. Discussion: The results of this study indicate that increasing EMG channel count beyond the clinical standard of 8 channels can benefit myoelectric pattern recognition users.

Management of second ipsilateral breast tumor event: An advocacy for a randomized trial.

For a second ipsilateral breast tumor event, salvage mastectomy is the standard of care while second conservative treatment is a possible option. However, level 1 proofs are missing, leading to perform salvage mastectomy for patients who could receive second conservative treatment and consequently avoid psychological/quality of life salvage mastectomy deleterious impacts. A phase 3 randomized trial comparing salvage mastectomy to second conservative treatment is needed. Here we discuss what would be to us the optimal design of such trial to confirm the non-inferiority between the two salvage options, with a focus on methodological aspects in terms of patient characteristics and statistical issues.

Effect of proline content and histidine ligation on the dynamics of Ω-loop D and the peroxidase activity of iso-1-cytochrome c.

To study how proline residues affect the dynamics of Ω-loop D (residues 70 to 85) of cytochrome c, we prepared G83P and G83A variants of yeast iso-1-cytochrome c (iso-1-Cytc) in the presence and absence of a K73H mutation. Ω-loop D is important in controlling both the electron transfer function of Cytc and the peroxidase activity of Cytc used in apoptosis because it provides the Met80 heme ligand. The G83P and G83A mutations have no effect on the global stability of iso-1-Cytc in presence or absence of the K73H mutation. However, both mutations destabilize the His73-mediated alkaline conformer relative to the native state. pH jump stopped-flow experiments show that the dynamics of the His73-mediated alkaline transition are significantly enhanced by the G83P mutation. Gated electron transfer studies show that the enhanced dynamics result from an increased rate of return to the native state, whereas the rate of loss of Met80 ligation is unchanged by the G83P mutation. Thus, the G83P substitution does not stiffen the conformation of the native state. Because bis-His heme ligation occurs when Cytc binds to cardiolipin-containing membranes, we studied the effect of His73 ligation on the peroxidase activity of Cytc, which acts as an early signal in apoptosis by causing oxygenation of cardiolipin. We find that the His73 alkaline conformer suppresses the peroxidase activity of Cytc. Thus, the bis-His ligated state of Cytc formed upon binding to cardiolipin is a negative effector for the peroxidase activity of Cytc early in apoptosis.

Stereotactic body radiation therapy to postpone systemic therapy escalation for castration-resistant prostate cancer: A multicenter retrospective analysis.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligoprogressive metastatic castration-resistant prostate cancer (omCRPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omCRPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local relapse (LR), distant (DP) and isolated biochemical (iBP) progressions were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 50 pts with omCRPC underwent SBRT. With a MFU of 23 months [3---100], median STE-FS was 13.1 months (95 %CI 10.8 - 36.4). Median OS was not reached and PFS was 13 months (CI95% 10.1 - 20.8). Post-SBRT PSA remained stable or decreased in 19 pts (38 %). Progression events (LR, DP, iBP) were observed in 34 pts (68 %), among whom 6 relapsed in the irradiated area (local control rate: 88 %). DP and iBP were observed in 28 pts (56 %) and 4 pts (8 %) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 2 pts. Conclusion: With excellent local control and tolerance, SBRT for omCRPC patients represents an acceptable approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

Place of radiotherapy for treatment of metastatic cervical, vaginal and endometrial uterine cancer.

Beyond classical palliative-intent irradiation schemes, there are increasing data suggesting a benefit for intensive locoregional treatments in metastatic gynecological cancers. Such approach aims at avoiding local symptoms related to tumor progression, but may also improve survival outcome by shrinking tumor burden to a microscopic state. This strategy is rarely considered upfront (in highly selected patients with very limited oligometastatic disease), but rather after systemic treatment. In case of tumor response (especially if complete response) of the metastatic sites, pelvic±para-aortic radiotherapy can be considered in combination with a brachytherapy boost to obtain long-term local control, in particular in cervical or vaginal cancer patients. Such approach seems particularly relevant when there is isolated persistence or progression of macroscopic disease within the pelvis. In parallel, there is also an increasing place for radiotherapy of oligo-metastatic sites. We review the literature on the place of radiotherapy in the management of cancers of the cervix and metastatic endometrial cancer.

