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Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK , PMVK , MVD , or FDPS —genes in the mevalonate pathway—cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1 , another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1 , representing FDFT1 -associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1 , indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells. [Display omitted] We identified a skin disease associated with gene-specific epigenetic mosaicism. Biallelic genetic alterations and/or promoter hypermethylation of FDFT1 cause porokeratosis, a clonal keratinization disorder. While germline variants underlie hereditary porokeratosis, epigenetic silencing in a mosaic manner causes non-hereditary porokeratosis, predisposing specific skin areas to the disease. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed enantioselective C−H bond functionalizations have become efficient methods for the synthesis of complex optically active molecules. Heterogeneous catalysts for this chemistry remain largely unexplored despite the advantages they offer in terms of ease of separation and reuse of catalysts. Herein, we report the development of heterogeneous chiral Rh catalysts for continuous‐flow enantioselective hydroacylations. Heterogeneous catalysts could be prepared simply by mixing supports and Rh complexes. The prepared catalysts exhibited excellent activity and enantioselectivity affording optically active ketones in quantitative yields with 99 % ee's. Under the optimized reaction conditions, a turnover number >300 was achieved without the leaching of Rh species. The catalysts exhibited a wide substrate scope and in sequential‐flow reactions with other heterogeneous catalysts, the syntheses of biologically active molecules and functional materials were demonstrated. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed enantioselective C−H bond functionalizations have become efficient methods for the synthesis of complex optically active molecules. Heterogeneous catalysts for this chemistry remain largely unexplored despite the advantages they offer in terms of ease of separation and reuse of catalysts. Herein, we report the development of heterogeneous chiral Rh catalysts for continuous‐flow enantioselective hydroacylations. Heterogeneous catalysts could be prepared simply by mixing supports and Rh complexes. The prepared catalysts exhibited excellent activity and enantioselectivity affording optically active ketones in quantitative yields with 99 % ee's. Under the optimized reaction conditions, a turnover number >300 was achieved without the leaching of Rh species. The catalysts exhibited a wide substrate scope and in sequential‐flow reactions with other heterogeneous catalysts, the syntheses of biologically active molecules and functional materials were demonstrated. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis. [ABSTRACT FROM AUTHOR]

Estimation of rice yield components is required to optimize cultivation management in fields. The leaf area index (LAI) can be a parameter for this estimation, but it has not been evaluated in farmers' fields. In this study, we analyzed the relationship between the LAI and yield components using data collected over a five-year period in farmers' fields for the cultivar Hitomebore. Leaf area dynamics (LAD) were parameterized by fitting a growth function to the time-series data of LAI measured using a canopy analyzer. The contribution of LAD to yield components was analyzed using multiple regression. The LAIs at five points during the growing season (effective integrated temperatures of 200, 400, 600, 800, and 1000 °Cd) were calculated using the growth function and the relationship between them and the yield components were analyzed using linear regression. The results of the multiple regression analysis showed that all function parameters significantly affected the yield components at the 5% probability level, with the greatest contribution from the LAI. The LAI at effective integrated temperatures of 400 to 600 °Cd significantly affected most of the yield components. However, the correlation coefficients between the LAI and yield components were not high (R = 0.18–0.61). The LAIs at almost all periods significantly affected the grain number per panicle and 1000-grain weight at the 5% probability level. These results suggest that the LAI could be used for monitoring trends in yield components, while further research on the development of accurate estimation methods is needed. [ABSTRACT FROM AUTHOR]

The status of human papilloma virus (HPV) and p16 overexpression for nasal vestibule squamous cell carcinoma (NVSCC) is unclear. The purpose of this retrospective study was to analyze the presence of HPV and the role of p16 overexpression as a surrogate marker in cases of NVSCC. Retrospective analysis was performed on patients who were diagnosed and treated for NVSCC at the University of Tokyo Hospital, Japan. p16 immunohistochemistry was considered positive with at least moderate staining intensity and diffuse staining (≥75% of tumor cells), according to the 8th edition of the American Joint Commission on Cancer. HPV-DNA testing was performed using multiplex polymerase chain reaction. Five patients were included in the study. Ages ranged from 55 to 78 years; there were two men and three women; two had T2N0, and three had T4aN0. Surgery was performed in one case, surgery plus radiation therapy (RT) in one case, and chemoradiation therapy (CRT) in three cases. Four of the five tumors showed p16 overexpression. One of five cases had an HPV-16 genotype. The mean follow-up period was 73 months, and all the patients survived. One patient with p16-negative carcinoma had local recurrence and underwent salvage surgery. Of the four patients with p16-positive carcinoma, one with CRT and one with surgery plus RT, each had delayed cervical lymph node metastasis, which was salvaged with neck dissection subsequent RT. In NVSCC, four of the five cases were p16-positive, and one was high-risk HPV infection. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between obesity and heart failure with preserved ejection fraction (HFpEF). The prevalence of both obesity and HFpEF is increasing, and studies have shown a strong connection between the two. The article focuses on the diagnostic and therapeutic implications of obesity-related HFpEF. It also examines the effects of an interatrial shunt device on patients with HFpEF and obesity. The study found that while obesity had an impact on various clinical and hemodynamic parameters, it did not significantly affect the outcomes of atrial shunt therapy. The authors suggest that further research is needed to develop unique therapies for obese patients with HFpEF. Additionally, the article highlights the challenges of diagnosing HFpEF in obese patients, as obesity can affect natriuretic peptide levels and echocardiographic assessments. The authors recommend exploring alternative diagnostic approaches for obese patients with HFpEF. [Extracted from the article]

