Relationship between gait quality measures and modular neuromuscular control parameters in chronic post-stroke individuals.

BACKGROUND: Recent evidence suggests that disinhibition and/or hyperexcitation of the brainstem descending pathways and intraspinal motor network diffuse spastic synergistic activation patterns after stroke. This results in simplified or merged muscle sets (i.e., muscle modules or synergies) compared to non-impaired individuals and this leads to poor walking performance. However, the relations of how these neuromuscular deficits influence gait quality (e.g., symmetry or natural walking patterns) are still unclear. The objective of this exploratory study was to investigate the relations of modular neuromuscular framework and gait quality measures in chronic stroke individuals. METHODS: Sixteen chronic post-stroke individuals participated in this study. Full lower body three-dimensional kinematics and electromyography (EMG) were concurrently measured during overground walking at a comfortable speed. We first examined changes in gait quality measures across the number of muscle modules using linear regression model. Then, a stepwise multiple regression was used to investigate the optimal combination of the neuromuscular parameters that associates with gait quality measures. RESULTS: We observed that subjects who had a lower number of muscle modules revealed reduced function (i.e., speed) and greater asymmetry in the kinematic parameters including limb length, footpath area, knee flexion/extension, and hip abduction/adduction (all p < 0.05). We also found that the combination of input variables from the modular neuromuscular control framework significantly associated with gait quality measures (average [Formula: see text]). Those variables included variability accounted for ([Formula: see text]) information from the muscle modules and area under the EMG envelope curves of the quadriceps (i.e., rectus femoris and vastus lateralis) and tibialis anterior muscles. CONCLUSIONS: The results suggest that there exists a significant correlation between the neuromuscular control framework and the gait quality measures. This study helps to understand the underlying mechanism of disturbances in gait quality and provides insight for a more comprehensive outcome measure to assess gait impairment after stroke.

Implementation of a real-time, ultrasound-guided prostate HDR brachytherapy program.

This work presents a comprehensive commissioning and workflow development process of a real-time, ultrasound (US) image-guided treatment planning system (TPS), a stepper and a US unit. To adequately benchmark the system, commissioning tasks were separated into (1) US imaging, (2) stepper mechanical, and (3) treatment planning aspects. Quality assurance US imaging measurements were performed following the AAPM TG-128 and GEC-ESTRO recommendations and consisted of benchmarking the spatial resolution, accuracy, and low-contrast detectability. Mechanical tests were first used to benchmark the electronic encoders within the stepper and were later expanded to evaluate the needle free length calculation accuracy. Needle reconstruction accuracy was rigorously evaluated at the treatment planning level. The calibration length of each probe was redundantly checked between the calculated and measured needle free length, which was found to be within 1 mm for a variety of scenarios. Needle placement relative to a reference fiducial and coincidence of imaging coordinate origins were verified to within 1 mm in both sagittal and transverse imaging planes. The source strength was also calibrated within the interstitial needle and was found to be 1.14% lower than when measured in a plastic needle. Dose calculations in the TPS and secondary dose calculation software were benchmarked against manual TG-43 calculations. Calculations among the three calculation methods agreed within 1% for all calculated points. Source positioning and dummy coincidence was tested following the recommendations of the TG-40 report. Finally, the development of the clinical workflow, checklists, and planning objectives are discussed and included within this report. The commissioning of real-time, US-guided HDR prostate systems requires careful consideration among several facets including the image quality, dosimetric, and mechanical accuracy. The TPS relies on each of these components to develop and administer a treatment plan, and as such, should be carefully examined.

Optimization of ScSZ/GDC bilayer thin film electrolyte for anodic aluminum oxide supported low temperature solid oxide fuel cells.

