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Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1–3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4–7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation.Serial femtosecond crystallography reveals the structural dynamics of photosystem II during the S-state transitions that produce dioxygen, providing insight into electron transfer, water insertion, proton release and O–O bond formation on sub-microsecond timescales. [ABSTRACT FROM AUTHOR]

In this study, a real-time tsunami estimation method was developed using the linear superposition of Green's functions, which account for nonlinear tsunami effects around coastal areas. To this end, first, the nonlinear effects associated with the inundation and bottom friction and advection terms in a nonlinear long-wave model were investigated, focusing on large tsunamis around Urado Bay in Kochi Prefecture, Japan, which is at risk of future damage from tsunamis produced by the Nankai Trough earthquake. The results indicate that the effects of advection play a more significant role than those of the inundation and bottom friction in terms of accurately estimating near-shore tsunami propagation. Then, based on these results, Green's functions were modified to account for the linearly approximated effects of the advection terms. By applying the developed method to tsunamis around Urado Bay, it was demonstrated that accurate estimations of the water surface level and flow velocity changes could be quickly obtained at any location around the bay. The developed method can be applied to real-time tsunami inundation forecasting and off-shore evacuation simulations of vessels to support optimal evacuation decisions. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of a new oral rinse containing sodium hyaluronate and other functional ingredients in reducing xerostomia‐associated symptoms. Materials and Methods: In this 8‐week, double‐blind crossover study, xerostomia subjects used all three of GUM®HYDRAL™ Oral Rinse, placebo rinse, and Biotene® Oral Rinse as active control. Visual Analog Scale, a dry mouth questionnaire, Oral Health Impact Profile‐14, unstimulated saliva flow rate (USFR), and Revised Oral Assessment Guide (ROAG) were assessed before and after 2 weeks of treatments. Results: Thirty‐seven patients completed all three treatment modalities. Subjective measurements were significantly decreased by test product and active control; however, no significant difference was observed between the treatments. Test product and active control demonstrated a significant increase in USFR over 0.2 ml/min, a normal threshold of hyposalivation. Both test product and active control improved a total score of ROAG, whereas the effectiveness of the test product was significantly better than that of other two treatments. Conclusions: The new oral rinse may be beneficial to improve the quality of life of xerostomia patients as dry mouth symptoms were reduced for both subjective and objective measurements. Test oral rinse was found to be more effective than placebo or active control for some of the objective measurements. [ABSTRACT FROM AUTHOR]

Patients with uncommon EGFR-mutated non-small-cell lung cancer (NSCLC) demonstrated lower clinical efficacy of first-generation EGFR-tyrosine kinase inhibitors compared with patients harboring common EGFR-mutated NSCLC. The US FDA has approved afatinib for uncommon EGFR mutation positive NSCLC based on the pooled analysis in the first- or second-line setting. Osimertinib has limited evidence in the small sample sizes of phase 2 studies in any-line settings. The aim of the present single-arm, multicenter, phase 2 study is to evaluate the efficacy of osimertinib for previously untreated NSCLC. The primary end point is to assess the overall response to osimertinib. The secondary end points include disease control rate, progression-free survival, duration of time-to-treatment failure, overall survival and safety. Clinical trial registration: jRCTs071200002. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This study aimed to develop and evaluate the Brief Older Adults' Physical Activity Questionnaire (BOPAQ), which was designed to quickly assess moderate‐to‐vigorous physical activity (MVPA) in community‐dwelling older adults.We used a cross‐sectional study design involving 165 older participants. The BOPAQ calculated weekly MVPA duration based on two questions regarding the number of days per week engaged in MVPA and the daily duration of activity. Validity was assessed by correlating the MVPA durations derived from the BOPAQ with those obtained from the ActiGraph and International Physical Activity Questionnaire short form. Reliability was evaluated using the intraclass correlation coefficient, and measurement errors were analyzed using Bland–Altman plots.The BOPAQ reasonably correlated with accelerometer‐based MVPA (rho = 0.297) and showed good test–retest reliability (intraclass correlation coefficient of 0.78, 95% CI 0.64–0.87). In contrast, the correlation between the International Physical Activity Questionnaire short form and accelerometer‐based MVPA was poor (rho = 0.139). The cut‐off value for the BOPAQ was set to identify participants engaging in <150 min of objectively measured physical activity per week, corresponding to the 150‐min threshold. However, the area under the curve in the receiver operating characteristic analyses was not significantly high (0.601, 95% CI 0.514–0.688). The Bland–Altman plots showed an underestimation bias of 51.72 min/week (95% CI 1.61–101.84) and showed heteroscedasticity.Despite some measurement errors, the BOPAQ is an available tool for assessing MVPA in community‐dwelling older adults. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

