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Abstract Background To identify risk factors for mental distress and investigate whether the factors were different between men and women during the coronavirus disease 2019 (COVID-19), using KOKOROBO data, which is an online platform that aims to facilitate access to mental health services. Methods We used baseline data on KOKOROBO users 13 years of age or older in Japan who accessed it from October 11, 2021, to April 6, 2023, excluding those receiving treatment for mental health problems. Global severity, based on the most severe measure on Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI), was analyzed using multivariable logistic regression with baseline characteristics for each gender, and for under 30 and 30 years of age or older in women. We conducted the same analysis of suicidal ideation for each gender. Results In the 686 men and 1274 women, 117 (17.1%) and 100 (7.8%) had minimal global severity respectively, and the rest suffered from mental distress to some extent. For women, ages under 30 years (adjusted OR (aOR): 0.352, 95%CI: 0.231–0.539, P

Objectives: This study evaluated the endoscopic management and clinical outcomes of patients with colonic diverticular bleeding (CDB) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A total of 388 hospitalized patients diagnosed with CDB at two hospitals during (April 2020-March 2023) and before (April 2017-March 2020) the pandemic were enrolled in the study. We performed one-to-one propensity score matching (PSM) on the participants. We analyzed endoscopic management and clinical outcomes before and during the pandemic using a total of 264 patients matched in a PSM analysis. Results: A total of 213 (1.3%) and 172 (1.2%) colonoscopies were performed before and during the pandemic, respectively in patients with CDB (P = 0.70). After PSM, the number of early colonoscopies (63.6% vs. 76.5%, P = 0.03) and colonoscopies performed outside regular working hours (23.8% vs. 47.7%, P < 0.01) was significantly lower during the pandemic than before it. A univariate logistic regression analysis revealed that the risks of rebleeding within 30 days (odds ratio [OR]: 0.81, P = 0.42) and composite outcome (OR: 0.90, P = 0.69) were not increased during the pandemic. Conclusions: During the pandemic, the number of early colonoscopies and colonoscopies performed outside regular working hours decreased; however, this decrease did not influence rebleeding and composite outcome in patients with CDB.

Abstract Background Left ventricular outflow tract stenosis and atrioventricular valve regurgitation are often problems encountered in adulthood after complete atrioventricular septal defect repair. The surgical approach and indications for managing long-term outcomes such as left atrioventricular valve regurgitation and left ventricular outflow tract stenosis after complete atrioventricular septal defect repair have been discussed. Case presentation A 23-year-old woman with intellectual disability was diagnosed with complete atrioventricular septal defect and underwent two-patch repair without cleft closure in childhood. Follow-up examination in adulthood demonstrated moderate left-sided atrioventricular valve regurgitation and left ventricular outflow tract stenosis with a circumferential ridge (peak velocity, 3.7 m/s; pressure gradient, 54 mmHg). Intraoperative findings showed a circumferential ridge under the aortic valve, and we removed the ridge. In addition, a cleft was present at the anterior leaflet, and we completely closed the cleft. Anticoagulation therapy was not initiated, and no embolic complications occurred. Follow-up echocardiography demonstrated no ridge under the aortic valve and only mild-range left AVVR. Conclusions We successfully performed surgical treatment without valve replacement or anticoagulation therapy in a patient with poor medical compliance. Delayed reoperation leads to degeneration of the valve structure and makes more difficult to repair. Atrioventricular valve regurgitation should be evaluated in combination with based on the etiology of the regurgitation especially cleft related or not, in addition to the dilatation annulus, cleft size, and depth of the leaflet coaptation depth, and associated other valve diseases.

This retrospective study aimed to evaluate the impact of atezolizumab plus bevacizumab–transcatheter arterial chemoembolization (TACE) sequential therapy in unresectable hepatocellular carcinoma (HCC), especially in patients with intermediate-stage HCC. A total of 212 patients were enrolled and categorized into the Atez/Bev-TACE sequential therapy (n = 23) or Atez/Bev monotherapy group (n = 189) between 2020 and 2024. Of these, patients with intermediate-stage HCC were categorized into the Atez/Bev-TACE sequential (n = 18) or Atez/Bev monotherapy group (n = 91). The best objective response rate, disease control rate, and median progression-free survival (PFS) after TACE were 73.9%, 82.6%, and 6.1 months, respectively. The PFS after TACE was significantly higher in the Atez/Bev sequential therapy group than in the no-Atez/Bev-administration group after TACE (6.9 months vs. 5.0 months, p = 0.025). The median overall survival (OS) was significantly higher in the Atez/Bev-TACE sequential therapy group than in the Atez/Bev monotherapy group for intermediate-stage HCC (34.9 months vs. 17.8 months; p = 0.016). Independent factors associated with OS were low alpha-fetoprotein levels, modified albumin–bilirubin 1 or 2a levels, and Atez/Bev-TACE sequential therapy. Atez/Bev-TACE sequential therapy improved prognosis compared with Atez/Bev monotherapy in patients with intermediate-stage HCC. Moreover, Atez/Bev should be readministered after TACE.