Due to the poor chemical stability of CeO2-based materials, doped CeO2 electrolytes are generally used as a stabilized ZrO2 protection layer/doped CeO2 electrolyte bilayer structure. Since the ionic conductivity of stabilized ZrO2 materials is lower than that of doped CeO2 materials, the thickness of the ZrO2 protective layer needs to be optimized. Thus, in this study, nano-porous anodic aluminum oxide template based scandia stabilized zirconia (ScSZ)/gadolinia doped ceria (GDC) bilayer electrolyte low temperature solid oxide fuel cells (LT-SOFCs) are successfully fabricated and investigated. The optimized thickness of the ScSZ protection layer is revealed by physical and electrochemical characterizations to maximize the performance of LT-SOFCs. The 160 nm ScSZ/400 nm GDC bilayer electrolyte LT-SOFC achieves a maximum power density of 252 mW · cm-2 and an open circuit voltage of 1.02 V OCV at 450 °C.

Does the apex optimization line matter for single-channel vaginal cylinder brachytherapy planning?

The objective of this study is to test the impact of the use of the apex optimization line for new vaginal cylinder (VC) applicators. New single channel VC applicators (Varian) that have different top thicknesses but the same diameters as the old VC applicators (2.0 cm diameter, 2.3, 2.6, 3.0, and 3.5 cm) were compared using phantom studies. Old VC applicator plans without the apex optimization line were also compared to the plans with an apex optimization line. The apex doses were monitored at 5 mm depth doses (eight points) where a prescription dose (Rx) of 6 Gy was prescribed. VC surface doses (eight points) were also analyzed. The new VC applicator plans without apex optimization line presented significantly lower 5-mm depth doses over the Rx (on average -31 ± 7%, P < 0.00001) due to thicker VC tops (3.4 ± 1.1 mm thicker with the range of 1.2-4.4 mm) than the old VC applicators. Old VC applicator plans also showed a statistically significant reduction (P < 0.00001) due to the Ir-192 source anisotropic effect at the apex region, but the percent reduction over the Rx was only -7 ± 9%. However, by adding the apex optimization line to the new VC applicator plans, the plans improved 5-mm depth doses (-7 ± 9% over Rx) that were not statistically different from old VC applicator plans (P = 0.923), along with apex VC surface doses (-22 ± 10% over old VC vs -46 ± 7% without using apex optimization line). The use of the apex optimization line is important in order to avoid significant additional cold doses (-24 ± 2%) at the prescription depth (5 mm) of the apex, specifically for the new VC applicators that have thicker tops. A template-based vaginal cylinder planning reduced the intra- and inter-planner variations of manual generation of apex optimization line, along with treatment time.

Patient's specific integration of OAR doses (D2 cc) from EBRT and 3D image-guided brachytherapy for cervical cancer.

The objective of this study was to assess the recommended DVH parameter (e.g., D2 cc) addition method used for combining EBRT and HDR plans, against a reference dataset generated from an EQD2-based DVH addition method. A revised DVH parameter addition method using EBRT DVH parameters derived from each patient's plan was proposed and also compared with the reference dataset. Thirty-one biopsy-proven cervical cancer patients who received EBRT and HDR brachytherapy were retrospectively analyzed. A parametrial and/or paraaortic EBRT boost were clinically performed on 13 patients. Ten IMRT and 21 3DCRT plans were determined. Two different HDR techniques for each HDR plan were analyzed. Overall D2 cc and D0.1 cc OAR doses in EQD2 were statistically analyzed for three different DVH parameter addition methods: a currently recommended method, a proposed revised method, and a reference DVH addition method. The overall D2 ccEQD2 values for all rectum, bladder, and sigmoid for a conformal, volume optimization HDR plan generated using the current DVH parameter addition method were significantly underestimated on average -5 to -8% when compared to the values obtained from the reference DVH addition technique (P < 0.01). The revised DVH parameter addition method did not present statistical differences with the reference technique (P > 0.099). When PM boosts were considered, there was an even greater average underestimation of -8~-10% for overall OAR doses of conformal HDR plans when using the current DVH parameter addition technique as compared to the revised DVH parameter addition. No statistically significant differences were found between the 3DCRT and IMRT techniques (P > 0.3148). It is recommended that the overall D2 cc EBRT doses are obtained from each patient's EBRT plan.

