Shinshu University

LaTiO2N photocatalysts are attractive because they are responsive to visible light up to a wavelength of 600 nm. However, during the nitridation process to produce LaTiO2N from La2Ti2O7, the introduction of defects can cause a reduction in the hydrogen evolution activity of the photocatalyst, which limits its application to overall water splitting. Such defects can arise due to the change in crystal structure and the occurrence of overnitridation. Herein, it is demonstrated that nitridation of a metastable La–Ti oxide obtained by flame spray pyrolysis (FSP) can suppress the formation of such defects. A detailed analysis of the transition pathway during nitridation reveals that a combination of FSP and Al doping is essential for suppressing mesopore formation resulting from the volume change and Ti⁴⁺ reduction due to overnitridation. This leads to an increase in the apparent quantum yield for Al‐doped LaTiO2N during the visible‐light‐driven hydrogen evolution reaction, compared to that for undoped LaTiO2N. In the present study, insights are provided into the importance of minimizing structural changes during the synthesis of oxynitride photocatalysts by designing isostructural precursors for enhanced photocatalytic activity.

Introduction First‐line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR‐tyrosine kinase inhibitor (TKI) is often performed after first‐line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR‐TKI rechallenge after first‐line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR‐TKI rechallenge with another TKI. Methods This multicenter prospective observational study enrolled patients with EGFR‐mutated NSCLC who received first‐line osimertinib and another EGFR‐TKI as second‐ or third‐line treatment between September 2018 and August 2020. Results Fifty‐three patients received rechallenge with another EGFR‐TKI in the second‐line (n = 38, 71.7%) or third‐line (n = 15, 28.3%) setting. The primary reason for first‐line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR‐TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real‐world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR‐TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis. Conclusion EGFR‐TKI rechallenge with another TKI is well tolerated in patients with EGFR‐mutated NSCLC. Thus, it may be a useful treatment option after first‐line osimertinib failure, especially after osimertinib discontinuation due to toxicity.

The novel HLA‐C*04:535 allele differs from HLA‐C*04:01:01:01 by two substitutions in exon 3 and 3′UTR.

Objectives: To investigate the current state of primary palliative care practice in Japanese critical care settings, identify care perceived as equivalent to primary palliative care, and explore the barriers. Methods: We employed a quantitative descriptive questionnaire survey with a nationwide cross-sectional design involving 740 critical care specialist nurses. Results: Questionnaires were received from 384 nurses, yielding a response rate of 51.9%. Nurses recognized typical palliative care provided to cancer patients, such as “relieving suffering at end-of-life” (95.3%), “pain management” (88.8%), and “caring for patients’ psychological suffering” (88.3%), as primary palliative care in the critical care setting. They also recognized “monitoring and management of delirium” (68.5%), “caring for patients’ social suffering” (63.5%), and “preventing post-intensive care syndromes” (61.7%) less frequently as aspects of primary palliative care in critical care settings. Additionally, the recognition was lower among emergency department nurses than intensive care unit nurses. The nurses recognized inadequate overall palliative care practices, especially regarding patients’ social (72.1%) and spiritual (76.8%) suffering. They recognized “insufficient knowledge and skills among critical care medical staff” (70.6%) and “unable to confirm the patients’ preferences to treatment goals” (54.4%) as barriers to providing primary palliative care. The barriers that nurses recognized less often were “uncertainty about palliative care in critical care settings” (6.8%) and “disagreements among nursing teams regarding providing palliative care” (8.3%). Conclusion: Specialist nurses understood palliative care but felt unprepared in primary palliative care due to limited knowledge. Improved education in primary palliative care and patient-family communication is needed in Japan’s critical care settings.

Creating genetically modified (GM) animals using CRISPR/Cas mediated through the electroporation of two-cell stage embryos, rather than fertilized eggs, holds considerable potential. The full potential of genome editing using two-cell stage embryos is only beginning to be explored. We developed an improved electroporation method to prevent blastomere fusion in two-cell-stage embryos, enabling efficient genome editing. Using this method, we demonstrated that the indel mutation rates and ssODN knock-in (KI) efficiencies in two-cell-stage embryos are comparable to those in fertilized eggs, with a tendency for higher efficiency in long DNA KI. This study highlights the potential value of two-cell-stage embryos and provides enhanced animal model production opportunities. Furthermore, realizing genome editing in two-cell-stage embryos extends the editing timeframe from fertilized egg to two-cell-stage embryo, offering promising avenues for future research in embryo genome editing techniques. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-81198-0.