Abstract Country of origin (COO) literally refers to “country” but also signifies states and regions, as in “Designed in California” and “Made in Asia,” respectively. Several studies have examined the effect of COO on consumer choices, but none have discussed the effects of the cardinal directions. This study bridged that gap. Randomized controlled trials verified the effect of the four cardinal directions on the attractiveness of products/services in Japan. To derive generalized results independent of any specific industry, this study focused on four diverse industries/product categories: apartment, trip/travel, cheese, and water. Attractiveness was highest when a southern COO was provided and lowest with the north, and the Chi-square test showed a significant difference only in the north and south. In terms of gender, the south effect was more pronounced for women. Although some countries are disadvantageous for COO, it is possible that many countries could benefit from the declaration of direction.

The increasing global competitiveness of university admissions has propelled the need to understand the critical factors underlying students’ loyalty. Although extensive research has been conducted on student loyalty, it focuses predominantly on student-centric activities, targeting only inward-looking measures aimed at students. In the corporate context, employees are considered the “second audience” for external marketing promotions, and the impact of these promotions on employee job satisfaction has been well researched. However, in the university context, little is known about how external policies affect student loyalty. Therefore, this study aimed to clarify the influence of both inward- and outward-looking activities on student loyalty in Japanese universities. An online survey was conducted for 1,000 Japanese university students. The results of applying structural equation modeling to the survey data confirm the positive effect of inward-looking measures on student loyalty. Significant effects were found for lectures (β = 0.670, p-value < 0.000) and job hunting (β = 0.250, p-value < 0.000), while campuses also showed a positive effect (β = 0.148, p-value = 0.039). Among outward-looking measures, only celebrity endorsements contributed positively to loyalty (β = 0.136, p-value = 0.026), while sports and digital channel promotions had negative effects, contrary to expectations. This may be attributed to the reliance of sports on wins and losses and digital channel promotions often inducing feelings of envy when students observe others’ successes. Therefore, when university policymakers implement measures to strengthen their external brands, they must consider their impact on enrolled students.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G–CSF)–mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Abstract Introduction Metastasis of malignant melanoma to urinary tract is reported to be rare. According to retrospective analysis of a single center study, improvement of overall survival was observed in patients with metastasis to the gastrointestinal tract that had undergone metastasectomy with curative intent. However, there is no significant evidence regarding resection for metastasis to urinary tract. Case presentation Case 1: an 86-year-old Japanese man was diagnosed with a small bladder tumor by computed tomography scan during post operative follow-up of malignant melanoma in the choroid of the left eye. Cystoscopy revealed black, nonpapillary tumors, suggesting metastatic malignant melanoma. Because no apparent invasive growth to muscle layer was observed by magnetic resonance imaging, transurethral resection was performed. Pathological appearance was compatible with metastatic malignant melanoma. No recurrence in urinary tract was observed; however, multiple liver metastasis was diagnosed at 3 months after surgery. Case 2: a 57-year-old Japanese man was diagnosed with right hydronephrosis due to ureteral tumor. He had a past history of subungual malignant melanoma to the left thumb 2 years prior to his visit. Right nephroureterectomy was performed, and pathological evaluation revealed metastatic malignant melanoma. He revisited 2 years later due to dysuria, and a large bladder tumor was revealed by ultrasound. Cystoscopy showed black-colored nonpapillary tumor, suggesting malignant melanoma. Total cystectomy was recommended; however, the patient withheld consent. Therefore, we performed transurethral resection. The resulting pathological finding was compatible with metastatic malignant melanoma without invasion to muscle layer. He remained free from local recurrence and metastasis for 22 years after surgery. Conclusion We successfully performed metastasectomy for bladder and ureteral metastases without recurrence in the urinary tract. Long recurrence-free survival was observed in case 2. Complete resection for metastasis of malignant melanoma may have the potential to improve survival.

