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ABSTRACT Introduction Methods Results Conclusions The appropriate duration of therapy for uncomplicated gram‐negative bloodstream infection (GN‐BSI) in liver transplant (LTx) recipients remains unknown. This study aims to explore the effectiveness of a short‐course antimicrobial therapy.This retrospective study was performed in a single LTx center in Japan. All LTx recipients with GN‐BSI receiving 6–16 days of therapy with adequate source control between 2010 and 2022 were included. We collected data on demographics, underlying medical conditions, clinical manifestations, laboratory and microbiology data, ID consultation, oral switch therapy, and subsequent clinical course through chart review. We compared the 30‐day composite outcome comprising mortality and recurrence of BSI or local infection between patients receiving a short‐course (6–10 days) therapy and those receiving a long‐course (11–16 days) therapy.Of 91 study participants, 27 (29.7%) and 64 (70.3%) received short‐course and long‐course antimicrobial therapy, respectively. Cholangitis was the most common source of BSI (57/91 [62.6%]). Overall, the primary composite outcome occurred in 18 patients (19.8%), most of which was the recurrence of local infection (n = 14). The primary composite outcome was numerically compatible between these groups (5/27 [18.5%] vs. 13/64 [20.3%]; p = 0.84).A short‐course therapy may be an effective option in selected LTx recipients with uncomplicated GN‐BSI. Whether a short‐course oral switch therapy is a viable option or not warrants further research. [ABSTRACT FROM AUTHOR]

SUMMARY: Plants acquire phosphorus (P) primarily as inorganic phosphate (Pi) from the soil. Under Pi deficiency, plants induce an array of physiological and morphological responses, termed phosphate starvation response (PSR), thereby increasing Pi acquisition and use efficiency. However, the mechanisms by which plants adapt to Pi deficiency remain to be elucidated. Here, we report that deposition of a β‐1,3‐glucan polymer called callose is induced in Arabidopsis thaliana root hairs under Pi deficiency, in a manner independent of PSR‐regulating PHR1/PHL1 transcription factors and LPR1/LPR2 ferroxidases. Genetic studies revealed PMR4 (GSL5) callose synthase being required for the callose deposition in Pi‐depleted root hairs. Loss of PMR4 also reduces Pi acquisition in shoots and plant growth under low Pi conditions. The defects are not recovered by simultaneous disruption of SID2, mediating defense‐associated salicylic acid (SA) biosynthesis, excluding SA defense activation from the cause of the observed pmr4 phenotypes. Grafting experiments and characterization of plants expressing PMR4 specifically in root hair cells suggest that a PMR4 pool in the cell type contributes to shoot growth under Pi deficiency. Our findings thus suggest an important role for PMR4 in plant adaptation to Pi deficiency. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Materials and Methods Results Discussion Insulin icodec is a basal insulin designed for once‐weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D).In a randomized, open‐label, crossover study, 24 Japanese individuals with T1D (20–64 years; glycated hemoglobin ≤9.0%) received once‐weekly icodec for 8 weeks and once‐daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run‐in with glargine U100 titrated to prebreakfast self‐measured plasma glucose (SMPG) of 4.4–7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady‐state glucose‐lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24–48 h and 150–168 h after last icodec dose and 0–24 h after last glargine U100 dose. One‐week glucose‐lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods.Icodec pharmacokinetic steady state was achieved on average after 2–3 weeks of treatment. Model‐derived daily glucose‐lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <3.0 mmol/L) were 37.3 vs 30.6 episodes per patient‐year of exposure for icodec vs glargine U100.Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once‐weekly dosing in Japanese individuals with diabetes. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of food allergies and accidental allergic reactions in children, highlighting the need for tailored strategies based on age and severity. A multicenter survey involving caregivers of children with food allergies explored factors contributing to accidental exposure, such as age, food allergens, and pre-hospital responses. Findings suggest the importance of enhanced awareness, parental supervision, and patient education to prevent severe reactions and improve pre-hospital medication management, especially in children aged 4-6 years. The study emphasizes the necessity of age-appropriate education and guidance for children with food allergies to mitigate risks of accidental exposure. [Extracted from the article]

Background: S‐1, an oral fluoropyrimidine derivative, is standard adjuvant therapy for resected biliary tract cancer (BTC), based on the results of the JCOG1202, a phase III trial evaluating the survival benefit with adjuvant S‐1 following curative resection for BTC compared to surgery alone. This multicenter ancillary study of the JCOG1202 aimed to evaluate the prognostic impact of the 5‐fluorouracil (5‐FU) metabolic pathway genes including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Methods: The 5‐FU metabolic pathway genes were measured in tumor cells from formalin‐fixed paraffin‐embedded resected specimens from 183 patients (surgery alone: n = 94; adjuvant S‐1: n = 89). We randomly divided them into training (n = 96) and validation sets (n = 87) for evaluating the interaction between gene levels and RFS benefits in the treatment arm. Results: RFS benefits of adjuvant S‐1 were observed in the low DPD (HR = 0.440 and 0.748, respectively in the training and validation sets) and the low TP groups (HR = 0.709 and 0.602, respectively). Clinicopathological characteristics were well balanced between low and high DPD populations. More advanced stage tumors were observed in high TP populations as compared to those in low TP populations (p =.0332). Conclusion: The results suggest the RFS benefit of adjuvant S‐1 in resected BTC patients with low DPD and low TP gene expressions. [ABSTRACT FROM AUTHOR]