Aims: Pulmonary hypertension (PH) and pulmonary vascular remodelling are common in patients with heart failure with preserved ejection fraction (HFpEF). Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non‐invasively by the mean pulmonary artery pressure–cardiac output relationship (mPAP/CO slope). We sought to characterize the pathophysiology of disproportionate exercise‐induced PH in relation to CO (DEi‐PH) and its prognostic impact in patients with HFpEF. Methods and results: A total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi‐PH was defined as the mPAP/CO slope >5.2 mmHg/L/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi‐PH. Compared with controls (n = 179) and HFpEF without DEi‐PH (n = 83), HFpEF with DEi‐PH (n = 83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV–pulmonary artery coupling, limitation in CO augmentation, more right‐sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan–Meier analyses showed that HFpEF patients with DEi‐PH had higher rates of composite outcomes of all‐cause mortality or heart failure events than those without (log‐rank p = 0.0002). Conclusion: Patients with HFpEF and DEi‐PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi‐PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF. [ABSTRACT FROM AUTHOR]

To understand how sleep-wakefulness cycles are regulated, it is essential to disentangle structural and functional relationships between the preoptic area (POA) and lateral hypothalamic area (LHA), since these regions play important yet opposing roles in the sleep-wakefulness regulation. GABA- and galanin (GAL)-producing neurons in the ventrolateral preoptic nucleus (VLPO) of the POA (VLPOGABA and VLPOGAL neurons) are responsible for the maintenance of sleep, while the LHA contains orexin-producing neurons (orexin neurons) that are crucial for maintenance of wakefulness. Through the use of rabies virus-mediated neural tracing combined with in situ hybridization (ISH) in male and female orexin-iCre mice, we revealed that the vesicular GABA transporter (Vgat, Slc32a1)- and galanin (Gal)-expressing neurons in the VLPO directly synapse with orexin neurons in the LHA. A majority (56.368.1%) of all VLPO input neurons connecting to orexin neurons were double-positive for Vgat and Gal. Using projection-specific rabies virus-mediated tracing in male and female Vgat-ires-Cre and Gal-Cre mice, we discovered that VLPOGABA and VLPOGAL neurons that send projections to the LHA received innervations from similarly distributed input neurons in many brain regions, with the POA and LHA being among the main upstream areas. Additionally, we found that acute optogenetic excitation of axons of VLPOGABA neurons, but not VLPOGAL neurons, in the LHA of male Vgat-ires-Cre mice induced wakefulness. This study deciphers the connectivity between the VLPO and LHA, provides a large-scale map of upstream neuronal populations of VLPOfiLHA neurons, and reveals a previously uncovered function of the VLPOGABAfiLHA pathway in the regulation of sleep and wakefulness. [ABSTRACT FROM AUTHOR]

Background: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. Methods: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. Results: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. Conclusion: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) may potentially differentiate heart failure (HF) with preserved ejection fraction (HFpEF) from noncardiac causes of dyspnea (NCD). While contemporary guidelines for HF recommend using CPET for identifying causes of unexplained dyspnea, data supporting this practice are limited. This study aimed to determine the diagnostic value of expired gas analysis to distinguish HFpEF from NCD. Exercise stress echocardiography with simultaneous expired gas analysis was performed in patients with HFpEF (n = 116) and those with NCD (n = 112). Participants without dyspnea symptoms were also enrolled as controls (n = 26). Exercise capacity was impaired in patients with HFpEF than in controls and those with NCD, evidenced by lower oxygen consumption (VO2), but there was a substantial overlap between HFpEF and NCD. Receiver operating characteristic curve analyses showed modest diagnostic abilities of expired gas analysis data in differentiating individuals with HFpEF from the controls; however, none of these variables clearly differentiated between HFpEF and NCD (all areas under the curve < 0.61). Expired gas analysis provided objective assessments of exercise capacity; however, its diagnostic value in identifying HFpEF among patients with symptoms of exertional dyspnea was modest. [ABSTRACT FROM AUTHOR]

Background: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. Methods: We conducted a retrospective nationwide observational study on patients with T3–T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. Results: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%–19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. Conclusion: Omission of END during laryngectomy for T3–T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time. [ABSTRACT FROM AUTHOR]

Few studies have dealt with lower-limb kinematics during the timed up and go (TUG) test in subjects with locomotive syndrome (LS). This study aimed to evaluate the characteristics of lower-limb kinematics during the TUG test in subjects with LS using the wearable sensor-based H-Gait system. A total of 140 participants were divided into the non-LS (n = 28), the LS-stage 1 (n = 78), and LS-stage 2 (n = 34) groups based on the LS risk test. Compared with the non-LS group, the LS-stage 1 and LS-stage 2 groups showed significantly smaller angular velocity of hip and knee extension during the sit-to-stand phase. The LS-stage 2 group showed significantly smaller peak angles of hip extension and flexion during the walking-out phase compared to the non-LS group. These findings indicate that the evaluation of the lower-limb kinematics during the TUG test using the H-Gait system is highly sensitive to detect LS, compared with the evaluation of the lower-limb kinematics when simply walking. [ABSTRACT FROM AUTHOR]

