Antioxidant Activity and Hypoallergenicity of Egg Protein Matrices Containing Polyphenols from Citrus Waste.

This study reports on the interactions of egg proteins, which represent a major health concern in food allergy, with polyphenols obtained from orange and lemon peels. The antioxidant properties of such citrus peel extracts prior to protein binding were evaluated. The resulting edible, and therefore inherently safe, matrices exhibit reduced IgE binding compared to pure proteins in indirect immunological assays (ELISA) using individual sera from patients allergic to ovalbumin and lysozyme. The reduced allergenicity could arise from the interactions with polyphenols, which alter the structure and functionality of the native proteins. It is hypothesized that the anti-inflammatory and antioxidant properties of the polyphenols, described as inhibitors of the allergic response, could add immunomodulatory features to the hypoallergenic complexes. A docking analysis using lysozyme was conducted to scrutinize the nature of the protein-polyphenol interactions. An in silico study unravelled the complexity of binding modes depending on the isoforms considered. Altogether, the presented results validate the antioxidant properties and reduced allergenicity of polyphenol-fortified proteins. Lastly, this study highlights the upgrading of vegetable wastes as a source of natural antioxidants, thus showing the benefits of a circular economy in agri-food science.

Achieving accurate prostate auto-segmentation on CT in the absence of MR imaging.

BACKGROUND: Magnetic resonance imaging (MRI) is considered the gold standard for prostate segmentation. Computed tomography (CT)-based segmentation is prone to observer bias, potentially overestimating the prostate volume by âˆ¼ 30 % compared to MRI. However, MRI accessibility is challenging for patients with contraindications or in rural areas globally with limited clinical resources. PURPOSE: This study investigates the possibility of achieving MRI-level prostate auto-segmentation accuracy using CT-only input via a deep learning (DL) model trained with CT-MRI registered segmentation. METHODS AND MATERIALS: A cohort of 111 definitive prostate radiotherapy patients with both CT and MRI images was retrospectively grouped into training (n = 37) and validation (n = 20) (where reference contours were derived from CT-MRI registration), and testing (n = 54) sets. Two commercial DL models were benchmarked against the reference contours in the training and validation sets. A custom DL model was incrementally retrained using the training dataset, quantitatively evaluated on the validation dataset, and qualitatively assessed by two different physician groups on the validation and testing datasets. A contour quality assurance (QA) model, established from the proposed model on the validation dataset, was applied to the test group to identify potential errors, confirmed by human visual inspection. RESULTS: Two commercial models exhibited large deviations in the prostate apex with CT-only input (median: 0.77/0.78 for Dice similarity coefficient (DSC), and 0.80 cm/0.83 cm for 95 % directed Hausdorff Distance (HD95), respectively). The proposed model demonstrated superior geometric similarity compared to commercial models, particularly in the apex region, with improvements of 0.05/0.17 cm and 0.06/0.25 cm in median DSC/HD95, respectively. Physician evaluation on MRI-CT registration data rated 69 %-78 % of the proposed model's contours as clinically acceptable without modifications. Additionally, 73 % of cases flagged by the contour quality assurance (QA) model were confirmed via visual inspection. CONCLUSIONS: The proposed incremental learning strategy based on CT-MRI registration information enhances prostate segmentation accuracy when MRI availability is limited clinically.

Dose Deintensified 3-Day Photon, Proton, or Brachytherapy: A Nonrandomized Controlled Partial Breast Irradiation Trial.

PURPOSE: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS AND MATERIALS: A multicenter nonrandomized controlled trial with the primary outcome of adverse cosmesis at 3 years versus before PBI. Eligibility criteria were age ≥50 years treated with breast-conserving surgery for node-negative estrogen receptor-positive (ER+) invasive breast cancer or any ductal carcinoma in situ (DCIS) measuring ≤2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (relative biological effectiveness) and brachytherapy 21 Gy in 3 fractions. Radiation therapy technique and adjuvant endocrine therapy were selected at physician and patient discretion. RESULTS: Between June 17, 2015, and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. One hundred twenty-six (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). Fifty-four percent of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to the prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline and 2.3% at 3 years (difference, -12.2%; 95% CI, -100% to -6.4%). Adverse cosmesis at the last follow-up, with a median follow-up of 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient-reported outcomes, and just 2 grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. Five-year local recurrence-free survival and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences among 60 patients with invasive breast cancer and Ki67 ≤13.25%. CONCLUSIONS: Deintensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the prespecified criteria for acceptability. This approach is an attractive option for patients with small node-negative ER+ breast cancer and DCIS.

