Search

Abstract Aims Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline‐directed medical therapies. The haemodynamic effects of vericiguat remain unclear. Methods and results This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II–IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline‐recommended therapies between March and December 2022, with follow‐ups completed in June 2023. A balloon‐tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5 mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5 mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30 min after (both P

Introduction The pathologic evaluation and clinical course of cytoreductive nephrectomy after combined immuno‐oncology therapy were reviewed to understand the benefits of cytoreductive nephrectomy. Case presentation Three patients with clear cell carcinoma underwent tumor biopsy before combined immuno‐oncology therapy. Case 1 was found to have a sarcomatoid component upon nephrectomy and continued with combined immuno‐oncology therapy. Case 2 discontinued combined immuno‐oncology therapy due to adverse events but maintained tumor shrinkage. The patient was found to have viable cells in most nephrectomy specimens but has had no recurrence after combined immuno‐oncology therapy was discontinued. In case 3, the residual tumor was deemed resectable with combined immuno‐oncology therapy, and nephrectomy and metastasectomy were performed. No viable cells were observed in either specimen, and the patient has had no recurrence. Conclusion Cytoreductive nephrectomy after combined immuno‐oncology therapy may be useful to allow pathologic evaluation of treatment and provide an indicator for subsequent treatment.

This study assesses the impact of defoliation applied to three developmental stages across three cropping seasons from 2021 to 2023 on growth, yield and forage quality in maize. The experimental design included three treatments: defoliation of three expanded leaves at the 3rd–4th leaf stage (DF1), the 5th–6th expanded leaves by leaf punch (DF2) and expanding leaves with the DF2 treatment (DF3) at the 6th–7th leaf stages, compared with no defoliation (control). Over three years, the most significant decrease in dry matter (DM) yield occurred in DF1 during spring sowing, while in summer sowing, the largest reduction was in DF3, both of which were correlated with changes in the number of grains per ear. The DM yields at harvest were positively correlated with plant leaf areas at the silking stage. The digestibility of forage in in vitro DM decreased concomitantly with an increase in acid detergent fiber content, indicating a decrease in forage quality. Given the frequent severe damage observed in summer sown maize and the detrimental effects of early growth stage leaf feeding on quality and quantity of spring sown maize, the application of registered insecticides is advised to reduce pest damage to maize crops.

Background and objectivesCognitive reserve (CR) is a property of the brain that allows for better–than–expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting–state EEG, moderate the relationship between hippocampal volume and episodic memory.MethodsParticipants were recruited as part of the National Center for Geriatrics and Gerontology–Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson–Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal–memory association.ResultsA total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of β = −0.00012 (95% CI: −0.00024; −0.00001, p = 0.040), and VAN with a slope of β = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond −914.6, the hippocampal volume was no longer significantly associated with word-list memory.DiscussionOur results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve.

Abstract Early preventive measures against depression have become important with unprecedented global aging. Increase in one’s perceived value (PV) may correspond to better mental health outcomes. This cross-sectional observation study aimed to clarify whether the PV of adopting new behaviors is associated with depressive symptoms. The participants were 5266 community-dwelling older adults aged ≥ 65 years. We developed a questionnaire to measure the PV of adopting new behaviors, specifically activities beneficial for preventing depressive symptoms (physical, cognitive, and social activities) in older adults. The questionnaire asked whether adopting the ten selected behaviors was valuable. The scores were added, and the total score ranged from − 20 to 20. The odds ratios (OR) of depressive symptoms were calculated using binomial logistic regression according to the PV score quartiles. Depressive symptoms were reported by 595 (11.3%) participants. After adjusting for potential confounders, higher quartiles of PV scores were significantly associated with lower prevalence of depressive symptoms: vs Q1; Q2 OR 0.76 (95% confidence interval: 0.59–0.97); Q3 0.67 (0.51–0.87); Q4 0.54 (0.40–0.73) (P for trend

