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Background: We aimed to quantify the incidence of atrial fibrillation (AF) in patients with cryptogenic stroke globally, as well as separately in patients in and outside of Japan, using an implantable loop recorder from a prospective, observational, Reveal LINQ Registry., Methods and Results: Patients developing cryptogenic stroke and monitored by implantable loop recorder for searching AF were studied. The primary end point was incidence of AF within 36 months after insertion. Secondary end points were recurrent ischemic stroke/transient ischemic attack and AF-related treatment strategies. A total of 271 patients (61.6±14.3 years, 170 men, 60 from Japan) were enrolled from 12 countries. AF was detected in 28.2% at 36 months. The median time from enrollment to AF detection was 7.9 months. During the first 12 months, the AF detection rate slope was relatively steeper in the Japanese subgroup versus non-Japanese patients. However, by 3 years, the cumulative incidence of AF detection did not differ between groups. Age was the only variable associated with AF detection (hazard ratio, 1.05 [95% CI, 1.02-1.07] per year), trending higher in older age groups. Of the 271 patients, 11 (4.1%) developed recurrent ischemic stroke/transient ischemic attack; AF was detected by implantable loop recorder in only 1 of these patients. Patients with detected AF were more commonly taking oral anticoagulation than those without AF at the last follow-up (64.7% versus 25.3%, P <0.001)., Conclusions: The rate of AF detection was similar to other studies in stroke populations monitored by implantable loop recorders, including CRYSTAL-AF (Cryptogenic Stroke and Underlying Atrial Fibrillation), STROKE-AF (Stroke of Unknown Cause and Underlying Atrial Fibrillation) and PER-DIEM (Post-Embolic Rhythm Detection With Implantable Versus External Monitoring). Patients with detected AF more commonly initiated anticoagulation than those without AF.

Objective Digital evacuation (DE) is an intervention used to address severe constipation. Literature exists on easily administered laxatives; however, reports on mildly invasive DE usage are limited. This study aimed to elucidate the fundamental data regarding constipation management using a comprehensive national database of DE incidence. Methods This observational epidemiological study analyzed the age- and sex-stratified DE incidence per 1,000 person-years during 2014-2021 using the medical receipt database in Japan. The annual trends were evaluated using Poisson regression models. We examined the month-stratified incidence during 2019-2021 to assess potential seasonal variations using a one-way analysis of variance and unpaired t-tests with the Bonferroni correction for comparisons across the four seasons. Correlation coefficients were calculated to determine the relationship between the meteorological variables and DE incidence. Results Over the 8-year period, the DE incidence amounted to 32,361,846 procedures, with a median of 10.3 procedures per 1,000 person-years. A demographic analysis revealed a minor peak, nadir, and progressive increase peaking in the 0-4-year (22.1 procedures), 5-9-year (1.5 procedures), and ≥90-year (370.7 procedures) age groups, respectively. The age-adjusted DE incidence across all age groups per 1,000 person-years showed a declining annual trend [incidence rate ratio: 0.971 (P<0.0001)]. A seasonal analysis revealed a significant increase in DE procedures during winter compared with summer (P<0.0125). A correlation was observed between the DE incidence and certain meteorological variables, particularly the temperature. Conclusion This study highlights the notable demographic patterns and the impact of seasonal and meteorological factors on the DE incidence.

Background & Aims: The diagnostic criteria for cachexia, as proposed by the Asian Working Group for Cachexia (AWGC), include weight loss, a low body mass index, and additional factors such as a low handgrip strength (HGS), anorexia, or elevated CRP levels. This study aimed to evaluate the significance of low HGS as a diagnostic criterion in patients with advanced cancer., Methods: This single-centre, retrospective cohort study was conducted between April 2019 and March 2023. Patients aged ≥18 years with malignant diseases were included. Patients without records on HGS were excluded. Low HGS was defined as a HGS <28 kg for men and <18 kg for women. The overall median survival time (MST) was analysed by univariate and multivariate analyses., Results: A total of 894 patients were analysed. Cachexia was prevalent in 74 %, though only 3.4 % were diagnosed based solely on low HGS. The MST in patients with cachexia was 122 days, and in those with low HGS was 73 days. The associations between low HGS and high mortality remained significant after adjusting for AWGC criteria, modified weight loss grading system, age, gender, performance status, calf circumferenceand fluid retention. The MST varied with the number of additional factors being met: 422 days for one criterion, 92 days for two, and 55 days for all three (p < 0.0001)., Conclusion: This study supports that HGS serve as important prognostic tool in patients with various cancers., Competing Interests: Declaration of competing interest No conflicts of interest to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Phytocannabinoids inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer's disease protein β amyloid (Aβ). We characterised the capacity of five proprietary medical cannabis extracts, heated and non-heated, with varying ratios of cannabidiol and Δ 9 -tetrahydrocannabinol and their parent carboxylated compounds to protect against lipid peroxidation and Aβ-evoked neurotoxicity in PC12 cells., Methods: Neuroprotection against lipid peroxidation and Aβ 1-42 -induced cytotoxicity was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ 1-42 aggregation and fluorescence microscopy., Results: Tetrahydrocannabinol (THC)/tetrahydrocannabinolic acid (THCA)-predominant cannabis extracts demonstrated the most significant overall neuroprotection against Aβ 1-42 -induced loss of PC12 cell viability. These protective effects were still significant after heating of extracts, while none of the extracts provided significant neuroprotection to lipid peroxidation via tbhp exposure. Modest inhibition of Aβ 1-42 aggregation was demonstrated only with the non-heated BC-401 cannabis extract, but overall, there was no clear correlation between effects on fibrils and conferral of neuroprotection., Conclusions: These findings highlight the variable neuroprotective activity of cannabis extracts containing major phytocannabinoids THC/THCA and cannabidiol (CBD)/cannabidiolic acid (CBDA) on Aβ-evoked neurotoxicity and inhibition of amyloid β aggregation. This may inform the future use of medicinal cannabis formulations in the treatment of Alzheimer's disease and dementia., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Polymer-based tubular micromotors, featuring an inner layer of Pt nanoparticles (PtNPs), exhibit vigorous propulsion by emitting H 2 bubbles in an aqueous ammonia borane (NH 3 BH 3 ) solution. The hydrolysis of NH 3 BH 3 on the PtNPs facilitates the continuous release of H 2 gas from the open-end terminus, driving its forward movement. Unlike conventional O 2 bubbles' systems that rely on hydrogen peroxide (H 2 O 2 ) as fuel, these micromotors can operate in the presence of live cells within the NH 3 BH 3 medium. Consequently, micromotors functionalized with the lectin concanavalin A demonstrate the capability to capture and release Escherichia coli ( E. coli ) without inducing cell death. Remaining bacteria can be detected by using standard culture techniques. Conversely, micromotors coated with TiO 2 nanoparticles enable photosterilization of E. coli without fuel-induced damage. The self-stirring motion of the tubes enhances both bacterial capture and sterilization efficiency. These advancements obviate the necessity for H 2 O 2 as a fuel source, and pave the way for the applications of micromotors in biological contexts.