Evaluating the partial contribution of the P3 event-related potential elicited by auditory oddball stimuli during the Stroop task.

The cognitive load of a precisely timed task, such as the Stroop task, may be measured through the use of event-related potentials (ERPs). To determine the time at which cognitive load is at its peak, oddball tones may be applied at various times surrounding a cognitive task. However, we need to determine whether the simultaneous presentation of auditory and visual stimuli would mask a potential change in P3 in an ERP-producing task. If the contribution of the Stroop stimulus is too large, then Stroop ERP with oddball stimuli occurring at different timepoints may not be directly comparable across the various timepoints due to the contribution of the Stroop ERP. The aim of this study was to measure the magnitude of the difference wave between that of simultaneously presented stimuli and that of linearly added stimuli of separate responses. Participants were fitted with a dry-sensor EEG cap and were presented with a series of Stroop and auditory stimuli. For some Stroop stimuli, auditory stimuli occurred simultaneously or in a close time proximity to the Stroop stimuli. We sought to estimate the linear contribution of the ERP from Stroop and oddball stimuli. We found that the magnitude of the difference waves were 3.07 ± 1.65 µV and 2.82 ± 1.34 µV for congruent and incongruent stimuli, respectively. As the average amplitude in the P3 region for both the congruent and incongruent difference waves was lower than the magnitude of the auditory oddball presented simultaneously with Stroop stimuli (12.13 ± 1.00 µV for congruent and 11.78 ± 1.05 µV for incongruent Stroop), we expect that the contribution of P3 auditory oddball would not mask a potential Stroop effect even if the timing of the auditory oddball stimuli were experimentally manipulated, a direction that we hope to explore in future work. In conclusion, we determine this paradigm is suitable for measuring cognitive load in precisely timed tasks.Clinical Relevance- This study establishes the efficacy of presenting a Stroop task as a proxy for a cognitive challenge that could cause cognitive overload.

Machine Learning-Based Gait Mode Prediction for Hybrid Knee Prosthesis Control.

Recently, hybrid prosthetic knees, which can combine the advantages of passive and active prosthetic knees, have been proposed for individuals with a transfemoral amputation. Users could potentially take advantage of the passive knee mechanics during walking and the active power generation during stair ascent. One challenge in controlling the hybrid knees is accurate gait mode prediction for seamless transitions between passive and active modes. However, data imbalance between passive and active modes may impact the performance of a classifier. In this study, we used a dataset collected from nine individuals with a unilateral transfemoral amputation as they ambulated over level ground, inclines, and stairs. We evaluated several machine learning-based classifiers on the prediction of passive (level-ground walking, incline walking, descending stairs, and donning and doffing the prosthesis) and active mode (ascending stairs). In addition, we developed a generative adversarial network (GAN) to create synthetic data for improving classification performance. The results indicated that linear discriminant analysis and random forest might be the best classifiers regarding sensitivity to the active mode and overall accuracy, respectively. Further, we demonstrated that using the GAN-based synthetic data for training improves the sensitivity of classifiers.

Total wash elimination for solid phase peptide synthesis.

We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10-15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics.

For plantar taping, direction of elasticity matters.