Commissioning of a 3D image-based treatment planning system for high-dose-rate brachytherapy of cervical cancer.

The objective of this work is to present commissioning procedures to clinically implement a three-dimensional (3D), image-based, treatment-planning system (TPS) for high-dose-rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8-1.0 mm on MRI when compared with X-rays. In-house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose-volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image-based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End-to-end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image-based TPS for HDR BT for GYN cancer.

Tumor control probability reduction in gated radiotherapy of non-small cell lung cancers: a feasibility study.

We studied the feasibility of evaluating tumor control probability (TCP) reductions for tumor motion beyond planned gated radiotherapy margins. Tumor motion was determined from cone-beam CT projections acquired for patient setup, intrafraction respiratory traces, and 4D CTs for five non-small cell lung cancer (NSCLC) patients treated with gated radiotherapy. Tumors were subdivided into 1 mm sections whose positions and doses were determined for each beam-on time point. (The dose calculation model was verified with motion phantom measurements.) The calculated dose distributions were used to generate the treatment TCPs for each patient. The plan TCPs were calculated from the treatment planning dose distributions. The treatment TCPs were compared to the plan TCPs for various models and parameters. Calculated doses matched phantom measurements within 0.3% for up to 3 cm of motion. TCP reductions for excess motion greater than 5mm ranged from 1.7% to 11.9%, depending on model parameters, and were as high as 48.6% for model parameters that simulated an individual patient. Repeating the worst case motion for all fractions increased TCP reductions by a factor of 2 to 3, while hypofractionation decreased these reductions by as much as a factor of 3. Treatment motion exceeding gating margins by more than 5 mm can lead to considerable TCP reductions. Appropriate margins for excess motion are recommended, unless applying daily tumor motion verification and adjusting thegating window.

Bladder and rectum dose estimations on digitized radiographs for vaginal brachytherapy after hysterectomy.

The purpose of this study was to evaluate the feasibility of assessing bladder and rectal point doses, using orthogonal radiographs without treatment planning, for vaginal cylinder applicator (VC), high-dose-rate (HDR) vaginal cuff brachytherapy (BT) after hysterectomy. Thirty-three VC HDR BT treatment plans from 31 postop- erative endometrial cancer patients were retrospectively analyzed. Single-channel VC with four differing diameters - 2.0 cm, 2.3 cm, 2.6 cm, and 3.0 cm - were analyzed. Dose-distance modeling was performed to estimate bladder and rectal point doses by measuring distances on each orthogonal radiograph without treat- ment planning. The estimated doses were then compared with doses calculated on treatment planning system (TPS). Their percent (%) dose differences were recorded. Analysis was performed for each VC size, ICRU bladder and rectal points, and the closest rectal point. The estimated doses obtained from dose-distance modeling displayed on average less than 2.5% difference when compared with TPS doses at ICRU bladder and rectal points for each VC size. Dose percent differences between estimated values and TPS values were on average 1.9% and 2.5% for ICRU blad- der and rectal point, respectively, regardless of VC sizes. Dose-distance modeling for closest rectal point presented on average 5.4% dose difference when compared with TPS values of all VC sizes. It was feasible to estimate rectal and bladder point doses by measuring distances on orthogonal radiographs without treatment plan- ning. Percent dose differences were 2.5% less for both ICRU bladder and rectal points, regardless of VC sizes. The use of closest rectal point is not recommended for estimating rectal dose. 

Shape Memory Alloy-Based Reactive Tubular (SMART) Brake for Compact and Energy-Efficient Wearable Robot Design.