Background: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor–stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. Methods: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin–eosin staining and cytokeratin AE1/AE3 immunostaining. Results: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. Conclusion: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC. [ABSTRACT FROM AUTHOR]

Recent studies reported that a convolutional neural network (CNN; a deep learning model) can detect elevated pulmonary artery wedge pressure (PAWP) from chest radiographs, the diagnostic images most commonly used for assessing pulmonary congestion in heart failure. However, no method has been published for quantitatively estimating PAWP from such radiographs. We hypothesized that a regression CNN, an alternative type of deep learning, could be a useful tool for quantitatively estimating PAWP in cardiovascular diseases. We retrospectively enrolled 936 patients with cardiovascular diseases who had undergone right heart catheterization (RHC) and chest radiography and estimated PAWP by constructing a regression CNN based on the VGG16 model. We randomly categorized 80% of the data as training data (training group, n = 748) and 20% as test data (test group, n = 188). Moreover, we tuned the learning rate—one of the model parameters—by 5-hold cross-validation of the training group. Correlations between PAWP measured by RHC [ground truth (GT) PAWP] and PAWP derived from the regression CNN (estimated PAWP) were tested. To visualize how the regression CNN assessed the images, we created a regression activation map (RAM), a visualization technique for regression CNN. Estimated PAWP correlated significantly with GT PAWP in both the training (r = 0.76, P < 0.001) and test group (r = 0.62, P < 0.001). Bland–Altman plots found a mean (SEM) difference between GT and estimated PAWP of − 0.23 (0.16) mm Hg in the training and − 0.05 (0.41) mm Hg in the test group. The RAM showed that our regression CNN model estimated high PAWP by focusing on the cardiomegaly and pulmonary congestion. In the test group, the area under the curve (AUC) for detecting elevated PAWP (≥ 18 mm Hg) produced by the regression CNN model was similar to the AUC of an experienced cardiologist (0.86 vs 0.83, respectively; P = 0.24). This proof-of-concept study shows that regression CNN can quantitatively estimate PAWP from standard chest radiographs in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 < ALT < 23 U/L, n = 1055), and third (ALT ≥ 23 U/L, n = 1003). The first tertile had an older age; lower body mass index (BMI); higher prevalence of heart failure; and lower hemoglobin, total cholesterol, and triglycerides (all P < 0.05). During median 39.2 months follow-up, the first tertile had significantly higher incidences of cardiovascular and all-cause mortality (log-rank P < 0.001). Lower ALT was significantly associated with the incidence of cardiovascular and all-cause mortality, even after adjusting for clinically relevant factors (P < 0.05). Low ALT may reflect aging, sarcopenia, and malnutrition and be independently associated with a high risk of all-cause mortality in patients with AF. [ABSTRACT FROM AUTHOR]

Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin–bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤ − 2.62, n = 91)), second tertile (− 2.62 < ALBI < − 2.13, n = 92), and third tertile (ALBI ≥ − 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9–60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients. [ABSTRACT FROM AUTHOR]

Heterogeneous set-to-set matching, applied to fashion outfit recommendations, no longer depends on the similarity but on compatibility between items in sets. Existing state-of-the-art methods apply self- and cross-attention mechanisms to transform item vectors closer or farther apart and compute the matching score based on transformed item vectors. However, the transformation by attention mechanisms with fewer items in sets is performed in rather limited spaces, and the complex computation of scores in the head network would cause the instability of the training of entire networks. To overcome these problems, we propose to add a trainable set representative vector into each set and to embed discriminative information of items onto the vector through originally extended asymmetric attention mechanisms. This enables dynamic transformation in wider spaces and stable training without gradient vanishing problems to generate discriminative matching scores. Through experiments with heterogeneous set-to-set matching tasks, even-total, and fashion outfit matching tasks, we show the effectiveness of our proposed method. [ABSTRACT FROM AUTHOR]

Background: Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors.Methods: We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7-16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the "H-Gait system", which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups.Results: There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001).Conclusions: The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2. [ABSTRACT FROM AUTHOR]

(1) Sesame oil aroma has stress-relieving properties, but there is little information on its effective use and active ingredients. (2) Methods: ICR male mice were housed under water-immersion stress for 24 h. Then, the scent of sesame oil or a typical ingredient was inhaled to the stress groups for 30, 60, or 90 min. We investigated the effects of sesame oil aroma on mice behavior and the expression of the dual specificity phosphatase 1 (DUSP1) gene, a candidate stress marker gene in the brain. (3) Results: In an elevated plus-maze test, the rate of entering into the open arm of a maze and the staying time were increased to a maximum after 60 min of inhalation, but these effects decreased 90 min after inhalation. As for the single component, anxiolytic effects were observed in the 2,5-dimethylpyrazine and 2-methoxy phenol group, but the effect was weakened in the furfuryl mercaptan group. The expression levels of DUSP1 in the hippocampus and striatum were significantly decreased in 2,5-dimethylpyrazine and 2-methoxy phenol groups. (4) Conclusions: We clarified the active ingredients and optimal concentrations of sesame oil for its sedative effect. In particular, 2,5-dimethylpyrazine and 2-methoxy phenol significantly suppressed the stress-induced changes in the expression of DUSP1, which are strong anti-stress agents. Our results suggest that these molecules may be powerful anti-stress agents. [ABSTRACT FROM AUTHOR]

Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence–associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes. Type-2 diabetic adipose tissue impairs transient senescence during wound healing with expression of different components of the senescence-associated secretory phenotype (SASP), and this is associated with deteriorated wound healing. [ABSTRACT FROM AUTHOR]

We describe the continuous‐flow synthesis of (R)‐tamsulosin, a blockbuster therapeutic drug employed for dysuria associated with urinary stones and benign prostatic hyperplasia, by utilizing sequential heterogeneous catalysis. Two heterogeneous catalysts have been developed for the synthesis, and the key step involves reductive amination of nitriles using dimethylpolysilane‐modified Pd on activated carbon/calcium phosphate. Overall, (R)‐tamsulosin was obtained in 60 % yield and 64 % ee (99 % ee after recrystallization) in a flow stream through four catalytic transformations without the need for the isolation or purification of any intermediates or byproduct. [ABSTRACT FROM AUTHOR]

We describe the continuous‐flow synthesis of (R)‐tamsulosin, a blockbuster therapeutic drug employed for dysuria associated with urinary stones and benign prostatic hyperplasia, by utilizing sequential heterogeneous catalysis. Two heterogeneous catalysts have been developed for the synthesis, and the key step involves reductive amination of nitriles using dimethylpolysilane‐modified Pd on activated carbon/calcium phosphate. Overall, (R)‐tamsulosin was obtained in 60 % yield and 64 % ee (99 % ee after recrystallization) in a flow stream through four catalytic transformations without the need for the isolation or purification of any intermediates or byproduct. [ABSTRACT FROM AUTHOR]

Vasospastic angina (VSA) is reportedly associated with several clinical characteristics such as smoking and high-density lipoprotein (HDL) cholesterol, in which gender differences are present. For instance, smoking rates among men are higher than those among women, and a normal range of HDL cholesterol differs across genders. However, their impact between men and women on VSA is unclear. A total of 797 patients (427 men and 370 women) undergoing intracoronary acetylcholine (ACh) provocation test to diagnose VSA were included. The positive ACh provocation test was defined as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes. Factors contributing to VSA across genders were evaluated by multivariable analyses. Of 797 patients, 414 (51.9%) had positive ACh provocation test. The incidence of positive ACh test was higher in men than in women (56.9% vs. 46.2%, p = 0.003). In the entire study population, current smoking and a lower HDL cholesterol level were determined as factors associated with VSA. In both men and women, an HDL cholesterol level was identified as a factor contributing to positive ACh test. Among patients suspected for VSA, men as compared with women were more likely to have positive ACh provocation test. While current smoking and an HDL cholesterol level were associated with VSA in the entire study population, a lower HDL cholesterol level was determined as the only factor contributing to positive ACh test across genders, suggesting that HDL cholesterol plays important roles in the mechanism of VSA. • Clinical factors associated with vasospastic angina (VSA) across genders are unclear. • Smoking and HDL cholesterol were factors associated with VSA in the entire population. • A lower HDL cholesterol level was the only factor for predicting VSA across genders. • HDL cholesterol may play an important role in the mechanism of VSA. [ABSTRACT FROM AUTHOR]

While continuous‐flow reactions with chiral heterogeneous catalysts provide a highly efficient method to synthesize optically active compounds, chiral heterogeneous Lewis acid catalysis has been less extensively explored. We have developed the first example of chiral heterogeneous Sc catalysts, which demonstrated excellent activity and selectivity for continuous‐flow enantioselective Friedel–Crafts reactions of isatins with indoles. Noncovalent interactions between chiral Sc complexes and heteropoly acid‐anchored amine‐functionalized SiO2 as support were utilized for the synthesis. The heteropoly acid was found to be crucial for the preparation, activity, and selectivity of the catalysts. The chiral ligand could be easily tuned without chemical modification and the continuous‐flow synthesis of a biologically active compound was achieved. [ABSTRACT FROM AUTHOR]

While continuous‐flow reactions with chiral heterogeneous catalysts provide a highly efficient method to synthesize optically active compounds, chiral heterogeneous Lewis acid catalysis has been less extensively explored. We have developed the first example of chiral heterogeneous Sc catalysts, which demonstrated excellent activity and selectivity for continuous‐flow enantioselective Friedel–Crafts reactions of isatins with indoles. Noncovalent interactions between chiral Sc complexes and heteropoly acid‐anchored amine‐functionalized SiO2 as support were utilized for the synthesis. The heteropoly acid was found to be crucial for the preparation, activity, and selectivity of the catalysts. The chiral ligand could be easily tuned without chemical modification and the continuous‐flow synthesis of a biologically active compound was achieved. [ABSTRACT FROM AUTHOR]

Photo-stimuli response in materials is a fascinating feature with many potential applications. A photoresponsive gel of poly(heptazine imide), PHI, termed PHIG, exhibits photochromism, photoconductivity, and photo-induced charge accumulation, and is generated using ionic liquids and PHI. Although there are several examples of ionic liquid gels that exhibit photochromism and photoconductivity, this is the first report of an ionic liquid gel that exhibits both these properties as well as charge accumulation. We conducted experimental and theoretical investigations to understand the mechanism of the photostimulus response of PHIG, especially charge accumulation. The proposed model explains both the mechanism of charge accumulation and dark photocatalysis by PHI and provides new concepts in the field of photofunctional materials. [ABSTRACT FROM AUTHOR]

Background: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. Objective: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. Materials and methods: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. Results: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). Conclusion: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI. [ABSTRACT FROM AUTHOR]