Enhancing Activity and Stability of Pd-on-TiO2 Single-Atom Catalyst for Low-Temperature CO Oxidation through in Situ Local Environment Tailoring.

The development of efficient Pd single-atom catalysts for CO oxidation, crucial for environmental protection and fundamental studies, has been hindered by their limited reactivity and thermal stability. Here, we report a thermally stable TiO2-supported Pd single-atom catalyst that exhibits enhanced intrinsic CO oxidation activity by tunning the local coordination of Pd atoms via H2 treatment. Our comprehensive characterization reveals that H2-treated Pd single atoms have reduced nearest Pd-O coordination and form short-distanced Pd-Ti coordination, effectively stabilizing Pd as isolated atoms even at high temperatures. During CO oxidation, partial replacement of the Pd-Ti coordination by O or CO occurs. This unique Pd local environment facilitates CO adsorption and promotes the activity of the surrounding oxygen species, leading to superior catalytic performance. Remarkably, the turnover frequency of the H2-treated Pd single-atom catalyst at 120 °C surpasses that of the O2-treated Pd single-atom catalyst and the most effective Pd/Pt single-atom catalysts by an order of magnitude. These findings open up new possibilities for the design of high-performance single-atom catalysts for crucial industrial and environmental applications.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer.

Purpose/objectives: The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methods: The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher's exact tests. Results: Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15-20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25-30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. Conclusion: Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

The role of training variability for model-based and model-free learning of an arbitrary visuomotor mapping.

A fundamental feature of the human brain is its capacity to learn novel motor skills. This capacity requires the formation of vastly different visuomotor mappings. Using a grid navigation task, we investigated whether training variability would enhance the flexible use of a visuomotor mapping (key-to-direction rule), leading to better generalization performance. Experiments 1 and 2 show that participants trained to move between multiple start-target pairs exhibited greater generalization to both distal and proximal targets compared to participants trained to move between a single pair. This finding suggests that limited variability can impair decisions even in simple tasks without planning. In addition, during the training phase, participants exposed to higher variability were more inclined to choose options that, counterintuitively, moved the cursor away from the target while minimizing its actual distance under the constrained mapping, suggesting a greater engagement in model-based computations. In Experiments 3 and 4, we showed that the limited generalization performance in participants trained with a single pair can be enhanced by a short period of variability introduced early in learning or by incorporating stochasticity into the visuomotor mapping. Our computational modeling analyses revealed that a hybrid model between model-free and model-based computations with different mixing weights for the training and generalization phases, best described participants' data. Importantly, the differences in the model-based weights between our experimental groups, paralleled the behavioral findings during training and generalization. Taken together, our results suggest that training variability enables the flexible use of the visuomotor mapping, potentially by preventing the consolidation of habits due to the continuous demand to change responses.

Learning to Move and Plan like the Knight: Sequential Decision Making with a Novel Motor Mapping.

Many skills that humans acquire throughout their lives, such as playing video games or sports, require substantial motor learning and multi-step planning. While both processes are typically studied separately, they are likely to interact during the acquisition of complex motor skills. In this work, we studied this interaction by assessing human performance in a sequential decision-making task that requires the learning of a non-trivial motor mapping. Participants were tasked to move a cursor from start to target locations in a grid world, using a standard keyboard. Notably, the specific keys were arbitrarily mapped to a movement rule resembling the Knight chess piece. In Experiment 1, we showed the learning of this mapping in the absence of planning, led to significant improvements in the task when presented with sequential decisions at a later stage. Computational modeling analysis revealed that such improvements resulted from an increased learning rate about the state transitions of the motor mapping, which also resulted in more flexible planning from trial to trial (less perseveration or habitual responses). In Experiment 2, we showed that incorporating mapping learning into the planning process, allows us to capture (1) differential task improvements for distinct planning horizons and (2) overall lower performance for longer horizons. Additionally, model analysis suggested that participants may limit their search to three steps ahead. We hypothesize that this limitation in planning horizon arises from capacity constraints in working memory, and may be the reason complex skills are often broken down into individual subroutines or components during learning.