Background/Purpose: We evaluated the minimally invasive surgery for congenital biliary dilatation (CBD) in adults and children and analyzed the surgical outcomes, especially in children aged <6 years. Methods: Characteristics and surgical outcomes of patients with CBD who underwent minimally invasive surgery at our hospital between 2013 and 2023 were retrospectively reviewed. Results: Overall, 129 patients (89 children aged <6 years, 9 children aged between 6 and 18 years, and 21 adults) were included in this study. Children exhibited more protein plug presence and abnormal biochemical data than adults. Incidence of postoperative pancreatic fistulas was highest in the adult group (3.4%, 11%, and 33%, respectively, p <.01). In children aged <6 years, postoperative bile leakage and pancreatic fistulas occurred in 9.0% and 3.4% of patients, respectively. Multivariate logistic regression analysis revealed that the Todani IVA was associated with a decrease in postoperative bile leakage (odds ratio: −1.7; 95% confidence interval: (−3.3)–(−0.22), p =.03). Conclusion: Adults with CBD required prolonged operative times and had more short‐term complications than children with CBD. In children aged <6 years, minimally invasive surgery for CBD can be safely performed; however, a small diameter of the bile duct may be associated with bile leakage. Nakagawa and colleagues found that minimally invasive surgery for congenital biliary dilatation resulted in longer operative times and more short‐term complications, especially pancreatic fistula, in adults than in children. While the procedure is safe in children under age 6, a small bile duct diameter may be associated with bile leakage. [ABSTRACT FROM AUTHOR]

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR‐related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR‐related PVs were examined. Kaplan–Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR‐related. HRR‐PV‐positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR‐PV‐positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression‐free survival. HRR‐related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000–2019), the limited use of bevacizumab and poly (ADP‐ribose) polymerase inhibitors as maintenance therapy should be recognized. [ABSTRACT FROM AUTHOR]

Background: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB). Methods: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application. We analyzed the QRS morphology of the VAs with and without RBBB during sinus beats. Results: Twenty‐four patients (age 59 ± 17 years, female 14) developed RBBB at some point during their procedure. The successful ablation sites of the VAs were the right ventricular outflow tract (RVOT) in 12 patients, pulmonary artery in one, left coronary cusp in five, right coronary cusp in three, right‐left cusp junction in two, and great cardiac vein in two. QRS‐morphology change was observed in five (20%) cases. The successful ablation sites in that group were the left coronary cusp in three cases, right coronary cusp in one, and RVOT septum in one. The QRS duration of the VAs increased during RBBB. Conclusions: There are some cases of OT‐VAs in which the QRS waveform changes with the appearance of catheter induced RBBB. We need to be aware that when QRS morphology changes during an OT‐VA ablation, it does not necessarily mean that the origin or exit of the VA has changed. [ABSTRACT FROM AUTHOR]

Allorecognition—the ability of an organism to discriminate between self and nonself—is crucial to colonial marine animals to avoid invasion by other individuals in the same habitat. The cnidarian hydroid Hydractinia has long been a major research model in studying invertebrate allorecognition, establishing a rich knowledge foundation. In this study, we introduce a new cnidarian model Cladonema radiatum (C. radiatum). C. radiatum is a hydroid jellyfish which also forms polyp colonies interconnected with stolons. Allorecognition responses—fusion or regression of stolons—are observed when stolons encounter each other. By transmission electron microscopy, we observe rapid tissue remodeling contributing to gastrovascular system connection in fusion. Meanwhile, rejection responses are regulated by reconstruction of the chitinous exoskeleton perisarc, and induction of necrotic and autophagic cellular responses at cells in contact with the opponent. Genetic analysis identifies allorecognition genes: six Alr genes located on the putative allorecognition complex and four immunoglobulin superfamily genes on a separate genome region. C. radiatum allorecognition genes show notable conservation with the Hydractinia Alr family. Remarkedly, stolon encounter assays of inbred lines reveal that genotypes of Alr1 solely determine allorecognition outcomes in C. radiatum. RESEARCH HIGHLIGHTS: Introduction of the hydrozoan jellyfish Cladonema radiatum as a new cnidarian animal model, for studying invertebrate allorecognitionC. radiatum possesses effective allorecognition mechanisms mediated by a single gene Alr1. [ABSTRACT FROM AUTHOR]

Aim: Nutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol‐associated liver disease. Methods: In this retrospective cohort study, we included 211 patients with alcohol‐associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all‐cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders. Results: Among the patients (median age 67 years; 88% men; and median Model for End‐Stage Liver Disease score, 9), 86 (39%) were in the high‐frequency (≥2) nutritional counseling group. The high‐frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5 years than the low‐frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36–0.63) and overt HE (HR 0.64; 95% CI 0.42–0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19–0.59) and overt HE (HR 0.31; 95% CI 0.11–0.87). Conclusions: Nutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol‐associated liver disease, thereby proving essential for the management of these patients. [ABSTRACT FROM AUTHOR]

In immunocompetent individuals, Fusarium spp. stands out as the causative agent of onychomycosis, among the non‐dermatophyte molds. Despite evidence indicating that Fusarium oxysporum organizes itself in the form of a biofilm causing onychomycosis, there is little literature on the etiopathogenesis of the biofilm on the nail, specifically the signaling molecules present, known as quorum sensing (QS). Thus, this study detected the presence of a molecule related to QS from the ex vivo biofilm of F. oxysporum on human nail and investigated its effect on preformed biofilm in vitro. The detection and physicochemical characterization of a QS molecule, from the extracellular matrix (ECM), was carried out by Fourier transform infrared (FTIR) spectroscopy with an attenuated total reflectance (ATR) accessory and by headspace gas chromatography coupled to mass spectrometry (GC–MS) analyses. Determination of viable cells, cell activity, total biomass, ECM components and scanning electron microscopy (SEM) were performed to evaluate the influence of the QS molecule on the in vitro biofilm of F. oxysporum. The beginning, in the ex vivo biofilm of F. oxysporum on human nails, the volatile organic compound 2‐ethyl‐1‐hexanol (2EH) was detected as a component of QS. Thereafter in vitro analyses, synthetic 2EH was able to modulate the biofilm by stimulating its filament, increasing total biomass and ECM production in terms of total carbohydrates, but with a reduction in total proteins and nucleic acids. We thus evidence, for the first time, the presence of 2EH in the biofilm of F. oxysporum, developed on the human nail, and the in vitro action of this compound as a QS molecule. [ABSTRACT FROM AUTHOR]

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high‐performance artificial intelligence (AI) model to detect osteosarcoma from X‐ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%–70%. In contrast, our model used a data‐centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X‐ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U‐net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high‐quality training data and advocates a shift towards data‐centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care. [ABSTRACT FROM AUTHOR]