This study examined the degree to which goals perceived by occupational therapists (OTs) matched those perceived by their clients. A total of 100 clients and 79 OTs were recruited from seven subacute rehabilitation wards in Japan. Matched pairs of OTs and their clients were independently asked for their perception about the clients' occupational therapy goals through semi-structured interviews. Collectively, the OTs reported 239 goals, while the clients reported 161 goals. While both the OTs and the clients reported a high level of client engagement in the goal setting process, 79% of the goal statements were mismatched between pairs of OTs and their clients. Goal matching was slightly better for goals about activities of daily living or participation than for goals about body structure or body function. Although most OTs and their clients perceived that they engaged in goal-setting together, only 21% of reported goals actually matched between OTs and clients. It would also be worth investigating whether there is any correlation between the content of goals, patient engagement in goal setting, degree of goal matching, and health outcomes achieved by clients following discharge from rehabilitation services. Although most occupational therapists (OTs) and their clients perceived that they engaged in goal-setting together, 79% of the goals independently reported by OTs and their clients did not match in seven post-acute rehabilitation wards across Japan. Goals were slightly more likely to match if the topic of the goals related to instrumental activities of daily living or participation (30.3%) or basic activities of daily living (24.7%) than if the topic of the goals were about body structure or body function (11.2%); however, the overall rate of goal matching was low. Japanese OTs need to develop more effective methods for recording or communicating goals in ways that clients can understand; this may be the same for other countries. [ABSTRACT FROM AUTHOR]

Background: Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women's Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients. Methods: This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF). Results: Tumor diameter > 2 cm (p < 0.0001), tumor thickness > 6 mm (p < 0.0001), invasion beyond the subcutaneous fat (p < 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p < 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size > 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4–6.2; p = 0.006], tumor thickness > 6.0 mm (HR 2.9, 95% CI 1.3–6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0–5.1; p = 0.045). Conclusion: Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients. [ABSTRACT FROM AUTHOR]

This document is a reply to a previous publication that reported on the pathophysiological features of disproportionate exercise-induced pulmonary hypertension (DEi-PH) in patients with heart failure with preserved ejection fraction (HFpEF). The author of the reply agrees with the original publication but points out that elevated pulmonary capillary wedge pressure (PCWP), inadequate systemic vasodilatation, and subclinical left ventricular (LV) systolic dysfunction could also contribute to the increase in pulmonary artery pressure. The author disagrees with the calculation of PCWP using the Nagueh formula and suggests that further invasive exercise hemodynamic studies are needed to determine pulmonary vascular dynamics during exercise. The document concludes that DEi-PH is an important phenotype of HFpEF and provides new insights into the role of exercise stress echocardiography in characterizing HFpEF. [Extracted from the article]

Background: Various features are provided in dental implants to improve initial fixation. Purpose To compare the implant stability of the nonself‐tapping tapered implant and self‐tapping hybrid implant over a 3‐month healing period. Materials and methods: A randomized controlled trial was conducted. Patients were randomly divided into tapered and self‐tapping groups. Patients in the tapered group received NobelReplace Tapered (Nobel Biocare, Sweden) implants, while those in the self‐tapping group received NobelSpeedy (Nobel Biocare, Sweden) implants. Implant stability was measured by resonance frequency analysis at surgery and 3 months following implant insertion. Data were analyzed using an independent t‐test. Results: Forty‐three patients (tapered group: 21, self‐tapping group: 22) received a total of 88 implants. Initial stability in the tapered group was significantly higher (mean: 60.14, SD: 12.40) than that in the self‐tapping group (mean: 54.72, SD: 7.92). Implant stability significantly increased 3 months after implantation in the tapered group (mean: 66.61, SD: 9.00) and self‐tapping group (mean: 64.01, SD: 5.78). No significant intergroup difference in implant stability was noted 3 months after surgery. Conclusions: The tapered shape affected initial fixation more than the self‐tapping function. However, during the second fixation, both implants showed good stability, and the difference disappeared. [ABSTRACT FROM AUTHOR]

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date.Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality.Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients).Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 . [ABSTRACT FROM AUTHOR]

The matching of asteroids and meteorites is a significant step toward a better understanding of the origin, structure, and history of the solar system. We propose a data‐driven approach for investigating common taxonomic structure between asteroids and meteorites; C‐, S‐, and V‐type for the former, and carbonaceous chondrite, ordinary chondrite, and howardite‐eucrite‐diogenite (HED) meteorite for the latter. In the numerical experiments, by checking whether the taxonomy information of meteorites improves classification for asteroid data, we examine the existence of common structure over the two domains. For this purpose, we compare the resultant accuracies of two clustering methods which are with/without the guidance of meteorite data. We observe that the guidance of meteorite taxonomy improves the accuracy for classifying asteroids, either with the reflectance spectra or major chemical compositions of meteorites. This fact serves as a piece of evidence that there is a common taxonomic structure and links between meteorites and asteroids, supporting a long‐standing hypothesis. [ABSTRACT FROM AUTHOR]

