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Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Methods and materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5–19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Moon Hee Lee,1 Seok-Kyu Yoon,1 Hyungsub Kim,2 Yong-Soon Cho,3 Sungpil Han,4 Shi Hyang Lee,1 Kyun-Seop Bae,1 Jina Jung,5 Sung Hee Hong,5 Hyeong-Seok Lim1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; 2Department of Emergency Medical Services, College of Health Sciences, Eulji University, Seongnam, Republic of Korea; 3Department of Pharmacology and Clinical Pharmacology, Inje University College of Medicine, Busan, Republic of Korea; 4Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of KoreaCorrespondence: Hyeong-Seok Lim, Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-4613, Fax +82-2-3010-4623, Email mdlhs@amc.seoul.krPurpose: The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects.Patients and Methods: Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs).Results: For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263– 1.1765) for Cmax and 1.1329 (1.0232– 1.2544) for AUClast. For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005– 0.9117) for Cmax and 0.8056 (0.7445– 0.8717) for AUClast. The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases.Conclusion: A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study.Keywords: bazedoxifene, cholecalciferol, drug-drug interaction, pharmacokinetics, tolerability

Su Eun Lim,* Ho Seok Kim,* Si Woo Lee, Kwang-Ho Bae, Young Hwa Baek KM Data Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Young Hwa Baek, KM Data Division Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea, Tel +82 10-2555-2138, Email aori79@kiom.re.krPurpose: The commercialization of sleep activity tracking devices has made it possible to manage sleep quality at home. However, it is necessary to verify the reliability and accuracy of wearable devices through comparison with polysomnography (PSG), which is the standard for tracking sleep activity. This study aimed to monitor overall sleep activity using Fitbit Inspire 2™ (FBI2) and to evaluate its performance and effectiveness through PSG under the same conditions.Patients and Methods: We compared the FBI2 and PSG data of nine participants (four male and five female participants; average age, 39 years) without severe sleeping problems. The participants wore FBI2 continuously for 14 days, considering the period of adaptation to the device. FBI2 and PSG sleep data were compared using paired t-tests, Bland–Altman plots, and epoch-by-epoch analysis for 18 samples by pooling data from two replicates.Results: The average values for each sleep stage obtained from FBI2 and PSG showed significant differences in the total sleep time (TST), deep sleep, and rapid eye motion (REM). In the Bland–Altman analysis, TST (P = 0.02), deep sleep (P = 0.05), and REM (P = 0.03) were significantly overstated in FBI2 compared to PSG. In addition, time in bed, sleep efficiency, and wake after sleep onset were overestimated, while light sleep was underestimated. However, these differences were not statistically significant. FBI2 showed a high sensitivity (93.9%) and low specificity (13.1%), with an accuracy of 76%. The sensitivity and specificity of each sleep stage was 54.3% and 62.3%, respectively, for light sleep, 84.8% and 50.1%, respectively, for deep sleep, and 86.4% and 59.1%, respectively for REM sleep.Conclusion: The use of FBI2 as an objective tool for measuring sleep in daily life can be considered appropriate. However, further research is warranted on its application in participants with sleep-wake problems.Keywords: wearable, sleep, tracking, polysomnography, validation study

Magnetic properties resulting from localized spins associated with antisite arsenic ions AsGa+ in Be-doped low-temperature-grown GaAs (LT-GaAs) layers were studied by measuring the magnetization of lift-off samples. With fast cooling, the magnetization of samples at 1.8 K becomes significantly lower than that expected from Curie-type paramagnetism in the range of the applied field to 7 T, and a transition from low magnetization to the magnetization of paramagnetism occurs upon the heating of samples to 4.5 K. With slow cooling, on the other hand, samples have a paramagnetic temperature dependence throughout the measurement-temperature range. The magnetization was found to decrease monotonically when a sample was kept at a fixed low temperature. These observations are explained by the cooperative transition of electron states of AsGa defects, which is closely related to the normal-metastable state transition of EL2 defects in semi-insulating GaAs. The results of the magnetization measurements in the present study suggest that AsGa+ ions are spontaneously displaced at low temperature without photoexcitation in Be-doped LT-GaAs. The similarity of the transition observed in this system to the normal-metastable state transition of the EL2 defect was also suggested by first-principle calculations of the electron state of an AsGa defect with a doped Be atom. [ABSTRACT FROM AUTHOR]

The purpose of the present clinical study was to evaluate the biologic stability of alumina-zirconia implant abutments by histologic and radiographic examination. Nineteen partially edentulous patients were treated with 37 external-hexagon implants. After a healing period of 3 to 6 months, alumina-zirconia abutments were connected and restored with cemented single crowns or short-span fixed partial dentures. Periapical radiographs were taken at the time of prosthesis delivery and after 3, 6, and 12 months of follow-up. Crestal alveolar bone level changes were assessed by digital subtraction of consecutive images, and 1-way analysis of variance was used for statistical analysis. No implant, abutment, or restoration failed during the observation period. Bone level changes were statistically insignificant and histologic examination revealed no signs of inflammation. Stable and healthy soft and hard tissue conditions may be expected around alumina-zirconia abutments after 1 year of clinical service. However, long-term data are needed to confirm the present results. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC. Methods: A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV). Results: In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05). Conclusions: CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.