In September 2023, the Japanese Society for Palliative Medicine (JSPM) issued this consensus statement on chronic pain treatment in cancer survivors. With recent advances in the early diagnosis and treatment of cancer, its prognosis has improved, so prolonged pain in cancer survivors is considered to represent chronic pain and should be addressed. In this statement, we emphasize that not all cancer survivor pain is cancer pain. Pain that is not cancer pain should be managed with analgesics other than opioids and nerve blocks, and pain that persists despite this approach should be treated as non-cancer chronic pain so as to prevent opioid overuse. In addition, cancer survivors at any stage of disease have a potentially life-threatening condition and constantly carry the fear of cancer recurrence. Therefore, even non-cancer pain should not be treated in the same way as general chronic pain, but should be managed with consideration of emotional distress. In the future, we plan to create educational tools for healthcare professionals and to conduct online seminars, both with the goal of providing cancer survivors with appropriate assessment and treatment of chronic pain.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages. Recently, a small case series reported the efficacy of dexamethasone palmitate (DP) in HLH. Here, we present the results of a nationwide survey in Japan detailing 14 cases of EBV-HLH treated with DP in children. One week after DP initiation, fever, cytopenia, and splenomegaly resolved in 77%, 38%, and 77% of patients (10, 5, and 10 of 13 patients, 1 missing). A 50% or greater reduction in ferritin levels was observed in 62% of patients (8 of 13 patients, 1 missing). In addition, the attending physician judged DP to be effective or partially effective in 12/14 (86%) patients. DP-related adverse events were uncommon, with only two infectious events reported. Thus, DP can be a therapeutic option for EBV-HLH.

Biomimetic periodic structures have garnered attention due to their excellent water repellency. The normal-taper angle, which is aspects of the cross-sectional structure, is important factor in achieving water repellency and pressure resistance; however, the underlying physical phenomenon has not been fully explained. Moreover, once a surface becomes hydrophobic, it is difficult to measure the apparent contact angle. The purpose of this paper is to clarify the taper angle that provides high water repellency under pressure impact conditions by formulating the relationship between the taper angle and the height of a droplet bouncing, instead of traditional contact angles, using experimental results. We fabricated multiple samples with different taper angles and groove width/tooth width ratios, through micro-processing using a femtosecond-pulsed laser and a control algorithm, and investigated their effects on water repellency. By using height of a droplet bouncing as an evaluation parameter, we were able to effectively differentiate between taper angles in terms of water repellency. Additionally, we suggested that in the bouncing phenomenon, where droplets are given velocity by falling, the sidewall of the periodic structure and the taper angle affect liquid repellency. To explain this phenomenon, we proposed a pressured-taper angle model where a droplet is pressed against the taper angle. Based on both experimental findings and the pressured-taper angle model, a relationship between the equilibrium contact angle, the taper angle, and the lifting force angle was revealed. Moreover, using this pressured-taper angle model, the taper angle of the periodic structure to achieve maximum liquid repellency was estimated from the equilibrium contact angle of the base material.

