Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.

BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aß) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. HIGHLIGHTS: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.

AI-based betting anomaly detection system to ensure fairness in sports and prevent illegal gambling.

This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model-a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70-80%.

Early-Onset Hearing Loss in Mouse Models of Alzheimer's Disease and Increased DNA Damage in the Cochlea.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polß+/-. The 3xTgAD/Polß+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polß+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

Evaluating the Efficacy of Machine Performance Checks as an Alternative to Winston-Lutz Quality Assurance Testing in the TrueBeam Linear Accelerator with HyperArc.

HyperArc is a preferred technique for treating brain metastases, employing a single isocenter for multiple lesions. Geometrical isocentricity in the TrueBeam linear accelerator with HyperArc is crucial. We evaluated machine performance checks (MPCs) as an alternative to the Winston-Lutz (WL) test to verify the treatment isocenter. Between January and July 2023, we assessed 53 data points using MPC and Winston-Lutz tests. The isocenter size obtained from the MPC and its sum, including the rotation-induced couch shift, were compared with the maximum total delta value from the Winston-Lutz test. The maximum total delta was 0.68 ± 0.10 mm, while the isocenter size was 0.28 ± 0.02 mm. The sum of the isocenter size and rotation-induced couch shift measured by MPC was 0.61 ± 0.03 mm. During the Winston-Lutz test (without couch rotation), the maximum total delta value was 0.56 ± 0.13 mm. A t-test analysis revealed a significant difference in the isocenter size averages between the Winston-Lutz and MPC outcomes, whereas the Pearson's correlation coefficient yielded no correlation. Our study highlights the necessity for separate MPC and Winston-Lutz tests for isocenter verification. Therefore, the Winston-Lutz test should precede stereotactic radiosurgery for isocenter verification.

Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice.

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.

Enhanced spin Seebeck effect via oxygen manipulation.

Spin Seebeck effect (SSE) refers to the generation of an electric voltage transverse to a temperature gradient via a magnon current. SSE offers the potential for efficient thermoelectric devices because the transverse geometry of SSE enables to utilize waste heat from a large-area source by greatly simplifying the device structure. However, SSE suffers from a low thermoelectric conversion efficiency that must be improved for widespread application. Here we show that the SSE substantially enhances by oxidizing a ferromagnet in normal metal/ferromagnet/oxide structures. In W/CoFeB/AlOx structures, voltage-induced interfacial oxidation of CoFeB modifies the SSE, resulting in the enhancement of thermoelectric signal by an order of magnitude. We describe a mechanism for the enhancement that results from a reduced exchange interaction of the oxidized region of ferromagnet, which in turn increases a temperature difference between magnons in the ferromagnet and electrons in the normal metal and/or a gradient of magnon chemical potential in the ferromagnet. Our result will invigorate research for thermoelectric conversion by suggesting a promising way of improving the SSE efficiency.

A Validation Study of a Deep Learning-Based Doping Drug Text Recognition System to Ensure Safe Drug Use among Athletes.

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used. The developed hybrid system, based on the Tesseract OCR model, can be accessed by both a smartphone and website. A total of 5379 words were extracted, and the system showed character recognition errors regarding 91 words, showing high accuracy (98.3%). The system correctly classified all 624 images for acceptable substances, 218 images for banned substances, and incorrectly recognized 44 of the banned substances as acceptable. The validity analysis showed a high level of accuracy (0.95), sensitivity (1.00), and specificity (0.93), suggesting system validity. The system has the potential of allowing athletes who lack knowledge about doping to quickly and accurately check whether they are taking banned substances. It may also serve as an efficient option to support the development of a fair and healthy sports culture.

Mitochondrial OGG1 expression reduces age-associated neuroinflammation by regulating cytosolic mitochondrial DNA.