Short‐chain esters, particularly isobutyl acetate and isoamyl acetate, hold significant industrial value due to their wide‐ranging applications in flavors, fragrances, solvents, and biofuels. In this study, we demonstrated the biosynthesis of acetate esters using Yarrowia lipolytica as a host by feeding alcohols to the yeast culture. Initially, we screened for optimal alcohol acyltransferases for ester biosynthesis in Y. lipolytica. Strains of Y. lipolytica expressing atf1 from Saccharomyces cerevisiae, produced 251 or 613 mg/L of isobutyl acetate or of isoamyl acetate, respectively. We found that introducing additional copies of ATF1 enhanced ester production. Furthermore, by increasing the supply of acetyl‐CoA and refining the culture conditions, we achieved high production of isoamyl acetate, reaching titers of 3404 mg/L. We expanded our study to include the synthesis of a range of acetate esters, facilitated by enriching the culture medium with various alcohols. This study underscores the versatility and potential of Y. lipolytica in the industrial production of acetate esters. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the factors influencing picky eating in children with disabilities based on the hypothesis that primary disease or oral function is involved in picky eating. The subjects were 242 children aged 3–6 years receiving outpatient feeding therapy at our clinic. The subjects' general and oral conditions and picky eating were assessed by their medical recodes. Resultingly, 79 children showed picky eating. Using logistic regression analysis, associated factors of picky eating were primary disease (p =.04), nutritional methods (p =.01), and oral hypersensitivity (p =.04). The relationship with the primary disease suggests the influence of the characteristics of the primary disease. The relationship with oral hypersensitivity may be attributed to avoiding certain sensations. Additionally, the study revealed that the subjects employed tube feeding to compensate for reduced nutritional intake due to picky eating. This study indicated that primary disease and nutritional method as general conditions and oral hypersensitivity as an oral function were possible factors for picky eating. Picky eating was found to occur at varying frequencies depending on the underlying primary disease, especially when the child struggled to tolerate different sensations experienced during meals. [ABSTRACT FROM AUTHOR]

Aim: A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease that manifests symptoms similar to those of Behçet's disease. However, little is known about the involvement of the liver in HA20. Here, we report a case of HA20 complicated by autoimmune hepatitis (AIH). Case presentation: A 33‐year‐old woman was previously diagnosed with HA20 and chronic thyroiditis, and was treated with prednisolone (PSL; 7.5 mg/day) and levothyroxine sodium hydrate (125 μg/day). She experienced general malaise and jaundice, and biochemical evaluation revealed elevated liver function with an aspartate aminotransferase level of 817 U/L, an alanine aminotransferase level of 833 U/L, and a total bilirubin of 8.3 mg/dL. Pathological evaluation of the liver biopsy revealed interface hepatitis and the patient was diagnosed with acute exacerbation of AIH. Upon increasing the PSL dose to 60 mg/day, the liver enzyme levels rapidly decreased. During tapering of PSL, azathioprine 50 mg/day was added, and there was no relapse of AIH with combination therapy of PSL 7 mg/day and azathioprine 50 mg/day. Conclusion: This is the first report of biopsy‐proven AIH in an Asian patient with HA20. This case has significant implications for the pathogenesis and treatment of AIH in patients with HA20. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusions Type 2 diabetes mellitus (T2DM) is a well‐known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease.Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross‐sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared.Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut‐off index (COI), α‐fetoprotein concentration ≥5 ng/mL, and des‐γ‐carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB‐4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years.In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging. [ABSTRACT FROM AUTHOR]

CT‐P47 is a candidate biosimilar of tocilizumab. This 12‐week, randomized, double‐blind, parallel‐design, phase 1 study aimed to demonstrate pharmacokinetic (PK) equivalence of CT‐P47 and reference tocilizumab. Participants were healthy Japanese adults aged 18–55 years. Participants were randomized (1:1:1) to receive a single intravenous dose (8 mg/kg) of CT‐P47, EU‐approved tocilizumab (EU‐tocilizumab), or US‐licensed tocilizumab (US‐tocilizumab). Primary PK endpoints were area under the concentration–time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum serum concentration. Additional PK variables, safety, and immunogenicity were evaluated. The study was conducted from January 20 to May 26, 2023, in three centers in Japan. In total, 133 male participants were randomized (n = 45 to CT‐P47, n = 44 to EU‐tocilizumab, and n = 44 to US‐tocilizumab). For all primary PK variables, 90% confidence intervals of the ratio of geometric least squares means were within the predefined equivalence margin of 0.80‐1.25. Secondary PK variables were similar across groups. The most common treatment‐emergent adverse event (TEAE) was neutrophil count decreased, occurring in 15 (33.3%), 13 (30.2%), and 12 (27.3%) participants in the CT‐P47, EU‐tocilizumab, and US‐tocilizumab groups, respectively. There were no serious TEAEs, deaths, or study drug discontinuations due to TEAEs. Few participants were anti‐drug antibody (ADA)‐ or neutralizing antibody (NAb)‐positive. At the end of study, four (8.9%), one (2.3%), and two (4.5%) participants in the CT‐P47, EU‐tocilizumab, and US‐tocilizumab groups, respectively, were ADA‐positive; two (4.4%), zero (0%), and one (2.3%) in the respective groups were NAb‐positive. CT‐P47 demonstrated PK equivalence and comparable safety to EU‐ and US‐tocilizumab. [ABSTRACT FROM AUTHOR]

Background and Aims: Because the accuracy of the Fibrosis‐4 (FIB‐4) index for predicting liver fibrosis changes with age, the need for different cut‐offs in various age groups has frequently been discussed. We developed the age‐independent score, the Fibrosis‐3 (FIB‐3) index, and have shown its usefulness in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB‐3 index to predict fibrosis progression using a large new patient cohort. Methods: The ability of the FIB‐3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB‐4 index using data from 1398 patients with MASLD enrolled in the Asia‐based clinical outcome NAFLD study. Results: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB‐3 and FIB‐4 indices in the entire cohort. Using the single ideal cut‐offs of the indices (3.41 for FIB‐3 index and 2.01 for FIB‐4 index), the predictive accuracy of the FIB‐3 index was not significantly different from that of the FIB‐4 index among patients aged <60 years; however, the accuracy of the FIB‐3 index was significantly higher than that of the FIB‐4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001). Conclusion: The high ability of the FIB‐3 index with a single cut‐off to predict liver fibrosis in patients with MASLD was confirmed. The FIB‐3 index could serve as a useful tool for assessing liver fibrosis regardless of age. [ABSTRACT FROM AUTHOR]