Abstract We evaluated the clinical impacts of the concurrent modification of post‐transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)‐initiation timing in 61 patients with human leukocyte antigen‐haploidentical transplantation. Reduced‐dose PTCy (80 mg/kg) was associated with a higher incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) than standard‐dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early‐initiation Tac (day ‐1) increased moderate‐to‐severe chronic GVHD than standard‐initiation Tac (day 5) in the reduced‐dose PTCy group (p = 0.032), whereas Tac‐initiation timing did not impact chronic GVHD in the standard‐dose PTCy group. These data indicate that the combination of reduced‐dose PTCy and early‐initiation Tac can amplify chronic GVHD.

Abstract Background Tumor tissues comprise cancer cells and stromal cells, and their interactions form the cancer microenvironment. Therefore, treatments targeting cells other than cancer cells are also actively being developed, and among them, treatment targeting PD-1, an immune checkpoint molecule that is important in tumor immune evasion, has also been indicated for head and neck cancer. PD-L1, a ligand of PD-1, is expressed in both tumor cells and stromal cells, and the scoring system based on the combined positivity rates of both types of cells, the combined positive score (CPS), is used for predicting treatment effect. However, much is unknown regarding the expression of PD-L1. In this study, we histopathologically examined factors controlling the expression of PD-1/PD-L1. This study included 37 patients who underwent resection surgery for tongue squamous cell carcinoma in the Department of Oral and Maxillofacial Surgery at Tokyo Dental College Suidobashi Hospital. The expression levels of PD-L1, α-SMA, and p53 were assessed by immunohistochemical staining. Results Seven participants had CPS ≥ 20, twenty-four participants had 1 ≤ CPS

This study introduces a compact, portable femtosecond fibre laser system designed for synchronization with SPring-8 synchrotron X-ray pulses in a uniform filling mode. Unlike traditional titanium–sapphire mode-locked lasers, which are fixed installations, our system utilizes fibre laser technology to provide a practical alternative for time-resolved spectroscopy, striking a balance between usability, portability and cost-efficiency. Comprehensive evaluations, including pulse characterization, timing jitter and frequency stability tests revealed a centre wavelength of 1600 nm, a pulse energy of 4.5 nJ, a pulse duration of 35 fs with a timing jitter of less than 9 ps, confirming the suitability of the system for time-resolved spectroscopic studies. This development enhances the feasibility of experiments that combine synchrotron X-rays and laser pulses, offering significant scientific contributions by enabling more flexible and diverse research applications.

Abstract Hydrogen spillover, the simultaneous diffusion of protons (H+) and electrons (e−) is considered to be applicable to ubiquitous technologies related to hydrogen but limited to over reducible metal oxides. The present work demonstrates that a non-reducible MgO with heteroatom Al dopants (Al–MgO) allows hydrogen spillover in the same way as reducible metal oxides. Furthermore, a H+ storage capacity of this material owing to hydrogen spillover is more than three times greater than those of various standard metal oxides based on H+ transport channels within its bulk region. Atomic hydrogen diffuses over the non-reducible Al–MgO produces active H+-e− pairs, as also occurs on reducible metal oxides, to enhance the catalytic performance of Ni during CO2 hydrogenation. The H+ and e− diffusion pathways generated by the heteroatom Al doping are disentangled based on systematic characterizations and calculations. This work provides a new strategy for designing functional materials intended to hydrogen spillover for diverse applications in a future hydrogen-based society.