Aging is accompanied by a decline in DNA repair efficiency, which leads to the accumulation of different types of DNA damage. Age-associated chronic inflammation and generation of reactive oxygen species exacerbate the aging process and age-related chronic disorders. These inflammatory processes establish conditions that favor accumulation of DNA base damage, especially 8-oxo-7,8 di-hydroguanine (8-oxoG), which in turn contributes to various age associated diseases. 8-oxoG is repaired by 8-oxoG glycosylase1 (OGG1) through the base excision repair (BER) pathway. OGG1 is present in both the cell nucleus and in mitochondria. Mitochondrial OGG1 has been implicated in mitochondrial DNA repair and increased mitochondrial function. Using transgenic mouse models and cell lines that have been engineered to have enhanced expression of mitochondria-targeted OGG1 (mtOGG1), we show that elevated levels of mtOGG1 in mitochondria can reverse aging-associated inflammation and improve functions. Old male mtOGG1Tg mice show decreased inflammation response, decreased TNFα levels and multiple pro-inflammatory cytokines. Moreover, we observe that male mtOGG1Tg mice show resistance to STING activation. Interestingly, female mtOGG1Tg mice did not respond to mtOGG1 overexpression. Further, HMC3 cells expressing mtOGG1 display decreased release of mtDNA into the cytoplasm after lipopolysacchride induction and regulate inflammation through the pSTING pathway. Also, increased mtOGG1 expression reduced LPS-induced loss of mitochondrial functions. These results suggest that mtOGG1 regulates age-associated inflammation by controlling release of mtDNA into the cytoplasm.

RecQ dysfunction contributes to social and depressive-like behavior and affects aldolase activity in mice.

RecQ helicase family proteins play vital roles in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biochemical and biological roles of RecQ helicases are rather well established, however, there is no systematic study comparing the behavioral changes among various RecQ-deficient mice including consequences of exposure to DNA damage. Here, we investigated the effects of ionizing irradiation (IR) on three RecQ-deficient mouse models (RecQ1, WRN and RecQ4). We find abnormal cognitive behavior in RecQ-deficient mice in the absence of IR. Interestingly, RecQ dysfunction impairs social ability and induces depressive-like behavior in mice after a single exposure to IR, suggesting that RecQ proteins play roles in mood and cognition behavior. Further, transcriptomic and metabolomic analyses revealed significant alterations in RecQ-deficient mice, especially after IR exposure. In particular, pathways related to neuronal and microglial functions, DNA damage repair, cell cycle, and reactive oxygen responses were downregulated in the RecQ4 and WRN mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our findings suggest that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing a potential therapeutic target.

Distribution and transformation of organophosphate esters in moving bed biofilm reactor.

A moving bed biofilm reactor (MBBR) process in wastewater treatment plants (WWTPs) uses plastic carriers, called biofilm carrier, to increase their treatment efficiency. Biofilm carrier is made up of plastic, containing the OPEs as flame retardants or plasticizers, so OPEs in biofilm carrier are possible to release from WWTPs to the river. This study investigated the effect of the MBBR process in WWTP on aquatic environments, focusing on OPEs. OPE eluted from the biofilm carrier by leaching test was tris(2-chloroethyl) phosphate (TCEP), and the concentration of the effluent compared to the influent was increased in the WWTP of the MBBR process. 3609 mg/day of TCEP would be discharged into the water using the second-order model with rate constant [Formula: see text] = 0.000451 (ng L-1)-1 h-1, which is the most suitable for the leaching concentration of TCEP. It was identified that TCEP in biofilm carrier was transformed into oxidative dechlorinated compounds and oxidative compounds by microorganisms in the bioreactor. As a result of the study, it was confirmed that not only TCEP but also transformation products of TCEP emitted into the water from the MBBR process of WWTP.

The effects of fluid absorption and plasma volume changes in athletes following consumption of various beverages.

BACKGROUND: To verify the hydration effects of oral rehydration solution (ORS) on athletes by comparing the degrees of fluid absorption and plasma volume changes following beverage consumption, including ORS. METHODS: Thirty-one participants visited the testing laboratory 4 times at 1-week intervals to consume 1 L of beverage (e.g., water, ORS, and two sports drinks [SpD]) for 30 min on each visit. The urine output was measured 4 times at 1 h, 2 h, 3 h, and 4 h after beverage consumption. A blood sample was collected 3 times at 1 h, 2 h, and 3 h after beverage consumption. Body weight was measured once in 4 h after beverage consumption. RESULTS: Body weight change was smaller for ORS than for water, SpD1, and SpD2 (p < 0.05). Cumulative urine output in 4 h was lower for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was lower for ORS than for SpD2 (p < 0.05). BHI in 4 h was higher for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was higher for ORS than for SpD2 (p < 0.05). There was no significant difference in PVC for different beverages at all test times, i.e.., 1 h, 2 h, and 3 h. CONCLUSIONS: We evaluated the hydration effects of the consumption of beverages, such as water, SpD, and ORS in athletes. ORS and SpD were more effective than water. A comparison between ORS and SpD showed that the result could vary depending on the type of SpD.