Soft wearable robots have been gaining increasing popularity for enhancing human physical abilities and assisting people who have physical limitations. These robots typically use tendon-driven mechanisms (TDMs) to enable remote actuation to provide better usability with compact design. TDMs comprise an actuator, an end-effector, and a transmission system by using cables or tendons to transfer forces from the actuator to the end-effector. Tendons are typically routed by frictionless guiding tubes to minimize force losses, variations in the force direction, and the volume. To make soft wearable robots even smaller, brakes need to be compacted because brakes are irreplaceable to ensure safety and energy efficiency. This study presents a shape memory alloy-based reactive tubular (SMART) brake for designing a compact and portable TDM-based device. The SMART brake actively adjusts the friction force between the brake and tendon, making it easy to achieve the desired friction state, ranging from low-friction states for free movement to high-friction states for effective braking. The brake is designed in a tubular shape, serving multifunctions as both a brake and a guiding tube. The brake's performance and theoretical model were validated through experiments and demonstrated by two wearable devices. The brake could hold a significant brake force of 19.37 N/11 mm while weighing only 0.3 g. These findings have major implications for the future development of TDM-based devices and soft wearable robots, paving the way for enhanced system portability, safety, and energy efficiency.

MRI-Guided High-Dose-Rate Gynecologic Brachytherapy Using an MR-Linac as an MR Simulator: A Single Institutional Experience.

PURPOSE: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development. METHODS AND MATERIALS: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New workflows were developed which were tested with a full dry run with a healthy volunteer including patient transfer, anesthesia considerations, and data transfer. Validation of the workflow was completed on 1 patient who received imaging on both the Unity magnetic resonance imaging (MRI) and on a dedicated 3 Tesla MRI simulator. RESULTS: Imaging analysis results were favorable with MR-linac images with a maximum distortion of 0.96 mm and a 1.36-mm over a 350-mm diameter spherical volume on the T1- and T2-weighted images, respectively, and the maximum effect of the applicator was 0.36 ppm of the main magnetic field. Reconstruction uncertainties of the Venezia applicator's tandem and 2 lunar-ovoids on the MR-linac images were within the 2-mm tolerance of the International Commission on Radiation Units and Measurements Report 89. Treatment planning and delivery was performed on the MR-HDR quality assurance phantom without issue. Dry run and healthy volunteer imaging showed adequate performance of both vital monitoring and HDR equipment. For the patient for which both the Unity MRI and 3 Tesla images were acquired, 95.78% and 95.80% of the high risk clinical target volume received 100% of the dose, respectively. Both plans were considered clinically acceptable. CONCLUSIONS: Unity MR-linac images were successfully used in gynecologic HDR brachytherapy treatment planning, and a usable workflow was established.

Hand Grasp Motion Intention Recognition Based on High-Density Electromyography in Chronic Stroke Patients.

Stroke is a debilitating condition that leads to a loss of motor function, inability to perform daily life activities, and ultimately worsening quality of life. Robot-based rehabilitation is a more effective method than conventional rehabilitation but needs to accurately recognize the patient's intention so that the robot can assist the patient's voluntary motion. This study focuses on recognizing hand grasp motion intention using high-density electromyography (HD-EMG) in patients with chronic stroke. The study was conducted with three chronic stroke patients and involved recording HD-EMG signals from the muscles involved in hand grasp motions. The adaptive onset detection algorithm was used to accurately identify the start of hand grasp motions accurately, and a convolutional neural network (CNN) was trained to classify the HD-EMG signals into one of four grasping motions. The average true positive and false positive rates of the grasp onset detection on three subjects were 91.6% and 9.8%, respectively, and the trained CNN classified the grasping motion with an average accuracy of 76.3%. The results showed that using HD-EMG can provide accurate hand grasp motion intention recognition in chronic stroke patients, highlighting the potential for effective robot-based rehabilitation.

The population percentile allowance method for determining systematic spatial error tolerances for temporary intensity modulated brachytherapy.