Abstract Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

Background: One factor contributing to rotational deformity of the first metatarsal in hallux valgus is torsion of the metatarsal itself. Hallux rigidus also involves reduction of the longitudinal arch, but metatarsal torsion has not been discussed. We hypothesized that metatarsal torsion may be a morphologic change unique to hallux valgus. We compared 3-dimensional (3D) torsion of the first to fifth metatarsals between feet with hallux valgus, feet with hallux rigidus, and healthy control feet to investigate differences in the effects on pathologic conditions. Methods: Participants were women of East Asian descent. There were 16, 16, and 14 feet in the control, hallux valgus, and hallux rigidus groups, respectively. One randomly selected control foot was designated as the reference foot. For comparison, nonweightbearing computed tomography images of the metatarsals were reconstructed in 3D, and the proximal and distal areas were superimposed on the reference foot. Torsion angle was defined as the rotational angle of the distal part of the articular axis relative to the proximal area. In the hallux valgus group, correlations of torsion angle with hallux valgus angle and intermetatarsal angle were calculated. Results: The hallux valgus group had greater average pronation torsion in the first metatarsal than the control group and hallux rigidus group (11 and 13 degrees greater, respectively, P .05). There was no significant correlation with hallux valgus angle or first-second intermetatarsal angle in the hallux valgus group ( P > .05). Conclusion: Hallux valgus feet had pronation deformities in the first metatarsals not observed in control or hallux rigidus feet, meaning that torsion toward pronation (eversion) in the first metatarsal was unique to hallux valgus. Improved surgical correction to diminish pronation may be necessary in patients with hallux valgus patients because of first metatarsal pronation in the first tarsometatarsal to normalize mechanical first-ray alignment. Level of Evidence : Level III, case-control stud.

Metallic phase change material was proposed and examined at melting/eutectic temperatures less than 600 °C for latent heat storage in concentrated solar power. The PCM alloy can potentially charge/discharge thermal energy as a sensible/latent heat at the temperature range of 414-527 °C. The working temperatures of PCM alloy are in operation temperatures of current molten-salt based CSP plant. In this study, thermal response testing of PCM alloy and sensible/latent storage unit that PCM alloy was loaded in a ceramic honeycomb were prepared in a laboratory scale. The thermal charging/discharging performance of PCM alloy and sensible/latent storage unit were experimentally examined and compared. The storage unit provided thermal release/absorption behaviour at close to temperatures of the thermodynamic equilibrium state.

ObjectivesThis study aimed to evaluate the efficacy of preoperative computed tomography in assessing mitral annulus anatomy and the posterior annular plication rate in mitral valve repair with annuloplasty.MethodsFrom July 2018 to August 2023, we performed robotic mitral valve repair with ring annuloplasty using a semi-rigid ring in 100 patients. Preoperative anatomical assessment of the mitral annulus was conducted by three-dimensional computed tomography. The ring size was selected based on the perioperative commissure-to-commissure length or the anterior leaflet area.ResultsThe mean commissure-to-commissure length, posterior mitral annular length, and minimum distance between the left circumflex artery and mitral annulus values were 31, 109, and 3.8 mm, respectively. No postoperative left circumflex artery injury or ring detachment was recorded. The mean plication rate (length of the posterior side of the prosthetic ring/posterior annular length) was 0.68, and it did not differ among each prosthetic ring size. The posterior plication rate (duplicate ring size 19.4) was a factor influencing the postoperative transmitral mean pressure gradient of 5 mmHg or higher. Freedom from moderate or severe mitral regurgitation was not different between the two groups above and below the posterior plication rate × ring size of 19.4 (p = 0.73), with an event-free rate of 97% vs. 96% in 3 years, respectively.ConclusionsPreoperative evaluation of the mitral annular anatomy is useful for safe mitral valve repair with ring annuloplasty. Determining ring size by focusing on the posterior annular plication rate may be a new method for ring size selection.

Abstract Intestinal stem cells (ISCs) of the fruit fly, Drosophila melanogaster, offer an excellent genetic model to explore homeostatic roles of ISCs in animal physiology. Among available genetic tools, the escargot (esg)-GAL4 driver, expressing the yeast transcription factor gene, GAL4, under control of the esg gene promoter, has contributed significantly to ISC studies. This driver facilitates activation of genes of interest in proximity to a GAL4-binding element, Upstream Activating Sequence, in ISCs and progenitor enteroblasts (EBs). While esg-GAL4 has been considered an ISC/EB-specific driver, recent studies have shown that esg-GAL4 is also active in other tissues, such as neurons and ovaries. Therefore, the ISC/EB specificity of esg-GAL4 is questionable. In this study, we reveal esg-GAL4 expression in the corpus allatum (CA), responsible for juvenile hormone (JH) production. When driving the oncogenic gene, Ras V12 , esg-GAL4 induces overgrowth in ISCs/EBs as reported, but also increases CA cell number and size. Consistent with this observation, animals alter expression of JH-response genes. Our data show that esg-GAL4-driven gene manipulation can systemically influence JH-mediated animal physiology, arguing for cautious use of esg-GAL4 as a “specific” ISC/EB driver to examine ISC/EB-mediated animal physiology.

Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. Methods This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. Results Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P

Introduction: During radiofrequency (RF) ablation, impedance monitoring has been used to avoid steam-pop caused by excessive intramyocardial temperature (IMT) rise. However, it is uncertain why the impedance decline is related to steam-pop and whether the impedance decline is correlated to IMT. Methods: Twenty-one bipolar ablations (40 W, 30-g contact, 120 s) were attempted for seven perfused porcine myocardium. Immediately after ablation, a temperature electrode was inserted into the mid-myocardial portion, and the recovery process of impedance and its correlation to IMT were assessed. Results: Transmural lesion was created in all 21 applications but steam-pop occurred in 5/21 applications with large impedance decline. In the 16 applications without steam-pop, impedance and IMT soon after ablation were 97.2 ± 4.0 Ω and 66.1 ± 4.8 °C, respectively. Reasonably high linear correlation was demonstrated between the maximum IMT after ablation and impedance differences before and after ablation. Recovery processes of the decreased impedance and the elevated IMT fit well to each equation of the single exponential decay function and showed symmetric shapes with no statistical difference of time constant (100.1 ± 34.5 s in impedance vs. 108.7 ± 27.3 s in IMT) and half-time of recovery (144.5 ± 49.8 s in impedance vs. 156.9 ± 39.4 s in IMT). Recovered impedance after ablation (104.8 ± 3.9 Ω) was 5.1 ± 2.0 Ω smaller than that before ablation (109.9 ± 2.7 Ω), suggesting several factors other than IMT rise participate in impedance decline in RF ablation. Conclusions: Recovery of impedance and IMT after ablation well correlated, which supports the usefulness of impedance monitoring for safe RF ablation.

Abstract Background A higher number of tumor buds in the invasive front of colorectal cancer (CRC) specimens has been shown to contribute to a poor prognosis in CRC patients. Because macrophages (Mφs) have been demonstrated to alter the phenotype of cancer cells, we hypothesized that the phenotype of CRC cells in the tumor budding (TB) area might be changed by the interaction between CRC cells and Mφs. Methods We assessed the expression of topoisomerase 1 in CRC cells to estimate the acquisition of chemoresistance in CRC. To demonstrate the tumor–stromal interaction between CRC cells and Mφs, we assessed two histological findings, the number of Mφs per single CRC cell and the proximity between CRC cells and Mφs by histological spatial analysis using HALO software. Results The expression levels of topoisomerase 1 in CRC cells were decreased in deeper areas, especially in the TB area, compared to the surface area. Our histological spatial analysis revealed that 2.6 Mφs located within 60 μm of a single CRC cell were required to alter the phenotype of the CRC cell. Double-immunofluorescence staining revealed that higher Mφs were positive for interleukin-6 (IL-6) in the TB area and that AE1/AE3-positive CRC cells were also positive for phospho-STAT3 (pSTAT3) in the TB area; thus, the IL-6 receptor (IL-6R)/STAT3 signaling pathway in CRC cells was upregulated by IL-6 derived from neighboring Mφs. Conclusion IL-6 secreted from the neighboring Mφs would alter the phenotype of CRC cells via IL-6R/STAT3 signaling pathway.

The literature on city branding has two main shortcomings. First, each related factor is evaluated individually, resulting in an insufficiently comprehensive evaluation. Second, the differences between brand image and loyalty factors have not been investigated sufficiently. Addressing these gaps, this study aimed to answer the following research question: ‘From the perspective of city residents, do brand image and loyalty factors differ?’ Structural equation modeling was performed, based on data from an online survey of 800 residents in 21 major Japanese cities. Results demonstrated that educational facilities and tourism resources had the most positive impact on brand image, while urban greenery and local governments had the most positive impact on loyalty. Brand image negatively affected loyalty. City branding needs differ between elite residents (e.g. those who own multiple homes/land in the city center and are keen on improving their brand image to increase land prices), tourists, and local residents (e.g. those who are worried about their mortgages). This is supported by numerous cases worldwide of famous tourist destinations – subject to overtourism – being the reason for conflict between local residents and tourists. The results underscore that practitioners need to clarify whether their objective is to strengthen external brand image or internal loyalty.