Copy number variants (CNVs) are robustly associated with psychiatric disorders and changes in brain structures. However, because CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknown how each gene encoded in the 22q11.2 region contributes to structural alterations, associated mental illnesses, and their dimensions. Our previous studies identified Tbx1, a T-box family transcription factor encoded in the 22q11.2 CNV, as a driver gene for social interaction and communication, spatial and working memory, and cognitive flexibility. However, it remains unclear how TBX1 impacts the volumes of various brain regions and their functionally linked behavioral dimensions. In this study, we used volumetric magnetic resonance imaging analysis to comprehensively evaluate brain region volumes and behavioral alterations relevant to affected structures in congenic Tbx1 heterozygous mice. Our data showed that the volumes of the anterior and posterior portions of the amygdaloid complex and its surrounding cortical regions were most robustly reduced in Tbx1 heterozygous mice. In an amygdala-dependent task, Tbx1 heterozygous mice were impaired in their ability to learn the incentive value of a social partner. The volumes of the primary and secondary auditory cortexes were increased, and acoustic, but not non-acoustic, sensorimotor gating was impaired in Tbx1 heterozygous mice. Our findings identify the brain's regional volume alterations and their relevant behavioral dimensions associated with Tbx1 heterozygosity., (© 2024. The Author(s).)

A 14-year-old spayed female mixed-breed cat weighing 3.4 kg was admitted to the Tokyo University of Agriculture and Technology Animal Medical Center for syncope after vomiting. Echocardiography, electrocardiography, and thoracic radiography revealed no abnormalities. Holter electrocardiography showed a paroxysmal high-grade atrioventricular block coinciding with the vomiting. Based on these findings, the cat was diagnosed as having situational syncope with paroxysmal high-grade atrioventricular block triggered by vomiting, which improved with antiemetic treatment alone. The cat subsequently died of chronic kidney disease approximately 3 years and 4 months after the initial diagnosis. This is the first reported case of situational syncope triggered by vomiting in a cat.

Background: In patients with coronavirus disease pneumonia, strong spontaneous breathing increases pulmonary vascular permeability and induces self-inflicted lung injury, prolonging the intensive care unit stay and worsening prognosis. Therefore, spontaneous respiration must be strictly controlled., Case Presentation: A 48-year-old man was admitted for respiratory management of severe coronavirus disease pneumonia. Despite immediate ventilatory management, ventilatory failure and air leak syndrome developed, necessitating venovenous extracorporeal membrane oxygenation, intravenous sedation, and muscle relaxation. Over time, the patient's inspiratory effort worsened and the requirement for transvenous anesthesia increased. Therefore, management was switched to inhalation anesthesia after discontinuation of all transvenous anesthetics, maintaining morphine-only analgesia. Subsequent management enabled effective control of spontaneous respiration, allowing eventual discontinuation of inhalation anesthesia, venovenous extracorporeal membrane oxygenation, and ventilation., Conclusion: Management of spontaneous respiration in coronavirus disease pneumonia can be complicated by resistance to transvenous anesthesia; however, the use of an inhaled anesthetic may present a valuable alternative., Competing Interests: The authors declare no conflict of interest associated with this manuscript., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Although the mechanism underlying flutamide- or bicalutamide-induced liver injury may be immune related, the details remain unclear. If this mechanism is immune related, steroid use may be considered as a treatment option., Aim: Disproportionality analysis was conducted to evaluate the effect of concomitant steroid use on flutamide- and bicalutamide-induced liver injury., Method: Male patients aged 20 years or older who were receiving nonsteroidal anti-androgens from April 2004 to October 2023 were screened from the Japanese Adverse Drug Event Report database. Data on liver injury, age, weight, height, steroid use, obesity, hepatic stenosis, alcohol-related hepatic disorders, hepatitis B and C, and common drugs known to cause drug-induced liver injury were analyzed. Liver injury was defined by the Standardized Medical Dictionary for Regulatory Activities query index (code 20000006, version 27.0)., Results: Among 142,430 patients, 2,316 were administered nonsteroidal anti-androgens. Reports of liver injury were disproportionate depending on the agents used (reporting odds ratio [ROR], 1.29; 95% confidence intervals [CI], 1.13-1.46), especially among flutamide or bicalutamide users (flutamide: ROR, 6.09; 95% CI, 4.51-8.23; bicalutamide: ROR, 1.24; 95% CI, 1.05-1.48). Multivariable logistic regression analysis correlated steroid use with a lower risk of flutamide- or bicalutamide-induced liver injury (flutamide: odds ratio, 0.07; 95% CI, 0.01-0.52; bicalutamide: odds ratio, 0.45; 95% CI, 0.21-0.96)., Conclusion: Our findings suggest that flutamide and bicalutamide may increase the risk of liver injury compared to enzalutamide, apalutamide, and darolutamide. Furthermore, our study indicated that steroid use could aid in the management of liver injury., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Transoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery., Methods: This study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated., Results: A total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate., Conclusion: This study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

This multicenter study evaluated the efficacy and safety of a novel cranial remolding helmet (baby band2), which is completely custom-made based on the shape of an infant's cranium. The study included 224 full-term infants from moderate to very severe positional plagiocephaly in Japan. Cranial geometry was assessed before and after helmet therapy using a three-dimensional scanner, and changes in the cranial vault asymmetry index (CVAI) were analyzed. The CVAI improved significantly in all patients, with the most significant improvement observed in the most severely affected group [very severe group: -9.1, severe group: -6.6, moderate group: -4.4 (mean values), p < 0.001]. The group that started therapy before the age of 7 months showed greater improvement compared to those who started therapy at the age of 7 months or older; however, both groups demonstrated significant improvement (<7 months group: -6.6, ≥7 months group: -4.4 (mean values), p < 0.001). No significant differences were observed in therapy efficacy between the centers ( p = 0.402) and sex ( p = 0.131). During the study period, helmet therapy did not lead to head circumference stunting, and the incidence of redness with baby band2 was five patients (2.2%). This study demonstrated that baby band2 is effective and safe for the therapy of positional plagiocephaly.