The Senhance® robotic system (Senhance [Asensus Surgical Inc., Naderhan, NC, USA]) is a new surgical assistive robot following the da Vinci Surgical System that has been demonstrated to be safe and efficacious. Herein, we report the first case series of pediatric pelvic surgery using Senhance. Two anorectoplasties and one rectal pull‐through coloanal anastomosis for rectal stenosis were performed in three children (5–9 months, 7–9 kg) using a 10‐mm three‐dimensional (3D) 4K camera and 3 and 5 mm forceps operated with Senhance. None of the patients had intraoperative complications or a good postoperative course. Pediatric pelvic surgery with Senhance could be performed precisely and safely with a small body cavity. With its beautiful 3D images, motion of forceps with reduced tremor, and availability of 3‐mm forceps, Senhance may be better suited for children compared with other models. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID‐19) pandemic has negatively affected research activities across various fields. This study aimed to determine nursing researchers' concerns about research activities during the COVID‐19 pandemic in Japan and subsequent changes brought on by it. For this study, we conducted descriptive statistics and text mining analyses using data from two surveys conducted by the Japan Academy of Nursing Science (JANS) in the early days of the pandemic (first survey: mid‐2020) and after 2 years (second survey: early 2022). Concerns about research activities were observed in 89% and 80% of the nursing researchers in the first and second surveys, respectively. Furthermore, concerns about "Difficulty in collecting research data" and "Content and quality of your research" were stronger in the second survey. Text mining analyses revealed that in the first survey, they were concerned about environmental changes and restrictions when proceeding with research during the COVID‐19 pandemic, which was unfamiliar at the time. In the second survey, after overcoming environmental changes in the early stages of the pandemic, nursing researchers' concerns shifted to anxiety about the future, such as concerns about degree acquisition, employment and career advancement, and research results. The current study highlights various concerns among nursing researchers regarding research activities that have evolved over time during the pandemic. Academic societies must flexibly construct support measures for nursing researchers when a new infectious disease occurs. Such measures should be sensitive to the prevailing social circumstances and the evolving needs of researchers. [ABSTRACT FROM AUTHOR]

Riverbeds often fine downstream, with a gravel‐bedded reach, a relatively abrupt gravel‐sand transition (GST), and a sand‐bedded reach. Underlying this behavior, bed grain size distributions are often bimodal, with a relative paucity (gap) around the range 1–5 mm. There is no general morphodynamic model capable of producing the grain size gap and gravel‐sand transition autogenically from a unimodal sediment supply. Here we use a one‐dimensional morphodynamic model including size‐specific bedload and suspended load transport, to show that bimodality readily evolves autogenically even under unimodal sediment feed. A GST forms when we include a floodplain width that abruptly increases at some point. Upstream of the transition, non‐gap gravel ceases to move and gap sediment is preferentially transported. At the transition, non‐gap sand rapidly deposits from suspension, enhancing gap sediment mobility and diluting its presence on the bed. Plain Language Summary: The bed surface layer of many rivers is a mixture of sand and gravel. This mixture is described by the probability distribution of grain sizes, and in particular by the median size. Consider the long profile of such a river. Surface median size commonly becomes finer downstream, but often changes abruptly from a value above 5 mm to a value below 1 mm over a short reach. The range 1–5 mm is termed "gap sediment." Here we explain how this abrupt change evolves, even when there is no deficit of gap sediment supplied to the reach, and even though particle abrasion is not included. The grain size distribution autogenically develops two peaks, one in the sand range and one in the gravel range above 5 mm. When abrupt floodplain widening is included, the gravel peak is stronger in the upper reach and the sand peak is stronger in the lower reach, leading to a relatively abrupt gravel‐sand transition. Gap sediment can be diluted both upstream and downstream by a combination of effects due to bedload and suspended load, so that it dominates nowhere in the grain size distribution. Key Points: Numerical simulations show that bed bimodality evolves autogenically, even with unimodal sediment feed and no abrasionAbrupt floodplain widening can lead to the formation of a distinct gravel‐sand transitionThe behavior can be explained by preferential mobility of 1–5 mm sediment over a sand bed combined with fallout of sand from suspension [ABSTRACT FROM AUTHOR]

Japan is lagging in cervical cancer prevention. The effectiveness of a self‐sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self‐sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self‐sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self‐sampling kit according to their ordering (opt‐in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV‐positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention‐to‐screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self‐sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV‐positive women. Efforts to increase cytology triage are essential to maximize precancer detections. [ABSTRACT FROM AUTHOR]

Aim: In Japan, noninvasive prenatal testing (NIPT) has been performed by facilities accredited by the Japanese Society of Obstetrics and Gynecology since 2013. However, since 2016, with the implementation of NIPT, which can only be performed by blood sampling, non‐obstetricians have been involved in prenatal testing. Therefore, in July 2022, a new government‐involved NIPT certification system based on Health Sciences Council guidelines was introduced to ensure access to prenatal testing information for pregnant women. Methods: This survey was conducted in February 2023 and was the first survey after the certification system implementation. We conducted a web‐based survey of 1227 pregnant women and nursing mothers who underwent NIPT after July 2022 to evaluate their experiences. Results: Respondents were categorized by certification status as certified (C: 56%), non‐certified (non‐C: 23%), or uncertain (Q: 20%). The C group with a higher mean age at examination (35.0 ± 4.5 years) paid lower examination fees, received longer pre‐ and post‐examination explanations, and underwent more weekday examinations (80%) than the other groups. Most respondents, 67%, 48%, and 53% in the C, non‐C, and Q groups, respectively (p < 0.0001), stated that "NIPT needs to be regulated by the government or academic societies." The non‐C group was more likely to say, "Insufficient post‐test explanations at the laboratory made me more anxious," than the other groups when the testing results were non‐negative (p = 0.015). Conclusions: Despite government regulation, some pregnant women choose convenience over certified facilities, risking inadequate care. The government should ensure that NIPT is a safe option for all pregnant women. [ABSTRACT FROM AUTHOR]

