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Abstract In Earth and planetary science, Pb isotopic composition is well known to play a key role in deciphering the origin and evolution of materials because they provide unique chronological and/or indigenous regional information as a radiogenic daughter nuclide from U and Th. To determine such an isotopic composition, mass spectrometers have been widely used over several decades, which requires a destructive/consuming treatment such as sputtering, laser ablation and thermal ionization. Here, we first report the non-destructive Pb isotopic measurement of natural galena (PbS) using the energy shift of muon-induced characteristic X-rays. The observed Pb isotopic composition of the natural galena is in good agreement with that obtained by conventional mass spectrometry. Such a muon-based Pb isotopic analysis method is expected to be applied to identify the production area of archaeological artefacts (e.g. bronze products), where non-destructive analysis is highly desirable compared to conventional mass spectrometry.

Aim of study: An adjuvant is a material that is added to a spray carrier to improve the application technology's efficiency but lacks phytosanitary qualities. Our objective was to determine the best option of combining fungicides and adjuvants to control soybean (Glycine max) leaf diseases in three cropping seasons. Area of study: The experiment was developed in the Campos Gerais region (PR - Brazil). Material and methods: The five treatments consisted of 1) control (without applying fungicides on soybean plants); 2) fungicide application on soybean plants without adjuvant; 3) fungicide with adjuvant based on mineral oil; 4) fungicide with adjuvant based on lecithin and 5) propionic acid and fungicide with 50% of the dose of adjuvant based on mineral oil + 50% of the dose of surfactant adjuvant based on lecithin and propionic acid. The analyzed variables were the physicochemical characteristics of the spray carrier, the incidence and severity of diseases, and the yield components. A completely randomized design was used to study the physicochemical characteristics of the carrier and in randomized blocks for the field experiment. We used five replicates per treatment. Main results: No foaming and mixing incompatibility of the spray carrier was observed in any treatment. The adjuvant based on lecithin and propionic acid further acidified the spray carrier and presented the same surface tension as mineral oil. The soybean plants that did not receive chemical treatment had a higher occurrence of diseases, which reduced the productive potential. Research highlights: Adding adjuvants to the spray carrier did not increase the performance of fungicides in controlling diseases and did not affect the yield components.

Gimeracil, a component in S-1 (an oral anticancer agent comprising tegafur, a prodrug of 5-fluorouracil (5-FU), potassium oxonate, and gimeracil), inhibits metabolic enzymes, thereby impeding 5-FU degradation. Therefore, the blood level of gimeracil is closely associated with the disposition of 5-FU, and quantification of gimeracil can provide important information if a case shows an inappropriate 5-FU blood concentration. Nevertheless, methods for quantifying gimeracil in human plasma are rarely reported. Herein, we aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying gimeracil, in addition to tegafur and 5-FU, levels in human plasma using a clinically applicable simplified pretreatment process and faster elution time. Hence, an acetamide-functionalized monolith silica disk-packed spin column was used to extract gimeracil and internal standard (IS; nicotinamide), whereas diatomaceous earth-based solid phase for liquid-liquid extraction was used to extract tegafur, 5-FU, and IS (5-chlorouracil) from plasma. Each extract was analyzed within 4 min of elution via LC-MS/MS using a shared LC column and mobile phase. Accuracy and precision analyses indicated lower limits of quantification of 5, 10, and 2 ng/mL for gimeracil, tegafur, and 5-FU, respectively. The calibration curves showed good linearity between 5 and 500 ng/mL for gimeracil, 10 and 5000 ng/mL for tegafur, and 2 and 1000 ng/mL for 5-FU. We confirmed that the levels of all analytes in the plasma of patients with cancer undergoing S-1-inclusive therapy were within the calibration range for each analyte. Thus, this newly developed quantification method is likely to be useful for optimization of S-1 therapy., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: Atezolizumab, one of the anti-PD-L1 antibodies, targets PD-L1 expressed on cancer cells and antigen-presenting cells. This immune checkpoint inhibitor is now commonly used in combination with chemotherapy. The objectives of this study were to confirm the treatment outcomes of combined atezolizumab plus chemotherapy, and to identify prognostic factors, with a particular focus on the impact of the site of metastasis in real-world clinical practice., Patients and Methods: A retrospective review of clinical information on non-small cell lung cancer patients who received combined atezolizumab plus chemotherapy from May 2018 to August 2024 at our 11 hospitals was conducted., Results: The 141 patients evaluated had a median progression-free survival of 8.0 months and a median overall survival of 19.0 months. Multivariate analyses showed that 'absence of liver metastases', 'absence of adrenal metastases', 'first-line combined atezolizumab plus chemotherapy', and 'good performance status' were associated with progression-free survival and overall survival. Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients., Conclusion: Efficacy and immune-related adverse events associated with the combination of atezolizumab and chemotherapy in non-small cell lung cancer patients were comparable to previous clinical trials. To ensure that appropriate patients receive the most effective treatment, it is important to identify detailed prognostic factors, including clinical information, such as the affected metastatic organs. Continued research and further accumulation of knowledge in this area are eagerly anticipated., Competing Interests: The Authors declare that they have no competing interests in relation to this study., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer rarely leads to disseminated BCG infections, most of which occur early after BCG instillations or in immunocompromised patients. We report late-onset disseminated BCG infection after intravesical BCG immunotherapy in a non-immunocompromised patient. A 78-year-old non-immunocompromised man was admitted with fever and hepatosplenomegaly. He had received intravesical BCG immunotherapy four years earlier. Granulomas were detected in multiple organs and BCG was identified in urine and bone marrow fluid, leading to a diagnosis of disseminated BCG infection. Longitudinal measurements of liver and spleen volumes by computed tomography were useful in determining treatment efficacy., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Human and animal rights: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Written informed consent to publish this report was obtained from the patient., (© 2024. Japanese Society of Gastroenterology.)