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently leads to right ventricular (RV) remodeling. Aldosterone promotes vascular and RV remodeling. The upregulation of steroidogenic acute regulatory protein (StAR) stimulates aldosterone synthesis. However, the expression of StAR in the myocardium under PAH conditions remains unknown. To investigate the expression of StAR in the myocardium and its association with RV remodeling in PAH, utilizing spironolactone as a treatment. A PAH model was created using male Sprague-Dawley rats, which received a subcutaneous injection of Sugen5416 (20 mg/kg) and were exposed to hypoxia (10% O 2 ) for 2 weeks, followed by 2 weeks of normoxia. The animals were then divided into two groups, with one group receiving spironolactone (25 mg/kg/day) for an additional 4 weeks, while the other group did not. H9c2 cells were cultured under hypoxic conditions (37 °C, 1% O 2 , 5% CO 2 ) with or without spironolactone treatment. In the model rats, RV systolic pressure and the Fulton index, both of which increased upon exposure to Sugen5416 and hypoxia, significantly decreased with spironolactone treatment. In H9c2 cells, hypoxic exposure elevated aldosterone levels, while spironolactone treatment significantly suppressed aldosterone production. Suppression of StAR expression in the myocardium via spironolactone contributes to the improvement of RV remodeling in PAH. Spironolactone may offer a valuable therapeutic strategy for RV remodeling in patients with PAH., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method., Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs., Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported., Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The neutron beam in boron neutron capture therapy (BNCT) exhibits poor directionality and significantly decreasing neutron flux with increasing distance. Therefore, the treatment site must be close to the irradiation aperture. Some patients with head and neck cancer may benefit from a sitting-position setup. The study aim was to evaluate the treatment-positioning accuracy and dose error in sitting patients receiving BNCT. Thirty-two patients with head and neck cancer who underwent sitting-position BNCT at Southern Tohoku BNCT Research Center were included in the study. Horizontal (ΔX) and vertical (ΔY) errors were defined as the displacement between the treatment planning system (TPS) digital reconstructed radiograph and the pre-treatment X-ray image. Using in-house software, image matching was performed. The beam-axial directional (ΔZ) error was compared with the parameters entered into the TPS and the actual pre-treatment measured values. The translational-position error was reflected in the TPS's patient coordinate system with respect to the reference plan. Re-dose calculations were performed to evaluate the effect of positional error on tumor and normal-tissue doses. The [ΔX, ΔY, ΔZ] DRR-CR mean ± 1SD were - 0.40 ± 2.0, 0.30 ± 2.3, and - 1.4 ± 1.5 mm, respectively. The D mean and D 98% tumor-dose errors were 1.22 % ± 1.44 % and 0.99 % ± 1.63 %, respectively. The D 2% pharyngeal and oral mucosal-dose errors were 0.98 % ± 1.91 % and 1.21 % ± 1.78 %, respectively. The tumor- and normal-tissue dose errors were typically < 5 %. High-precision treatment was feasible in sitting-positioned BNCT., 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 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Accelerator-based boron neutron capture therapy (AB-BNCT) systems are becoming commercially available and are expected to be widely used in hospitals. To ensure the safety of BNCT, establishing a quality assurance (QA) program and properly managing the stability of the system are necessary. In particular, a high level of beam output stability is required to avoid accidents because beam output is a major factor in patient dose. However, no studies have analyzed the long-term beam output stability of AB-BNCT systems., Purpose: This study aimed to retrospectively analyze the long-term stability of the beam output by statistical process control (SPC) based on the QA results over 3 years., Methods: The data analyzed are the results of daily QA (DQA) and weekly QA (WQA) in an AB-BNCT system and were taken between June 2020 and September 2023. The evaluation of the stability of the beam output was based on the reaction rate between gold and neutrons calculated using the activation foil method using a gold foil. In DQA, which can be performed in a short time, the gold foil was applied directly to the beam irradiation aperture in air. In WQA, measurements were performed at the phantom surface, 2-cm depth, and 6-cm depth using a dedicated water phantom. The acquired data were retrospectively analyzed by individuals and a moving range chart (I-MR chart), exponentially weighted moving average control chart (EWMA chart), and several process capability indexes (PCIs)., Results: Over 99% of the DQA I-MR chart results were within control limits, whereas the WQA I-MR chart results showed that 1.8%, 4.1%, and 2.0% of the measurements exceeded the control limits at the surface, 2-cm depth, and 6-cm depth, respectively. The variation in the reaction rate of the gold foil before and after the replacement of the target was <0.5%. The EWMA chart results revealed no significant beam output drift for either DQA or WQA. Most measured data were normal based on the results of the Anderson-Darling test and met the requirements for PCI evaluation; most PCI values were >1.0; however, the C pmk of DQA and the 2- and 6-cm depth WQAs between August 2021 and November 2022 in treatment course 2 were 0.83, 0.77, and 0.87, respectively, which were <1.0., Conclusions: The long-term stability of beam output was confirmed using SPC in an AB-BNCT system. The results of the control chart revealed no significant variation or drift in the beam output, and the quantitative evaluation using PCI revealed high stability. A routine QA program will enable us to provide safe BNCT., (© 2024 American Association of Physicists in Medicine.)

The ion exchange function of zeolite is useful for such a purpose as the removal of radioactive Cs species from water. In the very early days of zeolite science, the affinity of zeolites for metal cations was explained based on geometry. After the explanation presented above was proposed, many new zeolites and related materials were discovered or synthesized. Furthermore, it has become clear that the chemical nature of the ion exchange sites is strongly dependent on the framework topology. In this study, the ion exchange behavior between Na-form zeolites with different framework topologies and Cs-containing aqueous solutions was analyzed, and the equilibrium constant was calculated based on the Langmuir type equation to investigate the influence of the chemical nature of the zeolite framework on ion selectivity. The equilibrium constants at room temperature were in the order FAU < LTA < MFI < YFI < MOR . This order is the same as the order of Bro̷nsted acid strengths in the corresponding proton form zeolites. It is suggested that the delocalization of charge around the ion exchange site stabilizes a large cation whose charge is delocalized. In contrast, the equilibrium constant was not related to the pore and cavity size. This opens new insight into the influence of the chemical nature of zeolite on the affinity to cation.