Background The Naples prognostic score (NPS) is a remarkable marker of short‐ and long‐term outcomes in various types of cancer. However, its impact on the postoperative outcomes of hepatocellular carcinoma remains controversial. This study aimed to clarify the impact of the NPS on the prognosis and incidence of postoperative complications in hepatocellular carcinoma. Methods Patients with hepatocellular carcinoma ( n = 374) were categorized into high‐ and low‐Naples prognostic score groups; their postoperative outcomes were compared. Prognostic and risk factors for severe postoperative complications were identified using multivariate analyses. Results The low‐Naples prognostic score group had significantly longer overall and recurrence‐free survivals than the high‐Naples prognostic score group ( p = 0.03 and 0.04, respectively). Subgroup analysis revealed a superior predictive value of the NPS in the group with a single tumor ( p = 0.03), tumor diameter ≤5 cm ( p = 0.04), and tumor stage I or II ( p = 0.04). A high NPS was an independent prognostic factor for overall survival (hazard ratio, 1.45; 95% confidence interval (CI), 1.01–2.05; and p = 0.04). The NPS 2–4 group had a higher incidence of the Clavien–Dindo grade ≥ IIIa postoperative complications than the 0–1 group ( p = 0.03) and a score of 2–4 was identified as an independent risk factor for the Clavien–Dindo grade ≥ IIIa postoperative complications (odds ratio, 2.06; 95% CI, 1.01–4.20; and p = 0.05). Conclusions The NPS effectively predicts postoperative outcomes in patients with hepatocellular carcinoma.

Vascular anomalies are composed of two main types: vascular tumors and vascular malformations. Vascular tumors are most commonly infantile hemangioma and other rare related vascular tumors in children and adults. Vascular malformations are distinct from vascular tumors, as they are differentiated by their clinical appearance, imaging, and pathologic characteristics. Vascular tumors include infantile hemangioma, congenital hemangioma (rapidly involuting congenital hemangioma (RICH), partially involuting congenital hemangioma (PICH), or non-involuting congenital hemangioma (NICH)), kaposiform hemangioendothelioma, tufted angioma, pyogenic granuloma, and hemangiopericytoma. Various imaging methods are used for diagnosing vascular malformations, and these techniques should be based on their clinical findings and the purpose of imaging, whether it be for diagnosis, pre- and intra-treatment assessment, or follow-up.

The purposes of the study are to assess the diagnostic performance of preoperative imaging for staging factors in gastric-type endocervical adenocarcinoma (GEA) and to compare the performance for GEA with that of usual-type endocervical adenocarcinoma (UEA) among patients preoperatively deemed locally early stage (DLES) (< T2b without distant metastasis). For this multi-center retrospective study, 58 patients were enrolled. All had undergone MRI with or without CT and FDG PET-CT preoperatively and had been pathologically diagnosed with GEA at five institutions. Based on the medical charts and radiological reports, the diagnostic performances of preoperative imaging for the International Federation of Gynecology and Obstetrics staging factors were assessed retrospectively. Next, the imaging performance was assessed in preoperatively DLES-GEA (n = 36) and DLES-UEA (n = 136, with the same inclusion criteria). The proportions of underestimation of GEA and UEA were compared using Fisher’s exact test. Imaging diagnostic performance for GEA was limited, especially for sensitivity: parametrial invasion, 0.49; vaginal invasion, 0.54; pelvic lymph node metastasis (PELNM), 0.48; para-aortic lymph node metastasis, 0.00; and peritoneal dissemination, 0.25. Among preoperatively DLES patients, the proportions of underestimation were significantly higher in GEA than in UEA; parametrial invasion, 35% vs. 5% (p < 0.01); vaginal invasion, 28% vs. 6% (p < 0.01); PELNM, 24% vs. 6% (p < 0.05); peritoneal dissemination, 6% vs. 0% (p < 0.05). At present, preoperative imaging diagnostic performance for staging factors in GEA does not meet clinical expectations, especially for sensitivity. Among patients preoperatively DLES, the proportions of underestimation in GEA were significantly higher than in UEA. Future incorporation of approaches specifically emphasizing GEA is desirable to improve imaging performance.