BACKGROUND: Multiple approaches are under development for delivering temporary intensity modulated brachytherapy (IMBT) using partially shielded applicators wherein the delivered dose distributions are sensitive to spatial uncertainties in both the applicator position and shield orientation, rather than only applicator position as with conventional high-dose-rate brachytherapy (HDR-BT). Sensitivity analyses to spatial uncertainties have been reported as components of publications on these emerging technologies, however, a generalized framework for the rigorous determination of the spatial uncertainty tolerances of dose-volume parameters is needed. PURPOSE: To derive and present the population percentile allowance (PPA) method, a generalized mathematical and statistical framework to evaluate the tolerance of temporary IMBT approaches to spatial uncertainties in applicator position and shield orientation. METHODS: A mathematical formalism describing geometric applicator position and shield orientation shifts was derived that supports straight and curved applicators and applies to serial and helical rotating shield brachytherapy (RSBT) and direction modulated brachytherapy (DMBT). The PPA method entails defining the percentage of a patient population receiving a given therapy that is, allowed to receive dose-volume errors in the target volume and specified organs at risk of a defined percentage or less, then determining what combinations of applicator position and shield orientation systematic errors would be expected to produce that outcome in the population. The PPA method was applied to the use case of multi-shield helical 169 Yb-based RSBT for cervical cancer, with 45° and 180° shield emission angles. A total of 37 cervical cancer patients were considered in the population, with average (± 1 standard deviation) HR-CTV volumes of 79 cm3  ± 37 cm3 and optimized baseline treatment plans (no spatial uncertainties applied) created for each patient to meet dose-volume requirements of 85 GyEQD2 (equivalent uniform dose in 2 Gy fraction), with D2cc tolerance doses of 90 GyEQD2 , 75 GyEQD2 , and 75 GyEQD2 for bladder, rectum, and sigmoid colon, respectively. RESULTS: For the PPA requirement that 90% of cervical cancer patients receiving multi-shield helical RSBT could have a maximum dose-volume uncertainty of 10% for high-risk clinical target volume (HR-CTV) D90 (minimum dose to hottest 90%) and bladder, rectum, and sigmoid colon D2cc (minimum dose to hottest 2 cm3 ), the tolerance systematic applicator position and shield orientation uncertainties were approximately ± 1.0 mm and ± 4.25°, respectively. For ± 1.5 mm and ± 5° systematic applicator position and shield orientation tolerances, 90% of the patients considered would have a maximum dose-volume uncertainty of 12.8% or less. CONCLUSION: The PPA method was formalized to determine the temporary IMBT spatial uncertainty tolerances that would be expected to result in an allowed percentage of a population of patients receiving relative dose-volume errors above a defined percentage. Multi-shield, helical 169 Yb-based RSBT for cervical cancer was evaluated and tolerances determined, which, if applied on each treatment fraction, would represent an extreme situation. The PPA method is applicable to a variety of temporary IMBT approaches and can be used to rigorously determine the design parameters for the delivery systems such as mechanical driver motor accuracy, shield angle backlash, applicator rotation, and applicator fixation stability.

Predictive power of deep-learning segmentation based prognostication model in non-small cell lung cancer.

Purpose: The study aims to create a model to predict survival outcomes for non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT) using deep-learning segmentation based prognostication (DESEP). Methods: The DESEP model was trained using imaging from 108 patients with NSCLC with various clinical stages and treatment histories. The model generated predictions based on unsupervised features learned by a deep-segmentation network from computed tomography imaging to categorize patients into high and low risk groups for overall survival (DESEP-predicted-OS), disease specific survival (DESEP-predicted-DSS), and local progression free survival (DESEP-predicted-LPFS). Serial assessments were also performed using auto-segmentation based volumetric RECISTv1.1 and computer-based unidimensional RECISTv1.1 patients was performed. Results: There was a concordance between the DESEP-predicted-LPFS risk category and manually calculated RECISTv1.1 (φ=0.544, p=0.001). Neither the auto-segmentation based volumetric RECISTv1.1 nor the computer-based unidimensional RECISTv1.1 correlated with manual RECISTv1.1 (p=0.081 and p=0.144, respectively). While manual RECISTv1.1 correlated with LPFS (HR=6.97,3.51-13.85, c=0.70, p<0.001), it could not provide insight regarding DSS (p=0.942) or OS (p=0.662). In contrast, the DESEP-predicted methods were predictive of LPFS (HR=3.58, 1.66-7.18, c=0.60, p<0.001), OS (HR=6.31, 3.65-10.93, c=0.71, p<0.001) and DSS (HR=9.25, 4.50-19.02, c=0.69, p<0.001). The promising results of the DESEP model were reproduced for the independent, external datasets of Stanford University, classifying survival and 'dead' group in their Kaplan-Meyer curves (p = 0.019). Conclusion: Deep-learning segmentation based prognostication can predict LPFS as well as OS, and DSS after SBRT for NSCLC. It can be used in conjunction with current standard of care, manual RECISTv1.1 to provide additional insights regarding DSS and OS in NSCLC patients receiving SBRT. Summary: While current standard of care, manual RECISTv1.1 correlated with local progression free survival (LPFS) (HR=6.97,3.51-13.85, c=0.70, p<0.001), it could not provide insight regarding disease specific survival (DSS) (p=0.942) or overall survival (OS) (p=0.662). In contrast, the deep-learning segmentation based prognostication (DESEP)-predicted methods were predictive of LPFS (HR=3.58, 1.66-7.18, c=0.60, p<0.001), OS (HR=6.31, 3.65-10.93, c=0.71, p<0.001) and DSS (HR=9.25, 4.50-19.02, c=0.69, p<0.001). DESEP can be used in conjunction with current standard of care, manual RECISTv1.1 to provide additional insights regarding DSS and OS in NSCLC patients.