Background: Childhood cerebral type of Adrenoleukodystrophy (CC-ALD) is fatal without hematopoietic stem cell transplantation (HSCT). We consider whether EEGs showing focal paroxysmal delta waves can be a candidate of early detector of the apparent ALD and HSCT therapy., Methods: Twenty-two male children with ALD (5-16 years; 10.4 ± 2.8) were evaluated. Fourteen children were diagnosed as CC-ALD and the rest 8 were yet asymptomatic both clinical and MRI findings. CC-ALD patients with frontal or occipital MRI main lesions were classified as Types F and O (4 and 10 patients). Asymptomatic patients were classified as Type A whose clinical types had not been known. Awake electroencephalogram was recorded during cognitive tasks and analyzed using fast Fourier transform (FFT). Eight children (1/4 F, 3/10 O and 4/8 A patients) were evaluated pre- and post-HSCT., Results: FFT analysis revealed the high voltage slow wave characterized by an increased delta band wave power volume (DBPV) in all children. The DBPV of Type F and O patients showed anterior and posterior dominance in 4/4 and 9/10 patients. Dominant DBPV in Type A patients were anterior and posterior in 6/8 and 1/8, respectively. We classified them as Type F' and O'. DBPV decreased in all (8/8) patients after HSCT therapy., Conclusion: All patients showed paroxysmal delta wave. In symptomatic patients, abnormal delta wave appeared in their corresponding cortical lesions and decreased after therapy. In asymptomatic patients it may be the first sign of the apparent ALD onset and suggesting when to consider HSCT therapy., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients., Competing Interests: Declaration. Conflict of interest: Tadao Ishida: Research funding received from Alexion pharma, BMS, GSK, Janssen, Pfizer, Prothena, Sanofi, and Takeda. Honoraria received from BMS, CSL Behring, Janssen, Ono, Pfizer, Sanofi, and Takeda. Yoshiaki Kuroda: Payment or honoraria received from Amgen, Asahi Kasei Pharma, Astrazeneca, BMS, Janssen, Ono, Sanofi, SymBio Pharmaceuticals, and Takeda Pharmaceuticals. Kosei Matsue: Grants or contract received from Astrazeneca. Takuya Komeno: Grants or contracts received from Abbvie, BMS, Janssen Pharmaceutical K.K., and Sanofi. Takuro Ishiguro: Payment or honoraria received from Janssen Pharmaceutical K.K., Sanofi, BMS, Ono Pharmaceutical, Takeda Pharmaceutical Company Limited, and Novartis. Jun Ishikawa: None. Toshiro Ito: None. Hiroshi Kosugi: Payment or honoraria received from Abbvie G.K., Asahi Kasei Pharma, Astrazeneca K.K., Beckton Dickinson K.K., BMS K.K., Chugai, GSK K.K., Janssen Pharmaceutical K.K., Japan Blood Products Organization, Kyowa Kirin, Kissei Pharmaceutical, Nippon Shinyaku, Novartis Pharma K.K., Novo Nordisk Pharma Japan, Ono, Sanofi K.K., and Takeda. Kazutaka Sunami: Research funding received from: Abbvie, Beigene, BMS, Chugai, GSK, Incyte, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Otsuka, Pfizer, and Sanofi. Honoraria received from BMS, Janssen, and Sanofi. Kazuko Nishikawa: Employee of Janssen Pharmaceutical K.K. Kazuhiro Shibayama: Employee of Janssen Pharmaceutical K.K., and own stock or stock options in Johnson & Johnson. Kensuke Aida: Employee of Janssen Pharmaceutical K.K. Hiroshi Yamazaki: Employee of Janssen Pharmaceutical K.K., own stocks or stock options in Kameya Shoji Co., Ltd. Mitsuo Inagaki: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson & Johnson. Hisanori Kobayashi: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson and Johnson. Shinsuke Iida: All support for the present manuscript received from Janssen. Grants received from Abbvie, Amgen, BMS, Daiichi Sankyo, GSK, Janssen, Novartis, Ono, Otsuka, Pfizer Sanofi, Shionogi, and Takeda. Consulting fees received from Abbvie, Astrazeneca, BMS, GSK, Janssen, Novartis, Otsuka, Pfizer, and Sanofi. Payment or honoraria received from Astrazeneca, BMS, Janssen, Ono, Pfizer, Sanofi, and Takeda. Other financial or non-financial interests received from Chugai. Ethical approval: The study protocol and associated study documents were approved by the Institutional Review Board. Good Clinical Practice (GCP) guidelines, established by the International Council for Harmonization (ICH), and all relevant regulatory requirements were followed during the conduct of this study., (© 2024. The Author(s).)