Optimized Adaptive Radiotherapy with Individualized Plan Library for Muscle-Invasive Bladder Cancer Using Internal Target Volume Generation.

The bladder is subject to filling variation, which poses a challenge to radiotherapy (RT) delivery. We aimed to assess feasibility and clinical outcomes in patients with bladder cancer treated with adaptive RT (ART) using individualized plan libraries. We retrospectively analyzed 19 patients who underwent RT for muscle-invasive bladder cancer (MIBC) in 2015-2021. Four planning computed tomography (CT) scans were acquired at 15-min intervals, and a library of three intensity-modulated RT plans were generated using internal target volumes (ITVs). A post-treatment cone-beam CT (CBCT) scan was acquired daily to assess intra-fraction filling and coverage. All patients completed the treatment, with 408 post-treatment CBCT scans. The bladder was out of the planning target volume (PTV) range in 12 scans. The volumes of the evaluated PTV plans were significantly smaller than those of conventional PTV. The 1-year and 2-year overall survival rates were 88.2% and 63.7%, respectively. Of eight cases that experienced recurrence, only two developed MIBC. There were no grade 3 or higher RT-related adverse events. ART using plan libraries and ITVs demonstrated good survival outcomes with a high local control rate. Irradiated normal tissue volume and treatment margins may be reduced through this approach, potentially resulting in lower toxicity rates.

Fabrication of 3D printed head phantom using plaster mixed with polylactic acid powder for patient-specific QA in intensity-modulated radiotherapy.

This study aimed to fabricate a heterogeneous phantom replicating the commercial Rando phantom by mixing plaster powder and polylactic acid (PLA) powder. Producing a heterogeneous phantom using Plaster and PLA is cheaper because it can be easily obtained in the commercial market. Additionally, patient-specific Quality Assurance can be easily performed because the phantom can be produced based on the patient's CT image. PLA has been well studied in the field of radiation therapy and was found to be safe and effective. To match the mean Hounsfield unit (HU) values of the Rando phantom, the bone tissue was changed using plaster and 0-35% PLA powder until an appropriate HU value was obtained, and soft tissue was changed using the PLA infill value until an appropriate HU value was obtained. Bone tissue (200 HU or higher), soft issue (- 500 to 200 HU), and air cavity (less than - 500 HU) were modeled based on the HU values on the computed tomography (CT) image. The bone tissue was modeled as a cavity, and after three-dimensional (3D) printing, a solution containing a mixture of plaster and PLA powder was poured. To evaluate the bone implementation of the phantom obtained by the mixture of plaster and PLA powder, the HU profile of the CT images of the 3D-printed phantom using only PLA and the Rando phantom printed using only PLA was evaluated. The mean HU value for soft tissue in the Rando phantom (- 22.5 HU) showed the greatest similarity to the result obtained with an infill value of 82% (- 20 HU). The mean HU value for bone tissue (669 HU) showed the greatest similarity to the value obtained with 15% PLA powder (680 HU). Thus, for the phantom composed of plaster mixed with PLA powder, soft tissue was fabricated using a 3D printer with an infill value of 82%, and bone tissue was fabricated with a mixture containing 15% PLA powder. In the HU profile, this phantom showed a mean difference of 61 HU for soft tissue and 109 HU for bone tissue in comparison with the Rando phantom. The ratio of PLA powder and plaster can be adjusted to achieve an HU value similar to bone tissue. A simple combination of PLA powder and plaster enabled the creation of a custom phantom that showed similarities to the Rando phantom in both soft tissue and bone tissue.

The efficacy and safety of Codonopsis lanceolata water extract for sarcopenia: A study protocol for randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: This study aimed to propose a protocol to demonstrate the efficacy of Codonopsis lanceolata water extract for the improvement of skeletal muscle mass (SMM) and function (muscle strength or performance function) and its safety compared to a placebo in adults with reduced muscle strength. METHODS AND ANALYSIS: A randomized double-blind placebo-controlled clinical trial was conducted. Participants will be recruited from the Korean Medicine Hospital in South Korea. One hundred and four adults with reduced muscle strength will be randomly assigned a 1:1 ratio to either the experimental or placebo comparator groups. The participants will consume the product corresponding to their assigned group for the following 12 weeks, and efficacy and safety tests will be conducted. This is the first clinical trial of C lanceolata water extract in adults with reduced muscle strength. The results of this study would provide a clinical basis for the efficacy and safety of C lanceolata water extract in patients with sarcopenia. ETHICS AND DISSEMINATION: This trial was approved by the Institutional Review Board (IRB) of Kyung Hee University Korean Medicine Hospital at Gangdong on July 15, 2021 (amendment number: MLB_DDE_H01 [ver. 01]). When a change was made in the clinical trial plan, the IRB reviewed and approved the revised clinical trial plan. The study was registered on the Clinical Research Information Service website on December 3, 2021 (registration number: PRE20211203-003; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=20841&status=1&seq_group=20841&search_page=M). The results of this clinical trial will be reported in the future. Every document related to the clinical trial, such as the electronic case report form, will be recorded and classified by the subject identification code and not by the subject name.