Photoluminescence, scintillation, and thermoluminescence characteristics of the Tb3+-activated gallate glasses (20K2O–(11-x/2)La2O3–69Ga2O3–x/2Tb4O7, x = 0.1–1.0) were investigated. The Tb3+-activated gallate glasses exhibited photoluminescence with some peaks at approximately 490, 540, 595, and 625 nm that were attributable to the 4f→4f transition of Tb3+. These peaks also appeared under X-ray radiation, and the x = 1.0 gallate glass showed the highest intensity. Moreover, a broad thermoluminescence glow peak appeared at 90 °C, and the thermoluminescence peak intensity decreased with increasing the Tb concentration. A complimentary relation between the scintillation and thermoluminescence intensity was observed.

The Ca2+-dependent activator protein for secretion (CAPS/CADPS) family protein facilitates catecholamine release through the dense-core vesicle exocytosis in model neuroendocrine cell lines. However, it remains unclear if it induces dopamine release in the central neurons. This study aimed to examine the expression and function of CADPS2, one of the two CADPS paralogs, in dopamine neurons of the mouse midbrain. This study shows that CADPS2 was expressed in tyrosine hydroxylase and the vesicular monoamine transporter 2 (VMAT2)-positive dopaminergic neurons of the midbrain samples and primary mesencephalic cell cultures. Subcellular fractions rich in dopamine were collected using immunoaffinity for CADPS2 from midbrain protein extracts. Cell imaging using fluorescent false neurotransmitter FFN511 as a substrate for VMAT2 showed decreased activity-dependent dopamine release in Cadps2-deficient cultures, compared to that in wild-type cultures. These results suggest that CADPS2 is involved in dopamine release from the central neurons, indicating its involvement in the central dopamine pathway.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p

The Auxin-inducible degron (AID) system is a genetic tool that induces rapid target protein depletion in an auxin-dependent manner. Recently, two advanced AID systems—the super-sensitive AID and AID 2—were developed using an improved pair of synthetic auxins and mutated TIR1 proteins. In these AID systems, a nanomolar concentration of synthetic auxins is sufficient as a degradation inducer for target proteins. However, despite these advancements, AID systems still require the fusion of an AID tag to the target protein for degradation, potentially affecting its function and stability. To address this limitation, we developed an affinity linker–based super-sensitive AID (AlissAID) system using a single peptide antibody known as a nanobody. In this system, the degradation of GFP- or mCherry-tagged target proteins is induced in a synthetic auxin (5-Ad-IAA)–dependent manner. Here, we introduce a simple method for generating AlissAID strains targeting GFP or mCherry fusion proteins in budding yeasts.

Background: People worldwide are routinely exposed to tellurium mainly via dietary ingestion. There has been no study to clarify the contribution of tellurium to blood pressure in humans or animals. Methods: In this cross-sectional study conducted in a general population of 2592 residents in Japan, the associations of urinary tellurium levels with blood pressure and prevalence of hypertension were investigated. The potential sources of tellurium were also investigated. An interventional study in mice confirmed the effect of tellurium exposure on blood pressure. Results: Linear and logistic regression analyses with consideration of confounders including urinary sodium–potassium ratio showed significant positive associations of urinary tellurium level with prevalence of hypertension and blood pressure. Cereals/beans and vegetables/fruits were determined to be potential dietary sources of tellurium exposure. Intermediary analysis suggested that increased intake of cereals/beans, but not that of vegetables/fruits, is positively associated with the tellurium-mediated risk of hypertension. Correspondingly, the mouse study showed that exposure to a putative human-equivalent dose of tellurium via drinking water increased blood pressure with an elevated level of urinary tellurium. The temporally increased blood pressure was decreased to the normal level by a break of tellurium exposure with a reduced level of urinary tellurium. Conclusions: The interdisciplinary approach provided the first evidence that tellurium exposure is a potential risk for increase of blood pressure. Since the human urinary tellurium level in this study is comparable with the levels in general populations in other Asian and European countries in previous studies, exposure to tellurium may be a latent universal risk for hypertension.