Background Hypouricemia, defined as a serum uric acid (SUA) level ≤2 mg/dL, could be a risk factor for death in hospitalized patients. However, how explanatory variables can explain hypouricemia as an objective variable in a logistic regression analysis remains unknown. Purpose To predict the risk factors for hypouricemia in hospitalized patients using a robust Bayesian logistic (RBL) model. Methods This study retrospectively enrolled patients who visited Yonago Medical Center between April 2020 and March 2021. The association between potential risk factors and hypouricemia was analyzed using the RBL model in Python-modulated PyMC3. The final model was selected based on the lowest Watanabe-Akaike information criterion (WAIC). Results Of the 618 patients, 64 (10.4%) had hypouricemia. Based on the model according to the lowest WAIC, independent risk factors for hypouricemia were febuxostat [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.32-13.4], amino acids in parenteral nutrition (OR 5.19, 95% CI 1.62-15.1), TMP-SMX (OR 4.20, 95% CI 1.66-10.9), emaciation (OR 3.48, 95% CI 1.75-7.21), and serum sodium level (OR 0.90, 95% CI 0.84-0.96). Conclusion The RBL model predicted amino acids in parenteral nutrition, TMP-SMX, emaciation, and low serum sodium levels for hypouricemia, in addition to the authentic risk factor febuxostat.

Background/aim: We herein examined T cell immunity in esophageal cancer patients with and without Helicobacter pylori infection to establish a foundation for immunotherapeutic strategies targeting esophageal cancer in the presence of H. pylori infection., Materials and Methods: Twenty-six patients with esophageal squamous cell carcinoma between 2015 and 2017 were enrolled in the present study. Serum antibodies against H. pylori were measured. Fresh tumor tissues were obtained by endoscopic biopsy or from surgical resection. A cell suspension of these tissues was subjected to a flow cytometric analysis., Results: Among the 26 patients analyzed, 10 (38.5%) were seropositive for H. pylori. The flow cytometric analysis of tumor-infiltrating lymphocytes revealed that the percentage of CD103 + CD4 + T cells in esophageal tumors was significantly lower in H. pylori-positive patients than in H. pylori-negative patients (p=0.0105). Conversely, the percentage of CD45RA-CD25hi effector Treg cells in esophageal tumors was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (p=0.0022), indicating an immunosuppressive tumor microenvironment in the former. Following neoadjuvant chemotherapy, the number of CD45RA-CD25hi effector Treg cells decreased (p=0.0248)., Conclusion: The tumor immune microenvironment of esophageal cancer patients with H. pylori infection exhibited an immunosuppressive phenotype. The targeting of Treg cells has potential in immunotherapy for this patient population., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Acute care surgeons are experts in trauma treatment, emergency surgery, and critical surgical care. Here, we analyzed the association of acute care surgeons on postoperative outcomes of emergency general surgery., Methods: This retrospective study included 92 patients who underwent emergency general surgery at our institution between January 2020 and September 2021. Propensity score matching was used to analyze postoperative outcomes. The primary outcome was postoperative complications, while secondary outcomes included perioperative management and surgery-related and postoperative complications. Logistic regression analysis was used to estimate the odds ratios for all complications. In this study, acute care surgeons were defined as acute care surgery (ACS)-certified surgeons by the Japanese Society for Acute Care Surgery., Results: Overall, 30 patients were treated by an acute care surgeon and general surgeons (ACS group), and 62 patients were treated by general surgeons (non-ACS group), respectively. Propensity score matching identified 30 patients with balanced baseline covariates, in each group. The ACS group had lower complication rates (Clavien-Dindo classification ≥2) than the non-ACS group (17% versus 40%, P = 0.08). The ACS group had a significantly shorter surgery duration than the non-ACS group (75 min versus 96 min, P = 0.014). In the logistic analysis, acute care surgeon involvement was identified as an independent predictor for the decrease in all complications (odds ratio, 0.15; 95% confidence interval, 0.02-0.64)., Conclusions: It was suggested that the involvement of acute care surgeons may reduce the overall complication rate in emergency general surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Synthetic genes for the two subunits of phenylalanyl-tRNA synthetase (PheRS) from wheat were expressed in Escherichia coli . When each gene was induced individually, the α subunit with a cleavable 6 × His tag at the amino terminus was largely soluble, while the β subunit was almost completely insoluble. When the two subunits were co-expressed, a soluble fraction containing the two subunits were obtained. This was purified by a standard method in which the tag was cleaved off with a specific protease after affinity purification. As the sample contained slightly more PheRSα than PheRSβ, we further resolved the sample by gel filtration to obtain the fraction that showed the size of the conventional α 2 β 2 tetrameric complex and contains an almost equal amount of the two subunits. The final yield was 0.6 mg per 1 liter of the culture medium, and the specific activity was 28 nmol min -1  mg -1 , which was higher than that of a fraction purified from wheat germ. This recombinant PheRS was used, along with purified samples of the elongation factors and the ribosomes from wheat germ, for a poly(U)-dependent poly(Phe) synthesis reaction. The reaction was dependent on the added components and lasted for more than several hours.

Photonic crystals, characterized by their periodic structures, have been extensively studied for their ability to manipulate light. Typically, the development of 2D photonic crystals requires either sophisticated equipment or precise orientation of spherical nanoparticles. However, liquid-crystalline (LC) materials offer a promising alternative, facilitating the formation of periodic structures without the need for complex manipulation. Despite this advantage, the development of 2D photonic periodic structures using LC materials is limited to a few colloidal nanodisk liquid crystals. Herein, 2D photonic colloidal liquid crystals composed of biomineral-based nanorods and water is reported. The soft photonic materials with 2D structure by self-assembled LC colloidal nanorods are unique and a new class of photonic materials different from conventional solid 2D photonic materials. These colloids exhibit bright structural colors with high reflectance (>50%) and significant angular dependency. The structural colors are adjusted by controlling the concentration and size of the LC colloidal nanorods. Furthermore, mechanochromic hydrogel thin films with 2D photonic structure are developed. The hydrogels exhibit reversible mechanochromic properties with angular dependency, which can be used for an advanced stimuli responsible sensor., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

The cytosolic peptide:N-glycanase (PNGase) is involved in the quality control of N-glycoproteins via the endoplasmic reticulum-associated degradation (ERAD) pathway. Mutations in the gene encoding cytosolic PNGase (NGLY1 in humans) cause NGLY1 deficiency. Recent findings indicate that the F-box protein FBS2 of the SCF FBS2 ubiquitin ligase complex can be a promising drug target for NGLY1 deficiency. Here, we determined the crystal structure of bovine FBS2 complexed with the adaptor protein SKP1 and a sugar ligand, Man 3 GlcNAc 2 , which corresponds to the core pentasaccharide of N-glycan. Our crystallographic data together with NMR data revealed the structural basis of disparate sugar-binding specificities in homologous FBS proteins and identified a potential druggable pocket for in silico docking studies. Our results provide a potential basis for the development of selective inhibitors against FBS2 in NGLY1 deficiency., (© 2024 Federation of European Biochemical Societies.)