Plantar taping has been used in clinical settings as a short-term conservative treatment for plantar heel pain and related pathologies. The rise of at-home taping methods may offer patients more independence, but effectiveness has not been established. The purpose of this study was to evaluate the effects of plantar taping on foot mechanics during gait. We hypothesized that material compliance would drive mechanical effectiveness, with longitudinally inelastic tape reducing medial longitudinal arch (MLA) motion and anterior/posterior (A/P) plantar tissue spreading forces, and laterally inelastic tape reducing medial/lateral (M/L) tissue spreading. We also hypothesized that these effects would be influenced by foot structure. Fifteen healthy participants were tested in a randomized cross-over study design. Barefoot (BF) plus four taping methods were evaluated, including two inelastic tapes (Low-Dye, LD, and FasciaDerm, FD) along with longitudinally elastic kinesiology tape (KT) and a novel laterally elastic kinesiology tape (FAST, FS). Participants' arch height and flexibility were measured followed by instrumented gait analysis with a multi-segment foot model. Ankle eversion and MLA drop/rise were calculated from rearfoot and forefoot reference frames, while plantar tissue spreading was calculated from shear stresses. ANOVAs with Holm pairwise tests evaluated tape effects while correlations connected arch structure and taping effectiveness (α = 0.05). The three longitudinally inelastic tapes (LD, FD, FS) reduced MLA drop by 11-15% compared with KT and BF. In late stance, these tapes also inhibited MLA rise (LD by 29%, FD and FS by 10-15%). FS and FD reduced A/P spreading forces, while FD reduced M/L spreading forces compared with all other conditions. Arch height had a moderately strong correlation (r = -0.67) with the difference in MLA drop between BF and FS. At-home plantar taping can affect the mechanical function of the foot, but tape elasticity direction matters. Longitudinally elastic kinesiology tape has little effect on mechanics, while inelastic tapes control MLA drop but also restrict MLA rise in late stance. Lateral elasticity does not limit tissue spreading and may increase comfort without sacrificing MLA control. At-home taping has the potential to broaden conservative treatment of plantar heel pain, flat foot deformity, and related pathologies, but additional studies are needed to connect mechanics with symptom relief.

The neuronal calcium sensor NCS-1 regulates the phosphorylation state and activity of the Gα chaperone and GEF Ric-8A.

The neuronal calcium sensor 1 (NCS-1), an EF-hand Ca2+ binding protein, and Ric-8A coregulate synapse number and probability of neurotransmitter release. Recently, the structures of Ric-8A bound to Gα have revealed how Ric-8A phosphorylation promotes Gα recognition and activity as a chaperone and guanine nucleotide exchange factor. However, the molecular mechanism by which NCS-1 regulates Ric-8A activity and its interaction with Gα subunits is not well understood. Given the interest in the NCS-1/Ric-8A complex as a therapeutic target in nervous system disorders, it is necessary to shed light on this molecular mechanism of action at atomic level. We have reconstituted NCS-1/Ric-8A complexes to conduct a multimodal approach and determine the sequence of Ca2+ signals and phosphorylation events that promote the interaction of Ric-8A with Gα. Our data show that the binding of NCS-1 and Gα to Ric-8A are mutually exclusive. Importantly, NCS-1 induces a structural rearrangement in Ric-8A that traps the protein in a conformational state that is inaccessible to casein kinase II-mediated phosphorylation, demonstrating one aspect of its negative regulation of Ric-8A-mediated G-protein signaling. Functional experiments indicate a loss of Ric-8A guanine nucleotide exchange factor (GEF) activity toward Gα when complexed with NCS-1, and restoration of nucleotide exchange activity upon increasing Ca2+ concentration. Finally, the high-resolution crystallographic data reported here define the NCS-1/Ric-8A interface and will allow the development of therapeutic synapse function regulators with improved activity and selectivity.

[Survey by SFRO, SNRO and AFPPE about the evolution of the radiation therapist profession in France]. / Enquête SFRO­SNRO­AFPPE sur l'évolution du métier de manipulateur exerçant en radiothérapie en France.

