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Liddle syndrome (LS) is an autosomal dominant genetic disorder characterized by early onset hypertension, hypokalemia, and low plasma aldosterone or renin concentration. It is caused by mutations in subunits of the epithelial sodium channel (ENaC). The clinical phenotypes of LS are variable and nonspecific, making it prone to both misdiagnosis and missed diagnosis. Genetic analysis is necessary to confirm the diagnosis of LS. Herein, we report the case of a 42-year-old male with LS and a 30-year history of hypertension. He was being treated for possible primary aldosteronism (PA) over the preceding 7 years; however, his hypertension was poorly controlled despite intensive combination therapy. His 13-year-old son served as a proband for a diagnosis of LS, as he had hypertension, hypokalemia, and a significant family history of hypertension. Genetic testing revealed a heterozygous pathological variant in the SCNN1B gene. This led to a diagnosis of LS, as the father was found to harbor the same mutation. Both were treated with ENaC inhibitors and a salt-restricted diet, which improved their symptoms markedly. The son’s genetic diagnosis facilitated the subsequent proper diagnosis and treatment of his father. LS causes early onset hypertension; hence, its early diagnosis and treatment can prevent complications. Hereditary hypertension should be considered in cases of early onset hypertension with a significant family history. Patients diagnosed with PA using outdated criteria may have concomitant LS and require careful evaluation of biochemical and endocrine tests according to the current criteria.

Gaussian process Bayesian optimization (GPBO) based on the upper confidence bound is a method for finding the approximate maximum solution using observations maximizing $E + \beta V^{1/2}$ consisting of the estimated average E and variance V obtained by Gaussian process regression. The exploration weight $\beta $ is the coefficient for adjusting the exploration-exploitation trade-off, which affects search performance. In previous studies, constant value, logarithmic decay, and probabilistic value as the exploration weight have been proposed, and they exhibit good search performance. For better search performance, we propose a method for setting the exploration weight using estimated variance integration (EVI) as a novel meta-heuristics algorithm. Because the integration of the estimated variance V represents the total amount of uncertainty in an entire search space, using it as the exploration weight, we can expect the search performance to be higher than that of previous methods. In this study, an exact analytical solution for integrating the estimated variance in the Gaussian kernel case was provided to realize EVI-GPBO. Experiments on searching for the global optimum using benchmark functions for evaluating approximate search algorithms were conducted to evaluate EVI-GPBO. The results indicate that EVI-GPBO can find optimal solutions with a high percentage compared to the existing methods. In a more realistic setting, an experiment on hyperparameter tuning for a support vector machine was conducted. The results indicate that EVI-GPBO obtained a higher score than the other existing methods. In summary, we conclude that EVI-GPBO is an effective search algorithm.

Objectives: Postmenopausal women with osteoporosis are frequently underdiagnosed. In Japan, general dental practitioners have begun using the cortical shape of the mandible on dental panoramic radiographs (PRs) to identify and refer women at risk of osteoporosis to medical professionals. It remains unclear whether dental students, after relevant education, possess the ability to identify these at-risk individuals. This study evaluated the ability of dental students to screen for osteoporosis on PRs. Methods: A cohort of 113 fifth-year dental students participated in a lecture on osteoporosis screening using PRs. The students then categorized the mandibular inferior cortex on PRs from 30 postmenopausal women (11 with osteoporosis) as normal, mildly to moderately eroded, or severely eroded. Interobserver agreement between the students and an expert oral radiologist using two cortical groups (normal to moderately eroded and severely eroded) was assessed through kappa statistics. Screening ability for osteoporosis detection by identifying severely eroded cortices was calculated and compared with that of the Osteoporosis Self-assessment Tool for Asians (OSTA). Results: Twenty-one (18.6%) students demonstrated moderate to substantial agreement with the expert. The mean sensitivity, specificity, and positive and negative predictive values for these students in identifying osteoporosis were 60.2%, 88.0%, 76.3%, and 80.0%, respectively. For the OSTA, sensitivity, specificity, and positive and negative predictive values were 27.3%, 68.4%, 33.3%, and 61.9%, respectively. Conclusions: Even with minimal education, approximately one-fourth of dental students may accurately identify postmenopausal women with osteoporosis on PRs, outperforming questionnaire-based screening tools.

Abstract Background The therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients. Methods This retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups. Results Of the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075). Conclusion The study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy.