Prospective Study of 4 Gy Radiotherapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma (FORMAL).

External beam radiotherapy is effective for stage I orbital mucosa-associated lymphoid tissue lymphoma (MALToma). Hence, very-low-dose radiotherapy is increasingly being investigated. We conducted a single-center prospective phase II trial to evaluate the effectiveness of very-low-dose radiotherapy of 4 Gy (2 Gy × 2 fractions) in pathologically confirmed stage I orbital MALToma. In this first prospective trial, patients with complete response were observed after 3-6 months of follow-up. For patients without complete remission, a radiation dose of 24 Gy/12 fractions was additionally delivered. The primary endpoint was complete response rate; secondary endpoints were overall survival, local control, and progression-free survival. Seventeen patients were screened and three patients refused enrollment during October 2018-October 2021. Thus, 14 patients (17 eyes) were analyzed (median follow-up, 28.2 months). The overall response rate was 100% (complete remission: 11 lesions; partial remission: six lesions). In all lesions with residual disease, additional radiation therapy (dose: 24 Gy) was performed. One local failure was observed. Therefore, 4 Gy ultralow-dose radiation therapy for orbital MALToma was safely performed with a planned second-line treatment in patients without complete remission. This is the first prospective study to report the effectiveness of ultralow-dose radiotherapy of 4 Gy for stage I orbital MALToma treatment.

Efficacy and Optimal Pressure of Continuous Positive Airway Pressure in Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer.

We aimed to determine the optimal pressure of continuous positive airway pressure (CPAP) for radiotherapy (RT) through changes in the dosimetric parameters and lung volume according to pressure. Patients with locally advanced lung cancer, who underwent CPAP during computed tomography (CT) simulation, were included. The air pressure was raised in five steps of 4, 7, 10, 14, and 17 cmH2O and a CT scan was performed at the baseline and at each pressure step, accompanied by contouring and RT planning. Paired t- and Wilcoxon signed rank tests were used to compare the volumetric and dosimetric parameters according to pressure and interpressure. A total of 29 patients were selected, and 158 CT datasets were obtained. The lung volume increased significantly at all pressures (p < 0.01). The Dmean of the lung decreased significantly from 7 cmH2O (p < 0.01), the V5, V10, V15, and V20 of the lung decreased significantly from 7 cmH2O with increasing pressure, and the Dmean and V5 of the heart decreased significantly from 14 cmH2O with increasing pressure. The V50 showed no significant differences at any pressure. We recommend the use of at least 7 cmH2O with 14 cmH2O as the optimal pressure to achieve the effect of heart preservation.

Efficacy of an Integrated Mobile Application System for Patients with Radiation Therapy: A Pilot Study.

The use of IT applications for patients undergoing radiotherapy is limited. This study aimed to develop an integrated system for communication between patients and radiation oncologists using IT technology and report the first test results for the system "Assisted Radiation Oncology Mobile Application" (AROMA). This system consisted of a manager program, a server running on a PC, and a mobile application on a smartphone. A prospective survey was conducted to evaluate the usefulness of this system from October 2020 to January 2021. The survey consisted of a specific questionnaire on basic information and application use by the patients. The management program was designed such that the user (doctor) edits the treatment schedule, member (patient and doctor) information, self-management, disease information, and side effect questionnaire. The mobile application for patients consisted of the current schedule, treatment schedule calendar, side effect questionnaire, side effect management method, and disease information entered by the doctor. A total of 41 patients were enrolled in this study. The mean adverse event response time was 4.4 days. In the survey, the mobile application received positive views (8.6/10 points). Most responses related to the side effect reporting function (94%) and communication using the application (91%) were positive. Satisfaction with the application design and each menu item was high, with an average of ≥8 and ≥8.5 points in most cases, respectively. The survey showed good satisfaction with the design, operability, and reporting system. Therefore, the system can facilitate communication between patients and radiation oncologists in the future.

