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Background and Purpose: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT)., Materials and Methods: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test., Results: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116)., Conclusion: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Wisdom is the hallmark of social judgment, but how people across cultures recognize wisdom remains unclear-distinct philosophical traditions suggest different views of wisdom's cardinal features. We explore perception of wise minds across 16 socio-economically and culturally diverse convenience samples from 12 countries. Participants assessed wisdom exemplars, non-exemplars, and themselves on 19 socio-cognitive characteristics, subsequently rating targets' wisdom, knowledge, and understanding. Analyses reveal two positively related dimensions-Reflective Orientation and Socio-Emotional Awareness. These dimensions are consistent across the studied cultural regions and interact when informing wisdom ratings: wisest targets-as perceived by participants-score high on both dimensions, whereas the least wise are not reflective but moderately socio-emotional. Additionally, individuals view themselves as less reflective but more socio-emotionally aware than most wisdom exemplars. Our findings expand folk psychology and social judgment research beyond the Global North, showing how individuals perceive desirable cognitive and socio-emotional qualities, and contribute to an understanding of mind perception., (© 2024. The Author(s).)

Purpose: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost., Materials and Methods: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival., Results: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases., Conclusion: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer., Study Registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845)., (© 2024. The Author(s).)

Purpose: An optimal radiotherapy field for superficial esophageal carcinoma is yet to be established. We evaluated the long-term outcomes and recurrence patterns of involved-field radiotherapy (IFRT) in older patients with superficial thoracic esophageal squamous cell carcinoma (ESCC)., Materials and Methods: Fifty-four patients (49 men and 5 women; mean age, 77 [range: 66-90] years) who underwent IFRT for superficial thoracic ESCC between January 2003 and January 2019 were retrospectively reviewed. Concurrent chemotherapy was administered at the discretion of the attending physician. The primary endpoint was overall survival. The secondary endpoints were progression-free survival and complete response rate., Results: The tumors were localized in the upper, middle, and lower thoracic esophagus in 2, 40, and 12 patients, respectively. All patients underwent IFRT using anteroposterior and anterior-posterior oblique opposed beams (off-cord). The prescribed total doses were 50.4, 59.4-61.2, and 66-70 Gy for 6, 40, and 8 patients, respectively. Concurrent chemotherapy was administered to 33 patients. The median follow-up duration was 57 months. The median overall survival was 115 months. The 5-year overall and progression-free survival rates were 71.7% and 60.1%, respectively. Forty-nine patients had a complete response at one month after IFRT (complete response rate: 90.7%). Twenty patients had recurrence; there were 13 in-field and 7 out-of-field recurrence cases. The radiation-related adverse events were generally mild. Grade 3 late toxicity was observed in one patient., Conclusions: The efficacy of IFRT was suggested to be comparable to that of standard treatments. Therefore, IFRT can be a promising approach for treating superficial ESCC in older adults, especially those with severe comorbidities., (© 2024. The Author(s).)

Purpose: This study aimed to quantify the changes in intratumoral blood flow after carbon-ion radiation therapy (CIRT) for early-stage breast cancer and analyze their clinical significance., Patients and Methods: We included 38 patients with early-stage breast cancer who underwent CIRT. Dynamic imaging was performed using a 3T superconducting magnetic resonance scanner to quantify the washin index (idx), which reflects contrast uptake, and washout idx, which reflects the rate of contrast washout from tumor tissue. The changes in the apparent diffusion coefficient, washin idx, and washout idx were examined before CIRT and at 1 and 3 months after treatment. Clinical factors and imaging features were examined using univariate and receiver operating characteristic curve analyses to identify factors predicting clinical complete response (cCR)., Results: The median observation period after CIRT was 51 (range: 12-122) months. During the observation period, 31 of the 38 patients achieved cCR, and 22 achieved cCR within 12 months. Tumor size ( P  < .001), washin idx ( P  = .043), and washout idx ( P  < .001) decreased significantly 1-month after CIRT. In contrast, the apparent diffusion coefficient values ( P  < .001) increased significantly 1-month after CIRT. Univariate analysis suggested that the washin idx after 1 and 3 months of CIRT was associated with cCR by 12 months post-CIRT ( P  = .028 and .021, respectively). No other parameters were associated with cCR by 12 months post-CIRT. Furthermore, receiver operating characteristic curve analyses showed that the area under the curve values of washin idx after 1 and 3 months of CIRT was 0.78 (specificity 75%, sensitivity 80%) and 0.73 (specificity 75%, sensitivity 71%), respectively., Conclusion: Tumor changes can be quantified early after CIRT using contrast-enhanced magnetic resonance imaging in patients with breast cancer. Washin idx values 1 and 3 months after CIRT were associated with cCR within 12 months post-CIRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations., Purpose: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations., Methods: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs., Results: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula., Conclusions: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations., (© 2023 American Association of Physicists in Medicine.)

Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases., Case Presentation: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy., Conclusions: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD., (© 2024. The Author(s).)

We report the first sequencing of morpholino antisense oligonucleotides (phosphorodiamidate morpholino oligomers, PMOs) using electron capture dissociation (ECD) mass spectrometry. In this research, we found dissociation of the backbone of 18- to 25-mer PMOs to produce d and z ions as the major ions, and 100% cleavage coverage (sequence coverage) was obtained with these ions. This is a critical contrast with beam-type collision-induced dissociation, which dominantly induces base loss, so it is difficult to obtain sequence information. The results showed that an electron beam energy (typically 15 eV) can be used universally for PMOs with different sequences, lengths, and charge states so that no detailed optimization is required for multiprecursor targeting liquid chromatography coupled with tandem mass spectrometry measurements. We also confirmed that the ECD reaction speed was compatible with the high-performance liquid chromatography time scale. Finally, we demonstrated a liquid chromatography electron capture dissociation tandem mass spectrometry workflow to survey the modification sites of the emulated PMO impurities.

Objectives: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan., Methods: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome., Results: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months., Conclusions: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Agaro-oligosaccharides (AOSs) are known to have biological activities, such as anti-inflammatory, anti-tumor, and anti-obesity effects. Although existing evidence suggests the presence of AOSs in peripheral tissues after oral administration, whether AOSs permeate into the blood circulation remains unknown. Thus, we hypothesized that AOSs with low-molecular weight can permeate the human gastrointestinal tract. To test this hypothesis, the time course of absorption was examined by analyzing plasma samples before and 1, 2, and 4 h after ingestion. Analysis was performed using liquid chromatography/mass spectrometry after labeling with p -aminobenzoic ethyl ester. Our results showed that the plasma concentration of agarobiose (Abi) was higher than that of agarotetraose (Ate); however, agarohexaose was not detected. Additionally, plasma levels of Abi and Ate were proportional to the dose. These results suggest that permeation efficiency is dependent on the molecular weight and that the systemic absorption of Abi via the gastrointestinal tract is better than that of Ate. These findings will contribute to a better understanding of the bioactivity of orally administered AOSs in peripheral tissues., Competing Interests: IS and KK are employees of Ina Food Industry Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shirai, Iwasaki, Karasawa, Shigemura and Katayama.)

As the world's population is aging, it is necessary to create societies in which older adults and young people can live together comfortably. Reducing young people's negative attitudes toward older adults is a pressing issue. Given the unique characteristics of older adults, which most people will eventually become, we focused on how long people believe it will be before they become older adults (i.e., the subjective time of becoming older). To examine our hypotheses, we performed a Bayesian analysis, which has attracted considerable attention in psychological research in recent years. In Studies 1 and 2, even after controlling for variables such as youth identity and aging anxiety, those with a longer subjective time of becoming older had more negative attitudes toward older adults and lower advocacy for policies to support older adults. In Study 3, we examined the effect of shortening the participants' subjective time of becoming older by presenting an explanatory text on the stereotype embodiment theory and several related empirical findings. We observed decreased negative attitudes toward both the young-old and old-old groups and increased advocacy for policies to support older adults. In the supplemental experiment, the experimental manipulation used in Study 3 reduced participants' aging anxiety. Future studies should elaborate on the negative attitudes toward a broad subgroup of older adults, and examine the perceived relative importance of policies to support older adults compared with policies in other areas., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The biological activities of substances in the brain are shaped by their spatiotemporal dynamics in brain tissues, all of which are regulated by water dynamics. In contrast to solute dynamics, water dynamics have been poorly characterized, owing to the lack of appropriate analytical tools. To overcome this limitation, we apply stimulated Raman scattering multimodal multiphoton microscopy to live brain tissues. The microscopy system allows for the visualization of deuterated water, fluorescence-labeled solutes, and cellular structures at high spatiotemporal resolution, revealing that water moves faster than fluorescent molecules in brain tissues. Detailed analyses demonstrate that water, unlike solutes, diffuses homogeneously in brain tissues without differences between the intra- and the extracellular routes. Furthermore, we find that the water dynamics are steady during development and ischemia, when diffusions of solutes are severely affected. Thus, our approach reveals routes and uniquely robust properties of water diffusion in brain tissues., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