The global impact of the COVID-19 pandemic is widely recognized as a significant concern, with human flow playing a crucial role in its propagation. Consequently, recent research has focused on identifying and analyzing factors that can effectively regulate human flow. However, among the multiple factors that are expected to have an effect, few studies have investigated those that are particularly associated with human flow during the COVID-19 pandemic. In addition, few studies have investigated how regional characteristics and the number of vaccinations for these factors affect human flow. Furthermore, increasing the number of verified cases in countries and regions with insufficient reports is important to generalize conclusions. Therefore, in this study, a group-level analysis was conducted for Narashino City, Chiba Prefecture, Japan, using a human flow prediction model based on machine learning. High-importance groups were subdivided by regional characteristics and the number of vaccinations, and visual and correlation analyses were conducted at the factor level. The findings indicated that tree-based models, especially LightGBM, performed better in terms of prediction. In addition, the cumulative number of vaccinated individuals and the number of newly infected individuals are likely explanatory factors for changes in human flow. The analyses suggested a tendency to move with respect to the number of newly infected individuals in Japan or Tokyo, rather than the number of new infections in the area where they lived when vaccination had not started. With the implementation of vaccination, attention to the number of newly infected individuals in their residential areas may increase. However, after the spread of vaccination, the perception of infection risk may decrease. These findings can contribute to the proposal of new measures for efficiently controlling human flows and determining when to mitigate or reinforce specific measures.

Sarcopenia negatively affects the quality of life and health of older individuals. Physical exercise is a standard treatment for sarcopenia. Recently, the potential benefits of green tea catechins (GTCs) in sarcopenia have gained considerable attention. In this study, we investigated the effects of a combination of GTCs and physical exercise on the symptoms and pathologies of sarcopenia using male senescence-accelerated mouse prone 8 (SAMP8). These mice were divided into four groups: control, GTCs, exercise (Ex), and GTCs + Ex. GTC-fed mice were fed a diet containing 0.33 % GTCs. The mice were subjected to exercise training (voluntary wheel running) for 12 weeks, from 5 to 8 months of age, and grip strength and gastrocnemius muscle alterations were investigated. SAMP8 mice exhibited symptoms and pathologies of sarcopenia, including loss of muscle mass, decreased grip strength, reduced mitochondrial capacity, increased oxidative stress, reduced number of satellite cells, and an increased ratio of 5-bromo-2′-deoxyuridine (BrdU)-positive nuclei located within the muscle cells in the aged muscle. The GTCs and/or Ex groups showed improved symptoms and pathologies of sarcopenia. In addition, the GTCs + Ex group exhibited enhanced mitochondrial capacity, myogenic differentiation, and maturation in aged skeletal muscle than that observed in the GTCs group. Our findings suggested that GTCs and/or Ex are effective in ameliorating several age-related changes in muscle morphology and function. Notably, GTCs intake, together with habitual exercise, may enhance the beneficial effects on the symptoms and pathologies of sarcopenia in aged muscle.

Summary: Background: The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations. Methods: In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness. Furthermore, we examined cytokine production in exon 2-mutated THP-1 cells (a monocytic cell line) and microbiome analysis. Findings: Of the 396 patients diagnosed with IBDU, 60.1% had MEFV mutations. Exon 2 mutations were the most common (83.7%). Among patients with available clinical information, 43.3% of patients with IBDU had typical Familial Mediterranean fever (FMF). The efficacy of colchicine in patients with IBDU carrying MEFV mutations was 84.6%. Significant differences were noted in the production of inflammatory; cytokines between THP-1 cells with and without MEFV mutations. Microbial compositions differed between patients with IBDU carrying MEFV mutations and patients with IBD and healthy controls. Interpretation: Patients with IBDU carrying MEFV mutations responded well to colchicine treatment. A notable subset of patients met the criteria for typical FMF. Alterations in intestinal microbiota may contribute to disease pathogenesis. Funding: This work was supported by the Japan Agency for Medical Research and Development (21ek0410057h0003), a grant from the Uehara Memorial Foundation, and the Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease; Grant Number 20316729).

