Himeji University

Background/AimImmune checkpoint inhibitors (ICIs) have become central in the treatment of non-small cell lung cancer (NSCLC). The occurrence of immune-related adverse events (irAEs) is a critical issue in the management of patients with NSCLC receiving ICIs. Recent studies have suggested that patients who develop irAEs may have a better prognosis than those who do not. However, the most problematic cases involved the development of severe irAEs. This study aimed to investigate the clinical impact of severe irAEs (grade ≥3) in patients with NSCLC treated with ICIs.Patients and MethodsWe analyzed 122 patients from a prospective database of consecutive patients with NSCLC who received first-line ICI-containing treatment between November 2018 and October 2024. Patients were classified into two groups: 48 treated with anti-programmed death-ligand 1 (anti-PD-L1) therapy and 74 treated with anti-programmed death-1 (anti-PD-1) therapy. We retrospectively compared the incidence of severe irAEs between the two groups and evaluated the clinical outcomes of severe irAEs on the survival.ResultsAmong 122 patients, 24 (19.7%) experienced severe irAEs. The incidence of severe irAEs was significantly higher among patients treated with anti-PD-1 than among those treated with anti-PD-L1. The incidence of irAE-related death was also higher in the anti-PD-1 group than in the anti-PD-L1 group, with pneumonitis accounting for most of these fatalities (87.5%). There were no significant differences in the progression-free or overall survival between patients with and without severe irAEs. A multivariable analysis showed that the use of anti-PD-1 therapy was associated with a worse overall survival.ConclusionTreatment with anti-PD-1 was associated with an increased risk of severe irAEs. The incidence of severe irAEs was not associated with an improved survival rate.

This paper proposes a novel computationally efficient algorithm for optimal sizing of Battery Energy Storage Systems (BESS) considering renewable energy bidding strategies. Unlike existing two-stage methods, our algorithm enables the co-optimization of both by updating the BESS size during the training of the bidding policy, leveraging an extended reinforcement learning (RL) framework inspired by advancements in embodied cognition. By integrating the Deep Recurrent Q-Network (DRQN) with a distributed RL framework, the proposed algorithm effectively manages uncertainties in renewable generation and market prices while enabling parallel computation for efficiently handling long-term data.

Abstract Line width roughness (LWR) in EUV lithography is known to be caused by “Stochastic effects”, such as the chemical composition distribution within the resist thin film and the non-uniformity of chemical reactions. The compositions of chemically amplified resists before coating film on silicon wafer typically include a base polymer, a photoacid generator, a quencher, and a solvent. In this paper, we investigated about solvent effect, which is the main volume of the resist solution. We investigated solvent effect of resist solution by dynamic light scattering (DLS) measurement. The particle size of polymer in several solvents revealed diameters from 4 to 6 nm. The solvent effect in thin film was measured by resonant soft X-ray scattering (RSoXS) method. It was found the distribution of resist compositions differs depending on the type of solvents and the pre-bake temperatures. These results suggested the selection of resist solvent may also contribute to reducing LWR.

The purpose of this study was to determine the effect of the COVID-19 pandemic on infant development. The study investigated the development of infants at 10-11 months of age between 2020 and 2023 by using the Kyoto Scale of Psychological Development-2020 (KSPD2020), an individualized developmental scale, and the Kinder Infant Developmental Scale (KIDS), a developmental questionnaire. We compared the results of the KSPD2020 with those of a pre-pandemic developmental research and compared the developmental age (DA) of KIDS with children's chronological age (CA). Moreover, the same developmental research was conducted again on the same children at 18-24 months of age. DA for receptive language and expressive language was lower in the KIDS compared to CA in the investigation at 10-11 months. However, in the investigation at 18-24 months, there were no areas where KIDS' DA was lower than CA, and DA in the areas of manipulation, receptive language, social relationship with adults, discipline, and eating was higher than CA. On the other hand, using the KSPD2020, there were no differences when compared to pre-pandemic data in the investigation at 10-11 months. Furthermore, the investigation at 18-24 months showed that developmental quotient (DQ) was lower in the Language-Social (L-S) areas than in the investigation at 10-11 months. The lower DQ of L-S in this study was also evident in comparison to the 18-24 months pre-pandemic data. These results suggested that to investigate the medium- and long-term effects of the COVID-19 pandemic on children's development, it is necessary to use not only parent-filled questionnaires but also individualized developmental scales. In addition, the finding that results may differ depending on the method of developmental assessment is considered important not only for developmental researchers but also for professionals involved in supporting children's development.

Masakazu Nakai, a Kyoto School aesthetician who discussed sports as philosophy, considered the concepts of “type” and “common sense”. The influence of Yasukazu Fukada, Nakaiʼs aesthetic mentor, and Kitaro Nishida is important in interpreting Nakaiʼs insights. It can be observed that Nakai references Nishidaʼs discourse on “type”, highlighting its connection to “common sense”. He then expands the discourse by referencing Fukadaʼs reflections on aesthetic aspects related to “Mood” (Stimmung).