We developed phosphorylation reagents with a nitrobenzyl hydrophobic tag and used them for 5'-phosphorylation of chemically or transcriptionally synthesized RNA. The capability of hydrophobic tags to synthesize 5'-monophosphorylated RNA was evaluated based on the yield of the desired oligonucleotides, stability of protecting groups during cleavage/deprotection, separation ability in reverse-phase HPLC (RP-HPLC), and deprotection efficiency after RP-HPLC purification. The results showed that a nitrobenzyl derivative with a tert-butyl group at the benzyl position was most suitable for RNA 5'-phosphorylation. Using the developed phosphorylation reagent, we chemically synthesized 5'-phosphorylated RNA and confirmed that it could be purified by RP-HPLC and the following deprotection. In addition, we demonstrated complete chemical synthesis of minimal mRNA by chemical capping of 5'-monophosphorylated RNA. Ribonucleoside 5'-monophosphates with hydrophobic protecting groups have also been developed and used as substrates to transcriptionally synthesize 5'-phosphorylated RNA with >1000 bases. From the mixture of the by-products and the desired RNA, only 5'-monophosphorylated RNA could be effectively isolated by RP-HPLC. Furthermore, monophosphorylated RNA can be converted into circular mRNA via RNA ligase-mediated cyclization. Circular mRNA expression of nanoluciferase in cultured cells and mice. These techniques are important for the production of chemically synthesized mRNA and circular mRNA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates., Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates., Design, Setting, and Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled., Main Outcomes and Measures: For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population., Results: The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes., Conclusions and Relevance: This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.

The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding. The excitatory synapses in mutant mice had abnormal synaptic vesicle clustering and postsynaptic density elongation, more silent synapses, and fewer active synapses, which additionally exhibited enhanced basal transmission with impaired release probability. Alongside these phenotypes, we observed aberrant synaptic protein phosphorylation, but no differences in the neurotrophin signaling pathway. Consistent with reports linking these aberrantly phosphorylated proteins to neuropsychiatric disorders, mutant TrkC knock-in mice displayed impaired social responses and increased avoidance behavior. Thus, through its regulation of synaptic protein phosphorylation, the TrkC-PTPσ complex is crucial for the maturation, but not formation, of excitatory synapses in vivo., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Microcystic stromal tumors (MCST) are rare sex cord-stromal tumors with distinctive microcystic features and stromal tumor immunophenotypes. Few reports have discussed MCST from the perspective of magnetic resonance imaging (MRI). In this report, we describe the MRI findings of MCST, review our case, and discuss it based on previous reports. A 24-year-old female with a history of familial adenomatous polyposis (FAP) presented to the emergency department with complaints of lower abdominal pain. A plain abdominal computed tomography scan revealed a huge ovarian tumor measuring 19 cm. MRI revealed an isointense ovarian tumor on T1-weighted images and a heterogeneous high signal intensity on T2-weighted images. Contrast-enhanced MRI demonstrated enhancement confined to the capsular structures. Based on the tumor size and MRI findings, malignancy could not be definitively excluded. However, considering the clinical presentation, a diagnosis of tumor infection was made, and an open adnexectomy was subsequently performed. Pathological examination confirmed the diagnosis of MCST, and the patient's condition progressed without apparent recurrence one year after surgery. In previous reports, MCST has been associated with FAP, and almost all cases were benign. Patients diagnosed with FAP can reduce the risk of acute abdominal pain by using less invasive treatments, as long as they keep up with regular checkups and screenings., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsuji et al.)

Objectives: To date, there have been no reports on the long-term effects of a method that combines external hemorrhoidectomy with aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy. This study aimed to investigate the efficacy and safety of external hemorrhoidectomy combined with ALTA sclerotherapy (EA) in reducing postoperative complications associated with conventional hemorrhoidectomy., Methods: EA was performed under sacral epidural anesthesia, and ALTA sclerotherapy was applied to the remaining internal hemorrhoids after resection of the external hemorrhoids. Mixed internal and external hemorrhoids were treated with EA, whereas internal hemorrhoids without external hemorrhoids were treated with ALTA sclerotherapy. The three EA patterns were defined as EA1, EA2, and EA3, depending on the number of EAs performed., Results: This study included 3,403 patients who underwent EA for grade II-IV mixed hemorrhoids. EA1 was the most common, with 1,789 (52.6%) cases, followed by EA2 (36.2%) and EA3 (11.2%). Postoperative complications occurred in 120 (3.5%) patients and increased with the number of EAs, with fever and bleeding being common in the early postoperative period, and perianal abscess and/or fistula being common after 1 month. The mean postoperative follow-up period was 26.4 months, and 136 (4.0%) patients underwent reoperation for recurrent internal or mixed hemorrhoids. The reoperation rate for EA1 was significantly higher than that for EA2 and EA3. The 5- and 10-year cumulative recurrence-free rates were 92.5% and 67.2%, respectively., Conclusions: EA is as curative as conventional hemorrhoidectomy and reduces postoperative complications. Therefore, EA is the preferred procedure for patients with mixed hemorrhoids., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Cyclic peptides have attracted attention as new modalities for drug development owing to their unique pharmacokinetic and pharmacodynamic properties. Destruxin E, a 19-membered cyclodepsipeptide, is a promising candidate drug for cancer therapy. The purpose of the present study was to clarify the molecular mechanisms underlying membrane transport, metabolism, and the binding for target molecules of destruxin E in human cervical carcinoma HeLa cells used as a model of cancer cells. The influx transport and the intracellular metabolism of destruxin E were non-saturable and saturable, respectively, at up to 10 μM. The intracellular amounts of destruxin E and destruxin E-diol after incubation of destruxin E with the cells significantly decreased at 4 °C compared to those at 37 °C. Destruxin E-diol, but not destruxin E, undergoes efflux transport out of cells via P-gp/MDR1/ABCB1 and BCRP/ABCG2. The epoxide hydrolase EPHX2 functions as a potent metabolizing enzyme that can convert the epoxide of destruxin E to the destruxin E-diol. Treatment with an EPHX2 inhibitor increased the intracellular destruxin E levels and enhanced the inhibitory activity of vacuolar type-H + ATPase. These results suggest that epoxide hydrolase could be a regulatory factor for intracellular destruxin E levels and its pharmacological activity., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