Exaggerations through which product features are excessively highlighted are common in current advertisements. The impact of such exaggerated expressions on consumers perception have been widely discussed. While much of the existing research has focused on the negative consequences of exaggeration, positive effects have been suggested under two conditions: (1) when consumers already hold a favorable attitude towards the brand, and (2) when the national culture is more accepting of exaggeration. However, these studies often rely on consumer attitudes and attributes, and there is a scarcity of discussion on the exaggerated elements that are perceived to be attractive by consumers. Therefore, this study focuses on fabric softener advertisements, identifying fragrance (private benefit) and ethicality (public benefit) as exaggerated elements. Two hypotheses were formulated for the attractiveness of advertisements when each element is excessively emphasized: H1: excessive representation of the fragrance element (personal benefit) in fabric softener advertisements negatively influences the attractiveness of the ad; and H2: excessive representation of the ethical element (public benefit) in fabric softener advertisements positively influences the attractiveness of the ad. The results of a randomized controlled trial supported both hypotheses. Thus, exaggerated expression of the public benefit element enhances the perceived attractiveness of advertisements, suggesting that companies should actively incorporate such elements to enhance consumer perception of ad appeal.

Although consumers express their willingness to adopt ethical products, they rarely actually purchase such products. The reason for this attitude-behavior gap is that social desirability bias leads to positive attitudes in marketing surveys, while ambiguity of benefits leads to negative behavior in real life. To resolve this discrepancy, there is a need to evaluate the main factors of a product comprehensively, but current literature is limited to ethical factors only. This study complements this knowledge with two surveys targeting the Japanese coffee market. In the first study, loyalty factors were examined using structural equation modeling. Positive effects were found for brand, product quality, and sales channels, with a negative effect only for ethical factors. In other words, the survey obtained responses that were not subject to social desirability bias. Hence, we conducted a demonstration to ensure that ethical factors are recognized as a value. The second study showed through a randomized controlled trial that the concept of product quality brought about by good working conditions on farms is more appealing than the concept of presenting poverty issues.

Abstract Post-stroke gait disorders involve altered lower limb kinematics. Recently, the endpoint of the lower limb has been used as a control variable to understand gait kinematics better. In a cross-sectional study of sixty-seven post-stroke patients, the limb extension angle and effective limb length during gait were used as input variables with a mixed Gaussian model-based probabilistic clustering approach to identify five distinct clusters. Each cluster had unique characteristics related to motor paralysis, spasticity, balance ability, and gait strategy. Cluster 1 exhibited high limb extension angle and length values, indicating increased spasticity. Cluster 2 had moderate extension angles and high limb lengths, indicating increased spasticity and reduced balance ability. Cluster 3 had low limb extension angles and high limb length, indicating reduced balance ability, more severe motor paralysis, and increased spasticity. Cluster 4 demonstrated high extension angles and short limb lengths, with a gait strategy that prioritized stride length in the component of gait speed. Cluster 5 had moderate extension angles and short limb lengths, with a gait strategy that prioritized cadence in the component of gait speed. These findings provide valuable insights into post-stroke gait impairment and can guide the development of personalized and effective rehabilitation strategies.

Abstract Background This study aimed to: (1) identify assessment methods that can detect greater ankle dorsiflexion range of motion (DROM) limitation in the injured limb; (2) determine whether differences in weightbearing measurements exist even in the absence of DROM limitations in the injured limb according to non-weightbearing measurements; and (3) examine associations between DROM in the weightbearing and non-weightbearing positions and compare those between a patient group with foot and ankle injuries and a healthy group. Methods Eighty-two patients with foot and ankle injuries (e.g., fractures, ligament and tendon injuries) and 49 healthy individuals participated in this study. Non-weightbearing DROM was measured under two different conditions: prone position with knee extended and prone position with knee flexed. Weightbearing DROM was measured as the tibia inclination angle (weightbearing angle) and distance between the big toe and wall (weightbearing distance) at maximum dorsiflexion. The effects of side (injured, uninjured) and measurement method on DROM in the patient groups were assessed using two-way repeated-measures ANOVA and t-tests. Pearson correlations between measurements were assessed. In addition, we analyzed whether patients without non-weightbearing DROM limitation (≤ 3 degrees) showed limitations in weightbearing DROM using t-tests with Bonferroni correction. Results DROM in patient groups differed significantly between legs with all measurement methods (all: P