The alternative pathway (AP) plays a major role in many complement‐mediated human diseases. Factor D (FD), a rate‐limiting enzyme in AP complement activation, is an attractive therapeutic target. Unlike other complement proteins, FD is synthesized primarily in adipose tissue, and its levels in human blood are relatively low. However, because of FD's high turnover rate, therapeutic targeting with monoclonal antibodies and chemical inhibitors has been challenging. The recent discovery that FD activity is regulated by mannose‐binding lectin‐associated serine protease 3 (MASP3), through conversion of a zymogen to mature FD, has sparked interest in MASP3 inhibition as a new way to block FD function and AP complement activity. Here, we review studies of mouse models of FD and MASP3 inhibition. We additionally discuss the lessons learned from these studies and their implications for therapeutic targeting of human FD and MASP3. [ABSTRACT FROM AUTHOR]

Cultivated rice (Oryza sativa) produces a variety of diterpenoid‐type phytoalexins. Diterpene synthase genes that are responsible for the biosynthesis of momilactones, phytocassanes, and oryzalexins have been identified in O. sativa cv. Nipponbare. OsKSL10 (Os12t0491800 in RAP and LOC_Os12g30824 in MSU) was previously identified as an enzyme catalyzing the conversion of ent‐copalyl diphosphate to ent‐sandaracopimaradiene for the production of oryzalexins A to F. Our previous study on Oryza rufipogon, a wild progenitor of Asian cultivated rice, showed that both OrKSL10 and OrKSL10ind from O. rufipogon accessions W1943 and W0106, respectively, closely related to the japonica and indica subspecies, converted ent‐copalyl diphosphate to ent‐miltiradiene. Thus, the functional conversion of ent‐miltiradiene synthase into ent‐sandaracopimaradiene synthase is implied to have occurred through natural amino acid mutations, the details of which have not been elucidated. In this study, we show that introduction of A654G substitution into OrKSL10 significantly alters its function into more closely resembling that of OsKSL10. Moreover, double substitution V546I/A654G almost completely converts the function of OrKSL10 into that of OsKSL10. On the other hand, the reversed substitution I546V/G654A was insufficient to convert the function of OsKSL10 into OrKSL10, indicating the introduction of additional substitution S522I is required for the functionality of OsKSL10. Lastly, point mutations at the 654A residue in OrKSL10 suggest that hydrophobic side chains at this position have a negative influence on the production of ent‐sandaracopimaradiene. [ABSTRACT FROM AUTHOR]

Background and Aim: Increased liver fibrosis scores (LFS), such as fibrosis‐4 index (FIB‐4) or non‐alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID‐19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID‐19. Methods: Participants comprised consecutive Japanese COVID‐19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB‐4, NFS, aspartate aminotransferase‐to‐platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID‐19. Results: Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID‐19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB‐4 and NFS were risk factors for death, severe COVID‐19, and oxygen demand; that increased BARD was a risk factor for severe COVID‐19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID‐19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID‐19 and oxygen demand. Conclusions: This study showed that FIB‐4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID‐19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID‐19 and oxygen demand. [ABSTRACT FROM AUTHOR]

Aim: To conduct a post hoc subgroup analysis of patients with type 2 diabetes (T2D) from the RECAP study, who were treated with sodium‐glucose cotransporter‐2 (SGLT2) inhibitor and glucagon‐like peptide 1 receptor agonist (GLP‐1RA) combination therapy, focusing only on those patients who had chronic kidney disease (CKD), to examine whether the composite renal outcome differed between those who received SGLT2 inhibitor treatment first and those who received a GLP‐1RA first. Methods: We included 438 patients with CKD (GLP‐1RA‐first group, n = 223; SGLT2 inhibitor‐first group, n = 215) from the 643 T2D patients in the RECAP study. The incidence of the composite renal outcome, defined as progression to macroalbuminuria and/or a ≥50% decrease in estimated glomerular filtration rate (eGFR), was analysed using a propensity score (PS)‐matched model. Furthermore, we calculated the win ratio for these composite renal outcomes, which were weighted in the following order: (1) both a ≥50% decrease in eGFR and progression to macroalbuminuria; (2) a decrease in eGFR of ≥50% only; and (3) progression to macroalbuminuria only. Results: Using the PS‐matched model, 132 patients from each group were paired. The incidence of renal composite outcomes did not differ between the two groups (GLP‐1RA‐first group, 10%; SGLT2 inhibitor‐first group, 17%; odds ratio 1.80; 95% confidence interval [CI] 0.85 to 4.26; p = 0.12). The win ratio of the GLP‐1RA‐first group versus the SGLT2 inhibitor‐first group was 1.83 (95% CI 1.71 to 1.95; p < 0.001). Conclusion: Although the renal composite outcome did not differ between the two groups, the win ratio of the GLP‐1RA‐first group versus the SGLT2 inhibitor‐first group was significant. These results suggest that, in GLP‐1RA and SGLT2 inhibitor combination therapy, the addition of an SGLT2 inhibitor to baseline GLP‐1RA treatment may lead to more favourable renal outcomes. [ABSTRACT FROM AUTHOR]

Cyclam is a well‐known example of a polyaza macrocycle. However, there are few reports of its optically active versions. In this study, we synthesized highly symmetric optically active cyclam (S,S,S,S)‐5,7,12,14‐tetraphenyl‐1,4,8,11‐tetraazacyclotetradecane, which has four phenyl groups on the cyclam skeleton, and derivatized it in various ways. We were able to synthesize a chiral Cu complex, an N‐ethyl derivative, and a dithiourea from this optically active cyclam. The structures of the chiral Cu complex and dithiourea were verified by single‐crystal X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Recent policy discourse on the localisation of disaster management and humanitarian assistance lacks attention to the culture, history, and traditions of the Global South. This special issue of Disasters argues that it is imperative to recognise the dynamic, interactive, contested, and negotiated nature of local knowledge. Such local knowledge saves lives by enabling responders to situate ad hoc, one‐off events such as disasters in the broader and deeper context of community relationships, thereby providing more appropriate and more effective aid. Through the cases of China, Japan, Indonesia, and the Philippines, this special issue examines such dynamic local knowledge using an analytical framework consisting of three manifestations of local knowledge, namely: social capital; contextual historical memories; and adaptation to new ideas. These three manifestations show the ways in which local knowledge creates local capacity, via which local, national, and international disaster respondents can centre their response coordination, and in turn, demonstrate how local capacity reformulates local knowledge. [ABSTRACT FROM AUTHOR]