Functional MRI Assessment of Brain Activity During Hand Rehabilitation with an MR-Compatible Soft Glove in Chronic Stroke Patients: A Preliminary Study.

Brain plasticity plays a significant role in functional recovery after stroke, but the specific benefits of hand rehabilitation robot therapy remain unclear. Evaluating the specific effects of hand rehabilitation robot therapy is crucial in understanding how it impacts brain activity and its relationship to rehabilitation outcomes. This study aimed to investigate the brain activity pattern during hand rehabilitation exercise using functional magnetic resonance imaging (fMRI), and to compare it before and after 3-week hand rehabilitation robot training. To evaluate it, an fMRI experimental environment was constructed to facilitate the same hand posture used in rehabilitation robot therapy. Two stroke survivors participated and the conjunction analysis results from fMRI scans showed that patient 1 exhibited a significant improvement in activation profile after hand rehabilitation robot training, indicative of improved motor function in the bilateral motor cortex. However, activation profile of patient 2 exhibited a slight decrease, potentially due to habituation to the rehabilitation task. Clinical results supported these findings, with patient 1 experiencing a greater increase in FMA score than patient 2. These results suggest that hand rehabilitation robot therapy can induce different brain activity patterns in stroke survivors, which may be linked to patient-specific training outcomes. Further studies with larger sample sizes are necessary to confirm these findings.

Modification of mixed-nitrogen anions configuration for accelerating lithium ions transport in the LiFePO4 electrode.

Olivine-type LiFePO4 (LFP) is considered a promising cathode material for lithium-ion batteries (LIBs) owing to its abundance, high specific capacity, and cycling performance. However, its poor electronic and ionic transportation properties degrade the high rate capability, which limits its use in high-energy-density LIBs for applications such as electric vehicles. Therefore, in this study, we propose a modification of the anion configuration through nitrogen substitution using ion implantation to improve electronic and ionic transport during lithiation/delithiation. We found that nitrogen substitution at the oxygen sites effectively improved the electrochemical properties through surface modification and charge-transfer kinetics. In particular, the increased amount of nitrogen substitution at the surface regions resulted in reduced ionic and electronic resistances. These modified characteristics led to a remarkable rate capability with a high capacity (128.2 mA h g-1 at 10C). We expect that these modified anion effects on the electrochemical properties can be effective in the design of cathode materials for LIBs.

Acute coronary event (ACE) prediction following breast radiotherapy by features extracted from 3D CT, dose, and cardiac structures.