Abstract INTRODUCTION This study aimed to determine whether the concomitance of hearing impairment and isolation with lack of conversation, which is considered self‐evident but has not been investigated extensively, is associated with the occurrence of dementia. METHODS A total of 2745 participants were divided into four groups according to the presence/absence of hearing impairment and isolation with lack of conversation. The association of dementia with hearing impairment and isolation with lack of conversation was analyzed using Cox proportional hazards regression. RESULTS The combined hearing impairment and isolation with lack of conversation (hazard ratio: 1.69, 95% confidence interval: 1.09‐2.61) and non‐hearing impairment and isolation with lack of conversation (hazard ratio: 1.60, 95% confidence: 1.07‐2.39) were associated with the development of dementia. DISCUSSION These findings emphasize the importance of promoting high‐quality social relationships throughout life by adopting preventive measures against isolation with lack of conversation from the early stage of awareness of hearing impairment. Highlights Dementia affects 12.9% of those with hearing impairment and isolation. Hearing impairment and isolation are associated with increased risk of dementia. Addressing these risk factors may help reduce the risk of developing dementia. Preventing isolation and promoting quality social relationships is important.

Abstract Background Neurodegeneration and structural changes in the brain due to amyloid deposition have been observed even in individuals with mild cognitive impairment (MCI). EEG measurement is considered an effective tool because it is noninvasive, has few restrictions on the measurement environment, and is simple and easy to use. In this study, we investigated the neurophysiological characteristics of community-dwelling older adults with MCI using EEG. Methods Demographic characteristics, cognitive function, physical function, resting-state MRI and electroencephalogram (rs-EEG), event-related potentials (ERPs) during Simon tasks, and task proportion of correct responses and reaction times (RTs) were obtained from 402 healthy controls (HC) and 47 MCI participants. We introduced exact low-resolution brain electromagnetic tomography-independent component analysis (eLORETA-ICA) to assess the rs-EEG network in community-dwelling older adults with MCI. Results A lower proportion of correct responses to the Simon task and slower RTs were observed in the MCI group (p

Abstract Tumor cells generally require large amounts of nucleotides, and thus activate de novo purine synthesis (dnPS). In the dnPS reactions, 10-formyltetrahydorofolate (10-fTHF) supplied by one-carbon metabolism is utilized as a formyl group donor. We focused on aldehyde dehydrogenase 1 family member L1 (ALDH1L1), which metabolizes 10-fTHF to tetrahydrofolate and whose expression is often attenuated in hepatocellular carcinoma (HCC). We generated ALDH1L1-expressing HuH-7 cells to perform metabolome analysis and found that intracellular levels of serine were reduced and glycine was increased. In addition, 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP), a dnPS intermediate, accumulated due to the consumption of 10-fTHF by ALDH1L1, which inhibited ZMP formylation. Importantly, ALDH1L1-expressing cells showed reduced ZMP sensitivity and higher mitochondrial activity. The suppression of mitochondrial serine catabolism by ALDH1L1 expression was speculated to be closely related to this phenotype. Gene set enrichment analysis utilizing The Cancer Genome Atlas data revealed that genes related to oxidative phosphorylation were enriched in HCC patients with high ALDH1L1 expression. Moreover, drug sensitivity data analysis demonstrated that HCC cell lines with low expression of ALDH1L1 were sensitive to ZMP and cordycepin, a structural analog of ZMP and AMP. Our study revealed that ZMP and AMP analogs might be effective in the pharmacotherapy of HCC patients with low expression of ALDH1L1.

The purpose of this study was to conduct a cross-sectional analysis of the association between hearing aid use and cognitive decline in community-dwelling older adults with hearing impairment, stratified by cardiovascular risk level. This cross-sectional study covers 1857 hearing-impaired individuals selected among 10,674 community-dwelling older adults (≥65 years of age) in Japan. We investigate the association between hearing aid use and cognitive decline stratified by cardiovascular risk level, by assessing self-reported hearing impairment and hearing aid use, absolute cardiovascular risk, cognitive function, and potential confounding factors. The association between hearing impairment severity and increased cardiovascular risk, and the benefit of hearing aid use in preventing cognitive decline, were examined in a binomial logistic regression analysis, with the presence of cognitive decline as the objective variable. In the low cardiovascular risk group, hearing aid users had a lower odds ratio for decline in executive function than non-users (odds ratio = 0.61, 95% confidence interval: 0.39–0.98). However, there was no significant association between hearing aid use and cognitive decline in the high cardiovascular risk group (p > 0.05). Among older adults with hearing impairment, hearing aid use was associated with the maintenance of executive function in individuals of low cardiovascular risk.