• We propose novel training algorithms for vocoder-free text-to-speech synthesis using STFT spectra based on generative adversarial networks (GANs). • We demonstrate that using GANs with the original-frequency-resolution amplitude spectra degrades the synthetic speech quality. • We show that the proposed low-frequency-resolution GANs improves the synthetic speech quality. • We also show that using the inverse mel scale for the proposed algorithm further improves the synthetic speech quality. This paper proposes novel training algorithms for vocoder-free text-to-speech (TTS) synthesis based on generative adversarial networks (GANs) that compensate for short-term Fourier transform (STFT) amplitude spectra in low/multi frequency resolution. Vocoder-free TTS using STFT amplitude spectra can avoid degradation of synthetic speech quality caused by the vocoder-based parameterization used in conventional TTS. Our previous work for the vocoder-based TTS proposed a method for incorporating the GAN-based distribution compensation into acoustic model training to improve synthetic speech quality. This paper extends the algorithm to the vocoder-free TTS and propose a GAN-based training algorithm using low-frequency-resolution amplitude spectra to overcome the difficulty in modeling complicated distribution of the high-dimensional spectra. In the proposed algorithm, amplitude spectra are transformed into low-frequency-resolution amplitude spectra by applying an average pooling function along with a frequency axis; then the GAN-based distribution compensation is performed in the low-frequency-resolution domain. Because the low-frequency-resolution amplitude spectra approximately emulate filter banks, the proposed algorithm is expected to improve synthetic speech quality by reducing differences in spectral envelopes of natural and synthetic speech. Furthermore, various frequency scales that are related to human speech perception (e.g., mel and inverse mel frequency scales) can be introduced to the proposed training algorithm by applying an frequency warping function to amplitude spectra. This paper also proposes a GAN-based training algorithm using multi-frequency-resolution amplitude spectra that uses both low- and original-frequency-resolution amplitude spectra to reduce the differences in not only spectral envelopes but also fine structures. Experimental results demonstrate that (1) GANs using low-frequency-resolution amplitude spectra improve speech quality and work robustly against the settings of the frequency resolution and hyperparameters, (2) in comparison among low-, original-, and multi-frequency-resolution amplitude spectra, the use of low-frequency-resolution ones work best improve the synthetic speech quality, and (3) the use of the inverse mel frequency scale for obtaining low-frequency-resolution amplitude spectra further improves synthetic speech quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with cardiovascular-related mortality, leading to a higher mortality rate compared the general population. However, few reports have examined cardiovascular events in non-obese MASLD mouse models. Through the present study, we highlight a non-obese steatohepatitis mouse model with cardiac dysfunction produced using co-diet ethanol added to a high-fat/high-cholesterol diet (STHD-01) for 6 or 12 weeks. Incorporating ethanol into the STHD-01 diet regimen intensifies liver issues, such as inflammation and fibrosis, as well as cardiac dysfunction, potentially due to enhanced sympathetic nervous system activity. Alcohol, even when completely metabolized on the day of drinking, is a factor that exacerbates the progression of non-obese MASLD and cardiac dysfunction. Non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with cardiovascular-related mortality, leading to a higher mortality rate compared to the general population. However, few reports have examined cardiovascular events in non-obese MASLD mouse models. In this study we created a mouse model to mimic this condition. In this study involving seven-week-old C57BL/6J male mice, two dietary conditions were tested: a standard high-fat/high-cholesterol diet (STHD-01) and a combined diet of STHD-01 and ethanol. Over periods of 6 and 12 weeks, we analyzed the effects on liver and cardiac tissues using various staining techniques and PCR. Echocardiography and blood tests were also performed to assess cardiac function and liver damage. The results showed that mice on the ethanol-supplemented STHD-01 diet developed signs of steatohepatitis and cardiac dysfunction, along with increased sympathetic activity, as early as 6 weeks. At 12 weeks, more pronounced exacerbations accompanied with cardiac dilation, advanced liver fibrosis, and activated myocardial fibrosis with sympathetic activation were observed. This mouse model effectively replicated non-obese MASLD and cardiac dysfunction over a 12-week period using a combined diet of STHD-01 and ethanol. This dietary approach highlighted that both liver inflammation and fibrosis, as well as cardiac dysfunction, could be significantly worsened due to the activation of the sympathetic nervous system. Our results indicate that alcohol, even when completely metabolized on the day of drinking, exacerbates the progression of non-obese MASLD and cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Background The transverse cervical artery is less commonly used than other external carotid arteries as a recipient vessel. Therefore, we aimed to compare the utility of the transverse cervical artery as a recipient vessel with that of the external carotid artery system for microvascular head and neck reconstruction by quantitative analysis of dynamic-enhanced computed tomography. Methods Fifty-one consecutive patients who underwent free jejunum transfer following total pharyngolaryngectomy between January 2017 and December 2020 were retrospectively reviewed. Ninety-four pairs of the diameters of the transverse cervical artery, superior thyroid artery, and lingual artery, measured via computed tomography angiography, were analyzed. Operative outcomes were compared between the following groups based on the recipient artery: transverse cervical artery (n = 27), superior thyroid artery (n = 17), and other artery (n = 7) groups. Results In the analysis of the computed tomography angiography, nine transverse cervical arteries (9.6%) could not be identified. However, the percentage was significantly lower than the percentage of superior thyroid arteries (20.2%) and lingual arteries (18.1%) (p < 0.01). Among the identified vessels, the transverse cervical arteries (2.09 ± 0.41 mm) and the lingual arteries (1.97 ± 0.40 mm) were significantly larger than the superior thyroid arteries (1.70 ± 0.36 mm) in diameter at the commonly used level (p < 0.01). Multivariate analysis revealed that prior radiation therapy was not an independent factor significantly affecting transverse cervical artery diameter (p = 0.17). Intraoperative anastomotic revision was required in only two cases of the superior thyroid artery. Conclusion The transverse cervical artery can offer a larger caliber and more reliable candidate than the superior thyroid artery for a recipient artery. More liberal use of the transverse cervical artery may improve the safety of microsurgical head and neck reconstruction. [ABSTRACT FROM AUTHOR]