Targeting cow's milk allergy using hypoallergenic protein-polyphenol formulas: A proof of concept.

Cow's milk allergy caused by a hypersensitivity to milk proteins has increased over the last years. Hypoallergenic responses can be induced by altering the structure of such proteins with chemical modifiers; this paper is about the creation of edible matrices based on polyphenols from orange peel. Some compounds were able to significantly lower the IgE binding from ß-lactoglobulin allergic serum in sensitized patients. Such effects could also be observed for casein allergic serum in patients sensitized to both proteins. A certain inter-individual variability is observed, although polyphenols do actually induce salient structural changes. This indicates that molecular modifications aimed at oral treatments against food allergy may or may not correlate with reduced allergenicity, and hence the necessity for serum monitoring through immunological assays. Overall, the results are promising enough to validate the polyphenol-fortified approach. In addition, this study highlights the upgrading of vegetable waste, consistent with a circular economy in food chemistry.

Online Adaptive Proton Therapy Facilitated by Artificial Intelligence-Based Autosegmentation in Pencil Beam Scanning Proton Therapy.

PURPOSE: Online adaptive proton therapy (oAPT) is essential to address interfractional anatomical changes in patients receiving pencil beam scanning proton therapy. Artificial intelligence (AI)-based autosegmentation can increase the efficiency and accuracy. Linear energy transfer (LET)-based biological effect evaluation can potentially mitigate possible adverse events caused by high LET. New spot arrangement based on the verification computed tomography (vCT) can further improve the replan quality. We propose an oAPT workflow that incorporates all these functionalities and validate its clinical implementation feasibility with patients with prostate cancer. METHODS AND MATERIALS: AI-based autosegmentation tool AccuContour (Manteia) was seamlessly integrated into oAPT. Initial spot arrangement tool on the vCT for reoptimization was implemented using raytracing. An LET-based biological effect evaluation tool was developed to assess the overlap region of high dose and high LET in selected organs at risk. Eleven patients with prostate cancer were retrospectively selected to verify the efficacy and efficiency of the proposed oAPT workflow. The time cost of each component in the workflow was recorded for analysis. RESULTS: The verification plan showed significant degradation of the clinical target volume coverage and rectum and bladder sparing due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality. No overlap regions of high dose and high LET distributions were observed in bladder or rectum in replans. Three-dimensional γ analyses in patient-specific quality assurance confirmed the accuracy of the replan doses before delivery (γ passing rate, 99.57% ± 0.46%) and after delivery (98.59% ± 1.29%). The robustness of the replans passed all clinical requirements. The average time for the complete execution of the workflow was 9.12 ± 0.85 minutes, excluding manual intervention time. CONCLUSIONS: The AI-facilitated oAPT workflow demonstrated to be both efficient and effective by generating a replan that significantly improved the plan quality in prostate cancer treated with pencil beam scanning proton therapy.

Long-chain fatty acids block allergic reaction against lipid transfer protein Sola l 7 from tomato seeds.