Chinese humanitarian actors have worked frequently with the Chinese diaspora in disaster‐affected areas, but little, if any, research has been conducted into the important role of the diaspora in disaster response and humanitarian assistance. This paper investigates what local knowledge the Chinese diaspora has offered to humanitarian actors from the People's Republic of China (PRC), and how this has contributed to their effectiveness. Based on a case study of the semi‐autonomous Indonesian province of Aceh in the aftermath of the Indian Ocean tsunami of 2004, this paper argues that the diaspora can serve as a linchpin in local and international humanitarian action. It can do so by strengthening networks and bringing together local ethnic communities, local governments, and the PRC's humanitarian actors, while also offering local knowledge in the form of contextual memory. Such local knowledge may have to be fully utilised to address any underlying ethnic tensions in disaster‐affected areas. [ABSTRACT FROM AUTHOR]

Background and Aim: We conducted a study using the Fibrosis‐3 (FIB‐3) index, which is the established age‐independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB‐4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population. Methods: We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB‐3 index by age group. In addition, we examined the age distribution of the FIB‐3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver. Results: In terms of age‐specific distribution, the FIB‐3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB‐3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB‐3. index ≥1.5, and some had FIB‐3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB‐3 index and the presence of fatty liver. Conclusions: The FIB‐3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastrointestinal stromal tumors (GISTs) are treated as malignant gastric subepithelial lesions (SELs), and resection is recommended. However, small gastric SELs < 20 mm with no malignant features are monitored without histopathological examination, and the frequency of malignancy is unknown. This study aimed to clarify the clinicopathological findings and clinical course of gastric SELs < 20 mm measured by endoscopic ultrasound (EUS). Methods: This retrospective cohort study included consecutive patients with small gastric SELs < 20 mm diagnosed using EUS at a tertiary referral center between 2009 and 2021. The clinical course after diagnosis using EUS‐guided fine‐needle aspiration (EUS‐FNA) was reviewed. Results: Among 333 patients with small gastric SELs, 104 patients with 105 lesions underwent EUS‐FNA. The pathological diagnosis was confirmed in 87 patients. GISTs were the most common pathology (47%). Among the 87 patients, 43 underwent therapeutic interventions, including tumor resection and chemotherapy. In groups of tumor resection, the pathological tumor size on the resected specimen was significantly larger than the size measured by EUS (19.5 mm vs 15.0 mm, P < 0.001), and 37% of resected SELs were 20 mm or over. No recurrence was observed after tumor resection during a mean follow‐up period of 40 months. Conclusions: Approximately 40% of small gastric SELs were malignant tumors, such as GIST, with most of them requiring treatment. Additionally, considering that the EUS measurement is 5 mm smaller than the pathological tumor diameter, further examinations, such as systematic EUS‐FNA, may be required for SEL, including those smaller than 20 mm. [ABSTRACT FROM AUTHOR]

Introduction: Previously, we identified eight effective consultation skills to support decision‐making in the voluntary surrender of older adult drivers' licences in super‐aged Japan. This study aimed to clarify the transferability of these skills. Methods: We collected text data by interviewing 11 safe‐driving counsellors (four police officers, four clerical staff and three nurses) in the License Division of the National Police Agency from February to March 2022. Interviews were semi‐structured and conducted by telephone or email. During the interview, participants were asked to recall their experiences as counsellors providing decision‐making support to older drivers and to compare their experiences with the eight consultation skills. We analysed the content of the responses by quantitative text analysis with KH Coder 3 software. Results: As a characteristic of the words and phrases used by counsellors in their narratives about consultation skills, the most frequently extracted words from among 3147 words were think, parties and family, and promote had the highest mediation centrality. The eight subgraphs were 'Respecting the will of relevant parties from their standpoint is natural', 'Listening attentively and empathetically to relevant parties is effective', 'Presenting objective data to guide decisions is successful', 'Showing cognitive functioning test results is often effective', 'Counselors with medical expertise can elicit positive counseling outcomes', 'Intervention by medical or police counselors facilitates the decision to surrender voluntarily', 'Counseling skills need to be improved' and 'A diagram of the 8 skills is helpful for inexperienced counselors'. Conclusion: The results suggest that the eight consultation skills have similarities and are transferable. This transferability might contribute to practical application or cohort follow‐up study research. These skills can be incorporated into counsellor training, and counsellors can be expected to use these skills in the future. Regardless of the safe‐driving counsellor's years of experience, the skills can help them provide uniform and accurate support in decision‐making regarding the voluntary surrender of older adult drivers' licences. These skills are a promising approach to help older adults lead safe and secure lives as they age. [ABSTRACT FROM AUTHOR]

The anti‐CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara– group) and those administered Dara (Dara+ group), the 1‐year progression‐free survival (PFS) rates were 87.4% and 77.3% and the 1‐year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara– group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara– group. [ABSTRACT FROM AUTHOR]

Objective: We previously reported that CD14+ dendritic‐shaped cells exhibit a dendritic morphology, engage in pseudo‐emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14highCD90intermediate(int) cells function as dendritic cells. In this study, we investigated the dendritic cell–differentiation potential of CD14highCD90int cells. Methods: The localization and number of CD14highCD90int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell–differentiation potential of CD14highCD90int cells was examined by measuring interleukin‐6 and tumor necrosis factor‐α levels in the supernatant and CD83 and human leukocyte antigen (HLA)‐DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co‐cultured with lymphocytes, and the activation of these cells was examined. Results: CD14highCD90int cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14highCD90int cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell–differentiation culture, but CD83 and HLA‐DR expression were significantly increased in the CD14highCD90int cell group. When co‐cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction. Conclusion: CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14highCD90int cells in contact with lymphocytes differentiate into HLA‐DR+ dendritic cells, which contribute to chronic inflammation in RA. [ABSTRACT FROM AUTHOR]