α-Lactalbumin (α-LA) and β-lactoglobulin (β-LG) are major whey proteins in bovine milk. We studied the effects of these molecules on the intestinal cell response by comparing the native form with the denatured form containing oligomers obtained by treatment with 2,2,2-trifluoroethanol (TFE). We previously reported that proteins in native and TFE-treated forms exhibited cell growth stimulation and cytotoxicity, respectively, in undifferentiated rat crypt IEC-6 and human colon Caco-2 cells. However, neither whey protein showed cytotoxicity even in the TFE-treated form in differentiated Caco-2 cells. Only undifferentiated immature intestinal cells can distinguish between these native and denatured proteins. Moreover, α-LA and β-LG exhibited different oligomer formation characteristics during the TFE treatment. In the present study, we compared the effects of native and TFE-treated whey proteins on IEC-6 cells in more detail. The native forms of both whey proteins exhibited cell proliferative effects in a concentration-dependent manner. For the TFE-treated forms, α-LA showed rapid and potent cytotoxicity, whereas β-LG altered cell responses depending on its concentration and exposure time; lower concentration/shorter exposure and higher concentration/longer exposure induced cell growth stimulation and cytotoxicity, respectively. Pre-treatment of the cell membrane with cholesterol suppressed the effects on the cell response only in TFE-treated β-LG (TFE-β-LG). In a preliminary examination using inhibitors of signal transduction, TFE-treated α-LA acted on the intrinsic apoptosis pathway via Bcl-2-associated X and p53, whereas the action of TFE-LG did not require this pathway. Tyrosine phosphorylation is necessary for the cell proliferation effect of both native whey proteins; however, native α-LA, but not native β-LG, also required activation of the pathway with selective epidermal growth factor receptor tyrosine kinase and Janus kinase 2/3. In summary, the two major bovine milk whey proteins induced similar yet discrete responses in undifferentiated intestinal cells. Even when oligomers are formed, β-LG may be much less hazardous to immature intestinal cells than α-LA.

Objectives: We explored the connection between varicose vein and edema, by investigating extracellular water ratio (E/T) using bioelectrical impedance analysis., Methods: In a prospective cohort study 120 patients underwent varicose vein surgery with extracellular fluid to total body water ratio (E/T) and E/T postop divided by E/Tpreop (E/T ratio) measured using a body composition analyzer. Edema was defined as E/T ≥0.390. Seventy-nine patients received unilateral treatment, while 41 underwent bilateral. p < .05 is statistically significant., Results: Preoperatively, patients exhibited edema (E/T) in the treated leg (0.394 ± 0.009), untreated leg (0.392 ± 0.009), trunk (0.390 ± 0.007), and whole body (0.391 ± 0.007). Postoperatively, E/T decreased across body ( p < .05). The lowest E/T ratio was observed in the treated leg (0.991 ± 0.012), followed by the untreated leg (0.994 ± 0.012), the trunk (0.995 ± 0.009), and the whole body (0.994 ± 0.009). E/T ratio of bilateral group were lower than unilateral group ( p < .05)., Conclusion: Varicose vein contributes to generalized edema, and treatment alleviates edema in the treated leg and the entire body., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Manidipine (MP) is a dihydropyridine drug, which is treated for the reduction of high blood pressure. The aim of this study is to clarify the photochemical behavior of MP in the case of ultraviolet light (UV) irradiation for MP tablets (Calslot ® tablets). The tablets and its altered forms (powders and suspensions) were UV-irradiated using a black light, and residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography (HPLC). Due to the photoproducts of MP were detected in HPLC chromatograms, the elucidation of their chemical structures was carried out utilizing electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). As a result, APIs in Calslot ® tablets were almost completely photodegraded in the case that Calslot ® tablets were suspended in an aqueous media along with the generation of some MP photoproducts. LC-ESI-MS/MS analysis clarified the chemical structures of three MP photoproducts, indicating that they were a pyridine analogue, benzophenone and a hydrolysate. Benzophenone was a main MP photoproduct. It was possible that MP might be firstly oxidized to form its pyridine analogue, followed by the oxidation of a dimethyl methylene moiety. This moiety seemed to be eliminated as a benzophenone, and the cleavage of an ester bond of the residual moiety resulted in the generation of a hydrolysate. Finally, toxicological potencies of MP and its photoproducts were predicted in silico toxicity evaluation, suggesting some of biological effects of the photoproducts might be altered compared with MP., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Calcified amorphous tumor (CAT) of the heart is a rare, non-neoplastic cardiac mass with mitral valves and annuli being the most common sites. The presence of mitral annular calcification (MAC) is associated with an increased risk of stroke or other systemic embolisms. Here, we report a case of CAT showing rapid growth with MAC and investigate the link between the two., Case Presentation: A 71-year-old man presented at our hospital with dyspnea and had been undergoing hemodialysis for 26 years for chronic glomerulonephritis. Transthoracic echocardiography (TTE) revealed moderate mitral stenosis with bulky MAC. Two months later, the patient developed progressive dyspnea, and follow-up TTE revealed a highly mobile mass (8 × 5 mm) attached to the left ventricular (LV) side of the posterior MAC. He underwent surgery because of congestive heart failure and a high risk of embolization. Surgical inspection revealed that the tumor was attached beneath the P3 segment of the mitral valve on the LV side and was removed. When removing the MAC, toothpaste-like contents drained from the encapsulated mass inside the MAC at the P3 segment, where the tumor was located. After reconstructing the posterior mitral annulus defect with a bovine pericardial patch, mitral valve replacement with a mechanical prosthesis, a maze procedure, and left appendage closure were performed. Histopathological examination revealed that the excised tumor contained fibrin and calcium deposits. The mass was diagnosed as a CAT., Conclusions: CAT may be one of the causes of stroke induced by MAC. Routine follow-up echocardiography should be recommended for patients with MAC, especially those undergoing hemodialysis., (© 2024. The Author(s).)