Cells regularly repair numerous mutations. However, the effect of CRISPR/Cas9-induced dsDNA breaks on the repair processes of naturally occurring genome-wide mutations is unclear. In this study, we used TSCE5 cells with the heterozygous thymidine kinase genotype (TK +/- ) to examine these effects. We strategically inserted the target sites for guide RNA (gRNA)/Cas9 and I-SceI into the functional allele and designed the experiment such that deletions of > 81 bp or base substitutions within exon five disrupted the TK gene, resulting in a TK -/- genotype. TSCE5 cells in the resting state exhibited 16 genome-wide mutations that affected cellular functions. After gRNA/Cas9 editing, these cells produced 859 mutations, including 67 high-impact variants that severely affected cellular functions under standard culture conditions. Mutation profile analysis indicated a significant accumulation of C to A substitutions, underscoring the widespread induction of characteristic mutations by gRNA/Cas9. In contrast, gRNA/Cas9-edited cells under conditions of S∼G2/M arrest and cyclin-dependent kinase 1 inhibition showed only five mutations. Transcriptomic analysis revealed the downregulation of DNA replication genes and upregulation of alternative DNA repair genes, such as zinc finger protein 384 (ZNF384) and dual specificity phosphatase, under S∼G2/M conditions. Additionally, activation of nucleotide and base excision repair gene, including O-6-methylguanine-DNA methyltransferase and xeroderma pigmentosum complementation group C, was observed. This study highlights the profound impact of CRISPR/Cas9 editing on genome-wide mutation processes and underscores the emergence of novel DNA repair pathways. Finally, our findings provide significant insights into the maintenance of genome integrity during genome editing., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

As tumor-associated macrophages (TAMs) exercise a plethora of pro-tumor and immune evasive functions, novel strategies targeting TAMs to inhibit tumor progression have emerged within the current arena of cancer immunotherapy. Activation of the mannose receptor 1 (Mrc1; CD206) is a recent approach that recognizes immune suppressive CD206high M2-like TAMs as a drug target. Ligation of CD206 both induces reprogramming of CD206high TAMs towards a pro-inflammatory phenotype and selectively triggers apoptosis in these cells. CD206-activating therapeutics are currently limited to the linear, 10mer peptide RP-182, 1, which is not a drug candidate. Here we sought to identify a better suitable candidate for future clinical development by synthesizing and evaluating a series of RP-182 analogues. Surprisingly, fatty acid derivative 1a (RP-182-PEG3-K(palmitic acid)) not only showed improved stability but also increased affinity to the CD206 receptor through enhanced interaction with a hydrophobic binding motif of CD206. Peptide 1a showed superior in vitro activity in cell-based assays of macrophage activation which was restricted to CD206high M2-polarized macrophages. Improvement of responses was disproportionally skewed towards improved induction of phagocytosis including cancer cell phagocytosis. 1a reprogrammed the immune landscape in genetically engineered murine KPC pancreatic tumors towards increased innate immune surveillance and improved tumor control, and effectively suppressed tumor growth of murine B16 melanoma allografts.

Transmitral myectomy for hypertrophic obstructive cardiomyopathy is compatible with minimally invasive surgery compared with traditional transaortic access. It has often been performed in conjunction with mitral valve replacement or temporary detachment of the anterior leaflet from its annulus. We present a novel approach: longitudinal incision at the midline of the anterior mitral leaflet for septal myectomy. The procedure is ideally conducted endoscopically or robotically through the right chest. Cardiopulmonary bypass is established in the usual manner. After cardioplegic arrest, the mitral valve is exposed, and the anterior mitral leaflet is incised longitudinally at the midline. Both parts of the leaflet are tentatively fixed to the atrial wall with sutures to keep them open. Using the look-up mode of a 30° scope, the right cusp of the aortic valve is observed. Myectomy is initiated close to the aortic annulus using the pure-cut mode of electrocautery and scissors, then extended apically as necessary. After myectomy, the anterior leaflet is reapproximated with interrupted sutures. This technique is simpler than the detachment of the anterior leaflet and does not require patch materials that could lead to durability issues for the reconstruction of the anterior leaflet., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

This study aims to evaluate the feasibility of using a commercially available boron neutron capture therapy (BNCT) dose calculation program (NeuCure ® Dose Engine) in terms of calculation accuracy and computation time. Treatment planning was simulated under the following calculation parameters: 1.5-5.0 mm grid sizes and 1-10% statistical uncertainties. The calculated monitor units (MUs) and computation times were evaluated. The MUs calculated on grid sizes larger than 2 mm were overestimated by 2% compared with the result of 1.5 mm grid. We established the two-step method for the routine administration of BNCT: multiple calculations involved in beam optimization should be done at a 5 mm grid and a 10% statistical uncertainty (the shortest computation time: 10.3 ± 2.1 min) in the first-step, and final dose calculations should be performed at a 2 mm grid and a 10% statistical uncertainty (satisfied clinical accuracy: 6.9 ± 0.3 h) in the second-step., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Structural colouration observed in antimony phosphate nanosheet suspensions has been known for two decades, but the stability of their inner structures has not been a topic in colloidal nanosheet systems. In this study, we investigate the time evolution of structures in suspension using UV-visible spectrometry and small-angle X-ray scattering. Here, we report that antimony phosphate nanosheet systems re-organise their inner structures, especially at lower concentrations (isotropic or biphasic region), and that the basal spacing decreases with time after sample preparation, although the evolution speed depends on the sample concentration. The stability of the inner structure of the suspension is essential for their application as structural colour materials in sensors and colourants.