Abstract The developmental biology underlying the morphogenesis of mushrooms remains poorly understood despite the essential role of fungi in the terrestrial environment and global carbon cycle. The mushroom Coprinopsis cinerea is a leading model system for the molecular and cellular basis of fungal morphogenesis. The dikaryotic vegetative hyphae of this fungus grow by tip growth with clamp cell formation, conjugate nuclear division, septation, subapical peg formation, and fusion of the clamp cell to the peg. Studying these processes provides many opportunities to gain insights into fungal cell morphogenesis. Here, we report the dynamics of five septins, as well as the regulators CcCla4, CcSpa2, and F-actin, visualized by tagging with fluorescent proteins, EGFP, PA-GFP or mCherry, in the growing dikaryotic vegetative hyphae. We also observed the nuclei using tagged Sumo proteins and histone H1. The five septins colocalized at the hyphal tip in the shape of a dome with a hole (DwH). CcSpa2-EGFP signals were observed in the hole, while CcCla4 signals were observed as the fluctuating dome at the hyphal tip. Before septation, CcCla4-EGFP was also occasionally recruited transiently around the future septum site. Fluorescent protein-tagged septins and F-actin together formed a contractile ring at the septum site. These distinct specialized growth machineries at different sites of dikaryotic vegetative hyphae provide a foundation to explore the differentiation program of various types of cells required for fruiting body formation.

Abstract Background The current study examines the negative impact of the coronavirus disease 2019 (COVID-19) emergency declarations on physical activity among the community-dwelling older adults, the participants of a physical activity measurement program, in Japan. Methods This retrospective observational study included 1,773 community-dwelling older adults (aged 74.6 ± 6.3 years, 53.9% women) who had participated in the physical activity measurement project from February 2020 to July 2021. We measured physical activity using a tri-axial accelerometer during 547 consecutive days. Three emergency declarations, requesting people to avoid going outside, occurred during the observational period. We multiply-imputed missing values for daily physical activity, such as steps, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) for several patterns of datasets according to the maximum missing rates on a person level. We mainly report the results based on less than 50% of the maximum missing rate (n = 1,056). Other results are reported in the supplemental file. Changes in physical activity before and after the start of each emergency declaration were examined by the regression discontinuity design (RDD) within 14-, 28-, and 56-day bandwidths. Results For all the participants in the multiply-imputed data with the 14-day bandwidth, steps (coefficients [ $${\widehat{\gamma }}_{1}$$ γ ^ 1 ] $$,$$ , 964.3 steps), LPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , 5.5 min), and MVPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , 4.9 min) increased after the first emergency declaration. However, the effects were attenuated as the RDD bandwidths were widened. No consistent negative impact was observed after the second and third declarations. After the second declaration, steps ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -609.7 steps), LPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -4.6 min), and MVPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -2.8 min) decreased with the 14-day bandwidth. On the other hand, steps ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , 143.8 steps) and MVPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , 1.3 min) increased with the 56-day bandwidth. For the third declaration, LPA consistently decreased with all the bandwidths ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -2.1, -3.0, -0.8 min for the 14, 28, 56-day bandwidth), whereas steps ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -529 steps) and MVPA ( $${\widehat{\gamma }}_{1},$$ γ ^ 1 , -2.6 min) decreased only with the 28-day bandwidth. Conclusions For the community-dwelling older adults who regularly self-monitor their physical activity, the current study concludes that there is no evidence of consistently negative impacts of the emergency declarations by the COVID-19 pandemic.

Introduction A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation The patient was a 65‐year‐old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion Sunitinib after an IO‐drug showed a significant effect in spite of only slight efficacy with other VEGFR‐TKIs, which may have occurred through the alteration of the immunological microenvironment.

Dyslipidemia (DL) is one of the most common lifestyle-related diseases. There are few reports showing the causal relationship between gut microbiota (GM) and DL. In the present study, we used a linear non-Gaussian acyclic model (LiNGAM) to evaluate the causal relationship between GM and DL. A total of 79 men and 82 women aged 40 years or older living in Shika-machi, Ishikawa Prefecture, Japan were included in the analysis, and their clinical information was investigated. DNA extracted from the GM was processed to sequence the 16S rRNA gene using next-generation sequencing. Participants were divided into four groups based on sex and lipid profile information. The results of one-way analysis of covariance, linear discriminant analysis effect size, and least absolute value reduction and selection operator logistic regression model indicated that several bacteria between men and women may be associated with DL. The LiNGAM showed a presumed causal relationship between different bacteria and lipid profiles in men and women. In men, Prevotella 9 and Bacteroides were shown to be potentially associated with changes in low- and high-density lipoprotein cholesterol levels. In women, the LiNGAM results showed two bacteria, Akkermansia and Escherichia/Shigella, had a presumptive causal relationship with lipid profiles. These results may provide a new sex-based strategy to reduce the risk of developing DL and to treat DL through the regulation of the intestinal environment using specific GM.