Flexible control of motor timing is crucial for behavior. Before volitional movement begins, the frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets. This activity in the cortico-basal ganglia loop may function as an adjustable 'timer,' triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviors, distinguishing their individual roles in this timer function remains challenging. To address this, we conducted perturbation experiments combined with multi-regional electrophysiology in mice performing a flexible lick-timing task. Following transient silencing of the frontal cortex, cortical and striatal activity swiftly returned to pre-silencing levels and resumed ramping, leading to a shift in lick timing close to the silencing duration. Conversely, briefly inhibiting the striatum caused a gradual decrease in ramping activity in both regions, with ramping resuming from post-inhibition levels, shifting lick timing beyond the inhibition duration. Thus, inhibiting the frontal cortex and striatum effectively paused and rewound the timer, respectively. These findings suggest the striatum is a part of the network that temporally integrates input from the frontal cortex and generates ramping activity that regulates motor timing.

This study was to compare glutaminase and Na + , K + -ATPase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three triterpenes from the selected extract of Eucalyptus globulus Labill. Three triterpenes, ursolic acid ( 1 ), robustanic acid ( 2 ) and ursolic acid lactone ( 3 ), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC 50 values of 1 - 3 and the control compound against glutaminase, 6-diazo-5-oxo-l-norleucine (DON), were 443 μM, 334 μM, 963 μM and 134 μM, respectively. The IC 50 values of 1 , 2 and the control compound against Na + , K + -ATPase and ouabain, were 180 μM, 56 μM and 0.5 μM, respectively. Compounds 1 and 2 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase and Na + , K + -ATPase. This is the first report on glutaminase and Na + , K + -ATPase inhibitory activities of 2., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Ibrutinib is a first-in-class Bruton kinase inhibitor against B-cell neoplasms including Waldenström macroglobulinemia (WM). This study evaluated the efficacy and safety of ibrutinib-rituximab in Japanese patients with WM. Patients received ibrutinib 420 mg orally once daily plus weekly rituximab 375 mg/m 2 IV (8 infusions total). The primary end point was major response rate (MRR; PR or better) by Independent Review Committee assessment. Secondary endpoints were progression-free survival (PFS), safety, pharmacokinetics, and biomarkers. Primary analysis was conducted in 16 patients [baseline, treatment naïve: 8 (50.0%); relapsed/refractory WM: 8 (50.0%)] who received ibrutinib-rituximab, after all patients completed Week 57 or end of treatment. At primary analysis, MRR was 87.5% [14/16 patients; 95% CI: 61.7, 98.4%; p < 0.0001 (null hypothesis: 32% response rate)]. At final analysis (median study intervention duration: 34.4 months, median follow-up: 35.0 months), MRR was unchanged at 87.5%, but VGPR [6/16 (37.5%)] and PR [8/16 (50.0%)] improved. Prior treatment status did not affect response. At final analysis, median PFS was not reached [36-month PFS rate: 86% (95% CI: 55, 96%)]. No critical safety signals were reported. This study demonstrated a positive benefit/risk profile of ibrutinib-rituximab in Japanese patients with WM, consistent with the iNNOVATE study., (© 2024. The Author(s).)