Setup uncertainties and appropriate setup margins in the head-tilted supine position of whole-brain radiotherapy (WBRT).

Various applications of head-tilting techniques in whole-brain radiotherapy (WBRT) have been introduced. However, a study on the setup uncertainties and margins in head-tilting techniques has not been reported. This study evaluated the setup uncertainties and determined the appropriate planning target volume (PTV) margins for patients treated in the head-tilted supine (ht-SP) and conventional supine position (c-SP) in WBRT. Thirty patients who received WBRT at our institution between October 2020 and May 2021 in the c-SP and ht-SP were investigated. The DUON head mask (60124, Orfit Industries, Wijnegem, Belgium) was used in the c-SP, and a thermoplastic U-Frame Mask (R420U, Klarity Medical & Equipment Co. Ltd., Lan Yu, China) was used in the ht-SP. Daily setup verification using planning computed tomography (CT) and cone-beam CT was corrected for translational (lateral, longitudinal, and vertical) and rotational (yaw) errors. In the c-SP, the means of systematic errors were -0.80, 0.79, and 0.37 mm and random errors were 0.27, 0.54, and 0.39 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. Whereas, for the ht-SP, the means of systematic errors were -0.07, 0.73, and -0.63 mm, and random errors were 0.75, 1.39, 1.02 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. The PTV margins were calculated using Stroom et al.'s [2Σ+0.7σ] and van Herk et al.'s recipe [2.5Σ+0.7σ]. Appropriate PTV margins with van Herk et al.'s recipe in WBRT were <2 mm and 1.5° in the c-SP and <3 mm and 2° in the ht-SP in the translational and rotational directions, respectively. Although the head tilt in the supine position requires more margin, it can be applied as a sufficiently stable and effective position in radiotherapy.

Voltage-driven gigahertz frequency tuning of spin Hall nano-oscillators.

Spin Hall nano-oscillators (SHNOs) exploiting current-driven magnetization auto-oscillation have recently received much attention because of their potential for neuromorphic computing. Widespread applications of neuromorphic devices with SHNOs require an energy-efficient method of tuning oscillation frequency over broad ranges and storing trained frequencies in SHNOs without the need for additional memory circuitry. While the voltage-driven frequency tuning of SHNOs has been demonstrated, it was volatile and limited to megahertz ranges. Here, we show that the frequency of SHNOs is controlled up to 2.1 GHz by an electric field of 1.25 MV/cm. The large frequency tuning is attributed to the voltage-controlled magnetic anisotropy (VCMA) in a perpendicularly magnetized Ta/Pt/[Co/Ni]n/Co/AlOx structure. Moreover, the non-volatile VCMA effect enables cumulative control of the frequency using repetitive voltage pulses which mimic the potentiation and depression functions of biological synapses. Our results suggest that the voltage-driven frequency tuning of SHNOs facilitates the development of energy-efficient neuromorphic devices.

The patterns and spatial locations of local recurrence in breast cancer with implant-based reconstruction after mastectomy.

BACKGROUND AND PURPOSE: The European Society for Radiotherapy and Oncology (ESTRO) recently defined delineation guidelines for the clinical target volume for postmastectomy radiation therapy (PMRT) after immediate implant-based reconstruction for early-stage breast cancer. We analyzed the three-dimensional location and pattern of local recurrence in accordance with the reconstruction type and ESTRO-target volume. MATERIALS AND METHODS: This retrospective study involved patients who had undergone mastectomy with implant reconstruction between 2010 and 2019 and who had local recurrence as the first event. For mapping analysis, one subpectoral and one prepectoral implant patient were selected. All recurrence lesions were contoured and mapped in a representative case. RESULTS: A total of 1327 patients with breast cancer who underwent mastectomy and implant-based breast reconstruction were identified; 51 were enrolled with a total of 65 lesions. In subpectoral implant patients, 93% of recurrences were located in the ESTRO-target volume. No recurrence occurred in the implant pocket, but 7% of the recurrent tumors developed in the pectoralis major and deep thoracic muscle. In prepectoral implant patients, all recurrent tumors occurred within the ESTRO-target volume. CONCLUSION: The ESTRO-target volume in PMRT after reconstruction encompassed most local recurrences in patients who underwent mastectomy with immediate implant reconstruction. Our results support the application of the ESTRO Advisory Committee for Radiation Oncology Practice consensus guideline for target volume of PMRT after immediate implant-based reconstruction for early-stage breast cancer.