Background: CARTONET® enables automatic ablation site classification and reconnection site prediction using machine learning. However, the accuracy of the site classification model and trends of the site prediction model for potential reconnection sites are uncertain., Methods: We studied a total of 396 cases. About 313 patients underwent pulmonary vein isolation (PVI), including a cavotricuspid isthmus (CTI) ablation (PVI group) and 83 underwent PVI and additional ablation (i.e., box isolation) (PVI+ group). We investigated the sensitivity and positive predictive value (PPV) for automatic site classification in the total cohort and compared these metrics for PV lesions versus non-PV lesions. The distribution of potential reconnection sites and confidence level for each site was also investigated., Results: A total of 29,422 points were analyzed (PV lesions [ n  = 22 418], non-PV lesions [ n  = 7004]). The sensitivity and PPV of the total cohort were 71.4% and 84.6%, respectively. The sensitivity and PPV of PV lesions were significantly higher than those of non-PV lesions (PV lesions vs. non-PV lesions, %; sensitivity, 75.3 vs. 67.5, p  < .05; PPV, 91.2 vs. 67.9, p  < .05). CTI and superior vena cava could not be recognized or analyzed. In the potential reconnection prediction model, the incidence of potential reconnections was highest in the posterior, while the confidence was the highest in the roof., Conclusion: The automatic site classification of the CARTONET®R12.1 model demonstrates relatively high accuracy in pulmonary veins excluding the carina. The prediction of potential reconnection sites feature tends to anticipate areas with poor catheter stability as reconnection sites., Competing Interests: HM received lecture fees from Biosense Webster Japan and Boston Scientific Japan. Our department received grant support from Boston Scientific Japan and Abbott Medical Japan., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Although previous studies have reported that pre-mRNA splicing factors (SFs) are involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), their exact role in promoting HR remains poorly understood. Here, we showed that SART1, an SF upregulated in several types of cancer, promotes DSB end resection, an essential first step of HR. The resection-promoting function of SART1 requires phosphorylation at threonine 430 and 695 by ATM/ATR. SART1 is recruited to DSB sites in a manner dependent on transcription and its RS domain. SART1 is epistatic with BRCA1, a major HR factor, in the promotion of resection, especially transcription-associated resection in the G2 phase. SART1 and BRCA1 accumulate at DSB sites in an interdependent manner, and epistatically counteract the resection blockade posed by 53BP1 and RIF1. Furthermore, chromosome analysis demonstrated that SART1 and BRCA1 epistatically suppressed genomic alterations caused by DSB misrepair in the G2 phase. Collectively, these results indicate that SART1 and BRCA1 cooperatively facilitate resection of DSBs arising in transcriptionally active genomic regions in the G2 phase, thereby promoting faithful repair by HR, and suppressing genome instability., (© 2024. The Author(s).)

Background: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated., Methods and Results: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46)., Conclusions: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Introduction: Transvenous lead extractions (TLEs) for cardiac implantable electronic device complications often encounter difficulties with strong adhesions to the myocardium or vessels. In this report, we introduce a novel "Four-Stage Rocket" technique for effective TLE in cases where conventional methods fail., Methods and Results: Two challenging cases where conventional TLE methods failed were treated using a combination of four devices: Needle's Eye Snare, Agilis NxT Steerable Introducer, GlideLight Laser sheath, and GORE® DrySeal Flex Introducer sheath, employed via the inferior vena cava. The "Four-Stage Rocket" technique successfully detached firmly adhered leads near the tricuspid valve annulus, where the traditional superior vena cava approach was inadequate., Conclusion: The "Four-Stage Rocket" technique offers a potential alternative in complex TLE cases, aligning the laser direction with the adhesion detachment and reducing the tissue damage risk., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Thoracoscopic esophagectomy (TE) with carbon dioxide (CO 2 )   insufflation is increasingly performed for esophageal cancer; however, there is limited evidence of the long-term outcomes of CO 2 insufflation on postoperative survival., Objectives: We investigated the long-term outcomes of TE with or without CO 2 insufflation., Methods: We enrolled 182 patients who underwent TE for esophageal cancer between January 2003 and October 2013 and categorized them into two groups: with and without CO 2 insufflation. The primary endpoint was five-year overall survival (5y-OS). Secondary endpoints included long-term outcomes, such as five-year relapse-free survival (5y-RFS) and five-year cancer-specific survival (5y-CSS), and short-term outcomes, such as surgical and non-surgical complications and reoperation within 30 days., Results: Follow-up until death or the five-year postoperative period was 98.9% (median follow-up duration was six years in survivors). After adjusting for age, sex, and yield pathologic tumor, node, and metastasis (TNM) stage, we found no significant differences in 5y-OS (HR 1.12, 95% CI 0.66-1.91), 5y-RFS (HR 1.12, 95% CI 0.67-1.83), or 5y-CSS rates (HR 1.00, 95% CI 0.57-1.75). For short-term outcomes, significant intergroup differences in operation time (p=0.02), blood loss (p<0.001), postoperative length of stay (p<0.001), and incidence of atelectasis (p=0.004) were observed. The results of the sensitivity analysis were similar to the main results., Conclusions: In thoracoscopic procedures, CO 2 insufflation significantly improved short-term outcomes, and it appears that the recurrence risk of esophageal cancer may not impact the long-term prognosis. While the influence of CO 2 insufflation in thoracoscopic esophageal surgery remains unclear, our study suggests that the long-term prognosis is not compromised in other thoracic surgeries., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Showa University School of Medicine issued approval 2256. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Otsuka et al.)

The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was double-structured small sphere composed of an inner drug core and an outer dried-gel layer, however, had problem of insufficient physical strength. In this study, it was attempted to use dextrin (DEX), one of oligosaccharides, to strengthen the xerogel pill. DEX was co-dissolved in the dropping fluid in the DFD process and co-loaded in the conventional pill, which was mainly composed of mannitol (MNT) as a filler, to prepare the rigid body. DEX-loaded pill could be successfully prepared with high recovery (>90 %) by optimizing the ratio of DEX and MNT. Further, the representative pills with and without DEX (P-DEX and P-MNT, respectively) were hardening-processed under humidification. The physical strength of P-DEX pill was significantly increased when humidified under severe condition, resulting in enough hardness (>5N) and friability (<1.0 %). Processed P-DEX was found to have dense structure covered with a thick outer shell, which would be formed by interparticle bridge of DEX. It was also found that processed P-DEX pill suppressed initial drug dissolution significantly and exhibited sustained dissolution behavior, suggesting the potential function of bitter taste masking. Processed P-DEX pill had excellent sliding behavior with low friction forces as a result of lubricant effect of xanthan gum (XG) surrounding the pills. Furthermore, the sliding test also suggested that processed P-DEX pill had hard candy-like texture, in contrast unprocessed P-DEX pill had orally disintegrating (OD) tablet-like texture. Various xerogel pills with such different swallowing texture would have a potential to accommodate the children's preferences when taking medication., 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: Insertion of electrode catheters into the coronary sinus (CS) through the right internal jugular vein (RIJV) carries risks of pneumothorax and severe hematoma formation. This study was performed to compare the safety and feasibility of catheterization through the left cubital superficial vein versus the RIJV., Methods: This prospective nonrandomized study involved consecutive patients who underwent catheter ablation from September 2021 to February 2023. Blind puncture techniques were used in the left cubital vein group; ultrasound-guided insertion was performed in the RIJV group. The success rates of sheath insertion and CS catheterization, the procedure and fluoroscopy times of CS cannulation, and complications were compared between groups., Results: The left cubital vein group comprised 152 patients, and the RIJV group comprised 58 patients. The sheath insertion success rate was significantly lower in the cubital vein group than in the RIJV group (84.9% vs 100%, respectively; p  = .0008). In the cubital vein group, blind puncture attempts failed in 20 patients; three patients developed guidewire-induced venous injury. One arterial puncture occurred in the RIJV group. After successful sheath insertion, no significant differences were observed in the CS cannulation success rate (97% vs 100%, p  = .55), procedure time (median [range], 93 [51-174] vs 74 [44-129] s; p  = .19), or fluoroscopy time (median [range], 66 [36-134] vs 48 [30-92] s; p  = .17). No serious complications requiring procedural discontinuation occurred., Conclusion: The left cubital vein approach is practical, offering a viable alternative to the RIJV approach., Competing Interests: Authors declare no conflict of interests for this article., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