In Japan, the number of older adults living alone who require nursing care continues to rise. The purpose of this study was to identify factors associated with care managers’ experiences of making proxy decisions about life directions for older adults who live alone and whose intentions cannot be fully confirmed. The participants were care managers of in-home long-term care support providers nationwide. An original self-report questionnaire was created with reference to previous research and a web-based survey was conducted. The responses were obtained from 241 people and 211 people were included in the analysis. Two factors were identified that were related to care managers’ experiences of proxy decision-making about the life direction of older adults living alone whose intentions could not be fully confirmed: the ability to perform administrative tasks (odds ratio [OR] 3.38, 95% confidence interval [CI]: 1.39–8.22) and the observed cognitive deterioration (OR 2.89, 95% CI: 1.06–7.83). Even if older adults living alone can independently perform administrative tasks, observed cognitive deterioration may be a prodromal sign that such adults will be unable to make decisions about their future life.

Larval settlement drives population and community dynamics and evolution of marine invertebrates. While it is well known that larvae sense a variety of biological and environmental factors, there is limited information on how they react to specific factors so as to locate settlement sites. Proteinaceous Waterborne Settlement Pheromone (WSP) was purified from adult barnacles, Amphibalanus amphitrite, in a previous study, but it is unclear how WSP guides barnacle cyprids to the source. Here, a series of settlement assays were conducted to investigate the concentration dependence of recombinant WSP. We report that low concentrations of barnacle WSP decrease the probability of settlement of conspecific cyprids, whereas high concentrations have the opposite effect. We suggest that this is because weak WSP informs cyprids that suitable settlement sites with adult barnacles are distant, inducing them to extend the larval phase. The present study clearly shows that larvae use WSP concentration, rather than presence/absence information. In barnacles, several other conspecific chemical/visual cues also attract larvae. This study opens the door to future research to determine how these cues influence larval behavior in nature.

Benzyl isothiocyanate (BITC), derived from cruciferous vegetables, is an organosulfur compound exerting antiproliferative effects in several human cancer cells. In this study, we assessed BITC as a potential osteoclastogenesis inhibitor and investigated its underlying mechanism. BITC at 5 μM significantly decreased the viability of the osteoclast-like differentiating RAW264.7 cells, coinciding with the downregulation of the primary biomarkers for osteoclast differentiation, such as the tartrate-resistant acid phosphatase activity and nuclear factor of activated T-cells gene expression. Not only BITCbut also its metabolites, inhibited cell proliferation in the normal RAW264.7 cells, suggesting that BITC shows an anti-osteoclastogenesis effect in vivo after its ingestion and metabolism, possibly through an antiproliferative action. Both BITC and its metabolites also enhanced the DNA fragmentation and the caspase-3 activity, whereas their higher concentrations tended to suppress these effects. BITC was intracellularly accumulated when the cells were treated with its metabolites via their degradation into the free form. A quantitative experiment using the proteolysis/high performance liquid chromatography technique showed that the amount of BITC-lysine thiourea in the cells was also increased in a time-dependent manner, suggesting that lysine modification of the cellular proteins actually took place in the cells treated by BITC. Among the cellular proteins, the cleaved caspase-3 was identified as a potential target for lysine modification by BITC. Taken together, BITC dissociated from its metabolites as well as its free form might modulate osteoclastogenesis, possibly through inhibition of cell proliferation by protein modification.

Here, we report a case of a pulmonary invasive mucinous adenocarcinoma harboring KRAS G12D, diagnosed from tumor samples containing a very small amount of tumor cells using next‐generation sequencing (NGS) and the recently developed Lung Cancer Compact Panel. A 79‐year‐old woman without any respiratory symptoms underwent chest computed tomography, which revealed a tumor in the left lower lobe. During endobronchial ultrasound (EBUS)‐guided transbronchial biopsy (TBB) using a guide sheath (GS), a sufficient specimen for pathological diagnosis could not be obtained because the patient had a severe cough and pulmonary bullae located adjacent to the tumor. In the absence of EBUS transbronchial biopsy findings using a guide sheath, brush cytology was used to categorize the tumor as class II (Papanicolaou classification). However, the wash fluid from the cytological examination contained enough cells to obtain sufficient nucleic acid for use in sequencing analysis. The latter revealed KRAS G12D expression. Although the patient underwent surgery without pathological evidence, the evaluation of the surgical specimen confirmed a diagnosis of pulmonary invasive mucinous adenocarcinoma. Use of the Lung Cancer Compact Panel enabled the detection of KRAS G12D in the wash fluid of a brush cytology sample and thus a diagnosis of pulmonary invasive mucinous adenocarcinoma.