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Summary: Aims: A multi‐stakeholder consensus has proposed MASLD (metabolic dysfunction‐associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid‐term mortality of patients with biopsy‐proven MASLD in Japan. Methods: We enrolled 1349 patients with biopsy‐proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data‐mining analysis. Results: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty‐five patients with MASLD died. Of these, liver‐related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9‐fold and 1.8‐fold risk of mortality, respectively. In the decision‐tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid‐term prognosis of patients with MASLD. Conclusions: In patients with biopsy‐proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver‐related events. Hepatic inflammation and fibrosis were significant factors influencing mid‐term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD. [ABSTRACT FROM AUTHOR]

The relationship of histopathological changes and the infection of Piscine orthoreovirus 2 (PRV‐2) was investigated in coho salmon that were suffering from the erythrocytic inclusion body syndrome (EIBS). Immunohistochemical observations revealed abundant σ1 protein of PRV‐2 in the spongy layer of the ventricle of the heart, where severe myocarditis was observed. In the spleen, the virus protein was detected in many erythrocytes, some of which were spherical‐shaped and apparently dead. The number of erythrocytes was decreased in the spleen compared to the apparently healthy fish. The virus protein was also detected in some erythrocytes in blood vessels. The viral protein was often detected in many macrophages ingesting erythrocytes or dead cell debris in the spleen or in the kidney sinusoids. Large amounts of the viral genomic segment L2 were also detected in these organs by RT‐qPCR. Many necrotic foci were found in the liver, although the virus protein was not detected in the hepatocytes. These results suggest that the primary targets of PRV‐2 are myocardial cells and erythrocytes and that clinical symptoms such as anaemia or jaundice and histopathological changes such as myocarditis in EIBS‐affected coho salmon are caused by PRV‐2 infection. [ABSTRACT FROM AUTHOR]

Biopsy has recently become a preferred protocol for sampling the skin and blubber of many cetacean species, although it is desirable to collect as minimally invasive as possible. Here, the effect of biopsy sampling on the captive common bottlenose dolphins was evaluated by analyzing the process of wound healing and changes in hematological and blood biochemical parameters after biopsy using a puncher developed to collect up to the inner layer of the dolphin blubber. Results showed that the wounds caused by biopsy were closed in as early as 1 day and completely covered with the epidermis within 5–11 days. Blood fibrinogen, which generally increases due to a wound‐induced inflammatory response or activation of the coagulation system, was significantly elevated after the biopsy indicating ongoing tissue repair, while other parameters did not exhibit significant differences. Furthermore, histological observation and RNA extraction of samples were performed to investigate the versatility of this method to cetacean research. Histological examination revealed three distinct layers of the blubber in the biopsy samples. Moreover, total RNA extracted from biopsy samples exhibited sufficient quality and quantity for gene expression analyses. Overall, the puncher utilized in our study represents a valuable and minimally invasive tool for investigating various aspects of small cetacean studies. Research highlights: •The developed biopsy puncher is a minimally invasive device that can collect up to inner layer of common bottlenose dolphin blubber, and can be used in a variety of investigations to better understand the metabolic activity and physiology of blubber. [ABSTRACT FROM AUTHOR]

Background: The concept of ablation index (AI) was introduced to evaluate radiofrequency (RF) ablation lesions. It is calculated from power, contact force (CF), and RF duration. However, other factors may also affect the quality of ablation lesions. To examine the difference in RF lesions made during sinus rhythm (SR) and atrial fibrillation (AF). Methods: Sixty patients underwent index pulmonary vein isolation during SR (n = 30, SR group) or AF (n = 30, AF group). All ablations were performed with a power of 50 W, a targeted CF of 5-15 g, and AI of 400-450 using Thermocool Smarttouch SF. The CF, AI, RF duration, temperature rise (Δtemp), impedance drop (Δimp), and the CF stability of each ablation point quantified as the standard deviation of the CF (CF-SD) were compared between the two groups. Results: A total of 3579 ablation points were analyzed, which included 1618 and 1961 points in the SR and the AF groups, respectively. Power, average CF, RF duration per point, and the resultant AI (389 ± 59 vs. 388 ± 57) were similar for the two rhythms. However, differences were seen in the CF-SD (3.5 ± 2.2 vs. 3.8 ± 2.1 g, p < .01), Δtemp (3.8 ± 1.3 vs. 4.0 ± 1.3°C, p < .005), and Δimp (10.3 ± 5.8 vs. 9.4 ± 5.4 Ω, p < .005). Conclusions: Despite similar AI, various RF parameters differed according to the underlying atrial rhythm. Ablation delivered during SR demonstrated less CF variability and temperature increase and greater impedance drop than during AF. [ABSTRACT FROM AUTHOR]

Aims: The application of indices in the context of metabolic dysfunction‐associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate the ability of alanine aminotransferase (ALT), fatty liver index (FLI), and hepatic steatosis index (HSI) to identify MASLD during health checkups. Methods: We recruited 627 participants and utilized their health checkup data and ultrasound to assess the potential of using ALT, FLI, and HSI as indices for MASLD; this was indicated by the area under the curve (AUC) and restricted cubic spline (RCS) model. The optimal, rule‐out (sensitivity ≥90%), and rule‐in (specificity ≥90%) cutoff values of each index for identifying MASLD were reported. Results: Among participants with a median age of 46 years, the prevalence of MASLD was 28% in total (38% in males and 18% in females). RCS models confirmed a linear association between indices and MASLD. ROC analyses indicated that the AUC of ALT in identifying MASLD was 0.79 for the total cohort, 0.81 for males, and 0.69 for females. The optimal, rule‐out, and rule‐in cutoff values for ALT were 21, 13, and 29, respectively. Similarly, the AUC of FLI/HSI in identifying MASLD was 0.90/0.88 for the total cohort, 0.86/0.85 for males, and 0.93/0.90 for females. Considering the reference cutoff values, distinct cutoff values were observed between the sexes for FLI, while HSI had similar cutoff values. Conclusion: This study demonstrated that ALT > 30 IU/L is a reasonable cutoff value to rule‐in MASLD. ALT, FLI, and HSI are reliable indices for identifying MASLD during health checkups. [ABSTRACT FROM AUTHOR]