Background: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC., Methods: This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival., Results: Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m 2 ), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325-4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016-3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009-3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups., Conclusion: Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Yamamoto is a proctor for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy., Methods: Eighty patients who had undergone pancreaticoduodenectomy for pancreatic cancer between July 2010 and December 2023 were included in this study. The psoas muscle index was used to assess sarcopenia. The C-reactive protein-to-albumin ratio, prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were used to calculate the preoperative inflammatory marker levels. The prognostic factors for overall survival were determined using Cox regression analysis., Results: Twenty-four patients were diagnosed with sarcopenia. Sarcopenia showed a significant association with advanced tumor stage. Univariate analysis revealed a significant reduction in overall survival in patients with a prognostic nutritional index of <45, C-reactive protein-to-albumin ratio of ≥0.047, cancer antigen 19-9 levels of ≥130 U/mL, sarcopenia, lymph node metastasis, and vascular invasion. Multivariate analysis revealed that a C-reactive protein-to-albumin ratio of ≥0.047 (hazards ratio, 3.383; 95% confidence interval: 1.384-8.689; p< 0.001), cancer antigen 19-9 levels of ≥130 U/mL (hazards ratio, 2.720; 95% confidence interval: 1.291-6.060; p = 0.008), sarcopenia (hazards ratio, 3.256; 95% confidence interval: 1.535-7.072; p = 0.002) and vascular invasion (hazards ratio, 2.092; 95% confidence interval: 1.057-4.170; p = 0.034) were independent predictors of overall survival. Overall survival in the sarcopenia and high C-reactive protein-to-albumin ratio groups was significantly poorer than that in the non-sarcopenia and low C-reactive protein-to-albumin ratio and sarcopenia or high C-reactive protein-to-albumin ratio groups., Conclusion: Sarcopenia and a high C-reactive protein-to-albumin ratio are independent prognostic factors in patients with pancreatic cancer after pancreaticoduodenectomy. Thus, sarcopenia may have a better prognostic value when combined with the C-reactive protein-to-albumin ratio., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Utsumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigated the utility of optical coherence tomography (OCT) for staging iris pigmented lesions in cats. Eighteen cats that underwent OCT examination for unilateral iris pigmented lesion were included. The cats were either suspected of melanosis due to clinical features ( n = 8) or had been definitively diagnosed through histopathology with iris melanosis ( n = 3), early feline diffuse iris melanoma (FDIM) ( n = 4), or mid-stage or advanced FDIM ( n = 3). From OCT images, mean iris thickness (MIT) was measured, and the ratio of pigmented lesion to normal iris (PN) was calculated. OCT images depicted the entire iris layer in all eyes with suspected melanosis, iris melanosis, and early FDIM, but observing the entire lesion in mid-stage/advanced FDIM was challenging. No significant difference in MIT was observed among the groups. Conversely, PN ratio was significantly higher ( p < 0.05) in early FDIM (1.29 ± 0.16) than in suspected melanosis (1.02 ± 0.10) or iris melanosis (0.99 ± 0.09). Furthermore, OCT imaging revealed hyperreflective lines in 75% of eyes with suspected melanosis and in all the eyes with iris melanosis, corresponding to the pigmented lesions. Our results demonstrate that OCT is capable of detecting subtle differences in iris thickness and features in early-stage FDIM, indicating its potential utility in distinguishing between iris melanosis and early FDIM. Further study is warranted to verify the reliability of such OCT findings.

Background/aim: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival., Patients and Methods: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities., Results: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%)., Conclusion: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC)., Methods: Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant., Results: Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m 2 ), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively)., Conclusion: Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We herein report a case of recurrent infection caused by Verruconis gallopava, which is known to cause fatal phaeohyphomycosis. A 71-year-old man presented with a fever, and computed tomography revealed right chest wall thickening. Eleven years earlier, he had undergone autologous peripheral blood stem cell transplantation for a hematological malignancy. One year earlier, he had undergone excision of a solitary pulmonary nodule, from which had been detected V. gallopava. On this occasion, right chest wall surgery was performed to investigate the cause of the fever, which led to the diagnosis of recurrent infection. Even if a localized lesion is excised, additional antifungal therapy should be performed.

Bacteriophage Mu is a temperate phage known to infect various species of Enterobacteria, playing a role in bacterial mutation induction and horizontal gene transfer. The phage possesses two types of tail fibers important for host recognition, which enable it to expand its range of hosts. The alternate tail fibers are formed through the action of genes 49-50 or 52-51, allowing the Mu phage to recognize different surfaces of host cells. In a previous study, we presented the X-ray crystal structure of the C-terminal lipopolysaccharide (LPS)-binding domain of gene product (gp) 49, one of the subunits comprising the Mu tail fiber. In this study, we have determined the structure of the alternative tail fiber subunit, gp52, and compared it with other tail fibers. The results revealed that Mu phage employs different structural motifs for two individual tail fibers for recognizing different hosts., Competing Interests: Declaration of competing interest The authors have no declarations and conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glutaminase is an important target that is often over-expressed in neurodegenerative and lifestyle-related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Three compounds isolated from fresh leaves of Diospyros kaki Thunberg, ursolic acid ( 1 ), rotungenic acid ( 2 ) and barbinervic acid ( 3 ), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC 50 values of 1 - 3 and 6-diazo-5-oxo-L-norleucine (DON) as control were 775, 13, 14, and 434 μM, respectively. Compounds 2 and 3 showed higher glutaminase inhibitory activities than DON. Compounds 2 and 3 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of 2 and 3 .

This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients., (© 2024. The Author(s).)

Background/aim: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged ≥80 years) with resected biliary tract cancer., Patients and Methods: Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models., Results: Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged ≥ 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher T-stage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival., Conclusion: Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged ≥80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer., Competing Interests: The Authors declare that they have no competing interests., (Copyright 2024, International Institute of Anticancer Research.)