The clinical efficacy of transthyretin (TTR) tetramer stabilisers and TTR gene silencers in addition to liver transplantation has been established for hereditary ATTR (ATTRv) amyloidosis. Accordingly, non-central nervous system (CNS) systemic amyloidosis manifestations, such as peripheral neuropathy and cardiomyopathy, are now being overcome. However, emerging disease-modifying therapeutics have limited effects on CNS amyloidosis since they target the blood-circulating TTR produced in the liver, and not the cerebral spinal fluid (CSF) TTR synthesised in the choroid plexus. CNS involvement is therefore becoming the most common and severe complication in patients with ATTRv amyloidosis, including transient focal neurologic episodes, haemorrhagic and ischaemic stroke, cognitive decline, and cranial nerve dysfunction. Pathologically, extensive amyloid depositions are observable in the leptomeninges and leptomeningeal vessels, which are in direct contact with the CSF. Amyloid positron emission tomography is a useful biomarker for the early detection and treatment evaluation of early-onset ATTRv amyloidosis with the V30M (p.V30M) variant. Treatment-wise, blood-brain barrier-permeable stabilisers, intrathecal injection of silencers, and monoclonal antibodies against misfolded TTR and/or ATTR amyloid may potentially ameliorate CNS ATTR amyloidosis. The development of novel imaging/CSF biomarkers and disease-modifying therapies are the greatest unmet medical need in ATTRv amyloidosis and require further clinical trials.

Background and Aim Peutz–Jeghers syndrome (PJS) and juvenile polyposis syndrome (JPS) are autosomal dominant diseases associated with high cancer risk. In Japan, knowledge about the prevalence and incidence of PJS and JPS is lacking despite being crucial for providing appropriate medical support. We aimed to determine the prevalence and incidence of these diseases. Methods In 2022, a nationwide questionnaire survey was conducted to determine the number of patients with PJS or JPS by sex and the number of newly confirmed cases from 2019 to 2021. The target facilities included gastroenterology, pediatrics, and pediatric surgery departments, which were stratified into seven classes on the basis of the total number of beds. We randomly selected target facilities using different extraction rates in each class, resulting in 1748/2912 facilities (extraction rate: 60%) as the final sample. We calculated the estimated number of patients using the response and extraction rates. Results A total of 1077 facilities responded to the survey. The estimated numbers of patients with PJS and JPS were 701 (95% confidence interval [CI]: 581–820) and 188 (95% CI: 147–230), respectively. The 3‐year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively. Male patients constituted 53.5% and 59.6% in the PJS and JPS groups, respectively. Conclusions We determined the prevalence and incidence of PJS and JPS in Japan for the first time. Further research is needed to obtain more detailed information, including the clinical differences and outcomes in Japan.

In patients with papillary thyroid carcinoma, metastasis to Rouviere’s lymph node is considered to be relatively rare. Surgical excision is the first-line treatment, and although various approaches to Rouviere’s lymph node have been reported, transcervical approach is the most commonly adopted. Dysphagia is a major postoperative complication of surgery via the transcervical approach, and while there have been reports of this complication, there are few reports describing the postoperative course in detail. A 31-year-old man diagnosed as having papillary thyroid carcinoma with lymph node metastasis was treated by total thyroidectomy and lymph node dissection (including dissection of Rouviere’s lymph node). He developed postoperative dysphagia and was managed by swallowing rehabilitation, including balloon dilatation. He was discharged on the 49th postoperative day and resumed intake of a regular diet. No recurrence or metastasis was observed after one year. The cervical approach to dissection of Rouviere’s lymph node resulted in transient injury of the pharyngeal branch of the vagus nerve and the pharyngeal nerve plexus, causing postoperative dysphagia. Balloon dilatation was found to be effective for opening the upper esophageal sphincter (UES) in this patient with UES-related dysphagia.

Purpose] Citrate drinks are readily available and effectively remove lactate from blood, improving performance. However, whether they are more beneficial when consumed before or after exercise is unclear. We aimed to examine the effect of citrate drink intake timing on blood lactate removal. [Participants and Methods] We randomly assigned 41 healthy male students to four conditions: citric acid intake before exercise, citric acid intake after, water intake after, and no intake. The participants performed a 5-min ergometer cycle, and we measured the blood lactate levels before and at 0, 5, 10, 20, and 30 min after exercise. We calculated the reduction rate of blood lactate levels by subtracting the respective blood lactate values from those at 0 min and then dividing by the blood lactate value at 0 min (Ex-5, Ex-10, Ex-20, and Ex-30). [Results] The measured blood lactate values or their reduction rates were not significantly different between the four conditions. Significant differences were observed between the pre- and post-citric acid conditions for Ex-5, Ex-10, Ex-20, and Ex-30. [Conclusion] The effects of different timings of citric acid intake on blood lactate removal were not significantly different, and the reduction rate of blood lactate values continued to increase with citric acid intake, regardless of timing.