Due to the benefits of tomato as an antioxidant and vitamin source, allergy to this vegetable food is a clinically concerning problem. Sola l 7, a class I lipid transfer protein found in tomato seeds, has been identified as an allergen linked to severe anaphylaxis. However, the role of lipid binding in Sola l 7-induced allergy remains unclear. Here, the three-dimensional structure of recombinant Sola l 7 (rSola l 7) has been elucidated using nuclear magnetic resonance spectroscopy (NMR). Its interaction with free fatty acids has been deeply studied; fluorescence emission spectroscopy revealed that different long-chain fatty acids interact with the protein, affecting the only tyrosine residue present in Sola l 7. On the contrary, no changes in the overall secondary structure were observed after the analysis of the circular dichroism spectra in the presence of fatty acids. Unsaturated oleic and linoleic fatty acids presented higher affinity and promoted more significant changes than saturated or short-chain fatty acids. 1H-15N HSQC NMR spectra allowed to determine the regions of the protein that were modified when rSola l 7 interacts with the fatty acids, suggesting epitope modification after the interaction. For corroboration, IgG and IgE binding to rSola l 7 were assessed in the presence of free fatty acids, revealing that both IgE and IgG binding were significantly lower than in their absence, suggesting a potential protective role of unsaturated fatty acids in tomato allergy.

Sistema robótico HUGO RAS, componentes y pasos para el acoplamiento en cirugía ginecológica

Video de sección "Imágenes en ginecología y obstetricia" donde se muestra los componentes y los 7 pasos de acomplamiento para la cirugía ginecológica utilizando laparoscópica asistida por robot (HUGO RAS).

Video of the section "Imaging in gynecology and obstetrics" showing the components and the 7 steps for gynecological surgery using robotas sisted laparoscopic surgery (HUGO RAS).

Synallactesmcdanieli sp. nov., a new species of sea cucumber from British Columbia, Canada and the Gulf of Alaska, USA (Holothuroidea, Synallactida).

Background: The family Synallactidae comprises mostly deep-sea forms and is the least-studied large taxon amongst deep-sea cucumbers. They are part of the abyssal megafauna and play an important role in modifying the sediment landscape and structuring the communities that live within it. The family embraces the genus Synallactes, which contains approximately twenty-five species from the Pacific, Atlantic (six species), Indian (seven species) and Antarctic Oceans (one species). New information: Synallactesmcdanieli sp. nov. is described from the Northeast Pacific, Knight Inlet, British Columbia, Canada to Kodiak Island, Gulf of Alaska, USA, at depths from 21 to 438 m. This new species is unique amongst the species of the genus Synallactes because of the number and arrangement of dorsal papillae, number of Polian vesicles, together with the entire ossicle arrangement. In addition, this species has the shallowest bathymetric distribution ever recorded for this genus.

Spanish adaptation and validation of sexual distress scale in Colombian population.

Background/Objective: The adaptation and validation of measures to assess Sexual Distress (SD) are crucial for the diagnosis and treatment of sexual dysfunction. This study aimed to adapt and validate the Spanish Sexual Distress Scale (SDS) in a Colombian sample and provide a percentile ranking score for a comprehensive understanding of sexual distress among the population. Method: Five hundred ninety-six people from Colombia (50.08 % women; 49.92 % men) aged 18-60 participated in the study. Exploratory and confirmatory factorial analyses and a convergent validity analysis were performed. Results: The SDS showed a high internal consistency (Ω = .95, α = .94) and a unidimensional model. Significative correlations were found between the SDS and related measures with sexual functioning, further supporting its convergent validity. Conclusions: The SDS is a valid and reliable measure to evaluate SD in Colombians, with implications for clinical practice and sexual health research. More investigations are needed to address the limitations, strengthen the validity and reliability of the scale, and develop specific interventions based on its results.

Evaluation of knowledge-based planning models for male pelvic CBCT-based online adaptive radiotherapy on conventional linear accelerators.