A new method to synthesise functionalised cycloheptatrienes was established using the anionic 8π-electrocyclic reaction of β-ketoester-derived dienyne substrates. The cyclised products were converted to a variety of cycloheptatriene derivatives including tropones. Using this method, a concise, first total synthesis of (-)-orobanone, a natural sesquiterpenoid, was achieved.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: The efficacy of neuraxial analgesia varies with spinal canal pathology. Notably, a secondary epidural catheter has been shown to increase neuraxial labor analgesia in women with spinal lesions. Therefore, we present a case in which catheter withdrawal played a critical role in achieving effective labor analgesia in a woman with epidural adhesions after lumbar discectomy who had inadequate analgesia with two epidural catheters., Case Presentation: We encountered a patient with L5 lumbar epidural adhesions who reported pain even after receiving two epidural catheters. The catheters were placed in the L1/2 and L5/S intervertebral spaces. Analgesic effects were exerted when the L5/S catheter was withdrawn by 1 cm, suggesting that the catheter tip was initially placed inside the adhesion., Conclusions: Careful consideration of catheter placement and adjustments by withdrawing the catheter are crucial in managing labor analgesia in patients with known epidural adhesions., (© 2024. The Author(s).)

Background: The expansion of artificial intelligence (AI) within large language models (LLMs) has the potential to streamline healthcare delivery. Despite the increased use of LLMs, disparities in their performance particularly in different languages, remain underexplored. This study examines the quality of ChatGPT responses in English and Japanese, specifically to questions related to anaesthesiology., Methods: Anaesthesiologists proficient in both languages were recruited as experts in this study. Ten frequently asked questions in anaesthesia were selected and translated for evaluation. Three non-sequential responses from ChatGPT were assessed for content quality (accuracy, comprehensiveness, and safety) and communication quality (understanding, empathy/tone, and ethics) by expert evaluators., Results: Eight anaesthesiologists evaluated English and Japanese LLM responses. The overall quality for all questions combined was higher in English compared with Japanese responses. Content and communication quality were significantly higher in English compared with Japanese LLMs responses (both P <0.001) in all three responses. Comprehensiveness, safety, and understanding were higher scores in English LLM responses. In all three responses, more than half of the evaluators marked overall English responses as better than Japanese responses., Conclusions: English LLM responses to anaesthesia-related frequently asked questions were superior in quality to Japanese responses when assessed by bilingual anaesthesia experts in this report. This study highlights the potential for language-related disparities in healthcare information and the need to improve the quality of AI responses in underrepresented languages. Future studies are needed to explore these disparities in other commonly spoken languages and to compare the performance of different LLMs., (© 2024 The Author(s).)

Self-assemblies of anisotropic colloidal particles into colloidal liquid crystals and well-defined superlattices are of great interest for hierarchical nanofabrications that are applicable for various functional materials. Inorganic nanosheets obtained by exfoliation of layered crystals have been highlighted as the intriguing colloidal units; however, the size polydispersity of the nanosheets has been preventing precise design of the assembled structures and their functions. Here, we demonstrate that the anionic titanate nanosheets with monodisperse size reversibly form very unusual superstructured mesophases through finely tunable weak attractive interactions between the nanosheets. Transmission electron microscopy, polarizing optical microscopy, small-angle x-ray scattering, and confocal laser scanning microscopy clarified the reversible formation of the mesophases (columnar nanofibers, columnar nematic liquid crystals, and columnar nanofiber bundles) as controlled by counter cations, nanosheet concentration, solvent, and temperature.

Background: Large language models have propelled recent advances in artificial intelligence technology, facilitating the extraction of medical information from unstructured data such as medical records. Although named entity recognition (NER) is used to extract data from physicians' records, it has yet to be widely applied to pharmaceutical care records., Objective: In this study, we aimed to investigate the feasibility of automatic extraction of the information regarding patients' diseases and symptoms from pharmaceutical care records. The verification was performed using Medical Named Entity Recognition-Japanese (MedNER-J), a Japanese disease-extraction system designed for physicians' records., Methods: MedNER-J was applied to subjective, objective, assessment, and plan data from the care records of 49 patients who received cefazolin sodium injection at Keio University Hospital between April 2018 and March 2019. The performance of MedNER-J was evaluated in terms of precision, recall, and F 1 -score., Results: The F 1 -scores of NER for subjective, objective, assessment, and plan data were 0.46, 0.70, 0.76, and 0.35, respectively. In NER and positive-negative classification, the F 1 -scores were 0.28, 0.39, 0.64, and 0.077, respectively. The F 1 -scores of NER for objective (0.70) and assessment data (0.76) were higher than those for subjective and plan data, which supported the superiority of NER performance for objective and assessment data. This might be because objective and assessment data contained many technical terms, similar to the training data for MedNER-J. Meanwhile, the F 1 -score of NER and positive-negative classification was high for assessment data alone (F 1 -score=0.64), which was attributed to the similarity of its description format and contents to those of the training data., Conclusions: MedNER-J successfully read pharmaceutical care records and showed the best performance for assessment data. However, challenges remain in analyzing records other than assessment data. Therefore, it will be necessary to reinforce the training data for subjective data in order to apply the system to pharmaceutical care records., (©Yukiko Ohno, Riri Kato, Haruki Ishikawa, Tomohiro Nishiyama, Minae Isawa, Mayumi Mochizuki, Eiji Aramaki, Tohru Aomori. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.06.2024.)