PURPOSE: Heart toxicity, such as major acute coronary events (ACE), following breast radiation therapy (RT) is of utmost concern. Thus, many studies have been investigating the effect of mean heart dose (MHD) and dose received in heart sub-structures on toxicity. Most studies focused on the dose thresholds in the heart and its sub-structures, while few studies adopted such computational methods as deep neural networks (DNN) and radiomics. This work aims to construct a feature-driven predictive model for ACE after breast RT. METHODS: A recently proposed two-step predictive model that extracts a number of features from a deep auto-segmentation network and processes the selected features for prediction was adopted. This work refined the auto-segmenting network and feature processing algorithms to enhance performance in cardiac toxicity prediction. In the predictive model, the deep convolutional neural network (CNN) extracted features from 3D computed tomography (CT) images and dose distributions in three automatically segmented heart sub-structures, including the left anterior descending artery (LAD), right coronary artery (RCA), and left ventricle (LV). The optimal feature processing workflow for the extracted features was explored to enhance the prediction accuracy. The regions associated with toxicity were visualized using a class activation map (CAM)-based technique. Our proposed model was validated against a conventional DNN (convolutional and fully connected layers) and radiomics with a patient cohort of 84 cases, including 29 and 55 patient cases with and without ACE. Of the entire 84 cases, 12 randomly chosen cases (5 toxicity and 7 non-toxicity cases) were set aside for independent test, and the remaining 72 cases were applied to 4-fold stratified cross-validation. RESULTS: Our predictive model outperformed the conventional DNN by 38% and 10% and radiomics-based predictive models by 9% and 10% in AUC for 4-fold cross-validations and independent test, respectively. The degree of enhancement was greater when incorporating dose information and heart sub-structures into feature extraction. The model whose inputs were CT, dose, and three sub-structures (LV, LAD, and RCA) reached 96% prediction accuracy on average and 0.94 area under the curve (AUC) on average in the cross-validation, and also achieved prediction accuracy of 83% and AUC of 0.83 in the independent test. On 10 correctly predicted cases out of 12 for the independent test, the activation maps implied that for cases of ACE toxicity, the higher intensity was more likely to be observed inside the LV. CONCLUSIONS: The proposed model characterized by modifications in model input with dose distributions and cardiac sub-structures, and serial processing of feature extraction and feature selection techniques can improve the predictive performance in ACE following breast RT.

Redox regulation of rotation of the cyanobacterial F1-ATPase containing thiol regulation switch.

F(1)-ATP synthase (F(1)-ATPase) is equipped with a special mechanism that prevents the wasteful reverse reaction, ATP hydrolysis, when there is insufficient proton motive force to drive ATP synthesis. Chloroplast F(1)-ATPase is subject to redox regulation, whereby ATP hydrolysis activity is regulated by formation and reduction of the disulfide bond located on the γ subunit. To understand the molecular mechanism of this redox regulation, we constructed a chimeric F(1) complex (α(3)ß(3)γ(redox)) using cyanobacterial F(1), which mimics the regulatory properties of the chloroplast F(1)-ATPase, allowing the study of its regulation at the single molecule level. The redox state of the γ subunit did not affect the ATP binding rate to the catalytic site(s) and the torque for rotation. However, the long pauses caused by ADP inhibition were frequently observed in the oxidized state. In addition, the duration of continuous rotation was relatively shorter in the oxidized α(3)ß(3)γ(redox) complex. These findings lead us to conclude that redox regulation of CF(1)-ATPase is achieved by controlling the probability of ADP inhibition via the γ subunit inserted region, a sequence feature observed in both cyanobacterial and chloroplast ATPase γ subunits, which is important for ADP inhibition (Sunamura, E., Konno, H., Imashimizu-Kobayashi, M., Sugano, Y., and Hisabori, T. (2010) Plant Cell Physiol. 51, 855-865).

Characterization of the relationship between ADP- and epsilon-induced inhibition in cyanobacterial F1-ATPase.