PURPOSE: To assess the practicality of employing a commercial knowledge-based planning tool (RapidPlan) to generate adapted intact prostate and prostate bed volumetric modulated arc therapy (VMAT) plans on iterative cone-beam computed tomography (iCBCT) datasets. METHODS AND MATERIALS: Intact prostate and prostate bed RapidPlan models were trained utilizing planning data from 50 and 44 clinical cases, respectively. To ensure that refined models were capable of producing adequate clinical plans with a single optimization, models were tested with 50 clinical planning CT datasets by comparing dose-volume histogram (DVH) and plan quality metric (PQM) values between clinical and RapidPlan-generated plans. The RapidPlan tool was then used to retrospectively generate adapted VMAT plans on daily iCBCT images for 20 intact prostate and 15 prostate bed cases. As before, DVH and PQM metrics were utilized to dosimetrically compare scheduled (iCBCT Verify) and adapted (iCBCT RapidPlan) plans. Timing data was collected to further evaluate the feasibility of integrating this approach within an online adaptive radiotherapy workflow. RESULTS: Model testing results confirmed the models were capable of producing VMAT plans within a single optimization that were overall improved upon or dosimetrically comparable to original clinical plans. Direct application of RapidPlan on iCBCT datasets produced satisfactory intact prostate and prostate bed plans with generally improved target volume coverage/conformality and rectal sparing relative to iCBCT Verify plans as indicated by DVH values, though bladder metrics were marginally increased on average. Average PQM values for iCBCT RapidPlans were significantly improved compared to iCBCT Verify plans. The average time required [in mm:ss] to generate adapted plans was 06:09 ± 02:06 (intact) and 07:12 ± 01:04 (bed). CONCLUSION: This study demonstrated the feasibility of leveraging RapidPlan to expeditiously generate adapted VMAT intact prostate and prostate bed plans on iCBCT datasets. In general, adapted plans were dosimetrically improved relative to scheduled plans, emphasizing the practicality of the proposed approach.

Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial.

PURPOSE: We aimed to determine if ultrahypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is noninferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. METHODS AND MATERIALS: This study was a multicenter, randomized, controlled, noninferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, Prostate-specific antigen <10 ng/mL, and clinical stage T1-T2a N0 M0 according to 7th edition of the American Joint Committee on Cancer tumor-node-metastasis cancer staging system. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Noninferiority for FFF was determined based on 1-sided confidence intervals. Toxicities were compared at different time points using Fisher's exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. RESULTS: Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR, 3.9-5.2). The 2-year FFF was 100% for both groups, with the 1-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI, -1.70% to 6.96%), favoring the SBRT arm, thus fulfilling the prespecified criteria for noninferiority of SBPT compared with CFPT. Rates of gastrointestinal and genitourinary G2 and G3 toxicities did not differ significantly between groups. Further, HRQoL metrics did not differ significantly between groups over the study's median follow-up. CONCLUSIONS: SBPT is noninferior to CFPT regarding FFF, with similar long-term genitourinary and gastrointestinal toxicity rates and minimal impact in patient-reported HRQoL over time.

Walnut Jug r 1 is Responsible for Primary Sensitization among Patients Suffering Walnut-Hazelnut 2S Albumin Cross-Reactivity.

Walnut and hazelnut coallergy is a frequent manifestation in clinical practice whose molecular basis remains unclear. For this purpose, walnut-hazelnut cross-reactivity was evaluated in 20 patients allergic to one or both tree nuts and sensitized to their 2S albumins. Immunoblotting assays showed that 85% of patients recognized Jug r 1, walnut 2S albumin, which was associated with the development of severe symptoms; 50% of them corecognized hazelnut 2S albumin, Cor a 14. Both allergens were isolated using chromatographic techniques. Inhibition ELISAs revealed that Jug r 1 strongly inhibited the binding of Cor a 14-specific IgE, but Cor a 14 only partially inhibited Jug r 1-specific IgE binding. Our results showed that patients sensitized to walnut/hazelnut 2S albumins were not a homogeneous population. There were patients sensitized to specific epitopes of walnut 2S albumins and patients sensitized to cross-reactive epitopes between walnut and hazelnut, with Jug r 1 being the primary sensitizer.

Association of dead space fraction to mortality in patients with COVID-19-related ARDS: A historical cohort observational study.

OBJECTIVE: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DESIGN: Observational study of a historical cohort. SETTING: University hospital in Medellin, Colombia. PARTICIPANTS: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. INTERVENTIONS: Measurement of VD/VT, CMV, and VR in COVID-19 patients. MAIN VARIABLES OF INTEREST: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. RESULTS: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017). CONCLUSIONS: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Working memory constraints for visuomotor retrieval strategies.