We aimed to clarify whether prophylactic cranial irradiation (PCI) is associated with improved outcomes in limited-stage small-cell lung cancer (LS-SCLC) in the current era of magnetic resonance imaging (MRI). Data from patients with LS-SCLC who achieved a complete response to definitive chemoradiotherapy (CRT) at two medical centers were retrospectively reviewed. Propensity score-matching was performed in a 2:1 ratio to balance the baseline characteristics of the no-PCI and PCI groups. The endpoints were the incidence of brain metastasis (BM), neurological causes of death and overall survival (OS). Overall, 80% patients underwent head MRI during the initial staging and 75 patients (no-PCI, n = 50; PCI, n = 25) were matched. Their baseline characteristics were generally well-balanced except for age; patients in the no-PCI group tended to be older. The median follow-up period was 29 months. Although the incidence of BMs tended to be higher in the no-PCI group (1-year BM occurrence: 26% vs 17%, P = 0.22), the incidence of multiple BMs (defined as >4 metastases) was similar between groups (1-year multiple BMs occurrence: 8% vs 9%, P = 0.65). The 2-year neurological causes of death and OS rate did not significantly differ between the groups (6% and 9%; P = 0.85; and 70% and 79%; P = 0.36, respectively). The 1-year occurrence of multiple BMs did not increase, even without PCI, when modern imaging modalities were integrated into the initial diagnosis, suggesting that PCI could be omitted after CRT, if MRI was incorporated into the initial diagnosis and follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective The current standard treatment for locally advanced, unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CCRT) and durvalumab administration. Although reports have indicated that the prognosis of squamous cell carcinoma is poorer than that of adenocarcinoma, real-world data are currently inadequate. Methods The present study analyzed patients with stage III NSCLC who received CCRT at the study center between April 2018 and February 2022. These patients were retrospectively classified into adenocarcinoma and squamous cell carcinoma groups for an analysis of the progression-free survival (PFS), overall survival (OS), and patient background factors, including the age, performance status, smoking history, and pre-CCRT laboratory data. Results A total of 109 patients were included for the analysis; 25 were excluded, and 44 and 40 patients were classified into the adenocarcinoma and squamous cell carcinoma groups, respectively. The median PFS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [27.9 (95% confidence interval (CI): 15.2-not achieved) vs. 9.63 (95% CI: 5.88-13.9) months; p<0.01]. Similarly, the median OS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [not achieved (95% CI: 48.1-not achieved) vs. 23.8 (95% CI; 14.6-not achieved) months; p<0.01]. In the multivariate Cox proportional hazard analysis, the histological type was the only prognostic factor for the PFS (p<0.05) and OS (p<0.05). Conclusion The median PFS and OS were poorer in patients with squamous cell carcinoma than in those with stage III NSCLC treated with CCRT and durvalumab. The histological type was an independent factor affecting the PFS and OS.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8 + T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8 + T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13 , as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13 , tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1 (PD-1)/ TNFRSF9 (4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients ( p  = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8 + T cells in MPE, which are associated with patients' prognosis. (233 words)., Competing Interests: This study was partly funded by NEC Corporation., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Patients with uncommon EGFR- mutated non-small-cell lung cancer (NSCLC) demonstrated lower clinical efficacy of first-generation EGFR-tyrosine kinase inhibitors compared with patients harboring common EGFR- mutated NSCLC. The US FDA has approved afatinib for uncommon EGFR mutation positive NSCLC based on the pooled analysis in the first- or second-line setting. Osimertinib has limited evidence in the small sample sizes of phase 2 studies in any-line settings. The aim of the present single-arm, multicenter, phase 2 study is to evaluate the efficacy of osimertinib for previously untreated NSCLC. The primary end point is to assess the overall response to osimertinib. The secondary end points include disease control rate, progression-free survival, duration of time-to-treatment failure, overall survival and safety. Clinical trial registration: jRCTs071200002.