The ATPase activity of chloroplast and bacterial F(1)-ATPase is strongly inhibited by both the endogenous inhibitor ε and tightly bound ADP. Although the physiological significance of these inhibitory mechanisms is not very well known for the membrane-bound F(0)F(1), these are very likely to be important in avoiding the futile ATP hydrolysis reaction and ensuring efficient ATP synthesis in vivo. In a previous study using the α(3)ß(3)γ complex of F(1) obtained from the thermophilic cyanobacteria, Thermosynechococcus elongatus BP-1, we succeeded in determining the discrete stop position, ∼80° forward from the pause position for ATP binding, caused by ε-induced inhibition (ε-inhibition) during γ rotation (Konno, H., Murakami-Fuse, T., Fujii, F., Koyama, F., Ueoka-Nakanishi, H., Pack, C. G., Kinjo, M., and Hisabori, T. (2006) EMBO J. 25, 4596-4604). Because γ in ADP-inhibited F(1) also pauses at the same position, ADP-induced inhibition (ADP-inhibition) was assumed to be linked to ε-inhibition. However, ADP-inhibition and ε-inhibition should be independent phenomena from each other because the ATPase core complex, α(3)ß(3)γ, also lapses into the ADP-inhibition state. By way of thorough biophysical and biochemical analyses, we determined that the ε subunit inhibition mechanism does not directly correlate with ADP-inhibition. We suggest here that the cyanobacterial ATP synthase ε subunit carries out an important regulatory role in acting as an independent "braking system" for the physiologically unfavorable ATP hydrolysis reaction.

Development and Clinical Evaluation of a Novel Foot Stretching Robot That Simultaneously Stretches Plantar Fascia and Achilles Tendon for Treatment of Plantar Fasciitis.

OBJECTIVE: This paper presents the development and clinical evaluation of a foot stretching robot that simultaneously stretches the plantar fascia and Achilles tendon for the treatment of plantar fasciitis. The therapeutic effectiveness of the robot and feasibility of using metatarsophalangeal joint stiffness as an indicator of recovery were identified through the clinical evaluations. METHODS: The robot implements an effective foot stretching protocol through a novel mechanism design that simultaneously stretches the plantar fascia and Achilles tendon using a single motor. Thirty patients with plantar fasciitis and fifteen healthy participants volunteered in the cross-sectional clinical evaluation, and nine patients from the patients group participated in the one-month clinical trial. Four main outcomes (Foot Function Index, Visual Analogue Scale-Foot and Ankle, plantar fascia thickness, and metatarsophalangeal joint stiffness) were used for the clinical evaluations. RESULTS: In the cross-sectional clinical evaluation, the symptomatic feet of patients showed moderate negative correlation between normalized metatarsophalangeal joint stiffness and plantar fascia thickness with statistical significance. In the one-month clinical trial, all the main outcomes showed significant improvement after using the developed robot. Comparing our results with previous studies also indicated a therapeutic superiority of our robot for treating plantar fasciitis. CONCLUSION: Our foot stretching robot had significant therapeutic effect on plantar fasciitis, and normalized metatarsophalangeal joint stiffness measured by our robot could be used as a monitoring indicator for recovery from plantar fasciitis. SIGNIFICANCE: This study contributed to practical issues related to treatment of plantar fasciitis, and our results could be applied to effective treatment of plantar fasciitis and progressive monitoring of recovery.

N+-Implantation on Nb Coating as Protective Layer for Metal Bipolar Plate in PEMFCs and Their Electrochemical Characteristics.

Nitrogen ions were implanted into the coated Nb layer by plasma immersion ion implantation to improve resistance to corrosion of a metal bipolar plate. Due to nitrogen implantation, the corrosion behavior of the Nb layer was enhanced. The electron microscope observation reveals that the microstructure of the Nb layer became denser and had fewer defects with increasing implantation energy. As a result, the densified structure effectively prevented direct contact with the corrosive electrolyte. In addition, at a higher implantation rate (6.40 × 1017 N2/cm2), a thin amorphous layer was formed on the surface, and the implanted nitrogen ions reacted at neighboring Nb sites, resulting in the localized formation of nitrides. Such phase and structural changes contributed to further improve corrosion resistance. In particular, the implanted Nb layer at bias voltage of 10 kV exhibited a current density more than one order of magnitude smaller with a two times faster stabilization than the as-deposited Nb layer under the PEMFC operating conditions.