Blood glucose levels fluctuate during daily life, and the oxygen concentration is low compared to the atmosphere. Vascular endothelial cells (ECs) maintain vascular homeostasis by sensing changes in glucose and oxygen concentrations, resulting in collective migration. However, the behaviors of ECs in response to high-glucose and hypoxic environments and the underlying mechanisms remain unclear. In this study, we investigated the collective migration of ECs simultaneously stimulated by changes in glucose and oxygen concentrations. Cell migration in EC monolayer formed inside the media channels of microfluidic devices was observed while varying the glucose and oxygen concentrations. The cell migration increased with increasing glucose concentration under normoxic condition but decreased under hypoxic condition, even in the presence of high glucose levels. In addition, inhibition of mitochondrial function reduced the cell migration regardless of glucose and oxygen concentrations. Thus, oxygen had a greater impact on cell migration than glucose, and aerobic energy production in mitochondria plays an important mechanistic role. These results provide new insights regarding vascular homeostasis relative to glucose and oxygen concentration changes., (© 2024. The Author(s).)

We developed chemically modified PCR primers that allow the design of flexible sticky ends by introducing a photo-cleavable group at the phosphate moiety. Nucleic acid derivatives containing o -nitrobenzyl photo-cleavable groups with a tert -butyl group at the benzyl position were stable during strong base treatment for oligonucleotide synthesis and thermal cycling in PCR reactions. PCR using primers incorporating these nucleic acid derivatives confirmed that chain extension reactions completely stopped at position 1 before and after the site of the photo-cleavable group was introduced. DNA fragments of 2 and 3 kbp, with sticky ends of 50 bases, were successfully concatenated with a high yield of 77%. A plasmid was constructed using this method. Finally, we applied this approach to construct a 48.5 kbp lambda phage DNA, which is difficult to achieve using restriction enzyme-based methods. After 7 days, we were able to confirm the generation of DNA of the desired length. Although the efficiency is yet to be improved, the chemically modified PCR primer offers potential to complement enzymatic methods and serve as a DNA concatenation technique., Competing Interests: The authors declare that they have no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Background and Objectives : Our research group developed a robot-assisted diabetes self-management monitoring system to support Certified Diabetes Care and Education Specialists (CDCESs) in tracking the health status of patients with type 2 diabetes (T2D). This study aimed to evaluate the impact of this system on glycemic control and to identify suitable candidates for its use. Materials and Methods : After obtaining written informed consent from all participants with T2D, the CDCESs conducted remote interviews with the patients using RoBoHoN. All participants completed a questionnaire immediately after the experiment. HbA1c was assessed at the time of the interview and two months later, and glycemic control status was categorized as either "Adequate" or "Inadequate" based on the target HbA1c levels outlined in the guidelines for adult and elderly patients with type 2 diabetes by the Japan Diabetes Society. Patients who changed their medication regimens within the two months following the interview were excluded from the study. Results : The clinical characteristics of the 28 eligible patients were as follows: 67.9 ± 14.8 years old, 23 men (69%), body mass index (24.7 ± 4.9 kg/m 2 ), and HbA1c levels 7.16 ± 1.11% at interview and two months later. Glycemic control status (GCS) was Adequate (A) to Inadequate (I): 1 case; I to A: 7 cases; A to A good: 14 cases; I to I: 6 cases ( p -value = 0.02862 by Chi-square test). Multiple regression analyses showed that Q1 (Did RoBoHoN speak clearly?) and Q7 (Was RoBoHoN's response natural?) significantly contributed to GCS, indicating that the naturalness of the responses did not impair the robot-assisted interviews. The results suggest that to improve the system in the future, it is more beneficial to focus on the content of the conversation rather than pursuing superficial naturalness in the responses. Conclusions : This study demonstrated the efficacy of a robot-assisted diabetes management system that can contribute to improved glycemic control.

To study transcriptome dynamics without harming cells, it is essential to convert chemical bases. 4-Thiouridine (4sU) is a biocompatible uridine analogue that can be converted into a cytidine analogue. Although several reactions can convert 4sU into a cytidine analogue, few studies have compared the features of these reactions. In this study, we performed three reported base conversion reactions, including osmium tetroxide, iodoacetamide, and sodium periodate treatment, as well as a new reaction using 2,4-dinitrofluorobenzene. We compared the reaction time, conversion efficacy, and effects on reverse transcription. These reactions successfully converted 4sU into a cytidine analogue quantitatively using trinucleotides. However, the conversion efficacy and effect on reverse transcription vary depending on the reaction with the RNA transcript. OsO 4 treatment followed by NH 4 Cl treatment showed the best base-conversion efficiency. Nevertheless, each reaction has its own advantages and disadvantages as a tool for studying the transcriptome. Therefore, it is crucial to select the appropriate reaction for the target of interest., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: Double incontinence (DI), which is the co-occurrence of fecal incontinence (FI) and urinary incontinence (UI), increases with age and has a greater negative impact on the quality of life (QOL) than either incontinence alone. We aimed to assess lower urinary tract symptoms (LUTS) in patients with FI to elucidate the prevalence and characteristics of DI., Methods: This study enrolled consecutive patients who visited our hospital with FI symptoms. FI was evaluated using the Cleveland Clinic Florida Fecal Incontinence Score (CCFIS). LUTS were assessed using the International Prostate Symptom Score (IPSS), QOL score (IPSS-QOL) and Overactive Bladder Symptom Score (OABSS)., Results: This study evaluated 140 patients (96 women [mean age: 70.7 years] and 44 men [mean age: 74.4 years]). The mean IPSS was significantly higher in men than in women (12.0 vs. 7.5, p = 0.003). A positive correlation was found between IPSS and CCFIS in women (r = 0.256, p = 0.012) but not in men. For both sexes, the older group (aged ≥70 years) had higher OABSS scores and more urge UI instances than the younger group (aged ≤69 years). Of the 140 patients with FI, 78 (55.7%) had DI, and DI was more common in women than in men (63.5% vs. 38.6%, p = 0.006)., Conclusions: The characteristics of LUTS and UI in patients with FI were comparable to those in the general population for both sexes; however, the prevalence of DI was much higher among patients with FI than that in the general population., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20-1.03 wt% depth-selectively, without sample destruction., (© 2024. The Author(s).)