BackgroundOlder people with high cardiovascular risk, including those without cardiovascular diseases, are an at-risk population for dementia. Regular physical activity is generally recommended to maintain brain health; however, the optimal intensity of physical activity for maintaining brain volume in older adults with cardiovascular risk remains unclear. We examined the associations between intensity-specific physical activity and brain volume stratified by absolute cardiovascular risk level in older adults without cardiovascular diseases.Methods and resultsThis cross-sectional study involved 725 community-dwelling older Japanese adults without cardiovascular diseases. We estimated absolute cardiovascular risk using the World Health Organization risk estimation charts, which include variables such as age, sex, diabetes mellitus, smoking, systolic blood pressure, and total cholesterol, and stratified cardiovascular risk level into three risk categories: low (≤ 9%), moderate (10–14%), and high (≥15%). We measured daily physical activity using a triaxial accelerometer, and calculated the average time spent in moderate-to-vigorous intensity physical activity (MVPA) and light intensity physical activity (LPA). We performed brain T1-weighted magnetic resonance imaging and calculated the volume of the cortical gray matter, subcortical gray matter, and cerebral white matter, using the FreeSurfer software. In the overall sample, multivariable linear regression analysis showed that greater MVPA was significantly associated with greater volume of the cortical gray matter and cerebral white matter, and greater LPA was significantly associated with greater volume of the cerebral white matter. Additionally, in the analysis of the sample stratified by absolute cardiovascular risk level, cerebral white matter volume was significantly associated with both MVPA and LPA in the high cardiovascular risk group.ConclusionsThe association between physical activity and brain volume differed according to cardiovascular risk level in community-dwelling older adults. In a population at high cardiovascular risk, maintaining or increasing LPA might be a practical and achievable strategy for healthy brain aging.

To reduce both the platform motion and dynamic loads of floating offshore wind turbine-generator systems, feedforward control for high wind speed regions is developed by combining with the wind speed previewed by a nacelle-mounted lidar. First, the wind speed preview using a nacelle-mounted lidar was simulated by considering the floating platform velocity and the temporal difference of laser casting. Feedforward control, in which the blade pitch is manipulated according to the preview wind speed so as to maintain the rated generator speed, is combined with gain-scheduling feedback control of the generator speed. This feedforward control is characterized by employing the first-order lag filter with the delay compensator for the preview wind speed. The effectiveness of the developed feedforward-feedback controller is analyzed through an aero-elastic-hydro-control coupled nonlinear dynamic simulation of a 5-MW floating offshore wind turbine-generator system under turbulent wind fields and irregular wave height variations. The feedforward-feedback controller provides the stabilization of the platform pitching motion and the reduction in the dynamic load variations at the blade root and drivetrain as well as the tower base in comparison to the conventional gain-scheduling feedback control of the generator speed. Moreover, the sensitivity of the settings of the first-order lag filter and the delay compensator in the wind speed preview is clarified for their optimal design.

Subjective cognitive decline (SCD) in older adults has been identified as a risk factor for dementia. However, the literature is inconsistent, and the underlying mechanisms are not well understood. We aimed to determine whether older adults with SCD had more modifiable protective factors against the risk of dementia and a lower risk of developing objective cognitive decline (OCD). We included 4363 older adults (71.7 ± 5.3 [mean ± standard deviation] years of age; 2239 women) from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes. SCD, OCD, and protective factors against dementia, such as lifestyle and activity, were assessed using interviews and objective cognitive-assessment tools. Based on initial cognitive status, participants were categorized into normal cognition, SCD-only, OCD-only, and both SCD and OCD groups. After 4 years, participants were classified as having either no impairment or mild or global cognitive impairment (i.e., OCD). Binomial logistic regression analyses were performed with the cognitive statuses of the groups at follow-up and baseline as the dependent and independent variables, respectively. After adjusting for potential confounding factors, we found that the SCD-only group had more modifiable protective factors against the risk of dementia than the OCD-only group. Community-dwelling older adults with normal cognition or those part of the SCD-only group had a lower risk of developing OCD during the 4-year follow-up, which may have been due to having more modifiable protective factors against the risk of dementia. Additionally, these factors may contribute to the inconsistencies in the literature on SCD outcomes.