PURPOSE: As part of the multidisciplinary team, radiation therapists are in charge of elements of treatment preparation and delivery of radiotherapy to cancer patients. Helping scientific and technological improvements, more and more patients with cancer were treated with radiotherapy including hypofractionnated radiotherapy, that explain the increase of demands on services. The professional impacted by this increase of demands are radiation oncologists and medical physicists. The opportunity to push forward the radiation therapist's competencies appears with the possibility to shift them some tasks. In this context, a first work was performed with objectives to have an overview of the tasks shifted to radiation therapists in France, the tasks that they could perform but also to evaluate some criteria of job satisfaction. MATERIAL AND METHODS: The committee of "new status and value of status" including six radiation oncologists (the French society of radiation oncology [SFRO] et national union of radiation oncologists [SNRO]) and six radiation therapists committee members of the French association of radiation therapists (AFPPE), built a questionnaire including three parts: demographic characteristics, tasks shifted and job satisfaction criteria. In total, the questionnaire included 19 questions and 24 items assessed with a four point-Likert scale (ranging from "completely disagree" to "completely agree"). This survey, formatting with google form, was tested by the committee members and the final version was sent to the SFRO, AFPPE and SNRO members, before being disseminated on the social networks. RESULTS: From November 18th 2022 to December 31st 2022, 492 responses were received (response rate=18.3%): 55 % of the respondents had at least 11 years of experience in radiotherapy. The respondents worked in different type of health facilities (36 % in specialized cancer centres, 19.5 % in private centers, 17.5% in university and general hospital, 10.2% in general hospital). More than » of the respondents had a teaching lecturer activity, 20% had a management team activity and a research activity for 18%. Less than 10% of the respondents had another degree than that of radiation therapist: university degree (n=27), degree in dosimetry (n=11) and master (n=3). More than 76% would like to be trained and to have access to the advanced practice, more than 50% would like expend competencies with a university degree, 30% with a master and 67% would like to participate in research. Forty-two percent of the respondents were involved in a task shifting (excluding decree relating to acts and activities carried out by radiation therapists) and among the radiation therapists non-involved, 63% would be interested in being. Regarding job satisfaction, 53% of the respondents were satisfied with their job and their salary and 68% believed that their job occupation is in line with their professional aspirations. More than 2/3 of the respondents described a significant workload and mental load, 53% thought to have time for their patient care and 70% felt some organisational difficulties. CONCLUSION: This survey shows: (i) A significant involvement of radiation therapists in the task shifting; (ii) A very strong demand for career development, in particular with existing degrees or to be created degree such as advanced practice; and (iii) The need to reinforce a job satisfaction for almost the half of the respondents, linked to a workload, a mental load and some organisational difficulties.

High-Accuracy Prediction of Stabilizing Surface Mutations to the Three-Helix Bundle, UBA(1), with EmCAST.

The accurate modeling of energetic contributions to protein structure is a fundamental challenge in computational approaches to protein analysis and design. We describe a general computational method, EmCAST (empirical Cα stabilization), to score and optimize the sequence to the structure in proteins. The method relies on an empirical potential derived from the database of the Cα dihedral angle preferences for all possible four-residue sequences, using the data available in the Protein Data Bank. Our method produces stability predictions that naturally correlate one-to-one with the experimental results for solvent-exposed mutation sites. EmCAST predicted four mutations that increased the stability of a three-helix bundle, UBA(1), from 2.4 to 4.8 kcal/mol by optimizing residues in both helices and turns. For a set of eight variants, the predicted and experimental stabilizations correlate very well (R2 = 0.97) with a slope near 1 and with a 0.16 kcal/mol standard error for EmCAST predictions. Tests against literature data for the stability effects of surface-exposed mutations show that EmCAST outperforms the existing stability prediction methods. UBA(1) variants were crystallized to verify and analyze their structures at an atomic resolution. Thermodynamic and kinetic folding experiments were performed to determine the magnitude and mechanism of stabilization. Our method has the potential to enable the rapid, rational optimization of natural proteins, expand the analysis of the sequence/structure relationship, and supplement the existing protein design strategies.