For the purpose of creating learning support tool for singing instruction, three acoustical parameters based on Singer's formant shown in classical singing voice is defined and discussed. Since Singer's formant is considered to be related to proficiency of classical singing voice, acoustical parameters that represent the relationship between them is required. SFR, Q, and the second convex point represent ratio, sharpness, and height of Singer's formant, respectively. SFR is defined based on the FFT spectrum. Q and the second convex point are defined based on the LPC spectrum. Three analytical questions as follow are examined and shown. (1) Definition of autocorrelation varies sharpness of spectral envelope, and it changes value of Q. (2) The second convex point is in the relation of the logarithm of Q. (3) To keep order of value of Q of various singings, adequate LPC analysis order is 12.

The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery are screening tests for dementia. The go/no-go task offers an alternative approach for evaluating dementia patients. However, its role in screening for dementia remains unclear. We aimed to explore the feasibility of using the go/no-go task as a screening test for dementia via a cross-sectional design. Twenty-four Japanese individuals were evaluated using the go/no-go task, the MMSE, and the MoCA. The total MMSE and MoCA scores were correlated with the total number of errors in the go/no-go task (r=-0.699, p < 0.01; r=-0.756, p < 0.01). Moreover, When the MoCA cutoff value was 25 for MCI, the optimal cutoff score for the total number of error in the go/no-go task to detect MCI was 2, with an Area Under curve (AUC) of 0.98, a sensitivity of 0.94. When the MMSE cutoff value was 27 for MCI, the optimal cutoff score for the total number of error in the go/no-go task to detect MCI was 6, with an AUC of 0.89, a sensitivity of 0.76, showed respectively values close to 1. The go/no-go task is possible a practical screening test for dementia.

BaTaO2N has a valence and conduction band position which make the material a promising candidate for photocatalytic water splitting. However, the material shows a very low solar to hydrogen (STH) efficiency. It is generally assessed that the reason for the low STH is the presence of defects at the surface of the material which act as recombination centers for the excited electrons and holes. Here we show with high resolution transmission electron microscopy (HR TEM) an amorphous layer at the surface BaTaO2N which may be a cause of low STH. We demonstrate the amorphous layer can be removed through etching. Subsequently, the valence band structure is analyzed with UV photoelectron spectroscopy (UPS) and valence band X-ray photoelectron spectroscopy (VBXPS), where the latter has a significantly larger probing depth than the first. UPS reveals that non-etched BaTaO2N has a low density of states (DOS) whereas the VBXPS results are compatible with the optical band gap of the material. However, the DOS of BaTaO2N samples etched with H2SO4 solution were consistent with the optical band gap for both UPS and VBXPS measurements, indicating that after removal of the amorphous layer BaTaO2N is a suitable candidate for photocatalytic water splitting.

This study constructs a path-following controller (rider model) based on nonlinear model predictive control (NMPC) with steering torque as the control input. By combining this with the dynamics model derived by Hatakeyama et al. (2024), we propose a simulation model that considers the main dynamic characteristics of a motorcycle, such as weave and wobble modes. In particular, the internal model used in NMPC has been simplified to ensure a reasonable response when the simulation time is shorter than the real time. In the path-following controller, the parts that calculate the reference roll angle from the reference path and those that calculate the steering torque input from the reference roll angle are handled separately. These components are constructed as cascade structures of outer and inner loops, respectively. This allows the two loops to appropriately use different sampling periods and prediction horizon settings for NMPC, enabling fast computation. In addition, an optimal NMPC solver can be used for both the outer and inner loops, further enhancing fast computation. In riding simulations involving high speeds and large roll angles, where nonlinearities are stronger, stable responses that are roughly consistent with actual riding were obtained in a simulation time shorter than the assumed time for one lap in actual circuit riding. The developed simulation model can be used as a reliable and practical support tool for motorcycle designing.