Abstract Background Infective endocarditis (IE) is defined as endocarditis caused by microorganisms (bacteria or fungi) involving either the heart or great vessels. The clinical course of IE can be complicated by cardiac dysfunction and bacterial embolization to virtually any organ. Staphylococcus aureus and viridans group streptococci are the most common causative organisms, whereas group A Streptococcus (GAS) is less common. Although some GAS serotypes have been associated with severe disease, there are few reports of IE associated with GAS serotypes. Here, we report two cases of GAS endocarditis and review the associated literature. Case presentations Patient 1 was a previously healthy 14-year-old girl who developed bacteremia and disseminated intravascular coagulation secondary to left foot cellulitis. She was administered intravenous antibiotics. Two of three blood cultures grew Streptococcus pyogenes (T6 M6, emm6.104). Three days later, a new systolic ejection murmur was heard and echocardiography showed mitral regurgitation with mitral valve vegetation. Because of the resultant severity of the mitral regurgitation, she underwent mitral valve repair after 10 weeks of antibiotic treatment. Patient 2 was a 17-month old boy who presented with a fever. He had a history of spontaneous closure of a ventricular septal defect (VSD). He was started on intravenous antibiotics for possible bacteremia. Two consecutive blood cultures with an interval of more than 12 h grew S. pyogenes (T4 M4, emm4.0). Five days later, echocardiography showed vegetation on a membranous ventricular septal aneurysm. The patient responded well to antibiotics, and recovered fully with no complications. Conclusions Although both patients developed GAS endocarditis, patient 1 did not have any predisposing conditions for IE, and patient 2 had a only a low-risk predisposing condition, a VSD that had closed spontaneously at five months of age. We found twelve reports in the literature of GAS endocarditis with information on serotypes. All patients in these reports had GAS endocarditis caused by serotypes generally associated with milder infections, but no specific risk trends were identified. A greater accumulation of cases is necessary to more clearly elucidate the association between GAS IE and specific serotypes.

The present study developed a simplified decision-tree algorithm for fall prediction with easily measurable predictors using data from a longitudinal cohort study: 2520 community-dwelling older adults aged 65 years or older participated. Fall history, age, sex, fear of falling, prescribed medication, knee osteoarthritis, lower limb pain, gait speed, and timed up and go test were assessed in the baseline survey as fall predictors. Moreover, recent falls were assessed in the follow-up survey. We created a fall-prediction algorithm using decision-tree analysis (C5.0) that included 14 nodes with six predictors, and the model could stratify the probabilities of fall incidence ranging from 30.4% to 71.9%. Additionally, the decision-tree model outperformed a logistic regression model with respect to the area under the curve (0.70 vs. 0.64), accuracy (0.65 vs. 0.62), sensitivity (0.62 vs. 0.50), positive predictive value (0.66 vs. 0.65), and negative predictive value (0.64 vs. 0.59). Our decision-tree model consists of common and easily measurable fall predictors, and its white-box algorithm can explain the reasons for risk stratification; therefore, it can be implemented in clinical practices. Our findings provide useful information for the early screening of fall risk and the promotion of timely strategies for fall prevention in community and clinical settings.

Leptospirosis is considered underdiagnosed because of its nonspecific presentation and lack of proper understanding of its epidemiology. Early diagnosis and treatment are crucial. However, few data are available on confirmed leptospirosis cases in children in industrialized countries. We therefore aimed to describe epidemiologic and clinical characteristics of laboratory-confirmed childhood leptospirosis in Okinawa, Japan. We reviewed the national surveillance data of pediatric leptospirosis in Okinawa, Japan from January 2003 through December 2015. The database included all of laboratory-confirmed leptospirosis diagnosed at the only central laboratory for leptospirosis in the region. There were 44 children (0-20 years of age) with laboratory-confirmed leptospirosis. Of these, 90% were male, 91% were 10-20 years of age, and 96% of cases occurred in August and September. The number of laboratory-confirmed patients ranged from 0 to 11 per year (mean: 3.3 per year), and the estimated annual rate was 1.0 per 100,000 pediatric populations. In all cases, the presumed infection route was recreational exposure to river water. Commonly observed manifestations include fever (95%), myalgia (52%), and conjunctival suffusion (52%). Childhood leptospirosis in Okinawa, Japan occurred predominantly in teenage boys after freshwater exposure in summer, and most patients had characteristic conjunctival suffusion. Cohort studies would be helpful to better understand more detailed clinical manifestations in association with prognosis.