Aims: To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. Methods: Eligible patients in Japan (aged 18–59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self‐reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9‐item (PHQ‐9), Generalized Anxiety Disorder 7‐item (GAD‐7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5‐Dimension 5‐Levels questionnaire (EQ‐5D‐5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. Results: In total, 3376 patients were included in the analysis (56% male; 48% aged 50–59 years). Overall, 67.1% of patients self‐reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ‐9, GAD‐7, WSAS, and EQ‐5D‐5L scores (correlation coefficients: 0.67, 0.55, 0.56, −0.51, respectively; all p < 0.0001). Descriptive analyses showed that one‐third of patients reporting EB symptoms did not tell their physician, with two‐thirds finding these symptoms distressing and likely to affect recovery. Conclusion: EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD. [ABSTRACT FROM AUTHOR]

Here, an unprecedented phenomenon in which 7‐coordinate lanthanide metallomesogens, which align via hydrogen bonds mediated by coordinated H2O molecules, form micellar cubic mesophases at room temperature, creating body‐centered cubic (BCC)‐type supramolecular spherical arrays, is reported. The results of experiments and molecular dynamics simulations reveal that spherical assemblies of three complexes surrounded by an amorphous alkyl domain spontaneously align in an energetically stable orientation to form the BCC structure. This phenomenon differs greatly from the conventional self‐assembling behavior of 6‐coordinated metallomesogens, which form columnar assemblies due to strong intermolecular interactions. Since the magnetic and luminescent properties of different lanthanides vary, adding arbitrary functions to spherical arrays is possible by selecting suitable lanthanides to be used. The method developed in this study using 7‐coordinate lanthanide metallomesogens as building blocks is expected to lead to the rational development of micellar cubic mesophases. [ABSTRACT FROM AUTHOR]

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video‐tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2‐ and parvalbumin‐GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by α,β‐methylene ATP (10 μM) but not prazosin (1 μM). Tadalafil (100 nM), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by N‐ω‐propyl‐l‐arginine hydrochloride (l‐NPA, 1 μM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co‐expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1 μM) pre‐constricted rat or mouse urethral arterioles, nerve‐evoked vasodilatations or transient SMC Ca2+ reductions were largely diminished by l‐nitroarginine (l‐NA, 10 μM), a broad‐spectrum NOS inhibitor, but not by l‐NPA. The CGRP receptor antagonist BIBN‐4096 (1 μM) shortened the vasodilatory responses, while atropine (1 μM) abolished the l‐NA‐resistant transient vasodilatory responses. Nerve‐evoked endothelial Ca2+ transients were abolished by atropine plus guanethidine (10 μM), indicating its neurotransmitter origin and absence of non‐adrenergic non‐cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre‐ and post‐synaptically to restrict arteriolar contractility. Key points: Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder.In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline.NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre‐synaptic inhibition of sympathetic transmission as well as post‐synaptic arteriolar smooth muscle relaxation.Acetylcholine released from parasympathetic nerves contributes to endothelium‐dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO‐mediated vasodilatations.PDE5 inhibitors could be beneficial to maintain and/or improve urethral blood supply and in turn the volume and contractility of urethral musculature. [ABSTRACT FROM AUTHOR]

Summary: In Catharanthus roseus, monoterpenoid indole alkaloids (MIAs) are produced through the cooperation of four cell types, with final products accumulating in specialized cells known as idioblasts and laticifers. To explore the relationship between cellular differentiation and cell type‐specific MIA metabolism, we analyzed the expression of MIA biosynthesis in germinating seeds.Embryos from immature and mature seeds were observed via stereomicroscopy, fluorescence microscopy, and electron microscopy. Time‐series MIA and iridoid quantification, along with transcriptome analysis, were conducted to determine the initiation of MIA biosynthesis. In addition, the localization of MIAs was examined using alkaloid staining and imaging mass spectrometry (IMS).Laticifers were present in embryos before seed maturation. MIA biosynthesis commenced 12 h after germination. MIAs accumulated in laticifers of embryos following seed germination, and MIA metabolism is induced after germination in a tissue‐specific manner.These findings suggest that cellular morphological differentiation precedes metabolic differentiation. Considering the well‐known toxicity and defense role of MIAs in matured plants, MIAs may be an important defense strategy already in the delicate developmental phase of seed germination, and biosynthesis and accumulation of MIAs may require the tissue and cellular differentiation. [ABSTRACT FROM AUTHOR]

Aim: The inability to quickly react to an external event can lead to an increased risk for accidents (e.g., falls, car crashes) in patients with cirrhosis. The aim of this study was to determine whether a novel clinically feasible measure of simple reaction time (SRT) and reaction accuracy (RA)—a go/no‐go task occurring within 400 ms—could differentiate patients with cirrhosis from controls. Methods: This retrospective study included 160 patients with cirrhosis and 160 controls assessed between January 2010 and October 2022. SRT and RA were evaluated using a ruler drop paradigm and compared using propensity score matching. Factors distinguishing patients with cirrhosis from controls were assessed using logistic regression and receiver operating characteristics curve (ROC) analyses. Results: Propensity score matching identified 112 participants in each group with comparable baseline characteristics. As compared with controls, patients with cirrhosis exhibited significantly prolonged SRT (200 vs. 174 ms; P < 0.001) and diminished total RA (63% vs. 73%; P < 0.001). After adjustment for confounding factors, SRT and RA independently identified patients with cirrhosis. ROC analyses showed that SRT more effectively identified patients with cirrhosis than did the number‐connection test/trail‐making test‐B (area under the curve, 0.87 vs. 0.60; P < 0.001). Conclusions: Patients with cirrhosis demonstrated impairments in short‐latency cognitive function. Given that SRT and RA are associated with balance, falls, and response to perturbation, these parameters may present a task‐specific method to identify patients with cirrhosis at high risk of falls and motor vehicle crashes. Geriatr Gerontol Int 2024; 24: 25–31. [ABSTRACT FROM AUTHOR]