[Interprofessional recommendations on behalf of Société française de radiothérapie oncologique for the prevention, protection and management of cyberattacks in radiation oncology]. / Prévention, protection, et gestion des cyberattaques en oncologie radiothérapie : recommandations interprofessionnelles au nom de la Société française de radiothérapie oncologique.

Cybersecurity is currently a major issue. Large hospitals are no longer the only main targets of attacks, but all healthcare organizations and establishments, without distinction of size or activities. The information system is defined as all the resources needed to collect images, store and process them with general distribution of multiple information within an organization. Systems are therefore crucial for the functioning of a medical department. Radiation oncology is one of the specialties most dependent on digital resources, for imaging, data transfer, dosimetry, treatment and so on.. Radiation oncology departments are therefore a prime target for ransomware attacks, which have increased significantly in recent years. Cybersecurity can be likened to a viral or bacterial attack. It is based on the two usual pillars of antimicrobial protection : hygiene and prophylaxis. In this article, we will detail by analogy the three classic levels of prevention of a bacillary attack: "primary prevention", which acts upstream of the infection; "secondary prevention", which acts at an early stage of its evolution; and "tertiary prevention", which acts on complications and risks of recurrence. This article is the result of an interprofessional group on behalf of SFRO, the French society of radiation oncology, with the aim of helping all teams to implement safety adapted to the specificities of a radiation oncology department in France.

Generating synthetic gait patterns based on benchmark datasets for controlling prosthetic legs.

BACKGROUND: Prosthetic legs help individuals with an amputation regain locomotion. Recently, deep neural network (DNN)-based control methods, which take advantage of the end-to-end learning capability of the network, have been proposed. One prominent challenge for these learning-based approaches is obtaining data for the training, particularly for the training of a mid-level controller. In this study, we propose a method for generating synthetic gait patterns (vertical load and lower limb joint angles) using a generative adversarial network (GAN). This approach enables a mid-level controller to execute ambulation modes that are not included in the training datasets. METHODS: The conditional GAN is trained on benchmark datasets that contain the gait data of individuals without amputation; synthetic gait patterns are generated from the user input. Further, a DNN-based controller for the generation of impedance parameters is trained using the synthetic gait pattern and the corresponding synthetic stiffness and damping coefficients. RESULTS: The trained GAN generated synthetic gait patterns with a coefficient of determination of 0.97 and a structural similarity index of 0.94 relative to benchmark data that were not included in the training datasets. We trained a DNN-based controller using the GAN-generated synthetic gait patterns for level-ground walking, standing-to-sitting motion, and sitting-to-standing motion. Four individuals without amputation participated in bypass testing and demonstrated the ambulation modes. The model successfully generated control parameters for the knee and ankle based on thigh angle and vertical load. CONCLUSIONS: This study demonstrates that synthetic gait patterns can be used to train DNN models for impedance control. We believe a conditional GAN trained on benchmark datasets can provide reliable gait data for ambulation modes that are not included in its training datasets. Thus, designing gait data using a conditional GAN could facilitate the efficient and effective training of controllers for prosthetic legs.

Systemic therapy escalation after stereotactic body radiation therapy for oligometastatic hormone-sensitive prostate cancer.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligometastatic hormone-sensitive prostate cancer (omHSPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omHSPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local (LR), distant (DR), prostatic (PR) and isolated biochemical (iBR) relapses were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 119 pts with omHSPC underwent SBRT. With a MFU of 34 months [12-97], median STE-FS was 33.4 months (95%CI 26.6---40.1). Median OS was not reached and PFS was 22.7 months (CI95% 18.6---32.3). Post-SBRT-PSA remained stable or decreased in 87 pts (73.1%). Progression events (LR, MR, PR, iBR) were observed in 72 pts (60.5%), among whom 6 relapsed in the irradiated area (local control rate: 95%). DR, BR, PR were observed in 44 pts (37%), 21pts (17.7%) and 2 pts (1.7%) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 1pt. Conclusion: With excellent local control and tolerance, SBRT for omHSPC patients represents an attractive approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.