Background: People with schizophrenia have a lower colorectal screening rate than the general population. A previous study reported an intervention using case management to encourage colorectal cancer screening for patients with schizophrenia in psychiatric outpatient settings. In this feasibility study, we developed provider-level implementation strategies and evaluated the feasibility of conducting a definitive trial in terms of the penetration of the intervention assessed at the patient level. Additionally, we examined the fidelity of strategies to implement the intervention at the provider level in a routine clinical psychiatric setting., Methods: This was a multicenter, single-arm feasibility study with medical staff at psychiatric hospitals in Japan. The provider-level implementation strategies developed in this study included three key elements (organizing an implementation team appointed by the facility director, interactive assistance using a clear guide that outlines who in the hospital should do what, and developing accessible educational materials) to overcome major barriers to implementation of the intervention and four additional elements (progress monitoring, joint meetings and information sharing among participating sites, adaptation of encouragement methods to specific contexts, and education of on-site staff), with reference to the elements identified in the Expert Recommendations for Implementing Change (ERIC). The feasibility of the strategies was evaluated by the proportion of patients who were eligible for encouragement (patients with schizophrenia aged 40, 50, or 60) who received encouragement. We set the goal of providing encouragement to at least 40% of eligible patients at each site., Results: Two public and four private psychiatric hospitals in Okayama and Shimane prefectures participated in this study. Regarding fidelity, all elements of the strategies were conducted as planned. Following the procedures in the guide, each team prepared and provided encouragement according to their own facility and region. Penetration, defined as the proportion of eligible patients who received encouragement, ranged from 33.3 to 100%; five of the six facilities achieved the target proportion., Conclusions: The provider-level implementation strategies to implement encouragement were feasible in terms of penetration of the intervention assessed at the patient level. The results support the feasibility of proceeding with a future definitive trial of these strategies., Trial Registration: jRCT, jRCT1060220026 . Registered on 06/04/2022., (© 2023. The Author(s).)

Background: Near-misses in the workplace indicate potential safety hazards, and their adequate management is considered extremely important in preventing occupational accidents. However, the impact of a company's response to near-misses on the occurrence of subsequent accidents remains unclear. This study examined the relationship between the adequacy of a company's responses to near-misses and the occurrence of occupational accidents., Methods: We conducted a 1-year prospective cohort study using an online self-administered questionnaire, targeting workers in Japan. The study included 2755 participants who had experienced and reported near-misses. We categorized company responses to these near-misses as adequate, inadequate, or no response. The outcome was the incidence of occupational accidents over the past year. We calculated odds ratios (ORs) and 95% CIs using multilevel logistic regression adjusting for covariates., Results: Among all participants, 59.0% were in the adequate response group, 30.1% were in the inadequate response group, and 10.8% were in the no response group. In the multivariate-adjusted model, the ORs of the inadequate response and the no response groups were 1.53 (95% CI, 1.25-1.88; P < .001) and 1.75 (95% CI, 1.32-2.33; P < .001), respectively., Conclusions: Our results suggest that the adequacy of a company's response to near-misses reported by workers can be significantly related to the occurrence of subsequent occupational accidents. Companies need to thoroughly respond to near-misses reported by workers and adequately inform workers about the company's safety activities. This may lead to a reduction in the number of subsequent occupational accidents., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

Objectives: Given current labor force conditions, including population aging, keeping older workers engaged in work and motivated is important. Aging may alter the effects that psychological and environmental factors have on work engagement. We conducted a systematic review to understand the features of work engagement among older workers., Methods: A systematic search was conducted in July 2022 using 4 databases. The review included relevant articles that focused on participants aged 40 years and older., Results: Fifty articles were selected for our review, which were grouped into 5 categories: (1) studies examining the relationship between chronological age and work engagement, (2) studies investigating the moderating effects of age on the relationship between job-related psychological factors and work environment factors and work engagement, (3) studies comparing the relationship of job-related psychological factors and work environment factors with work engagement across different age groups, (4) studies exploring the relationship between work engagement and retirement intentions or continued employment beyond retirement age, and (5) other studies discussing work engagement in the context of older workers. Most articles focused on workers in Europe and the United States and used observational study designs., Conclusions: Work engagement increases with age, and is mainly mediated by increased emotional regulation. In addition, age moderates the relationships between various job-related psychological and work-environmental factors and work engagement. Work engagement is associated with working beyond retirement age. Organizations should understand the characteristics of work engagement among older workers and make age-conscious efforts to support them in adapting to social changes., (© The Author(s) [2023]. Published by Oxford University Press on behalf of Journal of Occupational Health.)