Introduction: Cell processing facilities are susceptible to environmental bacteria and must maintain sterile environments to safeguard cell products. This process involves circulating air through high-efficiency particulate air (HEPA) filters, which incurs significant maintenance costs. While cost-reduction strategies have been explored in the semiconductor industry, validations specific to cell processing facilities remain unreported. This study aims to verify whether optimizing air-conditioning management in cell processing facilities can achieve energy savings by using particle counters to measure air quality during both non-operational and hypothetical operational conditions. Methods: The study assessed particle generation under varying air conditions to evaluate potential savings and the impact of reducing air-change rates. The air conditions were defined as follows: Condition 1 (C1) represented normal air conditions (100 %), followed by C2 (72.87 %), C3 (45.74 %), C4 (18.60 %), and C5 (0 %). The number of particles was evaluated across these conditions. Particle counters measured the quantity of particles during non-operational periods and during a 2-min walking motion. The time taken for particle levels to stabilize and become undetectable was also analyzed. Theoretical electricity cost savings were estimated for hypothetical operating and non-operating hours, with calculations adjusted for facilities ranging in size from small (100 m2) to large (1000 m2). Results: Results indicated that under air conditions C1, C2, C3, and C4, almost no particles were detected, whereas in C5, where air conditioning was halted, particle counts still remained below guideline values. Total particle counts at the four positions were significantly higher at both 0.5 and 5 μm under conditions C4 and C5 compared to other settings. The study also demonstrated that the rate of particle increase during operation varied by air-conditioning condition and position. Notably, reducing the air-change rate significantly enhanced energy savings, especially in larger facilities. For instance, annual electricity consumption in a large facility could potentially be reduced from approximately 31 million yen to approximately 9.6 million yen, yielding savings of approximately 20 million yen. Conclusions: Even with a reduced air-change rate during non-operation, it was possible to maintain the cleanliness standards for each grade. The findings suggest that current operational practices are often excessive and that significant reductions in operating costs can be achieved by adjusting ventilation frequencies during non-operational periods. This study provides crucial insights for managing cell processing facilities facing challenges such as low production rates, the necessity of operating at full capacity due to on-demand autotransplantation, and high maintenance costs.

We report successful percutaneous retrieval of a foreign body located in an infant's right pulmonary artery using the new boomerang loop–snare technique. The case was an 18-month-old girl. A central venous catheter for chemotherapy was inserted from the right subclavian vein during treatment for myelodysplastic syndrome at another hospital. A postprocedural chest X-ray showed a foreign body in her right lung, and contrast-enhanced computed tomography confirmed the linear foreign body was located in the right pulmonary artery. The patient was transferred to our hospital to retrieve the foreign body. Under cooperation with pediatric cardiologists, a 6 Fr sheath was inserted via the right femoral vein, and a guiding catheter was advanced into the right pulmonary artery. Owing to the risk of vascular injury when using endoscopic forceps, we decided to use the loop–snare technique. We successfully crossed over the foreign body using a steerable microcatheter and a long microguidewire. The microguidewire was reinserted into the guiding catheter, and a loop was created by grasping the end of the wire using a microsnare catheter, which was inserted coaxially within the guiding catheter. By pulling the microsnare catheter, we were able to pull the foreign body into the guiding catheter and successfully retrieved it. There were no complications, such as pulmonary artery injuries or thrombi. The recovered foreign body was a piece of a guidewire. The boomerang loop–snare technique using a small-diameter system is useful for the retrieval of a foreign body in infants.

Location data collected from mobile devices via global positioning system often lack semantic information and can form sparse trajectories in space and time. This study investigates whether user age groups can be accurately classified solely from such sparse spatial–temporal trajectories. We propose a feature extraction method based on a Gaussian mixture model (GMM), which assigns representative points (RPs) by clustering the location data and aggregating user trajectories into these RPs. We then construct three machine learning (ML) models—support vector classifier (SVC), random forest (RF), and deep neural network (DNN)—using the GMM-based features and compare their performance with that of the improved DNN (IDNN), which is an existing feature extraction approach. In our experiments, we introduced a missing value ratio θth to quantify trajectory sparsity and analyzed the effect of trajectory sparsity on the classification accuracy and generalizability performance of the ML models. The results indicate that GMM-based features outperform IDNN-based features in both classification accuracy and generalization performance. Notably, the RF model achieved the highest accuracy, whereas the SVC model displayed stable generalizability. As the missing value ratio θth increases, the IDNN becomes more susceptible to overfitting, whereas the GMM-based approach preserves accuracy and robustness. These findings suggest that sparse trajectories can still offer meaningful classification performance with appropriate feature design and model selection even without semantic information. This approach holds promise for domains where large-scale, sparse trajectory data are common, including urban planning, marketing analysis, and public policy.