Background and Aims: The clinical characteristics and risk factors involved in the development of liver fibrosis in the subtypes of steatotic liver disease (SLD) remain unknown. We examined the clinical characteristics of SLD subtypes using a large Japanese cohort. Methods: We performed a cross-sectional analysis (total n = 108,446). In this cohort, SLD was diagnosed by ultrasonography. Individuals with none of the cardiometabolic risk factors were excluded. Results: According to their nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) status based on the database, participants with cardiometabolic criteria were allocated to the MASLD, MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) with metabolic dysfunction groups. Of 30,857 subjects with SLD, 21,488 (69.6%) had NAFLD, and 20,922 (67.8%) had MASLD. There were few differences in the clinical characteristics between NAFLD and MASLD. After adjustment for clinical variables, we found that male patients with MetALD [odds ratio (OR) 2.26; 95% confidence interval (CI) 1.87–2.84] and ALD with metabolic dysfunction (OR 3.92; 95% CI 2.85–5.39) had a significantly higher risk for advanced liver fibrosis (diagnosed by Fibrosis-4 (FIB-4) index >2.67) compared to those with MASLD. In female patients with ALD, metabolic dysfunction (OR 5.80; 95% CI 2.51–13.4) and systemic blood pressure of ≥130 mmHg were significant risk factors for high FIB-4 (males: OR 3.38, 95% CI 2.51–4.55; females: OR 4.34, 95% CI 2.66–7.07, P < .001). Conclusion: Alcohol intake and systolic blood pressure are independent contributors to liver fibrosis progression assessed by FIB-4 in SLD.

Background and Aims: Precise diagnostic biomarkers are urgently required for pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of this study was to identify PDAC-specific exosomal microRNAs (Ex-miRs) from pancreatic juice (PJ) and evaluate their diagnostic potential. Methods: Exosomes in PJ and serum were extracted using ultracentrifugation and confirmed morphologically and biochemically. PDAC-specific Ex-miRs were identified using our original miR arrays, in which “Ex-miRs derived from the PJ of patients with chronic pancreatitis (CP)” were subtracted from Ex-miRs commonly expressed in both “human PDAC cell lines” and “the PJ of patients with PDAC.” We verified the expression of these miRs using quantitative real-time reverse transcription polymerase chain reaction. Changes in serum Ex-miR levels were assessed in 2 patients with PDAC who underwent curative resection. In situ hybridization was performed to directly visualize PDAC-specific miR expression in cancer cells. Results: We identified novel Ex-miR-4516 and Ex-miR-4674 from the PJ of patients with PDAC, and they showed 80.0% and 81.8% sensitivity, 80.8% and 73.3% specificity, and 90.9% and 80.8% accuracy, respectively. The sensitivity, specificity, and accuracy of a triple assay of Ex-miR-4516/4674/PJ cytology increased to 93.3%, 81.8%, and 88.5%, respectively. In serum samples (n = 88), the sensitivity, specificity, and accuracy of Ex-miR-4516 were 97.5%, 34.3%, and 68%, respectively. Presurgical levels of serum-derived Ex-miR-4516 in 2 patients with relatively early disease stages declined after curative resection. In situ hybridization demonstrated that Ex-miR-4516 expression exclusively occurred in cancer cells. Conclusion: Liquid assays using the in situ-proven Ex-miR-4516 may have a high potential for detecting relatively early-stage PDAC and monitoring its clinical course.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Abstract Background Acupuncture is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD), but its mechanism remains unknown. Whether acupuncture improves exercise capacity in patients with COPD through alleviation of leg fatigue and dyspnea is examined by applying causal mediation analysis to previous trial data. Methods Sixty-two patients with COPD completed treatments with either real or placebo acupuncture once a week for 12 weeks. Walk distance measured using the 6-minute walk test and intensities of leg fatigue and dyspnea in the modified Borg scale were evaluated at baseline and after treatment. The intervention effect of acupuncture against the placebo acupuncture on two mediators, changes in leg fatigue and dyspnea, and whether they mediated improvements in walk distance, were analyzed. Results Linear regression analysis showed that the unstandardized regression coefficients [95% confidence interval (CI)] for the intervention effect by acupuncture were -4.9 (-5.8–-4.0) in leg fatigue and -3.6 (-4.3–-2.9) in dyspnea. Mediation analysis showed that when changes in leg fatigue were considered as a mediator, direct effect, indirect effect and proportion mediated were 47.1 m (95% CI, 4.6–85.1), 34.3 m (-2.1–82.1), and 42.1%, respectively, and when changes in dyspnea were considered as a mediator, they were 9.8 m (-32.9–49.9), 72.5 m (31.3–121.0), and 88.1%, respectively, and the effects of joint mediator were -5.8 m (-55.4–43.9), 88.9 m (32.7–148.5), and 107.0%, respectively. Conclusion The improvement in exercise capacity by acupuncture is explained by changes in both leg fatigue and dyspnea.