DNA-binding transcription factors (TFs) play a central role in transcriptional regulation mechanisms, mainly through their specific binding to target sites on the genome and regulation of the expression of downstream genes. Therefore, a comprehensive analysis of the function of these TFs will lead to the understanding of various biological mechanisms. However, the functions of TFs in vivo are diverse and complicated, and the identified binding sites on the genome are not necessarily involved in the regulation of downstream gene expression. In this study, we investigated whether DNA structural information around the binding site of TFs can be used to predict the involvement of the binding site in the regulation of the expression of genes located downstream of the binding site. Specifically, we calculated the structural parameters based on the DNA shape around the DNA binding motif located upstream of the gene whose expression is directly regulated by one TF AoXlnR from Aspergillus oryzae , and showed that the presence or absence of expression regulation can be predicted from the sequence information with high accuracy ([Formula: see text]-1.0) by machine learning incorporating these parameters.

Monoclonal antibodies (mAbs) represent a significant segment of biopharmaceuticals, with the market for mAb therapeutics expected to reach $200 billion in 2021. Chinese Hamster Ovary (CHO) cells are the industry standard for large-scale mAb production owing to their adaptability and genetic engineering capabilities. However, maintaining consistent product quality is challenging, primarily because of the inherent genetic instability of CHO cells. In this study, we address the need for advanced technologies for quality monitoring of host cells in biopharmaceuticals. We highlight the limitations of traditional cell assessment techniques such as flow cytometry and propose a noninvasive, label-free image-based analysis method. By utilizing advanced image processing and machine learning, this technique aims to non-invasively and quantitatively evaluate subtle quality changes in suspension cells. The research aims to investigate the use of morphological analysis for identifying subtle alterations in mAb productivity of CHO cells, employing cells stimulated by compounds as a model for this study. Our results show that the mAb productivity of CHO cells (day 8) can be predicted only from their early morphological profile (day 3). Our study also discusses the importance of strategic methods for forecasting host cell mAb productivity using morphological profiles, as inferred from our machine learning models specialized in predictive score prediction and anomaly prediction., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Trovafloxacin is a quinolone antibiotic drug with broad-spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury. The characteristics of trovafloxacin-induced liver injury are consistent with an idiosyncratic reaction; however, the details of the mechanism have not been elucidated. We examined whether trovafloxacin induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes. We also tested ciprofloxacin, levofloxacin, gatifloxacin, and grepafloxacin for their ability to activate inflammasomes. Drug bioactivation was performed with human hepatocarcinoma functional liver cell-4 (FLC-4) cells, and THP-1 cells (human monocyte cell line) were used for the detection of inflammasome activation. The supernatant from the incubation of trovafloxacin with FLC-4 cells for 7 days increased caspase-1 activity and production of IL-1ß by THP-1 cells. In the supernatant of FLC-4 cells that had been incubated with trovafloxacin, heat shock protein (HSP) 40 was significantly increased. Addition of a cytochrome P450 inhibitor to the FLC-4 cells prevented the release of HSP40 from the FLC-4 cells and inflammasome activation in THP-1 cells by the FLC-4 supernatant. These results suggest that reactive metabolites of trovafloxacin can cause the release of DAMPs from hepatocytes that can activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by trovafloxacin, which, in some patients, can cause immune-related liver injury., (© 2024 John Wiley & Sons Ltd.)

Introduction Decreased renal function after radical nephroureterectomy is one of the most important complications because it contributes to the decision to initiate adjuvant chemotherapy. This study aimed to investigate clinical factors associated with changes in renal function after radical nephroureterectomy in elderly patients. Methodology A total of 145 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma were evaluated. The renal function was calculated preoperatively, postoperatively, and one month postoperatively, and the long-term change in renal function was investigated once a year. The association between clinical factors and changes in renal function following radical nephroureterectomy in univariate and multivariate analyses was stratified by age ≥75 years and <75 years. Results The median age of the patients was 71 years, with 94 patients (65%) aged <75 years and 51 patients (35%) aged ≥75 years. The median estimated glomerular filtration rates (eGFRs) were 57.1 (21.8-100) preoperatively, 36.1 (9.1-100) postoperatively, and 42.4 (19.5-100) in one month after radical nephroureterectomy. The median eGFRs in elderly patients were 50.8 (21.8-85.4) preoperatively. In the elderly group, only 8% had an eGFR of ≥50 as cisplatin-eligible at one month postoperatively. The long-term renal function in the elderly may decline further than during the stable postoperative periods. In the multivariate analysis, hydronephrosis (HN) was a significant predictor of decreased renal function in patients aged ≥75 years between the pre- and postoperative periods. Conclusions Elderly patients with HN who have upper tract urothelial carcinoma have a lower risk of decreased renal function after radical nephroureterectomy. This result may be useful in determining adjuvant therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Iwate Medical University issued approval 2019-083. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Kawamura et al.)

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease., (© 2024. The Author(s).)

Introduction: Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia., Methods: This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria., Results: Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group., Conclusions: The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: We aimed to determine whether unfractionated heparin (UH) and low molecular weight heparin (LH) contribute to aberrant carnitine metabolism in patients receiving hemodialysis., Methods: The rate of increase in serum free fatty acids (FFAs) and the ratio of acylcarnitine to free carnitine (AC/FC) from before to after hemodialysis were determined in patients receiving UH and LH. Additionally, the effect of switching patients to UH from LH was examined., Results: AC/FC was significantly higher in the UH group. In addition, serum FFAs in that group increased to 0.825 ± 0.270 after dialysis from 0.172 ± 0.160 before dialysis, showing a positive correlation with AC/FC. Furthermore, AC/FC was observed to be significantly higher in patients who were switched to UH from LH at 3 months after the change., Conclusion: Compared with UH, LH has a lesser effect on lipid metabolism, suggesting that it also has a lesser effect on carnitine metabolism., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Competing Interests: Y.I. received an honorarium from Medtronic Japan as a speaker and a procedure trainer. R.K. received an honorarium from Medtronic Japan as a speaker. All other authors report no conflicts of interest.

A novel chiral photoswitch composed of a binaphthyl unit and a hexafluorocyclopentene ring has been synthesized. This chiral photoswitch exhibited thermally reversible photochromism between the binaphthyl and helicenoid forms based on 6π-electrocyclization. The helicity of the binaphthyl moiety was reversed upon stereospecific photocyclization and reverted back during the thermal ring opening.

Purpose: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors., Methods: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS., Results: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified., Conclusion: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)