A series of new gold nanocomposite materials, GNC_LCx (x = 6–11), was obtained from a series of non-linear liquid crystal oligomers, LCx (x = 6–11), with a gold nanocluster (GNC) possessing a formulation of [Au25(SC12H25)18]TOA, which is represented as Au25. The oligomers consist of a central disulphide (S–S) linkage wherein the length of the inner alkyl spacer n1 varied from 6 to 11, whilst the outer alkyl length n2 was fixed at 6. The synthesis of Au25 was verified using UV-vis and TEM, whereas the properties of Au25, LCx, and GNC_LCx were validated using UV-vis, PL, DLS, and TEM. However, the fundamental results of GNC_LCX suggest the possibility of core alteration, indicating that the GNC in GNC_LCx may no longer be the same Au25. The occurrence of some kind of complexation or more than one intermolecular interaction (other than hydrophobic interaction) is proposed that might contribute to the exisiting outcome. The primary findings implied that the synthesis of the nanocomposites was successful and the enhancement of the thermal stability of the transition temperatures of crystal–isotropic (TCr–I) and isotropic–nematic (TI–N) transitions along with the photoluminescence property were observed. [ABSTRACT FROM AUTHOR]

Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA A receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old Japanese man who was admitted to the hospital with history of mucosal lesions and painful skin. The patient also had the history of hypertension and was treated using candesartan. Dermatological examination of the man revealed an oral ulcer and scattering of vesicles over his thighs and trunk. The treatment of the patient was done using candesartan, carvedilol and doxazosin mesylate.

To identify intestinal bacteria that produce phenols (phenol and p-cresol), we screened 153 strains within 152 species in 44 genera by culture-based assay using broth media supplemented with 200 µM each of tyrosine and its predicted microbial metabolic intermediates (4-hydroxyphenylpyruvate, DL-4-hydroxyphenyllactate, 3-(p-hydroxyphenyl)propionate, 4-hydroxyphenylacetate and 4-hydroxybenzoate). Phenol-producing activity was found in 36 strains and p-cresol-producing activity in 55 strains. Sixteen strains had both types of activity. Phylogenetic analysis based on the 16S rRNA gene sequences of strains that produced 100 µM or more of phenols revealed that 16 phenol producers belonged to the Coriobacteriaceae, Enterobacteriaceae, Fusobacteriaceae and Clostridium clusters I and XIVa; four p-cresol-producing bacteria belonged to the Coriobacteriaceae and Clostridium clusters XI and XIVa; and one strain producing both belonged to the Coriobacteriaceae. A genomic search for protein homologs of enzymes involved in the metabolism of tyrosine to phenols in 10 phenol producers and four p-cresol producers, the draft genomes of which were available in public databases, predicted that phenol producers harbored tyrosine phenol-lyase or hydroxyarylic acid decarboxylase, or both, and p-cresol producers harbored p-hydroxyphenylacetate decarboxylase or tyrosine lyase, or both. These results provide important information about the bacterial strains that contribute to production of phenols in the intestine. We newly identified phenol- and p-cresol-producing bacteria by culture-based screening, and elucidated phylogenetic distribution of phenol- andp-cresol-producers. [ABSTRACT FROM AUTHOR]

The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. We further characterized GABAergic neurons electrophysiologically in the VLPO (GABAVLPO neurons) that make direct synaptic contact with these hypothalamic arousal-related neurons. These neurons (GABAVLPO→HDC or GABAVLPO→orexin neurons) were both potently inhibited by noradrenaline and serotonin, showing typical electrophysiological characteristics of sleep-promoting neurons in the VLPO. This work provides direct evidence of monosynaptic connectivity between GABAVLPO neurons and hypothalamic arousal neurons and identifies the effects of monoamines on these neuronal pathways. [ABSTRACT FROM AUTHOR]

We report a bioinspired synthesis of 2,5-dihydropentalene-based chromophores from an aliphatic oligoketone bearing 1,3- and 1,4-diketone subunits. Unlike the natural polyketone sequence, fused five-membered rings were formed via an intramolecular aldol condensation. A subsequent Knoevenagel condensation reaction with malononitrile furnished a multiply cross-conjugated π-system with low-lying LUMO levels. Furthermore, pentalenes obtained from a non-conjugated aliphatic chain exhibited visible absorption and solid-state fluorescence. [ABSTRACT FROM AUTHOR]

The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells. [ABSTRACT FROM AUTHOR]