Recent work has shown the fundamental role that cognitive strategies play in visuomotor adaptation. Although algorithmic strategies, such as mental rotation, are flexible and generalizable, they are computationally demanding. To avoid this computational cost, people can instead rely on memory retrieval of previously successful visuomotor solutions. However, such a strategy is likely subject to stimulus-response associations and rely heavily on working memory. In a series of five experiments, we sought to estimate the constraints in terms of capacity and precision of working memory retrieval for visuomotor adaptation. This was accomplished by leveraging different variations of visuomotor item-recognition and visuomotor rotation tasks where we associated unique rotations with specific targets in the workspace and manipulated the set size (i.e., number of rotation-target associations). Notably, from experiment 1 to 4, we found key signatures of working memory retrieval and not mental rotation. In particular, participants were less accurate and slower for larger set sizes and less recent items. Using a Bayesian latent-mixture model, we found that such decrease in performance was the result of increasing guessing behavior and less precise memories. In addition, we estimated that participants' working memory capacity was limited to two to five items, after which guessing increasingly dominated performance. Finally, in experiment 5, we showed how the constraints observed across experiments 1 to 4 can be overcome when relying on long-term memory retrieval. Our results point to the opportunity of studying other sources of memories where visuomotor solutions can be stored (e.g., episodic memories) to achieve successful adaptation.NEW & NOTEWORTHY We show that humans can adapt to feedback perturbations in different variations of the visuomotor rotation task by retrieving the successful solutions from working memory. In addition, using a Bayesian latent-mixture model, we reveal that guessing and low-precision memories are both responsible for the decrease in participants' performance as the number of solutions to memorize increases. These constraints can be overcome by relying on long-term memory retrieval resulting from extended practice with the visuomotor solutions.

The Status and Challenges for Prostate Stereotactic Body Radiation Therapy Treatments in United States Proton Therapy Centers: An NRG Oncology Practice Survey.

Purpose: To report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and Methods: A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial.

Purpose: Treatment options for recurrent esophageal cancer (EC) previously treated with radiation therapy (RT) are limited. Reirradiation (reRT) with proton beam therapy (PBT) can offer lower toxicities by limiting doses to surrounding tissues. In this study, we present the first multi-institutional series reporting on toxicities and outcomes after reRT for locoregionally recurrent EC with PBT. Methods and Materials: Analysis of the prospective, multicenter, Proton Collaborative Group registry of patients with recurrent EC who had previously received photon-based RT and underwent PBT reRT was performed. Patient/tumor characteristics, treatment details, outcomes, and toxicities were collected. Local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Event time was determined from reRT start. Results: Between 2012 and 2020, 31 patients received reRT via uniform scanning/passive scattering (61.3%) or pencil beam scanning (38.7%) PBT at 7 institutions. Median prior RT, PBT reRT, and cumulative doses were 50.4 Gy (range, 37.5-110.4), 48.6 Gy (relative biological effectiveness) (25.2-72.1), and 99.9 Gy (79.1-182.5), respectively. Of these patients, 12.9% had 2 prior RT courses, and 67.7% received PBT with concurrent chemotherapy. Median follow-up was 7.2 months (0.9-64.7). Post-PBT, there were 16.7% locoregional only, 11.1% distant only, and 16.7% locoregional and distant recurrences. Six-month LC, DMFS, and OS were 80.5%, 83.4%, and 69.1%, respectively. One-year LC, DMFS, and OS were 67.1%, 83.4%, and 27%, respectively. Acute grade ≥3 toxicities occurred in 23% of patients, with 1 acute grade 5 toxicity secondary to esophageal hemorrhage, unclear if related to reRT or disease progression. No grade ≥3 late toxicities were reported. Conclusions: In the largest report to date of PBT for reRT in patients with recurrent EC, we observed acceptable acute toxicities and encouraging rates of disease control. However, these findings are limited by the poor prognoses of these patients, who are at high risk of mortality. Further research is needed to better assess the long-term benefits and toxicities of PBT in this specific patient population.