In today's world, where clinical options are ever increasing and patients' needs are more diverse, it is not possible to conclude that simply practicing medical care based on pathophysiological data and medical evidence is sufficient for patients, particularly in terms of seeing each patient as an individual. Medical professionals must maintain a close relationship with their patients and seek treatment and care methods that reflect the patient's values and views on life and death, based on their own ethics in medical care. Ethics education should be provided on a continuing basis from the beginning of medical/pharmacy school. However, ethics education in pharmacy departments is often delivered in a lecture format attended by many students and/or as group training using case studies and hypothetical situations, i.e., "paper" patients. With these teaching methods, there are limited opportunities for the students to foster a sense of ethics or to think deeply about their values and views on life and death with respect to the patients they care for. Therefore, in this study, we conducted ethics exercises for pharmacy students in a group study format using a documentary film of real patients who were facing death. By retrospectively analyzing the results of the questionnaires collected before and after the assignments and exercises, we verified the educational effects and changes in the students' sense of ethics from participating in the group learning exercise; moreover, our results revealed the insight gained by the students in examining the experiences and challenges faced by terminally ill patients.

Aims: There is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries., Materials and Methods: Eighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions., Results: Between February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4-100.0) and 96.3% (95% confidence interval 93.2-99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed., Conclusion: Although further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The relationship between the grading of toxicities based on toxicity criteria and longitudinal changes in quality of life (QOL) scores after permanent prostate brachytherapy (PPB) for localized prostate cancer remains unclear. This study aimed to evaluate these relationships., Materials and Methods: We assessed 107 patients treated with PPB using Iodine-125 alone from May 2007 to April 2010. Disease-specific QOL scores before PPB and at 1, 3, 6, 12, and 24 months after PPB were retrospectively evaluated with the Expanded Prostate Cancer Index Composite (EPIC), focusing on urinary domains. Toxicities were graded using the Radiation therapy oncology group and the European organization for research and treatment of cancer toxicity criteria., Results: The median follow-up duration was 116 (range 18-148) months. Thirty-four patients (31.8%) developed grade ≥ 2 acute genitourinary (GU) toxicities; six (5.6%) developed grade ≥ 2 late GU toxicities. The general urinary domain score dropped significantly at 1 month (77.1 ± 14.1) post-PPB compared to the baseline score (92.2 ± 8.2), and then gradually returned to the baseline level by 12 months (93.7 ± 8.3) post-PPB. Reductions in the general urinary domain scores, including its subscale scores at 1, 3, and 6-months post-PPB were significantly greater among patients with grade ≥ 2 GU toxicity than among those with grade 0-1 GU toxicity. Changes in urinary domain scores demonstrated a close relationship with acute GU toxicity grades after PPB., Conclusions: Longitudinal assessments of the EPIC QOL scores provided additional information regarding time-course changes in GU toxicities after PPB., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

Brain metastases from bladder cancer are rare, with a poor prognosis. There is no standard treatment for bladder cancer with brain metastases; thus, palliative therapy is generally provided. We report a case of abscopal effect in a single brain metastasis from bladder cancer in a patient treated with focal stereotactic radiotherapy (total dose = 52 Gy, administered in eight fractions) with immune checkpoint blockade therapy for lung metastases, who achieved long-term disease-free survival (> 4 years). To our knowledge, although there have been some reports on abscopal effects in bladder cancer, there are no previous reports on patients with brain metastases. To date, the brain metastasis, which showed an "abscopal effect," continues to maintain complete regression., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Accelerated hypofractionated radiotherapy with 3 Gy per fraction is routinely performed for central lung tumors in Japan. However, the tolerable doses to mediastinal organs at risk during this procedure are unclear. This study aimed to clarify the rate of toxicities and tolerable doses to mediastinal organs., Methods: Patients treated with accelerated hypofractionated radiotherapy using a total dose of 60-75 Gy, with 3 Gy per fraction, for central lung tumors (July 2009-April 2021) were retrospectively reviewed. We extracted patients who received ≥30 Gy irradiation to each mediastinal organ and analyzed dosimetric factors, including doses to 0.03, 0.5, 1, 4 and 10 mL of each organ, in relation to grade 3-5 toxicities, except for radiation pneumonitis., Results: In total, 251 organs in 91 (ultra-central, 24) lesions were analyzed, with a median follow-up duration of 26 months (range, 4-94). The prescribed doses were 75/72/69/66/63/60 Gy for 52/14/16/3/2/4 lesions, respectively. Grade 3 bronchopulmonary hemorrhage was confirmed in two (2.2%) patients, whose tumors were located ultra-centrally. The two patients with toxicity received up to 74.5 and 71.6 Gy to the bronchus. Among patients who received 70 Gy or more to the bronchus, the incidence rate was 7% (2/28 patients)., Conclusion: The rate of severe toxicities was low (2.2%). Although we did not identify the dose tolerance of the organs, because of the low incidence rate, we did note that doses of >70 Gy to the bronchus were likely to cause bronchopulmonary hemorrhage., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)