Introduction: Renin-angiotensin system (RAS) inhibitors have been increasingly prescribed due to their beneficial effects on end-organ protection. Iatrogenic hyperkalemia is a well-known life-threatening complication of RAS inhibitor use in chronic kidney disease (CKD) patients. We hypothesized that CKD patients treated with RAS inhibitors frequently develop hyperkalemia after hospital discharge even if they were normokalemic during their hospitalization because their lifestyles change substantially after discharge. The present study aimed to examine the incidence of newly diagnosed hyperkalemia, the timing of hyperkalemia, and its risk factors in CKD patients treated with RAS inhibitors at the time of hospital discharge. Methods: We retrospectively enrolled patients aged 20 years or older with CKD G3-5 (estimated glomerular filtration rate < 60 mL/min/1.73 m2) and who were treated with RAS inhibitors and discharged from St. Luke’s International Hospital between July 2011 and December 2015. Patients who were under maintenance dialysis or had hyperkalemic events before discharge were excluded. Data regarding the patients’ age, sex, CKD stage, diabetes mellitus status, malignancy status, combined use of RAS inhibitors, concurrent medication, and hyperkalemic events after discharge were extracted from the hospital database. Our primary outcome was hyperkalemia, defined as serum potassium ≥ 5.5 mEq/L. Multiple logistic regression and Kaplan-Meier analyses were performed to identify the risk factors for and the timing of hyperkalemia, respectively. Results: Among the 986 patients, 121 (12.3%) developed hyperkalemia after discharge. In the regression analysis, relative to CKD G3a, G3b [odds ratio (OR): 1.88, 95% confidence interval 1.20–2.97] and G4-5 (OR: 3.40, 1.99–5.81) were significantly associated with hyperkalemia. The use of RAS inhibitor combinations (OR: 1.92, 1.19–3.10), malignancy status (OR: 2.10, 1.14–3.86), and baseline serum potassium (OR: 1.91, 1.23–2.97) were also significantly associated with hyperkalemia. The Kaplan-Meier analysis showed that hyperkalemia was most frequent during the early period after discharge, particularly within one month. Conclusion: Hyperkalemia was frequent during the early period after discharge among previously normokalemic CKD patients who were treated with RAS inhibitors. Appropriate follow-up after discharge should be required for these patients, particularly those with advanced CKD or malignancy status, such as hematological malignancy or late-stage malignancy, and those who are treated with multiple RAS inhibitors. [ABSTRACT FROM AUTHOR]

In recent years, it has become common for consumers to familiarize themselves with the latest fashion trends through the internet and engage in their own fashion-inspired shopping activities. Therefore, making fashion-inspired shopping and browsing activities (internet surfing in the fashion domain) comfortable is essential because it leads to interactions in the fashion industry. However, fashion is a fuzzy and complex domain that contains many abstract elements, and this ambiguity and complexity can hinder users' deep interest in the fashion industry. Therefore, we define a novel technology and domain called "fashion intelligence" and propose a system based on a visual-semantic embedding method for automatically learning and interpreting fashion and obtaining answers to users' questions. Our proposed method can embed the abundant abstract tag information in the same projective space as outfit images. Mapping of images and tags in a projective space helps search for outfit images using fashion-specific abstract words. In addition, visually estimating the degree of relevance between images and tags helps interpret abstract words. As a result, this research helps decrease fashion-specific ambiguity and complexity and supports the marketing activities and fashion choices of both experts and non-experts. • A novel technology and research area called "fashion intelligence" is defined. • Full-body outfit images are embedded with rich fashion-specific abstract tags. • Effective learning methods with broad, complex backgrounds are presented. • Various applications of the system for real-world service are introduced. • Interpretation of fashion using the proposed system is demonstrated. [ABSTRACT FROM AUTHOR]

We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 ( Lgr5 ) decreased in enteroids grown in Met deprivation conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A ( ChgA ) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. [ABSTRACT FROM AUTHOR]

Objective: There is current debate regarding whether body weight variability is associated with cardiovascular events. Recently, high body fat percentage (BF%) has been shown to be a cardiovascular risk factor. We therefore hypothesized that BF% variability would present a stronger cardiovascular risk than body weight variability. Methods: A single-center retrospective cohort study of medical check-up examinees aged 20 years or older at baseline (2005) was performed. Examinees were followed in 2007, 2009, and 2013–2014. BF% variability in 2005, 2007 and 2009 was calculated as the root-mean square error (RMSE) using a simple linear regression model. Multiple logistic regression models estimated the association between BF%-RMSE and new diagnoses of cardiovascular risk factors occurring between the 2009 and 2013–2014 visits. Results: In total, 11,281 participants (mean age: 51.3 years old, 48.8% were male) were included in this study. The average BF%-RMSE of our subjects was 0.63, and the average BMI-RMSE was 0.24. The high BF%-RMSE group (76-100th percentile) had a higher incidence of hypertension and a lower incidence of diabetes mellitus than the low BF%-RMSE group (1-25th percentile). This tendency was particularly evident in male participants. BMI-RMSE was not associated with any cardiovascular risks in our study. Conclusions: This study indicates that body fat variability has contrasting effects on cardiovascular risk factors, while body weight variability has no significant effects. [ABSTRACT FROM AUTHOR]

Hydrogenation of nitriles to primary amines with heterogeneous catalysts under liquid-phase continuous-flow conditions is described. Newly developed polysilane/SiO2-supported Pd was found to be an effective catalyst and various nitriles were converted into primary amine salts in almost quantitative yields under mild reaction conditions. Interestingly, a complex mixture was obtained under batch conditions. Lifetime experiments showed that this catalyst remained active for more than 300 h ( TON≥10 000) without loss of selectivity and no metal leaching from the catalyst occurred. By using this continuous-flow hydrogenation, synthesis of venlafaxine, an antidepressant drug, has been accomplished. [ABSTRACT FROM AUTHOR]