We obtained the spin Seebeck effect enhancement in Y3Fe5O12 (YIG)/Pt system by inserting a very thin Ni80Fe20 at the interface of YIG/Pt. One of important parameters determining the spin Seebeck coefficient is the spin mixing conductance at the interface between magnetic oxide and nonmagnetic metal, and it was theoretically reported that the spin mixing conductance depends on the magnetic density at the interface. However, a ferrimagnetic oxide such as YIG has a small magnetic moment density. In this report, we fabricated YIG (1 mm)/Ni80Fe20 (t nm)/Pt (5 nm) and the spin Seebeck coefficient of t=0.6 nm becomes 2.1 times larger than that of t=0. It is considered owing to improvement of the magnetic moment density and the spin mixing conductance.

In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method„ to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ERα ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2− BC indicates decreased likelihood of benefiting from ET.

BackgroundSeawater temperature is the main factor restricting shallow-water zooxanthellate coral reefs to low latitudes. As temperatures increase, coral species and perhaps reefs may move into higher-latitude waters, increasing the chances of coral reef ecosystems surviving despite global warming. However, there is a growing need to understand the structure of these high-latitude coral communities in order to analyze their future dynamics and to detect any potential changes.Methodology/principal findingsThe high-latitude (32.75°N) community surveyed was located at Tatsukushi, Shikoku Island, Japan. Coral cover was 60±2% and was composed of 73 scleractinian species partitioned into 7 functional groups. Although only 6% of species belonged to the 'plate-like' functional group, it was the major contributor to species coverage. This was explained by the dominance of plate-like species such as Acropora hyacinthus and A. solitaryensis. Comparison with historical data suggests a relatively recent colonization/development of A. hyacinthus in this region and a potential increase in coral diversity over the last century. Low coverage of macroalgae (2% of the benthic cover) contrasted with the low abundance of herbivorous fishes, but may be reasonably explained by the high density of sea urchins (12.9±3.3 individuals m⁻²).Conclusions/significanceThe structure and composition of this benthic community are relatively remarkable for a site where winter temperature can durably fall below the accepted limit for coral reef development. Despite limited functionalities and functional redundancy, the current benthic structure might provide a base upon which a reef could eventually develop, as characterized by opportunistic and pioneer frame-building species. In addition to increasing seawater temperatures, on-going management actions and sea urchin density might also explain the observed state of this community. A focus on such 'marginal' communities should be a priority, as they can provide important insights into how tropical corals might cope with environmental changes.

In this article, we review studies which have been conducted to investigate the hormonal influence on metamorphosis in bullfrog (Rana catesbeiana) and Japanese toad (Bufo japonicus) larvae, in addition to studies conducted on the hormonal and pheromonal control of reproductive behavior in red-bellied newts (Cynops pyrrhogaster). Metamorphosis was studied with an emphasis on the roles of prolactin (PRL) and thyrotropin (TSH). The release of PRL was shown to be regulated by thyrotropin-releasing hormone (TRH) and that of TSH was evidenced to be regulated by corticotropin-releasing factor. The significance of the fact that the neuropeptide that controls the secretion of TSH is different from those encountered in mammals is discussed in consideration of the observation that the release of TRH, which stimulates the release of PRL, is enhanced when the animals are subjected to a cold temperature. Findings that were made by using melanin-rich cells of Bufo embryos and larvae, such as the determination of the origin of the adenohypophyseal primordium, identification of the pancreatic chitinase, and involvement of the rostral preoptic recess organ as the hypothalamic inhibitory center of α-melanocyte-stimulating hormone (α-MSH) secretion, are mentioned in this article. In addition, the involvement of hormones in eliciting courtship behavior in male red-bellied newts and the discovery of the peptide sex pheromones and hormonal control of their secretion are also discussed in the present article., (© 2023 Japanese Society of Developmental Biologists.)